Sample records for vancomycin resistant enterococci

  1. Risk of vancomycin-resistant enterococci bloodstream infection among patients colonized with vancomycin-resistant enterococci.

    PubMed

    Kara, Ahu; Devrim, İlker; Bayram, Nuri; Katipoğlu, Nagehan; Kıran, Ezgi; Oruç, Yeliz; Demiray, Nevbahar; Apa, Hurşit; Gülfidan, Gamze

    2015-01-01

    Vancomycin-resistant enterococci colonization has been reported to increase the risk of developing infections, including bloodstream infections. In this study, we aimed to share our experience with the vancomycin-resistant enterococci bloodstream infections following gastrointestinal vancomycin-resistant enterococci colonization in pediatric population during a period of 18 months. A retrospective cohort of children admitted to a 400-bed tertiary teaching hospital in Izmir, Turkey whose vancomycin-resistant enterococci colonization was newly detected during routine surveillances for gastrointestinal vancomycin-resistant enterococci colonization during the period of January 2009 and December 2012 were included in this study. All vancomycin-resistant enterococci isolates found within 18 months after initial detection were evaluated for evidence of infection. Two hundred and sixteen patients with vancomycin-resistant enterococci were included in the study. Vancomycin-resistant enterococci colonization was detected in 136 patients (62.3%) while they were hospitalized at intensive care units; while the remaining majority (33.0%) were hospitalized at hematology-oncology department. Vancomycin-resistant enterococci bacteremia was present only in three (1.55%) patients. All these patients were immunosuppressed due to human immunodeficiency virus (one patient) and intensive chemotherapy (two patients). In conclusion, our study found that 1.55% of vancomycin-resistant enterococci-colonized children had developed vancomycin-resistant enterococci bloodstream infection among the pediatric intensive care unit and hematology/oncology patients; according to our findings, we suggest that immunosupression is the key point for developing vancomycin-resistant enterococci bloodstream infections. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

  2. OCCURRENCE OF VANCOMYCIN RESISTANT ENTEROCOCCI IN ANIMAL FECES

    EPA Science Inventory

    A survey was conducted to determine the occurrence of vancomycin resistant Enterococci (VRE) in animal and human fecal samples. A selective agar mEI, and mEI supplemented with 4 micrograms/ml vancomycin was used in a membrane filtration procedure to determine quantitative levels ...

  3. Vancomycin resistant enterococci in farm animals – occurrence and importance

    PubMed Central

    Nilsson, Oskar

    2012-01-01

    The view on enterococci has over the years shifted from harmless commensals to opportunistic but important pathogens mainly causing nosocomial infections. One important part of this development is the emergence of vancomycin resistance enterococci (VRE). The term VRE includes several combinations of bacterial species and resistance genes of which the most clinically important is Enterococcus faecium with vanA type vancomycin resistance. This variant is also the most common VRE among farm animals. The reason for VRE being present among farm animals is selection by extensive use of the vancomycin analog avoparcin for growth promotion. Once the use of avoparcin was discontinued, the prevalence of VRE among farm animals decreased. However, VRE are still present among farm animals and by spread via food products they could potentially have a negative impact on public health. This review is based on the PhD thesis Vancomycin Resistant Enterococci in Swedish Broilers – Emergence, Epidemiology and Elimination and makes a short summary of VRE in humans and food producing animals. The specific situation regarding VRE in Swedish broiler production is also mentioned. PMID:22957131

  4. OCCURRENCE OF INTRINSIC VANCOMYCIN RESISTANT ENTEROCOCCI IN ANIMAL FECES

    EPA Science Inventory

    A survey was conducted to determine the occurrence of vancomycin resistant enterococci (VRE) in animal and human fecal samples. Fecal samples from 14 animal species and humans were analyzed by quantitative culture for enterococci and VRE. Over 800 VRE isolates were characterize...

  5. Detection of vancomycin resistances in enterococci within 3 1/2 hours

    NASA Astrophysics Data System (ADS)

    Schröder, U. -Ch.; Beleites, C.; Assmann, C.; Glaser, U.; Hübner, U.; Pfister, W.; Fritzsche, W.; Popp, J.; Neugebauer, U.

    2015-02-01

    Vancomycin resistant enterococci (VRE) constitute a challenging problem in health care institutions worldwide. Novel methods to rapidly identify resistances are highly required to ensure an early start of tailored therapy and to prevent further spread of the bacteria. Here, a spectroscopy-based rapid test is presented that reveals resistances of enterococci towards vancomycin within 3.5 hours. Without any specific knowledge on the strain, VRE can be recognized with high accuracy in two different enterococci species. By means of dielectrophoresis, bacteria are directly captured from dilute suspensions, making sample preparation very easy. Raman spectroscopic analysis of the trapped bacteria over a time span of two hours in absence and presence of antibiotics reveals characteristic differences in the molecular response of sensitive as well as resistant Enterococcus faecalis and Enterococcus faecium. Furthermore, the spectroscopic fingerprints provide an indication on the mechanisms of induced resistance in VRE.

  6. DETECTION OF INTRINSIC VANCOMYCIN RESISTANT ENTEROCOCCI IN ANIMAL AND HUMAN FECES

    EPA Science Inventory

    A survey was conducted to determine the occurrence of vancomycin resistant enterococci (VRE) in animal and human fecal samples. Fecal samples from 14 animal species and humans were analyzed by quantitative culture for enterococci and VRE. Over 800 VRE isolates were characterize...

  7. Molecular Characterization of Virulence Genes in Vancomycin-Resistant and Vancomycin-Sensitive Enterococci

    PubMed Central

    Biswas, Priyanka Paul; Dey, Sangeeta; Sen, Aninda; Adhikari, Luna

    2016-01-01

    Background: The aim of this study was to find out the correlation between presence of virulence (gelatinase [gel E], enterococcal surface protein [esp], cytolysin A [cyl A], hyaluronidase [hyl], and aggregation substance [asa1]) and vancomycin-resistant genes (van A and van B) in enterococci, with their phenotypic expression. Materials and Methods: A total of 500 isolates (250 each clinical and fecal) were processed. Enterococci were isolated from various clinical samples and from fecal specimens of colonized patients. Various virulence determinants namely asa1, esp, hyl, gel E, and cyl were detected by phenotypic methods. Minimum inhibitory concentration (MIC) of vancomycin was determined by agar dilution method. Multiplex polymerase chain reaction (PCR) was used to detect the presence of virulence and van genes. Results: Out of all the samples processed, 12.0% (60/500) isolates carried van A or van B genes as confirmed by MIC test and PCR methods. Genes responsible for virulence were detected by multiplex PCR and at least one of the five was detected in all the clinical vancomycin-resistant enterococci (VRE) and vancomycin-sensitive enterococci (VSE). gel E, esp, and hyl genes were found to be significantly higher in clinical VRE. Of the fecal isolates, presence of gel E, esp, and asa1 was significantly higher in VRE as compared to VSE. The presence of hyl gene in the clinical VRE was found to be statistically significant (P = 0.043) as against the fecal VRE. Correlation between the presence of virulence genes and their expression as detected by phenotypic tests showed that while biofilm production was seen in 61.1% (22/36) of clinical VRE, the corresponding genes, i.e., asa1 and esp were detected in 30.5% (11/36) and 27.8% (10/36) of strains only. Conclusion: Enterococcus faecium isolates were found to carry esp gene, a phenomenon that has been described previously only for Enterococcus faecalis, but we were unable to correlate the presence of esp with their

  8. [Vancomycin-resistant enterococci - the nature of resistance and risk of transmission from animals to humans].

    PubMed

    Hermanovská, Lýdia; Bardoň, Jan; Čermák, Pavel

    2016-06-01

    Enterococci are part of the normal intestinal flora of humans and animals. Under certain circumstances, they are capable of extraintestinal conversion to opportunistic pathogens. They cause endogenous as well as exogenous community and nosocomial infections. The gastrointestinal tract of mammals provides them with favorable conditions for acquisition and spread of resistance genes, for example to vancomycin (van), from other symbiotic bacteria. Thus, vancomycin-resistant enterococci (VRE) become potential reservoirs and vectors of the van genes. Their occurrence in the population of the Czech Republic was first reported by Kolář et al. in 1997. Some variants of the vanA gene cluster carried on Tn1546 which encode resistance to vancomycin are identical in humans and in animals. It means that animals, especially cattle, poultry and pigs, could be an important reservoir of VRE for humans. Kolář and Bardoň detected VRE in animals in the Czech Republic for the first time in 2000. In Europe, the glycopeptide antibiotic avoparcin, used as a growth stimulator, is responsible for selection of VRE strains in animals. Strains of Enterococcus faecium from animals may offer genes of antimicrobial resistance to other enterococci or they can be directly dangerous to human. This is demonstrated by finding isolates of E. faecalis from human patients and from pigs having very similar profiles of resistance and virulence genes. The goal of the paper was to point out the similarity between isolates of human and animal strains of enterococci resistant to vancomycin, and the possibility of their bilateral transfer between humans and animals.

  9. Vancomycin-resistance phenotypes, vancomycin-resistance genes, and resistance to antibiotics of enterococci isolated from food of animal origin.

    PubMed

    Gousia, Panagiota; Economou, Vangelis; Bozidis, Petros; Papadopoulou, Chrissanthy

    2015-03-01

    In the present study, 500 raw beef, pork, and chicken meat samples and 100 pooled egg samples were analyzed for the presence of vancomycin-resistant enterococci, vancomycin-resistance phenotypes, and resistance genes. Of 141 isolates of enterococci, 88 strains of Enterococcus faecium and 53 strains of E. faecalis were identified. The most prevalent species was E. faecium. Resistance to ampicillin (n = 93, 66%), ciprofloxacin (n = 74, 52.5%), erythromycin (n = 73, 51.8%), penicillin (n = 59, 41.8%) and tetracycline (n = 52, 36.9%) was observed, while 53.2% (n = 75) of the isolates were multiresistant and 15.6% (n = 22) were susceptible to all antibiotics. Resistance to vancomycin was exhibited in 34.1% (n = 30) of the E. faecium isolates (n = 88) and 1.9% (n = 1) of the E. faecalis isolates (n = 53) using the disc-diffusion test and the E-test. All isolates were tested for vanA and vanB using real-time polymerase chain reaction (PCR) and multiplex PCR, and for vanC, vanD, vanE, vanG genes using multiplex PCR only. Among E. faecalis isolates, no resistance genes were identified. Among the E. faecium isolates, 28 carried the vanA gene when tested by multiplex PCR and 29 when tested with real-time PCR. No isolate carrying the vanC, vanD, vanE, or vanG genes was identified. Melting-curve analysis of the positive real-time PCR E. faecium isolates showed that 22 isolates carried the vanA gene only, 2 isolates the vanB2,3 genes only, and seven isolates carried both the vanA and vanB2,3 genes. Enterococci should be considered a significant zoonotic pathogen and a possible reservoir of genes encoding resistance potentially transferred to other bacterial species.

  10. Antibiotic Resistance Patterns of Enterococci and Occurrence of Vancomycin-Resistant Enterococci in Raw Minced Beef and Pork in Germany

    PubMed Central

    Klein, Günter; Pack, Alexander; Reuter, Gerhard

    1998-01-01

    The food chain, especially raw minced meat, is thought to be responsible for an increase in the incidence of vancomycin-resistant enterococci (VRE) in human nosocomial infections. Therefore, 555 samples from 115 batches of minced beef and pork from a European Union-licensed meat-processing plant were screened for the occurrence of VRE. The processed meat came from 45 different slaughterhouses in Germany. Enterococci were isolated directly from Enterococcosel selective agar plates and also from Enterococcosel selective agar plates supplemented with 32 mg of vancomycin per liter. In addition, peptone broth was used in a preenrichment procedure, and samples were subsequently plated onto Enterococcosel agar containing vancomycin. To determine resistance, 209 isolates from 275 samples were tested with the glycopeptides vancomycin, teicoplanin, and avoparcin and 19 other antimicrobial substances by using a broth microdilution test. When the direct method was used, VRE were found in 3 of 555 samples (0.5%) at a concentration of 1.0 log CFU/g of minced meat. When the preenrichment procedure was used, 8% of the samples were VRE positive. Our findings indicate that there is a low incidence of VRE in minced meat in Germany. In addition, the resistance patterns of the VRE isolates obtained were different from the resistance patterns of clinical isolates. A connection between the occurrence of VRE in minced meat and nosocomial infections could not be demonstrated on the basis of our findings. PMID:9572958

  11. Vancomycin-Resistant Enterococci and Bacterial Community Structure following a Sewage Spill into an Aquatic Environment

    PubMed Central

    Young, Suzanne; Nayak, Bina; Sun, Shan; Badgley, Brian D.; Rohr, Jason R.

    2016-01-01

    ABSTRACT Sewage spills can release antibiotic-resistant bacteria into surface waters, contributing to environmental reservoirs and potentially impacting human health. Vancomycin-resistant enterococci (VRE) are nosocomial pathogens that have been detected in environmental habitats, including soil, water, and beach sands, as well as wildlife feces. However, VRE harboring vanA genes that confer high-level resistance have infrequently been found outside clinical settings in the United States. This study found culturable Enterococcus faecium harboring the vanA gene in water and sediment for up to 3 days after a sewage spill, and the quantitative PCR (qPCR) signal for vanA persisted for an additional week. Culturable levels of enterococci in water exceeded recreational water guidelines for 2 weeks following the spill, declining about five orders of magnitude in sediments and two orders of magnitude in the water column over 6 weeks. Analysis of bacterial taxa via 16S rRNA gene sequencing showed changes in community structure through time following the sewage spill in sediment and water. The spread of opportunistic pathogens harboring high-level vancomycin resistance genes beyond hospitals and into the broader community and associated habitats is a potential threat to public health, requiring further studies that examine the persistence, occurrence, and survival of VRE in different environmental matrices. IMPORTANCE Vancomycin-resistant enterococci (VRE) are harmful bacteria that are resistant to the powerful antibiotic vancomycin, which is used as a last resort against many infections. This study followed the release of VRE in a major sewage spill and their persistence over time. Such events can act as a means of spreading vancomycin-resistant bacteria in the environment, which can eventually impact human health. PMID:27422829

  12. Enterocin A Mutants Identified by Saturation Mutagenesis Enhance Potency Towards Vancomycin-Resistant Enterococci

    PubMed Central

    McClintock, Maria K.; Kaznessis, Yiannis N.; Hackel, Benjamin J.

    2016-01-01

    Vancomycin-resistant Enterococci infections are a significant clinical problem. One proposed solution is to use probiotics, such as lactic acid bacteria, to produce antimicrobial peptides at the site of infection. Enterocin A, a class 2a bacteriocin, exhibits inhibitory activity against E. faecium and E. faecalis, which account for 86% of vancomycin-resistant Enterococci infections. In this study, we aimed to engineer enterocin A mutants with enhanced potency within a lactic acid bacterial production system. Peptide mutants resulting from saturation mutagenesis at sites A24 and T27 were efficiently screened in a 96-well plate assay for inhibition of pathogen growth. Several mutants exhibit increased potency relative to wild-type enterocin A in both liquid- and solid-medium growth assays. In particular, A24P and T27G exhibit enhanced inhibition of multiple strains of E. faecium and E. faecalis, including clinically isolated vancomycin-resistant strains. A24P and T27G enhance killing of E. faecium 8 by 13±3- and 18±4-fold, respectively. The engineered enterocin A/lactic acid bacteria systems offer significant potential to combat antibiotic-resistant infections. PMID:26191783

  13. Enterocin A mutants identified by saturation mutagenesis enhance potency towards vancomycin-resistant Enterococci.

    PubMed

    McClintock, Maria K; Kaznessis, Yiannis N; Hackel, Benjamin J

    2016-02-01

    Vancomycin-resistant Enterococci infections are a significant clinical problem. One proposed solution is to use probiotics, such as lactic acid bacteria, to produce antimicrobial peptides at the site of infection. Enterocin A, a class 2a bacteriocin, exhibits inhibitory activity against E. faecium and E. faecalis, which account for 86% of vancomycin-resistant Enterococci infections. In this study, we aimed to engineer enterocin A mutants with enhanced potency within a lactic acid bacterial production system. Peptide mutants resulting from saturation mutagenesis at sites A24 and T27 were efficiently screened in a 96-well plate assay for inhibition of pathogen growth. Several mutants exhibit increased potency relative to wild-type enterocin A in both liquid- and solid-medium growth assays. In particular, A24P and T27G exhibit enhanced inhibition of multiple strains of E. faecium and E. faecalis, including clinically isolated vancomycin-resistant strains. A24P and T27G enhance killing of E. faecium 8 by 13 ± 3- and 18 ± 4-fold, respectively. The engineered enterocin A/lactic acid bacteria systems offer significant potential to combat antibiotic-resistant infections. © 2015 Wiley Periodicals, Inc.

  14. Vancomycin-Resistant Enterococci and Bacterial Community Structure following a Sewage Spill into an Aquatic Environment.

    PubMed

    Young, Suzanne; Nayak, Bina; Sun, Shan; Badgley, Brian D; Rohr, Jason R; Harwood, Valerie J

    2016-09-15

    Sewage spills can release antibiotic-resistant bacteria into surface waters, contributing to environmental reservoirs and potentially impacting human health. Vancomycin-resistant enterococci (VRE) are nosocomial pathogens that have been detected in environmental habitats, including soil, water, and beach sands, as well as wildlife feces. However, VRE harboring vanA genes that confer high-level resistance have infrequently been found outside clinical settings in the United States. This study found culturable Enterococcus faecium harboring the vanA gene in water and sediment for up to 3 days after a sewage spill, and the quantitative PCR (qPCR) signal for vanA persisted for an additional week. Culturable levels of enterococci in water exceeded recreational water guidelines for 2 weeks following the spill, declining about five orders of magnitude in sediments and two orders of magnitude in the water column over 6 weeks. Analysis of bacterial taxa via 16S rRNA gene sequencing showed changes in community structure through time following the sewage spill in sediment and water. The spread of opportunistic pathogens harboring high-level vancomycin resistance genes beyond hospitals and into the broader community and associated habitats is a potential threat to public health, requiring further studies that examine the persistence, occurrence, and survival of VRE in different environmental matrices. Vancomycin-resistant enterococci (VRE) are harmful bacteria that are resistant to the powerful antibiotic vancomycin, which is used as a last resort against many infections. This study followed the release of VRE in a major sewage spill and their persistence over time. Such events can act as a means of spreading vancomycin-resistant bacteria in the environment, which can eventually impact human health. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  15. Low prevalence of vancomycin- and bifunctional aminoglycoside-resistant enterococci isolated from poultry farms in Malaysia.

    PubMed

    Chan, Yean Yean; Abd Nasir, Mohd Hafiz B; Yahaya, Mohd Azli B; Salleh, Noor Mohamad Amin B; Md Dan, Azril Deenor B; Musa, Abd Majid B; Ravichandran, M

    2008-02-29

    A total of 225 samples from poultry farms and the surrounding environment were screened for vancomycin-resistant enterococci (VRE) and bifunctional aminoglycoside-resistant enterococci using conventional microbiological tests and a nanoplex polymerase chain reaction (PCR) assay. Three (1.3%) of the samples were found to contain vancomycin-resistant isolates (MIC>256 microg/mL) that had a vanA genotype. The three vanA positive VRE isolates were identified as different species. Only one isolate (Enterococcus faecium F 4/13_54) was sensitive to teicoplanin (MIC<0. 12-0.35 microg/mL); the other two VRE (E. faecalis A 21_35 and E. gallinarum F 5/10_1) were resistant to teicoplanin (MIC 3.6-->16 microg/mL). The vanC genotype was observed in nine (4%) of the samples collected. High-level gentamicin-resistant (HLGR) enterococci (with MIC ranging between 100 and 500 microg/mL) were detected in 44 samples. However, only 40 of these were found to possess the aac(6')-aph(2'') gene. The overall prevalence of VRE among the samples from the poultry farms and environment was 5.3%, but the prevalence of the clinically significant vanA VRE was 1.3%, and the prevalence of bifunctional aminoglycoside-resistant enterococci was slightly higher, at 19.5%.

  16. Cell Wall Remodeling by a Synthetic Analog Reveals Metabolic Adaptation in Vancomycin Resistant Enterococci.

    PubMed

    Pidgeon, Sean E; Pires, Marcos M

    2017-07-21

    Drug-resistant bacterial infections threaten to overburden our healthcare system and disrupt modern medicine. A large class of potent antibiotics, including vancomycin, operate by interfering with bacterial cell wall biosynthesis. Vancomycin-resistant enterococci (VRE) evade the blockage of cell wall biosynthesis by altering cell wall precursors, rendering them drug insensitive. Herein, we reveal the phenotypic plasticity and cell wall remodeling of VRE in response to vancomycin in live bacterial cells via a metabolic probe. A synthetic cell wall analog was designed and constructed to monitor cell wall structural alterations. Our results demonstrate that the biosynthetic pathway for vancomycin-resistant precursors can be hijacked by synthetic analogs to track the kinetics of phenotype induction. In addition, we leveraged this probe to interrogate the response of VRE cells to vancomycin analogs and a series of cell wall-targeted antibiotics. Finally, we describe a proof-of-principle strategy to visually inspect drug resistance induction. Based on our findings, we anticipate that our metabolic probe will play an important role in further elucidating the interplay among the enzymes involved in the VRE biosynthetic rewiring.

  17. Characterisation of the selective binding of antibiotics vancomycin and teicoplanin by the VanS receptor regulating type A vancomycin resistance in the enterococci.

    PubMed

    Hughes, C S; Longo, E; Phillips-Jones, M K; Hussain, R

    2017-08-01

    A-type resistance towards "last-line" glycopeptide antibiotic vancomycin in the leading hospital acquired infectious agent, the enterococci, is the most common in the UK. Resistance is regulated by the VanR A S A two-component system, comprising the histidine sensor kinase VanS A and the partner response regulator VanR A . The nature of the activating ligand for VanS A has not been identified, therefore this work sought to identify and characterise ligand(s) for VanS A . In vitro approaches were used to screen the structural and activity effects of a range of potential ligands with purified VanS A protein. Of the screened ligands (glycopeptide antibiotics vancomycin and teicoplanin, and peptidoglycan components N-acetylmuramic acid, D-Ala-D-Ala and Ala-D-y-Glu-Lys-D-Ala-D-Ala) only glycopeptide antibiotics vancomycin and teicoplanin were found to bind VanS A with different affinities (vancomycin 70μM; teicoplanin 30 and 170μM), and were proposed to bind via exposed aromatic residues tryptophan and tyrosine. Furthermore, binding of the antibiotics induced quicker, longer-lived phosphorylation states for VanS A , proposing them as activators of type A vancomycin resistance in the enterococci. Copyright © 2017 Diamond Light Source Ltd. Published by Elsevier B.V. All rights reserved.

  18. Nurses' experience with vancomycin-resistant enterococci (VRE).

    PubMed

    Mitchell, Ann; Cummins, Teresa; Spearing, Natalie; Adams, June; Gilroy, Lisa

    2002-01-01

    The emergence and spread of resistant organisms, in particular vancomycin-resistant enterococci (VRE), is an issue facing all staff in acute hospitals. This study explored how nurses coped with the responsibility of halting further spread of this organism during an outbreak. VRE-positive patients were cohorted with nurses who cared for them in an endeavour to contain the spread of VRE. The majority of nurses found the situation extremely stressful because of the need to act as 'gatekeepers' responsible for educating and monitoring the practices of staff and visitors. The nurses reported that they felt they were inadequately supported, were blamed for the outbreak, and that they had an increased workload as they took on duties of other staff. The results reinforce the need for a multidisciplinary team approach to education and control of VRE, more support for nursing staff cohorted with VRE-positive patients, and stringent adherence to infection control measures by all hospital staff.

  19. Tapering Courses of Oral Vancomycin Induce Persistent Disruption of the Microbiota That Provide Colonization Resistance to Clostridium difficile and Vancomycin-Resistant Enterococci in Mice.

    PubMed

    Tomas, Myreen E; Mana, Thriveen S C; Wilson, Brigid M; Nerandzic, Michelle M; Joussef-Piña, Samira; Quiñones-Mateu, Miguel E; Donskey, Curtis J

    2018-05-01

    Vancomycin taper regimens are commonly used for the treatment of recurrent Clostridium difficile infections. One rationale for tapering and pulsing of the dose at the end of therapy is to reduce the selective pressure of vancomycin on the indigenous intestinal microbiota. Here, we used a mouse model to test the hypothesis that the indigenous microbiota that provide colonization resistance against C. difficile and vancomycin-resistant enterococci (VRE) is repopulated during tapering courses of vancomycin. Mice were treated orally with vancomycin daily for 10 days, vancomycin in a tapering dose for 42 days, fidaxomicin for 10 days, or saline. To assess colonization resistance, subsets of mice were challenged with 10 4 CFU of C. difficile or VRE at multiple time points during and after completion of treatment. The impact of the treatments on the microbiome was measured by cultures, real-time PCR for selected anaerobic bacteria, and deep sequencing. Vancomycin taper-treated mice developed alterations of the microbiota and disruption of colonization resistance that was persistent 18 days after treatment. In contrast, mice treated with a 10-day course of vancomycin exhibited recovery of the microbiota and of colonization resistance by 15 days after treatment, and fidaxomicin-treated mice maintained intact colonization resistance. These findings demonstrate that alteration of the indigenous microbiota responsible for colonization resistance to C. difficile and VRE persist during and after completion of tapering courses of vancomycin. Copyright © 2018 American Society for Microbiology.

  20. Vancomycin-Resistant Enterococci: Epidemiology, Infection Prevention, and Control.

    PubMed

    Reyes, Katherine; Bardossy, Ana Cecilia; Zervos, Marcus

    2016-12-01

    Vancomycin-resistant enterococci (VRE) infections have acquired prominence as a leading cause of health care-associated infections. Understanding VRE epidemiology, transmission modes in health care settings, risk factors for colonization, and infection is essential to prevention and control of VRE infections. Infection control strategies are pivotal in management of VRE infections and should be based on patient characteristics, hospital needs, and available resources. Hand hygiene is basic to decrease acquisition of VRE. The effectiveness of surveillance and contact precautions is variable and controversial in endemic settings, but important during VRE outbreak investigations and control. Environmental cleaning, chlorhexidine bathing, and antimicrobial stewardship are vital in VRE prevention and control. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Near Absence of Vancomycin-Resistant Enterococci but High Carriage Rates of Quinolone-Resistant Ampicillin-Resistant Enterococci among Hospitalized Patients and Nonhospitalized Individuals in Sweden

    PubMed Central

    Torell, Erik; Cars, Otto; Olsson-Liljequist, Barbro; Hoffman, Britt-Marie; Lindbäck, Johan; Burman, Lars G.

    1999-01-01

    Rates of colonization with enterococci with acquired resistance to vancomycin (vancomycin-resistant enterococci [VRE]) and ampicillin (ampicillin-resistant enterococci [ARE]) were determined by using fecal samples from 670 nonhospitalized individuals and 841 patients in 27 major hospitals. Of the hospitalized patients, 181 (21.5%) were carriers of ARE and 9 (1.1%) were carriers of VRE. In univariate analyses, length of hospital stay (odds ratio [OR], 4.6; 95% confidence interval [CI], 2.5 to 8.9) and antimicrobial therapy (OR, 4.7; 95% CI, 3.3 to 6.7) were associated with ARE colonization, as were prior treatment with penicillins (OR, 3.1; 95% CI, 1.8 to 5.5), cephalosporins (OR, 2.9; 95% CI, 1.7 to 5.0), or quinolones (OR, 2.7; 95% CI, 1.5 to 4.7). In logistic regression analysis, antimicrobial therapy for at least 5 days was independently associated with ARE carriage (adjusted OR, 3.8; 95% CI, 2.6 to 5.4). Over 90% of the ARE isolates were fluoroquinolone resistant, whereas 14% of the ampicillin-susceptible Enterococcus faecium isolates were fluoroquinolone resistant. ARE carriage rates correlated with the use of fluoroquinolones (P = 0.04) but not with the use of ampicillin (P = 0.68) or cephalosporins (P = 0.40). All nine VRE isolates were E. faecium vanB and were found in one hospital. Seven of these isolates were related according to their types as determined by pulsed-field gel electrophoresis. Among the nonhospitalized individuals, the ARE carriage rate was lower (6%; P < 0.05), and only one person, who had recently returned from Africa, harbored VRE (E. faecium vanA). The absence of VRE colonization in nonhospitalized individuals reflects an epidemiological situation in Sweden radically different from that in countries in continental Europe where glycopeptides have been widely used for nonmedical purposes. PMID:10523543

  2. Evaluation of BBL CHROMagar VanRE for detection of vancomycin-resistant Enterococci in rectal swab specimens.

    PubMed

    Stamper, Paul D; Shulder, Stephanie; Bekalo, Pearl; Manandhar, Deepika; Ross, Tracy L; Speser, Sharon; Kingery, Julie; Carroll, Karen C

    2010-11-01

    A study was performed on 517 surveillance rectal swabs to evaluate a selective and differential chromogenic medium, the BBL CHROMagar VanRE (CVRE), which enables recovery and identification of VanA- and VanB-containing Enterococcus faecium (ENFM) and Enterococcus faecalis (ENFS) isolates. Compared to BBL Enterococcosel agar, a bile-esculin-azide-vancomycin (BEAV) agar, the initial overall sensitivity, specificity, and positive and negative predictive values of CVRE for the detection of vancomycin-resistant ENFM and ENFS were 99.1% and 94.8% and 84.2% and 99.7%, respectively. Among our patient population, more vancomycin-resistant enterococci (VRE) were recovered with CVRE than BEAV.

  3. Evaluation of BBL CHROMagar VanRE for Detection of Vancomycin-Resistant Enterococci in Rectal Swab Specimens▿

    PubMed Central

    Stamper, Paul D.; Shulder, Stephanie; Bekalo, Pearl; Manandhar, Deepika; Ross, Tracy L.; Speser, Sharon; Kingery, Julie; Carroll, Karen C.

    2010-01-01

    A study was performed on 517 surveillance rectal swabs to evaluate a selective and differential chromogenic medium, the BBL CHROMagar VanRE (CVRE), which enables recovery and identification of VanA- and VanB-containing Enterococcus faecium (ENFM) and Enterococcus faecalis (ENFS) isolates. Compared to BBL Enterococcosel agar, a bile-esculin-azide-vancomycin (BEAV) agar, the initial overall sensitivity, specificity, and positive and negative predictive values of CVRE for the detection of vancomycin-resistant ENFM and ENFS were 99.1% and 94.8% and 84.2% and 99.7%, respectively. Among our patient population, more vancomycin-resistant enterococci (VRE) were recovered with CVRE than BEAV. PMID:20739492

  4. Screening municipal wastewater effluent and surface water used for drinking water production for the presence of ampicillin and vancomycin resistant enterococci.

    PubMed

    Taučer-Kapteijn, Maja; Hoogenboezem, Wim; Heiliegers, Laura; de Bolster, Danny; Medema, Gertjan

    2016-07-01

    The emergence of clinical enterococcal isolates that are resistant to both ampicillin and vancomycin is a cause of great concern, as therapeutic alternatives for the treatment of infections caused by such organisms are becoming limited. Aquatic environments could play a role in the dissemination of antibiotic resistant enterococci. This study investigated the presence of ampicillin and vancomycin resistant enterococci in the treated effluent of six wastewater treatment plants (WWTPs) and in surface water used as a source for drinking water production in the Netherlands. Membrane filtration in combination with selective media with ampicillin or vancomycin was applied to determine the presence of ampicillin resistant Enterococcus (ARE) and vancomycin resistant Enterococcus (VRE) species. Ampicillin resistant Enterococcus faecium (minimal inhibitory concentration (MIC) >16μg/mL; n=1033) was observed in all studied WWTP effluents. In surface water used for drinking water production (intake locations), no ARE or VRE were observed. At both types of location, intrinsic vancomycin resistant Pediococcus spp., Leuconostoc spp. and Lactobacillus spp. were isolated with the vancomycin medium. The ampicillin resistant E. faecium (AREfm) isolates (n=113) did not contain the vanA or vanB gene, but MIC testing for vancomycin showed intermediate vancomycin resistance (2-8μgmL(-1)) to occur in these AREfm strains. This study documents the discharge of ampicillin resistant E. faecium strains with intermediate vancomycin resistance by the WWTPs into the surface water, but no presence of these strains downstream at intake locations for drinking water production. Copyright © 2016 Elsevier GmbH. All rights reserved.

  5. Vancomycin-Resistance Enterococci Infections in the Department of the Defense: Annual Report 2013

    DTIC Science & Technology

    2014-08-01

    str.r.:lioos, S€’ £l "r:’hi fl!’:: lil<i~lin ,:l ddc ~o.r-c.;s, !]:l:ho:>r rr:, aY. nflinttlirir~ :he !::f;, ·nod c ol ’ HO: Io ~:·rnhlir’U ;;· ;d ro...16. Morris JG, et al. Enterococci resistant to multiple antimicrobial agents, including vancomycin: establishment of endemicity in a university

  6. [Microbiological and epidemiological characteristics of vancomycin-dependent enterococci].

    PubMed

    Hwang, Keumrock; Sung, Heungsup; Namgoong, Seung; Yoon, Nam Surp; Kim, Mi-Na

    2009-08-01

    Vancomycin-dependent enterococci (VDE) are clinically equivalent to vancomycin-resistant enterococci (VRE), but more difficult to detect. This study was purposed to characterize VDE microbiologically and epidemiologically. The patients from whom VDE were detected from April 2007 to March 2008 were investigated. For available isolates, minimal inhibitory concentrations (MICs) of and the levels of dependence on vancomycin and teicoplanin were measured by E test (AB Biodisk, Sweden), and a test for reversion of VDE to non-dependent VRE (NDVRE) and pulsed field gel electrophoresis (PFGE) were performed. Patients' demographic and clinical findings were reviewed via electronic medical records. VDE were recovered from 6 (2.2%) of 272 patients carrying VRE during this study period. All patients were already colonized or infected by VRE and treated with vancomycin for 13 to 107 days. VDE were isolated from pleural fluid (one), urine (four), and stool (one). All isolates carried vanA with vancomycin MICs of >256 microg/mL, but two of them had intermediate susceptibilities to teicoplanin. Because 4 VDE isolates were reverted to NDVRE with single passage, vancomycin dependence was measurable for only two isolates as equal and above 0.064 and 0.5 microg/mL respectively, and was reverted after 5 and 7 passages, respectively. Six VDE isolates showed no related clones in PFGE analysis, and 3 of 4 available pairs of initial VRE isolates and subsequent VDE isolates were identical clones. VDE were not rare and seemed to emerge independently from VRE with a prolonged use of vancomycin. Vancomycin-dependence was reverted within several passages.

  7. Discontinuation of reflex testing of stool samples for vancomycin-resistant enterococci resulted in increased prevalence.

    PubMed

    Bodily, Mandy; McMullen, Kathleen M; Russo, Anthony J; Kittur, Nupur D; Hoppe-Bauer, Joan; Warren, David K

    2013-08-01

    Discontinuation of reflex testing of stool submitted for Clostridium difficile testing for vancomycin-resistant enterococci (VRE) led to an increase in the number of patients with healthcare-associated VRE bacteremia and bacteriuria (0.21 vs 0.36 cases per 1,000 patient-days; P<.01). Cost-benefit analysis showed reflex screening and isolation of VRE reduced hospital costs.

  8. Infrequent occurrence of vancomycin-resistant enterococci in poultry from Malaysian wet markets.

    PubMed

    Ong, C H S; Asaad, M; Lim, K C; Ngeow, Y F

    2002-12-01

    Fifty samples of chicken, duck and geese faeces were obtained from 13 wet markets in Kuala Lumpur to study the prevalence of vancomycin-resistant enterococci (VRE) among local market poultry. Biotyping of colonies grown on azide agar incubated at 45 degrees C yielded E. pseudoavium, E. faecalis, E. faecium and E. gallinarum from chicken faeces and E. malodoratus, E. faecalis, E. faecium, E. gallinarum, E. hirae/dispar, and E. durans from goose and duck faeces. On agar containing 6 mg/ l of vancomycin, one strain of E. flavescens was identified, giving a VRE detection rate of 2.0%. This isolate had a vancomycin M.I.C. of 8 mg/l as determined by the Etest, and the van C-3 gene that was identified by PCR followed by sequence analysis. The prevalence of VRE among poultry sold in local markets appears to be low, and may reflect the infrequent use of antimicrobials in our poultry farms. Nevertheless, the possibility of human acquisition of microbes via the food chain cautions against the use of antimicrobials in animal husbandry that may encourage the emergence and spread of multi-drug resistant organisms like the VRE among animal microbial flora.

  9. Vancomycin resistant enterococci (VRE) in Swedish sewage sludge.

    PubMed

    Sahlström, Leena; Rehbinder, Verena; Albihn, Ann; Aspan, Anna; Bengtsson, Björn

    2009-05-29

    Antimicrobial resistance is a serious threat in veterinary medicine and human healthcare. Resistance genes can spread from animals, through the food-chain, and back to humans. Sewage sludge may act as the link back from humans to animals. The main aims of this study were to investigate the occurrence of vancomycin resistant enterococci (VRE) in treated sewage sludge, in a Swedish waste water treatment plant (WWTP), and to compare VRE isolates from sewage sludge with isolates from humans and chickens. During a four month long study, sewage sludge was collected weekly and cultured for VRE. The VRE isolates from sewage sludge were analysed and compared to each other and to human and chicken VRE isolates by biochemical typing (PhenePlate), PFGE and antibiograms. Biochemical typing (PhenePlate-FS) and pulsed field gel electrophoresis (PFGE) revealed prevalence of specific VRE strains in sewage sludge for up to 16 weeks. No connection was found between the VRE strains isolated from sludge, chickens and humans, indicating that human VRE did not originate from Swedish chicken. This study demonstrated widespread occurrence of VRE in sewage sludge in the studied WWTP. This implies a risk of antimicrobial resistance being spread to new farms and to the society via the environment if the sewage sludge is used on arable land.

  10. Effect of Surotomycin, a Novel Cyclic Lipopeptide Antibiotic, on Intestinal Colonization with Vancomycin-Resistant Enterococci and Klebsiella pneumoniae in Mice

    PubMed Central

    Deshpande, Abhishek; Hurless, Kelly; Cadnum, Jennifer L.; Chesnel, Laurent; Gao, Lihong; Chan, Luisa; Kundrapu, Sirisha; Polinkovsky, Alexander

    2016-01-01

    Surotomycin (formerly called CB-183,315) is a novel, orally administered cyclic lipopeptide antibacterial in development for the treatment of Clostridium difficile infection (CDI) that has potent activity against vancomycin-resistant enterococci (VRE) but limited activity against Gram-negative bacilli, including Bacteroides spp. We used a mouse model to investigate the impact of surotomycin exposure on the microbiome, and to test the consequences of the disruption on colonization by vancomycin-resistant enterococci (VRE) and extended-spectrum β-lactamase-producing Klebsiella pneumoniae (ESBL-KP), in comparison with the effects of oral vancomycin and metronidazole. Mice (8 per group) received saline, vancomycin, metronidazole, or surotomycin through an orogastric tube daily for 5 days and were challenged with 105 CFU of VRE or ESBL-KP administered through an orogastric tube on day 2 of treatment. The concentrations of the pathogens in stool were determined during and after treatment by plating on selective media. A second experiment was conducted to determine if the antibiotics would inhibit established VRE colonization. In comparison to controls, oral vancomycin promoted VRE and ESBL-KP overgrowth in stool (8 log10 to 10 log10 CFU/g; P < 0.001), whereas metronidazole did not (<4 log10 CFU/g; P > 0.5). Surotomycin promoted ESBL-KP overgrowth (>8 log10 CFU/g; P, <0.001 for comparison with saline controls) but not VRE overgrowth. Surotomycin suppressed preexisting VRE colonization, whereas metronidazole and vancomycin did not. These results suggest that treatment of CDI with surotomycin could reduce levels of VRE acquisition and overgrowth from those with agents such as vancomycin and metronidazole. However, surotomycin and vancomycin may promote colonization by antibiotic-resistant Gram-negative bacilli. PMID:26976870

  11. Vancomycin resistant enterococci in urine cultures: Antibiotic susceptibility trends over a decade at a tertiary hospital in the United Kingdom.

    PubMed

    Toner, Liam; Papa, Nathan; Aliyu, Sani H; Dev, Harveer; Lawrentschuk, Nathan; Al-Hayek, Samih

    2016-03-01

    Enterococci are a common cause of urinary tract infection and vancomycin-resistant strains are more difficult to treat. The purpose of this surveillance program was to assess the prevalence of and determine the risk factors for vancomycin resistance in adults among urinary isolates of Enterococcus sp. and to detail the antibiotic susceptibility profile, which can be used to guide empirical treatment. From 2005 to 2014 we retrospectively reviewed 5,528 positive Enterococcus sp. urine cultures recorded in a computerized laboratory results database at a tertiary teaching hospital in Cambridge, United Kingdom. Of these cultures, 542 (9.8%) were vancomycin resistant. No longitudinal trend was observed in the proportion of vancomycin-resistant strains over the course of the study. We observed emerging resistance to nitrofurantoin with rates climbing from near zero to 40%. Ampicillin resistance fluctuated between 50% and 90%. Low resistance was observed for linezolid and quinupristin/dalfopristin. Female sex and inpatient status were identified as risk factors for vancomycin resistance. The incidence of vancomycin resistance among urinary isolates was stable over the last decade. Although resistance to nitrofurantoin has increased, it still serves as an appropriate first choice in uncomplicated urinary tract infection caused by vancomycin-resistant Enterococcus sp.

  12. Contamination of the Clinical Microbiology Laboratory with Vancomycin-Resistant Enterococci and Multidrug- Resistant Enterobacteriaceae: Implications for Hospital and Laboratory Workers

    PubMed Central

    Collins, Susan M.; Hacek, Donna M.; Degen, Lisa A.; Wright, Marc O.; Noskin, Gary A.; Peterson, Lance R.

    2001-01-01

    We surveyed environmental surfaces in our clinical microbiology laboratory to determine the prevalence of vancomycin-resistant enterococci (VRE) and multidrug-resistant Enterobacteriaceae (MDRE) during a routine working day. From a total of 193 surfaces, VRE were present on 20 (10%) and MDRE were present on 4 (2%) of the surfaces tested. In a subsequent survey after routine cleaning, all of the 24 prior positive surfaces were found to be negative. Thus, those in the laboratory should recognize that many surfaces may be contaminated by resistant organisms during routine processing of patient specimens. PMID:11574615

  13. Vancomycin tolerance in enterococci.

    PubMed

    Saribas, Suat; Bagdatli, Yasar

    2004-11-01

    Tolerance can be defined as the ability of bacteria to grow in the presence of high concentrations of bactericide antimicrobics, so that the killing action of the drug is avoided but the minimal inhibitory concentration (MIC) remains the same. We investigated vancomycin tolerance in the Enterococcus faecium and Enterococcus faecalis strains isolated from different clinical specimens. Vancomycin was obtained from Sigma Chemical Co. We studied 100 enterococci strains. Fifty-six and 44 of Enterococcus strains were idendified as E. feacalis and E. faecium, respectively. To determine MICs and minimal bactericidal concentration (MBC), we inoculated strains from an overnight agar culture to Muller-Hinton broth and incubated them for 4-6 h at 37 degrees C with shaking to obtain a logarithmic phase culture. The inoculum was controlled by performing a colony count for each test. We determined MBC values and MBC/MIC ratios to study tolerance to vancomycin. Vancomycin tolerance was defined as a high MBC value and an MBC/MIC ratio > or =32. Fifty-six and 44 of the Enterococcus strains were identified as E. faecium and E. faecalis, respectively. Thirty-one E. faecium and 48 E. faecalis were found to be susceptible to vancomycin and these susceptible strains were included in this study. The MICs of susceptible strains ranged from < or =1 to 4 mg/l, the MBCs were > or =512 mg/l. Tolerance was detected in all E. faecalis and E. faecium strains. The standard E. faecalis 21913 strain also exhibited tolerance according to the high MBC value and the MBC/MIC ratio. We defined the tolerant strains as having no bactericidal effect and MBC/MIC > or =32. We found that a 100% tolerance was present in susceptible strains. One of the hypotheses for tolerance is that tolerant cells fail to mobilize or create the autolysins needed for enlargement and division. Our data suggests that tolerance may compromise glycopeptide therapy of serious enterococci infections. To add an aminoglycoside to the

  14. Genetic characteristics and molecular epidemiology of vancomycin-resistant Enterococci isolates from Caribbean countries

    PubMed Central

    Jayaratne, Padman; Wilson, Clyde; Golding, George R.; Nicholson, Alison M.; Lewis, Delores B.; Hermelijn, Sandra M.

    2017-01-01

    Emergence of vancomycin-resistant Enterococci (VRE) that first appeared on the stage about three decades ago is now a major concern worldwide as it has globally reached every continent. Our aim was to simply undertake a multinational study to delineate the resistance and virulence genes of clinical isolates of VRE isolates from the Caribbean. We employed both conventional (standard microbiological methods including use of E-test strips, chromogenic agar) and molecular methods (polymerase chain reactions–PCR, pulsed-field gel electrophoresis–PFGE and multilocus sequence typing–MLST) to analyze and characterize 245 Enterococci species and 77 VRE isolates from twelve hospitals from eight countries in the Caribbean. The PCR confirmed and demonstrated the resistance and virulence genes (vanA and esp) among all confirmed VRE isolates. The PFGE delineated clonally related isolates from patients from the same country and other countries in the region. The main sequence types of the VRE isolates from the region included STs 412, 750, 203, 736 and 18, all from the common ancestor for clonal complex 17 (CC17). Despite this common ancestor and association of outbreaks of this lineage clones, there has been no reports of outbreaks of infection by VRE in several hospitals in the Caribbean. PMID:29020115

  15. A Comparison of Environmental Contamination by Patients Infected or Colonized with Methicillin-Resistant Staphylococcus aureus or Vancomycin-Resistant Enterococci: A Multicenter Study

    PubMed Central

    Knelson, Lauren P.; Williams, David A.; Gergen, Maria F.; Rutala, William A.; Weber, David J.; Sexton, Daniel J.; Anderson, Deverick J.

    2014-01-01

    A total of 1,023 environmental surfaces were sampled from 45 rooms with patients infected or colonized with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE) before terminal room cleaning. Colonized patients had higher median total target colony-forming units (CFU) of MRSA or VRE than did infected patients (median, 25 CFU [interquartile range, 0–106 CFU] vs 0 CFU [interquartile range, 0–29 CFU]; P = .033). PMID:24915217

  16. Enterococcus in surface waters from the Des Moines River (Iowa) watershed: location, persistence and vancomycin resistance.

    PubMed

    Larsen, Bryan; Essmann, Michael K; Geletta, Simon; Duff, Barbara

    2012-01-01

    The object of this study was to quantify vancomycin-resistant enterococci in surface water from Central Iowa obtained from April 2007 to August 2007. Water from established sampling sites in four watersheds was plated on bile-esculin agar. Presumptively identified enterococci were categorized as "above the level of concern" if the sample contained ≥ 107 CFU per 100 ml. Confirmation of isolates as enterococci was based on growth at elevated temperature in high salt and on Enterococcus agar. Isolates that grew on 6 μg/ml vancomycin agar were deemed resistant. PCR analysis of resistant strains characterized vancomycin resistance genes. 77.2% of surface water samples from Central Iowa contained enterococci. Among enterococcal isolates, 10.4% grew on media containing 6 μg/ml vancomycin. PCR analysis of resistance genes showed a preponderance of VanC2/C3 in the area studied and VanB was not detected. Vancomycin-resistant Enterococcus is present in Central Iowa surface waters but resistance rarely involved VanA genotypes. Nevertheless, the potential for community-acquired infections remains a risk.

  17. Nisin, alone and combined with peptidoglycan-modulating antibiotics: activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci.

    PubMed

    Brumfitt, W; Salton, M R J; Hamilton-Miller, J M T

    2002-11-01

    We have sought ways to circumvent resistance, by combining nisin with other antibiotics known to target bacterial cell wall biosynthesis. Twenty strains each of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) were tested in vitro by standardized methods against nisin alone and combined with bacitracin, ramoplanin and chloramphenicol. Ramoplanin was the most potent compound, and bacitracin had the least activity. Two-way synergy was observed with nisin and ramoplanin. However, chloramphenicol was clearly antagonistic to the activity of nisin. Observations of synergy between nisin and ramoplanin against MRSA and VRE offer a promising approach to the concept of combining nisin with inhibitors of cell wall peptidoglycan. Further investigations are needed in order to develop this approach as a clinical possibility.

  18. Recovery of vancomycin-resistant enterococci on fingertips and environmental surfaces.

    PubMed

    Noskin, G A; Stosor, V; Cooper, I; Peterson, L R

    1995-10-01

    To determine the recovery of vancomycin-resistant enterococci (VRE) on fingertips, gloved fingertips, and environmental surfaces commonly encountered in the healthcare setting, and to examine the importance of handwashing on the removal of these organisms. Two clinical isolates of VRE (Enterococcus faecalis and Enterococcus faecium) were inoculated onto the hands of healthy human volunteers and the following environmental surfaces: countertops, bedrails, telephones, and stethoscopes. Following inoculation, samples were obtained at various time intervals to determine rates of recovery of organisms. To evaluate the effects of handwashing on enterococcal recovery, two different soap preparations were tested. Hands were washed with water alone or with one of the soaps and water. The soap and water studies were performed with a 5-second and a 30-second wash. Both enterococcal strains survived for at least 60 minutes on gloved and ungloved fingertips. The E faecalis was recoverable from countertops for 5 days; the E faecium persisted for 7 days. For bedrails, both enterococcal species survived for 24 hours without significant reduction in colony counts. The bacteria persisted for 60 minutes on the telephone handpiece and for 30 minutes on the diaphragmatic surface of the stethoscope. A 5-second wash with water alone resulted in virtually no change in recovery of enterococci; a 30-second wash with water plus either soap was necessary to eradicate the bacteria from hands completely. VRE are capable of prolonged survival on hands, gloves, and environmental surfaces. Hands should be washed thoroughly and gloves removed following contact with patients infected or colonized with these multidrug-resistant bacteria. Finally, environmental surfaces may serve as potential reservoirs for nosocomial transmission of VRE and need to be considered when formulating institutional infection control policies.

  19. Characterization of fecal vancomycin-resistant enterococci with acquired and intrinsic resistance mechanisms in wild animals, Spain.

    PubMed

    Lozano, Carmen; Gonzalez-Barrio, David; Camacho, Maria Cruz; Lima-Barbero, Jose Francisco; de la Puente, Javier; Höfle, Ursula; Torres, Carmen

    2016-11-01

    The objectives were to evaluate the presence of vancomycin-resistant enterococci with acquired (VRE-a) and intrinsic (VRE-i) resistance mechanisms in fecal samples from different wild animals, and analyze their phenotypes and genotypes of antimicrobial resistance. A total of 348 cloacal/rectal samples from red-legged partridges (127), white storks (81), red kites (59), and wild boars (81) (June 2014/February 2015) were inoculated in Slanetz-Bartley agar supplemented with vancomycin (4 μg/mL). We investigated the susceptibility to 12 antimicrobials and the presence of 19 antimicrobial resistance and five virulence genes. In addition, we performed multilocus sequence typing, detection of IS16 and studied Tn1546 structure. One VRE-a isolate was identified in one wild boar. This isolate was identified as Enterococcus faecium, harbored vanA gene included into Tn1546 (truncated with IS1542/IS1216), and belonged to the new ST993. This isolate contained the erm(A), erm(B), tet(M), dfrG, and dfrK genes. Neither element IS16 nor the studied virulence genes were detected. Ninety-six VRE-i isolates were identified (89 Enterococcus gallinarum and seven Enterococcus casseliflavus), with the following prevalence: red kites (71.2 %), white storks (46.9 %), red-legged partridges (7.9 %), and wild boars (4.9 %). Most E. gallinarum isolates showed resistance to tetracycline (66.3 %) and/or erythromycin (46.1 %). High-level resistance to aminoglycosides was present among our VRE-i isolates: kanamycin (22.9 %), streptomycin (11.5 %), and gentamicin (9.4 %). In general, VRE-i isolates of red kites showed higher rates of resistance for non-glycopeptide agents than those of other animal species. The dissemination of acquired resistance mechanisms in natural environments could have implications in the global spread of resistance with public health implications.

  20. Molecular epidemiology of vancomycin resistant enterococci in a tertiary care hospital in Saudi Arabia.

    PubMed

    Somily, Ali M; Al-Mohizea, Maha M; Absar, Muhammed M; Fatani, Amal J; Ridha, Afaaf M; Al-Ahdal, Mohammed N; Senok, Abiola C; Al-Qahtani, Ahmed A

    2016-08-01

    Vancomycin-resistant enterococci (VRE) are a major cause of nosocomial infections with high mortality and morbidity. There is limited data on the molecular characterization of VRE in Saudi Arabia. This study was carried out to investigate the premise that a shift in VRE epidemiology is occurring in our setting. Enterococcus species identification and susceptibility testing plus VRE phenotypic confirmation by vancomycin and teicoplanin E-test were carried out. Vancomycin resistance genes were detected by PCR. Strain typing was conducted using PFGE. Among the strains of Enterococcus spp. investigated in this study, 17 (4.5%) were VRE. With the exception of one isolate from rectal swab, all others were clinical specimens with blood being the commonest source (n = 11; 64.7%), followed by urine (n = 3; 17.6%). The 17 VRE isolates were Enterococcus faecium (n/N = 13/17) and Enterococcus gallinarum (n/N = 4/17). Among E. faecium isolates, vanA(+)/vanB(+) (n/N = 8/13; 62%) exhibiting VanB phenotype were predominant. One of the five vanA(+)E. faecium isolates exhibited a VanB phenotype indicative of vanA genotype-VanB phenotype incongruence. E. gallinarum isolates exhibited a Van C phenotype although two were vanA(+)/vanC1(+). PFGE revealed a polyclonal distribution with eight pulsotypes. These findings indicate an evolving VRE epidemiology with vanA(+)/vanB(+) isolates and vanA genotype-VanB phenotype incongruence isolates, which were previously described as colonizers, are now causing clinical infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Wounds, Functional Disability, and Indwelling Devices Are Associated With Cocolonization by Methicillin-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococci in Southeast Michigan

    PubMed Central

    Wang, Linda; Zöllner, Sebastian; Foxman, Betsy; Mobley, Harry L. T.; Mody, Lona

    2011-01-01

    Background. Methicillin-resistant Staphylococcus aureus (MRSA) remains sensitive to vancomycin; when vancomycin-resistant S. aureus (VRSA) emerges, treatment becomes more complex. VRSA emergence is attributed to conjugative transfer of the vancomycin-resistance gene cluster from vancomycin-resistant enterococci (VRE) to MRSA. Because cocolonization with MRSA and VRE precedes VRSA development, this study investigates the epidemiology of cocolonization in skilled nursing facility (SNF) residents at high risk for MRSA or VRE colonization. Methods. A prospective observational study conducted at 15 SNFs in southeast Michigan. Overall, 178 residents (90 with indwelling urinary catheters and/or feeding tubes and 88 device-free) were cultured monthly for MRSA and VRE, and clinical data were recorded. Results. The incidence of MRSA/VRE cocolonization among residents with indwelling devices was 6.5 per 100 resident-months; 5.2 (95% confidence interval [CI]: 1.49–18.1) times that among those without devices. MRSA/VRE cocolonization in the device group occurred most frequently in wounds (4.1 per 100 resident-months). In a logistic regression analysis limited to residents with devices, functional disability (rate ratio [RR], 1.3; 95% CI: 1.1–1.4) and wound presence (RR, 3.4; 95% CI: 1.4–8.6) were independent risk factors of cocolonization. Conclusions. In a population of SNF residents, individuals with indwelling devices who also had functional disability or wounds were at greatest risk of MRSA/VRE cocolonization. These individuals should be routinely monitored for the presence of VRSA colonization. PMID:22080118

  2. The potential of vancomycin-resistant enterococci to persist in fermented and pasteurised meat products.

    PubMed

    Houben, J H

    2003-11-15

    Experiments with 148 isolates of vancomycin-resistant enterococci (VRE) were performed to assess their potential to persist and grow in fermented sausages and pasteurised meat products. All strains were meat isolates and Van-type A, except a single VanC1 strain. In total, 143 strains of Enterococcus faecium were involved. Eight selected strains were examined for their potential to grow at high salt and nitrite levels and at reduced pH. The same isolates were used in experiments with fermented sausages. All available strains were subjected to heating tests in meat suspensions with added curing ingredients. All but one of the eight tested isolates grew at pH 4.0 in tryptone soya broth (TSB). With the combination of 8% w/w NaCl, 400 ppm NaNO2 and 0.5% w/w glucose in the meat suspension, all isolates grew at 37 degrees C, whereas none grew at 7 degrees C even after 56 days. With the addition of 10% w/w NaCl, 200 ppm NaNO2 and 0.5% w/w glucose, still one E. faecium isolate grew at 37 degrees C, although very slowly. Overall, the strains tolerated high salt and nitrite concentrations and reduced pH very well, even beyond levels applied in the regular production of fermented and/or pasteurised meat products. The tested strains could be isolated after the fermentation and further ripening of "boerenmetworst" and "snijworst". Overall, their colony counts decreased on average about 1 log-unit over a period of 60 days after batter manufacture. All 148 isolates demonstrated a relatively weak thermal resistance compared to results for selected vancomycin-sensitive enterococci strains reported in the literature and to results collected under identical experimental conditions in this laboratory. None of the strains (log inoculation level about 5-6 ml(-1) for each isolate) could be cultured after heating at 70 degrees C for 10 min.

  3. Phenylthiazole Antibacterial Agents Targeting Cell Wall Synthesis Exhibit Potent Activity in Vitro and in Vivo against Vancomycin-Resistant Enterococci.

    PubMed

    Mohammad, Haroon; Younis, Waleed; Chen, Lu; Peters, Christine E; Pogliano, Joe; Pogliano, Kit; Cooper, Bruce; Zhang, Jianan; Mayhoub, Abdelrahman; Oldfield, Eric; Cushman, Mark; Seleem, Mohamed N

    2017-03-23

    The emergence of antibiotic-resistant bacterial species, such as vancomycin-resistant enterococci (VRE), necessitates the development of new antimicrobials. Here, we investigate the spectrum of antibacterial activity of three phenylthiazole-substituted aminoguanidines. These compounds possess potent activity against VRE, inhibiting growth of clinical isolates at concentrations as low as 0.5 μg/mL. The compounds exerted a rapid bactericidal effect, targeting cell wall synthesis. Transposon mutagenesis suggested three possible targets: YubA, YubB (undecaprenyl diphosphate phosphatase (UPPP)), and YubD. Both UPPP as well as undecaprenyl diphosphate synthase were inhibited by compound 1. YubA and YubD are annotated as transporters and may also be targets because 1 collapsed the proton motive force in membrane vesicles. Using Caenorhabditis elegans, we demonstrate that two compounds (1, 3, at 20 μg/mL) retain potent activity in vivo, significantly reducing the burden of VRE in infected worms. Taken altogether, the results indicate that compounds 1 and 3 warrant further investigation as novel antibacterial agents against drug-resistant enterococci.

  4. Occurrence of vancomycin-resistant and -susceptible Enterococcus spp. in reclaimed water used for spray irrigation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Carey, Stephanie Ann; Goldstein, Rachel E. Rosenberg; Gibbs, Shawn G.

    Reclaiming municipal wastewater for agricultural, environmental, and industrial purposes is increasing in the United States to combat dwindling freshwater supplies. However, there is a lack of data regarding the microbial quality of reclaimed water. In particular, no previous studies have evaluated the occurrence of vancomycin-resistant enterococci (VRE) in reclaimed water used at spray irrigation sites in the United States. To address this knowledge gap, we investigated the occurrence, concentration, and antimicrobial resistance patterns of VRE and vancomycin-susceptible enterococci at three U.S. spray irrigation sites that use reclaimed water. We collected 48 reclaimed water samples from one Mid-Atlantic and two Midwestmore » spray irrigation sites, as well as their respective wastewater treatment plants, in 2009 and 2010. Samples were analyzed for total enterococci and VRE using standard membrane filtration. Isolates were purified and then confirmed using biochemical tests and PCR. Antimicrobial susceptibility testing was conducted using the Sensititre® microbroth dilution system. Data were analyzed by two-sample proportion tests and one-way analysis of variance. We detected total enterococci and VRE in 71% (34/48) and 4% (2/48) of reclaimed water samples, respectively. Enterococcus faecalis was the most common species identified. At the Mid-Atlantic spray irrigation site, UV radiation decreased total enterococci to undetectable levels; however, subsequent storage in an open-air pond at this site resulted in increased concentrations of enterococci. E. faecalis isolates recovered from the Mid-Atlantic spray irrigation site expressed intrinsic resistance to quinupristin/dalfopristin; however, non-E. faecalis isolates expressed resistance to quinupristin/dalfopristin (52% of isolates), vancomycin (4%), tetracycline (13%), penicillin (4%) and ciprofloxacin (17%). Our findings show that VRE are present in low numbers in reclaimed water at point-of-use at the

  5. Elucidation of the active conformation of vancomycin dimers with antibacterial activity against vancomycin-resistant bacteria.

    PubMed

    Nakamura, Jun; Yamashiro, Hidenori; Hayashi, Sayaka; Yamamoto, Mami; Miura, Kenji; Xu, Shu; Doi, Takayuki; Maki, Hideki; Yoshida, Osamu; Arimoto, Hirokazu

    2012-10-01

    Covalently linked vancomycin dimers have attracted a great deal of attention among researchers because of their enhanced antibacterial activity against vancomycin-resistant strains. However, the lack of a clear insight into the mechanisms of action of these dimers hampers rational optimization of their antibacterial potency. Here, we describe the synthesis and antibacterial activity of novel vancomycin dimers with a constrained molecular conformation achieved by two tethers between vancomycin units. Conformational restriction is a useful strategy for studying the relationship between the molecular topology and biological activity of compounds. In this study, two vancomycin units were linked at three distinct positions of the glycopeptide (vancosamine residue (V), C terminus (C), and N terminus (N)) to form two types of novel vancomycin cyclic dimers. Active NC-VV-linked dimers with a stable conformation as indicated by molecular mechanics calculations selectively suppressed the peptidoglycan polymerization reaction of vancomycin-resistant Staphylococcus aureus in vitro. In addition, double-disk diffusion tests indicated that the antibacterial activity of these dimers against vancomycin-resistant enterococci might arise from the inhibition of enzymes responsible for peptidoglycan polymerization. These findings provide a new insight into the biological targets of vancomycin dimers and the conformational requirements for efficient antibacterial activity against vancomycin-resistant strains. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Iterative Chemical Engineering of Vancomycin Leads to Novel Vancomycin Analogs With a High in Vitro Therapeutic Index.

    PubMed

    Mishra, Nigam M; Stolarzewicz, Izabela; Cannaerts, David; Schuermans, Joris; Lavigne, Rob; Looz, Yannick; Landuyt, Bart; Schoofs, Liliane; Schols, Dominique; Paeshuyse, Jan; Hickenbotham, Peter; Clokie, Martha; Luyten, Walter; Van der Eycken, Erik V; Briers, Yves

    2018-01-01

    Vancomycin is a glycopeptide antibiotic that inhibits transpeptidation during cell wall synthesis by binding to the D-Ala-D-Ala termini of lipid II. For long, it has been used as a last resort antibiotic. However, since the emergence of the first vancomycin-resistant enterococci in 1987, vancomycin resistance has become widespread, especially in hospitals. We have synthesized and evaluated 110 vancomycin analogs modified at the C-terminal carboxyl group of the heptapeptide moiety with R 2 NHR 1 NH 2 substituents. Through iterative optimizations of the substituents, we identified vancomycin analogs that fully restore (or even exceed) the original inhibitory activity against vancomycin-resistant enterococci (VRE), vancomycin-intermediate (VISA) and vancomycin-resistant Staphylococcus aureus (VRSA) strains. The best analogs have improved growth inhibitory activity and in vitro therapeutic indices against a broad set of VRE and methicillin-resistant S. aureus (MRSA) isolates. They also exceed the activity of vancomycin against Clostridium difficile ribotypes. Vanc-39 and Vanc-42 have a low probability to provoke antibiotic resistance, and overcome different vancomycin resistance mechanisms (VanA, VanB, and VanC1).

  7. Characterization and risk factors of vancomycin-resistant Enterococci (VRE) among animal-affiliated workers in Malaysia.

    PubMed

    Getachew, Y; Hassan, L; Zakaria, Z; Zaid, C Z M; Yardi, A; Shukor, R A; Marawin, L T; Embong, F; Aziz, S A

    2012-11-01

    This study determined the risk factors and characteristics of vancomycin-resistant Enterococci (VRE) among individuals working with animals in Malaysia. Targeted cross-sectional studies accompanied with laboratory analysis for the identification and characterization of resistance and virulence genes and with genotype of VRE were performed. VRE were detected in 9·4% (95% CI: 6·46-13·12) of the sampled populations. Enterococcus faecium, Enterococcus faecalis and Enterococcus gallinarum were isolated, and vanA was detected in 70% of the isolates. Enterococcus faecalis with vanB was obtained from one foreign poultry worker. At least one virulence gene was detected in >50% of Ent. faecium and Ent. faecalis isolates. The esp and gelE genes were common among Ent. faecium (58·3%) and Ent. faecalis (78%), respectively. The VRE species showed diverse RAPD profiles with some clustering of strains based on the individual's background. However, the risk factors found to be significantly associated with the prevalence of VRE were age (OR: 5·39, 95% CI: 1·98-14·61) and previous hospitalization (OR: 4·06, 95% CI: 1·33-12·35). VRE species isolated from individuals in this study have high level of vancomycin resistance, were genetically diverse and possessed the virulence traits. Age of individuals and history of hospitalization rather than occupational background determined VRE colonization. This study provides comprehensive findings on the epidemiological and molecular features of VRE among healthy individuals working with animals. © 2012 The Authors Journal of Applied Microbiology © 2012 The Society for Applied Microbiology.

  8. [Vancomycin-resistant enterococcus--chronicle of a foretold problem].

    PubMed

    Bonten, Marc J M; Willems, Rob J

    2012-01-01

    There have recently been 12 outbreaks of infection caused by vancomycin-resistant enterococci (VRE) in Dutch hospitals. Although the first VRE outbreaks were reported almost 12 years ago, such outbreaks remained uncommon and the question is why they are occurring now. Based on molecular epidemiological studies we have learned that a subpopulation of Enterococcus faecium, resistant to amoxicillin but susceptible to vancomycin, has become highly endemic in Dutch hospitals in the past 12 years. Initial analyses suggest that several transposons containing vancomycin-resistance genes have been introduced into this population, followed by nosocomial spread. We recommend that hospitals without detected VRE outbreaks screen high-risk patients for the presence of VRE. If transmission has already occurred in many hospitals, it will be extremely difficult (and costly) to eradicate VRE.

  9. Comparative study of selective chromogenic (chromID VRE) and bile esculin agars for isolation and identification of vanB-containing vancomycin-resistant enterococci from feces and rectal swabs.

    PubMed

    Grabsch, E A; Ghaly-Derias, S; Gao, W; Howden, B P

    2008-12-01

    The new chromogenic agar chromID VRE (cIDVRE; bioMérieux) was compared with bile esculin agar (BD) containing 6 mg/liter vancomycin for the detection of colonization with vanB-containing vancomycin-resistant enterococci (VRE). At 48 h of incubation, the results obtained with both media were comparable. However, cIDVRE detected significantly more VRE at 24 h (39.3% versus 21.3%, P = 0.003), and its use may facilitate the timely implementation of infection control procedures.

  10. Optimal control of vancomycin-resistant enterococci using preventive care and treatment of infections.

    PubMed

    Lowden, Jonathan; Miller Neilan, Rachael; Yahdi, Mohammed

    2014-03-01

    The rising prevalence of vancomycin-resistant enterococci (VRE) is a major health problem in intensive care units (ICU) because of its association with increased mortality and high health care costs. We present a mathematical framework for determining cost-effective strategies for prevention and treatment of VRE in the ICU. A system of five ordinary differential equations describes the movement of ICU patients in and out of five VRE-related states. Two control variables representing the prevention and treatment of VRE are incorporated into the system. The basic reproductive number is derived and calculated for different levels of the two controls. An optimal control problem is formulated to minimize VRE-related deaths and costs associated with prevention and treatment controls over a finite time period. Numerical solutions illustrate optimal single and dual allocations of the controls for various cost values. Results show that preventive care has the greatest impact in reducing the basic reproductive number, while treatment of VRE infections has the most impact on reducing VRE-related deaths. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Accuracy of the VITEK 2 System To Detect Glycopeptide Resistance in Enterococci

    PubMed Central

    van den Braak, Nicole; Goessens, Wil; van Belkum, Alex; Verbrugh, Henri A.; Endtz, Hubert P.

    2001-01-01

    We evaluated the accuracy of the VITEK 2 fully automated system to detect and identify glycopeptide-resistant enterococci (GRE) compared to a reference agar dilution method. The sensitivity of vancomycin susceptibility testing with VITEK 2 for the detection of vanA, vanB, and vanC1 strains was 100%. The sensitivity of vancomycin susceptibility testing of vanC2 strains was 77%. The sensitivity of teicoplanin susceptibility testing of vanA strains was 90%. Of 80 vanC enterococci, 78 (98%) were correctly identified by VITEK 2 as Enterococcus gallinarum/Enterococcus casseliflavus. Since the identification and susceptibility data are produced within 3 and 8 h, respectively, VITEK 2 appears a fast and reliable method for detection of GRE in microbiology laboratories. PMID:11136798

  12. Use of daptomycin in the treatment of vancomycin-resistant enterococcal urinary tract infections: a short case series.

    PubMed

    Ramaswamy, Divya Pradeep; Amodio-Groton, Maria; Scholand, Stephen J

    2013-07-16

    Vancomycin-resistant enterococci are a leading cause of hospital-acquired urinary tract infection and a growing concern for the clinician. The aim of this study was to evaluate the effectiveness of daptomycin in the treatment of patients with vancomycin-resistant enterococcal urinary tract infection treated in our 200-bed community-based institution. Patients with confirmed symptomatic vancomycin-resistant enterococcal urinary tract infection identified by infectious disease consultation between January 1, 2007, and December 8, 2009, vancomycin-resistant enterococci-positive urine culture, and urinary symptoms and/or pyuria on urinalysis, and treated with daptomycin, were included in this case series. Daptomycin was generally administered at a planned dosage regimen of ≥ 5 mg/kg every 24 hours in patients with normal to moderately impaired kidney function or every 48 hours in patients with severe kidney disease. Microbiologic cure was defined as eradication of vancomycin-resistant enterococci in urine cultures taken after the completion of daptomycin treatment. Clinical cure was defined by symptom resolution, as assessed by the infectious disease clinician caring for the patient. Included in this case series are 10 patients who received daptomycin for confirmed vancomycin-resistant enterococcal urinary tract infection. Patients had a history of extensive hospital stays. Chart review revealed that all levels of kidney function (3, 2, 3, and 2 patients with kidney disease classified as normal, mild, moderate, and severe/kidney failure, respectively) were represented in the sample and that patients with (n = 5) or without (n = 5) previous urinary tract infection and with (n = 3) or without (n = 7) Foley catheters were included. Treatment with daptomycin achieved clinical cure and vancomycin-resistant enterococcal eradication in all cases in this series. Treatment with daptomycin was well tolerated and effective in all patients in this series, regardless of renal

  13. Chlorhexidine Induces VanA-Type Vancomycin Resistance Genes in Enterococci

    PubMed Central

    Bhardwaj, Pooja; Ziegler, Elizabeth

    2016-01-01

    Chlorhexidine is a bisbiguanide antiseptic used for infection control. Vancomycin-resistant E. faecium (VREfm) is among the leading causes of hospital-acquired infections. VREfm may be exposed to chlorhexidine at supra- and subinhibitory concentrations as a result of chlorhexidine bathing and chlorhexidine-impregnated central venous catheter use. We used RNA sequencing to investigate how VREfm responds to chlorhexidine gluconate exposure. Among the 35 genes upregulated ≥10-fold after 15 min of exposure to the MIC of chlorhexidine gluconate were those encoding VanA-type vancomycin resistance (vanHAX) and those associated with reduced daptomycin susceptibility (liaXYZ). We confirmed that vanA upregulation was not strain or species specific by querying other VanA-type VRE. VanB-type genes were not induced. The vanH promoter was found to be responsive to subinhibitory chlorhexidine gluconate in VREfm, as was production of the VanX protein. Using vanH reporter experiments with Bacillus subtilis and deletion analysis in VREfm, we found that this phenomenon is VanR dependent. Deletion of vanR did not result in increased chlorhexidine susceptibility, demonstrating that vanHAX induction is not protective against chlorhexidine. As expected, VanA-type VRE is more susceptible to ceftriaxone in the presence of sub-MIC chlorhexidine. Unexpectedly, VREfm is also more susceptible to vancomycin in the presence of subinhibitory chlorhexidine, suggesting that chlorhexidine-induced gene expression changes lead to additional alterations in cell wall synthesis. We conclude that chlorhexidine induces expression of VanA-type vancomycin resistance genes and genes associated with daptomycin nonsusceptibility. Overall, our results indicate that the impacts of subinhibitory chlorhexidine exposure on hospital-associated pathogens should be further investigated in laboratory studies. PMID:26810654

  14. In vitro activity of salicylamide derivatives against vancomycin-resistant enterococci.

    PubMed

    Pospisilova, Sarka; Michnova, Hana; Kauerova, Tereza; Pauk, Karel; Kollar, Peter; Vinsova, Jarmila; Imramovsky, Ales; Cizek, Alois; Jampilek, Josef

    2018-07-01

    A series of 13 salicylamide derivatives was assessed for antibacterial activity against three isolates of vancomycin-resistant Enterococcus faecalis (VRE) and Enterococcus faecalis ATCC 29212 as a quality standard. The minimum inhibitory concentration was determined by the broth microdilution method with subsequent subcultivation of aliquots to assess minimum bactericidal concentration. The growth kinetics was established by the time-kill assay. Ampicillin, ciprofloxacin, tetracycline and vancomycin were used as the reference antibacterial drugs. Three of the investigated compounds showed strong bacteriostatic activity against VRE (0.199-25 µM) comparable to or more potent than ampicillin and ciprofloxacin. In addition, these compounds were tested for synergistic effect with vancomycin, ciprofloxacin and tetracycline, while 5-chloro-2-hydroxy-N-[4-(trifluoromethyl)phenyl]benzamide showed the highest potency as well as synergistic activity with vancomycin against VRE 368. Screening of the cytotoxicity of the most effective compounds was performed using human monocytic leukemia THP-1 cells, and based on LD 50 values, it can be stated that the compounds have insignificant toxicity against human cells. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Faster and economical screening for vancomycin-resistant enterococci by sequential use of chromogenic agar and real-time polymerase chain reaction.

    PubMed

    Tan, Thean Yen; Jiang, Boran; Ng, Lily Siew Yong

    2017-08-01

    Screening for vancomycin-resistant enterococci (VRE) by culture takes days to generate results, while polymerase chain reaction (PCR) testing directly from clinical specimens lacks specificity. The aims of this study were to develop a real-time PCR to detect and identify Enterococcus faecium, Enterococcus faecalis, and vanA and vanB genes, and to evaluate the impact of this PCR on test-reporting times when performing it directly from suspect VRE isolates present on screening chromogenic media. The tetraplex PCR primers were designed to amplify E. faecium, E. faecalis, and vanA and vanB genes, with melt-curve analysis of PCR products. Following analytical and clinical validation of the molecular assay, PCR testing was performed for target colonies present on VRE chromogenic media. PCR results were evaluated against conventional phenotypic identification and susceptibility testing, with the time to result being monitored for both modalities. A total of 519 colonies from clinical specimens were tested concurrently by real-time PCR and phenotypic methods. In all, 223 isolates were identified with phenotypic vancomycin resistance (vanA, n = 108; vanB, n = 105; non-vanA/vanB = 10), with complete agreement between PCR and phenotypic testing for vancomycin-resistant E. faecium and E. faecalis. The majority (88.6%) of PCR results were reported, on average, 24.8 hours earlier than those of phenotypic testing, with 68% reduction in total costs. The use of culture on selective media, followed by direct colony PCR confirmation allows faster and economical VRE screening. Copyright © 2015. Published by Elsevier B.V.

  16. Amino acid substitutions in the VanS sensor of the VanA-type vancomycin-resistant Enterococcus strains result in high-level vancomycin resistance and low-level teicoplanin resistance.

    PubMed

    Hashimoto, Y; Tanimoto, K; Ozawa, Y; Murata, T; Ike, Y

    2000-04-15

    The vancomycin-resistant enterococci GV1, GV2 and GV3, which were isolated from droppings from broiler farms in Japan have been characterized as VanA-type VRE, which express high-level vancomycin resistance (256 or 512 microg ml(-1), MIC) and low-level teicoplanin resistance (1 or 2 microg ml(-1), MIC). The vancomycin resistances were encoded on plasmids. The vancomycin resistance conjugative plasmid pMG2 was isolated from the GV2 strain. The VanA determinant of pMG2 showed the same genetic organization as that of the VanA genes encoded on the representative transposon Tn1546, which comprises vanRSHAXYZ. The nucleotide sequences of all the genes, except the gene related to the vanS gene on Tn1546, were completely identical to the genes encoded on Tn1546. Three amino acid substitutions in the N-terminal region of the deduced VanS were detected in the nucleotide sequence of vanS encoded on pMG2. There were also three amino acid substitutions in the vanS gene of the GV1 and GV3 strains in the same positions as in the vanS gene of pMG2. Vancomycin induced the increased teicoplanin resistance in these strains.

  17. Surveillance for vancomycin-resistant enterococci: type, rates, costs, and implications.

    PubMed

    Shadel, Brooke N; Puzniak, Laura A; Gillespie, Kathleen N; Lawrence, Steven J; Kollef, Marin; Mundy, Linda M

    2006-10-01

    To evaluate 2 active surveillance strategies for detection of enteric vancomycin-resistant enterococci (VRE) in an intensive care unit (ICU). Thirty-month prospective observational study. ICU at a university-affiliated referral center. All patients with an ICU stay of 24 hours or more were eligible for the study. Clinical active surveillance (CAS), involving culture of a rectal swab specimen for detection of VRE, was performed on admission, weekly while the patient was in the ICU, and at discharge. Laboratory-based active surveillance (LAS), involving culture of a stool specimen for detection of VRE, was performed on stool samples submitted for Clostridium difficile toxin detection. Enteric colonization with VRE was detected in 309 (17%) of 1,872 patients. The CAS method initially detected 280 (91%) of the 309 patients colonized with VRE, compared with 25 patients (8%) detected by LAS; colonization in 4 patients (1%) was initially detected by analysis of other clinical specimens. Most patients with colonization (76%) would have gone undetected by LAS alone, whereas use of the CAS method exclusively would have missed only 3 patients (1%) who were colonized. CAS cost Dollars 1,913 per month, or Dollars 57,395 for the 30-month study period. Cost savings of CAS from preventing cases of VRE colonization and bacteremia were estimated to range from Dollars 56,258 to Dollars 303,334 per month. A patient-based CAS strategy for detection of enteric colonization with VRE was superior to LAS. In this high-risk setting, CAS appeared to be the most efficient and cost-effective surveillance method. The modest costs of CAS were offset by the averted costs associated with the prevention of VRE colonization and bacteremia.

  18. Dispersion of the Vancomycin Resistance Genes vanA and vanC of Enterococcus Isolated from Nile Tilapia on Retail Sale: A Public Health Hazard.

    PubMed

    Osman, Kamelia M; Ali, Mohamed N; Radwan, Ismail; ElHofy, Fatma; Abed, Ahmed H; Orabi, Ahmed; Fawzy, Nehal M

    2016-01-01

    Although normally regarded harmless commensals, enterococci may cause a range of different infections in humans, including urinary tract infections, sepsis, and endocarditis. The acquisition of vancomycin resistance by enterococci (VRE) has seriously affected the treatment and infection control of these organisms. VRE are frequently resistant to all antibiotics that are effective treatment for vancomycin-susceptible enterococci, which leaves clinicians treating VRE infections with limited therapeutic options. With VRE emerging as a global threat to public health, we aimed to isolate, identify enterococci species from tilapia and their resistance to van-mediated glycopeptide (vanA and vanC) as well as the presence of enterococcal surface protein (esp) using conventional and molecular methods. The cultural, biochemical (Vitek 2 system) and polymerase chain reaction results revealed eight Enterococcus isolates from the 80 fish samples (10%) to be further identified as E. faecalis (6/8, 75%) and E gallinarum (2/8, 25%). Intraperitoneal injection of healthy Nile tilapia with the eight Enterococcus isolates caused significant morbidity (70%) within 3 days and 100% mortality at 6 days post-injection with general signs of septicemia. All of the eight Enterococcus isolates were found to be resistant to tetracycline. The 6/6 E. faecalis isolates were susceptible for penicillin, nitrofurantoin, gentamicin, and streptomycin. On the other hand 5/6 were susceptible for ampicillin, vancomycin, chloramphenicol, and ciprofloxacin. The two isolates of E. gallinarum were sensitive to rifampicin and ciprofloxacin and resistant to vancomycin, chloramphenicol, and erythromycin. Molecular characterization proved that they all presented the prototypic vanC element. On the whole, one of the two vancomycin resistance gene was present in 3/8 of the enterococci isolates, while the esp virulence gene was present in 1/8 of the enterococci isolates. The results in this study emphasize the

  19. Detection of Methicillin-resistant Staphylococcus aureus and Vancomycin-resistant Enterococci by Healthcare Workers on Infection Control Gown and Gloves

    PubMed Central

    Snyder, Graham M.; Thom, Kerri A.; Furuno, Jon P.; Perencevich, Eli N.; Roghmann, Mary-Claire; Strauss, Sandra M.; Netzer, Giora; Harris, Anthony D.

    2008-01-01

    Objective To assess the frequency of detection and risk factors for detection of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) by healthcare workers on infection control protective gown and gloves. Design We observed interactions between healthcare workers and patients during routine clinical activities. Cultures were taken of healthcare workers’ hands prior to entering the room, disposable infection control gown and gloves after completing patient care activities, and of hands immediately following removal of infection control protective gown and gloves. Setting A 29-bed medical intensive care unit at an urban tertiary-care academic hospital, the University of Maryland Medical Center. Results Seventeen percent (24/137, 95%CI ± 6.4%) of healthcare workers caring for a patient with MRSA and/or VRE acquired that organism on their gloves, gown or both. Contacting an endotracheal tube or tracheostomy (P < 0.05), contacting the head and/or neck of a patient (P < 0.05), and the presence of a percutaneous endoscopic gastrostomy/jejunostomy tube (P < 0.05) were associated with increased risk of detection of antibiotic-resistant organisms. Conclusions Gloves and gowns are frequently contaminated with MRSA and VRE during routine care duties. Contact with the head or neck, care for an endotracheal tube or tracheostomy, and the presence of an endotracheal tube or tracheostomy may increase the risk of detection of antibiotic-resistant organisms. PMID:18549314

  20. Multidrug-resistant enterococci in animal meat and faeces and co-transfer of resistance from an Enterococcus durans to a human Enterococcus faecium.

    PubMed

    Vignaroli, Carla; Zandri, Giada; Aquilanti, Lucia; Pasquaroli, Sonia; Biavasco, Francesca

    2011-05-01

    Forty-eight isolates resistant to at least two antibiotics were selected from 53 antibiotic-resistant enterococci from chicken and pig meat and faeces and analysed for specific resistance determinants. Of the 48 multidrug-resistant (MDR) strains, 31 were resistant to two antibiotics (29 to erythromycin and tetracycline, 1 to erythromycin and vancomycin, 1 to vancomycin and tetracycline), 14 to three (erythromycin, tetracycline and vancomycin or ampicillin) and 3 to four (erythromycin, vancomycin, ampicillin and gentamicin). erm(B), tet(M), vanA and aac (6')-Ie aph (2'')-Ia were the antibiotic resistance genes most frequently detected. All 48 MDR enterococci were susceptible to linezolid and daptomycin. Enterococcus faecalis (16), Enterococcus faecium (8), Enterococcus mundtii (2) and Enterococcus gallinarum (1) were identified in meat, and E. faecium (13) and Enterococcus durans (13) in faeces. Clonal spread was not detected, suggesting a large role of gene transfer in the dissemination of antibiotic resistance. Conjugative transfer of resistance genes was more successful when donors were enterococcal strains isolated from faeces; co-transfer of vanA and erm(B) to a human E. faecium occurred from both E. faecium and E. durans pig faecal strains. These data show that multidrug resistance can be found in food and animal species other than E. faecium and E. faecalis, and that these species can efficiently transfer antibiotic resistance to human strains in inter-specific matings. In particular, the occurrence of MDR E. durans in the animal reservoir could have a role in the emergence of human enterococcal infections difficult to eradicate with antibiotics.

  1. High-level vancomycin resistant Enterococcus faecium related to humans and pigs found in dust from pig breeding facilities.

    PubMed

    Braga, Teresa M; Pomba, Constança; Lopes, M Fátima Silva

    2013-01-25

    Environmental dust from animal breeding facilities was never screened for the presence of enterococci, nor of vancomycin-resistant enterococci (VRE), despite the possibility of being a vehicle of transmission of strains and antibiotic resistance genes between food-producing animals and man. Bio-security measures in pig facilities include disinfection with biocides to avoid the dissemination of opportunistic pathogenic bacteria, namely enterococci and in particular VRE. We thus undertook collection of enterococci and VRE in a representative number of breeding pig facilities in Portugal (n=171) and analyzed their susceptibility to benzalkonium chloride (BC) and chlorhexidine (CHX). A prevalence of 15% of VRE was found, with 6% high-level resistance found, and MIC values for CHX and BC were similar to those commonly found among enterococcal isolates from related environments, 8 μg/ml and 4 μg/ml, respectively. Among the isolated high-level vancomycin resistant Enterococcus faecium carrying the vanA genotype, we found multilocus sequence types closely related to pig and human isolates from European countries and Brazil. These results strongly advise constant surveillance of this environment and its inclusion in future epidemiologic studies on VRE. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Controlling for endogeneity in attributable costs of vancomycin-resistant enterococci from a Canadian hospital.

    PubMed

    Lloyd-Smith, Patrick

    2017-12-01

    Decisions regarding the optimal provision of infection prevention and control resources depend on accurate estimates of the attributable costs of health care-associated infections. This is challenging given the skewed nature of health care cost data and the endogeneity of health care-associated infections. The objective of this study is to determine the hospital costs attributable to vancomycin-resistant enterococci (VRE) while accounting for endogeneity. This study builds on an attributable cost model conducted by a retrospective cohort study including 1,292 patients admitted to an urban hospital in Vancouver, Canada. Attributable hospital costs were estimated with multivariate generalized linear models (GLMs). To account for endogeneity, a control function approach was used. The analysis sample included 217 patients with health care-associated VRE. In the standard GLM, the costs attributable to VRE are $17,949 (SEM, $2,993). However, accounting for endogeneity, the attributable costs were estimated to range from $14,706 (SEM, $7,612) to $42,101 (SEM, $15,533). Across all model specifications, attributable costs are 76% higher on average when controlling for endogeneity. VRE was independently associated with increased hospital costs, and controlling for endogeneity lead to higher attributable cost estimates. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  3. Vancomycin-resistant enterococci with vanA gene in treated municipal wastewater and their association with human hospital strains.

    PubMed

    Oravcova, Veronika; Mihalcin, Matus; Zakova, Jana; Pospisilova, Lucie; Masarikova, Martina; Literak, Ivan

    2017-12-31

    Vancomycin-resistant enterococci (VRE) are pathogens of increasing medical importance. In Brno, Czech Republic, we collected 37 samples from the effluent of a wastewater treatment plant (WWTP), 21 surface swabs from hospital settings, and 59 fecal samples from hospitalized patients and staff. Moreover, we collected 284 gull cloacal swabs from the colony situated 35km downstream the WWTP. Samples were cultured selectively. Enterococci were identified using MALDI-TOF MS, phenotypically tested for susceptibility to antibiotics, and by PCR for occurrence of resistance and virulence genes. Pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) were used to examine genotypic diversity. VRE carrying the vanA gene were found in 32 (86%, n=37) wastewater samples, from which we obtained 49 isolates: Enterococcus faecium (44) and Enterococcus gallinarum (2), Enterococcus casseliflavus (2), and Enterococcus raffinosus (1). From 33 (69%) of 48 inpatient stool samples, we obtained 39 vanA-carrying VRE, which belonged to E. faecium (33 isolates), Enterococcus faecalis (4), and Enterococcus raffinosus (2). Nearly one-third of the samples from hospital surfaces contained VRE with the vanA gene. VRE were not detected among gulls. Sixty-seven (84%, n=80) E. faecium isolates carried virulence genes hyl and/or esp. Virulence of E. faecalis was encoded by gelE, asa1, and cylA genes. A majority of the E. faecium isolates belonged to the clinically important sequence types ST17 (WWTP: 10 isolates; hospital: 4 isolates), ST18 (9;8), and ST78 (5;0). The remaining isolates belonged to ST555 (2;0), ST262 (1;6), ST273 (3;0), ST275 (1;0), ST549 (2;0), ST19 (0;1), ST323 (3;0), and ST884 (7;17). Clinically important enterococci carrying the vanA gene were almost continually detectable in the effluent of the WWTP, indicating insufficient removal of VRE during wastewater treatment and permanent shedding of these antibiotic resistant pathogens into the environment from this

  4. Molecular characterization of vancomycin-resistant Enterococcus faecium isolates from Bermuda

    PubMed Central

    Akpaka, Patrick Eberechi; Kissoon, Shivnarine; Wilson, Clyde; Jayaratne, Padman; Smith, Ashley; Golding, George R.

    2017-01-01

    Molecular characteristics of vancomycin resistant enterococci isolates from Bermuda Island is currently unknown. This study was conducted to investigate phenotypic and genotypic characteristics of VRE isolates from Bermuda Island using the chromogenic agar, E-tests, polymerase chain reaction (PCR), pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Eighteen E. faecium isolates were completely analyzed and were all resistant to vancomycin, susceptible to linezolid and quinupristin/dalfopristin, positive for vanA and esp genes. The MLST analysis confirmed most isolates were of the sequence types linked to clonal complex 17 (CC17) that is widely associated with outbreaks in hospitals. Infection control measures, antibiotic stewardship, and surveillance activities will continue to be a priority in hospital on the Island. PMID:28267763

  5. Molecular characterization of vancomycin-resistant Enterococcus faecium isolates from Bermuda.

    PubMed

    Akpaka, Patrick Eberechi; Kissoon, Shivnarine; Wilson, Clyde; Jayaratne, Padman; Smith, Ashley; Golding, George R

    2017-01-01

    Molecular characteristics of vancomycin resistant enterococci isolates from Bermuda Island is currently unknown. This study was conducted to investigate phenotypic and genotypic characteristics of VRE isolates from Bermuda Island using the chromogenic agar, E-tests, polymerase chain reaction (PCR), pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Eighteen E. faecium isolates were completely analyzed and were all resistant to vancomycin, susceptible to linezolid and quinupristin/dalfopristin, positive for vanA and esp genes. The MLST analysis confirmed most isolates were of the sequence types linked to clonal complex 17 (CC17) that is widely associated with outbreaks in hospitals. Infection control measures, antibiotic stewardship, and surveillance activities will continue to be a priority in hospital on the Island.

  6. Validation of VITEK 2 Version 4.01 Software for Detection, Identification, and Classification of Glycopeptide-Resistant Enterococci

    PubMed Central

    Abele-Horn, Marianne; Hommers, Leif; Trabold, René; Frosch, Matthias

    2006-01-01

    We evaluated the ability of the new VITEK 2 version 4.01 software to identify and detect glycopeptide-resistant enterococci compared to that of the reference broth microdilution method and to classify them into the vanA, vanB, vanC1, and vanC2 genotypes. Moreover, the accuracy of antimicrobial susceptibility testing with agents with improved potencies against glycopeptide-resistant enterococci was determined. A total of 121 enterococci were investigated. The new VITEK 2 software was able to identify 114 (94.2%) enterococcal strains correctly to the species level and to classify 119 (98.3%) enterococci correctly to the glycopeptide resistance genotype level. One Enterococcus casseliflavus strain and six Enterococcus faecium vanA strains with low-level resistance to vancomycin were identified with low discrimination, requiring additional tests. One of the vanA strains was misclassified as the vanB type, and one glycopeptide-susceptible E. facium wild type was misclassified as the vanA type. The overall essential agreements for antimicrobial susceptibility testing results were 94.2% for vancomycin, 95.9% for teicoplanin, 100% for quinupristin-dalfopristin and moxifloxacin, and 97.5% for linezolid. The rates of minor errors were 9% for teicoplanin and 5% for the other antibiotic agents. The identification and susceptibility data were produced within 4 h to 6 h 30 min and 8 h 15 min to 12 h 15 min. In conclusion, use of VITEK 2 version 4.01 software appears to be a reliable method for the identification and detection of glycopeptide-resistant enterococci as well as an improvement over the use of the former VITEK 2 database. However, a significant reduction in the detection time would be desirable. PMID:16390951

  7. Isolation and Biochemical Fingerprinting of Vancomycin-Resistant Enterococcus faecium From Meat, Chicken and Cheese.

    PubMed

    Talebi, Malihe; Sadeghi, Javad; Rahimi, Fateh; Pourshafie, Mohammad Reza

    2015-04-01

    Vancomycin-resistant enterococci (VRE) are important nosocomial pathogens and food chain has been considered as an assumed source for dissemination of VRE to human. The presence of VRE isolates from food samples and typing of these isolates with Phene plate, a biochemical fingerprinting method, were investigated. Thirty samples of meat, chicken and cheese were analyzed for VRE during 2010. Antibiotic susceptibility tests and minimum inhibitory concentration (MIC) were also examined. VRE isolates were typed with the Phene plate system (PhPlate), a biochemical fingerprinting method. A total of 70 VRE isolates were obtained and identified as Enterococcus faecium by species-specific PCR. All the isolates carried vanA, while none of them harbored vanB. The VRE isolates included 35, 27, and 8 isolates from meat, chicken and cheese, respectively. Typing with the PhPlate revealed a diversity index of 0.78 for E. faecium, containing 10 common and four single types. The results of antibiotic susceptibility and MIC tests showed an increased resistance to ciprofloxacin, erythromycin, ampicillin and gentamicin, to which, 100%, 100%, 100%, and 95% of VRE isolates were resistant, respectively. Only 5% of the isolates were resistant to chloramphenicol and the MIC of the isolates for vancomycin and teicoplanin was ≥ 256 µg/mL and for gentamicin-resistant isolates it was 1024 µg/mL. Conventional and molecular identification tests exhibited that all the isolates were E. faecium carrying vanA. None of the isolates harbored vanB. The results showed that enterococci are common contaminants in food. Indeed, this study indicates a high prevalence of multidrug-resistant enterococci in food of animal origin in Iran. Isolating some persisting enterococcal isolates revealed that continuous surveillance of antimicrobial resistance in enterococci from food is essential.

  8. Antimicrobial resistance and virulence genes in enterococci from wild game meat in Spain.

    PubMed

    Guerrero-Ramos, Emilia; Cordero, Jorge; Molina-González, Diana; Poeta, Patrícia; Igrejas, Gilberto; Alonso-Calleja, Carlos; Capita, Rosa

    2016-02-01

    A total of 55 enterococci (45 Enterococcus faecium, 7 Enterococcus faecalis, and three Enterococcus durans) isolated from the meat of wild game animals (roe deer, boar, rabbit, pheasant, and pigeon) in North-Western Spain were tested for susceptibility to 14 antimicrobials by the disc diffusion method. All strains showed a multi-resistant phenotype (resistance to between three and 10 antimicrobials). The strains exhibited high percentages of resistance to erythromycin (89.1%), tetracycline (67.3%), ciprofloxacin (92.7%), nitrofurantoin (67.3%), and quinupristin-dalfopristin (81.8%). The lowest values (9.1%) were observed for high-level resistance to gentamicin, kanamycin, and streptomycin. The average number of resistances per strain was 5.8 for E. faecium isolates, 7.9 for E. faecalis, and 5.7 for E. durans. Genes encoding antimicrobial resistance and virulence were studied by polymerase chain reaction. A total of 15 (57.7%) of the 26 vancomycin-resistant isolates harboured the vanA gene. Other resistance genes detected included vanB, erm(B) and/or erm(C), tet(L) and/or tet(M), acc(6')-aph(2″), and aph(3')-IIIa in strains resistant to vancomycin, erythromycin, tetracycline, gentamicin, and kanamycin, respectively. Specific genes of the Tn5397 transposon were detected in 54.8% of the tet(M)-positive enterococci. Nine virulence factors (gelE, agg, ace, cpd, frs, esp, hyl, efaAfs and efaAfm) were studied. All virulence genes, with the exception of the frs gene, were found to be present in the enterococcal isolates. At least one virulence gene was detected in 20.0% of E. faecium, 71.4% of E. faecalis and 33.3% of E. durans isolates, with ace and cpd being the most frequently detected genes (6 isolates each). This suggests that wild game meat might play a role in the spreading through the food chain of enterococci with antimicrobial resistance and virulence determinants to humans. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Reengineering Antibiotics to Combat Bacterial Resistance: Click Chemistry [1,2,3]-Triazole Vancomycin Dimers with Potent Activity against MRSA and VRE.

    PubMed

    Silverman, Steven M; Moses, John E; Sharpless, K Barry

    2017-01-01

    Vancomycin has long been considered a drug of last resort. Its efficiency in treating multiple drug-resistant bacterial infections, particularly methicillin-resistant Staphylococcus aureus (MRSA), has had a profound effect on the treatment of life-threatening infections. However, the emergence of resistance to vancomycin is a cause for significant worldwide concern, prompting the urgent development of new effective treatments for antibiotic resistant bacterial infections. Harnessing the benefits of multivalency and cooperativity against vancomycin-resistant strains, we report a Click Chemistry approach towards reengineered vancomycin derivatives and the synthesis of a number of dimers with increased potency against MRSA and vancomycin resistant Enterococci (VRE; VanB). These semi-synthetic dimeric ligands were linked together with great efficiency using the powerful CuAAC reaction, demonstrating high levels of selectivity and purity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Survey of Virulence Determinants among Vancomycin Resistant Enterococcus faecalis and Enterococcus faecium Isolated from Clinical Specimens of Hospitalized Patients of North west of Iran

    PubMed Central

    Sharifi, Yaeghob; Hasani, Alka; Ghotaslou, Reza; Varshochi, Mojtaba; Hasani, Akbar; Aghazadeh, Mohammad; Milani, Morteza

    2012-01-01

    Recent data indicates an increasing rate of vancomycin resistance in clinical enterococcal isolates worldwide. The nosocomial enterococci are likely to harbor virulence elements that increase their ability to colonize hospitalized patients. The aim of this study was to characterize virulence determinants in vancomycin-resistant enterococci (VRE) obtained from various clinical sources. During the years 2008 to 2010, a total of 48 VRE isolates were obtained from three University teaching hospitals in Northwest, Iran. Initially, phenotypic speciation was done and minimum inhibitory concentrations (MICs) of vancomycin were determined by agar dilution method and E-test. Then, species identification and resistance genotypes along with detection of virulence genes (asa1, esp, gelE, ace and cpd) of the isolates were performed by multiplex PCR. Thirty eight isolates were identified as vancomycin-resistant Enterococcus faecium (VREfm) and ten as E. faecalis (VREfs). Irrespective of the species, vanA gene (89.58%) was dominant and three phenotypically vancomycin susceptible E. faecium isolates carried the vanB gene. Among virulence genes investigated, the esp was found in 27(71%) VREfm strains, but did not in any VREfs. Other virulence determinants were highly detected in VREfs strains. Our data indicate a high prevalence of E. faecium harboring vancomycin resistance with vanA genotype and the two VRE species displayed different virulence genes. PMID:22582098

  11. Performance of the EUCAST Disk Diffusion Method, the CLSI Agar Screen Method, and the Vitek 2 Automated Antimicrobial Susceptibility Testing System for Detection of Clinical Isolates of Enterococci with Low- and Medium-Level VanB-Type Vancomycin Resistance: a Multicenter Study

    PubMed Central

    Giske, Christian G.; Haldorsen, Bjørg; Matuschek, Erika; Schønning, Kristian; Leegaard, Truls M.; Kahlmeter, Gunnar

    2014-01-01

    Different antimicrobial susceptibility testing methods to detect low-level vancomycin resistance in enterococci were evaluated in a Scandinavian multicenter study (n = 28). A phenotypically and genotypically well-characterized diverse collection of Enterococcus faecalis (n = 12) and Enterococcus faecium (n = 18) strains with and without nonsusceptibility to vancomycin was examined blindly in Danish (n = 5), Norwegian (n = 13), and Swedish (n = 10) laboratories using the EUCAST disk diffusion method (n = 28) and the CLSI agar screen (n = 18) or the Vitek 2 system (bioMérieux) (n = 5). The EUCAST disk diffusion method (very major error [VME] rate, 7.0%; sensitivity, 0.93; major error [ME] rate, 2.4%; specificity, 0.98) and CLSI agar screen (VME rate, 6.6%; sensitivity, 0.93; ME rate, 5.6%; specificity, 0.94) performed significantly better (P = 0.02) than the Vitek 2 system (VME rate, 13%; sensitivity, 0.87; ME rate, 0%; specificity, 1). The performance of the EUCAST disk diffusion method was challenged by differences in vancomycin inhibition zone sizes as well as the experience of the personnel in interpreting fuzzy zone edges as an indication of vancomycin resistance. Laboratories using Oxoid agar (P < 0.0001) or Merck Mueller-Hinton (MH) agar (P = 0.027) for the disk diffusion assay performed significantly better than did laboratories using BBL MH II medium. Laboratories using Difco brain heart infusion (BHI) agar for the CLSI agar screen performed significantly better (P = 0.017) than did those using Oxoid BHI agar. In conclusion, both the EUCAST disk diffusion and CLSI agar screening methods performed acceptably (sensitivity, 0.93; specificity, 0.94 to 0.98) in the detection of VanB-type vancomycin-resistant enterococci with low-level resistance. Importantly, use of the CLSI agar screen requires careful monitoring of the vancomycin concentration in the plates. Moreover, disk diffusion methodology requires that personnel be trained in interpreting zone edges

  12. High-level aminoglycoside resistance and virulence characteristics among Enterococci isolated from recreational beaches in Malaysia.

    PubMed

    Dada, Ayokunle Christopher; Ahmad, Asmat; Usup, Gires; Heng, Lee Yook; Hamid, Rahimi

    2013-09-01

    We report the first study on the occurrence of high-level aminoglycoside-resistant (HLAR) Enterococci in coastal bathing waters and beach sand in Malaysia. None of the encountered isolates were resistant to high levels of gentamicin (500 μg/mL). However, high-level resistance to kanamycin (2,000 μg/mL) was observed in 14.2 % of tested isolates, the highest proportions observed being among beach sand isolates. High-level resistance to kanamycin was higher among Enterococcus faecalis and Enterococcus faecium than Enterococcus spp. Chi-square analysis showed no significant association between responses to tested antibiotics and the species allocation or source of isolation of all tested Enterococci. The species classification of encountered Enterococci resistance to vancomycin was highest among Enterococcus spp. (5.89 %) followed by E. faecium (4.785) and least among E. faecalis. A total of 160 isolates were also tested for virulence characteristics. On the whole, caseinase production was profoundly highest (15.01 %) while the least prevalent virulence characteristic observed among tested beach Enterococci was haemolysis of rabbit blood (3.65 %). A strong association was observed between the source of isolation and responses for each of caseinase (C = 0.47, V = 0.53) and slime (C = 0.50, V = 0.58) assays. Analysis of obtained spearman's coefficient showed a strong correlation between caseinase and each of the slime production (p = 0.04), gelatinase (p = 0.0035) and haemolytic activity on horse blood (p = 0.004), respectively. Suggestively, these are the main virulent characteristics of the studied beach Enterococci. Our findings suggest that recreational beaches may contribute to the dissemination of Enterococci with HLAR and virulence characteristics.

  13. Performance Characteristics of the Cepheid Xpert vanA Assay for Rapid Identification of Patients at High Risk for Carriage of Vancomycin-Resistant Enterococci

    PubMed Central

    Gilhuley, Kathleen; Cianciminio-Bordelon, Diane; Tang, Yi-Wei

    2012-01-01

    We compared the performance characteristics of culture and the Cepheid Xpert vanA assay for routine surveillance of vancomycin-resistant enterococci (VRE) from rectal swabs in patients at high risk for VRE carriage. The Cepheid Xpert vanA assay had a limit of detection of 100 CFU/ml and correctly detected 101 well-characterized clinical VRE isolates with no cross-reactivity in 27 non-VRE and related culture isolates. The clinical sensitivity, specificity, positive predictive value, and negative predictive value of the Xpert vanA PCR assay were 100%, 96.9%, 91.3%, and 100%, respectively, when tested on 300 consecutively collected rectal swabs. This assay provides excellent predictive values for prompt identification of VRE-colonized patients in hospitals with relatively high rates of VRE carriage. PMID:22972822

  14. Is the mazEF toxin-antitoxin system responsible for vancomycin resistance in clinical isolates of Enterococcus faecalis?

    PubMed

    Sadeghifard, Nourkhoda; Soheili, Sara; Sekawi, Zamberi; Ghafourian, Sobhan

    2014-01-01

    The current study was conducted to investigate the relationship between vancomycin-resistant Enterococcus faecalis (VRE) and the presence of mazEF toxin-antitoxin (TA) system, which may be useful as target for novel antimicrobial therapy concepts. The susceptibility of E. faecalis was determined by MIC, and the presence of the mazEF TA system was evaluated by PCR. Among 200 E. faecalis isolates 39.5% showed resistance to vancomycin (VRE), while 60.5% were susceptible strains (VSE). The mazEF TA system was positive in all VRE isolates (100%), but less prevalent (38/121, 31.4%) among the 121 VSE strains. In conclusion, our study demonstrated a positive relationship between the presence of vancomycin resistance and mazEF TA system. This observation may introduce therapeutic options against a novel antimicrobial target in enterococci.

  15. Is the mazEF toxin-antitoxin system responsible for vancomycin resistance in clinical isolates of Enterococcus faecalis?

    PubMed Central

    Sadeghifard, Nourkhoda; Soheili, Sara; Sekawi, Zamberi; Ghafourian, Sobhan

    2014-01-01

    The current study was conducted to investigate the relationship between vancomycin-resistant Enterococcus faecalis (VRE) and the presence of mazEF toxin-antitoxin (TA) system, which may be useful as target for novel antimicrobial therapy concepts. The susceptibility of E. faecalis was determined by MIC, and the presence of the mazEF TA system was evaluated by PCR. Among 200 E. faecalis isolates 39.5% showed resistance to vancomycin (VRE), while 60.5% were susceptible strains (VSE). The mazEF TA system was positive in all VRE isolates (100%), but less prevalent (38/121, 31.4%) among the 121 VSE strains. In conclusion, our study demonstrated a positive relationship between the presence of vancomycin resistance and mazEF TA system. This observation may introduce therapeutic options against a novel antimicrobial target in enterococci. PMID:24653969

  16. Results of Four-Year Rectal Vancomycin-Resistant Enterococci Surveillance in a Pediatric Hematology-Oncology Ward: From Colonization to Infection.

    PubMed

    Aktürk, Hacer; Sütçü, Murat; Somer, Ayper; Karaman, Serap; Acar, Manolya; Ünüvar, Ayşegül; Anak, Sema; Karakaş, Zeynep; Özdemir, Aslı; Sarsar, Kutay; Aydın, Derya; Salman, Nuran

    2016-09-05

    To investigate the clinical impact of vancomycin-resistant enterococci (VRE) colonization in patients with hematologic malignancies and associated risk factors. Patients colonized and infected with VRE were identified from an institutional surveillance database between January 2010 and December 2013. A retrospective case-control study was performed to identify the risk factors associated with development of VRE infection in VRE-colonized patients. Fecal VRE colonization was documented in 72 of 229 children (31.4%). Seven VRE-colonized patients developed subsequent systemic VRE infection (9.7%). Types of VRE infections included bacteremia (n=5), urinary tract infection (n=1), and meningitis (n=1). Enterococcus faecium was isolated in all VRE infections. Multivariate analysis revealed severe neutropenia and previous bacteremia with another pathogen as independent risk factors for VRE infection development in colonized patients [odds ratio (OR): 35.4, confidence interval (CI): 1.7-72.3, p=0.02 and OR: 20.6, CI: 1.3-48.6, p=0.03, respectively]. No deaths attributable to VRE occurred. VRE colonization has important consequences in pediatric cancer patients.

  17. Proactive infection control measures to prevent nosocomial transmission of vancomycin-resistant enterococci in Hong Kong.

    PubMed

    Cheng, Vincent Chi-Chung; Tai, Josepha Wai-Ming; Chen, Jonathan Hon-Kwan; So, Simon Yung-Chun; Ng, Wing-Chun; Hung, Ivan Fan-Ngan; Leung, Sally Sau-Man; Wong, Sally Cheuk-Ying; Chan, Tuen-Ching; Chan, Felix Hon-Wai; Ho, Pak-Leung; Yuen, Kwok-Yung

    2014-10-01

    The study describes a proactive infection control approach to prevent nosocomial transmission of vancomycin-resistant enterococci (VRE) and tests if this approach is effective for controlling multiple-drug resistant organisms in a nonendemic setting. In response to the increasing prevalence of VRE in Hong Kong since 2011, we adopted a multifaceted assertive approach in our health care network. This included active surveillance culture, extensive contact tracing, directly observed hand hygiene in conscious patients before they received meals and medications, stringent hand hygiene and environmental cleanliness, and an immediate feedback antimicrobial stewardship program. We report the occurrence of VRE outbreaks in our hospital after institution of these measures and compared with the concurrent occurrence in other public hospitals in Hong Kong. Between July 1, 2011 and November 13, 2013, VRE was identified in 0.32% (50/15,851) of admission episodes by active surveillance culture. The risk of VRE carriage was three times higher in patients with a history of hospitalization outside our hospital networks in the past 3 months (0.56% vs. 0.17%; p = 0.001) compared with those who were not. Extensive contact tracing involving 3277 patient episodes was performed in the investigation for the 25 VRE index patients upon whom implementation of contact precautions was delayed (more than 48 hours of hospitalization). One episode of VRE outbreak was identified in our hospital network, compared with the 77 VRE outbreaks reported in the other hospital networks (controls) without these proactive infection control measures. Our multifaceted assertive proactive infection control approach can minimize the nosocomial transmission and outbreak of VRE in a nonendemic area. Copyright © 2014. Published by Elsevier B.V.

  18. Application of DNA probes for rRNA and vanA genes to investigation of a nosocomial cluster of vancomycin-resistant enterococci.

    PubMed Central

    Woodford, N; Morrison, D; Johnson, A P; Briant, V; George, R C; Cookson, B

    1993-01-01

    DNA probes specific for genes encoding rRNA and the glycopeptide resistance gene vanA were used to investigate a cluster of vancomycin-resistant (MICs, > 512 mg/liter) Enterococcus faecalis and Enterococcus faecium isolated from separate patients in a renal unit in a London hospital. When digested with BamHI, 12 of 13 vancomycin-resistant E. faecalis isolates exhibited a common restriction fragment length polymorphism pattern of rRNA genes (ribotype). A vanA probe hybridized with chromosomal DNA in these 12 isolates. The other isolate of vancomycin-resistant E. faecalis had a different ribotype and the vanA gene was located on plasmid DNA. These data suggest that cross-infection with a single strain of vancomycin-resistant E. faecalis occurred in most instances. In contrast, 23 vancomycin-resistant E. faecium isolates showed greater heterogeneity, comprising 8 ribotypes, suggesting that multiple strains were present in the unit. Twenty-one of these 23 isolates harbored a 24-MDa plasmid which hybridized with the vanA probe, implying that interstrain dissemination of a vancomycin resistance plasmid may have occurred among E. faecium isolates in the renal unit. Images PMID:8096216

  19. Epidemiology of vancomycin-resistant enterococci in children with acute lymphoblastic leukemia at two referral centers in Tehran, Iran: a descriptive study.

    PubMed

    Nateghian, A; Robinson, J L; Arjmandi, K; Vosough, P; Karimi, A; Behzad, A; Navidnia, M

    2011-05-01

    Risk factors for colonization with vancomycin-resistant enterococci (VRE) vary by population and locale. The objective of this study was to determine the prevalence of and risk factors for VRE colonization in children with acute lymphoblastic leukemia (ALL) in Tehran. Stools were collected from children with ALL at the Ali Asghar Children's Hospital and the Mahak Pediatric Oncology Center between March 2007 and October 2008. Demographic features and potential risk factors for VRE colonization, including duration of ALL, presence of severe neutropenia in the preceding month, receipt of antibiotics in the preceding 3 months, concurrent medical problems, days of hospitalization, and the need for intensive care since the time of diagnosis of ALL, were recorded. VRE was identified from stools in 33 of 130 children with ALL (25%). No clear risk factors were identified for VRE colonization in the current study, but there was a trend towards an increased prevalence in children admitted to the intensive care unit since their ALL diagnosis (p=0.07). The VanA genotype was found in 28 of the 33 stools (85%), with all other enterococci being VanB. The prevalence of VRE colonization in children with ALL in Tehran is high. Modifiable risk factors have not been identified. The implementation of routine surveillance for colonization and an increased emphasis on adherence to standard infection control precautions may prevent spread. Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  20. Mechanisms of antibiotic resistance in enterococci

    PubMed Central

    Miller, William R; Munita, Jose M; Arias, Cesar A

    2015-01-01

    Multidrug-resistant (MDR) enterococci are important nosocomial pathogens and a growing clinical challenge. These organisms have developed resistance to virtually all antimicrobials currently used in clinical practice using a diverse number of genetic strategies. Due to this ability to recruit antibiotic resistance determinants, MDR enterococci display a wide repertoire of antibiotic resistance mechanisms including modification of drug targets, inactivation of therapeutic agents, overexpression of efflux pumps and a sophisticated cell envelope adaptive response that promotes survival in the human host and the nosocomial environment. MDR enterococci are well adapted to survive in the gastrointestinal tract and can become the dominant flora under antibiotic pressure, predisposing the severely ill and immunocompromised patient to invasive infections. A thorough understanding of the mechanisms underlying antibiotic resistance in enterococci is the first step for devising strategies to control the spread of these organisms and potentially establish novel therapeutic approaches. PMID:25199988

  1. Longitudinal Multicenter Analysis of Outcomes After Cessation of Control Measures for Vancomycin-Resistant Enterococci.

    PubMed

    Lemieux, Camille; Gardam, Michael; Evans, Gerald; John, Michael; Suh, Kathryn N; vanWalraven, Carl; Vicencio, Elisa; Coulby, Cameron; Roth, Virginia; Hota, Susy

    2017-01-01

    OBJECTIVE To assess clinically relevant outcomes after complete cessation of control measures for vancomycin-resistant enterococci (VRE). DESIGN Quasi-experimental ecological study over 3.5 years. METHODS All VRE screening and isolation practices at 4 large academic hospitals in Ontario, Canada, were stopped on July 1, 2012. In total, 618 anonymized abstracted charts of patients with VRE-positive clinical isolates identified between July 1, 2010, and December 31, 2013, were reviewed to determine whether the case was a true VRE infection, a VRE colonization or contaminant, or a true VRE bacteremia. All deaths within 30 days of the last VRE infection were also reviewed to determine whether the death was fully or partially attributable to VRE. All-cause mortality was evaluated over the study period. Generalized estimating equation methods were used to cluster outcome rates within hospitals, and negative binomial models were created for each outcome. RESULTS The incidence rate ratio (IRR) for VRE infections was 0.59 and the associated P value was .34. For VRE bacteremias, the IRR was 0.54 and P=.38; for all-cause mortality the IRR was 0.70 and P=.66; and for VRE attributable death, the IRR was 0.35 and P=.49. VRE control measures were not significantly associated with any of the outcomes. Rates of all outcomes appeared to increase during the 18-month period after cessation of VRE control measures, but none reached statistical significance. CONCLUSION Clinically significant VRE outcomes remain rare. Cessation of all control measures for VRE had no significant attributable adverse clinical impact. Infect Control Hosp Epidemiol 2016;1-7.

  2. Virulence traits and antibiotic resistance among enterococci isolated from dogs with periodontal disease.

    PubMed

    Oliveira, Manuela; Tavares, Marta; Gomes, Diana; Touret, Tiago; São Braz, Berta; Tavares, Luís; Semedo-Lemsaddek, Teresa

    2016-06-01

    Periodontal disease - PD - is one of the most widespread diseases in dogs, but the role of this odontogenic infection in the dissemination of pathogenic bacteria present in the oral mucosa to other animals or pet owners is understudied. Trying to unveil the putative pathogenicity of enterococci present in the gums of dogs diagnosed with PD, thirty-two animals were investigated during routine visits to a private veterinary clinic. Seventy-one enterococci were recovered and characterized regarding species, genomic variability, virulence traits, antimicrobial resistance and biofilm-forming ability. Isolates were mainly identified as Enterococcus faecalis, with the large majority (95%) being able to produce biofilm. Regarding antibiotic resistance, all dog-enterococci were susceptible to ampicillin, amoxicillin/clavulanate, gentamicin-120, imipenem and vancomycin; while distinct levels of resistance were observed for chloramphenicol (10%), erythromycin (20%), streptomycin-300 (35%) and tetracycline (95%). For virulence traits incidence levels of 35% were observed for β-hemolysis and 25% for cylA, 25% for gelatinase and 35% for gelE; 85% harbor efaAfs and ebpABC; while ace, agg and esp are present respectively in 50, 30 and 10% of the dog-enterococci; efaAfm and acm were detected in all the Enterococcus faecium. Overall, the widespread prevalence of PD in dogs, associated with the close contact between companion animals, other animals and humans, may act as source for the dissemination of opportunistic pathogenic bacteria. Hence, aforementioned data on virulence and resistance features, emphasizes the need for active surveillance measures, such as the diagnose of PD in companion animals during routine visits to the veterinary clinic. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Two-tier approach combining molecular and culture-based techniques for optimized detection of vancomycin-resistant enterococci.

    PubMed

    Both, Anna; Franke, Gefion C; Mirwald, Nadine; Lütgehetmann, Marc; Christner, Martin; Klupp, Eva-Maria; Belmar Campos, Cristina; Büttner, Henning; Aepfelbacher, Martin; Rohde, Holger

    2017-12-01

    Given constantly high or even rising incidences of both colonization and infection with vancomycin-resistant enterococci (VRE), timely and accurate identification of carriers in high-risk patient populations is of evident clinical importance. In this study, a two-tier approach consisting of PCR-based screening and cultural confirmation of positive results is compared to the conventional approach solely based on culture on selective media. The 2-tier strategy was highly consistent with the conventional approach, and was found to possess high sensitivity and specificity (93.1% and 100%, respectively). The introduction of the PCR-based combined VRE screening approach significantly (P<0.0001) reduced median overall time to result by 44.3hours. The effect was found to be most pronounced in VRE negative samples. Positive vanA PCR was highly consistent with culture (PPV: 92.0%, 95% CI: 72.5-98.6%, NPV: 99.6%, 95% CI: 98.9-99.6%), thus allowing for preliminary reporting of VRE detection. In contrast, a vanB positive PCR does not allow for preliminary reporting (PPV: 58.5%, 95% CI: 44.2-71.6%, NPV: 99.8%, 95% CI: 99.2-100%). The introduction of a molecular assay for rapid detection of VRE from rectal swabs combined with cultural confirmation proved to be reliable and time saving, especially in a setting of low VRE prevalence and predominance of vanA positive strains. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Vancomycin Resistance in Staphylococcus aureus


    PubMed Central

    McGuinness, Will A.; Malachowa, Natalia; DeLeo, Frank R.

    2017-01-01

    The evolution of Staphylococcus aureus during the modern antibiotic era has been delineated by distinct strain emergence events, many of which include acquisition of antibiotic resistance. The relative high burden of methicillin-resistant S. aureus (MRSA) in healthcare and community settings is a major concern worldwide. Vancomycin, a glycopeptide antibiotic that inhibits cell wall biosynthesis, remains a drug of choice for treatment of severe MRSA infections. S. aureus strains exhibiting increased resistance to vancomycin, known as vancomycin intermediate-resistant S. aureus (VISA) (MIC = 4-8 µg/mL), were discovered in the 1990s. The molecular basis of resistance in VISA is polygenic and involves stepwise mutations in genes encoding molecules predominantly involved in cell envelope biosynthesis. S. aureus isolates with complete resistance to vancomycin (MIC ≥ 16 µg/mL) are termed vancomycin-resistant S. aureus (VRSA)—they were first reported in the U.S. in 2002. Resistance in VRSA is conferred by the vanA gene and operon, which is present on a plasmid. Although treatment of VRSA infections is challenging, the total number of human VRSA infections to date is limited (14 in the U.S.). By comparison, the burden of VISA is relatively high and the molecular mechanisms of resistance are less well-defined. VISA are associated with persistent infections, vancomycin treatment failure, and poor clinical outcomes. Here, we review in brief progress made toward understanding the acquisition of antibiotic resistance in S. aureus, with an emphasis on the molecular mechanisms underlying vancomycin resistance. PMID:28656013

  5. Vancomycin Resistance in Staphylococcus aureus
.

    PubMed

    McGuinness, Will A; Malachowa, Natalia; DeLeo, Frank R

    2017-06-01

    The evolution of Staphylococcus aureus during the modern antibiotic era has been delineated by distinct strain emergence events, many of which include acquisition of antibiotic resistance. The relative high burden of methicillin-resistant S. aureus (MRSA) in healthcare and community settings is a major concern worldwide. Vancomycin, a glycopeptide antibiotic that inhibits cell wall biosynthesis, remains a drug of choice for treatment of severe MRSA infections. S. aureus strains exhibiting increased resistance to vancomycin, known as vancomycin intermediate-resistant S. aureus (VISA) (MIC = 4-8 µg/mL), were discovered in the 1990s. The molecular basis of resistance in VISA is polygenic and involves stepwise mutations in genes encoding molecules predominantly involved in cell envelope biosynthesis. S. aureus isolates with complete resistance to vancomycin (MIC ≥ 16 µg/mL) are termed vancomycin-resistant S. aureus (VRSA)-they were first reported in the U.S. in 2002. Resistance in VRSA is conferred by the vanA gene and operon, which is present on a plasmid. Although treatment of VRSA infections is challenging, the total number of human VRSA infections to date is limited (14 in the U.S.). By comparison, the burden of VISA is relatively high and the molecular mechanisms of resistance are less well-defined. VISA are associated with persistent infections, vancomycin treatment failure, and poor clinical outcomes. Here, we review in brief progress made toward understanding the acquisition of antibiotic resistance in S. aureus , with an emphasis on the molecular mechanisms underlying vancomycin resistance.

  6. Influence of low-level resistance to vancomycin on efficacy of teicoplanin and vancomycin for treatment of experimental endocarditis due to Enterococcus faecium.

    PubMed Central

    Fantin, B; Leclercq, R; Arthur, M; Duval, J; Carbon, C

    1991-01-01

    Emergence of vancomycin-resistant strains among enterococci raises a new clinical challenge. Rabbits with aortic endocarditis were infected with Enterococcus faecium BM4172, a clinical strain resistant to low levels of vancomycin (MIC, 16 micrograms/ml) and susceptible to teicoplanin (MIC, 1 micrograms/ml), and against its susceptible variant E. faecium BM4172S obtained in vitro by insertional mutagenesis (MICs, 2 and 0.5 micrograms/ml, respectively). Control animals retained 8 to 10.5 log10 CFU/g of vegetation. We evaluated in this model the efficacy of vancomycin (30 mg/kg of body weight; mean peak and trough serum levels, 27 and 5 micrograms/ml, respectively), teicoplanin (standard dose, 10 mg/kg; mean peak and trough levels, 23 and 9 micrograms/ml, respectively; and high dose, 20 mg/kg; mean peak and trough levels, 63 and 25 micrograms/ml, respectively), gentamicin (6 mg/kg; mean peak and trough levels, 8.6 and less than 0.1 micrograms/ml, respectively), alone or in combination, given every 12 h intramuscularly for 5 days. Teicoplanin standard dose was as active as vancomycin against both strains. Vancomycin was not effective against E. faecium BM4172 but was highly effective against E. faecium BM4172S (7.5 +/- 1.1 log10 CFU/g of vegetation versus 4.9 +/- 1.0 log10 CFU/g of vegetation for vancomycin against E. faecium BM4172 and E. faecium BM4172S, respectively; P = 0.0012). A high dose of teicoplanin was more effective than vancomycin against E. faecium BM4172 (4.4 +/- 1.8 log10 CFU/g of vegetation versus 7.5 +/- 1.1 log10 CFU/g of vegetation for teicoplanin high dose and vancomycin, respectively; P less than 0.05). Against E. faecium BM4172 glycopeptide-gentamicin combinations were the most effective regimens in vitro and in vivo (2.8 +/- 0.7 and 3.5 +/- 1.3 log10 CFU/g of vegetation for vancomycin plus gentamicin and teicoplanin standard dose plus gentamicin, respectively; P < 0.05 versus single-drug regimens). We concluded that high-dose teicoplanin or the

  7. Treatment of Vancomycin-Resistant Enterococcal Infections in the Immunocompromised Host: Quinupristin-Dalfopristin in Combination with Minocycline

    PubMed Central

    Raad, Issam; Hachem, Ray; Hanna, Hend; Girgawy, Essam; Rolston, Kenneth; Whimbey, Estella; Husni, Rola; Bodey, Gerald

    2001-01-01

    Between February 1994 and November 1998, 56 oncology patients infected with vancomycin-resistant enterococci (VRE) were treated with quinopristin-dalfopristin (Q-D) plus minocycline (MIN). Infections included bacteremia, urinary tract infection, pneumonia, and wound infection. The response rate was 68%, and the most frequent adverse event was arthralgia or myalgia (36%). Q-D–MIN is effective for VRE infection in cancer patients but is associated with a substantial frequency of arthralgia or myalgia. PMID:11600379

  8. Prevalence, outcome and risk factor associated with vancomycin-resistant Enterococcus faecalis and Enterococcus faecium at a Tertiary Care Hospital in Northern India.

    PubMed

    Tripathi, A; Shukla, S K; Singh, A; Prasad, K N

    2016-01-01

    To determine the prevalence, genotype, risk factors and mortality in patients having vancomycin-resistant Enterococcus faecalis (VR E. faecalis) and Enterococcus faecium (VR E. faecium) infection or colonisation. A total of 1488 clinical isolates of E. faecalis and E. faecium were tested for vancomycin resistance by phenotypic (disk diffusion, E-test and broth micro-dilution test) and genotypic polymerase chain reaction methods. Records of all 1488 patients who had E. faecalis or E. faecium infection or colonisation were reviewed for the identification of host, hospital and medication related risk factors associated with VR E. faecalis and VR E. faecium. Of 1488 isolates, 118 (7.9%) were vancomycin-resistant and their distributions were as follows: E. faecalis=72 (61%) and E. faecium=46 (39%). All 118 vancomycin-resistant isolates were vanA genotype (minimum inhibitory concentration [MIC] to vancomycin ≥64 μg/ml and MIC to teicoplanin≥32 μg/ml) and none of the isolates was vanB genotype. Multivariate logistic regression analysis identified ventilator support and hospital stay for ≥48 h as independent risk factors associated with VR E. faecalis and VR E. faecium infection or colonisation. Hospital stay≥48 h was the only independent risk factor for mortality in patients infected with vancomycin-resistant enterococci. Strategies to limit the nosocomial infection especially in patients on ventilator support can reduce VRE incidence and related mortality.

  9. Characterization of Vancomycin-Resistant Enterococcus faecalis and Enterococcus faecium Isolated from Fresh Produces and Human Fecal Samples.

    PubMed

    Kim, Min-Chan; Cha, Min-Hyeok; Ryu, Jae-Gee; Woo, Gun-Jo

    2017-04-01

    Increased enterococcal infections in hospitals and multidrug-resistant and vancomycin-resistant enterococci (VRE) isolated from humans, animals, and food sources raised public health concern on the presence of VRE in multiple sources. We performed a comparative analysis of the antimicrobial resistance and genetics of VRE isolates derived from fresh produce and human fecal samples. Of 389 Enterococcus isolates, 8 fecal and 3 produce isolates were resistant to vancomycin and teicoplanin; all harbored vanA gene. The VRE isolates showed multidrug-resistant properties. The isolates from fresh produce in this study showed to have the common shared characteristics with the isolates from humans by the results of antimicrobial resistance, multilocus sequence typing, and Tn 1546 transposon analysis. Therefore, VRE isolates from fresh produce are likely related to VRE derived from humans. The results suggested that VRE may contaminate vegetables through the environment, and the contaminated vegetables could then act as a vehicle for human infections. Ongoing nationwide surveillance of antibiotic resistance and the promotion of the proper use of antibiotics are necessary.

  10. [Vancomycin-resistant Staphylococcus aureus].

    PubMed

    Rodríguez, Carlos Andrés; Vesga, Omar

    2005-12-01

    The evolution and molecular mechanisms of vancomycin resistance in Staphylococcus aureus were reviewed. Case reports and research studies on biochemestry, electron microscopy and molecular biology of Staphylococcus aureus were selected from Medline database and summarized in the following review. After almost 40 years of successful treatment of S. aureus with vancomycin, several cases of clinical failures have been reported (since 1997). S. aureus strains have appeared with intermediate susceptibility (MIC 8-16 microg/ml), as well as strains with heterogeneous resistance (global MIC < or =4 microg/ml), but with subpopulations of intermediate susceptibility. In these cases, resistance is mediated by cell wall thickening with reduced cross linking. This traps the antibiotic before it reaches its major target, the murein monomers in the cell membrane. In 2002, a total vancomycin resistant strain (MIC > or =32 microg/ml) was reported with vanA genes from Enterococcus spp. These genes induce the change of D-Ala-D-Ala terminus for D-Ala-D-lactate in the cell wall precursors, leading to loss of affinity for glycopeptides. Vancomycin resistance in S. aureus has appeared; it is mediated by cell wall modifications that trap the antibiotic before it reaches its action site. In strains with total resistance, Enterococcus spp. genes have been acquired that lead to modification of the glycopeptide target.

  11. Rapid Identification of Vancomycin Resistant Enterococcus Faecalis Clinical Isolates using a Sugar Fermentation Method

    PubMed Central

    Raeisi, Javad; Saifi, Mahnaz; Pourshafie, Mohammad Reza; Habibi, Mehri; Mohajerani, Hamid Reza; Akbari, Neda

    2017-01-01

    Introduction Vancomycin Resistant Enterococci (VRE) can be found all over the world. Thus, rapid detection of the isolates could be of high importance in the treatment or prevention of the associated disease. Aim To measure the turanose fermentation in Enterococcus faecalis clinical isolates for rapid differentiation of VRE and Vancomycin-Susceptible E. faecalis (VSE) isolates. Materials and Methods Forty E. faecalis samples were isolated from 200 clinical samples in Tehran Medical Center, Iran, from October 2012 to December 2012. These isolates were detected according to the standard microbial and biochemical tests. Detection of VRE isolates was originally performed by disk diffusion using 1 μg vancomycin disk, followed by Polymerase Chain Reaction (PCR) amplification of the vanA gene. Finally, the turanose consumption in 1%, 0.7% and 0.5% dilutions was detected by a phenotypic method. Results Among the 40 E. faecalis isolates, 20 vancomycin-susceptible and 20 vancomycin-resistant E. faecalis were isolated according to the disk diffusion and PCR of the vanA gene. There was a considerable difference between VRE and VSE isolates in 0.7% dilution of turanose. However, there was no significant difference between VRE and VSE in 1% and 0.5% dilutions of turanose. Conclusion Since detection of VRE isolates is of high importance, especially in nosocomial infections, phenotypic methods may be highly useful for this purpose. In conclusion, our data indicate that VRE isolated from clinical samples could be distinguished from VSE isolates by turanose fermentation at dilution 0.7%. PMID:28511382

  12. Characterization of Tn1546 in vancomycin-resistant Enterococcus faecium isolated from canine urinary tract infections: evidence of gene exchange between human and animal enterococci.

    PubMed

    Simjee, S; White, D G; McDermott, P F; Wagner, D D; Zervos, M J; Donabedian, S M; English, L L; Hayes, J R; Walker, R D

    2002-12-01

    Thirty-five enterococcal isolates were recovered from dogs diagnosed with urinary tract infections at the Michigan State University Veterinary Teaching Hospital over a 2-year period (1996 to 1998). Isolated species included Enterococcus faecium (n = 13), Enterococcus faecalis (n = 7), Enterococcus gallinarum (n = 11), and Enterococcus casseliflavus (n = 4). Antimicrobial susceptibility testing revealed several different resistance phenotypes, with the majority of the enterococcal isolates exhibiting resistance to three or more antibiotics. One E. faecium isolate, CVM1869, displayed high-level resistance to vancomycin (MIC > 32 micro g/ml) and gentamicin (MIC > 2,048 micro g/ml). Molecular analysis of this isolate revealed the presence of Tn1546 (vanA), responsible for high-level vancomycin resistance, and Tn5281 carrying aac6'-aph2", conferring high-level aminoglycoside resistance. Pulsed-field gel electrophoresis analysis revealed that CVM1869 was a canine E. faecium clone that had acquired Tn1546, perhaps from a human vancomycin-resistant E. faecium. Transposons Tn5281 and Tn1546 were located on two different conjugative plasmids. Sequence analysis revealed that in Tn1546, ORF1 had an 889-bp deletion and an IS1216V insertion at the 5' end and an IS1251 insertion between vanS and vanH. To date, this particular form of Tn1546 has only been described in human clinical vancomycin-resistant enterococcus isolates unique to the United States. Additionally, this is the first report of a vancomycin-resistant E. faecium isolated from a companion animal in the United States.

  13. Survival of Enterococci and Staphylococci on Hospital Fabrics and Plastic

    PubMed Central

    Neely, Alice N.; Maley, Matthew P.

    2000-01-01

    The transfer of gram-positive bacteria, particularly multiresistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), among patients is a growing concern. One critical aspect of bacterial transfer is the ability of the microorganism to survive on various common hospital surfaces. The purpose of this study was to determine the survival of 22 gram-positive bacteria (vancomycin-sensitive and -resistant enterococci and methicillin-sensitive and -resistant staphylococci) on five common hospital materials: smooth 100% cotton (clothing), 100% cotton terry (towels), 60% cotton–40% polyester blend (scrub suits and lab coats), 100% polyester (privacy drapes), and 100% polypropylene plastic (splash aprons). Swatches were inoculated with 104 to 105 CFU of a microorganism, assayed daily by placing the swatches in nutritive media, and examining for growth after 48 h. All isolates survived for at least 1 day, and some survived for more than 90 days on the various materials. Smaller inocula (102) survived for shorter times but still generally for days. Antibiotic sensitivity had no consistent effect on survival. The long survival of these bacteria, including MRSA and VRE, on commonly used hospital fabrics, such as scrub suits, lab coats, and hospital privacy drapes, underscores the need for meticulous contact control procedures and careful disinfection to limit the spread of these bacteria. PMID:10655374

  14. Three surveillance strategies for vancomycin-resistant enterococci in hospitalized patients: detection of colonization efficiency and a cost-effectiveness model.

    PubMed

    Lee, Todd A; Hacek, Donna M; Stroupe, Kevin T; Collins, Susan M; Peterson, Lance R

    2005-01-01

    To evaluate the cost-effectiveness and detection sensitivity associated with three active surveillance strategies for the identification of patients harboring vancomycin-resistant enterococci (VRE) to determine which is the most medically and economically useful. Culture for VRE from 200 consecutive stool specimens submitted for Clostridium difficile culture. Following this, risk factors were assessed for patients whose culture yielded VRE, and a cost-effectiveness evaluation was performed using a decision analytic model with a probabilistic analysis. A 688-bed, tertiary-care facility in Chicago, Illinois, with approximately 39,000 annual admissions, 7,000 newborn deliveries, 56,000 emergency department visits, and 115,000 home care and 265,000 outpatient visits. All stool specimens submitted to the clinical microbiology laboratory for C. difficile culture from hospital inpatients. From 200 stool samples submitted for C. difficile testing, we identified 5 patients with VRE in non-high-risk areas not screened as part of our routine patient surveillance. Medical record review revealed that all 5 had been hospitalized within the prior 2 years. Three of 5 had a history of renal impairment. The strategy that would involve screening the greatest number of patients (all those with a history of hospital admission in the prior 2 years) resulted in highest screening cost per patient admitted (dollars 2.48), lower per patient admission costs (dollars 480), and the best survival rates. An expanded VRE surveillance program that encompassed all patients hospitalized within the prior 2 years was a cost-effective screening strategy compared with a more traditional one focused on high-risk units.

  15. Antibiotic resistance, virulence determinants and production of biogenic amines among enterococci from ovine, feline, canine, porcine and human milk

    PubMed Central

    2013-01-01

    Background Recent studies have shown that mammalian milk represents a continuous supply of commensal bacteria, including enterococci. The objectives of this study were to evaluate the presence of enterococci in milk of different species and to screen them for several genetic and phenotypic traits of clinical significance among enterococci. Results Samples were obtained from, at least, nine porcine, canine, ovine, feline and human healthy hosts. Enterococci could be isolated, at a concentration of 1.00 × 102 -1.16 × 103 CFU/ml, from all the porcine samples and, also from 85, 50, 25 and 25% of the human, canine, feline and ovine ones, respectively. They were identified as Enterococcus faecalis, Enterococcus faecium, Enterococcus hirae, Enterococcus casseliflavus and Enterococcus durans. Among the 120 initial enterococcal isolates, 36 were selected on the basis of their different PFGE profiles and further characterized. MLST analysis revealed a wide diversity of STs among the E. faecalis and E. faecium strains, including some frequently associated to hospital infections and novel STs. All the E. faecalis strains possessed some of the potential virulence determinants (cad, ccf, cob, cpd, efaAfs, agg2, gelE, cylA, espfs) assayed while the E. faecium ones only harboured the efaAfm gene. All the tested strains were susceptible to tigecycline, linezolid and vancomycin, and produced tyramine. Their susceptibility to the rest of the antimicrobials and their ability to produce other biogenic amines varied depending on the strain. Enterococci strains isolated from porcine samples showed the widest spectrum of antibiotic resistance. Conclusions Enterococci isolated from milk of different mammals showed a great genetic diversity. The wide distribution of virulence genes and/or antibiotic resistance among the E. faecalis and E. faecium isolates indicates that they can constitute a reservoir of such traits and a risk to animal and human health. PMID:24325647

  16. Emergence of vancomycin resistance in the genus Streptococcus: characterization of a vanB transferable determinant in Streptococcus bovis.

    PubMed Central

    Poyart, C; Pierre, C; Quesne, G; Pron, B; Berche, P; Trieu-Cuot, P

    1997-01-01

    Streptococcus bovis NEM760 was isolated from a stool swab collected on admission from a patient as surveillance for vancomycin-resistant enterococci. Strain NEM760 was identified as S. bovis by conventional biochemical methods and partial sequence analysis of its 16S rRNA. This strain was resistant to a low level of vancomycin (MIC, 64 micrograms/ml) but was susceptible to teicoplanin (MIC, 1 micrograms/ml), and vancomycin induced resistance to both glycopeptides. The presence of a vanB-related gene in NEM760 was demonstrated in a PCR assay which enabled specific amplification of a 635-hp internal segment of vanB. Sequence analysis of the corresponding PCR product revealed that it was highly homologous (96% identity) to the prototype vanB sequence of Enterococcus faecalis V583. The VanB resistance of determinant of S. bovis NEM760 was transferred by conjugation to E. faecalis and Enterococcus faecium at a similar frequency of 2 x 10(-5) per donor. SmaI-digested genomic DNAs of independently obtained transconjugants of E. faecalis and E. faecium were analyzed by pulsed-field gel electrophoresis and Southern hybridization with a vanB DNA probe. The electrophoretic and hybridization patterns obtained with all transconjugants of the same species were indistinguishable and revealed vanB-containing chromosomal insertions of approximately 100 kb. These results suggest that the genes mediating VanB-type resistance in S. bovis NEM760 are part of large transferable genetic elements. The results presented in the report demonstrate for the first time the role of streptococci in the dissemination of vancomycin resistance among gram-positive bacteria. PMID:8980749

  17. Molecular Epidemiology of Vancomycin-Resistant Enterococcus faecalis and Enterococcus faecium Isolated from Clinical Specimens in the Northwest of Iran.

    PubMed

    Jahansepas, Ali; Ahangarzadeh Rezaee, Mohammad; Hasani, Alka; Sharifi, Yaeghob; Rahnamaye Farzami, Marjan; Dolatyar, Alireza; Aghazadeh, Mohammad

    2018-04-30

    This study was conducted to investigate the phenotypic and genotypic characteristics of vancomycin-resistant Enterococcus faecalis and Enterococcus faecium. Antibiotic resistance and virulence genes in the aforementioned resistant isolates were studied using the epsilometer (E)-test and polymerase chain reaction (PCR). These isolates were subjected to typing by pulsed-field gel electrophoresis (PFGE). Thirty vancomycin-resistant enterococci (VRE; 18.75%) were isolated from a total of 160 various clinical specimens cultured for any bacterial growth. Of these, 11 (36.7%) isolates were identified as E. faecalis and 19 (63.3%) as E. faecium. Minimum inhibitory concentrations (MICs) of vancomycin, teicoplanin, and three alternative therapeutic options (linezolid, daptomycin, and quinupristin/dalfopristin) were determined using the E-test. Multiplex PCR was done for confirming species, identification of the resistant genotypes, and the detection of the virulence genes. Finally, the clonal relationship of all VRE strains was studied by PFGE. All VRE strains showed vancomycin MIC ≥256 μg/mL, and 27 (90%) isolates carried the vanA gene, whereas none of the isolates carried vanB. The most common resistance antibiotic pattern observed was toward rifampicin (n = 30 [100%]). Among all virulence genes studied, gelE (n = 28 [93.33%]) was found as the most prevalent virulent gene. VRE isolates exhibited 90%, 46.67%, 100%, and 66.67% resistance to teicoplanin, linezolid, quinupristin/dalfopristin, and daptomycin, respectively. Molecular typing demonstrated 16 PFGE types of VRE isolates (A-P). Although vanA was carried by most of the isolates, PFGE displayed small clonal dissemination among VR E. faecium and VR E. faecalis species.

  18. Cornmeal-induced resistance to ciprofloxacin and erythromycin in enterococci.

    PubMed

    Yu, Dao-Jin; Lai, Bao-Se; Li, Jian; Ma, Yu-Fang; Yang, Fan; Li, Zhou; Luo, Xiao-Qing; Chen, Xia; Huang, Yi-Fan

    2012-09-01

    To establish a model ecosystem to study the impact of cornmeal on the appearance and persistence of the erythromycin (ERY)- and ciprofloxacin (CIP)-resistant phenotypes in waterborne enterococci. After the model ecosystem was established, the system was divided into six dose groups, with the addition of 8, 4, 1, 0.25, 0.05, and 0 g L(-1) sterilized cornmeal. System mud samples were collected at 0, 1, 3, 7, 14, 30, 40, 61, and 130 d, and enterococci present in the mud samples were evaluated for their sensitivities to CIP and ERY. PCR was employed to detect genes such as gyrA and ermB. The gyrA gene was sequenced, and codons 83 and 87 were analyzed for mutations. (1) The addition of 0.05-8 g L(-1) cornmeal had an impact on CIP resistance. The higher the dose of cornmeal added, the larger the impact it generated. Furthermore, the earlier the emergence of CIP-resistant strains, the greater the incidence of drug resistance. The impact of cornmeal on resistance to ERY was less consistent, and the degree of the impact was not in proportion to the dose of cornmeal added. (2) There were no mutations at codons 83 and 87 in the gyrA genes from 102 strains isolated from the model ecosystem. The incidence of ermB-positive strains of ERY-resistant enterococci (28 strains) was 78.6%, and the incidence of ermB-positive strains of ERY-sensitive enterococci (16 strains) was 0%. (1) Adding different doses of cornmeal can facilitate resistance to CIP and ERY in waterborne enterococci. In this study, the degree of resistance was related to the cornmeal dose. (2) In the model ecosystem, enterococcal CIP resistance was not caused by a gyrA gene mutation; however, in the vast majority of cases, resistance to ERY was related to the ermB resistance gene. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Vancomycin resistant Enterococcus spp. from crows and their environment in metropolitan Washington State, USA: Is there a correlation between VRE positive crows and the environment?

    PubMed

    Roberts, Marilyn C; No, David B; Marzluff, John M; Delap, Jack H; Turner, Robert

    2016-10-15

    Vancomycin-resistant enterococci [VRE] have been isolated from municipal, hospital and agricultural wastewater, recreational beaches, wild animals, birds and food animals around the world. In this study, American crows (Corvus brachyrhynchos) from sewage treatment plants (WWTP), dairy farms, and a large roost in a restored wetland with corresponding environmental samples were cultured for VRE. A total of 245 samples [156 crows, 89 environmental] were collected and screened for acquired vanA, vanB and/or intrinsic vanC1 genes. Samples were enriched overnight in BHI supplemented with 20μg/mL aztreonam, 4μg/mL vancomycin and plated on m-Enterococcus agar media supplemented with 6μg/mL vancomycin. Selected colonies were grown on BHI media supplemented with 18μg/mL vancomycin. Of these, 24.5% of the crow and 55% the environmental/cow samples were VRE positive as defined by Enterococcus spp. able to grow on media supplemented with 18μg/mL vancomycin. A total of 122 VRE isolates, 43 crow and 79 environmental isolates were screened, identified to species level using 16S sequencing and further characterized. Four vanA E. faecium and multiple vanC1 E. gallinarum were identified from crows isolated from three sites. E. faecium vanA and E. gallinarum vanC1 along with other Enterococcus spp. carrying vanA, vanB, vanC1 were isolated from three environments. All enterococci were multidrug resistant. Crows were more likely to carry vanA E. faecium than either the cow feces or wetland waters/soils. Comparing E. gallinarum vanC1 from crows and their environment would be useful in determining whether crows share VRE strains with their environment. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Impact of an Environmental Cleaning Intervention on the Presence of Methicillin-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococci on Surfaces in Intensive Care Unit Rooms

    PubMed Central

    Goodman, Eric R.; Platt, Richard; Bass, Richard; Onderdonk, Andrew B.; Yokoe, Deborah S.; Huang, Susan S.

    2009-01-01

    OBJECTIVES To evaluate the adequacy of discharge room cleaning and the impact of a cleaning intervention on the presence of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) on environmental surfaces in intensive care unit (ICU) rooms. DESIGN Prospective environmental study. SETTING AND SAMPLE Convenience sample of ICU rooms in an academic hospital. METHODS AND INTERVENTION The intervention consisted of (1) a change from the use of pour bottles to bucket immersion for applying disinfectant to cleaning cloths, (2) an educational campaign, and (3) feedback regarding adequacy of discharge cleaning. Cleaning of 15 surfaces was evaluated by inspecting for removal of a preapplied mark, visible only with an ultraviolet lamp (“black light”). Six surfaces were cultured for MRSA or VRE contamination. Outcomes of mark removal and culture positivity were evaluated by χ2 testing and generalized linear mixed models, clustering by room. RESULTS The black-light mark was removed from 44% of surfaces at baseline, compared with 71% during the intervention (P <.001). The intervention increased the likelihood of removal of black-light marks after discharge cleaning (odds ratio, 4.4; P < .001), controlling for ICU type (medical vs surgical) and type of surface. The intervention reduced the likelihood of an environmental culture positive for MRSA or VRE (proportion of cultures positive, 45% at baseline vs 27% during the intervention; adjusted odds ratio, 0.4; P = .02). Broad, flat surfaces were more likely to be cleaned than were doorknobs and sink or toilet handles. CONCLUSIONS Increasing the volume of disinfectant applied to environmental surfaces, providing education for Environmental Services staff, and instituting feedback with a black-light marker improved cleaning and reduced the frequency of MRSA and VRE contamination. PMID:18624666

  1. Characterization of multidrug-resistant diabetic foot ulcer enterococci.

    PubMed

    Semedo-Lemsaddek, Teresa; Mottola, Carla; Alves-Barroco, Cynthia; Cavaco-Silva, Patrícia; Tavares, Luís; Oliveira, Manuela

    2016-02-01

    Diabetes mellitus is a highly prevalent chronic progressive disease with complications that include diabetic-foot ulcers. Enterococci isolated from diabetic-foot infections were identified, evaluated by macro-restriction analysis, and screened for virulence traits and antimicrobial resistance. All isolates were considered multidrug-resistant, cytolysin and gelatinase producers, and the majority also demonstrated the ability to produce biofilms. These results indicate the importance of enterococci in diabetic-foot infection development and persistence, especially regarding their biofilm-forming ability and resistance to clinically relevant antibiotics. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  2. Evaluation of a New System, VITEK 2, for Identification and Antimicrobial Susceptibility Testing of Enterococci

    PubMed Central

    Garcia-Garrote, Fernando; Cercenado, Emilia; Bouza, Emilio

    2000-01-01

    We evaluated the new automated VITEK 2 system (bioMérieux) for the identification and antimicrobial susceptibility testing of enterococci. The results obtained with the VITEK 2 system were compared to those obtained by reference methods: standard identification by the scheme of Facklam and Sahm [R. R. Facklam and D. F. Sahm, p. 308–314, in P. R. Murray et al., ed., Manual of Clinical Microbiology, 6th ed., 1995] and with the API 20 STREP system and, for antimicrobial susceptibility testing, broth microdilution and agar dilution methods by the procedures of the National Committee for Clinical Laboratory Standards. The presence of vanA and vanB genes was determined by PCR. A total of 150 clinical isolates were studied, corresponding to 60 Enterococcus faecalis, 55 Enterococcus faecium, 26 Enterococcus gallinarum, 5 Enterococcus avium, 2 Enterococcus durans, and 2 Enterococcus raffinosus isolates. Among those isolates, 131 (87%) were correctly identified to the species level with the VITEK 2 system. Approximately half of the misidentifications were for E. faecium with low-level resistance to vancomycin, identified as E. gallinarum or E. casseliflavus; however, a motility test solved the discrepancies and increased the agreement to 94%. Among the strains studied, 66% were vancomycin resistant (57 VanA, 16 VanB, and 26 VanC strains), 23% were ampicillin resistant (MICs, ≥16 μg/ml), 31% were high-level gentamicin resistant, and 45% were high-level streptomycin resistant. Percentages of agreement for susceptibility and resistance to ampicillin, vancomycin, and teicoplanin and for high-level gentamicin resistance and high-level streptomycin resistance were 93, 95, 97, 97, and 96%, respectively. The accuracy of identification and antimicrobial susceptibility testing of enterococci with the VITEK 2 system, together with the significant reduction in handling time, will have a positive impact on the work flow of the clinical microbiology laboratory. PMID:10834961

  3. Vancomycin-resistant gene identification from live bacteria on an integrated microfluidic system by using low temperature lysis and loop-mediated isothermal amplification

    PubMed Central

    Chang, Wen-Hsin; Yu, Ju-ching; Yang, Sung-Yi; Lin, Yi-Cheng; Wang, Chih-Hung; You, Huey-Ling; Wu, Jiunn-Jong; Lee, Gwo-Bin

    2017-01-01

    Vancomycin-resistant Enterococcus (VRE) is a kind of enterococci, which shows resistance toward antibiotics. It may last for a long period of time and meanwhile transmit the vancomycin-resistant gene (vanA) to other bacteria. In the United States alone, the resistant rate of Enterococcus to vancomycin increased from a mere 0.3% to a whopping 40% in the past two decades. Therefore, timely diagnosis and control of VRE is of great need so that clinicians can prevent patients from becoming infected. Nowadays, VRE is diagnosed by antibiotic susceptibility test or molecular diagnosis assays such as matrix-assisted laser desorption ionization/time-of-flight mass spectrometry and polymerase chain reaction. However, the existing diagnostic methods have some drawbacks, for example, time-consumption, no genetic information, or high false-positive rate. This study reports an integrated microfluidic system, which can automatically identify the vancomycin resistant gene (vanA) from live bacteria in clinical samples. A new approach using ethidium monoazide, nucleic acid specific probes, low temperature chemical lysis, and loop-mediated isothermal amplification (LAMP) has been presented. The experimental results showed that the developed system can detect the vanA gene from live Enterococcus in joint fluid samples with detection limit as low as 10 colony formation units/reaction within 1 h. This is the first time that an integrated microfluidic system has been demonstrated to detect vanA gene from live bacteria by using the LAMP approach. With its high sensitivity and accuracy, the proposed system may be useful to monitor antibiotic resistance genes from live bacteria in clinical samples in the near future. PMID:28798845

  4. Characterisation of Phenotypic and Genotypic Antibiotic Resistance Profile of Enterococci from Cheeses in Turkey.

    PubMed

    Kürekci, Cemil; Önen, Sevda Pehlivanlar; Yipel, Mustafa; Aslantaş, Özkan; Gündoğdu, Aycan

    2016-01-01

    The aim of this study was to determine the prevalence of enterococci in cheese samples and to characterize their antimicrobial resistance profiles as well as the associated resistance genes. A total of 139 enterococci were isolated from 99 cheese samples, the isolates were identified as E. faecalis (61.2%), E. faecium (15.1%), E. gallinarum (12.9%), E. durans (5.0%), E. casseliflavis (2.9%) and E. avium (2.9%). The most frequent antimicrobial resistance observed in enterococci isolates was to lincomycin (88.5%), followed by kanamycin (84.2%), gentamycin (low level, 51.1%), rifampin (46.8%) and tetracycline (33.8%). Among the isolates, the frequencies of high level gentamycin and streptomycin resistant enterococci strains were 2.2% and 5.8%, respectively. Apart from the mentioned antibiotics, low levels of resistance to ciprofloxacin, erythromycin and chloramphenicol were found. Moreover no resistance was observed against penicillin and ampicillin. The antimicrobial resistance genes including tetM, tetL, ermB, cat, aph(3')-IIIa, ant(6)-Ia and aac(6')-Ieaph(2")-Ia were found in enterococci from Turkish cheese samples. In the current study, we provided data for antibiotic resistance and the occurrence of resistance genes among enterococci. Regulatory and quality control programs for milk and other dairy products from farms to retail outlets has to be established and strengthened to monitor trends in antimicrobial resistance among emerging food borne pathogens in Turkey.

  5. Prevalence and Antimicrobial Resistance of Enterococci Isolated from Retail Meats in the United States, 2002 to 2014.

    PubMed

    Tyson, Gregory H; Nyirabahizi, Epiphanie; Crarey, Emily; Kabera, Claudine; Lam, Claudia; Rice-Trujillo, Crystal; McDermott, Patrick F; Tate, Heather

    2018-01-01

    Bacteria of the genus Enterococcus are important human pathogens that are frequently resistant to a number of clinically important antibiotics. They are also used as markers of animal fecal contamination of human foods and are employed as sentinel organisms for tracking trends in resistance to antimicrobials with Gram-positive activity. As part of the National Antimicrobial Resistance Monitoring System (NARMS), we evaluated several retail meat commodities for the presence of enterococci from 2002 to 2014, and we found 92.0% to be contaminated. The majority of isolates were either Enterococcus faecalis (64.0%) or Enterococcus faecium (28.6%), and the antimicrobial resistance of each isolate was assessed by broth microdilution. The resistance prevalences for several drugs, including erythromycin and gentamicin, were significantly higher among poultry isolates, compared to retail beef or pork isolates. None of the isolates was resistant to the clinically important human drug vancomycin, only 1 isolate was resistant to linezolid, and resistance to tigecycline was below 1%. In contrast, a majority of both E. faecalis (67.5%) and E. faecium (53.7%) isolates were resistant to tetracycline. Overall, the robust NARMS testing system employed consistent sampling practices and methods throughout the testing period, with the only significant trend in resistance prevalence being decreased E. faecium resistance to penicillin. These data provide excellent baseline levels of resistance that can be used to measure future changes in resistance prevalence that may result from alterations in the use of antimicrobials in food animal production. IMPORTANCE Enterococci, including E. faecalis and E. faecium , are present in the guts of food-producing animals and are used as a measure of fecal contamination of meat. We used the large consistent sampling methods of NARMS to assess the prevalence of Enterococcus strains isolated from retail meats, and we found over 90% of meats to be

  6. Molecular Events for Promotion of Vancomycin Resistance in Vancomycin Intermediate Staphylococcus aureus

    PubMed Central

    Hu, Qiwen; Peng, Huagang; Rao, Xiancai

    2016-01-01

    Vancomycin has been used as the last resort in the clinical treatment of serious Staphylococcus aureus infections. Vancomycin-intermediate S. aureus (VISA) was discovered almost two decades ago. Aside from the vancomycin-intermediate phenotype, VISA strains from the clinic or laboratory exhibited common characteristics, such as thickened cell walls, reduced autolysis, and attenuated virulence. However, the genetic mechanisms responsible for the reduced vancomycin susceptibility in VISA are varied. The comparative genomics of vancomycin-susceptible S. aureus (VSSA)/VISA pairs showed diverse genetic mutations in VISA; only a small number of these mutations have been experimentally verified. To connect the diversified genotypes and common phenotypes in VISA, we reviewed the genetic alterations in the relative determinants, including mutations in the vraTSR, graSR, walKR, stk1/stp1, rpoB, clpP, and cmk genes. Especially, we analyzed the mechanism through which diverse mutations mediate vancomycin resistance. We propose a unified model that integrates diverse gene functions and complex biochemical processes in VISA upon the action of vancomycin. PMID:27790199

  7. Tedizolid susceptibility in linezolid- and vancomycin-resistant Enterococcus faecium isolates.

    PubMed

    Klupp, E-M; Both, A; Belmar Campos, C; Büttner, H; König, C; Christopeit, M; Christner, M; Aepfelbacher, M; Rohde, H

    2016-12-01

    Vancomycin-resistant enterococci (VRE) are of ever-increasing importance, most notably in high-risk patient populations. Therapy options are often limited for these isolates, and apart from tigecycline and daptomycin, oxazolidinone linezolid is frequently administered. The broad usage of linezolid, however, has driven the emergence of linezolid-resistant VRE strains (LR-VRE), further shortening therapeutic options. Second-generation oxazolidinone tedizolid has the advantage of being active against a specific subset of LR-VRE, i.e. isolates expressing the plasmid-encoded chloramphenicol-florfenicol resistance (cfr) gene. Here we tested tedizolid activity in a collection of 30 LR Enterococcus faecium VRE (MIC range 32-256 mg/l) isolated between 2012 and 2015 from clinical and screening specimens. By pulsed field gel electrophoresis (PFGE) isolates were assigned to 16 clonal lineages. In three cases, linezolid-susceptible progenitor isolates of LR-VRE were isolated, thus demonstrating the de-novo emergence of the linezolid-resistant phenotype. PCR did not detect cfr, cfr(B) or novel oxazolidinone resistance gene optrA in LR-VRE. All isolates, however, carried mutations within the 23S rDNA. Compared to linezolid, tedizolid MICs were lower in all isolates (MIC range 2-32 mg/l), but remained above the FDA tedizolid breakpoint for E. faecalis at 0.5 mg/l. Thus, related to the predominant resistance mechanism, tedizolid is of limited value for treatment of most LR-VRE and represents a therapeutic option only for a limited subset of isolates.

  8. Combination antibiotic therapy for the treatment of infective endocarditis due to enterococci.

    PubMed

    Leone, Sebastiano; Noviello, Silvana; Esposito, Silvano

    2016-06-01

    Enterococci are common causes of infective endocarditis (IE) in both health care and community-based setting. Enterococcal IE requires bactericidal therapy for an optimal outcome. For decades, cell-wall-active antimicrobial agents (penicillins or vancomycin) in combination with aminoglycosides were the cornerstone of the treatment; however, the emergence of antibiotic resistance has significantly reduced the efficacy of these regimens. Data for this review were identified by searches of MEDLINE and references from relevant articles on antibiotic combination regimens for the treatment of enterococcal IE. Abstracts presented in scientific conferences were not searched for. New effective and safe combination treatments, including double-β-lactam and daptomycin/β-lactam combination, are proving useful for the management of IE due to enterococci.

  9. Molecular epidemiology of vancomycin-resistant enterococcal bacteraemia: results from the Canadian Nosocomial Infection Surveillance Program, 1999-2009.

    PubMed

    McCracken, M; Wong, A; Mitchell, R; Gravel, D; Conly, J; Embil, J; Johnston, L; Matlow, A; Ormiston, D; Simor, A E; Smith, S; Du, T; Hizon, R; Mulvey, M R

    2013-07-01

    Vancomycin-resistant enterococci (VRE) can be associated with serious bacteraemia. The focus of this study was to characterize the molecular epidemiology of VRE from bacteraemia cases that were isolated from 1999 to 2009 as part of Canadian Nosocomial Infection Surveillance Program (CNISP) surveillance activities. From 1999 to 2009, enterococci were collected from across Canada in accordance with the CNISP VRE surveillance protocol. MICs were determined using broth microdilution. PCR was used to identify vanA, B, C, D, E, G and L genes. Genetic relatedness was examined using multilocus sequence typing (MLST). A total of 128 cases of bacteraemia were reported to CNISP from 1999 to 2009. In 2007, a significant increase in bacteraemia rates was observed in western and central Canada. Eighty-one of the 128 bacteraemia isolates were received for further characterization and were identified as Enterococcus faecium. The majority of isolates were from western Canada (60.5%), followed by central (37.0%) and eastern (2.5%) Canada. Susceptibilities were as follows: daptomycin, linezolid, tigecycline and chloramphenicol, 100%; quinupristin/dalfopristin, 96.3%; high-level gentamicin, 71.6%; tetracycline, 50.6%; high-level streptomycin, 44.4%; rifampicin, 21.0%; nitrofurantoin, 11.1%; clindamycin, 8.6%; ciprofloxacin, levofloxacin and moxifloxacin, 1.2%; and ampicillin, 0.0%. vanA contributed to vancomycin resistance in 90.1% of isolates and vanB in 9.9%. A total of 17 sequence types (STs) were observed. Beginning in 2006 there was a shift in ST from ST16, ST17, ST154 and ST80 to ST18, ST412, ST203 and ST584. The increase in bacteraemia observed since 2007 in western and central Canada appears to coincide with the shift of MLST STs. All VRE isolates remained susceptible to daptomycin, linezolid, chloramphenicol and tigecycline.

  10. Autolytic activity and molecular characteristics of Staphylococcus haemolyticus strains with induced vancomycin resistance.

    PubMed

    Kim, Jung Wook; Chung, Gyung Tae; Yoo, Jung Sik; Lee, Yeong Seon; Yoo, Jae Il

    2012-10-01

    The aim of this study was to investigate the molecular characteristics of induced vancomycin resistance in Staphylococcus haemolyticus. Autolytic properties and phenotypic characteristics of passage-selected vancomycin-resistant S. haemolyticus strains were examined. In addition, expression of autolysis-related genes (atl, lrgAB, sarA and lytS) was investigated using the RNase protection assay (RPA). The RPA results indicated that only the expression of the atl gene was significantly upregulated (2.5- to 6-fold increase) in vancomycin-intermediate and vancomycin-resistant strains. The vancomycin-resistant strains exhibited lower expression of murein hydrolase proteins and reduced autolytic activity compared with the parent strain. In addition, a reduced growth rate, cell wall thickening and higher survival rate in the presence of lysostaphin were observed in vancomycin-intermediate and vancomycin-resistant induced strains compared with the parent strain. In conclusion, altered autolytic properties, in particular upregulation of the atl gene, may contribute to vancomycin resistance in S. haemolyticus.

  11. Heat resistance of thermoduric enterococci isolated from milk.

    PubMed

    McAuley, Catherine M; Gobius, Kari S; Britz, Margaret L; Craven, Heather M

    2012-03-15

    Enterococci are reported to survive pasteurisation but the extent of their survival is unclear. Sixty-one thermoduric enterococci isolates were selected from laboratory pasteurised milk obtained from silos in six dairy factories. The isolates were screened to determine log(10) reductions incurred after pasteurisation (63°C/30 min) and ranked from highest to lowest log(10) reduction. Two isolates each of Enterococcus faecalis, Enterococcus faecium, Enterococcus durans and Enterococcus hirae, exhibiting the median and the greatest heat resistance, as well as E. faecalis ATCC 19433, were selected for further heat resistance determinations using an immersed coil apparatus. D values were calculated from survival curves plotted from viable counts obtained after heating isolates in Brain Heart Infusion Broth at 63, 69, 72, 75 and 78°C followed by rapid cooling. At 72°C, the temperature employed for High Temperature Short Time (HTST) pasteurisation (72°C/15s), the D values extended from 0.3 min to 5.1 min, depending on the isolate and species. These data were used to calculate z values, which ranged from 5.0 to 9.8°C. The most heat sensitive isolates were E. faecalis (z values 5.0, 5.7 and 7.5°C), while the most heat resistant isolates were E. durans (z values 8.7 and 8.8°C), E. faecium (z value 9.0°C) and E. hirae (z values 8.5 and 9.8°C). The data show that heat resistance in enterococci is highly variable. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Antibiotic and heavy metal resistance in enterococci from coastal marine sediment.

    PubMed

    Vignaroli, Carla; Pasquaroli, Sonia; Citterio, Barbara; Di Cesare, Andrea; Mangiaterra, Gianmarco; Fattorini, Daniele; Biavasco, Francesca

    2018-06-01

    Sediment samples from three coastal sites - two beach resorts (Beach 1 and Beach 2 sites) and an area lying between an oil refinery and a river estuary (Estuarine site) - were analyzed for antibiotic- and heavy metal (HM)-resistant enterococci. A total of 123 enterococci, 36 E. faecium, 34 E. casseliflavus, 33 E. hirae, 5 E. faecalis, 3 E. durans, 3 E. gallinarum, and 9 Enterococcus spp, were recovered. Strains resistant to erythromycin, tetracycline and quinupristin/dalfopristin (Q/D) were recovered from all sites, whereas multidrug-resistant isolates were recovered only from "Beach 2" (14%) and "Estuarine" (3.7%). As regards HM resistance, the strains showed a high frequency (68%) of cadmium and/or copper resistance and uniform susceptibility to mercury. The prevalence of cadmium-resistant strains was significantly higher among erythromycin-resistant than among erythromycin-susceptible strains. A significant association between cadmium or copper resistance and Q/D resistance was also observed at "Estuarine" site. The levels of the two HMs in sediment from all sites were fairly low, ranging from 0.070 to 0.126 μg/g, for cadmium and from 1.00 to 7.64 μg/g for copper. Mercury was always undetectable. These findings are consistent with reports that low HM concentrations may contribute to co-selection of antibiotic-resistant bacterial strains, including enterococci. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Determination of antimicrobial resistance to extended-spectrum cephalosporin, quinolones, and vancomycin in selected human enteric pathogens from Prince Edward Island, Canada.

    PubMed

    Awosile, Babafela; German, Gregory; Rodriguez-Lecompte, Juan Carlos; Saab, Matthew E; Heider, Luke C; McClure, J Trenton

    2018-04-05

    The aim of this study was to determine the frequency of fecal carriage of vancomycin-resistant Enterococcus spp. and Escherichia coli with reduced susceptibilities to extended-spectrum cephalosporins (ESCs) and quinolones in humans on Prince Edward Island, Canada. Convenience fecal samples from individuals on Prince Edward Island were screened phenotypically using selective culture and genotypically using multiplex polymerase chain reactions to detect E. coli and Enterococcus spp. resistant to critically important antimicrobials. Twenty-six (5.3%) of 489 individuals had E. coli with reduced susceptibility to ESCs. Twenty-five (96.2%) of the 26 isolates harbored bla TEM , 18 (69.2%) harbored bla CMY-2 , 16 (61.5%) harbored bla CTX-M groups, 2 (7.7%) harbored bla SHV genes. None of the ESC-resistant E. coli was positive for carbapenem resistance. Twenty-one (8.3%) of 253 individuals had E. coli isolates with reduced quinolone susceptibility. All 21 isolates were positive for at least 1 qnr gene, with 3 (14.3%) isolates positive for qnrB, 5 (23.8%) positive for qnrS, and 13 (61.9%) positive for both qnrB and qnrS genes. All the enterococci isolates were vancomycin-susceptible. Higher susceptibility to the critically important antimicrobials was found in this study. This study can serve as a baseline for future antimicrobial resistance surveillance within this region.

  14. Pharmacodynamic activity of ceftobiprole compared with vancomycin versus methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate Staphylococcus aureus (VISA) and vancomycin-resistant Staphylococcus aureus (VRSA) using an in vitro model.

    PubMed

    Zhanel, George G; Voth, Dylan; Nichol, Kim; Karlowsky, James A; Noreddin, Ayman M; Hoban, Daryl J

    2009-08-01

    This study compared the pharmacodynamics of ceftobiprole and vancomycin against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate S. aureus (VISA) and vancomycin-resistant S. aureus (VRSA) using an in vitro model. Two methicillin-susceptible S. aureus (MSSA), two community-associated (CA)-MRSA, one healthcare-associated (HA)-MRSA, three VISA and two VRSA were studied. The pharmacodynamic model was inoculated with a concentration of 1 x 10(6) cfu/mL and ceftobiprole dosed every 8 h (at 0, 8 and 16 h) to simulate the fC(max) and t(1/2) obtained after 500 mg intravenous (iv) every 8 h dosing (fC(max,) 30 mg/L; t(1/2,) 3.5 h). Vancomycin was dosed every 12 h (at 0 and 12 h) to simulate fC(max) and t(1/2) obtained after 1 g iv every 12 h dosing (fC(max), 20 mg/L; t(1/2), 8 h). Samples were collected over 24 h to assess viable growth. Ceftobiprole T > MIC of > or =100% (ceftobiprole MICs, < or =2 mg/L) was bactericidal (> or =3 log(10) killing) against MSSA, CA-MRSA, HA-MRSA, VISA and VRSA at 16 and 24 h. Vancomycin fAUC(24)/MIC of 340 (vancomycin MIC, 1 mg/L for MSSA and MRSA) resulted in a 1.8-2.6 log(10) reduction in colony count at 24 h. Vancomycin fAUC(24)/MIC of 85-170 (vancomycin MIC, 2-4 mg/L for VISA) resulted in a 0.4-0.7 log(10) reduction at 24 h. Vancomycin fAUC(24)/MIC of 5.3 (vancomycin MIC, 64 mg/L for VRSA) resulted in a limited effect. Ceftobiprole T > MIC of > or =100% (ceftobiprole MICs, < or =2 mg/L) was bactericidal (> or =3 log(10) killing) against MSSA, CA-MRSA, HA-MRSA, VISA and VRSA at 16 and 24 h. Vancomycin was bacteriostatic against MSSA, MRSA and VISA, while demonstrating no activity against VRSA.

  15. Vancomycin intermediate-resistant Staphylococcus aureus (VISA) isolated from a patient who never received vancomycin treatment.

    PubMed

    Zhu, Xuhui; Liu, Cailin; Gao, Sui; Lu, Yanfang; Chen, Zhongju; Sun, Ziyong

    2015-04-01

    With the abuse of antibiotics, the methicillin-resistant Staphylococcus aureus (MRSA) strain became prevalent. Furthermore, Staphylococcus aureus with a character of vancomycin intermediate-resistance (VISA) has been found globally since the first report in Japan. The main objectives of this study were to report a case of VISA isolated from a Chinese patient who had never undergone Vancomycin treatment, and to determine its molecular character. A total of 9 strains were recovered from a patient during the therapeutic process. Antimicrobial susceptibility testing was performed to determine their antibiotic susceptibility patterns. To detect the VISA strain's molecular epidemiological features, growth and morphological characters, we used multilocus sequence typing, autolysis assay and transmission electric microscope tests. Pulsed-field gel electrophoresis (PFGE) was performed to characterize the heterogeneities of all isolates. One isolate was found to exhibit vancomycin intermediated-resistant with MIC of 8 μg/ml. It was ST239-T030-agr-1, had thickened cell wall, and displayed a slower growth rate and reduced susceptibility to Triton X-100-induced autolysis than other strains. All 9 strains exhibited the same PFGE pattern. This is the first report of VISA found in central China from a patient who had never received vancomycin treatment. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Effect of gastrointestinal bleeding and oral medications on acquisition of vancomycin-resistant Enterococcus faecium in hospitalized patients.

    PubMed

    Cetinkaya, Yesim; Falk, Pamela S; Mayhall, C Glen

    2002-10-15

    There has been minimal investigation of medications that affect gastrointestinal function as potential risk factors for the acquisition of vancomycin-resistant enterococci (VRE). We performed a retrospective case-control study, with control subjects matched to case patients by time and location of hospitalization. Strict exclusion criteria were applied to ensure that only case patients with a known time of acquisition of VRE were included. Control patients were patients with > or =1 culture negative for VRE. The risk factors identified were use of vancomycin (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.7-6.0; P=.0003), presence of central venous lines (OR, 2.2; 95% CI, 1.04-4.6; P=.04), and use of antacids (OR, 2.9; 95% CI, 1.5-5.6; P=.002). Two protective factors included gastrointestinal bleeding (OR, 0.26; 95% CI, 0.08-0.79; P=.02) and use of Vicodin (Knoll Labs; hydrocodone and acetaminophen; OR, 0.93; 95% CI, 0.90-0.97; P=.0003). Changes in gastrointestinal function, whether due to bleeding or to the effects of oral medications, may affect whether patients become colonized with VRE.

  17. Abundance and characteristics of the recreational water quality indicator bacteria Escherichia coli and enterococci in gull faeces

    USGS Publications Warehouse

    Fogarty, L.R.; Haack, S.K.; Wolcott, M.J.; Whitman, R.L.

    2003-01-01

    Aims: To evaluate the numbers and selected phenotypic and genotypic characteristics of the faecal indicator bacteria Escherichia coli and enterococci in gull faeces at representative Great Lakes swimming beaches in the United States. Methods and Results: E. coli and enterococci were enumerated in gull faeces by membrane filtration. E. coli genotypes (rep-PCR genomic profiles) and E. coli (Vitek?? GNI+) and enterococci (API?? rapid ID 32 Strep and resistance to streptomycin, gentamicin, vancomycin, tetracycline and ampicillin) phenotypes were determined for isolates obtained from gull faeces both early and late in the swimming season. Identical E. coli genotypes were obtained only from single gull faecal samples but most faecal samples yielded more than one genotype (median of eight genotypes for samples with 10 isolates). E. coli isolates from the same site that clustered at ???85% similarity were from the same sampling date and shared phenotypic characteristics, and at this similarity level there was population overlap between the two geographically isolated beach sites. Enterococcus API?? profiles varied with sampling date. Gull enterococci displayed wide variation in antibiotic resistance patterns, and high-level resistance to some antibiotics. Conclusions: Gull faeces could be a major contributor of E. coli (105-109 CFU g-1) and enterococci (104-108 CFU g-1) to Great Lakes recreational waters. E. coli and enterococci in gull faeces are highly variable with respect to their genotypic and phenotypic characteristics and may exhibit temporal or geographic trends in these features. Significance and Impact of the Study: The high degree of variation in genotypic or phenotypic characteristics of E. coli or enterococci populations within gull hosts will require extensive sampling for adequate characterization, and will influence methods that use these characteristics to determine faecal contamination sources for recreational waters.

  18. In vitro activity of RP 59500, a semisynthetic injectable pristinamycin, against staphylococci, streptococci, and enterococci.

    PubMed Central

    Fass, R J

    1991-01-01

    The in vitro activity of RP 59500, a semisynthetic pristinamycin, was compared with the activities of vancomycin, oxacillin, ampicillin, gentamicin, ciprofloxacin, and rifampin against five Staphylococcus species, five Streptococcus species, and four Enterococcus species. For staphylococci, MICs were 0.13 to 1 microgram/ml and the MICs for 90% of the strains tested (MIC90s) were 0.13 to 0.5 microgram/ml; there were no differences between oxacillin-susceptible and -resistant strains. For streptococci, MICs were 0.03 to 4 micrograms/ml and MIC90s were 0.25 to 2 micrograms/ml; viridans group streptococci were the least susceptible streptococci. For enterococci, MICs were 0.25 to 32 micrograms/ml and MIC90s were 2 to 4 micrograms/ml; Enterococcus faecalis was the least susceptible. Vancomycin was the only comparative drug with consistent activity against all species of gram-positive cocci. With RP 59500, raising the inoculum 100-fold, lowering the pH of cation-adjusted Mueller-Hinton broth to 5.5, or omitting cation supplementation had little effect on MICs, but 50% serum increased MICs 2 to 4 dilution steps. The differences between MBCs and MICs were greater for staphylococci and enterococci than for streptococci. Time-kill studies with 24 strains indicated that RP 59500 concentrations 2-, 4-, and 16-fold greater than the MICs usually killed bacteria of each species at similar rates; reductions in CFU per milliliter were less than those observed with oxacillin or vancomycin against staphylococci and less than those observed with ampicillin against enterococci. RP 59500 antagonized the bactericidal activities of oxacillin and gentamicin against Staphylococcus aureus ATCC 29213 and that of ampicillin against E. faecalis ATCC 29212. Against the latter, combination with gentamicin was indifferent. RP 59500 has a broad spectrum of in vitro activity against gram-positive cocci; combining it with other drugs is not advantageous. PMID:1903912

  19. Antimicrobial resistance pattern and genetic correlation in Enterococcus faecium isolated from healthy volunteers.

    PubMed

    Asadian, M; Sadeghi, J; Rastegar Lari, A; Razavi, Sh; Hasannejad Bibalan, M; Talebi, M

    2016-03-01

    Enterococci are known as a cause of nosocomial infections and this aptitude is intensified by the growth of antibiotic resistance. In the present study, Enterococcus faecium isolates from healthy volunteers were considered to determine the antibiotic resistance profiles and genetic correlation. A total 91 normal flora isolates of enterococci were included in this study. Identification of Enterococcus genus and species were done by biochemical and PCR methods, respectively. Sensitivity for 10 antibiotics was determined and genetic relatedness of all isolates was assessed using Repetitive Element Palindromic PCR (REP-PCR) followed by Pulse Field Gel Electrophoresis (PFGE) on the representative patterns. None of the isolates were resistant to teicoplanin, vancomycin, quinupristin-dalfopristin, linezolid, chloramphenicol, ampicillin and high-level gentamicin. On the other hand, the resistance rate was detected in 30.7%, 23%, and 3.29% of isolates for erythromycin, tetracycline and ciprofloxacin, respectively. The results of PFGE showed 19 (61.5% of our isolates) common types (CT) and 35 (38.5%) single types (ST) amongst the isolates. This is the first study to describe antibiotic resistance pattern and genetic relationship among normal flora enterococci in Iran. This study showed no prevalence of Vancomycin Resistant Enterococci (VRE) and high degrees of diversity among normal flora isolates by genotyping using PFGE. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Emergence of daptomycin non-susceptibility in colonizing vancomycin-resistant Enterococcus faecium isolates during daptomycin therapy.

    PubMed

    Lellek, Heinrich; Franke, Gefion C; Ruckert, Carolin; Wolters, Manuel; Wolschke, Christiane; Christner, Martin; Büttner, Henning; Alawi, Malik; Kröger, Nicolaus; Rohde, Holger

    2015-12-01

    Infections due to vancomycin-resistant enterococci (VRE) are of significant importance in high-risk populations, and daptomycin is a bactericidal antibiotic to treat multidrug-resistant VRE in these patients. The emergence of daptomycin non-susceptibility invasive VRE during daptomycin therapy is a major clinical issue. Here the hypothesis was tested that systemic daptomycin therapy also induces the emergence of daptomycin non-susceptible (DNS-) isolates in colonizing VRE populations. 11 vancomycin-resistant Enterococcus faecium strain pairs recovered from rectal swabs were available for analysis. All initial isolates exhibited daptomycin MICs within the wild type MIC distribution of E. faecium (MIC≤4 mg/L). In follow-up isolates from five patients a 4-16-fold daptomycin MIC increase was detected. All patients carrying DNS-VRE received daptomycin (14-28 days) at 4 mg/kg body weight, while two patients in whom no DNS-VRE emerged were only treated with daptomycin for 1 and 4 days, respectively. Comparative whole genome sequencing identified DNS-VRE-specific single nucleotide polymorphisms (SNP), including mutations in cardiolipin synthase (Cls), and additional SNPs in independent genes potentially relevant for the DNS phenotype. Mutations within cls were also identified in three additional, colonizing DNS-VRE. Of these, at least one strain was transmitted within the hospital. In none of the VRE isolates tested, pre-existing or de novo mutations in the liaFSR operon were detected. This is the first report documenting the emergence of DNS-VRE in colonizing strains during daptomycin treatment, putting the patient at risk for subsequent DNS-VRE infections and priming the spread of DNS-VRE within the hospital environment. Copyright © 2015 Elsevier GmbH. All rights reserved.

  1. Development of a Real-Time PCR Protocol Requiring Minimal Handling for Detection of Vancomycin-Resistant Enterococci with the Fully Automated BD Max System.

    PubMed

    Dalpke, Alexander H; Hofko, Marjeta; Zimmermann, Stefan

    2016-09-01

    Vancomycin-resistant enterococci (VRE) are an important cause of health care-associated infections, resulting in significant mortality and a significant economic burden in hospitals. Active surveillance for at-risk populations contributes to the prevention of infections with VRE. The availability of a combination of automation and molecular detection procedures for rapid screening would be beneficial. Here, we report on the development of a laboratory-developed PCR for detection of VRE which runs on the fully automated Becton Dickinson (BD) Max platform, which combines DNA extraction, PCR setup, and real-time PCR amplification. We evaluated two protocols: one using a liquid master mix and the other employing commercially ordered dry-down reagents. The BD Max VRE PCR was evaluated in two rounds with 86 and 61 rectal elution swab (eSwab) samples, and the results were compared to the culture results. The sensitivities of the different PCR formats were 84 to 100% for vanA and 83.7 to 100% for vanB; specificities were 96.8 to 100% for vanA and 81.8 to 97% for vanB The use of dry-down reagents and the ExK DNA-2 kit for extraction showed that the samples were less inhibited (3.3%) than they were by the use of the liquid master mix (14.8%). Adoption of a cutoff threshold cycle of 35 for discrimination of vanB-positive samples allowed an increase of specificity to 87.9%. The performance of the BD Max VRE assay equaled that of the BD GeneOhm VanR assay, which was run in parallel. The use of dry-down reagents simplifies the assay and omits any need to handle liquid PCR reagents. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  2. Pathogenicity determinants and antibiotic resistance profiles of enterococci from foods of animal origin in Turkey.

    PubMed

    Elal Mus, Tulay; Cetinkaya, Figen; Cibik, Recep; Soyutemiz, Gul Ece; Simsek, Husniye; Coplu, Nilay

    2017-12-01

    In this study, the presence of genes responsible for the pathogenicity and antibiotic resistance profile of enterococci isolated from various foodstuffs of animal origin was investigated. The percentage prevalence of enterococci was 54.1% (203/375) and the average count was found to be 3.81 log cfu/ml-g. Species-specific primers revealed Enterococcus faecalis as the predominant species carrying one or more virulence-associated traits of efa, gelE, ace, esp and agg genetic markers. Only one E. faecium isolate (from milk) was positive for the esp gene. Regarding antibiotic resistance, the highest frequency of resistance was observed for tetracycline (21.7%), followed by quinupristin/dalfopristin (13.3%), ciprofloxacin (2.0%), penicillin (2.0%), linezolid (1.0%), ampicillin (1.0%), streptomycin (1.0%), and gentamicin (0.5%). Enterococcus faecalis showed a higher prevalence of antibiotic resistance than other enterococci. The percentage of multidrug resistance among the isolates was 3.4%. Twenty-nine E. faecalis isolates (26.6%) carrying one of the virulence-associated traits were at the same time resistant to at least one antibiotic. Our results show that foods of animal origin, including ready-to-eat products, may be reservoirs of antibiotic-resistant and potentially virulent enterococci.

  3. Comparison of performance of the novel chromogenic spectra VRE agar to that of bile esculin azide and Campylobacter agars for detection of vancomycin-resistant enterococci in fecal samples.

    PubMed

    Jenkins, S G; Raskoshina, L; Schuetz, A N

    2011-11-01

    A total of 142 stool specimens were evaluated for vancomycin-resistant enterococcus (VRE). Twenty-four-hour sensitivities and specificities, respectively, were 98% and 95% for Spectra VRE chromogenic agar (Remel, Lenexa, KS), 86% and 92% for bile esculin azide with vancomycin (BEAV; Remel), and 96.5% and 92% for Campylobacter agar (CAMPY; Remel). Spectra VRE and CAMPY are significantly more sensitive at 24 h than BEAV.

  4. Heterologous expression of glycopeptide resistance vanHAX gene clusters from soil bacteria in Enterococcus faecalis.

    PubMed

    Hasman, Henrik; Aarestrup, Frank M; Dalsgaard, Anders; Guardabassi, Luca

    2006-04-01

    The aim of the study was to determine whether glycopeptide resistance gene clusters from soil bacteria could be heterologously expressed in Enterococcus faecalis and adapt to the new host following exposure to vancomycin. The vanHAX clusters from Paenibacillus thiaminolyticus PT-2B1, Paenibacillus apiarius PA-B2B and Amycolatopsis coloradensis DSM 44225 were separately cloned in an appropriately constructed shuttle vector containing the two-component regulatory system (vanRS) of Tn1546. The complete vanA(PT) operon (vanRSHAXY) from P. thiaminolyticus PT-2B1 was cloned in the same shuttle vector lacking enterococcal vanRS. All plasmid constructs were electroporated into E. faecalis JH2-2 and the MICs of vancomycin and teicoplanin were determined for each recombinant strain before and following exposure to sublethal concentrations of vancomycin. The vanHAX clusters from P. thiaminolyticus and P. apiarius conferred high-level vancomycin resistance (MIC > or = 125 mg/L) in E. faecalis JH2-2. In contrast, cloning of the vanHAX cluster from A. coloradensis did not result in a significant increase of vancomycin resistance (MIC = 0.7 mg/L). Resistance to vancomycin was not observed after cloning the complete vanA(PT) operon from P. thiaminolyticus (MIC = 2 mg/L), but this recombinant rapidly adapted to high concentrations of vancomycin (MIC = 500 mg/L) following exposure to sub-lethal concentrations of this antibiotic. The results showed that vanA(PT) in P. thiaminolyticus is a possible ancestor of vanA-mediated glycopeptide resistance in enterococci. Experimental evidence supported the hypothesis that enterococci did not acquire glycopeptide resistance directly from glycopeptide-producing organisms such as A. coloradensis.

  5. Effect of vancomycin, tylosin, and chlortetracycline on vancomycin-resistant Enterococcus faecium colonization of broiler chickens during grow-out

    USDA-ARS?s Scientific Manuscript database

    Broiler chickens may serve as reservoirs for human colonization by vancomycin-resistant Enterococcus (VRE). We examined the effects of vancomycin and two commonly-used antimicrobial feed additives on VRE colonization in broiler chickens during grow-out. Chicks received unsupplemented feed or feed ...

  6. Phenotypic and genotypic study of biofilm formation in Enterococci isolated from urinary tract infections.

    PubMed

    Fallah, F; Yousefi, M; Pourmand, M R; Hashemi, A; Nazari Alam, A; Afshar, D

    2017-07-01

    Urinary tract infection (UTI) is one of the most frequent types of nosocomial and community acquired infections in humans. Management of multidrug-resistant Enterococci UTI due to the limited therapeutic options is a great challenge for physicians and clinical microbiologists. The role of bacterial biofilms in recurrent urinary tract infections and antimicrobial resistance has great importance for public health. The aim of this study was to investigate the antibiotic susceptibility pattern as well as the phenotypic and genotypic biofilm formation ability of Enterococci isolates from patients with UTI. A total of 57 isolates of Enterococci were collected from patients with UTI. Enterococcus species were identified using conventional microbiological methods. The antibiotic susceptibility patterns of the isolates were determined by the Kirby-Bauer disk-diffusion. The Modified Congo red agar (MCRA) and Microtiter plate methods used to assess the ability of biofilm formation. All enterococcal isolates were examined for determination of biofilm-related genes, esp, asa1 and ebpR using PCR method. Of 57 enterococcal isolates, 85.9% were recognized as E. faecalis and 14.1% of them were E. faecium. According to our results, linezolid, chloramphenicol and nitrofurantoin were the most effective agents against Enterococcus species. Overall, 26.5% of E. faecalis and 75% of E. faecium isolates were biofilm producers, respectively. Resistance to some antibiotics including penicillin G, ampicillin, vancomycin, nitrofurantoin and chloramphenicol, and ciprofloxacin was significantly higher among biofilm producers than non-biofilm producers Enterococci. The esp, asa1 and ebpR genes were present in 84.2%, 91.2% and 100% isolates. In this study, there was not a significant relationship between presence of these genes and biofilm formation. Our findings reinforce the role of biofilm formation in resistance to antimicrobial agents. Quinupristin/dalfopristin, tetracycline and rifampin

  7. Loss of Microbiota-Mediated Colonization Resistance to Clostridium difficile Infection With Oral Vancomycin Compared With Metronidazole

    PubMed Central

    Lewis, Brittany B.; Buffie, Charlie G.; Carter, Rebecca A.; Leiner, Ingrid; Toussaint, Nora C.; Miller, Liza C.; Gobourne, Asia; Ling, Lilan; Pamer, Eric G.

    2015-01-01

    Antibiotic administration disrupts the intestinal microbiota, increasing susceptibility to pathogens such as Clostridium difficile. Metronidazole or oral vancomycin can cure C. difficile infection, and administration of these agents to prevent C. difficile infection in high-risk patients, although not sanctioned by Infectious Disease Society of America guidelines, has been considered. The relative impacts of metronidazole and vancomycin on the intestinal microbiota and colonization resistance are unknown. We investigated the effect of brief treatment with metronidazole and/or oral vancomycin on susceptibility to C. difficile, vancomycin-resistant Enterococcus, carbapenem-resistant Klebsiella pneumoniae, and Escherichia coli infection in mice. Although metronidazole resulted in transient loss of colonization resistance, oral vancomycin markedly disrupted the microbiota, leading to prolonged loss of colonization resistance to C. difficile infection and dense colonization by vancomycin-resistant Enterococcus, K. pneumoniae, and E. coli. Our results demonstrate that vancomycin, and to a lesser extent metronidazole, are associated with marked intestinal microbiota destruction and greater risk of colonization by nosocomial pathogens. PMID:25920320

  8. Derivatives of a Vancomycin-Resistant Staphylococcus aureus Strain Isolated at Hershey Medical Center

    PubMed Central

    Bozdogan, Bülent; Ednie, Lois; Credito, Kim; Kosowska, Klaudia; Appelbaum, Peter C.

    2004-01-01

    Antimicrobial susceptibilities and genetic relatedness of the vancomycin-resistant Staphylococcus aureus strain (VRSA) isolated at Hershey, Pa. (VRSA Hershey), and its vancomycin-susceptible and high-level-resistant derivatives were studied and compared to 32 methicillin-resistant S. aureus strains (MRSA) isolated from patients and medical staff in contact with the VRSA patient. Derivatives of VRSA were obtained by subculturing six VRSA colonies from the original culture with or without vancomycin. Ten days of drug-free subculture caused the loss of vanA in two vancomycin-susceptible derivatives for which vancomycin MICs were 1 to 4 μg/ml. Multistep selection of three VRSA clones with vancomycin for 10 days increased vancomycin MICs from 32 to 1,024 to 2,048 μg/ml. MICs of teicoplanin, dalbavancin, and oritavancin were also increased from 4, 0.5, and 0.12 to 64, 1, and 32 μg/ml, respectively. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing analysis indicated that VRSA Hershey was the vanA-acquired variety of a common MRSA clone in our hospital with sequence type 5 (ST5). Three of five vancomycin-intermediate S. aureus strains tested from geographically different areas were also ST5, and the Michigan VRSA was ST371, a one-allele variant of ST5. Derivatives of VRSA Hershey had differences in PFGE profiles and the size of SmaI fragment that carries the vanA gene cluster, indicating instability of this cluster in VRSA Hershey. However induction with vancomycin increased glycopeptide MICs and stabilized the resistance. PMID:15561854

  9. Derivatives of a vancomycin-resistant Staphylococcus aureus strain isolated at Hershey Medical Center.

    PubMed

    Bozdogan, Bülent; Ednie, Lois; Credito, Kim; Kosowska, Klaudia; Appelbaum, Peter C

    2004-12-01

    Antimicrobial susceptibilities and genetic relatedness of the vancomycin-resistant Staphylococcus aureus strain (VRSA) isolated at Hershey, Pa. (VRSA Hershey), and its vancomycin-susceptible and high-level-resistant derivatives were studied and compared to 32 methicillin-resistant S. aureus strains (MRSA) isolated from patients and medical staff in contact with the VRSA patient. Derivatives of VRSA were obtained by subculturing six VRSA colonies from the original culture with or without vancomycin. Ten days of drug-free subculture caused the loss of vanA in two vancomycin-susceptible derivatives for which vancomycin MICs were 1 to 4 microg/ml. Multistep selection of three VRSA clones with vancomycin for 10 days increased vancomycin MICs from 32 to 1,024 to 2,048 microg/ml. MICs of teicoplanin, dalbavancin, and oritavancin were also increased from 4, 0.5, and 0.12 to 64, 1, and 32 microg/ml, respectively. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing analysis indicated that VRSA Hershey was the vanA-acquired variety of a common MRSA clone in our hospital with sequence type 5 (ST5). Three of five vancomycin-intermediate S. aureus strains tested from geographically different areas were also ST5, and the Michigan VRSA was ST371, a one-allele variant of ST5. Derivatives of VRSA Hershey had differences in PFGE profiles and the size of SmaI fragment that carries the vanA gene cluster, indicating instability of this cluster in VRSA Hershey. However induction with vancomycin increased glycopeptide MICs and stabilized the resistance.

  10. Mycobacterium tuberculosis Rv1152 is a Novel GntR Family Transcriptional Regulator Involved in Intrinsic Vancomycin Resistance and is a Potential Vancomycin Adjuvant Target

    PubMed Central

    Zeng, Jie; Deng, Wanyan; Yang, Wenmin; Luo, Hongping; Duan, Xiangke; Xie, Longxiang; Li, Ping; Wang, Rui; Fu, Tiwei; Abdalla, Abualgasim Elgaili; Xie, Jianping

    2016-01-01

    Novel factors involved in Mycobacteria antibiotics resistance are crucial for better targets to combat the ever-increasing drug resistant strains. Mycobacterium tuberculosis Rv1152, a novel GntR family transcriptional regulator and a promising vancomycin adjuvant target, was firstly characterized in our study. Overexpression of Rv1152 in Mycobacterium smegmatis decreased bacterial susceptibility to vancomycin. Moreover, a deficiency in MSMEG_5174, an Rv1152 homolog made M. smegmatis more sensitive to vancomycin, which was reverted by complementing the MSMEG_5174 deficiency with Rv1152 of M. tuberculosis. Rv1152 negatively regulated four vancomycin responsive genes, namely genes encoding the ribosome binding protein Hsp, small unit of sulfate adenylyltransferase CysD, L-lysine-epsilon aminotransferase Lat, and protease HtpX. Taken together, Rv1152 controls the expression of genes required for the susceptibility to vancomycin. This is the first report that links the GntR family transcriptional factor with vancomycin susceptibility. Inhibitors of Rv1152 might be ideal vancomycin adjuvants for controlling multi-drug resistant Mycobacterial infections. PMID:27349953

  11. Comparison of Performance of the Novel Chromogenic Spectra VRE Agar to That of Bile Esculin Azide and Campylobacter Agars for Detection of Vancomycin-Resistant Enterococci in Fecal Samples ▿

    PubMed Central

    Jenkins, S. G.; Raskoshina, L.; Schuetz, A. N.

    2011-01-01

    A total of 142 stool specimens were evaluated for vancomycin-resistant enterococcus (VRE). Twenty-four-hour sensitivities and specificities, respectively, were 98% and 95% for Spectra VRE chromogenic agar (Remel, Lenexa, KS), 86% and 92% for bile esculin azide with vancomycin (BEAV; Remel), and 96.5% and 92% for Campylobacter agar (CAMPY; Remel). Spectra VRE and CAMPY are significantly more sensitive at 24 h than BEAV. PMID:21880967

  12. Epidemiology of Extended-Spectrum β-Lactamase-Producing E. coli and Vancomycin-Resistant Enterococci in the Northern Dutch-German Cross-Border Region.

    PubMed

    Zhou, Xuewei; García-Cobos, Silvia; Ruijs, Gijs J H M; Kampinga, Greetje A; Arends, Jan P; Borst, Dirk M; Möller, Lieke V; Holman, Nicole D; Schuurs, Theo A; Bruijnesteijn van Coppenraet, Lesla E; Weel, Jan F; van Zeijl, Jan H; Köck, Robin; Rossen, John W A; Friedrich, Alexander W

    2017-01-01

    Objectives: To reveal the prevalence and epidemiology of extended-spectrum β-lactamase (ESBL)- and/or plasmid AmpC (pAmpC)- and carbapenemase (CP) producing Enterobacteriaceae and vancomycin-resistant enterococci (VRE) across the Northern Dutch-German border region. Methods: A point-prevalence study on ESBL/pAmpC/CP producing Enterobacteriaceae and VRE was carried out in hospitalized patients in the Northern Netherlands ( n = 445, 2012-2013) and Germany ( n = 242, 2012). Healthy individuals from the Dutch community ( n = 400, 2010-2012) were also screened. In addition, a genome-wide gene-by-gene approach was applied to study the epidemiology of ESBL- Escherichia coli and VRE. Results: A total of 34 isolates from 27 patients (6.1%) admitted to Dutch hospitals were ESBL/pAmpC positive and 29 ESBL- E. coli , three pAmpC- E. coli , one ESBL- Enterobacter cloacae , and one pAmpC- Proteus mirabilis were found. In the German hospital, 18 isolates (16 E. coli and 2 Klebsiella pneumoniae ) from 17 patients (7.7%) were ESBL positive. In isolates from the hospitalized patients CTX-M-15 was the most frequently detected ESBL-gene. In the Dutch community, 11 individuals (2.75%) were ESBL/pAmpC positive: 10 ESBL - E. coli (CTX-M-1 being the most prevalent gene) and one pAmpC E. coli . Six Dutch (1.3%) and four German (3.9%) hospitalized patients were colonized with VRE. Genetic relatedness by core genome multi-locus sequence typing (cgMLST) was found between two ESBL- E. coli isolates from Dutch and German cross-border hospitals and between VRE isolates from different hospitals within the same region. Conclusion: The prevalence of ESBL/pAmpC- Enterobacteriaceae was similar in hospitalized patients across the Dutch-German border region, whereas VRE prevalence was slightly higher on the German side. The overall prevalence of the studied pathogens was lower in the community than in hospitals in the Northern Netherlands. Cross-border transmission of ESBL- E. coli and VRE seems

  13. Vancomycin-Resistant Enterococci (VRE) in The Intensive Care Unit in a Nonoutbreak Setting: Identification of Potential Reservoirs and Epidemiological Associations Between Patient and Environmental VRE.

    PubMed

    McDermott, Hélène; Skally, Mairead; O'Rourke, James; Humphreys, Hilary; Fitzgerald-Hughes, Deirdre

    2018-01-01

    OBJECTIVE Among nosocomial bloodstream infections caused by enterococcal species, Ireland has the highest proportion caused by vancomycin-resistant enterococci (VRE) in Europe at 45.8%. The contribution of the near-patient environment to VRE transmission outside of outbreaks was investigated. DESIGN A prospective observational study was conducted during 7 sampling periods. METHODS Recovery of VRE isolates by swabbing the near-patient environment and patients in the intensive care unit (ICU) was conducted to identify reservoirs, clinical and molecular epidemiological associations, and the success of active surveillance cultures (ASCs). RESULTS Of 289 sampling occasions involving 157 patients and their bed spaces, VRE isolates were recovered from patient bed spaces, clinical samples, or both on 114 of 289 sampling occasions (39.4%). The patient and their bed space were positive for VRE on 34 of 114 VRE-associated sampling occasions (29.8%). Of 1,647 environment samples, 107 sites (6.5%) were VRE positive, with significantly greater VRE recovery from isolation rooms than from the open-plan area (9.1% vs 4.1%; P < .0001). The most frequently VRE-contaminated sites were the drip stand, bed control panel, and chart holders, which together accounted for 61% of contaminated sites. The use of ASCs resulted in a 172% increase in identification of VRE-colonized patients. Molecular typing revealed 2 environmental clusters, 1 cluster involving 3 patients and generally greater heterogeneity of patient isolates compared to environmental isolates. CONCLUSION Even outside of outbreaks, near-patient ICU environmental contamination with VRE is common. Better infection control policies that limit environmental transmission of VRE in the ICU and that are supported by molecular epidemiological studies, in real time, are needed. Infect Control Hosp Epidemiol 2018;39:40-45.

  14. Antimicrobial Activity Of Essential Oils Against Vancomycin-Resistant Enterococci (Vre) And Escherichia Coli O157:H7 In Feta Soft Cheese And Minced Beef Meat

    PubMed Central

    Selim, Samy

    2011-01-01

    Eleven essential oils (EOs) were evaluated for their antibacterial properties, against Vancomycin-Resistant Enterococci (VRE) and E. coli O157:H7. EOs were introduced into Brain Heart Infusion agar (BHI) (15ml) at a concentration of 0.25 to 2% (vol/vol) to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for each pathogen evaluated. Results showed that the most active essential oils against bacteria tested were thyme oil, with MIC90 and MBC90 for the VRA strains of 0.25% and 0.5%, respectively. Eucalyptus, juniper and clove oils were the least potent agent, with MIC90 and MBC90 of 2%. Furthermore, the inhibitory effect of these EO were evaluated against VRE and E. coli O157:H7, experimentally inoculated (103 cfu/g) in Feta soft cheese and minced beef meat, which was mixed with different concentrations (0.1%, 0.5% and 1%) of the EO and stored at 7 °C for 14 days. Out of eucalyptus, juniper, mint, rosemary, sage, clove and thyme oils tested against target bacteria sage and thyme showed the best results. Clove and mint did not show any effect on VRE and E. coli O157:H7 in both kinds of studied foods. The addition of thyme oil at concentrations of 0.5 and 1% caused best significant reduction in the growth rate of VRE and E. coli O157:H7 in cheese and meat at 7 oC. It is concluded that selected plant EOs can act as potent inhibitors of both microorganisms in a food product. The results revealed the potential of thyme oil as a natural preservative in feta soft cheese and minced beef meat against VRE and E. coli O157:H7 contamination. PMID:24031620

  15. First outbreak of linezolid-resistant vancomycin-resistant Enterococcus faecium in an Irish hospital, February to September 2014.

    PubMed

    O'Driscoll, C; Murphy, V; Doyle, O; Wrenn, C; Flynn, A; O'Flaherty, N; Fenelon, L E; Schaffer, K; FitzGerald, S F

    2015-12-01

    An outbreak of linezolid-resistant vancomycin-resistant Enterococcus faecium (LRVREfm) occurred in the hepatology ward of a tertiary referral hospital in Ireland between February and September 2014. LRVREfm was isolated from 15 patients; pulsed-field gel electrophoresis confirmed spread of a single clone. This is the first report of an outbreak of linezolid-resistant vancomycin-resistant enterococcus in Ireland. Copyright © 2015 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  16. OCCURRENCE OF HIGH-LEVEL AMINOGLYCOSIDE RESISTANCE IN ENVIRONMENTAL ISOLATES OF ENTEROCOCCI

    EPA Science Inventory

    High-level resistance fo aminoglycosides was observed in environmental isolates of enterococci. Various aquatic habitats, including agricultural runoff, creeks, rivers, wastewater, and wells, were analyzed. Strains of Enterococcus faecalis, e.faecium, E. gallinarum, and other Ent...

  17. Titanium-Tethered Vancomycin Prevents Resistance to Rifampicin in Staphylococcus aureus in vitro

    PubMed Central

    Hacking, S. Adam

    2012-01-01

    Rifampicin is currently recognized as the most potent drug against Gram positive implant related infections. The use of rifampicin is limited by the emergence of bacterial resistance, which is often managed by coadministration of a second antibiotic. The purpose of this study was to determine the effectiveness of soluble rifampicin in combination with vancomycin tethered to titanium metal as a means to control bacterial growth and resistance in vitro. Bacterial growth was inhibited when the vancomycin-tethered titanium discs were treated with Staphylococcus aureus inocula of ≤2×106 CFU, however inocula greater than 2×106 CFU/disc adhered and survived. The combination of surface-tethered vancomycin with soluble rifampicin enhanced the inhibitory effect of rifampicin for an inoculum of 106 CFU/cm2 by one dilution (combination MIC of 0.008 mg/L versus 0.015 mg/L for rifampicin alone). Moreover, surface tethered vancomycin prevented the emergence of a rifampicin resistant population in an inoculum of 2×108 CFU. PMID:23285213

  18. Vancomycin-resistant enterococci - hospital

    MedlinePlus

    Arias CA, Murray BE. Enterococcus species, Streptococcus gallolyticus group, and Leuconostoc species. In: Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious ...

  19. Speciation and antimicrobial resistance of Enterococci isolated from recreational beaches in Malaysia.

    PubMed

    Dada, Ayokunle Christopher; Ahmad, Asmat; Usup, Gires; Heng, Lee Yook

    2013-02-01

    We report the first study on the occurrence of antibiotic-resistant enterococci in coastal bathing waters in Malaysia. One hundred and sixty-five enterococci isolates recovered from two popular recreational beaches in Malaysia were speciated and screened for antibiotic resistance to a total of eight antibiotics. Prevalence of Enterococcus faecalis and Enterococcus faecium was highest in both beaches. E. faecalis/E. faecium ratio was 0.384:1 and 0.375:1, respectively, for isolates from Port Dickson (PD) and Bagan Lalang (BL). Analysis of Fisher's exact test showed that association of prevalence of E. faecalis and E. faecium with considered locations was not statistically significant (p < 0.05). Chi-square test revealed significant differences (χ(2) = 82.630, df = 20, p < 0.001) in the frequency of occurrence of enterococci isolates from the considered sites. Resistance was highest to nalidixic acid (94.84 %) and least for chloramphenicol (8.38 %). One-way ANOVA using Tukey-Kramer multiple comparison test showed that resistance to ampicillin was higher in PD beach isolates than BL isolates and the difference was extremely statistically significant (p < 0.0001). Frequency of occurrence of multiple antibiotic resistance (MAR) isolates were higher for PD beach water (64.29 %) as compared to BL beach water (13.51 %), while MAR indices ranged between 0.198 and 0.48. The results suggest that samples from Port Dickson may contain MAR bacteria and that this could be due to high-risk faecal contamination from sewage discharge pipes that drain into the sea water.

  20. Effect of nosocomial vancomycin-resistant enterococcal bacteremia on mortality, length of stay, and costs.

    PubMed

    Song, Xiaoyan; Srinivasan, Arjun; Plaut, David; Perl, Trish M

    2003-04-01

    To determine the impact of vancomycin-resistant enterococcal bacteremia on patient outcomes and costs by assessing mortality, excess length of stay, and charges attributable to it. A population-based, matched, historical cohort study. A 1,025-bed, university-based teaching facility and referral hospital. Two hundred seventy-seven vancomycin-resistant enterococcal bacteremia case-patients and 277 matched control-patients identified between 1993 and 2000. The crude mortality rate was 50.2% and 19.9% for case-patients and control-patients, respectively, yielding a mortality rate of 30.3% attributable to vancomycin-resistant enterococcal bacteremia. The excess length of hospital stay attributable to vancomycin-resistant enterococcal bacteremia was 17 days, of which 12 days were spent in intensive care units. On average, dollars 77,558 in extra charges was attributable to each vancomycin-resistant enterococcal bacteremia. To adjust for severity of illness, 159 pairs of case-patients and control-patients, who had the same severity of illness (All Patient Refined-Diagnosis Related Group complexity level), were further analyzed. When patients were stratified by severity of illness, the crude mortality rate was 50.3% among case-patients compared with 27.7% among control-patients, accounting for an attributable mortality rate of 22.6%. Attributable excess length of stay and charges were 17 days and dollars 81,208, respectively. Vancomycin-resistant enterococcal bacteremia contributes significantly to excess mortality and economic loss, once severity of illness is considered. Efforts to prevent these infections will likely be cost-effective.

  1. Evaluation of antimicrobial resistance and virulence of enterococci from equipment surfaces, raw materials, and traditional cheeses.

    PubMed

    Gaglio, Raimondo; Couto, Natacha; Marques, Cátia; de Fatima Silva Lopes, Maria; Moschetti, Giancarlo; Pomba, Constança; Settanni, Luca

    2016-11-07

    Forty enterococci isolated along the production chains of three traditional cheeses (PDO Pecorino Siciliano, PDO Vastedda della Valle del Belìce, and Caciocavallo Palermitano) made in Sicily (southern Italy) were studied for the assessment of their antibiotic resistance and virulence by a combined phenotypic/genotypic approach. A total of 31 Enterococcus displayed resistance to at least one or more of the antimicrobials tested. The strains exhibited high percentages of resistance to erythromycin (52.5%), ciprofloxacin (35.0%), quinupristin-dalfopristin (20.0%), tetracycline (17.5%), and high-level streptomycin (5.0%). The presence of tet(M), cat(pC221), and aadE genes for resistance to tetracycline, chloramphenicol, and streptomycin, respectively, was registered in all strains with resistance phenotype. The erm(B) gene was not detected in any erythromycin-resistant strain. The Enterococcus strains were further tested by PCR for the presence of virulence genes, namely, gelE, asa1, efaA, ace, and esp. Twenty strains were positive for all virulence genes tested. Among the enterococci isolated from final cheeses, three strains (representing 33.3% of total cheese strains) were sensible to all antimicrobials tested and did not carry any virulence factor. Although this study confirmed that the majority of dairy enterococci are vectors for the dissemination of antimicrobial resistance and virulence genes, only two strains showed a high resistance to aminoglycosides, commonly administered to combat enterococci responsible for human infections. Furthermore, the presence of the strains E. casseliflavus FMAC163, E. durans FMAC134B, and E. faecium PON94 without risk determinants, found at dominating levels over the Enterococcus populations in the processed products, stimulates further investigations for their future applications in cheese making. All strains devoid of the undesired traits were isolated from stretched cheeses. Thus, this cheese typology represents an

  2. Culture methods impact recovery of antibiotic-resistant Enterococci including Enterococcus cecorum from pre- and postharvest chicken.

    PubMed

    Suyemoto, M M; Barnes, H J; Borst, L B

    2017-03-01

    Pathogenic strains of Enterococcus cecorum (EC) expressing multidrug resistance have emerged. In National Antimicrobial Resistance Monitoring System (NARMS) data, EC is rarely recovered from chickens. Two NARMS methodologies (FDA and USDA) were compared with standard culture (SC) techniques for recovery of EC. NARMS methods failed to detect EC in 58 caecal samples, 20 chicken breast or six whole broiler samples. EC was recovered from 1 of 38 (2·6%) and 2 of 38 (5·2%) preharvest spinal lesions (USDA and FDA method, respectively). In contrast, using the SC method, EC was recovered from 44 of 53 (83%) caecal samples, all 38 (100%) spinal lesions, 14 of 20 (70%) chicken breast samples, and all three spinal lesions identified in whole carcasses. Compared with other Enterococcus spp., EC isolates had a higher prevalence of resistance to macrolides. The NARMS methods significantly affected recovery of enterococcal species other than EC. When the postharvest FDA method was applied to preharvest caecal samples, isolates of Enterococcus faecium were preferentially recovered. All 11 E. faecium isolates were multidrug resistant, including resistance to penicillin, daptomycin and linezolid. These findings confirm that current methodologies may not accurately identify the amount and range of antimicrobial resistance of enterococci from chicken sources. Enterococci are an important reservoir for antimicrobial resistance. This study demonstrates how current culture methods underreport resistance to macrolides in enterococci by selecting against strains of Enterococcus cecorum in pre- and postharvest chicken. Further, the application of postharvest surveillance methods to preharvest samples resulted in selective recovery of Enterococcus faecium over Enterococcus faecalis. Isolates of E. faecium recovered exhibited multidrug resistance including penicillin, daptomycin and linezolid resistance. These findings suggest that culture methodology significantly impacts the range and

  3. Treatment of methicillin-resistant Staphylococcus aureus: vancomycin and beyond.

    PubMed

    Holmes, Natasha E; Tong, Steven Y C; Davis, Joshua S; van Hal, Sebastiaan J

    2015-02-01

    There has been a welcome increase in the number of agents available for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). Vancomycin remains an acceptable treatment option, with moves toward individualized dosing to a pharmacokinetic/pharmacodynamic (PK/PD) target. Numerous practicalities, however, would need to be resolved before implementation. Lipoglycopeptides as a class show excellent in vitro potency. Their long half-lives and complex PKs may preclude these agents being used in critically ill patients. Anti-MRSA cephalosporins provide great promise in the treatment of MRSA. These agents, despite broad-spectrum activity, should be reserved for patients with MRSA infections as it is likely that usage will be associated with increased rates of resistance. Daptomycin is currently the only antibiotic to have shown noninferiority to vancomycin in the treatment of MRSA bacteremia. The results of an open-labeled trial to address the superiority of daptomycin compared with vancomycin in reduced vancomycin susceptibility infections are eagerly anticipated. No drug to date has shown superiority to vancomycin in the treatment of MRSA infections with the possible exception of linezolid in hospital-acquired pneumonia (HAP), making linezolid an important option in the treatment of MRSA-proven HAP. Whether these strengths and features are agent or class specific are unclear but will likely be answered with the marketing of tedizolid. There are insufficient data to recommend either quinupristin/dalfopristin or tigecycline, as first line in the treatment of severe MRSA infections. These agents however remain options in patients with no other alternatives. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  4. Vancomycin-resistant Staphylococcus aureus (VRSA) in hepatic cirrhosis patient: a case report

    NASA Astrophysics Data System (ADS)

    Ramazoni, M.; Siregar, M. L.; Jamil, K. F.

    2018-03-01

    The irrational use of vancomycin in methicillin-resistant Staphylococcus aureus (MRSA) infections result in the emergence of vancomycin-resistant Staphylococcus aureus (VRSA) pathogen, which can pose a threat to the world healthcare. A 32-year-old male with hepatic cirrhosis patient admitted with recurrent gastrointestinal bleeding with a wound in his left leg since 6 months ago; the result microbiological culture showed a VRSA with minimum inhibitory concentration (MIC) vancomycin ≥32μg/mL The patient was treated with trimethoprim/sulfamethoxazole combination according to cultural sensitivity. The second microbiological culture showed thesame result. VRSA is a rare and difficult condition to handle. The success of therapy for this VRSA case warn us how important to cut the S. aureus distribution chain with a high level of resistance.

  5. Titanium-tethered vancomycin prevents resistance to rifampicin in Staphylococcus aureus in vitro.

    PubMed

    Rottman, Martin; Goldberg, Joel; Hacking, S Adam

    2012-01-01

    Rifampicin is currently recognized as the most potent drug against Gram positive implant related infections. The use of rifampicin is limited by the emergence of bacterial resistance, which is often managed by coadministration of a second antibiotic. The purpose of this study was to determine the effectiveness of soluble rifampicin in combination with vancomycin tethered to titanium metal as a means to control bacterial growth and resistance in vitro. Bacterial growth was inhibited when the vancomycin-tethered titanium discs were treated with Staphylococcus aureus inocula of ≤2×10⁶ CFU, however inocula greater than 2×10⁶ CFU/disc adhered and survived. The combination of surface-tethered vancomycin with soluble rifampicin enhanced the inhibitory effect of rifampicin for an inoculum of 10⁶ CFU/cm² by one dilution (combination MIC of 0.008 mg/L versus 0.015 mg/L for rifampicin alone). Moreover, surface tethered vancomycin prevented the emergence of a rifampicin resistant population in an inoculum of 2×10⁸ CFU.

  6. Transport and persistence of tylosin-resistant enterococci, erm genes, and tylosin in soil and drainage water from fields receiving swine manure

    USDA-ARS?s Scientific Manuscript database

    Land application of manure from tylosin-treated swine introduces tylosin-resistant enterococci, erm genes, which confer resistance to tylosin, and tylosin. This study documents the occurrence and transport of tylosin-resistant enterococci, erm genes, and tylosin in tile-drained chisel plow and no-ti...

  7. Effect of in-feed administration and withdrawal of tylosin phosphate on antibiotic resistance in enterococci isolated from feedlot steers

    PubMed Central

    Beukers, Alicia G.; Zaheer, Rahat; Cook, Shaun R.; Stanford, Kim; Chaves, Alexandre V.; Ward, Michael P.; McAllister, Tim A.

    2015-01-01

    Tylosin phosphate is a macrolide commonly administered to cattle in North America for the control of liver abscesses. This study investigated the effect of in-feed administration of tylosin phosphate to cattle at subtherapeutic levels and its subsequent withdrawal on macrolide resistance using enterococci as an indicator bacterium. Fecal samples were collected from steers that received no antibiotics and steers administered tylosin phosphate (11 ppm) in-feed for 197 days and withdrawn 28 days before slaughter. Enterococcus species isolated from fecal samples were identified through sequencing the groES-EL intergenic spacer region and subject to antimicrobial susceptibility testing, identification of resistance determinants and pulsed-field gel electrophoresis profiling. Tylosin increased (P < 0.05) the proportion of eryR and tylR enterococci within the population. Just prior to its removal, the proportion of eryR and tylR resistant enterococci began decreasing and continued to decrease after tylosin was withdrawn from the diet until there was no difference (P > 0.05) between treatments on d 225. This suggests that antibiotic withdrawal prior to slaughter contributes to a reduction in the proportion of macrolide resistant enterococci entering the food chain. Among the 504 enterococci isolates characterized, Enterococcus hirae was found to predominate (n = 431), followed by Enterococcus villorum (n = 32), Enterococcus faecium (n = 21), Enterococcus durans (n = 7), Enterococcus casseliflavus (n = 4), Enterococcus mundtii (n = 4), Enterococcus gallinarum (n = 3), Enterococcus faecalis (n = 1), and Enterococcus thailandicus (n = 1). The diversity of enterococci was greater in steers at arrival than at exit from the feedlot. Erythromycin resistant isolates harbored the erm(B) and/or msrC gene. Similar PFGE profiles of eryR E. hirae pre- and post-antibiotic treatment suggest that increased abundance of eryR enterococci after administration of tylosin phosphate reflects

  8. Potential of houseflies to contaminate ready-to-eat food with antibiotic-resistant enterococci.

    PubMed

    Macovei, Lilia; Miles, Brett; Zurek, Ludek

    2008-02-01

    It was shown previously that houseflies in fast-food restaurants commonly carry antibiotic-resistant and potentially virulent enterococci. In this study, the potential of field-collected houseflies to contaminate ready-to-eat (RTE) food with enterococci was assessed by laboratory bioassays. Houseflies were collected with a sweep net in a cattle feedlot and exposed in groups of 5, 10, 20, and 40 to a beef patty (from an RTE hamburger) for 0.5, 1.0, 3.0, and 24 h. The exposure of RTE food to flies resulted in 100% contamination with enterococci in all bioassays, regardless of the number of houseflies and the length of exposure time. In addition, with the increasing number of houseflies as well as with the increasing time exposure, the concentration of enterococci in RTE food increased. Even a short time exposure (0.5 h) resulted in food contamination, ranging from 3.1 x 10(3) CFU/g (5 houseflies) to 8.4 x 10(4) CFU/g (40 houseflies). The analysis of 23 randomly selected enterococcal isolates from RTE food after the fly exposure revealed a single species, Enterococcus faecalis. In contrast, four Enterococcus species, including E. faecalis (57.1%), E. gallinarum (19.1%), E. hirae (14.3%), and E. faecium (9.5%), represented 21 randomly selected and identified isolates from houseflies. Phenotypic screening showed that E. faecalis isolates from RTE food were resistant to ciprofloxacin (17.4%), tetracycline (13.0%), erythromycin (13.0%), and chloramphenicol (4.3%). This study demonstrates a great potential of houseflies from a cattle feedlot to contaminate RTE food with enterococci in a short time.

  9. Presence of the vancomycin resistance gene cluster vanC1, vanXYc, and vanT in Enterococcus casseliflavus.

    PubMed

    Hölzel, Christina; Bauer, Johann; Stegherr, Eva-Maria; Schwaiger, Karin

    2014-04-01

    The three chromosomally located clustered genes vanC1, vanXYc, and vanT confer intrinsic resistance to vancomycin and are used for species identification of Enterococcus gallinarum. In this study, 28 strains belonging to the E. gallinarum/casseliflavus group isolated from cloacal swabs from laying hens were screened for the presence of vanC1. As confirmed by species-specific multiplex PCR, 11 vanC1-positive strains were identified as E. gallinarum. Surprisingly, one yellow pigmented strain, verified as E. casseliflavus by species-specific multiplex PCR, was also vanC1 positive; vanXYc and vanT were additionally detectable in this strain. To our knowledge, this is the first report of vanC1, vanXYc, and vanT in E. casseliflavus. The minimum inhibitory concentration of vancomycin was 4 mg/L. Real-time reverse transcription-PCR revealed that none of the clustered genes was expressed in this strain. Even if the genes seem not to be active, there is a certain risk that they will be transferred to other bacteria where they might be functionally expressed. Therefore, it may be advisable to expand the search for vanC1, vanXYc, and vanT from E. gallinarum to other (enterococcal) species. This study confirms that enterococci live up to their name as being reservoir bacteria and should therefore always be closely monitored.

  10. Molecular characterization of antibiotic resistance in enterococci recovered from seagulls (Larus cachinnans) representing an environmental health problem.

    PubMed

    Radhouani, Hajer; Igrejas, Gilberto; Pinto, Luís; Gonçalves, Alexandre; Coelho, Céline; Rodrigues, Jorge; Poeta, Patrícia

    2011-08-01

    Antimicrobial resistance and the mechanisms implicated were studied in 54 enterococci recovered from 57 seagull fecal samples. Almost 78% of the recovered enterococci showed resistance against one or more antibiotics and these isolates were identified to the species level. E. faecium was the most prevalent species (52.4%). High percentages of erythromycin and tetracycline resistances were found among our isolates (95.2%), and lower percentages were identified to other antibiotics. Most of the tetracycline-resistant strains carried the tet(M) and/or tet(L) genes. Genes associated with Tn916/Tn1545 and/or Tn5397 transposons were detected in 45% of tetracycline-resistant isolates. The erm(B) gene was detected in 65% of erythromycin-resistant isolates. The vat(D) and vat(E) genes were present in 5.9% and 11.8% of quinupristin/dalfopristin-resistant isolates, respectively. The ant(6)-Ia gene was identified in 57.1% of streptomycin-resistant isolates. All nine kanamycin-resistant isolates carried the aph(3)'-IIIa gene. The cat(A) gene was found in two chloramphenicol-resistant isolates. Seagulls should be considered a risk species for spreading in the environment antimicrobial resistant enterococci and can serve as a sentinel for antibiotic pressure from the surrounding farm and urban setting.

  11. Accumulation of phosphatidic acid increases vancomycin resistance in Escherichia coli.

    PubMed

    Sutterlin, Holly A; Zhang, Sisi; Silhavy, Thomas J

    2014-09-01

    In Gram-negative bacteria, lipopolysaccharide (LPS) contributes to the robust permeability barrier of the outer membrane, preventing entry of toxic molecules such as antibiotics. Mutations in lptD, the beta-barrel component of the LPS transport and assembly machinery, compromise LPS assembly and result in increased antibiotic sensitivity. Here, we report rare vancomycin-resistant suppressors that improve barrier function of a subset of lptD mutations. We find that all seven suppressors analyzed mapped to the essential gene cdsA, which is responsible for the conversion of phosphatidic acid to CDP-diacylglycerol in phospholipid biosynthesis. These cdsA mutations cause a partial loss of function and, as expected, accumulate phosphatidic acid. We show that this suppression is not confined to mutations that cause defects in outer membrane biogenesis but rather that these cdsA mutations confer a general increase in vancomycin resistance, even in a wild-type cell. We use genetics and quadrupole time of flight (Q-TOF) liquid chromatography-mass spectrometry (LC-MS) to show that accumulation of phosphatidic acid by means other than cdsA mutations also increases resistance to vancomycin. We suggest that increased levels of phosphatidic acid change the physical properties of the outer membrane to impede entry of vancomycin into the periplasm, hindering access to its target, an intermediate required for the synthesis of the peptidoglycan cell wall. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  12. High-Level Fosfomycin Resistance in Vancomycin-Resistant Enterococcus faecium

    PubMed Central

    Guo, Yan; Tomich, Adam D.; McElheny, Christi L.; Cooper, Vaughn S.; Tait-Kamradt, Amelia; Wang, Minggui; Hu, Fupin; Rice, Louis B.; Sluis-Cremer, Nicolas

    2017-01-01

    Of 890 vancomycin-resistant Enterococcus faecium isolates obtained by rectal screening from patients in Pittsburgh, Pennsylvania, USA, 4 had MICs >1,024 μg/mL for fosfomycin. These isolates had a Cys119Asp substitution in the active site of UDP-N-acetylglucosamine enolpyruvyl transferase. This substitution increased the fosfomycin MIC >4-fold and rendered this drug inactive in biochemical assays. PMID:29048285

  13. Typing of vancomycin-resistant enterococci with MALDI-TOF mass spectrometry in a nosocomial outbreak setting.

    PubMed

    Holzknecht, B J; Dargis, R; Pedersen, M; Pinholt, M; Christensen, J J

    2018-03-23

    To investigate the usefulness of matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) typing as a first-line epidemiological tool in a nosocomial outbreak of vancomycin-resistant Enterococcus faecium (VREfm). Fifty-five VREfm isolates, previously characterized by whole-genome sequencing (WGS), were included and analysed by MALDI-TOF MS. To take peak reproducibility into account, ethanol/formic acid extraction and other steps of the protocol were conducted in triplicate. Twenty-seven spectra were generated per isolate, and spectra were visually inspected to determine discriminatory peaks. The presence or absence of these was recorded in a peak scheme. Nine discriminatory peaks were identified. A characteristic pattern of these could distinguish between the three major WGS groups: WGS I, WGS II and WGS III. Only one of 38 isolates belonging to WGS I, WGS II or WGS III was misclassified. However, ten of the 17 isolates not belonging to WGS I, II or III displayed peak patterns indistinguishable from those of the outbreak strain. Using visual inspection of spectra, MALDI-TOF MS typing proved to be useful in differentiating three VREfm outbreak clones from each other. However, as non-outbreak isolates could not be reliably differentiated from outbreak clones, the practical value of this typing method for VREfm outbreak management was limited in our setting. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  14. Identification of VanN-type vancomycin resistance in an Enterococcus faecium isolate from chicken meat in Japan.

    PubMed

    Nomura, Takahiro; Tanimoto, Koichi; Shibayama, Keigo; Arakawa, Yoshichika; Fujimoto, Shuhei; Ike, Yasuyoshi; Tomita, Haruyoshi

    2012-12-01

    Five VanN-type vancomycin-resistant Enterococcus faecium strains were isolated from a sample of domestic chicken meat in Japan. All isolates showed low-level resistance to vancomycin (MIC, 12 mg/liter) and had the same pulsed-field gel electrophoresis profile. The vancomycin resistance was encoded on a large plasmid (160 kbp) and was expressed constitutively. The VanN-type resistance operon was identical to the first resistance operon to be reported, with the exception of a 1-bp deletion in vanT(N) and a 1-bp substitution in vanS(N).

  15. Occurrence of antibiotic resistance genes and mobile genetic elements in enterococci and genomic DNA during anaerobic digestion of pharmaceutical waste sludge with different pretreatments.

    PubMed

    Tong, Juan; Lu, XueTing; Zhang, JunYa; Sui, Qianwen; Wang, Rui; Chen, Meixue; Wei, Yuansong

    2017-07-01

    Pharmaceutical waste sludge harbors large amounts of antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs), and it is necessary to study the reduction of ARGs and MGEs during sludge treatment. Therefore, the antibiotic resistance phenotypes and genotypes of enterococci, and the ARGs and MGEs in genomic DNA were investigated during anaerobic digestion (AD) with microwave (MW), thermal hydrolysis (TH) and ozone pretreatment. Results showed that sludge pretreatment increased the occurrence of the resistance phenotypes and genotypes of enterococci. During AD, the resistance of enterococci to macrolides decreased, except for in the MW-pretreated sludge. Horizontal gene transfer and co-occurrence of ermB and tetM in enterococci resulted in increased tetracycline resistance of enterococci throughout the sludge treatment. MGEs such as intI1, ISCR1 and Tn916/1545 had a significant effect on the distribution of ARGs. AD with pretreatment, especially TH pretreatment, resulted in greater ARGs and MGEs reduction and improved methane production. Copyright © 2017. Published by Elsevier Ltd.

  16. Evolutionary dynamics of Enterococcus faecium reveals complex genomic relationships between isolates with independent emergence of vancomycin resistance

    PubMed Central

    Ip, Camilla L. C.; Ansari, M. Azim; Wilson, Daniel J.; Espedido, Bjorn A.; Jensen, Slade O.; Bowden, Rory

    2016-01-01

    Enterococcus faecium, a major cause of hospital-acquired infections, remains problematic because of its propensity to acquire resistance to vancomycin, which currently is considered first-line therapy. Here, we assess the evolution and resistance acquisition dynamics of E. faecium in a clinical context using a series of 132 bloodstream infection isolates from a single hospital. All isolates, of which 49 (37 %) were vancomycin-resistant, underwent whole-genome sequencing. E. faecium was found to be subject to high rates of recombination with little evidence of sequence importation from outside the local E. faecium population. Apart from disrupting phylogenetic reconstruction, recombination was frequent enough to invalidate MLST typing in the identification of clonal expansion and transmission events, suggesting that, where available, whole-genome sequencing should be used in tracing the epidemiology of E. faecium nosocomial infections and establishing routes of transmission. Several forms of the Tn1549-like element–vanB gene cluster, which was exclusively responsible for vancomycin resistance, appeared and spread within the hospital during the study period. Several transposon gains and losses and instances of in situ evolution were inferred and, although usually chromosomal, the resistance element was also observed on a plasmid background. There was qualitative evidence for clonal expansions of both vancomycin-resistant and vancomycin-susceptible E. faecium with evidence of hospital-specific subclonal expansion. Our data are consistent with continuing evolution of this established hospital pathogen and confirm hospital vancomycin-susceptible and vancomycin-resistant E. faecium patient transmission events, underlining the need for careful consideration before modifying current E. faecium infection control strategies. PMID:27713836

  17. Evolutionary dynamics of Enterococcus faecium reveals complex genomic relationships between isolates with independent emergence of vancomycin resistance.

    PubMed

    van Hal, Sebastiaan J; Ip, Camilla L C; Ansari, M Azim; Wilson, Daniel J; Espedido, Bjorn A; Jensen, Slade O; Bowden, Rory

    2016-01-19

    Enterococcus faecium , a major cause of hospital-acquired infections, remains problematic because of its propensity to acquire resistance to vancomycin, which currently is considered first-line therapy. Here, we assess the evolution and resistance acquisition dynamics of E. faecium in a clinical context using a series of 132 bloodstream infection isolates from a single hospital. All isolates, of which 49 (37 %) were vancomycin-resistant, underwent whole-genome sequencing. E. faecium was found to be subject to high rates of recombination with little evidence of sequence importation from outside the local E. faecium population. Apart from disrupting phylogenetic reconstruction, recombination was frequent enough to invalidate MLST typing in the identification of clonal expansion and transmission events, suggesting that, where available, whole-genome sequencing should be used in tracing the epidemiology of E. faecium nosocomial infections and establishing routes of transmission. Several forms of the Tn 1549 -like element- vanB gene cluster, which was exclusively responsible for vancomycin resistance, appeared and spread within the hospital during the study period. Several transposon gains and losses and instances of in situ evolution were inferred and, although usually chromosomal, the resistance element was also observed on a plasmid background. There was qualitative evidence for clonal expansions of both vancomycin-resistant and vancomycin-susceptible E. faecium with evidence of hospital-specific subclonal expansion. Our data are consistent with continuing evolution of this established hospital pathogen and confirm hospital vancomycin-susceptible and vancomycin-resistant E. faecium patient transmission events, underlining the need for careful consideration before modifying current E. faecium infection control strategies.

  18. Vancomycin-Resistant Gram-Positive Cocci Isolated from the Saliva of Wild Songbirds

    PubMed Central

    Ishihara, Shingo; Bitner, Jessica J.; Farley, Greg H.

    2014-01-01

    We analyzed highly vancomycin-resistant Gram-positive bacteria isolated from the saliva of migratory songbirds captured, sampled, and released from a birdbanding station in western Kansas. Individual bacterial isolates were identified by partial 16S rRNA sequencing. Most of the bacteria in this study were shown to be Staphylococcus succinus with the majority being isolated from the American Robin. Some of these bacteria were shown to carry vanA, vanB, and vanC vancomycin-resistance genes and have the ability to form biofilms. One of the van gene-carrying isolates is also coagulase positive, which is normally considered a virulence factor. Other organisms isolated included Staphylococcus saprophyticus as well as Enterococcus gallinarum. Given the wide range of the American Robin and ease of horizontal gene transfer between Gram-positive cocci, we postulate that these organisms could serve as a reservoir of vancomycin-resistance genes capable of transferring to human pathogens. PMID:23224296

  19. Vancomycin-resistant gram-positive cocci isolated from the saliva of wild songbirds.

    PubMed

    Ishihara, Shingo; Bitner, Jessica J; Farley, Greg H; Gillock, Eric T

    2013-04-01

    We analyzed highly vancomycin-resistant Gram-positive bacteria isolated from the saliva of migratory songbirds captured, sampled, and released from a bird-banding station in western Kansas. Individual bacterial isolates were identified by partial 16S rRNA sequencing. Most of the bacteria in this study were shown to be Staphylococcus succinus with the majority being isolated from the American Robin. Some of these bacteria were shown to carry vanA, vanB, and vanC vancomycin-resistance genes and have the ability to form biofilms. One of the van gene-carrying isolates is also coagulase positive, which is normally considered a virulence factor. Other organisms isolated included Staphylococcus saprophyticus as well as Enterococcus gallinarum. Given the wide range of the American Robin and ease of horizontal gene transfer between Gram-positive cocci, we postulate that these organisms could serve as a reservoir of vancomycin-resistance genes capable of transferring to human pathogens.

  20. Surface Ligand Density of Antibiotic-Nanoparticle Conjugates Enhances Target Avidity and Membrane Permeabilization of Vancomycin-Resistant Bacteria.

    PubMed

    Hassan, Marwa M; Ranzoni, Andrea; Phetsang, Wanida; Blaskovich, Mark A T; Cooper, Matthew A

    2017-02-15

    Many bacterial pathogens have now acquired resistance toward commonly used antibiotics, such as the glycopeptide antibiotic vancomycin. In this study, we show that immobilization of vancomycin onto a nanometer-scale solid surface with controlled local density can potentiate antibiotic action and increase target affinity of the drug. Magnetic nanoparticles were conjugated with vancomycin and used as a model system to investigate the relationship between surface density and drug potency. We showed remarkable improvement in minimum inhibitory concentration against vancomycin-resistant strains with values of 13-28 μg/mL for conjugated vancomycin compared to 250-4000 μg/mL for unconjugated vancomycin. Higher surface densities resulted in enhanced affinity toward the bacterial target compared to that of unconjugated vancomycin, as measured by a competition experiment using a surrogate ligand for bacterial Lipid II, N-Acetyl-l-Lys-d-Ala-d-Ala. High density vancomycin nanoparticles required >64 times molar excess of ligand (relative to the vancomycin surface density) to abrogate antibacterial activity compared to only 2 molar excess for unconjugated vancomycin. Further, the drug-nanoparticle conjugates caused rapid permeabilization of the bacterial cell wall within 2 h, whereas no effect was seen with unconjugated vancomycin, suggesting additional modes of action for the nanoparticle-conjugated drug. Hence, immobilization of readily available antibiotics on nanocarriers may present a general strategy for repotentiating drugs that act on bacterial membranes or membrane-bound targets but have lost effectiveness against resistant bacterial strains.

  1. Multidrug-resistant enterococci lack CRISPR-cas.

    PubMed

    Palmer, Kelli L; Gilmore, Michael S

    2010-10-12

    Clustered, regularly interspaced short palindromic repeats (CRISPR) provide bacteria and archaea with sequence-specific, acquired defense against plasmids and phage. Because mobile elements constitute up to 25% of the genome of multidrug-resistant (MDR) enterococci, it was of interest to examine the codistribution of CRISPR and acquired antibiotic resistance in enterococcal lineages. A database was built from 16 Enterococcus faecalis draft genome sequences to identify commonalities and polymorphisms in the location and content of CRISPR loci. With this data set, we were able to detect identities between CRISPR spacers and sequences from mobile elements, including pheromone-responsive plasmids and phage, suggesting that CRISPR regulates the flux of these elements through the E. faecalis species. Based on conserved locations of CRISPR and CRISPR-cas loci and the discovery of a new CRISPR locus with associated functional genes, CRISPR3-cas, we screened additional E. faecalis strains for CRISPR content, including isolates predating the use of antibiotics. We found a highly significant inverse correlation between the presence of a CRISPR-cas locus and acquired antibiotic resistance in E. faecalis, and examination of an additional eight E. faecium genomes yielded similar results for that species. A mechanism for CRISPR-cas loss in E. faecalis was identified. The inverse relationship between CRISPR-cas and antibiotic resistance suggests that antibiotic use inadvertently selects for enterococcal strains with compromised genome defense.

  2. Characterization of Class IIa Bacteriocin Resistance in Enterococcus faecium

    PubMed Central

    Geldart, Kathryn

    2017-01-01

    ABSTRACT Vancomycin-resistant enterococci, particularly resistant Enterococcus faecium, pose an escalating threat in nosocomial environments because of their innate resistance to many antibiotics, including vancomycin, a treatment of last resort. Many class IIa bacteriocins strongly target these enterococci and may offer a potential alternative for the management of this pathogen. However, E. faecium's resistance to these peptides remains relatively uncharacterized. Here, we explored the development of resistance of E. faecium to a cocktail of three class IIa bacteriocins: enterocin A, enterocin P, and hiracin JM79. We started by quantifying the frequency of resistance to these peptides in four clinical isolates of E. faecium. We then investigated the levels of resistance of E. faecium 6E6 mutants as well as their fitness in different carbon sources. In order to elucidate the mechanism of resistance of E. faecium to class IIa bacteriocins, we completed whole-genome sequencing of resistant mutants and performed reverse transcription-quantitative PCR (qRT-PCR) of a suspected target mannose phosphotransferase (ManPTS). We then verified this ManPTS's role in bacteriocin susceptibility by showing that expression of the ManPTS in Lactococcus lactis results in susceptibility to the peptide cocktail. Based on the evidence found from these studies, we conclude that, in accord with other studies in E. faecalis and Listeria monocytogenes, resistance to class IIa bacteriocins in E. faecium 6E6 is likely caused by the disruption of a particular ManPTS, which we believe we have identified. PMID:28115354

  3. Surveillance of bacterial contamination in small animal veterinary hospitals with special focus on antimicrobial resistance and virulence traits of enterococci.

    PubMed

    KuKanich, Kate S; Ghosh, Anuradha; Skarbek, Jennifer V; Lothamer, Kale M; Zurek, Ludek

    2012-02-15

    To determine the prevalence of bacterial contamination on 4 surfaces of 4 types of standard equipment in small animal veterinary hospitals. Surveillance study. 10 small animal veterinary hospitals. Each hospital was visited 3 times at 4-month intervals; at each visit, a cage door, stethoscope, rectal thermometer, and mouth gag were swabbed. Swab samples were each plated onto media for culture of enterococci and organisms in the family Enterobacteriaceae. Enterococci were identified via a species-specific PCR assay and sodA gene sequencing; species of Enterobacteriaceae were identified with a biochemical test kit. Antimicrobial susceptibility was assessed via the disk diffusion method. Enterococci were screened for virulence traits and genotyped to assess clonality. Among the 10 hospitals, enterococci were isolated from cage doors in 7, from stethoscopes in 7, from thermometers in 6, and from mouth gags in 1; contamination with species of Enterobacteriaceae was rare. Enterococci were mainly represented by Enterococcus faecium (35.4%), Enterococcus faecalis (33.2%), and Enterococcus hirae (28.3%). Antimicrobial resistance was common in E. faecium, whereas virulence traits were present in 99% of E. faecalis isolates but not in E. faecium isolates. Clonal multidrug-resistant E. faecium was isolated from several surfaces at 1 hospital over multiple visits, whereas sporadic nonclonal contamination was detected in other hospitals. Contamination of surfaces in small animal veterinary hospitals with multidrug-resistant enterococci is a potential concern for pets and humans contacting these surfaces. Implementing precautions to minimize enterococcal contamination on these surfaces is recommended.

  4. Characterization of antibiotic resistant enterococci isolated from untreated waters for human consumption in Portugal.

    PubMed

    Macedo, Ana S; Freitas, Ana R; Abreu, Cristina; Machado, Elisabete; Peixe, Luísa; Sousa, João C; Novais, Carla

    2011-01-31

    Untreated drinking water is frequently overlooked as a source of antibiotic resistance in developed countries. To gain further insight on this topic, we isolated the indicator bacteria Enterococcus spp. from water samples collected in wells, fountains and natural springs supplying different communities across Portugal, and characterized their antibiotic resistance profile with both phenotypic and genetic approaches. We found various rates of resistance to seven antibiotic families. Over 50% of the isolates were resistant to at least ciprofloxacin, tetracyclines or quinupristin-dalfopristin and 57% were multidrug resistant to ≥3 antibiotics from different families. Multiple enterococcal species (E. faecalis, E. faecium, E. hirae, E. casseliflavus and other Enterococcus spp) from different water samples harbored genes encoding resistance to tetracyclines, erythromycin or gentamicin [tet(M)-46%, tet(L)-14%, tet(S)-5%, erm(B)-22%, aac(6´)-Ie-aph(2″)-12%] and putative virulence factors [gel-28%, asa1-16%]. The present study positions untreated drinking water within the spectrum of ecological niches that may be reservoirs of or vehicles for antibiotic resistant enterococci/genes. These findings are worthy of attention as spread of antibiotic resistant enterococci to humans and animals through water ingestion cannot be dismissed. Copyright © 2010 Elsevier B.V. All rights reserved.

  5. DdlN from Vancomycin-Producing Amycolatopsis orientalis C329.2 Is a VanA Homologue with d-Alanyl-d-Lactate Ligase Activity

    PubMed Central

    Marshall, C. Gary; Wright, Gerard D.

    1998-01-01

    Vancomycin-resistant enterococci acquire high-level resistance to glycopeptide antibiotics through the synthesis of peptidoglycan terminating in d-alanyl-d-lactate. A key enzyme in this process is a d-alanyl-d-alanine ligase homologue, VanA or VanB, which preferentially catalyzes the synthesis of the depsipeptide d-alanyl-d-lactate. We report the overexpression, purification, and enzymatic characterization of DdlN, a VanA and VanB homologue encoded by a gene of the vancomycin-producing organism Amycolatopsis orientalis C329.2. Evaluation of kinetic parameters for the synthesis of peptides and depsipeptides revealed a close relationship between VanA and DdlN in that depsipeptide formation was kinetically preferred at physiologic pH; however, the DdlN enzyme demonstrated a narrower substrate specificity and commensurately increased affinity for d-lactate in the C-terminal position over VanA. The results of these functional experiments also reinforce the results of previous studies that demonstrated that glycopeptide resistance enzymes from glycopeptide-producing bacteria are potential sources of resistance enzymes in clinically relevant bacteria. PMID:9791137

  6. Prevalence of vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous VISA among methicillin-resistant S. aureus with high vancomycin minimal inhibitory concentrations in Taiwan: A multicenter surveillance study, 2012-2013.

    PubMed

    Huang, Sung-Hsi; Chen, Yee-Chun; Chuang, Yin-Ching; Chiu, Sheng-Kang; Fung, Chang-Phone; Lu, Po-Liang; Wang, Lih-Shinn; Wu, Tsu-Lan; Wang, Jann-Tay

    2016-10-01

    Intermediate-resistance and heteroresistance to vancomycin in methicillin-resistant Staphylococcus aureus (MRSA) is reported worldwide. A surveillance study in 2003 showed that the prevalence rates of vancomycin-intermediate S. aureus (VISA) and heterogeneous VISA (hVISA) in Taiwan were 0.2% and 0.7%, respectively. This study aimed to investigate the updated prevalence of VISA and hVISA in Taiwan. MRSA isolates from sterile sites with minimal inhibitory concentrations (MICs) of 1 μg/mL or more to vancomycin were collected from 15 participating hospitals in Taiwan. Enrolled MRSA isolates were submitted to antimicrobial susceptibility testing, staphylococcal cassette chromosome mec (SCCmec) element typing, and multilocus sequence typing. Isolates with vancomycin MIC of 1 μg/mL or 2 μg/mL were screened for vancomycin heterogeneous resistance by Etest glycopeptide-resistance detection (GRD). Those with positive GRD screening results were then analyzed by modified population analysis profiling-area under the curve method for confirmation of vancomycin heteroresistance. Between 2012 and 2013, a total of 622 MRSA isolates from sterile sites with vancomycin MIC of 1 μg/mL or more were studied. The prevalence rates of hVISA and VISA among these isolates were 10.0% and 2.7%, respectively. The hVISA prevalence increased significantly compared to that in 2003. Compared with vancomycin-susceptible S. aureus, hVISA and VISA isolates were less susceptible to ciprofloxacin, clindamycin, daptomycin, gentamicin, rifampin, and trimethoprim/sulfamethoxazole, and are thus, more likely to have SCCmec II or III element. A twofold increase in either vancomycin or teicoplanin MIC doubled the probability of being hVISA. Growing hVISA prevalence was highly suspected. Longitudinal surveillance of this phenomenon and monitoring of its clinical impact are necessary. Copyright © 2015. Published by Elsevier B.V.

  7. Ecology of Antibiotic Resistance Genes: Characterization of Enterococci from Houseflies Collected in Food Settings†

    PubMed Central

    Macovei, Lilia; Zurek, Ludek

    2006-01-01

    In this project, enterococci from the digestive tracts of 260 houseflies (Musca domestica L.) collected from five restaurants were characterized. Houseflies frequently (97% of the flies were positive) carried enterococci (mean, 3.1 × 103 CFU/fly). Using multiplex PCR, 205 of 355 randomly selected enterococcal isolates were identified and characterized. The majority of these isolates were Enterococcus faecalis (88.2%); in addition, 6.8% were E. faecium, and 4.9% were E. casseliflavus. E. faecalis isolates were phenotypically resistant to tetracycline (66.3%), erythromycin (23.8%), streptomycin (11.6%), ciprofloxacin (9.9%), and kanamycin (8.3%). Tetracycline resistance in E. faecalis was encoded by tet(M) (65.8%), tet(O) (1.7%), and tet(W) (0.8%). The majority (78.3%) of the erythromycin-resistant E. faecalis isolates carried erm(B). The conjugative transposon Tn916 and members of the Tn916/Tn1545 family were detected in 30.2% and 34.6% of the identified isolates, respectively. E. faecalis carried virulence genes, including a gelatinase gene (gelE; 70.7%), an aggregation substance gene (asa1; 33.2%), an enterococcus surface protein gene (esp; 8.8%), and a cytolysin gene (cylA; 8.8%). Phenotypic assays showed that 91.4% of the isolates with the gelE gene were gelatinolytic and that 46.7% of the isolates with the asa1 gene aggregated. All isolates with the cylA gene were hemolytic on human blood. This study showed that houseflies in food-handling and -serving facilities carry antibiotic-resistant and potentially virulent enterococci that have the capacity for horizontal transfer of antibiotic resistance genes to other bacteria. PMID:16751512

  8. Ecology of antibiotic resistance genes: characterization of enterococci from houseflies collected in food settings.

    PubMed

    Macovei, Lilia; Zurek, Ludek

    2006-06-01

    In this project, enterococci from the digestive tracts of 260 houseflies (Musca domestica L.) collected from five restaurants were characterized. Houseflies frequently (97% of the flies were positive) carried enterococci (mean, 3.1 x 10(3) CFU/fly). Using multiplex PCR, 205 of 355 randomly selected enterococcal isolates were identified and characterized. The majority of these isolates were Enterococcus faecalis (88.2%); in addition, 6.8% were E. faecium, and 4.9% were E. casseliflavus. E. faecalis isolates were phenotypically resistant to tetracycline (66.3%), erythromycin (23.8%), streptomycin (11.6%), ciprofloxacin (9.9%), and kanamycin (8.3%). Tetracycline resistance in E. faecalis was encoded by tet(M) (65.8%), tet(O) (1.7%), and tet(W) (0.8%). The majority (78.3%) of the erythromycin-resistant E. faecalis isolates carried erm(B). The conjugative transposon Tn916 and members of the Tn916/Tn1545 family were detected in 30.2% and 34.6% of the identified isolates, respectively. E. faecalis carried virulence genes, including a gelatinase gene (gelE; 70.7%), an aggregation substance gene (asa1; 33.2%), an enterococcus surface protein gene (esp; 8.8%), and a cytolysin gene (cylA; 8.8%). Phenotypic assays showed that 91.4% of the isolates with the gelE gene were gelatinolytic and that 46.7% of the isolates with the asa1 gene aggregated. All isolates with the cylA gene were hemolytic on human blood. This study showed that houseflies in food-handling and -serving facilities carry antibiotic-resistant and potentially virulent enterococci that have the capacity for horizontal transfer of antibiotic resistance genes to other bacteria.

  9. Development and evaluation of a Quadruplex Taq Man real-time PCR assay for simultaneous detection of clinical isolates of Enterococcus faecalis, Enterococcus faecium and their vanA and vanB genotypes.

    PubMed

    Naserpour Farivar, Taghi; Najafipour, Reza; Johari, Pouran; Aslanimehr, Masoumeh; Peymani, Amir; Jahani Hashemi, Hoasan; Mirzaui, Baman

    2014-10-01

    We developed and evaluated the utility of a quadruplex Taqman real-time PCR assay that allows simultaneous identification of vancomycin-resistant genotypes and clinically relevant enterococci. The specificity of the assay was tested using reference strains of vancomycin-resistant and susceptible enterococci. In total, 193 clinical isolates were identified and subsequently genotyped using a Quadruplex Taqman real-time PCR assay and melting curve analysis. Representative Quadruplex Taqman real-time PCR amplification curve were obtained for Enterococcus faecium, Enterococcus faecalis, vanA-containing E. faecium, vanB-containing E. faecalis. Phenotypic and genotypic analysis of the isolates gave same results for 82 enterococcal isolates, while in 5 isolates, they were inconsistent. We had three mixed strains, which were detected by the TaqMan real-time PCR assay and could not be identified correctly using phenotypic methods. Vancomycin resistant enterococci (VRE) genotyping and identification of clinically relevant enterococci were rapidly and correctly performed using TaqMan real-time multiplex real-time PCR assay.

  10. Outcomes of Aminopenicillin Therapy for Vancomycin-Resistant Enterococcal Urinary Tract Infections.

    PubMed

    Cole, Kelli A; Kenney, Rachel M; Perri, Mary Beth; Dumkow, Lisa E; Samuel, Linoj P; Zervos, Marcus J; Davis, Susan L

    2015-12-01

    Vancomycin-resistant urinary tract infections are often challenging to treat. This retrospective cohort study compared outcomes between patients treated for vancomycin-resistant enterococcal urinary tract infection with an aminopenicillin and those treated with a non-β-lactam antibiotic. Inpatients treated with an enterococcus-active agent for their first symptomatic vancomycin-resistant enterococcal urinary tract infection between 1 January 2012 and 31 December 2013 were considered for inclusion. Patients with colonization, on hospice, or receiving comfort care only were excluded. The primary endpoint of clinical cure was defined as resolution of clinical symptoms, or symptom improvement to the extent that no additional antibacterial drug therapy was necessary, and lack of microbiologic persistence. Secondary endpoints of 30-day readmission or retreatment and 30-day all-cause mortality were also compared. A total of 316 urinary isolates were screened, and 61 patients with symptomatic urinary tract infection were included. Twenty (35%) of the 57 isolates tested were ampicillin susceptible. Thirty-one patients received an aminopenicillin, and 30 received a non-β-lactam. Rates of clinical cure for aminopenicillin versus non-β-lactam treatment were 26/31 (83.9%) and 22/30 (73.3%) (P = 0.315), respectively. Rates of 30-day readmission (6/31, or 19.4%, versus 9/30, or 30%, respectively; P = 0.334), 30-day retreatment (4/31, or 12.9%, versus 4/30, 13.3%, respectively; P = 0.960), and 30-day all-cause mortality (2/31, or 6.5%, versus 1/30, or 3.3%, respectively; P = 0.573) were also not significantly different between groups. Aminopenicillins may be a viable option for treating vancomycin-resistant urinary tract infection regardless of the organism's ampicillin susceptibility. Prospective validation with larger cohorts of patients should be considered. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  11. Dissecting Vancomycin-Intermediate Resistance in Staphylococcus aureus Using Genome-Wide Association

    PubMed Central

    Alam, Md Tauqeer; Petit, Robert A.; Crispell, Emily K.; Thornton, Timothy A.; Conneely, Karen N.; Jiang, Yunxuan; Satola, Sarah W.; Read, Timothy D.

    2014-01-01

    Vancomycin-intermediate Staphylococcus aureus (VISA) is currently defined as having minimal inhibitory concentration (MIC) of 4–8 µg/ml. VISA evolves through changes in multiple genetic loci with at least 16 candidate genes identified in clinical and in vitro-selected VISA strains. We report a whole-genome comparative analysis of 49 vancomycin-sensitive S. aureus and 26 VISA strains. Resistance to vancomycin was determined by broth microdilution, Etest, and population analysis profile-area under the curve (PAP-AUC). Genome-wide association studies (GWAS) of 55,977 single-nucleotide polymorphisms identified in one or more strains found one highly significant association (P = 8.78E-08) between a nonsynonymous mutation at codon 481 (H481) of the rpoB gene and increased vancomycin MIC. Additionally, we used a database of public S. aureus genome sequences to identify rare mutations in candidate genes associated with VISA. On the basis of these data, we proposed a preliminary model called ECM+RMCG for the VISA phenotype as a benchmark for future efforts. The model predicted VISA based on the presence of a rare mutation in a set of candidate genes (walKR, vraSR, graSR, and agrA) and/or three previously experimentally verified mutations (including the rpoB H481 locus) with an accuracy of 81% and a sensitivity of 73%. Further, the level of resistance measured by both Etest and PAP-AUC regressed positively with the number of mutations present in a strain. This study demonstrated 1) the power of GWAS for identifying common genetic variants associated with antibiotic resistance in bacteria and 2) that rare mutations in candidate gene, identified using large genomic data sets, can also be associated with resistance phenotypes. PMID:24787619

  12. Is It Time to Replace Vancomycin in the Treatment of Methicillin-Resistant Staphylococcus aureus Infections?

    PubMed Central

    van Hal, Sebastiaan J.; Fowler, Vance G.

    2013-01-01

    For more than 4 decades, vancomycin has been the antibiotic of choice for methicillin-resistant Staphylococcus aureus (MRSA) infections. Recently, infections due to isolates with high but susceptible vancomycin minimum inhibitory concentrations have been associated with additional treatment failures and patient mortality. These poorer outcomes may in part be explained by the inability of attaining appropriate vancomycin levels in these patients. However, assumptions that these poor outcomes are solely due to failure to achieve optimal serum levels of vancomycin are premature. The availability of effective alternatives further erodes the position of vancomycin as first-line therapy. The emergence of resistance and cost considerations, however, favor a more measured approach when using alternative antimicrobials. Collectively, the current available data suggest that the optimal therapy for MRSA infections remains unclear. In the absence of further data, the Infectious Diseases Society of America guidelines remain relevant and inform clinicians of best practice for treating patients with MRSA infections. PMID:23511300

  13. Vancomycin-Resistant Enterococci (VRE):Overview

    MedlinePlus

    ... Operations Administrative Services Office of Biodefense Research & Surety Communications Government Relations Cyber Infrastructure Computational Biology Equal Employment Opportunity Ethics Global Research Office of Mission Integration and Financial ...

  14. Diversity of enterococcal species and characterization of high-level aminoglycoside resistant enterococci of samples of wastewater and surface water in Tunisia.

    PubMed

    Ben Said, Leila; Klibi, Naouel; Lozano, Carmen; Dziri, Raoudha; Ben Slama, Karim; Boudabous, Abdellatif; Torres, Carmen

    2015-10-15

    One hundred-fourteen samples of wastewater (n=64) and surface-water (n=50) were inoculated in Slanetz-Bartley agar plates supplemented or not with gentamicin (SB-Gen and SB plates, respectively) for enterococci recovery. Enterococci were obtained from 75% of tested samples in SB media (72% in wastewater; 78% in surface-water), and 85 enterococcal isolates (one/positive-sample) were obtained. Enterococcus faecium was the most prevalent species (63.5%), followed by Enterococcus faecalis (20%), Enterococcus hirae (9.4%), Enterococcus casseliflavus (4.7%), and Enterococcus gallinarum/Enterococcus durans (2.4%). Antibiotic resistance detected among these enterococci was as follows [percentage/detected gene (number isolates)]: kanamycin [29%/aph(3')-IIIa (n=22)], streptomycin [8%/ant(6)-Ia (n=4)], erythromycin [44%/erm(B) (n=34)], tetracycline [18%/tet(M) (n=6)/tet(M)-tet(L) (n=9)], chloramphenicol [2%/cat(A) (n=1)], ciprofloxacin [7%] and trimethoprim-sulfamethoxazole [94%]. High-level-gentamicin resistant (HLR-G) enterococci were recovered from 15 samples in SB-Gen or SB plates [12/64 samples of wastewater (19%) and 3/50 samples of surface-water (6%)]; HLR-G isolates were identified as E. faecium (n=7), E. faecalis (n=6), and E. casseliflavus (n=2). These HLR-G enterococci carried the aac(6')-Ie-aph(2")-Ia and erm(B) genes, in addition to aph(3')-IIIa (n=10), ant(6)-Ia (n=9), tet(M) (n=13), tet(L) (n=8) and cat(A) genes (n=2). Three HLR-G enterococci carried the esp virulence gene. Sequence-types detected among HLR-G enterococci were as follows: E. faecalis (ST480, ST314, ST202, ST55, and the new ones ST531 and ST532) and E. faecium (ST327, ST12, ST296, and the new ones ST985 and ST986). Thirty-two different PFGE patterns were detected among 36 high-level-aminoglycoside-resistant enterococci recovered in water samples. Diverse genetic lineages of HLR-G enterococci were detected in wastewater and surface-water in Tunisia. Water can represent an important source for the

  15. Requirement of the CroRS Two-Component System for Resistance to Cell Wall-Targeting Antimicrobials in Enterococcus faecium.

    PubMed

    Kellogg, Stephanie L; Little, Jaime L; Hoff, Jessica S; Kristich, Christopher J

    2017-05-01

    Enterococci are serious opportunistic pathogens that are resistant to many cell wall-targeting antibiotics. The CroRS two-component signaling system responds to antibiotic-mediated cell wall stress and is critical for resistance to cell wall-targeting antibiotics in Enterococcus faecalis Here, we identify and characterize an orthologous two-component system found in Enterococcus faecium that is functionally equivalent to the CroRS system of E. faecalis Deletion of croRS in E. faecium resulted in marked susceptibility to cell wall-targeting agents including cephalosporins and bacitracin, as well as moderate susceptibility to ampicillin and vancomycin. As in E. faecalis , exposure to bacitracin and vancomycin stimulates signaling through the CroRS system in E. faecium Moreover, the CroRS system is critical in E. faecium for enhanced beta-lactam resistance mediated by overexpression of Pbp5. Expression of a Pbp5 variant that confers enhanced beta-lactam resistance cannot overcome the requirement for CroRS function. Thus, the CroRS system is a conserved signaling system that responds to cell wall stress to promote intrinsic resistance to important cell wall-targeting antibiotics in clinically relevant enterococci. Copyright © 2017 American Society for Microbiology.

  16. Requirement of the CroRS Two-Component System for Resistance to Cell Wall-Targeting Antimicrobials in Enterococcus faecium

    PubMed Central

    Kellogg, Stephanie L.; Little, Jaime L.; Hoff, Jessica S.

    2017-01-01

    ABSTRACT Enterococci are serious opportunistic pathogens that are resistant to many cell wall-targeting antibiotics. The CroRS two-component signaling system responds to antibiotic-mediated cell wall stress and is critical for resistance to cell wall-targeting antibiotics in Enterococcus faecalis. Here, we identify and characterize an orthologous two-component system found in Enterococcus faecium that is functionally equivalent to the CroRS system of E. faecalis. Deletion of croRS in E. faecium resulted in marked susceptibility to cell wall-targeting agents including cephalosporins and bacitracin, as well as moderate susceptibility to ampicillin and vancomycin. As in E. faecalis, exposure to bacitracin and vancomycin stimulates signaling through the CroRS system in E. faecium. Moreover, the CroRS system is critical in E. faecium for enhanced beta-lactam resistance mediated by overexpression of Pbp5. Expression of a Pbp5 variant that confers enhanced beta-lactam resistance cannot overcome the requirement for CroRS function. Thus, the CroRS system is a conserved signaling system that responds to cell wall stress to promote intrinsic resistance to important cell wall-targeting antibiotics in clinically relevant enterococci. PMID:28223383

  17. Structural and Functional Adaptation of Vancomycin Resistance VanT Serine Racemases.

    PubMed

    Meziane-Cherif, Djalal; Stogios, Peter J; Evdokimova, Elena; Egorova, Olga; Savchenko, Alexei; Courvalin, Patrice

    2015-08-11

    Vancomycin resistance in Gram-positive bacteria results from the replacement of the D-alanyl-D-alanine target of peptidoglycan precursors with D-alanyl-D-lactate or D-alanyl-D-serine (D-Ala-D-Ser), to which vancomycin has low binding affinity. VanT is one of the proteins required for the production of D-Ala-D-Ser-terminating precursors by converting L-Ser to D-Ser. VanT is composed of two domains, an N-terminal membrane-bound domain, likely involved in L-Ser uptake, and a C-terminal cytoplasmic catalytic domain which is related to bacterial alanine racemases. To gain insight into the molecular function of VanT, the crystal structure of the catalytic domain of VanTG from VanG-type resistant Enterococcus faecalis BM4518 was determined. The structure showed significant similarity to type III pyridoxal 5'-phosphate (PLP)-dependent alanine racemases, which are essential for peptidoglycan synthesis. Comparative structural analysis between VanTG and alanine racemases as well as site-directed mutagenesis identified three specific active site positions centered around Asn696 which are responsible for the L-amino acid specificity. This analysis also suggested that VanT racemases evolved from regular alanine racemases by acquiring additional selectivity toward serine while preserving that for alanine. The 4-fold-lower relative catalytic efficiency of VanTG against L-Ser versus L-Ala implied that this enzyme relies on its membrane-bound domain for L-Ser transport to increase the overall rate of d-Ser production. These findings illustrate how vancomycin pressure selected for molecular adaptation of a housekeeping enzyme to a bifunctional enzyme to allow for peptidoglycan remodeling, a strategy increasingly observed in antibiotic-resistant bacteria. Vancomycin is one of the drugs of last resort against Gram-positive antibiotic-resistant pathogens. However, bacteria have evolved a sophisticated mechanism which remodels the drug target, the D-alanine ending precursors in cell wall

  18. Alternatives to vancomycin for the treatment of methicillin-resistant Staphylococcus aureus infections.

    PubMed

    Micek, Scott T

    2007-09-15

    Vancomycin remains the reference standard for the treatment of systemic infection caused by methicillin-resistant Staphylococcus aureus (MRSA). However, as a result of limited tissue distribution, as well as the emergence of isolates with reduced susceptibility and in vitro resistance to vancomycin, the need for alternative therapies that target MRSA has become apparent. New treatment options for invasive MRSA infections include linezolid, daptomycin, tigecycline, and quinupristin/dalfopristin. Additionally, a number of new anti-MRSA compounds are in development, including novel glycopeptides (dalbavancin, telavancin, and oritavancin), ceftobiprole, and iclaprim. The present article will review clinical issues surrounding the newly marketed and investigational agents with activity against MRSA.

  19. Characterization of Class IIa Bacteriocin Resistance in Enterococcus faecium.

    PubMed

    Geldart, Kathryn; Kaznessis, Yiannis N

    2017-04-01

    Vancomycin-resistant enterococci, particularly resistant Enterococcus faecium , pose an escalating threat in nosocomial environments because of their innate resistance to many antibiotics, including vancomycin, a treatment of last resort. Many class IIa bacteriocins strongly target these enterococci and may offer a potential alternative for the management of this pathogen. However, E. faecium 's resistance to these peptides remains relatively uncharacterized. Here, we explored the development of resistance of E. faecium to a cocktail of three class IIa bacteriocins: enterocin A, enterocin P, and hiracin JM79. We started by quantifying the frequency of resistance to these peptides in four clinical isolates of E. faecium We then investigated the levels of resistance of E. faecium 6E6 mutants as well as their fitness in different carbon sources. In order to elucidate the mechanism of resistance of E. faecium to class IIa bacteriocins, we completed whole-genome sequencing of resistant mutants and performed reverse transcription-quantitative PCR (qRT-PCR) of a suspected target mannose phosphotransferase (ManPTS). We then verified this ManPTS's role in bacteriocin susceptibility by showing that expression of the ManPTS in Lactococcus lactis results in susceptibility to the peptide cocktail. Based on the evidence found from these studies, we conclude that, in accord with other studies in E. faecalis and Listeria monocytogenes , resistance to class IIa bacteriocins in E. faecium 6E6 is likely caused by the disruption of a particular ManPTS, which we believe we have identified. Copyright © 2017 American Society for Microbiology.

  20. Characterization and modelling of VanT: a novel, membrane-bound, serine racemase from vancomycin-resistant Enterococcus gallinarum BM4174.

    PubMed

    Arias, C A; Martín-Martinez, M; Blundell, T L; Arthur, M; Courvalin, P; Reynolds, P E

    1999-03-01

    Sequence determination of a region downstream from the vanXYc gene in Enterococcus gallinarum BM4174 revealed an open reading frame, designated vanT, that encodes a 698-amino-acid polypeptide with an amino-terminal domain containing 10 predicted transmembrane segments. The protein contained a highly conserved pyridoxal phosphate attachment site in the C-terminal domain, typical of alanine racemases. The protein was overexpressed in Escherichia coli, and serine racemase activity was detected in the membrane but not in the cytoplasmic fraction after centrifugation of sonicated cells, whereas alanine racemase activity was located almost exclusively in the cytoplasm. When the protein was overexpressed as a polypeptide lacking the predicted transmembrane domain, serine racemase activity was detected in the cytoplasm. The serine racemase activity was partially (64%) inhibited by D-cycloserine, whereas host alanine racemase activity was almost totally inhibited (97%). Serine racemase activity was also detected in membrane preparations of constitutively vancomycin-resistant E. gallinarum BM4174 but not in BM4175, in which insertional inactivation of the vanC-1 D-Ala:D-Ser ligase gene probably had a polar effect on expression of the vanXYc and vanT genes. Comparative modelling of the deduced C-terminal domain was based on the alignment of VanT with the Air alanine racemase from Bacillus stearothermophilus. The model revealed that almost all critical amino acids in the active site of Air were conserved in VanT, indicating that the C-terminal domain of VanT is likely to adopt a three-dimensional structure similar to that of Air and that the protein could exist as a dimer. These results indicate that the source of D-serine for peptidoglycan synthesis in vancomycin-resistant enterococci expressing the VanC phenotype involves racemization of L- to D-serine by a membrane-bound serine racemase.

  1. Antimicrobial resistance profiles of Enterococcus faecalis and Enterococcus faecium isolated from artisanal food of animal origin in Argentina.

    PubMed

    Delpech, Gastón; Pourcel, Gisela; Schell, Celia; De Luca, María; Basualdo, Juan; Bernstein, Judith; Grenovero, Silvia; Sparo, Mónica

    2012-10-01

    Enterococci are part of the indigenous microbiota of human gastrointestinal tract and food of animal origin. Enterococci inhabiting non-human reservoirs play a critical role in the acquisition and dissemination of antimicrobial resistance determinants. The aim of this work was to investigate the antimicrobial resistance in Enterococcus faecalis and Enterococcus faecium strains recovered from artisanal food of animal origin. Samples of goat cheese (n = 42), cow cheese (n = 40), artisanal salami (n = 30), and minced meat for the manufacture of hamburgers (n = 60) were analyzed. Phenotypic and genotypic tests for species-level identification of the recovered isolates were carried out. Minimum inhibitory concentration (MIC) study for in vitro quantitative antimicrobial resistance assessment was performed, and 71 E. faecalis and 22 E. faecium were isolated. The recovered enterococci showed different multi-drug resistance patterns that included tretracycline, erythromycin, ciprofloxacin, linezolid, penicillin, ampicillin, vancomycin, teicoplanin, gentamicin (high-level resistance), and streptomycin (high-level resistance). VanA-type E. faecium were detected. β-lactamase activity was not observed. Artisanal foods of animal origin act as a non-human reservoir of E. faecalis and E. faecuim strains, expressing multi-resistance to antimicrobials. In conclusion, the implementation of a continuous antimicrobial resistance surveillance in enterococci isolated from artisanal food of animal origin is important.

  2. Bacterial resistance to vancomycin: overproduction, purification, and characterization of VanC2 from Enterococcus casseliflavus as a D-Ala-D-Ser ligase.

    PubMed

    Park, I S; Lin, C H; Walsh, C T

    1997-09-16

    The VanC phenotype for clinical resistance of enterococci to vancomycin is exhibited by Enterococcus gallinarum and Enterococcus casseliflavus. Based on the detection of the cell precursor UDP-N-acetylmuramic acid pentapeptide intermediate terminating in D-Ala-D-Ser instead of D-Ala-D-Ala, it has been predicted that the VanC ligase would be a D-Ala-D-Ser rather than a D-Ala-D-Ala ligase. Overproduction of the E. casseliflavus ATCC 25788 vanC2 gene in Escherichia coli and its purification to homogeneity allowed demonstration of ATP-dependent D-Ala-D-Ser ligase activity. The kcat/Km2 (Km2 = Km for D-Ser or C-terminal D-Ala) ratio for D-Ala-D-Ser/D-Ala-D-Ala dipeptide formation is 270/0.69 for a 400-fold selection against D-Ala in the C-terminal position. VanC2 also has substantial D-Ala-D-Asn ligase activity (kcat/Km2 = 74 mM-1min-1).

  3. WalK(S221P), a naturally occurring mutation, confers vancomycin resistance in VISA strain XN108.

    PubMed

    Peng, Huagang; Hu, Qiwen; Shang, Weilong; Yuan, Jizhen; Zhang, Xiaopeng; Liu, Hui; Zheng, Ying; Hu, Zhen; Yang, Yi; Tan, Li; Li, Shu; Hu, Xiaomei; Li, Ming; Rao, Xiancai

    2017-04-01

    Vancomycin-intermediate Staphylococcus aureus (VISA) strains have spread globally. We previously isolated an ST239 VISA (XN108) with a vancomycin MIC of 12 mg/L. The mechanism for XN108 resistance to vancomycin was investigated in this study. Genome comparison was performed to characterize mutations that might contribute to the XN108 resistance phenotype. The novel mutation WalK(S221P) was identified and investigated using allelic replacement experiments. Vancomycin susceptibilities, autolytic activities and morphologies of the strains were examined. Autophosphorylation activities of WalK and the WalK(S221P) mutant were determined in vitro with [λ- 32 P]ATP, and binding activity of WalK(S221P)-activated WalR to the promoter region of its target gene lytM was determined by electrophoretic mobility shift assay. Genome comparison revealed three mutations, GraS(T136I), RpoB(H481N) and WalK(S221P), which might be responsible for vancomycin resistance in XN108. The introduction of WalK(S221P) to the vancomycin-susceptible strain N315 increased its vancomycin MIC from 1.5 to 8 mg/L, whereas the allelic replacement of WalK(S221P) with the native N315 WalK allele in XN108 decreased its vancomycin MIC from 12 to 4 mg/L. The VISA strains have thickened cell walls and decreased autolysis, consistent with observed changes in the expression of genes involved in cell wall metabolism and virulence regulation. WalK(S221P) exhibited reduced autophosphorylation, which may lead to reduced phosphorylation of WalR. WalK(S221P)-phosphorylated WalR also exhibited a reduced capacity to bind to the lytM promoter. The naturally occurring WalK(S221P) mutation plays a key role in vancomycin resistance in XN108. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Occurrence of the Transferable Copper Resistance Gene tcrB among Fecal Enterococci of U.S. Feedlot Cattle Fed Copper-Supplemented Diets

    PubMed Central

    Amachawadi, R. G.; Alvarado, C. A.; Mainini, T. R.; Vinasco, J.; Drouillard, J. S.; Nagaraja, T. G.

    2013-01-01

    Copper, an essential micronutrient, is supplemented in the diet at elevated levels to reduce morbidity and mortality and to promote growth in feedlot cattle. Gut bacteria exposed to copper can acquire resistance, which among enterococci is conferred by a transferable copper resistance gene (tcrB) borne on a plasmid. The present study was undertaken to investigate whether the feeding of copper at levels sufficient to promote growth increases the prevalence of the tcrB gene among the fecal enterococci of feedlot cattle. The study was performed with 261 crossbred yearling heifers housed in 24 pens, with pens assigned randomly to a 2×2 factorial arrangement of treatments consisting of dietary copper and a commercial linseed meal-based energy protein supplement. A total of 22 isolates, each identified as Enterococcus faecium, were positive for tcrB with an overall prevalence of 3.8% (22/576). The prevalence was higher among the cattle fed diets supplemented with copper (6.9%) compared to normal copper levels (0.7%). The tcrB-positive isolates always contained both erm(B) and tet(M) genes. Median copper MICs for tcrB-positive and tcrB-negative enterococci were 22 and 4 mM, respectively. The transferability of the tcrB gene was demonstrated via a filter-mating assay. Multilocus variable number tandem repeat analysis revealed a genetically diverse population of enterococci. The finding of a strong association between the copper resistance gene and other antibiotic (tetracycline and tylosin) resistance determinants is significant because enterococci remain potential pathogens and have the propensity to transfer resistance genes to other bacteria in the gut. PMID:23666328

  5. Novel Inhibitors of Staphyloxanthin Virulence Factor in Comparison with Linezolid and Vancomycin versus Methicillin-Resistant, Linezolid-Resistant, and Vancomycin-Intermediate Staphylococcus aureus Infections in Vivo.

    PubMed

    Ni, Shuaishuai; Wei, Hanwen; Li, Baoli; Chen, Feifei; Liu, Yifu; Chen, Wenhua; Xu, Yixiang; Qiu, Xiaoxia; Li, Xiaokang; Lu, Yanli; Liu, Wenwen; Hu, Linhao; Lin, Dazheng; Wang, Manjiong; Zheng, Xinyu; Mao, Fei; Zhu, Jin; Lan, Lefu; Li, Jian

    2017-10-12

    Our previous work ( Wang et al. J. Med. Chem. 2016 , 59 , 4831 - 4848 ) revealed that effective benzocycloalkane-derived staphyloxanthin inhibitors against methicillin-resistant Staphylococcus aureus (S. aureus) infections were accompanied by poor water solubility and high hERG inhibition and dosages (preadministration). In this study, 92 chroman and coumaran derivatives as novel inhibitors have been addressed for overcoming deficiencies above. Derivatives 69 and 105 displayed excellent pigment inhibitory activities and low hERG inhibition, along with improvement of solubility by salt type selection. The broad and significantly potent antibacterial spectra of 69 and 105 were displayed first with normal administration in the livers and hearts in mice against pigmented S. aureus Newman, Mu50 (vancomycin-intermediate S. aureus), and NRS271 (linezolid-resistant S. aureus), compared with linezolid and vancomycin. In summary, both 69 and 105 have the potential to be developed as good antibacterial candidates targeting virulence factors.

  6. Role of Combination Antimicrobial Therapy for Vancomycin-Resistant Enterococcus faecium Infections: Review of the Current Evidence.

    PubMed

    Yim, Juwon; Smith, Jordan R; Rybak, Michael J

    2017-05-01

    Enterococcus species are the second most common cause of nosocomial infections in the United States and are particularly concerning in critically ill patients with preexisting comorbid conditions. Rising resistance to antimicrobials that were historically used as front-line agents for treatment of enterococcal infections, such as ampicillin, vancomycin, and aminoglycosides, further complicates the treatment of these infections. Of particular concern are Enterococcus faecium strains that are associated with the highest rate of vancomycin resistance. The introduction of antimicrobial agents with specific activity against vancomycin-resistant Enterococcus (VRE) faecium including daptomycin, linezolid, quinupristin-dalfopristin, and tigecycline did not completely resolve this clinical dilemma. In this review, the mechanisms of action and resistance to currently available anti-VRE antimicrobial agents including newer agents such as oritavancin and dalbavancin will be presented. In addition, novel combination therapies including β-lactams and fosfomycin, and the promising results from in vitro, animal studies, and clinical experience in the treatment of VRE faecium will be discussed. © 2017 Pharmacotherapy Publications, Inc.

  7. Diphenylurea derivatives for combating methicillin- and vancomycin-resistant Staphylococcus aureus.

    PubMed

    Eissa, Ibrahim H; Mohammad, Haroon; Qassem, Omar A; Younis, Waleed; Abdelghany, Tamer M; Elshafeey, Ahmed; Abd Rabo Moustafa, Mahmoud M; Seleem, Mohamed N; Mayhoub, Abdelrahman S

    2017-04-21

    A new class of diphenylurea was identified as a novel antibacterial scaffold with an antibacterial spectrum that includes highly resistant staphylococcal isolates, namely methicillin- and vancomycin-resistant Staphylococcus aureus (MRSA & VRSA). Starting with a lead compound 3 that carries an aminoguanidine functionality from one side and a n-butyl moiety on the other ring, several analogues were prepared. Considering the pharmacokinetic parameters as a key factor in structural optimization, the structure-activity-relationships (SARs) at the lipophilic side chain were rigorously examined leading to the discovery of the cycloheptyloxyl analogue 21n as a potential drug-candidate. This compound has several notable advantages over vancomycin and linezolid including rapid killing kinetics against MRSA and the ability to target and reduce the burden of MRSA harboring inside immune cells (macrophages). Furthermore, the potent anti-MRSA activity of 21n was confirmed in vivo using a Caenorhabditis elegans animal model. The present study provides a foundation for further development of diphenylurea compounds as potential therapeutic agents to address the burgeoning challenge of bacterial resistance to antibiotics. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  8. Vancomycin for the treatment of Clostridium difficile Infection: for whom is this expensive bullet really magic?

    PubMed

    Pepin, Jacques

    2008-05-15

    The epidemiology, clinical severity, and case-fatality ratio of Clostridium difficile infection (CDI) changed dramatically with the emergence of a toxin hyperproducing strain (BI/NAP1/027) in North America and Europe in 2000. For the treatment of CDI, metronidazole and vancomycin remain the 2 most commonly used drugs. The 3 randomized controlled trials published thus far, as well as the upcoming tolevamer trial, use intermediate outcomes, rather than the outcomes that now preoccupy clinicians: the frequency of complications or recurrence. The major advantage of metronidazole is its low price. The major advantage of orally administered vancomycin is its more favorable pharmacokinetics. Facilitating vancomycin-resistant enterococci colonization and/or infection is a potential drawback of both drugs. Pending the development of a prospectively validated scoring system, members of the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America expert committee will define severe CDI as present in any patient with a leukocyte count > or =15,000 cells/mm(3) or a creatinine level increased by > or =50% from baseline. For patients with mild-to-moderate CDI (defined by a leukocyte count <15000 cells/mm(3) and a creatinine level <1.5 times the baseline value), there is no evidence that treatment with vancomycin is superior to treatment with metronidazole (even for intermediate outcomes), and metronidazole therapy should be preferred. For patients with severe CDI who are not infected with BI/NAP1/027, there is reasonable evidence that the better pharmacokinetics of vancomycin translate into a lower probability of complications. For those patients who are infected with BI/NAP1/027, the superiority of vancomycin therapy remains to be proven. In practice, because it is not yet possible to rapidly type the strains, all patients with severe CDI should be treated with vancomycin. Future trials should use complicated CDI and recurrences as their primary

  9. Metabolic Mitigation of Staphylococcus aureus Vancomycin Intermediate-Level Susceptibility.

    PubMed

    Gardner, Stewart G; Marshall, Darrell D; Daum, Robert S; Powers, Robert; Somerville, Greg A

    2018-01-01

    Staphylococcus aureus is a major human pathogen whose infections are increasingly difficult to treat due to increased antibiotic resistance, including resistance to vancomycin. Vancomycin-intermediate S. aureus (VISA) strains develop resistance to vancomycin through adaptive changes that are incompletely understood. Central to this adaptation are metabolic changes that permit growth in the presence of vancomycin. To define the metabolic changes associated with adaptive resistance to vancomycin in S. aureus , the metabolomes of a vancomycin-sensitive and VISA strain pair isolated from the same patient shortly after vancomycin therapy began and following vancomycin treatment failure were analyzed. The metabolic adaptations included increases in acetogenesis, carbon flow through the pentose phosphate pathway, wall teichoic acid and peptidoglycan precursor biosynthesis, purine biosynthesis, and decreased tricarboxylic acid (TCA) cycle activity. The significance of these metabolic pathways for vancomycin-intermediate susceptibility was determined by assessing the synergistic potential of human-use-approved inhibitors of these pathways in combination with vancomycin against VISA strains. Importantly, inhibitors of amino sugar and purine biosynthesis acted synergistically with vancomycin to kill a diverse set of VISA strains, suggesting that combinatorial therapy could augment the efficacy of vancomycin even in patients infected with VISA strains. Copyright © 2017 American Society for Microbiology.

  10. Human health risks associated with antimicrobial-resistant enterococci and Staphylococcus aureus on poultry meat.

    PubMed

    Bortolaia, V; Espinosa-Gongora, C; Guardabassi, L

    2016-02-01

    Enterococci and staphylococci are frequent contaminants on poultry meat. Enterococcus faecalis, Enterococcus faecium and Staphylococcus aureus are also well-known aetiological agents of a wide variety of infections resulting in major healthcare costs. This review provides an overview of the human health risks associated with the occurrence of these opportunistic human pathogens on poultry meat with particular focus on the risk of food-borne transmission of antimicrobial resistance. In the absence of conclusive evidence of transmission, this risk was inferred using data from scientific articles and national reports on prevalence, bacterial load, antimicrobial resistance and clonal distribution of these three species on poultry meat. The risks associated with ingestion of antimicrobial-resistant enterococci of poultry origin comprise horizontal transfer of resistance genes and transmission of multidrug-resistant E. faecalis lineages such as sequence type ST16. Enterococcus faecium lineages occurring in poultry meat products are distantly related to those causing hospital-acquired infections but may act as donors of quinupristin/dalfopristin resistance and other resistance determinants of clinical interest to the human gut microbiota. Ingestion of poultry meat contaminated with S. aureus may lead to food poisoning. However, antimicrobial resistance in the toxin-producing strains does not have clinical implications because food poisoning is not managed by antimicrobial therapy. Recently methicillin-resistant S. aureus of livestock origin has been reported on poultry meat. In theory handling or ingestion of contaminated meat is a potential risk factor for colonization by methicillin-resistant S. aureus. However, this risk is presently regarded as negligible by public health authorities. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  11. A new risk factor for neonatal vancomycin-resistant Enterococcus colonisation: bacterial probiotics.

    PubMed

    Topcuoglu, Sevilay; Gursoy, Tugba; Ovalı, Fahri; Serce, Ozge; Karatekin, Guner

    2015-08-01

    Vancomycin-resistant Enterococcus (VRE) colonisation can be controlled with strict adherence to infection control measures. We describe a VRE outbreak coincident with bacterial probiotic trial. Relationship between probiotic and VRE colonisation, and other possible risk factors were investigated. Two hundred and ten infants with gestational age less than 32 weeks had been randomised for a trial with probiotic preparation containing Lactobacillus casei, Lactobacillus rhamnosus, Lactobacillus plantarum, Bifidobacterium lactis, fructooligosaccharide, galactooligosaccharide, colostrums and lactoferrin (NBL probiotic ATP®; Nobel, Istanbul, Turkey) between February 2012 and August 2013 when a VRE outbreak also took place. The existence of a relationship between this probiotic preparation and VRE colonisation was investigated. The begining and end of the outbreak were coincident with the beginning and end of the probiotic trial. Demographic and clinical features of neonates did not differ between VRE colonised (n = 94) and non-colonised infants (n = 116) except for vancomycin (p = 0.012) and probiotic (p < 0.001) use. Probiotic and vancomycin exposure were significant risk factors for VRE colonisation. The acquisition and transfer of resistance genes of bacteria may be mediated by probiotics. Therefore, the safety of probiotics is a concern and should be investigated further.

  12. Whole genome characterization of a naturally occurring vancomycin-dependent Enterococcus faecium from a patient with bacteremia.

    PubMed

    Mitchell, Stephanie L; Mattei, Lisa M; Alby, Kevin

    2017-08-01

    Vancomycin-dependent enterococci are a relatively uncommon phenotype recovered in the clinical laboratory. Recognition and recovery of these isolates are important, to provide accurate identification and susceptibility information to treating physicians. Herein, we describe the recovery of a vancomycin-dependent and revertant E. faecium isolates harboring vanB operon from a patient with bacteremia. Using whole genome sequencing, we found a unique single nucleotide polymorphism (S186N) in the D-Ala-D-Ala ligase (ddl) conferring vancomycin-dependency. Additionally, we found that a majority of in vitro revertants mutated outside ddl, with some strains harboring mutations in vanS, while others likely containing novel mechanisms of reversion. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. First detection of the staphylococcal trimethoprim resistance gene dfrK and the dfrK-carrying transposon Tn559 in enterococci.

    PubMed

    López, María; Kadlec, Kristina; Schwarz, Stefan; Torres, Carmen

    2012-02-01

    The trimethoprim resistance gene dfrK has been recently described in Staphylococcus aureus, but so far has not been found in other bacteria. A total of 166 enterococci of different species (E. faecium, E. faecalis, E. hirae, E. durans, E. gallinarum, and E. casseliflavus) and origins (food, clinical diseases in humans, healthy humans or animals, and sewage) were studied for their susceptibility to trimethoprim as determined by agar dilution (European Committee on Antimicrobial Susceptibility Testing) and the presence of (a) the dfrK gene and its genetic environment and (b) other dfr genes. The dfrK gene was detected in 49% of the enterococci (64% and 42% of isolates with minimum inhibitory concentrations of ≥2 mg/L or ≤1 mg/L, respectively). The tet(L)-dfrK linkage was detected in 21% of dfrK-positive enterococci. The chromosomal location of the dfrK gene was identified in one E. faecium isolate in which the dfrK was not linked to tet(L) gene but was part of a Tn559 element, which was integrated in the chromosomal radC gene. This Tn559 element was also found in 14 additional isolates. All combinations of dfr genes were detected among the isolates tested (dfrK, dfrG, dfrF, dfrK+dfrG, dfrK+dfrF, dfrF+dfrG, and dfrF+dfrG+dfrK). The gene dfrK gene was found together with other dfr genes in 58% of the tested enterococci. This study suggested an exchange of the trimethoprim resistance gene dfrK between enterococci and staphylococci, as previously observed for the trimethoprim resistance gene dfrG.

  14. Prevalence of Slow-Growth Vancomycin Nonsusceptibility in Methicillin-Resistant Staphylococcus aureus

    PubMed Central

    Azechi, Takuya; Miyazaki, Motoyasu; Takata, Tohru; Sekine, Miwa; Matsui, Hidehito; Hanaki, Hideaki; Yahara, Koji; Sasano, Hiroshi; Asakura, Kota; Takaku, Tomoiku; Ochiai, Tomonori; Komatsu, Norio; Chambers, Henry F.

    2017-01-01

    ABSTRACT We previously reported a novel phenotype of vancomycin-intermediate Staphylococcus aureus (VISA), i.e., “slow VISA,” whose colonies appear only after 72 h of incubation. Slow-VISA strains can be difficult to detect because prolonged incubation is required and the phenotype is unstable. To develop a method for detection of slow-VISA isolates, we studied 23 slow-VISA isolates derived from the heterogeneous VISA (hVISA) clinical strain Mu3. We identified single nucleotide polymorphisms (SNPs) in genes involved in various pathways which have been implicated in the stringent response, such as purine/pyrimidine synthesis, cell metabolism, and cell wall peptidoglycan synthesis. We found that mupirocin, which also induces the stringent response, caused stable expression of vancomycin resistance. On the basis of these results, we developed a method for detection of slow-VISA strains by use of 0.032 μg/ml mupirocin (Yuki Katayama, 7 March 2017, patent application PCT/JP2017/008975). Using this method, we detected 53 (15.6%) slow-VISA isolates among clinical methicillin-resistant S. aureus (MRSA) isolates. In contrast, the VISA phenotype was detected in fewer than 1% of isolates. Deep-sequencing analysis showed that slow-VISA clones are present in small numbers among hVISA isolates and proliferate in the presence of vancomycin. This slow-VISA subpopulation may account in part for the recurrence and persistence of MRSA infection. PMID:28827421

  15. COMPARISON BETWEEN AUTOMATED SYSTEM AND PCR-BASED METHOD FOR IDENTIFICATION AND ANTIMICROBIAL SUSCEPTIBILITY PROFILE OF CLINICAL Enterococcus spp

    PubMed Central

    Furlaneto-Maia, Luciana; Rocha, Kátia Real; Siqueira, Vera Lúcia Dias; Furlaneto, Márcia Cristina

    2014-01-01

    Enterococci are increasingly responsible for nosocomial infections worldwide. This study was undertaken to compare the identification and susceptibility profile using an automated MicrosScan system, PCR-based assay and disk diffusion assay of Enterococcus spp. We evaluated 30 clinical isolates of Enterococcus spp. Isolates were identified by MicrosScan system and PCR-based assay. The detection of antibiotic resistance genes (vancomycin, gentamicin, tetracycline and erythromycin) was also determined by PCR. Antimicrobial susceptibilities to vancomycin (30 µg), gentamicin (120 µg), tetracycline (30 µg) and erythromycin (15 µg) were tested by the automated system and disk diffusion method, and were interpreted according to the criteria recommended in CLSI guidelines. Concerning Enterococcus identification the general agreement between data obtained by the PCR method and by the automatic system was 90.0% (27/30). For all isolates of E. faecium and E. faecalis we observed 100% agreement. Resistance frequencies were higher in E. faecium than E. faecalis. The resistance rates obtained were higher for erythromycin (86.7%), vancomycin (80.0%), tetracycline (43.35) and gentamicin (33.3%). The correlation between disk diffusion and automation revealed an agreement for the majority of the antibiotics with category agreement rates of > 80%. The PCR-based assay, the van(A) gene was detected in 100% of vancomycin resistant enterococci. This assay is simple to conduct and reliable in the identification of clinically relevant enterococci. The data obtained reinforced the need for an improvement of the automated system to identify some enterococci. PMID:24626409

  16. Application of a plasmid classification system to determine prevalence of replicon families among multidrug resistant enterococci

    USDA-ARS?s Scientific Manuscript database

    The presence and transfer of plasmids from commensal bacteria to more pathogenic bacteria may contribute to dissemination of antimicrobial resistance. However, prevalence of plasmids from commensal bacteria in food animals such as the enterococci remains largely unknown. In this study, the prevale...

  17. Bactericidal efficacy of molybdenum oxide nanoparticles against antimicrobial-resistant pathogens.

    PubMed

    Lopes, E; Piçarra, S; Almeida, P L; de Lencastre, H; Aires-de-Sousa, M

    2018-06-25

    Multidrug-resistant bacteria pose a major threat to effective antibiotics and alternatives to fight multidrug-resistant pathogens are needed. We synthetized molybdenum oxide (MoO3) nanoparticles (NP) and determined their antibacterial activity against 39 isolates: (i) eight Staphylococcus aureus, including representatives of methicillin-resistant S. aureus epidemic clones; (ii) six enterococci, including vancomycin-resistant isolates; and (iii) 25 Gram-negative isolates (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacter cloacae), including extended spectrum beta-lactamases and carbapenemases producers. All isolates showed a MoO3 NP MIC of 700-800 mg l -1 . MoO3 NP produced a clear inhibition zone for S. aureus and all Gram-negative isolates at concentrations ≥25 mg ml -1 and ≥50 mg ml -1 for enterococci. When the NP solutions were adjusted to pH ~7, the biocidal activity was completely abolished. MoO3 NP create an acidic pH and show a universal antimicrobial activity against susceptible and resistant isolates belonging to the most relevant bacterial species responsible for hospital-acquired infections.

  18. Prevalence of Diverse Clones of Vancomycin-Resistant Enterococcus faecium ST78 in a Chinese Hospital.

    PubMed

    Yang, Jiyong; Jiang, Yufeng; Guo, Ling; Ye, LIyan; Ma, Yanning; Luo, Yanping

    2016-06-01

    Vancomycin-resistant Enterococcus (VRE) has been identified in China. However, little is known about the spread of VRE isolates. The genetic relatedness of vancomycin-resistant Enterococcus faecium (VREfm) isolates was analyzed by pulsed-field gel electrophoresis (PFGE), their antimicrobial susceptibilities were analyzed by E-test and the VITEK 2 AST-GP67 test Kit, and their sequence types (STs) were investigated by multilocus sequence typing (MLST). S1-PFGE was used for plasmid profiling, and PCR and subsequent sequencing were performed to identify the virulence genes. A total of 96 nonduplicated VREfm isolates were obtained and categorized into 38 PFGE types (type 1-38). The predominant MLST type was ST78, while ST17, ST341, and ST342 were also sporadically identified. All types of clinical VREfm strains harbored the vanA gene; however, they carried plasmids of different sizes. While 92.1%, 71.1%, and 60.5% of VREfm strains carried hyl, scm, and ecbA genes, respectively, all of them were positive for esp, acm, sgrA, pilA, and pilB genes. Clonal VREfm spread was observed, and nonplasmid-mediated horizontal transfer of vancomycin-resistant gene might have conveyed resistance to some vancomycin-susceptible E. faecium strains. E. faecium ST78 carrying vanA gene was the most prevalent clone in this study. The high prevalence of virulence genes, including esp, hyl, acm, scm, ecbA, sgrA, pilA, and pilB, confirmed their important roles in the emergence of VREfm ST78 in nosocomial infections.

  19. Multiple Antibiotic Resistance Gene Transfer from Animal to Human Enterococci in the Digestive Tract of Gnotobiotic Mice

    PubMed Central

    Moubareck, C.; Bourgeois, N.; Courvalin, P.; Doucet-Populaire, F.

    2003-01-01

    It has been proposed that food animals represent the source of glycopeptide resistance genes present in enterococci from humans. We demonstrated the transfer of vanA and of other resistance genes from porcine to human Enterococcus faecium at high frequency in the digestive tract of gnotobiotic mice. Tylosin in the drinking water favored colonization by transconjugants. PMID:12937011

  20. Vancomycin-Resistant Enterococci in Healthcare Settings

    MedlinePlus

    ... Personnel PPE Training Infection Control Assessment Tools Water Management Programs Map: HAI Prevention Activities Research CDC Supported Projects Prevention Epicenters (PE) Healthcare Safety Research (SHEPheRD) Environmental ...

  1. d-Ala-d-Ser VanN-Type Transferable Vancomycin Resistance in Enterococcus faecium▿

    PubMed Central

    Lebreton, François; Depardieu, Florence; Bourdon, Nancy; Fines-Guyon, Marguerite; Berger, Pierre; Camiade, Sabine; Leclercq, Roland; Courvalin, Patrice; Cattoir, Vincent

    2011-01-01

    Enterococcus faecium UCN71, isolated from a blood culture, was resistant to low levels of vancomycin (MIC, 16 μg/ml) but susceptible to teicoplanin (MIC, 0.5 μg/ml). No amplification was observed with primers specific for the previously described glycopeptide resistance ligase genes, but a PCR product corresponding to a gene called vanN was obtained using degenerate primers and was sequenced. The deduced VanN protein was related (65% identity) to the d-alanine:d-serine VanL ligase. The organization of the vanN gene cluster, determined using degenerate primers and by thermal asymmetric interlaced (TAIL)-PCR, was similar to that of the vanC operons. A single promoter upstream from the resistance operon was identified by rapid amplification of cDNA ends (RACE)-PCR. The presence of peptidoglycan precursors ending in d-serine and d,d-peptidase activities in the absence of vancomycin indicated constitutive expression of the resistance operon. VanN-type resistance was transferable by conjugation to E. faecium. This is the first report of transferable d-Ala-d-Ser-type resistance in E. faecium. PMID:21807981

  2. Removal of total and antibiotic resistant bacteria in advanced wastewater treatment by ozonation in combination with different filtering techniques.

    PubMed

    Lüddeke, Frauke; Heß, Stefanie; Gallert, Claudia; Winter, Josef; Güde, Hans; Löffler, Herbert

    2015-02-01

    Elimination of bacteria by ozonation in combination with charcoal or slow sand filtration for advanced sewage treatment to improve the quality of treated sewage and to reduce the potential risk for human health of receiving surface waters was investigated in pilot scale at the sewage treatment plant Eriskirch, Baden-Wuerttemberg/Germany. To determine the elimination of sewage bacteria, inflowing and leaving wastewater of different treatment processes was analysed in a culture-based approach for its content of Escherichia coli, enterococci and staphylococci and their resistance against selected antibiotics over a period of 17 month. For enterococci, single species and their antibiotic resistances were identified. In comparison to the established flocculation filtration at Eriskirch, ozonation plus charcoal or sand filtration (pilot-scale) reduced the concentrations of total and antibiotic resistant E. coli, enterococci and staphylococci. However, antibiotic resistant E. coli and staphylococci apparently survived ozone treatment better than antibiotic sensitive strains. Neither vancomycin resistant enterococci nor methicillin resistant Staphylococcus aureus (MRSA) were detected. The decreased percentage of antibiotic resistant enterococci after ozonation may be explained by a different ozone sensitivity of species: Enterococcus faecium and Enterococcus faecalis, which determined the resistance-level, seemed to be more sensitive for ozone than other Enterococcus-species. Overall, ozonation followed by charcoal or sand filtration led to 0.8-1.1 log-units less total and antibiotic resistant E. coli, enterococci and staphylococci, as compared to the respective concentrations in treated sewage by only flocculation filtration. Thus, advanced wastewater treatment by ozonation plus charcoal or sand filtration after common sewage treatment is an effective tool for further elimination of microorganisms from sewage before discharge in surface waters. Copyright © 2014 Elsevier

  3. Activity of plant flavonoids against antibiotic-resistant bacteria.

    PubMed

    Xu, H X; Lee, S F

    2001-02-01

    Thirty eight plant-derived flavonoids representing seven different structural groups were tested for activities against antibiotic-resistant bacteria using the disc-diffusion assay and broth dilution assay. Among the flavonoids examined, four flavonols (myricetin, datiscetin, kaempferol and quercetin) and two -flavones (flavone and luteolin) exhibited inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA). Myricetin was also found to inhibit the growth of multidrug-resistant Burkholderia -cepacia, vancomycin-resistant enterococci (VRE) and other medically important organisms such as -Klebsiella pneumoniae and Staphylococcus epidermidis. Myricetin was bactericidal to B. cepacia. The results of the radiolabel incorporation assay showed that myricetin inhibited protein synthesis by -B. cepacia. The structure-activity relationship of these flavonoids is discussed. Copyright 2001 John Wiley & Sons, Ltd.

  4. In Vitro Synergistic Effects of Double and Triple Combinations of β-Lactams, Vancomycin, and Netilmicin against Methicillin-Resistant Staphylococcus aureus Strains

    PubMed Central

    Rochon-Edouard, Stéphanie; Pestel-Caron, Martine; Lemeland, Jean-François; Caron, François

    2000-01-01

    Several studies have previously reported synergistic effects between vancomycin and a given β-lactam or a given aminoglycoside against methicillin-resistant Staphylococcus aureus (MRSA) strains. The aim of our study was to exhaustively compare the effects of different combinations of a β-lactam, vancomycin, and/or an aminoglycoside against 32 clinical MRSA strains with different aminoglycoside susceptibility patterns. The effects of 26 different β-lactam–vancomycin and 8 different aminoglycoside-vancomycin combinations were first studied using a disk diffusion screening method. The best interactions with vancomycin were observed with either imipenem, cefazolin, or netilmicin. By checkerboard studies, imipenem-vancomycin and cefazolin-vancomycin each provided a synergistic bacteriostatic effect against 22 strains; the mean fractional inhibitory concentration (FIC) indexes were 0.35 and 0.46 for imipenem-vancomycin and cefazolin-vancomycin, respectively. The vancomycin-netilmicin combination provided an indifferent effect against all of the 32 strains tested; the mean of FIC index was 1.096. The mean concentrations of imipenem, cefazolin, netilmicin, and vancomycin at which FIC indexes were calculated were clinically achievable. Killing experiments were then performed using imipenem, cefazolin, netilmicin, and vancomycin at one-half of the MIC, alone and in different combinations, against 10 strains. The vancomycin-netilmicin regimen was rarely bactericidal, even against strains susceptible to netilmicin. The imipenem-vancomycin and cefazolin-vancomycin combinations were strongly bactericidal against six and five strains, respectively. The addition of netilmicin markedly enhanced the killing activity of the combination of cefazolin or imipenem plus vancomycin, but only for the MRSA strains against which the β-lactam–vancomycin combinations had no bactericidal effect. It is noteworthy that the latter strains were both susceptible to netilmicin and

  5. Staphylococcus aureus: methicillin-susceptible S. aureus to methicillin-resistant S. aureus and vancomycin-resistant S. aureus.

    PubMed

    Rehm, Susan J; Tice, Alan

    2010-09-15

    The evolution of methicillin-resistant and vancomycin-resistant Staphylococcus aureus has demanded serious review of antimicrobial use and development of new agents and revised approaches to prevent and overcome drug resistance. Depending on local conditions and patient risk factors, empirical therapy of suspected S. aureus infection may require coverage of drug-resistant organisms with newer agents and novel antibiotic combinations. The question of treatment with inappropriate antibiotics raises grave concerns with regard to methicillin-resistant S. aureus selection, overgrowth, and increased virulence. Several strategies to reduce the nosocomial burden of resistance are suggested, including shortened hospital stays and outpatient parenteral antimicrobial therapy of the most serious infections.

  6. Comparison of telavancin and vancomycin lock solutions in eradication of biofilm-producing staphylococci and enterococci from central venous catheters.

    PubMed

    Luther, Megan K; Mermel, Leonard A; LaPlante, Kerry L

    2016-03-01

    Results of a study of the activity of antibiotic lock solutions of vancomycin and telavancin against biofilm-forming strains of Staphylococcus epidermidis, Enterococcus faecalis, and Staphylococcus aureus are reported. An established in vitro central venous catheter model was used to evaluate lock solutions containing vancomycin (5 mg/mL) or telavancin (5 mg/mL), with and without preservative-containing heparin sodium (with 0.45% benzyl alcohol) 2500 units/mL, heparin, and 0.9% sodium chloride solution. Lock solutions were introduced after 24-hour bacterial growth in catheters incubated at 35 °C. After 72 hours of exposure to the lock solutions, catheters were drained, flushed, and cut into segments for quantification of colony-forming units. Against S. epidermidis, vancomycin and telavancin (with or without heparin) had similar activity. Against E. faecalis, vancomycin alone was more active than telavancin alone (p < 0.01). Against S. aureus, vancomycin plus heparin had activity similar to that of vancomycin alone; both lock agents had greater activity than telavancin (p < 0.02). The addition of heparin was associated with reduced activity of the vancomycin lock solution against S. epidermidis and E. faecalis (p < 0.01). Telavancin activity was not significantly changed with the addition of heparin. In a central venous catheter model, vancomycin and telavancin activity was similar in reducing biofilm-producing S. epidermidis. However, vancomycin was more active than telavancin against E. faecalis and S. aureus. None of the tested agents eradicated biofilm-forming strains. The addition of preservative-containing heparin sodium 2500 units/mL to vancomycin was associated with reduced activity against S. epidermidis and E. faecalis. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  7. Structural and Functional Adaptation of Vancomycin Resistance VanT Serine Racemases

    PubMed Central

    Meziane-Cherif, Djalal; Stogios, Peter J.; Evdokimova, Elena; Egorova, Olga

    2015-01-01

    ABSTRACT Vancomycin resistance in Gram-positive bacteria results from the replacement of the d-alanyl–d-alanine target of peptidoglycan precursors with d-alanyl–d-lactate or d-alanyl–d-serine (d-Ala-d-Ser), to which vancomycin has low binding affinity. VanT is one of the proteins required for the production of d-Ala-d-Ser-terminating precursors by converting l-Ser to d-Ser. VanT is composed of two domains, an N-terminal membrane-bound domain, likely involved in l-Ser uptake, and a C-terminal cytoplasmic catalytic domain which is related to bacterial alanine racemases. To gain insight into the molecular function of VanT, the crystal structure of the catalytic domain of VanTG from VanG-type resistant Enterococcus faecalis BM4518 was determined. The structure showed significant similarity to type III pyridoxal 5′-phosphate (PLP)-dependent alanine racemases, which are essential for peptidoglycan synthesis. Comparative structural analysis between VanTG and alanine racemases as well as site-directed mutagenesis identified three specific active site positions centered around Asn696 which are responsible for the l-amino acid specificity. This analysis also suggested that VanT racemases evolved from regular alanine racemases by acquiring additional selectivity toward serine while preserving that for alanine. The 4-fold-lower relative catalytic efficiency of VanTG against l-Ser versus l-Ala implied that this enzyme relies on its membrane-bound domain for l-Ser transport to increase the overall rate of d-Ser production. These findings illustrate how vancomycin pressure selected for molecular adaptation of a housekeeping enzyme to a bifunctional enzyme to allow for peptidoglycan remodeling, a strategy increasingly observed in antibiotic-resistant bacteria. PMID:26265719

  8. Structural and functional adaptation of vancomycin resistance VanT serine racemases

    DOE PAGES

    Meziane-Cherif, Djalal; Stogios, Peter J.; Evdokimova, Elena; ...

    2015-08-11

    Vancomycin resistance in Gram-positive bacteria results from the replacement of the D-alanyl–D-alanine target of peptidoglycan precursors with D-alanyl–D-lactate or D-alanyl–D-serine (D-Ala-D-Ser), to which vancomycin has low binding affinity. VanT is one of the proteins required for the production of D-Ala-D-Ser-terminating precursors by converting L-Ser to D-Ser. VanT is composed of two domains, an N-terminal membrane-bound domain, likely involved in L-Ser uptake, and a C-terminal cytoplasmic catalytic domain which is related to bacterial alanine racemases. To gain insight into the molecular function of VanT, the crystal structure of the catalytic domain of VanT G from VanG-type resistant Enterococcus faecalis BM4518more » was determined. The structure showed significant similarity to type III pyridoxal 5'-phosphate (PLP)-dependent alanine racemases, which are essential for peptidoglycan synthesis. Comparative structural analysis between VanT G and alanine racemases as well as site-directed mutagenesis identified three specific active site positions centered around Asn 696 which are responsible for theL-amino acid specificity. This analysis also suggested that VanT racemases evolved from regular alanine racemases by acquiring additional selectivity toward serine while preserving that for alanine. The 4-fold-lower relative catalytic efficiency of VanT G against L-Ser versus L-Ala implied that this enzyme relies on its membrane-bound domain for L-Ser transport to increase the overall rate of D-Ser production. These findings illustrate how vancomycin pressure selected for molecular adaptation of a housekeeping enzyme to a bifunctional enzyme to allow for peptidoglycan remodeling, a strategy increasingly observed in antibiotic-resistant bacteria.« less

  9. β-Lactam Combinations with Vancomycin Show Synergistic Activity against Vancomycin-Susceptible Staphylococcus aureus, Vancomycin-Intermediate S. aureus (VISA), and Heterogeneous VISA.

    PubMed

    Tran, Kieu-Nhi; Rybak, Michael J

    2018-06-01

    Increasing utilization of vancomycin due to the high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infections has led to the emergence of vancomycin-intermediate S. aureus (VISA) and heterogeneous VISA (hVISA) strains. In vitro data suggest the potential for potent synergy between several beta-lactams and vancomycin. The objective of this study is to evaluate the synergy between beta-lactams and vancomycin against MRSA that is vancomycin susceptible, vancomycin-susceptible Staphylococcus aureus (VSSA), hVISA, and VISA. Fifty randomly selected clinical MRSA strains with various susceptibility levels to vancomycin were evaluated for vancomycin alone and vancomycin in combination with various concentrations of cefazolin (CFZ), cefepime (FEP), ceftaroline (CPT), and nafcillin (NAF). The potential for synergy was assessed by 24-h time-kill studies. Beta-lactams reduced vancomycin MIC values against all strains (4- to 16-fold reduction). In time-kill studies against MRSA, CFZ, FEP, CPT, and NAF all demonstrated similar degrees of killing at 24 h, and all showed synergistic activity with vancomycin against VSSA, hVISA, and VISA. Each of these combinations was also superior to any single agent against isolates of all three phenotypes, and each was bactericidal ( P < 0.001 for all comparisons). All single-agent exposures demonstrated no activity at 24 h. The combination of vancomycin and beta-lactams significantly improved antibacterial activity against VSSA, hVISA, and VISA strains compared to the activity of any agent alone, supporting the potential use of vancomycin-beta-lactam combination therapy in infections caused by MRSA. Further clinical research is warranted to investigate the synergy of vancomycin against these Staphylococcus strains. Copyright © 2018 American Society for Microbiology.

  10. Intermediate-type vancomycin resistance (VISA) in genetically-distinct Staphylococcus aureus isolates is linked to specific, reversible metabolic alterations.

    PubMed

    Alexander, Elizabeth L; Gardete, Susana; Bar, Haim Y; Wells, Martin T; Tomasz, Alexander; Rhee, Kyu Y

    2014-01-01

    Intermediate (VISA-type) vancomycin resistance in Staphylococcus aureus has been associated with a range of physiologic and genetic alterations. Previous work described the emergence of VISA-type resistance in two clonally-distinct series of isolates. In both series (the first belonging to MRSA clone ST8-USA300, and the second to ST5-USA100), resistance was conferred by a single mutation in yvqF (a negative regulator of the vraSR two-component system associated with vancomycin resistance). In the USA300 series, resistance was reversed by a secondary mutation in vraSR. In this study, we combined systems-level metabolomic profiling with statistical modeling techniques to discover specific, reversible metabolic alterations associated with the VISA phenotype.

  11. Weissella confusa: a rare cause of vancomycin-resistant Gram-positive bacteraemia.

    PubMed

    Kumar, Anil; Augustine, Deepthi; Sudhindran, S; Kurian, Anu M; Dinesh, Kavitha R; Karim, Shamsul; Philip, Rosamma

    2011-10-01

    We describe a case of bacteraemia caused by Weissella confusa in a 48-year-old male who was operated on for adenocarcinoma of the gastro-oesophageal junction and maintained on total parenteral nutrition. Blood cultures were positive for a vancomycin-resistant streptococcus-like organism which was identified as W. confusa by 16S rRNA gene sequencing.

  12. Selection of Fecal Enterococci Exhibiting tcrB-Mediated Copper Resistance in Pigs Fed Diets Supplemented with Copper † ▿

    PubMed Central

    Amachawadi, R. G.; Shelton, N. W.; Shi, X.; Vinasco, J.; Dritz, S. S.; Tokach, M. D.; Nelssen, J. L.; Scott, H. M.; Nagaraja, T. G.

    2011-01-01

    Copper, as copper sulfate, is increasingly used as an alternative to in-feed antibiotics for growth promotion in weaned piglets. Acquired copper resistance, conferred by a plasmid-borne, transferable copper resistance (tcrB) gene, has been reported in Enterococcus faecium and E. faecalis. A longitudinal field study was undertaken to determine the relationship between copper supplementation and the prevalence of tcrB-positive enterococci in piglets. The study was done with weaned piglets, housed in 10 pens with 6 piglets per pen, fed diets supplemented with a normal (16.5 ppm; control) or an elevated (125 ppm) level of copper. Fecal samples were randomly collected from three piglets per pen on days 0, 14, 28, and 42 and plated on M-Enterococcus agar, and three enterococcal isolates were obtained from each sample. The overall prevalence of tcrB-positive enterococci was 21.1% (38/180) in piglets fed elevated copper and 2.8% (5/180) in the control. Among the 43 tcrB-positive isolates, 35 were E. faecium and 8 were E. faecalis. The mean MICs of copper for tcrB-negative and tcrB-positive enterococci were 6.2 and 22.2 mM, respectively. The restriction digestion of the genomic DNA of E. faecium or E. faecalis with S1 nuclease yielded a band of ∼194-kbp size to which both tcrB and the erm(B) gene probes hybridized. A conjugation assay demonstrated cotransfer of tcrB and erm(B) genes between E. faecium and E. faecalis strains. The higher prevalence of tcrB-positive enterococci in piglets fed elevated copper compared to that in piglets fed normal copper suggests that supplementation of copper in swine diets selected for resistance. PMID:21705534

  13. Novel combinations of vancomycin plus ceftaroline or oxacillin against methicillin-resistant vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous VISA.

    PubMed

    Werth, B J; Vidaillac, C; Murray, K P; Newton, K L; Sakoulas, G; Nonejuie, P; Pogliano, J; Rybak, M J

    2013-05-01

    We demonstrated a significant inverse correlation between vancomycin and beta-lactam susceptibilities in vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous VISA (hVISA) isolates. Using time-kill assays, vancomycin plus oxacillin or ceftaroline was synergistic against 3 of 5 VISA and 1 of 5 hVISA isolates or 5 of 5 VISA and 4 of 5 hVISA isolates, respectively. Beta-lactam exposure reduced overall vancomycin-Bodipy (dipyrromethene boron difluoride [4,4-difluoro-4-bora-3a,4a-diaza-s-indacene] fluorescent dye) binding but may have improved vancomycin-cell wall interactions to improve vancomycin activity. Further research is warranted to elucidate the mechanism behind vancomycin and beta-lactam synergy.

  14. CARRIAGE OF MULTIDRUG RESISTANT ENTEROCOCCUS FAECIUM AND ENTEROCOCCUS FAECALIS AMONG APPARENTLY HEALTHY HUMANS.

    PubMed

    Adesida, Solayide A; Ezenta, Cynthia C; Adagbada, Ajoke O; Aladesokan, Amudat A; Coker, Akitoye O

    2017-01-01

    Enterococci are indigenous flora of the gastro-intestinal tracts of animals and humans. Recently, interest in two major species, E. faecium and E. faecalis , has heightened because of their ability to cause serious infections and their intrinsic resistance to antimicrobials. This study was aimed at determining the prevalence of E . faecium and E . faecalis in human faecal samples and evaluating the susceptibility of the isolates to antibiotics. One hundred faecal samples were collected from apparently healthy individuals and analysed using conventionalbacteriological methods. The susceptibility profile of the isolates to nine antibiotics were determined using disk diffusion method. Seventy-three (73) Enterococcus were phenotypically identified and 65 of the isolates were differentiated into 36 (55.4%) E. faecium and 29 (44.6%) E. faecalis . Eight (8) isolates could not be identified by the conventional biochemical methods employed. No dual colonization by the E. faecalis and E. faecium was observed and isolation rate was not dependent on sex of the participants. All the isolates were resistant to ceftriaxone, cefuroxime and ceftizoxime. Enterococcus faecium exhibited resistance toerythromycin (88.9%), gentamicin (77.8%), amoxicillin-clavulanate (63.9%), ofloxacin (44.4%), teicoplanin (19.4%) and vancomycin (16.7%). Enterococcus faecalis showed the least resistance to vancomycin (13.8%) and teicoplanin (27.7%). Remarkable multiple antibiotic resistances to the classes of antibiotic tested were observed among the two species. The high carriage rate of antibiotic resistant E. faecium and E. faecalis in this study provides information on the local antibiotic patterns of our enterococci isolates thereby suggesting that they could present as important reservoir and vehicle for dissemination of resistant genes in our community.

  15. Genetic Pathway in Acquisition and Loss of Vancomycin Resistance in a Methicillin Resistant Staphylococcus aureus (MRSA) Strain of Clonal Type USA300

    PubMed Central

    Gardete, Susana; Kim, Choonkeun; Hartmann, Boris M.; Mwangi, Michael; Roux, Christelle M.; Dunman, Paul M.; Chambers, Henry F.; Tomasz, Alexander

    2012-01-01

    An isolate of the methicillin-resistant Staphylococcus aureus (MRSA) clone USA300 with reduced susceptibility to vancomycin (SG-R) (i.e, vancomycin-intermediate S. aureus, VISA) and its susceptible “parental” strain (SG-S) were recovered from a patient at the end and at the beginning of an unsuccessful vancomycin therapy. The VISA phenotype was unstable in vitro generating a susceptible revertant strain (SG-rev). The availability of these 3 isogenic strains allowed us to explore genetic correlates of antibiotic resistance as it emerged in vivo. Compared to the susceptible isolate, both the VISA and revertant strains carried the same point mutations in yycH, vraG, yvqF and lspA genes and a substantial deletion within an intergenic region. The revertant strain carried a single additional frameshift mutation in vraS which is part of two component regulatory system VraSR. VISA isolate SG-R showed complex alterations in phenotype: decreased susceptibility to other antibiotics, slow autolysis, abnormal cell division and increased thickness of cell wall. There was also altered expression of 239 genes including down-regulation of major virulence determinants. All phenotypic properties and gene expression profile returned to parental levels in the revertant strain. Introduction of wild type yvqF on a multicopy plasmid into the VISA strain caused loss of resistance along with loss of all the associated phenotypic changes. Introduction of the wild type vraSR into the revertant strain caused recovery of VISA type resistance. The yvqF/vraSR operon seems to function as an on/off switch: mutation in yvqF in strain SG-R turns on the vraSR system, which leads to increase in vancomycin resistance and down-regulation of virulence determinants. Mutation in vraS in the revertant strain turns off this regulatory system accompanied by loss of resistance and normal expression of virulence genes. Down-regulation of virulence genes may provide VISA strains with a “stealth” strategy

  16. Sodium chloride-esculin hydrolysis test for rapid identification of enterococci.

    PubMed Central

    Qadri, S M; Flournoy, D J; Qadri, S G

    1987-01-01

    The ability of enterococci to cause severe disease in humans and their relative resistance to chemotherapeutic agents make it desirable to rapidly differentiate these organisms from other streptococci. We developed and evaluated a test that within 2 h distinguishes enterococci from other alpha-, beta-, or nonhemolytic streptococci in a buffered solution containing 0.2% esculin and 5% sodium chloride. All 239 strains of enterococci tested gave a positive reaction within 2 h, whereas 95 of 96 isolates of other streptococci remained negative at 4 h. PMID:3597753

  17. Prevalence, resistance patterns, and risk factors for antimicrobial resistance in bacteria from retail chicken meat in Colombia.

    PubMed

    Donado-Godoy, Pilar; Byrne, Barbara A; León, Maribel; Castellanos, Ricardo; Vanegas, Consuelo; Coral, Adriana; Arevalo, Alejandra; Clavijo, Viviana; Vargas, Mercedes; Romero Zuñiga, Juan J; Tafur, McAllister; Pérez-Gutierrez, Enrique; Smith, Woutrina A

    2015-04-01

    As a step toward implementing the Colombian Integrated Program for Antimicrobial Resistance Surveillance (COIPARS), this study aimed to establish the baseline antimicrobial resistance patterns of Salmonella serovars, Escherichia coli, and Enterococcus spp. isolates in retail poultry meat from independent stores and from a main chain distributor center. MICs of the isolates were determined for antimicrobials used both in humans and animals, using an automated system. Salmonella serovars were isolated from 26% of the meat samples and E. coli from 83%, whereas Enterococcus faecalis and Enterococcus faecium were detected in 81 and 13% of the meat samples, respectively. A principal finding of concern in this study was that almost 98% of isolates tested were multidrug resistant. Ceftiofur, enrofloxacin, nalidixic acid, and tetracycline were the antimicrobials that showed the highest frequency of resistance among Salmonella and E. coli isolates. For enterococci, 61.5% of E. faecium isolates were found to be resistant to quinupristin-dalfopristin; this is significant because it is used to treat nosocomial infections when vancomycin resistance is present. Vancomycin resistance was detected in 4% of the E. faecalis isolates. The results of our study highlight the need for rapid implementation of an integrated program for surveillance of antimicrobial resistance by the Colombian authorities in order to monitor trends, raise awareness, and help promote practices to safeguard later generation antimicrobial agents.

  18. Short communication: β-Lactam resistance and vancomycin heteroresistance in Staphylococcus spp. isolated from bovine subclinical mastitis.

    PubMed

    Mello, Priscila Luiza; Pinheiro, Luiza; Martins, Lisiane de Almeida; Brito, Maria Aparecida Vasconcelos Paiva; Ribeiro de Souza da Cunha, Maria de Lourdes

    2017-08-01

    The use of antimicrobial agents has led to the emergence of resistant bacterial strains over a relatively short period. Furthermore, Staphylococcus spp. can produce β-lactamase, which explains the survival of these strains in a focus of infection despite the use of a β-lactam antibiotic. The aim of this study was to evaluate the resistance of Staphylococcus spp. isolated from bovine subclinical mastitis to oxacillin and vancomycin (by minimum inhibitory concentration) and to detect vancomycin heteroresistance by a screening method. We also evaluated β-lactamase production and resistance due to hyperproduction of this enzyme and investigated the mecA and mecC genes and performed staphylococcal cassette chromosome mec typing. For this purpose, 181 Staphylococcus spp. isolated from mastitis subclinical bovine were analyzed. Using the phenotypic method, 33 (18.2%) of Staphylococcus spp. were resistant to oxacillin. In contrast, all isolates were susceptible to vancomycin, and heteroresistance was detected by the screening method in 13 isolates. Production of β-lactamase was observed in 174 (96%) of the Staphylococcus spp. isolates. The mecA gene was detected in 8 isolates, all of them belonging to the species Staphylococcus epidermidis, and staphylococcal cassette chromosome mec typing revealed the presence of type I and type IV isolates. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  19. Presence of the resistance genes vanC1 and pbp5 in phenotypically vancomycin and ampicillin susceptible Enterococcus faecalis.

    PubMed

    Schwaiger, Karin; Bauer, Johann; Hörmansdorfer, Stefan; Mölle, Gabriele; Preikschat, Petra; Kämpf, Peter; Bauer-Unkauf, Ilse; Bischoff, Meike; Hölzel, Christina

    2012-08-01

    Ampicillin and vancomycin are important antibiotics for the therapy of Enterococcus faecalis infections. The ampicillin resistance gene pbp5 is intrinsic in Enterococcus faecium. The vanC1 gene confers resistance to vancomycin and serves as a species marker for Enterococcus gallinarum. Both genes are chromosomally located. Resistance to ampicillin and vancomycin was determined in 484 E. faecalis of human and porcine origin by microdilution. Since E. faecalis are highly skilled to acquire resistance genes, all strains were investigated for the presence of pbp5 (and, in positive strains, for the penicillin-binding protein synthesis repressor gene psr) and vanC1 (and, in positive strains, for vanXYc and vanT) by using polymerase chain reaction (PCR). One porcine and one human isolate were phenotypically resistant to ampicillin; no strain was vancomycin resistant. Four E. faecalis (3/1 of porcine/human origin) carried pbp5 (MIC=1 mg/L), and four porcine strains were vanC1 positive (minimum inhibitory concentration [MIC]=1 mg/L). Real-time reverse transcriptase (RT)-PCR revealed that the genes were not expressed. The psr gene was absent in the four pbp5-positive strains; the vanXYc gene was absent in the four vanC1-positive strains. However, vanT of the vanC gene cluster was detected in two vanC1-positive strains. To our knowledge, this is the first report on the presence of pbp5, identical with the "E. faecium pbp5 gene," and of vanC1/vanT in E. faecalis. Even if resistance is not expressed in these strains, this study shows that E. faecalis have a strong ability to acquire resistance genes-and potentially to spread them to other bacteria. Therefore, close monitoring of this species should be continued.

  20. [Susceptibility of enterococci to natural and synthetic iron chelators].

    PubMed

    Lisiecki, Paweł; Mikucki, Jerzy

    2002-01-01

    A total of 79 strains of enterococci belonging to 10 species were tested for susceptibility to natural and synthetic iron chelators. All strains produced siderophores. These enterococci were susceptible to three synthetic iron chelators only: 8-hydroxyquinoline, disodium versenate (EDTA) and o-phenanthroline. They were resistant to all other synthetic chelators: ethylenediamine-di(o-hydroxyphenylacetic acid) (EDDHA), nitrilotriacetate, 2,2'-bipiridyl, salicylic acid, 8-hydroxy-5-sulphonic acid and to all natural chelators: ovotransferrine, human apotransferrine, horse apoferritine, desferrioxamine B, ferrichrome and rhodotorulic acid. The relations between susceptibility/resistance, iron assimilation and structure and stability constants of iron chelators were discussed.

  1. Nanoconjugated vancomycin: new opportunities for the development of anti-VRSA agents

    NASA Astrophysics Data System (ADS)

    Prasad Chakraborty, Subhankari; Sahu, Sumanta Kumar; Mahapatra, Santanu Kar; Santra, Susmita; Bal, Manjusri; Roy, Somenath; Pramanik, Panchanan

    2010-03-01

    More than 90% of Staphylococcus strains are resistant to penicillin. In 1961 S. aureus developed resistance to methicillin (MRSA), invalidating almost all antibiotics, including the most potent β-lactams. Vancomycin, a glycopeptide antibiotic, was used for the treatment of MRSA in 1980. Vancomycin inhibits the bio-synthesis of peptidoglycan and the assembly of NAM-NAG-polypeptide into the growing peptidoglycan chain. Vancomycin resistant S. aureus (VRSA) first appeared in the USA in 2002. Folic acid tagged chitosan nanoparticles are used as Trojan horses to deliver vancomycin into bacterial cells. These nanoparticles are biocompatible and biodegradable semisynthetic polymers. These nanosized vehicles enhance the transport of vancomycin across epithelial surfaces and show its efficient drug action, which has been understood from studies of the minimum inhibitory concentration and minimum bactericidal concentration of nanoparticles of a chitosan derivative loaded with vancomycin. Tolerance values distinctly show that vancomycin loaded into nanoconjugate is very effective and has a strong bactericidal effect on VRSA.

  2. Is faecal microbiota transplantation an option to eradicate highly drug-resistant enteric bacteria carriage?

    PubMed

    Davido, B; Batista, R; Michelon, H; Lepainteur, M; Bouchand, F; Lepeule, R; Salomon, J; Vittecoq, D; Duran, C; Escaut, L; Sobhani, I; Paul, M; Lawrence, C; Perronne, C; Chast, F; Dinh, A

    2017-04-01

    Carbapenem-resistant Enterobacteriaceae (CRE) or vancomycin-resistant enterococci (VRE) carriage present a major public health challenge. Decolonization strategies are lacking. We aimed to evaluate the impact of faecal microbiota transplantation (FMT) on a cohort of patients with digestive tract colonization by CRE or VRE. Eight patients were included: six carrying CRE and two colonized by VRE. One month after FMT, two patients were free from CRE carriage, and another patient was free from VRE after three months. In our experience, this strategy is safe. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  3. [Study of marine actinomycetes isolated from the central coast of Peru and their antibacterial activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis].

    PubMed

    León, Jorge; Aponte, Juan José; Rojas, Rosario; Cuadra, D'Lourdes; Ayala, Nathaly; Tomás, Gloria; Guerrero, Marco

    2011-06-01

    To determine the antimicrobial potential of marine actinomycetes against drug-resistant pathogens represented by strains of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE). Strains of actinomycetes (29) isolated from marine sediment were evaluated by their characteristics in two culture media and by testing their inhibitory capacity by in vitro antagonism against multi-drug resistant (MDR) pathogenic bacteria for MRSA and VRE. Organic extracts of 3 selected actinomicetes were processed to determine the minimum inhibitory concentration (MIC) of the active compound. Most isolated actinomycetes belong to a homogeneous group of write-gray actinomycetes with a good growth in Marine Agar. The inhibitory rates of the isolates were above 85% for both pathogens with inhibition zones greater than 69 and 78 mm in diameter for MRSA and VRE respectively. Dichloromethane extracts of 3 isolates (I-400A, B1-T61, M10-77) showed strong inhibitory activity of both pathogens, M10-77 being the highest actinomycete strain with antibiotic activity against methicillin-resistant S. aureus ATCC 43300 and vancomycin-resistant E. faecalis ATCC 51299 with a minimum inhibitory concentrations (MIC) of 7.9 and 31.7 μg/ml respectively. Phylogenetic analysis of M10-77 strain showed 99% similarity with the marine species Streptomyces erythrogriseus. Marine sediments of the central coast of Peru, are a source of actinomycetes strains showing high capacity to produce bioactive compounds able to inhibit pathogens classified as multi-drug-resistant such as methicillin-resistant S. aureus and vancomycin-resistant E. faecalis.

  4. Phenotypic changes of methicillin-resistant Staphylococcus aureus during vancomycin therapy for persistent bacteraemia and related clinical outcome.

    PubMed

    Kim, T; Kim, E S; Park, S Y; Sung, H; Kim, M-N; Kim, S-H; Lee, S-O; Choi, S-H; Jeong, J-Y; Woo, J H; Chong, Y P; Kim, Y S

    2017-08-01

    Persistent bacteraemia (PB) due to methicillin-resistant Staphylococcus aureus (MRSA) that fails to respond to glycopeptide therapy is a well-documented clinical problem. There are limited data on changes in agr functionality, vancomycin susceptibility and heteroresistance during MRSA PB. Thus, the frequency of these changes and their clinical significance remain unclear. Only patients with MRSA PB (≥7 days) from a prospective cohort of S. aureus bacteraemia were included. We collected isogenic paired strains and compared vancomycin MIC, vancomycin heteroresistance, and agr functionality between initial and final blood isolates. We also assessed the clinical outcome. A total of 49 patients had MRSA PB over 22 months. Bacteraemia persisted for a median of 13 days and most patients (98%) received glycopeptide as initial therapy. Among 49 isogenic pairs, only one pair showed a vancomycin MIC increase ≥2-fold by broth microdilution method, and only seven (14%) by E-test. Significant portions of initial isolates had vancomycin heteroresistance (49%) and agr dysfunction (76%). Development of vancomycin heteroresistance during PB occurred in four (16%) among 25 initial vancomycin-susceptible isolates, and acquisition of agr dysfunction occurred in two (16%) among 12 initial agr-functional isolates. Changes in the opposite direction occasionally occurred. These phenotypic changes during PB were not associated with mortality, whereas agr dysfunction of the initial isolates was significantly associated with mortality. During MRSA PB, phenotypic changes of MRSA isolates occurred occasionally under prolonged vancomycin exposure but were not significantly associated with clinical outcome. In contrast, initial agr dysfunction could be a predictor for mortality in MRSA PB.

  5. Selective digestive tract decontamination and vancomycin-resistant enterococcus isolation in the surgical intensive care unit.

    PubMed

    Dahms, R; Carlson, M; Lohr, B; Beilman, G

    2000-09-01

    Vancomycin-resistant Enterococcus (VRE) has emerged as a significant nosocomial pathogen in the surgical intensive care unit (SICU). We wished to test the hypothesis that the use of selective digestive tract decontamination (SDD) in the SICU affects the frequency of VRE isolation. A retrospective review of hospital records and the SICU database was performed using patients admitted to the SICU service for three or more days from January 1, 1996 to December 31, 1999 at our large tertiary-care teaching hospital. During this time use of SDD in selected patient populations decreased due to physician preference. Information gathered included length of SICU stay, presence of VRE infection or colonization, and use and duration of SDD protocol, vancomycin, and ceftazidime. There were 110 newly diagnosed VRE cases in the SICU during this time period. During the same time period 54 patients received SDD. Eight patients who received SDD had positive VRE cultures and seven had the initial positive culture after receiving SDD. Overall, 9.1% of eligible SICU patients received SDD, 18.5% of patients in the SICU for over 3 days had VRE, 7.3% of VRE patients received SDD, and 13.0% of the SICU patients who received SDD subsequently developed VRE. SDD use was not associated with VRE in univariate analysis. Logistic regression analysis showed higher odds ratios for SDD use in combination with vancomycin than for vancomycin use alone (OR=4.3 vs. 10.9). Odds ratios were over three times higher for SDD plus vancomycin plus ceftazidime use when compared to vancomycin plus ceftazidime use alone (OR=70.5 vs. 19.8). We conclude that administration of SDD alone did not correlate with increased VRE isolation, but that SDD use in conjunction with vancomycin and ceftazidime was associated with VRE isolation.

  6. Stimulated phase-shift acoustic nanodroplets enhance vancomycin efficacy against methicillin-resistant Staphylococcus aureus biofilms.

    PubMed

    Guo, Hao; Wang, Ziming; Du, Quanyin; Li, Pan; Wang, Zhigang; Wang, Aimin

    2017-01-01

    Bacterial biofilms on the surface of prostheses are becoming a rising concern in managing prosthetic joint infections. The inherent resistant features of biofilms render traditional antimicrobial therapy unproductive and revision surgery outcomes uncertain. This situation has prompted the exploration of novel antimicrobial strategies. The synergy of ultrasound microbubbles and vancomycin has been proposed as an efficient alternative for biofilm eradication. The purpose of this study was to evaluate the anti-biofilm effect of stimulated phase-shift acoustic nanodroplets (NDs) combined with vancomycin. We fabricated lipid phase-shift NDs with a core of liquid perfluoropentane. A new phase change mode for NDs incorporating an initial unfocused low-intensity pulsed ultrasound for 5 minutes and a subsequent incubation at 37°C into a 24-hour duration was developed. Methicillin-resistant Staphylococcus aureus (MRSA) biofilms were incubated with vancomycin and NDs under the hybrid stimulation. Biofilm morphology following treatment was determined using confocal laser scanning microscopy and scanning electron microscopy. Resazurin assay was used to quantify bactericidal efficacy against MRSA biofilm bacteria. NDs treated sequentially with ultrasound and heating at 37°C achieved gradual and substantial ND vaporization and cavitation in a successive process. NDs after stimulation were capable of generating stronger destruction on biofilm structure which was best characterized by residual circular arc margins and more dead bacteria. Furthermore, NDs combined with vancomycin contributed to significantly decreasing the metabolic activity of bacteria in MRSA biofilms ( P <0.05). Phase-shift acoustic NDs could exert a significant bactericidal effect against MRSA biofilms through a new stimulation mode. Acoustic NDs present advantages over microbubbles for biofilm damage. This anti-biofilm strategy could be used either alone or as an enhancer of traditional antibiotics in the

  7. An outbreak of vancomycin-resistant Enterococcus faecium in an acute care pediatric hospital: Lessons from environmental screening and a case-control study

    PubMed Central

    Drews, Steven J; Richardson, Susan E; Wray, Rick; Freeman, Renee; Goldman, Carol; Streitenberger, Laurie; Stevens, Derek; Goia, Cristina; Kovach, Danuta; Brophy, Jason; Matlow, Anne G

    2008-01-01

    BACKGROUND The present study describes a vancomycin-resistant enterococci (VRE) outbreak investigation and a case-control study to identify risk factors for VRE acquisition in a tertiary care pediatric hospital. OBJECTIVE To report an outbreak investigation and a case-control study to identify risk factors for VRE colonization or infection in hospitalized children. METHODS Screening for VRE cases was performed by culture or polymerase chain reaction. A case-control study of VRE-colonized patients was undertaken. Environmental screening was performed using standard culture and susceptibility methods, with pulsed-field gel electrophoresis to determine relationships between VRE isolates. Statistical analysis was performed using SAS version 9.0 (SAS Institute Inc, USA). RESULTS Thirty-four VRE-positive cases were identified on 10 wards between February 28, 2005, and May 27, 2005. Pulsed-field gel electrophoresis analysis confirmed a single outbreak strain that was also isolated from a video game found on one affected ward. Multivariate analysis identified cephalosporin use as the major risk factor for VRE colonization. CONCLUSIONS In the present study outbreak, VRE colonization was significantly associated with cephalosporin use. Because shared recreational items and environmental surfaces may be colonized by VRE, they warrant particular attention in housekeeping protocols, particularly in pediatric institutions. PMID:19412380

  8. Effect of Lactobacillus rhamnosus GG Administration on Vancomycin-Resistant Enterococcus Colonization in Adults with Comorbidities

    PubMed Central

    Hibberd, Patricia L.; Goldin, Barry; Thorpe, Cheleste; McDermott, Laura; Snydman, David R.

    2015-01-01

    Vancomycin-resistant enterococci (VRE) are endemic in health care settings. These organisms colonize the gastrointestinal tract and can lead to infection which is associated with increased mortality. There is no treatment for VRE colonization. We conducted a randomized, double-blind, placebo-controlled clinical trial to examine the safety and efficacy of administration of the probiotic Lactobacillus rhamnosus GG (LGG) for the reduction or elimination of intestinal colonization by VRE. Colonized adults were randomized to receive LGG or placebo for 14 days. Quantitative stool cultures for LGG and VRE were collected at baseline and days 7, 14, 21, 28, and 56. Day 14 stool samples from some subjects were analyzed by quantitative PCR (qPCR) for LGG. Patients were closely monitored for adverse events. Eleven subjects, of whom 5 received LGG and 6 received placebo, were analyzed. No differences in VRE colony counts were seen at any time points between groups. No decline in colony counts was seen over time in subjects who received LGG. LGG was detected by PCR in all samples tested from subjects who received LGG but was only isolated in culture from 2 of 5 subjects in the LGG group. No treatment-related adverse events were seen. We demonstrated that LGG could be administered safely to patients with comorbidities and is recoverable in some patients' stool cultures. Concomitant administration of antibiotics may have resulted in an inability to recover viable organisms from stool samples, but LGG DNA could still be detected by qPCR. LGG administration did not affect VRE colonization in this study. (This study was registered at Clinicaltrials.gov under registration no. NCT00756262.) PMID:26014940

  9. Automatic Digital Analysis of Chromogenic Media for Vancomycin-Resistant-Enterococcus Screens Using Copan WASPLab

    PubMed Central

    Faron, Matthew L.; Coon, Christopher; Liebregts, Theo; van Bree, Anita; Jansz, Arjan R.; Soucy, Genevieve; Korver, John

    2016-01-01

    Vancomycin-resistant enterococci (VRE) are an important cause of health care-acquired infections (HAIs). Studies have shown that active surveillance of high-risk patients for VRE colonization can aid in reducing HAIs; however, these screens generate a significant cost to the laboratory and health care system. Digital imaging capable of differentiating negative and “nonnegative” chromogenic agar can reduce the labor cost of these screens and potentially improve patient care. In this study, we evaluated the performance of the WASPLab Chromogenic Detection Module (CDM) (Copan, Brescia, Italy) software to analyze VRE chromogenic agar and compared the results to technologist plate reading. Specimens collected at 3 laboratories were cultured using the WASPLab CDM and plated to each site's standard-of-care chromogenic media, which included Colorex VRE (BioMed Diagnostics, White City, OR) or Oxoid VRE (Oxoid, Basingstoke, United Kingdom). Digital images were scored using the CDM software after 24 or 40 h of growth, and all manual reading was performed using digital images on a high-definition (HD) monitor. In total, 104,730 specimens were enrolled and automation agreed with manual analysis for 90.1% of all specimens tested, with sensitivity and specificity of 100% and 89.5%, respectively. Automation results were discordant for 10,348 specimens, and all discordant images were reviewed by a laboratory supervisor or director. After a second review, 499 specimens were identified as representing missed positive cultures falsely called negative by the technologist, 1,616 were identified as containing borderline color results (negative result but with no package insert color visible), and 8,234 specimens were identified as containing colorimetric pigmentation due to residual matrix from the specimen or yeast (Candida). Overall, the CDM was accurate at identifying negative VRE plates, which comprised 84% (87,973) of the specimens in this study. PMID:27413193

  10. Comparison of three PCR primer sets for identification of vanB gene carriage in feces and correlation with carriage of vancomycin-resistant enterococci: interference by vanB-containing anaerobic bacilli.

    PubMed

    Ballard, S A; Grabsch, E A; Johnson, P D R; Grayson, M L

    2005-01-01

    We assessed the sensitivities and specificities of three previously described PCR primers on enrichment broth cultures of feces for the accurate detection of fecal carriage of vancomycin-resistant enterococci (VRE). In addition, we investigated specimens that were vanB PCR positive but VRE culture negative for the presence of other vanB-containing pathogens. Feces from 59 patients (12 patients carrying vanB Enterococcus faecium strains and 47 patients negative for VRE carriage) were cultured for 36 h in aerobic brain heart infusion (BHI) broth, anaerobic BHI (AnO(2)BHI) broth, or aerobic Enterococcosel (EC) broth. DNA was extracted from the cultures and tested for the presence of vanB by using the PCR primers of Dutka-Malen et al. (S. Dutka-Malen, S. Evers, and P. Courvalin, J. Clin. Microbiol. 33:24-27, 1995), Bell et al. (J. M. Bell, J. C. Paton, and J. Turnidge, J. Clin. Microbiol. 36:2187-2190, 1998), and Stinear et al. (T. P. Stinear, D. C. Olden, P. D. R. Johnson, J. K. Davies, and M. L. Grayson, Lancet 357:855-856, 2001). The sensitivity (specificity) of PCR compared with the results of culture on BHI, AnO(2)BHI, and EC broths were 67% (96%), 50% (94%), and 17% (100%), respectively, with the primers of Dutka-Malen et al.; 92% (60%), 92% (45%), and 92% (83%), respectively, with the primers of Bell et al.; and 92% (49%), 92% (43%), and 100% (51%) respectively, with the primers of Stinear et al. The primers of both Bell et al. and Stinear et al. were significantly more sensitive than those of Dutka-Malen et al. in EC broth (P = 0.001 and P < 0.001, respectively). The poor specificities for all primer pairs were due in part to the isolation and identification of six anaerobic gram-positive bacilli, Clostridium hathewayi (n = 3), a Clostridium innocuum-like organism (n = 1), Clostridium bolteae (n = 1), and Ruminococcus lactaris-like (n = 1), from five fecal specimens that were vanB positive but VRE culture negative. All six organisms were demonstrated to contain

  11. Risk factors associated with fluoroquinolone-resistant enterococcal urinary tract infections in a tertiary care university hospital in north India.

    PubMed

    Banerjee, Tuhina; Anupurba, Shampa

    2016-10-01

    Fluoroquinolone resistance in both Gram-positive and Gram-negative bacteria has increased with the widespread use of fluoroquinolones. Fluoroquinolone resistance in Gram-negative bacilli has been widely studied, though staphylococci and enterococci are also notably resistant. Enterococci being the second most common cause of healthcare-associated urinary tract infections (UTIs) fluoroquinolones are often the drug of choice. This study was undertaken to assess the risk factors associated with fluoroquinolone-resistant enterococcal UTI in a tertiary level health facility in north India. A total of 365 patients with UTI caused by enterococci were studied over a period of two years. Patients with ciprofloxacin-resistant and susceptible UTI were considered as cases and controls, respectively. Resistance profile of the isolates against common antibiotics was studied by minimum inhibitory concentration (MIC) determination. Mechanisms for fluoroquinolone resistance was studied by efflux pump inhibitor activity and multiplex PCR targeting the qnr genes. A total of 204 (55.89%) cases and 161 (44.1%) controls were identified. The fluoroquinolone-resistant isolates were significantly resistant to ampicillin, high strength aminoglycosides and vancomycin. The majority (78%) of the resistant isolates showed efflux pump activity. Treatment in indoor locations, presence of urinary catheters and pregnancy along with recent exposure to antibiotics especially fluoroquinolones, third generation cephalosporins and piperacillin-tazobactam were identified as independent risk factors. Our results showed that fluoroquinolone resistance in enterococcal UTI was largely associated with indoor usage of antibiotics and use of indwelling devices. Knowledge of risk factors is important to curb this emergence of resistance.

  12. Identification and antimicrobial resistance of microflora colonizing feral pig (Sus scrofa) of Brazilian Pantanal.

    PubMed Central

    Lessa, SS; Paes, RCS; Santoro, PN; Mauro, RA; Vieira-da-Motta, O

    2011-01-01

    Antimicrobial resistance of bacteria is a worldwide problem affecting wild life by living with resistant bacteria in the environment. This study presents a discussion of outside factors environment on microflora of feral pigs (Sus scrofa) from Brazilian Pantanal. Animals had samples collected from six different body sites coming from two separated geographic areas, Nhecolandia and Rio Negro regions. With routine biochemical tests and commercial kits 516 bacteria were identified, with 240 Gram-positive, predominantly staphylococci (36) and enterococci (186) strains. Among Gram-negative (GN) bacteria the predominant specimens of Enterobacteriaceae (247) mainly represented by Serratia spp. (105), Escherichia coli (50), and Enterobacter spp. (40) and specimens not identified (7). Antimicrobial susceptibility was tested against 17 drugs by agar diffusion method. Staphylococci were negative to production of enterotoxins and TSST-1, with all strains sensitive towards four drugs and highest resistance toward ampicillin (17%). Enterococci presented the highest sensitivity against vancomycin (98%), ampicillin (94%) and tetracycline (90%), and highest resistance pattern toward oxacillin (99%), clindamycin (83%), and cotrimoxazole (54%). In GN the highest resistance was observed with Serratia marcescens against CFL (98%), AMC (66%) and AMP (60%) and all drugs was most effective against E. coli SUT, TET (100%), AMP, TOB (98%), GEN, CLO (95%), CFO, CIP (93%). The results show a new profile of oxacillin-resistant enterococci from Brazilian feral pigs and suggest a limited residue and spreading of antimicrobials in the environment, possibly because of low anthropogenic impact reflected by the drug susceptibility profile of bacteria isolated. PMID:24031689

  13. Emergence in Asian Countries of Staphylococcus aureus with Reduced Susceptibility to Vancomycin

    PubMed Central

    Song, Jae-Hoon; Hiramatsu, Keiichi; Suh, Ji Yoeun; Ko, Kwan Soo; Ito, Teruyo; Kapi, Maria; Kiem, Sungmin; Kim, Yeon-Sook; Oh, Won Sup; Peck, Kyong Ran; Lee, Nam Yong

    2004-01-01

    To investigate the prevalence of Staphylococcus aureus with reduced susceptibility to vancomycin among methicillin-resistant S. aureus (MRSA) strains in Asian countries, a total of 1,357 clinical isolates of MRSA collected from 12 Asian countries were screened by using brain heart infusion agar plates containing 4 mg of vancomycin per liter. The presence of strains that were heterointermediately resistant to vancomycin (hVISA) was confirmed by population analysis. Of 347 (25.6%) MRSA isolates that grew on the screening agar plates, 58 isolates (4.3%) were hVISA. hVISA strains were found in India, South Korea, Japan, the Philippines, Singapore, Thailand, and Vietnam. However, neither vancomycin-intermediate S. aureus nor vancomycin-resistant S. aureus isolates were found among MRSA isolates from Asian countries in this survey. PMID:15561884

  14. Molecular characterization of resistance, virulence and clonality in vancomycin-resistant Enterococcus faecium and Enterococcus faecalis: A hospital-based study in Beijing, China.

    PubMed

    Yang, Jing-xian; Li, Tong; Ning, Yong-zhong; Shao, Dong-hua; Liu, Jing; Wang, Shu-qin; Liang, Guo-wei

    2015-07-01

    The incidence of vancomycin-resistant enterococcus (VRE) in China is increasing, the molecular epidemiology of VRE in China is only partly known. This study was conducted to assess the molecular characterization of resistance, virulence and clonality of 69 vancomycin-resistant Enterococcus faecium (VREfm) and seven vancomycin-resistant Enterococcus faecalis (VREfs) isolates obtained from a Chinese hospital between July 2011 and July 2013. The glycopeptide resistance genes (VanA and VanB) were screened by multiplex PCR. The presence of five putative virulence genes (esp, gelE, asa1, hyl and cylA) were evaluated by another multiplex PCR. Multilocus sequence typing (MLST) scheme was used to assess the clonality. All 76 VRE isolates exhibited VanA phenotype and harbored VanA gene. Esp was the only gene detected both in VREfm and VREfs strains, accounting for 89.9% and 42.9%, respectively. The hyl gene was merely positive in 27.5% of VREfm strains. MLST analysis demonstrated three STs (ST6, ST4 and ST470) in VREfs and twelve STs (ST78, ST571, ST17, ST564, ST389, ST18, ST547, ST341, ST414, ST343, ST262 and ST203) in VREfm, which were all designated as CC17 by eBURST algorithm. An outbreak of VREfm belonging to ST571 was found to happen within the neurology ward in this hospital. To our knowledge, this is the first report of ST6 (CC2) VREfs strains in China and the first outbreak report of VREfm strains belonging to ST571 around the world. Our data could offer important information for understanding the molecular features of VRE in China. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Prevalence, antimicrobial resistance and genetic lineages of Enterococcus spp. from vegetable food, soil and irrigation water in farm environments in Tunisia.

    PubMed

    Ben Said, Leila; Klibi, Naouel; Dziri, Raoudha; Borgo, Francesca; Boudabous, Abdellatif; Ben Slama, Karim; Torres, Carmen

    2016-03-30

    The objective of this study was to determine the species, clonal diversity, antibiotic resistance and virulence of enterococci in different environments. Seventy-one samples of farm origin (34 of food vegetables, 27 of soil and ten of irrigation water) and 19 samples of vegetables from five markets, were inoculated in Slanetz-Bartley agar plates supplemented or not with gentamicin (SB-Gen and SB plates, respectively) for enterococci recovery. Enterococci were obtained from 72.2% of tested samples in SB media (food vegetables from farms, 88.2%; soil and irrigation water, 51%; food vegetables from markets, 84.2%), and 65 enterococcal isolates were obtained. Enterococcus faecium was the most prevalent species (52.3%), followed by E. hirae (35.4%), E. faecalis (6.15%), and E. casseliflavus (6.15%). Antibiotic resistance detected among these enterococci was as follows (percentage/detected gene): ciprofloxacin (60%), erythromycin (18.4%/erm(B)), tetracycline (15.4%/tet(M)-tet(L)), kanamycin (15.4%/aph(3')-III), chloramphenicol (7.7%), streptomycin (3%/ant(6)), vancomycin (6.15%/vanC2)), teicoplanin (0%) and ampicillin (0%). High-level gentamicin-resistant (HLR-G) enterococci were detected in SB-Gen plates in 14 of 90 tested samples (15.5%), and 15 isolates were characterized: ten E. faecalis, four E. faecium and one E. hirae. All HLR-G enterococci carried the aac(6')-aph(2″), erm(B) and tet(M) genes, among other resistance genes. The HLR-G isolates showed high genetic diversity (ten different PFGE profiles), and were ascribed to the sequence types ST2, ST16, ST28 and new ST528 (in E. faecalis), and ST56, new ST885 and new ST886 (in E. faecium). Food vegetables in the farm or market settings are frequently contaminated by HLR-G enterococci, and these microorganisms could reach the human intestine through the food chain, if hygienic conditions are not followed. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  16. Evolutionary origins of the emergent ST796 clone of vancomycin resistant Enterococcus faecium

    PubMed Central

    Buultjens, Andrew H.; Lam, Margaret M.C.; Ballard, Susan; Monk, Ian R.; Mahony, Andrew A.; Grabsch, Elizabeth A.; Grayson, M. Lindsay; Pang, Stanley; Coombs, Geoffrey W.; Robinson, J. Owen; Seemann, Torsten; Howden, Benjamin P.

    2017-01-01

    From early 2012, a novel clone of vancomycin resistant Enterococcus faecium (assigned the multi locus sequence type ST796) was simultaneously isolated from geographically separate hospitals in south eastern Australia and New Zealand. Here we describe the complete genome sequence of Ef_aus0233, a representative ST796 E. faecium isolate. We used PacBio single molecule real-time sequencing to establish a high quality, fully assembled genome comprising a circular chromosome of 2,888,087 bp and five plasmids. Comparison of Ef_aus0233 to other E. faecium genomes shows Ef_aus0233 is a member of the epidemic hospital-adapted lineage and has evolved from an ST555-like ancestral progenitor by the accumulation or modification of five mosaic plasmids and five putative prophage, acquisition of two cryptic genomic islands, accrued chromosomal single nucleotide polymorphisms and a 80 kb region of recombination, also gaining Tn1549 and Tn916, transposons conferring resistance to vancomycin and tetracycline respectively. The genomic dissection of this new clone presented here underscores the propensity of the hospital E. faecium lineage to change, presumably in response to the specific conditions of hospital and healthcare environments. PMID:28149688

  17. In vitro selection of Staphylococcus aureus mutants resistant to tigecycline with intermediate susceptibility to vancomycin.

    PubMed

    Herrera, Melina; Di Gregorio, Sabrina; Fernandez, Silvina; Posse, Graciela; Mollerach, Marta; Di Conza, José

    2016-03-08

    Tigecycline (TIG) is an antibiotic belonging to the glycylcyclines class and appears to be a good choice to fight infections caused by Staphylococcus aureus. To date, TIG exhibits good activity against this microorganism. The aim of this work was to obtain in vitro mutants of S. aureus resistant to TIG and evaluate possible changes in their susceptibility patterns to other antibiotics. Two mutants of S. aureus resistant to TIG (MIC = 16 µg/mL) were selected in vitro from clinical isolates of methicillin-resistant S. aureus. In both mutants, corresponding to different lineage (ST5 and ST239), an increase of efflux activity against TIG was detected. One mutant also showed a reduced susceptibility to vancomycin, corresponding to the VISA phenotype (MIC = 4 µg/mL), with a loss of functionality of the agr locus. The emergence of the VISA phenotype was accompanied by an increase in oxacillin and cefoxitin MICs. This study demonstrates that, under selective pressure, the increase of efflux activity in S. aureus is one of the mechanisms that may be involved in the emergence of tigecycline resistance. The emergence of this phenotype may eventually be associated to changes in susceptibility to other antibiotics such oxacillin and vancomycin.

  18. Vancomycin Ophthalmic Ointment 1% for methicillin-resistant Staphylococcus aureus or methicillin-resistant Staphylococcus epidermidis infections: a case series

    PubMed Central

    Sotozono, Chie; Fukuda, Masahiko; Ohishi, Masao; Yano, Keiko; Origasa, Hideki; Saiki, Yoshinori; Shimomura, Yoshikazu; Kinoshita, Shigeru

    2013-01-01

    Objectives To investigate the efficacy and safety of Vancomycin Ophthalmic Ointment 1% (Toa Pharmaceutical Co., Ltd, Toyama, Japan) in patients with external ocular infections caused by methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-resistant Staphylococcus epidermidis (MRSE). Design A case series. Setting This study was a multicentre, open-label, uncontrolled study in Japan approved as orphan drug status. Participants Patients with MRSA or MRSE external ocular infections unresponsive to the treatment of fluoroquinolone eye drops. Interventions Vancomycin Ophthalmic Ointment 1% was administered four times daily. Primary and secondary outcome measures The subjective and objective clinical scores and bacterial cultures were collected at days 0 (baseline), 3, 7 and 14. The primary outcome was clinical response evaluation (efficacy rate) determined as complete response, partial response, no response and worsening. Secondary outcome was the eradication of the bacteria. Safety was assessed by adverse events including cases in which neither MRSA nor MRSE was detected. Results Twenty-five cases with MRSA (20) or MRSE (5) infections were enrolled. Of these 25 cases, 4 discontinued the treatment due to the negative results for bacterial culture during screening or at baseline. Of the 21 cases with conjunctivitis (14), blepharitis (3), meibomitis (1), dacryocystitis (2) or keratitis (1), 14 (66.7%) cases were evaluated as being excellently (complete response, 2 cases) or well (partial response, 12 cases) treated. The eradication rates were 68.4% in MRSA (13 of 19 cases) and 100% in MRSE (2 of 2 cases). Ten adverse events occurred in 7 (28.0%) of 25 cases at the local administration site. Conclusions Vancomycin Ophthalmic Ointment 1% was considered to be useful for the treatment of intractable ocular MRSA/MRSE infections. PMID:23364319

  19. A novel combination approach of human polyclonal IVIG and antibiotics against multidrug-resistant Gram-positive bacteria

    PubMed Central

    Sallam, Mariam Madkour; Abou-Aisha, Khaled; El-Azizi, Mohamed

    2016-01-01

    Background Gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA) and enterococci, have shown a remarkable ability to develop resistance to antimicrobial agents. Objective We aimed to assess possible enhancement of the antimicrobial activity of vancomycin, amoxicillin, clarithromycin, and azithromycin by human polyclonal intravenous immunoglobulin G (IVIG) against 34 multidrug-resistant (MDR) bacterial isolates, including MRSA, Enterococcus faecium, and Enterococcus faecalis. Materials and methods Double combinations of the antibiotics with the IVIG were assessed by checkerboard assay, where the interaction was evaluated with respect to the minimum inhibitory concentration (MIC) of the antibiotics. The results of the checkerboard assay were verified in vitro using time-kill assay and in vivo using an invasive sepsis murine model. Results The checkerboard assay showed that IVIG enhanced the antimicrobial activity of amoxicillin and clarithromycin against isolates from the three groups of bacteria, which were resistant to the same antibiotics when tested in the absence of IVIG. The efficacy of vancomycin against 15% of the tested isolates was enhanced when it was combined with the antibodies. Antagonism was demonstrated in 47% of the E. faecalis isolates when clarithromycin was combined with the IVIG. Synergism was proved in the time-kill assay when amoxicillin was combined with the antibodies; meanwhile, antagonism was not demonstrated in all tested combinations, even in combinations that showed such response in checkerboard assay. Conclusion The suggested approach is promising and could be helpful to enhance the antimicrobial activity of not only effective antibiotics but also antibiotics that have been proven to be ineffective against MDR bacteria. To our knowledge, this combinatorial approach against MDR bacteria, such as MRSA and enterococci, has not been investigated before. PMID:27994476

  20. A controlled trial of universal gloving versus contact precautions for preventing the transmission of multidrug-resistant organisms.

    PubMed

    Bearman, Gonzalo M L; Marra, Alexandre R; Sessler, Curtis N; Smith, Wally R; Rosato, Adriana; Laplante, Justin K; Wenzel, Richard P; Edmond, Michael B

    2007-12-01

    Contact precautions are recommended to reduce the transmission of multidrug-resistant organisms. However, the optimal method for control of multidrug-resistant organisms remains unclear. A controlled trial was conducted in a medical intensive care unit. Phase 1 was a 3-month period of standard practice in which patients were placed in contact precautions per Centers for Disease Control and Prevention guidelines. In the second 3 months, phase 2, gloves were required for all patient contact, and no patients were placed in contact precautions. Compliance with contact precautions in phase 1 versus universal gloving in phase 2 was 75.7% versus 87.0%, respectively (P < .001). Hand hygiene compliance before patient care was significantly higher in phase 1 when compared with phase 2 (18.7% vs 11.4%, respectively, P < .001). Hand hygiene compliance after patient care was 57.7% in phase 1 versus 52.5% in phase 2 (P = .011). Nosocomial infection rates per 1000 device-days in phase 1 versus phase 2 were as follows: bloodstream infection, 6.2 versus 14.1, respectively (P < .001); urinary tract infection, 4.3 versus 7.4, respectively (P < .001); and ventilator-associated pneumonia, 0 versus 2.3, respectively (P < .001). There were no differences in vancomycin-resistant enterococci or methicillin-resistant Staphylococcus aureus acquisition in the 2 study phases; however, in both phases, the majority of vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus conversions were clonal. Compliance with universal gloving was significantly greater than compliance with contact precautions. However, greater compliance with hand hygiene was observed in the contact precautions phase. Measures must be in place to both increase and sustain hand hygiene compliance so as to minimize the risk of nosocomial cross transmission before reevaluating the concept of replacing contact precautions with universal gloving.

  1. Photobactericidal activity of methylene blue derivatives against vancomycin-resistant Enterococcus spp.

    PubMed

    Wainwright, M; Phoenix, D A; Gaskell, M; Marshall, B

    1999-12-01

    The toxicities and phototoxicities of methylene blue and its two methylated derivatives were measured against one standard and three vancomycin-resistant pathogenic strains of Enterococcus spp. Each of the compounds was bactericidal and the derivatives exhibited photobactericidal activity on illumination at a 'light' dose of 6.3 J/cm(2) against one or more of the strains. Increased bactericidal and photobactericidal activity in the methylated derivatives is thought to be due to their higher hydrophobicities allowing greater interaction with the bacterial cell wall. In addition, the derivatives exhibited higher inherent photosensitizing efficacies.

  2. Is it worth screening for vancomycin-resistant Enterococcus faecium colonization?: Financial burden of screening in a developing country.

    PubMed

    Ulu-Kilic, Aysegul; Özhan, Esra; Altun, Dilek; Perçin, Duygu; Güneş, Tamer; Alp, Emine

    2016-04-01

    The screening of critically ill patients at high risk of vancomycin resistant enterococci (VRE) colonization, to detect and isolate colonized patients, is recommended to prevent and control the transmission of VRE. Screening asymptomatic carriers brings financial burden for institutions. In this study, we performed risk analysis for VRE colonization and determined the financial burden of screening in a middle-income country, Turkey. We retrospectively analyzed the VRE surveillance data from a pediatric hospital between 2010 and 2014. A case-control study was conducted to identify the risk factors of colonization. Total cost of VRE screening and additional costs for a VRE colonized patient (including active surveillance cultures and contact isolation) were calculated. During the 4-year period, 6,372 patients were screened for perirectal VRE colonization. The rate of culture-positive specimens among all patients screened was 239 (3.75%). The rate of VRE infection was 0.04% (n = 3) among all patients screened. Length of hospital stay, malignancy, and being transferred from another institution were independently associated risk factors for colonization. Annual estimated costs for the laboratory were projected as $19,074 (76,295/4) for all patients screened. Cost of contact isolation for each patient colonized in a ward and an intensive care unit was $270 and $718, respectively. In developing countries, institutions should identify their own high-risk patients; screening priorities should be based on prevalence of infection and hospital financial resources. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  3. Complex Routes of Nosocomial Vancomycin-Resistant Enterococcus faecium Transmission Revealed by Genome Sequencing.

    PubMed

    Raven, Kathy E; Gouliouris, Theodore; Brodrick, Hayley; Coll, Francesc; Brown, Nicholas M; Reynolds, Rosy; Reuter, Sandra; Török, M Estée; Parkhill, Julian; Peacock, Sharon J

    2017-04-01

    Vancomycin-resistant Enterococcus faecium (VREfm) is a leading cause of nosocomial infection. Here, we describe the utility of whole-genome sequencing in defining nosocomial VREfm transmission. A retrospective study at a single hospital in the United Kingdom identified 342 patients with E. faecium bloodstream infection over 7 years. Of these, 293 patients had a stored isolate and formed the basis for the study. The first stored isolate from each case was sequenced (200 VREfm [197 vanA, 2 vanB, and 1 isolate containing both vanA and vanB], 93 vancomycin-susceptible E. faecium) and epidemiological data were collected. Genomes were also available for E. faecium associated with bloodstream infections in 15 patients in neighboring hospitals, and 456 patients across the United Kingdom and Ireland. The majority of infections in the 293 patients were hospital-acquired (n = 249) or healthcare-associated (n = 42). Phylogenetic analysis showed that 291 of 293 isolates resided in a hospital-associated clade that contained numerous discrete clusters of closely related isolates, indicative of multiple introductions into the hospital followed by clonal expansion associated with transmission. Fine-scale analysis of 6 exemplar phylogenetic clusters containing isolates from 93 patients (32%) identified complex transmission routes that spanned numerous wards and years, extending beyond the detection of conventional infection control. These contained both vancomycin-resistant and -susceptible isolates. We also identified closely related isolates from patients at Cambridge University Hospitals NHS Foundation Trust and regional and national hospitals, suggesting interhospital transmission. These findings provide important insights for infection control practice and signpost areas for interventions. We conclude that sequencing represents a powerful tool for the enhanced surveillance and control of nosocomial E. faecium transmission and infection. © The Author 2017. Published by Oxford

  4. The effectiveness of a single-stage versus traditional three-staged protocol of hospital disinfection at eradicating vancomycin-resistant Enterococci from frequently touched surfaces.

    PubMed

    Friedman, N Deborah; Walton, Aaron L; Boyd, Sarah; Tremonti, Christopher; Low, Jillian; Styles, Kaylene; Harris, Owen; Alfredson, David; Athan, Eugene

    2013-03-01

    Environmental contamination is a reservoir for vancomycin-resistant enterococcus (VRE) in hospitals. Environmental sampling of surfaces was undertaken anytime before disinfection and 1 hour after disinfection utilizing a sodium dichloroisocyanurate-based, 3-staged protocol (phase 1) or benzalkonium chloride-based, single-stage clean (phase 2). VRE colonization and infection rates are presented from 2010 to 2011, and audits of cleaning completeness were also analyzed. Environmental samples collected before disinfection were significantly more likely to be contaminated with VRE during phase 1 than phase 2: 25.2% versus 4.6%, respectively; odds ratio (OR), 7.01 (P < .01). Environmental samples collected after disinfection were also significantly more likely to yield VRE during phase 1 compared with phase 2: 11.2% versus 1.1%, respectively; OR, 11.73 (P < .01). Rates of VRE colonization were higher during 2010 than 2011. Cleaning audits showed similar results over both time periods. During use of a chlorine-based, 3-staged protocol, significantly higher residual levels of VRE contamination were identified, compared with levels detected during use of a benzalkonium chloride-based product for disinfection. This reduction in VRE may be due to a new disinfection product, more attention to the thoroughness of cleaning, or other supplementary efforts in our institution. Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

  5. [Effects of restrictions on use of vancomycin in a German university hospital].

    PubMed

    Glück, T; Linde, H J; Wiegrebe, E; Lehn, N; Reng, M; Schölmerich, J

    2000-02-15

    Recently, increasing antibiotic resistance has been observed among gram-positive bacteria. However, only few isolates were found to be resistant against glycopeptides. Therefore, internationally accepted guidelines recommend a restricted use of vancomycin and other glycopeptide antibiotics in order to prevent the development of resistance against these clinically important antibiotics. In many countries, the hospital pharmacies play a key role in control and reinforcement of antibiotic formulary restrictions. In Germany, however, the hospital pharmacies usually do not take over such control functions, and most wards keep a stock of regularly used drugs including antibiotics, which makes reinforcement of restrictions difficult. In an attempt to achieve a restriction of vancomycin use, the pharmacy of our university hospital was advised to deliver vancomycin to the wards only on request with a special order form signed by an attending, individually for every patient who should receive vancomycin. The efficacy of this restriction measure was evaluated in 3-month periods before and after the restriction became effective. Hospitalwide, this led to a 20.1% reduction of i.v. vancomycin and an 85.7% reduction of oral vancomycin use per 1000 patient days. If the hematology/oncology units were not considered, the reduction of i.v. vancomycin use was 41.8%, and the total use after the restriction 24.2 g per 1000 patient days. Microbiology results which justified the use of vancomycin decreased by 8.3% (10.9% hematology/oncology units not considered) between the 2 observation periods. Assuming a 7-day mean course of i.v. vancomycin therapy, the empirical use of i.v. vancomycin decreased from 39.9% to 8% after the restriction had been instituted. Allowing only experienced physicians (attendings) to decide on the use of vancomycin therapy, proved in our experience to be an effective measure to reduce unnecessary vancomycin use.

  6. Genome Sequence of Staphylococcus aureus VC40, a Vancomycin- and Daptomycin-Resistant Strain, To Study the Genetics of Development of Resistance to Currently Applied Last-Resort Antibiotics

    PubMed Central

    Berscheid, Anne; Jansen, Andrea; Oedenkoven, Marion; Szekat, Christiane; Strittmatter, Axel; Gottschalk, Gerhard; Bierbaum, Gabriele

    2012-01-01

    The increasing emergence of multidrug-resistant Staphylococcus aureus is a problem of global importance. Here, we report the genome of S. aureus VC40, which is resistant to the last-resort antibiotics vancomycin and daptomycin. Its genome sequence will allow insights into the mechanisms that convey full resistance to these compounds. PMID:22461548

  7. Gram-Positive Bacterial Infections: Research Priorities, Accomplishments, and Future Directions of the Antibacterial Resistance Leadership Group.

    PubMed

    Doernberg, Sarah B; Lodise, Thomas P; Thaden, Joshua T; Munita, Jose M; Cosgrove, Sara E; Arias, Cesar A; Boucher, Helen W; Corey, G Ralph; Lowy, Franklin D; Murray, Barbara; Miller, Loren G; Holland, Thomas L

    2017-03-15

    Antimicrobial resistance in gram-positive bacteria remains a challenge in infectious diseases. The mission of the Gram-Positive Committee of the Antibacterial Resistance Leadership Group (ARLG) is to advance knowledge in the prevention, management, and treatment of these challenging infections to improve patient outcomes. Our committee has prioritized projects involving methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) due to the scope of the medical threat posed by these pathogens. Approved ARLG projects involving gram-positive pathogens include (1) a pharmacokinetics/pharmacodynamics study to evaluate the impact of vancomycin dosing on patient outcome in MRSA bloodstream infection (BSI); (2) defining, testing, and validating innovative assessments of patient outcomes for clinical trials of MRSA-BSI; (3) testing new strategies for "step-down" antibiotic therapy for MRSA-BSI; (4) management of staphylococcal BSIs in neonatal intensive care units; and (5) defining the impact of VRE bacteremia and daptomycin susceptibility on patient outcomes. This article outlines accomplishments, priorities, and challenges for research of infections caused by gram-positive organisms. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  8. Glycopeptide Resistance vanA Operons in Paenibacillus Strains Isolated from Soil

    PubMed Central

    Guardabassi, Luca; Perichon, Bruno; van Heijenoort, Jean; Blanot, Didier; Courvalin, Patrice

    2005-01-01

    The sequence and gene organization of the van operons in vancomycin (MIC of >256 μg/ml)- and teicoplanin (MIC of ≥32 μg/ml)-resistant Paenibacillus thiaminolyticus PT-2B1 and Paenibacillus apiarius PA-B2B isolated from soil were determined. Both operons had regulatory (vanR and vanS), resistance (vanH, vanA, and vanX), and accessory (vanY, vanZ, and vanW) genes homologous to the corresponding genes in enterococcal vanA and vanB operons. The vanAPT operon in P. thiaminolyticus PT-2B1 had the same gene organization as that of vanA operons whereas vanAPA in P. apiarius PA-B2B resembled vanB operons due to the presence of vanW upstream from the vanHAX cluster but was closer to vanA operons in sequence. Reference P. apiarius strains NRRL B-4299 and NRRL B-4188 were found to harbor operons indistinguishable from vanAPA by PCR mapping, restriction fragment length polymorphism, and partial sequencing, suggesting that this operon was species specific. As in enterococci, resistance was inducible by glycopeptides and associated with the synthesis of pentadepsipeptide peptidoglycan precursors ending in d-Ala-d-Lac, as demonstrated by d,d-dipeptidase activities, high-pressure liquid chromatography, and mass spectrometry. The precursors differed from those in enterococci by the presence of diaminopimelic acid instead of lysine in the peptide chain. Altogether, the results are compatible with the notion that van operons in soil Paenibacillus strains and in enterococci have evolved from a common ancestor. PMID:16189102

  9. Glycopeptide resistance vanA operons in Paenibacillus strains isolated from soil.

    PubMed

    Guardabassi, Luca; Perichon, Bruno; van Heijenoort, Jean; Blanot, Didier; Courvalin, Patrice

    2005-10-01

    The sequence and gene organization of the van operons in vancomycin (MIC of >256 microg/ml)- and teicoplanin (MIC of > or =32 microg/ml)-resistant Paenibacillus thiaminolyticus PT-2B1 and Paenibacillus apiarius PA-B2B isolated from soil were determined. Both operons had regulatory (vanR and vanS), resistance (vanH, vanA, and vanX), and accessory (vanY, vanZ, and vanW) genes homologous to the corresponding genes in enterococcal vanA and vanB operons. The vanA(PT) operon in P. thiaminolyticus PT-2B1 had the same gene organization as that of vanA operons whereas vanA(PA) in P. apiarius PA-B2B resembled vanB operons due to the presence of vanW upstream from the vanHAX cluster but was closer to vanA operons in sequence. Reference P. apiarius strains NRRL B-4299 and NRRL B-4188 were found to harbor operons indistinguishable from vanA(PA) by PCR mapping, restriction fragment length polymorphism, and partial sequencing, suggesting that this operon was species specific. As in enterococci, resistance was inducible by glycopeptides and associated with the synthesis of pentadepsipeptide peptidoglycan precursors ending in D-Ala-D-Lac, as demonstrated by D,D-dipeptidase activities, high-pressure liquid chromatography, and mass spectrometry. The precursors differed from those in enterococci by the presence of diaminopimelic acid instead of lysine in the peptide chain. Altogether, the results are compatible with the notion that van operons in soil Paenibacillus strains and in enterococci have evolved from a common ancestor.

  10. Antibiotic resistant airborne bacteria and their multidrug resistance pattern at University teaching referral Hospital in South Ethiopia.

    PubMed

    Solomon, Fithamlak Bisetegen; Wadilo, Fiseha Wada; Arota, Amsalu Amache; Abraham, Yishak Leka

    2017-04-12

    Hospitals provide a reservoir of microorganisms, many of which are multi-resistant to antibiotics. Emergence of multi-drug resistant strains in a hospital environment, particularly in developing countries is an increasing problem to infection treatment. This study aims at assessing antibiotic resistant airborne bacterial isolates. A cross-sectional study was conducted at Wolaita Sodo university teaching and referral Hospital. Indoor air samples were collected by using passive air sampling method. Sample processing and antimicrobial susceptibility testing were done following standard bacteriological techniques. The data was analyzed using SPSS version 20. Medically important bacterial pathogens, Coagulase negative staphylococci (29.6%), Staphylococcus aureus (26.3%), Enterococci species, Enterococcus faecalis and Enterococcus faecium (16.5%), Acinetobacter species (9.5%), Escherichia coli (5.8%) and Pseudomonas aeruginosa (5.3%) were isolated. Antibiotic resistance rate ranging from 7.5 to 87.5% was detected for all isolates. Acinetobacter species showed a high rate of resistance for trimethoprim-sulfamethoxazole, gentamicin (78.2%) and ciprofloxacin (82.6%), 28 (38.9%) of S. aureus isolates were meticillin resistant, and 7.5% Enterococci isolates of were vancomycin resistant. 75.3% of all bacterial pathogen were multi-drug resistant. Among them, 74.6% were gram positive and 84% were gram negative. Multi-drug resistance were observed among 84.6% of P. aeruginosa, of 82.5% Enterococcii, E. coli 78.6%, S. aureus 76.6%, and Coagulase negative staphylococci of 73.6%. Indoor environment of the hospital was contaminated with airborne microbiotas, which are common cause of post-surgical site infection in the study area. Bacterial isolates were highly resistant to commonly used antibiotics with high multi-drug resistance percentage. So air quality of hospital environment, in restricted settings deserves attention, and requires long-term surveillance to protect both

  11. Emergence of endemic MLST non-typeable vancomycin-resistant Enterococcus faecium.

    PubMed

    Carter, Glen P; Buultjens, Andrew H; Ballard, Susan A; Baines, Sarah L; Tomita, Takehiro; Strachan, Janet; Johnson, Paul D R; Ferguson, John K; Seemann, Torsten; Stinear, Timothy P; Howden, Benjamin P

    2016-12-01

    Enterococcus faecium is a major nosocomial pathogen causing significant morbidity and mortality worldwide. Assessment of E. faecium using MLST to understand the spread of this organism is an important component of hospital infection control measures. Recent studies, however, suggest that MLST might be inadequate for E. faecium surveillance. To use WGS to characterize recently identified vancomycin-resistant E. faecium (VREfm) isolates non-typeable by MLST that appear to be causing a multi-jurisdictional outbreak in Australia. Illumina NextSeq and Pacific Biosciences SMRT sequencing platforms were used to determine the genome sequences of 66 non-typeable E. faecium (NTEfm) isolates. Phylogenetic and bioinformatics analyses were subsequently performed using a number of in silico tools. Sixty-six E. faecium isolates were identified by WGS from multiple health jurisdictions in Australia that could not be typed by MLST due to a missing pstS allele. SMRT sequencing and complete genome assembly revealed a large chromosomal rearrangement in representative strain DMG1500801, which likely facilitated the deletion of the pstS region. Phylogenomic analysis of this population suggests that deletion of pstS within E. faecium has arisen independently on at least three occasions. Importantly, the majority of these isolates displayed a vancomycin-resistant genotype. We have identified NTEfm isolates that appear to be causing a multi-jurisdictional outbreak in Australia. Identification of these isolates has important implications for MLST-based typing activities designed to monitor the spread of VREfm and provides further evidence supporting the use of WGS for hospital surveillance of E. faecium. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Contribution of Selected Gene Mutations to Resistance in Clinical Isolates of Vancomycin-Intermediate Staphylococcus aureus

    PubMed Central

    Hafer, Cory; Lin, Ying; Kornblum, John; Lowy, Franklin D.

    2012-01-01

    Infections with vancomycin-intermediate Staphylococcus aureus (VISA) have been associated with vancomycin treatment failures and poor clinical outcomes. Routine identification of clinical isolates with increased vancomycin MICs remains challenging, and no molecular marker exists to aid in diagnosis of VISA strains. We tested vancomycin susceptibilities by using microscan, Etest, and population analyses in a collection of putative VISA, methicillin-resistant S. aureus, and methicillin-sensitive S. aureus (VSSA) infectious isolates from community- or hospital-associated S. aureus infections (n = 77) and identified 22 VISA and 9 heterogeneous VISA (hVISA) isolates. Sequencing of VISA candidate loci vraS, vraR, yvqF, graR, graS, walR, walK, and rpoB revealed a high diversity of nonsynonymous single-nucleotide polymorphisms (SNPs). For vraS, vraR, yvqF, walK, and rpoB, SNPs were more frequently present in VISA and hVISA than in VSSA isolates, whereas mutations in graR, graS, and walR were exclusively detected in VISA isolates. For each of the individual loci, SNPs were only detected in about half of the VISA isolates. All but one VISA isolate had at least one SNP in any of the genes sequenced, and isolates with an MIC of 6 or 8 μg/ml harbored at least 2 SNPs. Overall, increasing vancomycin MICs were paralleled by a higher proportion of isolates with SNPs. Depending on the clonal background, SNPs appeared to preferentially accumulate in vraS and vraR for sequence type 8 (ST8) and in walK and walR for ST5 isolates. Taken together, by comparing VISA, hVISA, and VSSA controls, we observed preferential clustering of SNPs in VISA candidate genes, with an unexpectedly high diversity across these loci. Our results support a polygenetic etiology of VISA. PMID:22948864

  13. Vancomycin modifies the expression of the agr system in multidrug-resistant Staphylococcus aureus clinical isolates

    PubMed Central

    Cázares-Domínguez, Vicenta; Ochoa, Sara A.; Cruz-Córdova, Ariadnna; Rodea, Gerardo E.; Escalona, Gerardo; Olivares, Alma L.; Olivares-Trejo, José de Jesús; Velázquez-Guadarrama, Norma; Xicohtencatl-Cortes, Juan

    2015-01-01

    Staphylococcus aureus is an opportunistic pathogen that colonizes human hosts and causes a wide variety of diseases. Two interacting regulatory systems called agr (accessory gene regulator) and sar (staphylococcal accessory regulator) are involved in the regulation of virulence factors. The aim of this study was to evaluate the effect of vancomycin on hld and spa gene expression during the exponential and post-exponential growth phases in multidrug-resistant (MDR) S. aureus. Methods: Antibiotic susceptibility was evaluated by the standard microdilution method. The phylogenetic profile was obtained by pulsed-field gel electrophoresis (PFGE). Polymorphisms of agr and SCCmec (staphylococcal cassette chromosome mec) were analyzed by multiplex polymerase chain reaction (PCR). The expression levels of hld and spa were analyzed by reverse transcription-PCR. An enzyme-linked immunosorbent assay (ELISA) was performed to detect protein A, and biofilm formation was analyzed via crystal violet staining. Results: In total, 60.60% (20/33) of S. aureus clinical isolates were MDR. Half (10/20) of the MDR S. aureus isolates were distributed in subcluster 10, with >90% similarity among them. In the isolates of this subcluster, a high prevalence (100%) for the agrII and the cassette SCCmec II polymorphisms was found. Our data showed significant increases in hld expression during the post-exponential phase in the presence and absence of vancomycin. Significant increases in spa expression, protein A production and biofilm formation were observed during the post-exponential phase when the MDR S. aureus isolates were challenged with vancomycin. Conclusion: The polymorphism agrII, which is associated with nosocomial isolates, was the most prevalent polymorphism in MDR S. aureus. Additionally, under our study conditions, vancomycin modified hld and spa expression in these clinical isolates. Therefore, vancomycin may regulate alternative systems that jointly participate in the regulation of

  14. Analysis of the world epidemiological situation among vancomycin-resistant Enterococcus faecium infections and the current situation in Poland

    PubMed

    Talaga-Ćwiertnia, Katarzyna; Bulanda, Małgorzata

    2018-01-01

    Vancomycin-resistant Enterococcus faecium (VREfm) strains have become an important hospital pathogen due to their rapid spread, high mortality rate associated with infections and limited therapeutic options. Vancomycin resistance is predominantly mediated by VanA or VanB phenotypes, which differ as regards maintaining sensitivity to teicoplanin in the VanB phenotype. The majority of VREfm cases in the United States, Europe, Korea, South America and Africa are currently caused by the VanA phenotype. However, the epidemics in Australia and Singapore are chiefly brought about by the VanB phenotype. The rate of VREfm isolate spread varies greatly. The greatest percentage of VREfm is now recorded in the USA, Ireland and Australia. Supervision of VRE is implemented to varying degrees. Therefore, the epidemiological situation in some countries is difficult to assess due to limited data or lack thereof.

  15. Surprising Alteration of Antibacterial Activity of 5″-Modified Neomycin against Resistant Bacteria

    PubMed Central

    Zhang, Jianjun; Chiang, Fang-I; Wu, Long; Czyryca, Przemyslaw Greg; Li, Ding; Chang, Cheng-Wei Tom

    2009-01-01

    A facile synthetic protocol for the production of neomycin B derivatives with various modifications at the 5″ position has been developed. Structural activity relationship (SAR) against aminoglycoside resistant bacteria equipped with various aminoglycoside-modifying enzymes (AME's) was investigated. Enzymatic and molecular modeling studies reveal that the superb substrate promiscuity of AME's allows the resistant bacteria to cope with diverse structural modifications despite the observation that several derivatives show enhanced antibacterial activity than the parent neomycin. Surprisingly, when testing synthetic neomycin derivatives against other human pathogens, two leads exhibit prominent activity against both Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) that are known to exert high level of resistance against clinically used aminoglycosides. These findings can be extremely useful in developing new aminoglycoside antibiotics against resistant bacteria. Our result also suggests that new biological and antimicrobial activities can be obtained by chemical modifications of old drugs. PMID:19012394

  16. Is vancomycin MIC creep a worldwide phenomenon? Assessment of S. aureus vancomycin MIC in a tertiary university hospital

    PubMed Central

    2013-01-01

    Background Vancomycin is the primary treatment for infections caused by methicilin-resistant Staphylococcus aureus (MRSA). The association of vancomycin treatment failures with increased vancomycin minimum inhibitory concentration (MIC) is a well-recognized problem. A number of single-centre studies have identified progressive increases in glycopeptide MICs for S. aureus strains over recent years – a phenomenon known as vancomycin MIC creep. It is unknown if this is a worldwide phenomenon or if it is localized to specific centers. Methods The aim of this study was to evaluate the trend of vancomycin MIC for isolates of MRSA over a 3-year period in a tertiary university hospital in Portugal. MRSA isolates from samples of patients admitted from January 2007 to December 2009 were assessed. Etest method was used to determine the respective vancomycin MIC. Only one isolate per patient was included in the final analysis. Results A total of 93 MRSA isolates were studied. The vancomycin MICs were 0.75, 1, 1.5 and 2 mg/L for 1 (1.1%), 19 (20.4%), 38 (40.9%), 35 (37.6%) isolates, respectively. During the 3 year period, we observed a significant fluctuation in the rate of MRSA with a vancomycin MIC > 1 mg/L (2007: 86.2%; 2008: 93.3%; 2009: 58.8%, p = 0.002). No MRSA isolate presented a MIC > 2 mg/L. Conclusions We were unable to find in our institution data compatible to the presence of vancomycin MIC creep during the study period. This phenomenon seems not to be generalized; as a result each institution should systematically monitor MRSA vancomycin MIC over time. PMID:23422012

  17. In Vitro Activities of Co-Amoxiclav at Concentrations Achieved in Human Serum against the Resistant Subpopulation of Heteroresistant Staphylococcus aureus: a Controlled Study with Vancomycin

    PubMed Central

    Prieto, J.; Aguilar, L.; Giménez, M. J.; Toro, D.; Gómez-Lus, M. L.; Dal-Ré, R.; Balcabao, I. P.

    1998-01-01

    The effects of concentrations that simulated those in human serum after a single intravenous dose of amoxicillin (2 g), amoxicillin-clavulanic acid (2,000 and 200 mg, respectively), or vancomycin (500 mg), on the viability and β-lactamase activity of two isogenic (β-lactamase and non-β-lactamase producer) heteroresistant Staphylococcus aureus strains were studied in an in vitro pharmacodynamic model. A reduction of ≥97% of the initial inoculum was obtained with vancomycin and amoxicillin-clavulanic acid against both strains, with respect to the total bacterial population and the oxacillin-resistant subpopulation. The same pattern was observed with amoxicillin and the β-lactamase-negative strain. β-Lactamase activity in the β-lactamase-positive strain changed over time parallel to viability, decreasing with amoxicillin-clavulanic acid or vancomycin and increasing in the amoxicillin and control groups. Clavulanic acid concentrations achievable in serum that changed over time allowed amoxicillin to act against the β-lactamase-producing methicillin-resistant S. aureus to a similar extent as vancomycin. PMID:9660985

  18. Emergence of dalbavancin non-susceptible, vancomycin-intermediate Staphylococcus aureus (VISA) after treatment of MRSA central line-associated bloodstream infection with a dalbavancin- and vancomycin-containing regimen.

    PubMed

    Werth, B J; Jain, R; Hahn, A; Cummings, L; Weaver, T; Waalkes, A; Sengupta, D; Salipante, S J; Rakita, R M; Butler-Wu, S M

    2018-04-01

    Dalbavancin is a long-acting lipoglycopeptide with activity against gram-positives, including methicillin-resistant Staphylococcus aureus (MRSA). The potential for lipoglycopeptides, with half-lives greater than 1 week, to select for resistance is unknown. Here we explore a case of MRSA central line-associated bloodstream infection in which dalbavancin and vancomycin non-susceptibility emerged in a urine isolate collected after the patient was treated with vancomycin and dalbavancin sequentially. Isolates from blood and urine underwent susceptibility testing, and whole genome sequencing (WGS). The blood isolate was subjected to successive passage in vitro in the presence of escalating dalbavancin concentrations and the emergent isolate was subjected to repeat susceptibility testing and WGS. The blood isolate was fully susceptible to vancomycin; however, MICs of the urine isolate to dalbavancin, vancomycin, telavancin, and daptomycin were at least fourfold higher than the blood-derived strain. Both strains were indistinguishable by spa and variable number tandem repeat (VNTR) typing, and WGS revealed only seven variants, indicating clonality. Four variants affected genes, including a 3bp in-frame deletion in yvqF, a gene which has been implicated in glycopeptide resistance. Vancomycin and dalbavancin non-susceptibility emerged in the blood isolate after successive passage in vitro in the presence of dalbavancin, and WGS identified a single non-synonymous variant in yvqF. This is the first case in which VISA has emerged in the context of a dalbavancin-containing regimen. The selection for cross-resistance to vancomycin in vitro by dalbavancin exposure alone is troubling. Clinicians should be aware of the possibility for emergence of dalbavancin non-susceptibility and glycopeptide cross-resistance arising following therapy. Copyright © 2017. Published by Elsevier Ltd.

  19. Prevalence and phenotypic characterization of Enterococcus species isolated from clinical samples of pediatric patients in Jimma University Specialized Hospital, south west Ethiopia.

    PubMed

    Toru, Milkiyas; Beyene, Getnet; Kassa, Tesfaye; Gizachew, Zeleke; Howe, Rawleigh; Yeshitila, Biruk

    2018-05-08

    This study was done to determine the prevalence and phenotypic characterization of Enterococcus species isolated from clinical samples of pediatric patients in Jimma University Specialized Hospital, Southwest Ethiopia. The overall prevalence of Enterococci species was 5.5% (22/403). Five (22.7%) of Enterococci species were vancomycin resistant. Haemolysin, gelatinase and biofilm production was seen among 45.5, 68.2 and 77.3% of isolates respectively. The overall rate of antibiotic resistance was 95.5% (21/22). High resistance was observed against norfloxacin (87.5%), and tetracycline (77.3%). Whereas, low resistance (36.5%) was observed against ciprofloxacin and eighteen (80.8%) of the isolates were multi-drug resistant.

  20. First Report on a Randomized Investigation of Antimicrobial Resistance in Fecal Indicator Bacteria from Livestock, Poultry, and Humans in Tanzania.

    PubMed

    Katakweba, Abdul A S; Muhairwa, Amandus P; Lupindu, Athumani M; Damborg, Peter; Rosenkrantz, Jesper T; Minga, Uswege M; Mtambo, Madundo M A; Olsen, John E

    2018-04-01

    This study provides an estimate of antimicrobial resistance in intestinal indicator bacteria from humans (n = 97) and food animals (n = 388) in Tanzania. More than 70% of all fecal samples contained tetracycline (TE), sulfamethoxazole (STX), and ampicillin (AMP)-resistant coliforms, while cefotaxime (CTX)-resistant coliforms were observed in 40% of all samples. The average Log 10 colony forming units/g of CTX-resistant coliforms in samples from humans were 2.20. Of 390 Escherichia coli tested, 66.4% were resistant to TE, 54.9% to STX, 54.9% to streptomycin, and 36.4% to CTX. Isolates were commonly (65.1%) multiresistant. All CTX-resistant isolates contained bla CTX-M gene type. AMP- and vancomycin-resistant enterococci were rare, and the average concentrations in positive samples were low (log 10 0.9 and 0.4, respectively). A low-to-moderate resistance (2.1-15%) was detected in 240 enterococci isolates to the drugs tested, except for rifampicin resistance (75.2% of isolates). The average number of sulII gene copies varied between Log 10 5.37 and 5.68 with no significant difference between sample source, while cattle had significantly higher number of tetW genes than humans. These findings, based on randomly obtained samples, will be instrumental in designing antimicrobial resistance (AMR) intervention strategies for Tanzania.

  1. Healthcare-associated Staphylococcus aureus Bacteremia in Children: Evidence for Reverse Vancomycin Creep and Impact of Vancomycin Trough Values on Outcome.

    PubMed

    McNeil, J Chase; Kok, Eric Y; Forbes, Andrea R; Lamberth, Linda; Hulten, Kristina G; Vallejo, Jesus G; Mason, Edward O; Kaplan, Sheldon L

    2016-03-01

    Elevated vancomycin minimum inhibitory concentrations (MICs) in Staphylococcus aureus have been associated with worse clinical outcomes in adults. For invasive meticillin-resistant S. aureus (MRSA) infections in adults, the Infectious Diseases Society of America recommends targeting vancomycin serum trough concentrations between 15 and 20 μg/mL. We evaluated trends in vancomycin MICs from healthcare-associated (HCA) S. aureus bacteremia isolates in children in addition to correlating vancomycin serum trough levels with clinical outcomes. Patients and isolates were identified from a prospective S. aureus surveillance study at Texas Children's Hospital (TCH). HCA S. aureus bacteremia isolates from 2003 to 2013 were selected. Vancomycin MICs by E-test were determined and medical records were reviewed. Acute kidney injury (AKI) was defined as doubling of the baseline serum creatinine. Three hundred forty-one isolates met inclusion criteria. We observed a reverse vancomycin creep among MRSA isolates in the study period with a decline in the proportion of isolates with vancomycin MIC ≥ 2 μg/mL (from 32.7% to 5.6%; P < 0.001). However, the proportion of MSSA isolates with MIC ≥ 2 μg/mL increased (from 2.9% to 9%; P = 0.04). Among patients who had vancomycin troughs performed, there was no difference in duration of bacteremia or fever with vancomycin trough >15 versus <15 μg/mL. A vancomycin trough >15 μg/mL was, however, an independent risk factor for AKI. Vancomycin MICs are shifting among HCA S. aureus bacteremia isolates with significant differences between MRSA and MSSA at TCH. Higher vancomycin troughs did not improve outcomes in pediatric HCA S. aureus bacteremia but were associated with increased nephrotoxicity. Further studies are needed to better understand optimal management of children with S. aureus bacteremia.

  2. A report on the first case of vancomycin-intermediate Staphylococcus aureus (VISA) in Hawai'i.

    PubMed

    Chaiwongkarjohn, Suttirak; Pramyothin, Pornpoj; Suwantarat, Nuntra; Bankowski, Matthew J; Koyamatsu, Terrie; Seifried, Steven E; Bello, Erlaine F

    2011-11-01

    The state of Hawai'i has the highest prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infection in the United States. Since vancomycin is the most frequently-prescribed antibiotic for healthcare-associated MRSA infection, there is concern for development of vancomycin resistance. We report on a 61 year-old woman with history of previous successful treatments of MRSA bacteremia with vancomycin. She was later hospitalized for catheter-related MRSA bacteremia that persisted despite vancomycin treatment. The vancomycin minimal inhibitory concentration (MIC) was initially 1-2 µg/ml, suggesting susceptibility, but changed to 4 µg/ml. At this level, the organism was classified as a vancomycin-intermediate Staphylococcus aureus (VISA). Therapy was changed from vancomycin to daptomycin, and the patient's blood cultures were sterilized. High suspicion of VISA should be raised in MRSA-infected patients who fail or have a history of vancomycin therapy so that additional susceptibility testing and appropriate antibiotic therapy can be promptly commenced to reduce the morbidity associated with VISA infection.

  3. Leuconostoc garlicum: an unusual pathogen in the era of vancomycin therapy.

    PubMed

    Kumar, Anil; Augustine, Deepthi; Mehta, Asmita; Dinesh, Kavitha R; Viswam, Darsana; Philip, Rosamma

    2012-01-01

    Leuconostoc garlicum, belonging to the family of Leuconostocaceae, is a catalase-negative, Gram-positive ovoid cocci, intrinsically resistant to vancomycin. Clinical infection by Leuconostoc garlicum is rare. We report a case of respiratory tract infection subsequent to vancomycin therapy.

  4. Transcriptional Analysis of the vanC Cluster from Enterococcus gallinarum Strains with Constitutive and Inducible Vancomycin Resistance

    PubMed Central

    Panesso, Diana; Abadía-Patiño, Lorena; Vanegas, Natasha; Reynolds, Peter E.; Courvalin, Patrice; Arias, Cesar A.

    2005-01-01

    The vanC glycopeptide resistance gene cluster encodes enzymes required for synthesis of peptidoglycan precursors ending in d-Ala-d-Ser. Enterococcus gallinarum BM4174 and SC1 are constitutively and inducibly resistant to vancomycin, respectively. Analysis of peptidoglycan precursors in both strains indicated that UDP-MurNAc-tetrapeptide and UDP-MurNAc-pentapeptide[d-Ser] were synthesized in E. gallinarum SC1 only in the presence of vancomycin (4 μg/ml), whereas the “resistance” precursors accumulated in the cytoplasm of BM4174 cells under both inducing and noninducing conditions. Northern hybridization and reverse transcription-PCR experiments revealed that all the genes from the cluster, vanC-1, vanXYC, vanT, vanRC, and vanSC, were transcribed from a single promoter. In the inducible SC1 isolate, transcriptional regulation appeared to be responsible for inducible expression of resistance. Promoter mapping in E. gallinarum BM4174 revealed that the transcriptional start site was located 30 nucleotides upstream from vanC-1 and that the −10 promoter consensus sequence had high identity with that of the vanA cluster. Comparison of the deduced sequence of the vanSC genes from isolates with constitutive and inducible resistance revealed several amino acid substitutions located in the X box (R200L) and in the region between the F and G2 boxes (D312N, D312A, and G320S) of the putative sensor kinase proteins from isolates with constitutive resistance. PMID:15728903

  5. [New antimicrobials against Gram-positive organisms].

    PubMed

    Montejo, M

    2008-01-01

    Glycopeptides have been the antimicrobials most commonly used for infections by Gram-positive organisms and methicillin resistant S. aureus (MRSA). In recent years, however, glycopeptide resistance and tolerance have become a serious problem. Thus, enterococci highly resistant to vancomycin, vancomycin-intermediate/ resistant S. aureus (VISA), and vancomycin tolerance in S. aureus are found, and increased therapeutic failure and mortality are clinically reported with vancomycin MIC for S. aureus > or = 1.5-2 microg/mL. When faced with these organisms, we therefore need potent bactericidal antimicrobials that may be empirically administered, effective against susceptible and resistant pathogens, easily dosed, with few adverse effects and no significant interaction with other drugs, and that can be administered in an outpatient setting. In bacteremia by methicillin-susceptible S. aureus, use of vancomycin is associated to a greater failure and mortality rate as compared to semisynthetic penicillins. New treatment options for MRSA infections include daptomycin, linezolid, tygecycline, and quinupristin/dalfopristin. New anti-MRSA drugs are also under development, including glycopeptides (dalbavancin, telavancin, and oritavancin), ceftobiprole, and iclaprim. This paper reviews the new antimicrobials against Gram-positive organisms.

  6. Epidemiology and Resistance Patterns of Bacterial and Fungal Colonization of Biliary Plastic Stents: A Prospective Cohort Study

    PubMed Central

    Lübbert, Christoph; Wendt, Karolin; Feisthammel, Jürgen; Moter, Annette; Lippmann, Norman; Busch, Thilo; Mössner, Joachim; Hoffmeister, Albrecht; Rodloff, Arne C.

    2016-01-01

    Background Plastic stents used for the treatment of biliary obstruction will become occluded over time due to microbial colonization and formation of biofilms. Treatment of stent-associated cholangitis is often not effective because of inappropriate use of antimicrobial agents or antimicrobial resistance. We aimed to assess the current bacterial and fungal etiology of stent-associated biofilms, with particular emphasis on antimicrobial resistance. Methods Patients with biliary strictures requiring endoscopic stent placement were prospectively enrolled. After the retrieval of stents, biofilms were disrupted by sonication, microorganisms were cultured, and isolates were identified by matrix-associated laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry and/or biochemical typing. Finally, minimum inhibitory concentrations (MICs) were determined for various antimicrobial agents. Selected stents were further analyzed by fluorescence in situ hybridization (FISH). Results Among 120 patients (62.5% males, median age 64 years) with biliary strictures (35% malignant, 65% benign), 113 double pigtail polyurethane and 100 straight polyethylene stents were analyzed after a median indwelling time of 63 days (range, 1–1274 days). The stent occlusion rate was 11.5% and 13%, respectively, being associated with a significantly increased risk of cholangitis (38.5% vs. 9.1%, P<0.001). Ninety-five different bacterial and 13 fungal species were detected; polymicrobial colonization predominated (95.8% vs. 4.2%, P<0.001). Enterococci (79.3%), Enterobacteriaceae (73.7%), and Candida spp. (55.9%) were the leading pathogens. Candida species were more frequent in patients previously receiving prolonged antibiotic therapy (63% vs. 46.7%, P = 0.023). Vancomycin-resistant enterococci accounted for 13.7%, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae with co-resistance to ciprofloxacin accounted for 13.9%, and azole-resistant Candida spp. accounted for

  7. Epidemiology and Resistance Patterns of Bacterial and Fungal Colonization of Biliary Plastic Stents: A Prospective Cohort Study.

    PubMed

    Lübbert, Christoph; Wendt, Karolin; Feisthammel, Jürgen; Moter, Annette; Lippmann, Norman; Busch, Thilo; Mössner, Joachim; Hoffmeister, Albrecht; Rodloff, Arne C

    2016-01-01

    Plastic stents used for the treatment of biliary obstruction will become occluded over time due to microbial colonization and formation of biofilms. Treatment of stent-associated cholangitis is often not effective because of inappropriate use of antimicrobial agents or antimicrobial resistance. We aimed to assess the current bacterial and fungal etiology of stent-associated biofilms, with particular emphasis on antimicrobial resistance. Patients with biliary strictures requiring endoscopic stent placement were prospectively enrolled. After the retrieval of stents, biofilms were disrupted by sonication, microorganisms were cultured, and isolates were identified by matrix-associated laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry and/or biochemical typing. Finally, minimum inhibitory concentrations (MICs) were determined for various antimicrobial agents. Selected stents were further analyzed by fluorescence in situ hybridization (FISH). Among 120 patients (62.5% males, median age 64 years) with biliary strictures (35% malignant, 65% benign), 113 double pigtail polyurethane and 100 straight polyethylene stents were analyzed after a median indwelling time of 63 days (range, 1-1274 days). The stent occlusion rate was 11.5% and 13%, respectively, being associated with a significantly increased risk of cholangitis (38.5% vs. 9.1%, P<0.001). Ninety-five different bacterial and 13 fungal species were detected; polymicrobial colonization predominated (95.8% vs. 4.2%, P<0.001). Enterococci (79.3%), Enterobacteriaceae (73.7%), and Candida spp. (55.9%) were the leading pathogens. Candida species were more frequent in patients previously receiving prolonged antibiotic therapy (63% vs. 46.7%, P = 0.023). Vancomycin-resistant enterococci accounted for 13.7%, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae with co-resistance to ciprofloxacin accounted for 13.9%, and azole-resistant Candida spp. accounted for 32.9% of the respective

  8. Enterococci in the environment

    USGS Publications Warehouse

    Byappanahalli, Muruleedhara N.; Nevers, Meredith B.; Korajkic, Asja; Staley, Zachery R.; Harwood, Valerie J.

    2012-01-01

    Enterococci are common, commensal members of gut communities in mammals and birds, yet they are also opportunistic pathogens that cause millions of human and animal infections annually. Because they are shed in human and animal feces, are readily culturable, and predict human health risks from exposure to polluted recreational waters, they are used as surrogates for waterborne pathogens and as fecal indicator bacteria (FIB) in research and in water quality testing throughout the world. Evidence from several decades of research demonstrates, however, that enterococci may be present in high densities in the absence of obvious fecal sources and that environmental reservoirs of these FIB are important sources and sinks, with the potential to impact water quality. This review focuses on the distribution and microbial ecology of enterococci in environmental (secondary) habitats, including the effect of environmental stressors; an outline of their known and apparent sources, sinks, and fluxes; and an overview of the use of enterococci as FIB. Finally, the significance of emerging methodologies, such as microbial source tracking (MST) and empirical predictive models, as tools in water quality monitoring is addressed. The mounting evidence for widespread extraenteric sources and reservoirs of enterococci demonstrates the versatility of the genus Enterococcus and argues for the necessity of a better understanding of their ecology in natural environments, as well as their roles as opportunistic pathogens and indicators of human pathogens.

  9. Enterococci in the Environment

    PubMed Central

    Byappanahalli, Muruleedhara N.; Nevers, Meredith B.; Korajkic, Asja; Staley, Zachery R.

    2012-01-01

    Summary: Enterococci are common, commensal members of gut communities in mammals and birds, yet they are also opportunistic pathogens that cause millions of human and animal infections annually. Because they are shed in human and animal feces, are readily culturable, and predict human health risks from exposure to polluted recreational waters, they are used as surrogates for waterborne pathogens and as fecal indicator bacteria (FIB) in research and in water quality testing throughout the world. Evidence from several decades of research demonstrates, however, that enterococci may be present in high densities in the absence of obvious fecal sources and that environmental reservoirs of these FIB are important sources and sinks, with the potential to impact water quality. This review focuses on the distribution and microbial ecology of enterococci in environmental (secondary) habitats, including the effect of environmental stressors; an outline of their known and apparent sources, sinks, and fluxes; and an overview of the use of enterococci as FIB. Finally, the significance of emerging methodologies, such as microbial source tracking (MST) and empirical predictive models, as tools in water quality monitoring is addressed. The mounting evidence for widespread extraenteric sources and reservoirs of enterococci demonstrates the versatility of the genus Enterococcus and argues for the necessity of a better understanding of their ecology in natural environments, as well as their roles as opportunistic pathogens and indicators of human pathogens. PMID:23204362

  10. Deoxynybomycins inhibit mutant DNA gyrase and rescue mice infected with fluoroquinolone-resistant bacteria.

    PubMed

    Parkinson, Elizabeth I; Bair, Joseph S; Nakamura, Bradley A; Lee, Hyang Y; Kuttab, Hani I; Southgate, Emma H; Lezmi, Stéphane; Lau, Gee W; Hergenrother, Paul J

    2015-04-24

    Fluoroquinolones are one of the most commonly prescribed classes of antibiotics, but fluoroquinolone resistance (FQR) is widespread and increasing. Deoxynybomycin (DNM) is a natural-product antibiotic with an unusual mechanism of action, inhibiting the mutant DNA gyrase that confers FQR. Unfortunately, isolation of DNM is difficult and DNM is insoluble in aqueous solutions, making it a poor candidate for development. Here we describe a facile chemical route to produce DNM and its derivatives. These compounds possess excellent activity against FQR methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci clinical isolates and inhibit mutant DNA gyrase in-vitro. Bacteria that develop resistance to DNM are re-sensitized to fluoroquinolones, suggesting that resistance that emerges to DNM would be treatable. Using a DNM derivative, the first in-vivo efficacy of the nybomycin class is demonstrated in a mouse infection model. Overall, the data presented suggest the promise of DNM derivatives for the treatment of FQR infections.

  11. Deoxynybomycins inhibit mutant DNA gyrase and rescue mice infected with fluoroquinolone-resistant bacteria

    PubMed Central

    Parkinson, Elizabeth I.; Bair, Joseph S.; Nakamura, Bradley A.; Lee, Hyang Y.; Kuttab, Hani I.; Southgate, Emma H.; Lezmi, Stéphane; Lau, Gee W.; Hergenrother, Paul J.

    2015-01-01

    Fluoroquinolones are one of the most commonly prescribed classes of antibiotics, but fluoroquinolone resistance (FQR) is widespread and increasing. Deoxynybomycin (DNM) is a natural-product antibiotic with an unusual mechanism of action, inhibiting the mutant DNA gyrase that confers FQR. Unfortunately, isolation of DNM is difficult and DNM is insoluble in aqueous solutions, making it a poor candidate for development. Here we describe a facile chemical route to produce DNM and its derivatives. These compounds possess excellent activity against FQR methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci clinical isolates and inhibit mutant DNA gyrase in-vitro. Bacteria that develop resistance to DNM are re-sensitized to fluoroquinolones, suggesting that resistance that emerges to DNM would be treatable. Using a DNM derivative, the first in-vivo efficacy of the nybomycin class is demonstrated in a mouse infection model. Overall, the data presented suggest the promise of DNM derivatives for the treatment of FQR infections. PMID:25907309

  12. Hydrodynamics of the VanA-type VanS histidine kinase: an extended solution conformation and first evidence for interactions with vancomycin

    PubMed Central

    Phillips-Jones, Mary K.; Channell, Guy; Kelsall, Claire J.; Hughes, Charlotte S.; Ashcroft, Alison E.; Patching, Simon G.; Dinu, Vlad; Gillis, Richard B.; Adams, Gary G.; Harding, Stephen E.

    2017-01-01

    VanA-type resistance to glycopeptide antibiotics in clinical enterococci is regulated by the VanSARA two-component signal transduction system. The nature of the molecular ligand that is recognised by the VanSA sensory component has not hitherto been identified. Here we employ purified, intact and active VanSA membrane protein (henceforth referred to as VanS) in analytical ultracentrifugation experiments to study VanS oligomeric state and conformation in the absence and presence of vancomycin. A combination of sedimentation velocity and sedimentation equilibrium in the analytical ultracentrifuge (SEDFIT, SEDFIT-MSTAR and MULTISIG analysis) showed that VanS in the absence of the ligand is almost entirely monomeric (molar mass M = 45.7 kDa) in dilute aqueous solution with a trace amount of high molar mass material (M ~ 200 kDa). The sedimentation coefficient s suggests the monomer adopts an extended conformation in aqueous solution with an equivalent aspect ratio of ~(12 ± 2). In the presence of vancomycin over a 33% increase in the sedimentation coefficient is observed with the appearance of additional higher s components, demonstrating an interaction, an observation consistent with our circular dichroism measurements. The two possible causes of this increase in s – either a ligand induced dimerization and/or compaction of the monomer are considered. PMID:28397853

  13. Genetic Variability of Vancomycin-Resistant Enterococcus faecium and Enterococcus faecalis Isolates from Humans, Chickens, and Pigs in Malaysia

    PubMed Central

    Getachew, Yitbarek; Zakaria, Zunita; Abdul Aziz, Saleha

    2013-01-01

    Vancomycin-resistant enterococci (VRE) have been reported to be present in humans, chickens, and pigs in Malaysia. In the present study, representative samples of VRE isolated from these populations were examined for similarities and differences by using the multilocus sequence typing (MLST) method. Housekeeping genes of Enterococcus faecium (n = 14) and Enterococcus faecalis (n = 11) isolates were sequenced and analyzed using the MLST databases eBURST and goeBURST. We found five sequence types (STs) of E. faecium and six STs of E. faecalis existing in Malaysia. Enterococcus faecium isolates belonging to ST203, ST17, ST55, ST79, and ST29 were identified, and E. faecium ST203 was the most common among humans. The MLST profiles of E. faecium from humans in this study were similar to the globally reported nosocomial-related strain lineage belonging to clonal complex 17 (CC17). Isolates from chickens and pigs have few similarities to those from humans, except for one isolate from a chicken, which was identified as ST203. E. faecalis isolates were more diverse and were identified as ST4, ST6, ST87, ST108, ST274, and ST244, which were grouped as specific to the three hosts. E. faecalis, belonging to the high-risk CC2 and CC87, were detected among isolates from humans. In conclusion, even though one isolate from a chicken was found clonal to that of humans, the MLST analysis of E. faecium and E. faecalis supports the findings of others who suggest VRE to be predominantly host specific and that clinically important strains are found mainly among humans. The infrequent detection of a human VRE clone in a chicken may in fact suggest a reverse transmission of VRE from humans to animals. PMID:23666337

  14. Potential utility of a peptide deformylase inhibitor (NVP PDF-713) against oxazolidinone-resistant or streptogramin-resistant Gram-positive organism isolates.

    PubMed

    Jones, Ronald N; Moet, Gary J; Sader, Helio S; Fritsche, Thomas R

    2004-05-01

    To evaluate the potency of a novel peptide deformylase inhibitor, NVP PDF-713, against Gram-positive organisms having resistances to linezolid or quinupristin/dalfopristin. A total of 45 strains from three genera (six species groups) were tested by reference broth microdilution methods. The mechanism of resistance to the oxazolidinone was determined by sequencing of the gene encoding the ribosomal target. NVP PDF-713 retained activity against linezolid-resistant staphylococci (MIC range 0.25-2 mg/L), Streptococcus oralis (MIC 0.5 mg/L), Enterococcus faecalis (MIC range 2-4 mg/L) and Enterococcus faecium (MIC range 0.5-4 mg/L). Quinupristin/dalfopristin-resistant E. faecium (MIC range 1-2 mg/L) and staphylococci (MIC range 0.12-2 mg/L) were also inhibited by NVP PDF-713. Many (10 of 13 strains) of the linezolid-resistant enterococci were resistant to vancomycin and these clinical strains had a G2576U ribosomal target mutation. NVP PDF-713 appears to be a promising clinical candidate among the peptide deformylase inhibitors for the treatment of infections caused by Gram-positive organisms that possess resistances to oxazolidinones or streptogramin combinations.

  15. The Prevalence of Vancomycin-Intermediate Staphylococcus aureus and Heterogeneous VISA Among Methicillin-Resistant Strains Isolated from Pediatric Population in a Turkish University Hospital.

    PubMed

    Mirza, Hasan Cenk; Sancak, Banu; Gür, Deniz

    2015-10-01

    There are limited data regarding the prevalence of vancomycin-intermediate Staphylococcus aureus (VISA)/heterogeneous VISA (hVISA) among pediatric population. Our objective was to determine the distribution of vancomycin and daptomycin minimum inhibitory concentrations (MICs) and explore the phenomenon of vancomycin MIC creep and the VISA/hVISA prevalence among the methicillin-resistant Staphylococcus aureus (MRSA) strains belonging to pediatric population by population analysis profile-area under the curve (PAP-AUC) and Etest macromethod. Vancomycin and daptomycin susceptibilities of 94 pediatric isolates of MRSA were tested by broth microdilution (BMD) and Etest methods. To determine the prevalence of VISA/hVISA, Etest macromethod and PAP-AUC was performed on all isolates. All isolates were susceptible to vancomycin and daptomycin by both BMD and Etest methods. Twenty-eight (29.8%) isolates had vancomycin MICs of 2 μg/ml by BMD. No increase in vancomycin MICs was observed over time. There were no VISA among 94 MRSA tested but 20 (21.3%) hVISA isolates were identified by PAP-AUC. Results of Etest macromethod were compared to PAP-AUC. Etest macromethod was 60.0% sensitive and 90.5% specific. The hVISA isolates represented 53.6% of isolates with vancomycin MICs of 2 μg/ml. Also, 75% of hVISA isolates had vancomycin MICs of 2 μg/ml. To our knowledge, this is the first study investigating the prevalence of VISA/hVISA among MRSA isolated from pediatric patients by PAP-AUC method. Based on our findings, MRSA isolates, which have vancomycin MIC of 2 μg/ml can be investigated for the presence of hVISA. In this study, daptomycin showed potent activity against all isolates and may represent a therapeutic option for MRSA infections.

  16. Vancomycin

    MedlinePlus

    ... colitis (inflammation of the intestine caused by certain bacteria) that may occur after antibiotic treatment. Vancomycin is ... medications called glycopeptide antibiotics. It works by killling bacteria in the intestines. Vancomycin will not kill bacteria ...

  17. Comparison of routine prophylaxis with vancomycin or cefazolin for femoral neck fracture surgery: microbiological and clinical outcomes.

    PubMed

    Merrer, Jacques; Desbouchages, Laetitia; Serazin, Valérie; Razafimamonjy, Jimmy; Pauthier, François; Leneveu, Michel

    2006-12-01

    To assess the impact of antibiotic prophylaxis on the emergence of vancomycin-resistant strains of Enterococcus faecium, Enterococcus faecalis, and Staphylococcus aureus and the incidence of surgical site infection (SSI) after vancomycin or cefazolin prophylaxis for femoral neck fracture surgery. Prospective cohort study. A hospital with a high prevalence of methicillin-resistant S. aureus (MRSA) carriage. All patients admitted with a femoral neck fracture from March 1, 2004 through February 28, 2005 were prospectively identified and screened for MRSA and vancomycin-resistant (VRE) carriage at admission and at day 7. Deep incisional and organ/space SSIs were also recorded. Of 263 patients included in the study, 152 (58%) received cefazolin and 106 (40%) received vancomycin. At admission, the prevalence of MRSA carriage was 6.8%; it was 12% among patients with risk factors and 2.2% among patients with no risk factors (P=.002). At day 7 after surgery, there were 6 patients (2%) who had hospital-acquired MRSA, corresponding to 0.7% in the cefazolin group and 5% in the vancomycin group (P=.04); none of the MRSA isolates were resistant to glycopeptides. The rate of VRE carriage at admission was 0.4%. Three patients (1%) had acquired carriage of VRE (1 had E. faecium and 2 had E. faecalis); all 3 were in the cefazolin group (2% of patients) and none in the vancomycin group (P=.27). Eight SSIs (3%) occurred, 4% in the cefazolin group and 2% in the vancomycin group (P=.47). This preliminary study demonstrates that cefazolin and vancomycin prophylaxis have similar impacts on the emergence of glycopeptide-resistant pathogens. Neither MRSA infection nor increased rates of SSI with other bacteria were observed in the vancomycin group, suggesting that a larger multicenter study should be initiated.

  18. Evaluation of risk factors for vancomycin-induced nephrotoxicity.

    PubMed

    Park, So Jin; Lim, Na Ri; Park, Hyo Jung; Yang, Jae Wook; Kim, Min-Ji; Kim, Kyunga; In, Yong Won; Lee, Young Mee

    2018-05-09

    Background Vancomycin is a glycopeptide antibiotic of choice for the treatment of serious infections caused by multi-resistant Gram-positive bacteria. However, vancomycin-associated nephrotoxicity (VAN) often limits its use. Previous data suggested a few risk factors of VAN, including higher mean vancomycin trough level, higher daily doses, old age, long duration of vancomycin therapy, and concomitant nephrotoxins. Objective To evaluate the incidence and risk factors of VAN and determine whether higher vancomycin trough concentrations were associated with a greater risk for VAN. Settings A retrospective, observational, single-center study at the 1960-bed university-affiliated tertiary care hospital (Samsung Medical Center), Seoul, Korea. Method A retrospective analysis of adult patients who received vancomycin parenterally in a tertiary care medical center from March 1, 2013 to June 30, 2013 was performed. We excluded patients with a baseline serum creatinine level > 2 mg/dL and those who had a history of end-stage renal disease and dialysis at baseline. The clinical characteristics were compared between patients with nephrotoxicity and those without nephrotoxicity to identify the risk factors associated with VAN. Main outcome measure Incidence of VAN and VAN-associated risk factors were analyzed. Results Of the 315 vancomycin-treated patients, nephrotoxicity occurred in 15.2% of the patients. In multivariate analysis, higher vancomycin trough concentrations of > 20 mg∕L (OR 9.57, 95% CI 2.49-36.83, p < 0.01) and intensive care unit (ICU) residence (OR 2.86, 95% CI 1.41-5.82, p < 0.01) were independently associated with VAN. Conclusion Our findings suggest that higher vancomycin trough levels and ICU residence might be associated with a greater risk for VAN. More careful monitoring of vancomycin serum trough levels and patient status might facilitate the timely prevention of VAN.

  19. "Slow VISA," a novel phenotype of vancomycin resistance, found in vitro in heterogeneous vancomycin-intermediate Staphylococcus aureus strain Mu3.

    PubMed

    Saito, Michie; Katayama, Yuki; Hishinuma, Tomomi; Iwamoto, Akira; Aiba, Yoshifumi; Kuwahara-Arai, Kyoko; Cui, Longzhu; Matsuo, Miki; Aritaka, Nanae; Hiramatsu, Keiichi

    2014-09-01

    Heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) clinical strain Mu3 spontaneously generates VISA strains at an extremely high frequency (≥1×10(-6)). The generated VISA strains usually grow more slowly than does the parent hVISA strain, but they form colonies on vancomycin-containing agar plates before 48 h of incubation. However, we noticed a curious group of VISA strains, designated "slow VISA" (sVISA), whose colonies appear only after 72 h of incubation. They have extremely prolonged doubling times but have vancomycin MICs of 8 to ∼24 mg/liter when determined after 72 to ∼144 h of incubation. We established strain Mu3-6R-P (6R-P), which has a vancomycin MIC of 16 mg/liter (at 72 h), as a representative sVISA strain. Its cell wall was thickened and autolytic activity was decreased compared to the respective qualities of the parent hVISA strain Mu3. Whole-genome sequencing of 6R-P revealed only one mutation, encoded by rpoB (R512P), which replaced the 512th arginine of the RNA polymerase β-subunit with proline. Its VISA phenotype was unstable, and the strain frequently reverted to hVISA with concomitant losses of pinpoint colony morphology and cell wall thickness and reduced autolytic activity. Sequencing of the rpoB genes of the phenotypic revertant strains revealed mutations affecting the 512th codon, where the proline of 6R-P was replaced with leucine, serine, or histidine. Slow VISA generated in the tissues of an infected patient serves as a temporary shelter for hVISA to survive vancomycin therapy. The sVISA strain spontaneously returns to hVISA when the threat of vancomycin is lifted. The rpoB(R512P) mutation may be regarded as a regulatory mutation that switches the reversible phenotype of sVISA on and off. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  20. Impact of Initial Vancomycin Trough Concentration on Clinical and Microbiological Outcomes of Methicillin-Resistant Staphylococcus aureus Bacteremia in Children.

    PubMed

    Yoo, Ree Nar; Kim, Seo Hee; Lee, Jina

    2017-01-01

    It is important to use vancomycin in a proper manner to ensure optimal drug exposure. Despite extensive use of vancomycin in children, studies on its optimal trough concentration (Ctrough) in the pediatric population remained rare. This retrospective study included children < 18 years old with culture-confirmed methicillin-resistant Staphylococcus aureus (MRSA) bacteremia who were hospitalized in our institute from January 2010 to April 2014. Clinical characteristics, initial vancomycin dose, Ctrough and clinical/microbiological outcomes were retrospectively collected from medical records. Forty-six MRSA bacteremia cases occurring to the patients with a mean age of 22.0 ± 46.9 months were included and all of them were healthcare-associated. Severe diseases requiring intensive care unit (ICU) stay, mechanical ventilation and/or resulting in death were observed in 57.8% (26/45); all-cause 30-day fatality was 11.1% (5/45). An initial Ctrough ≥ 15 μg/mL was achieved in only 4 (8.7%) cases with an average vancomycin dosage of 40.6 ± 7.9 mg/kg/day. Persistent bacteremia at 48 hours after initiation of vancomycin was observed more frequently in children with initial Ctrough < 10 μg/mL than in those with Ctrough ≥ 10 μg/mL (P = 0.032). However, there was no statistically significant difference between the two groups in terms of 30-day mortality and recurrent bacteremia (P = 0.899, and P = 0.754, respectively). Although initial Ctrough may be a useful parameter for minimizing early microbiological failure, it does not predict 30-day fatality or recurrence in pediatric MRSA bacteremia. Further prospective data on vancomycin dosing are needed to find the optimal drug exposure and clarify its impact on clinical outcomes in pediatric populations.

  1. Zinc and copper in animal feed – development of resistance and co-resistance to antimicrobial agents in bacteria of animal origin

    PubMed Central

    Yazdankhah, Siamak; Rudi, Knut; Bernhoft, Aksel

    2014-01-01

    Farmed animals such as pig and poultry receive additional Zn and Cu in their diets due to supplementing elements in compound feed as well as medical remedies. Enteral bacteria in farmed animals are shown to develop resistance to trace elements such as Zn and Cu. Resistance to Zn is often linked with resistance to methicillin in staphylococci, and Zn supplementation to animal feed may increase the proportion of multiresistant E. coli in the gut. Resistance to Cu in bacteria, in particular enterococci, is often associated with resistance to antimicrobial drugs like macrolides and glycopeptides (e.g. vancomycin). Such resistant bacteria may be transferred from the food-producing animals to humans (farmers, veterinarians, and consumers). Data on dose-response relation for Zn/Cu exposure and resistance are lacking; however, it seems more likely that a resistance-driven effect occurs at high trace element exposure than at more basal exposure levels. There is also lack of data which could demonstrate whether Zn/Cu-resistant bacteria may acquire antibiotic resistance genes/become antibiotics resistant, or if antibiotics-resistant bacteria are more capable to become Zn/Cu resistant than antibiotics-susceptible bacteria. Further research is needed to elucidate the link between Zn/Cu and antibiotic resistance in bacteria. PMID:25317117

  2. Comparative Effectiveness of Vancomycin Versus Daptomycin for MRSA Bacteremia With Vancomycin MIC >1 mg/L: A Multicenter Evaluation.

    PubMed

    Moise, Pamela A; Culshaw, Darren L; Wong-Beringer, Annie; Bensman, Joyce; Lamp, Kenneth C; Smith, Winter J; Bauer, Karri; Goff, Debra A; Adamson, Robert; Leuthner, Kimberly; Virata, Michael D; McKinnell, James A; Chaudhry, Saira B; Eskandarian, Romic; Lodise, Thomas; Reyes, Katherine; Zervos, Marcus J

    2016-01-01

    Clinical studies comparing vancomycin with alternative therapy for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia are limited. The objective of this study was to compare outcomes of early daptomycin versus vancomycin treatment for MRSA bacteremia with high vancomycin MICs in a geographically diverse multicenter evaluation. This nationwide, retrospective, multicenter (N = 11), matched, cohort study compared outcomes of early daptomycin with vancomycin for MRSA bloodstream infection (BSI) with vancomycin MICs 1.5 to 2 µg/mL. Matching variables, based on propensity regression analysis, included age, intensive care unit (ICU), and type of BSI. Outcomes were as follows: (1) composite failure (60-day all-cause mortality, 7-day clinical or microbiologic failure, 30-day BSI relapse, or end-of-treatment failure (EOT; discontinue/change daptomycin or vancomycin because of treatment failure or adverse event]); (2) nephrotoxicity; and (2) day 4 BSI clearance. A total of 170 patients were included. The median (interquartile range) age was 60 years (50-74); the median (range) Acute Physiology and Chronic Health Evaluation II score was 15 (10-18); 31% were in an ICU; and 92% had an infectious disease consultation. BSI types included endocarditis/endovascular (39%), extravascular (55%), and central catheter (6%). The median daptomycin dose was 6 mg/kg, and the vancomycin trough level was 17 mg/L. Overall composite failure was 35% (59 of 170): 15% due to 60-day all-cause mortality, 14% for lack of clinical or microbiologic response by 7 days, and 17% due to failure at end of therapy (discontinue/change because of treatment failure or adverse event). Predictors of composite failure according to multivariate analysis were age >60 years (odds ratio, 3.7; P < 0.01) and ICU stay (odds ratio, 2.64; P = 0.03). Notable differences between treatment groups were seen with: (1) end of therapy failure rates (11% vs 24% for daptomycin vs vancomycin; P = 0.025); (2) acute kidney

  3. Thieno[2,3-d]pyrimidinedione derivatives as antibacterial agents

    PubMed Central

    Dewal, Mahender B.; Wani, Amit S.; Vidaillac, Celine; Oupicky, David; Rybak, Michael J.

    2012-01-01

    Several thieno[2,3-d]pyrimidinediones have been synthesized and examined for antibacterial activity against a range of Gram-positive and Gram-negative pathogens. Two compounds displayed potent activity (2–16 mg/L) against multi-drug resistant Gram-positive organisms, including methicillin, vancomycin-intermediate, and vancomycin-resistant Staphylococcus aureus (MRSA, VISA, VRSA) and vancomycin-resistant enterococci (VRE). Only one of these agents possessed moderate activity (16–32 mg/L) against Gram-negative strains. An examination of the cytotoxicity of these agents revealed that they displayed low toxicity (40–50 mg/L) against mammalian cell and very low hemolytic activity (2–7%). Taken together, these studies suggest that thieno[2,3-d]pyrimidinediones are interesting scaffolds for the development of novel Gram-positive antibacterial agents. PMID:22405289

  4. Annual Surveillance Summary: Vancomycin-Resistant Enterococci (VRE) Infections in the Military Health System (MHS), 2015

    DTIC Science & Technology

    2017-03-01

    Defense (DOD) and Department of the Navy (DON) active duty (AD) service members with deployment-related infections. In 2015, the annual VRE incidence rate...reporting of resistant strains.9 Additionally, active surveillance of high-risk patients has been cited as a pertinent control measure in healthcare...settings; one study demonstrated active surveillance with contact precautions prevented VRE infections in an intensive care unit (ICU) where 100% of

  5. vanC Cluster of Vancomycin-Resistant Enterococcus gallinarum BM4174

    PubMed Central

    Arias, Cesar A.; Courvalin, Patrice; Reynolds, Peter E.

    2000-01-01

    Glycopeptide-resistant enterococci of the VanC type synthesize UDP-muramyl-pentapeptide[d-Ser] for cell wall assembly and prevent synthesis of peptidoglycan precursors ending in d-Ala. The vanC cluster of Enterococcus gallinarum BM4174 consists of five genes: vanC-1, vanXYC, vanT, vanRC, and vanSC. Three genes are sufficient for resistance: vanC-1 encodes a ligase that synthesizes the dipeptide d-Ala-d-Ser for addition to UDP-MurNAc-tripeptide, vanXYC encodes a d,d-dipeptidase–carboxypeptidase that hydrolyzes d-Ala-d-Ala and removes d-Ala from UDP-MurNAc-pentapeptide[d-Ala], and vanT encodes a membrane-bound serine racemase that provides d-Ser for the synthetic pathway. The three genes are clustered: the start codons of vanXYC and vanT overlap the termination codons of vanC-1 and vanXYC, respectively. Two genes which encode proteins with homology to the VanS-VanR two-component regulatory system were present downstream from the resistance genes. The predicted amino acid sequence of VanRC exhibited 50% identity to VanR and 33% identity to VanRB. VanSC had 40% identity to VanS over a region of 308 amino acids and 24% identity to VanSB over a region of 285 amino acids. All residues with important functions in response regulators and histidine kinases were conserved in VanRC and VanSC, respectively. Induction experiments based on the determination of d,d-carboxypeptidase activity in cytoplasmic extracts confirmed that the genes were expressed constitutively. Using a promoter-probing vector, regions upstream from the resistance and regulatory genes were identified that have promoter activity. PMID:10817725

  6. An investigation of vancomycin minimum inhibitory concentration creep among methicillin-resistant Staphylococcus aureus strains isolated from pediatric patients and healthy children in Northern Taiwan.

    PubMed

    Chang, Chia-Ning; Lo, Wen-Tsung; Chan, Ming-Chin; Yu, Ching-Mei; Wang, Chih-Chien

    2017-06-01

    The phenomenon of vancomycin minimum inhibitory concentration (MIC) creep is an increasingly serious problem in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. In this study, we investigated the vancomycin and daptomycin MIC values of MRSA strains isolated from pediatric patients and MRSA colonized healthy children. Then, we assessed whether there was evidence of clonal dissemination for strains with an MIC to vancomycin of ≥ 1.5 μg/mL. We collected clinical MRSA isolates from pediatric patients and from healthy children colonized with MRSA during 2008-2012 at a tertiary medical center in northern Taiwan and obtained vancomycin and daptomycin MIC values using the Etest method. Pulse-field gel electrophoresis (PFGE) and staphylococcal cassette chromosome (SCCmec) typing were used to assess clonal dissemination for strains with an MIC to vancomycin of ≥ 1.5 μg/mL. A total 195 MRSA strains were included in this study; 87 were isolated patients with a clinical MRSA infection, and the other 108 strains from nasally colonized healthy children. Vancomycin MIC≥1.5 μg/mL was seen in more clinical isolates (60/87, 69%) than colonized isolates (32/108, 29.6%), p < 0.001. The PFGE typing of both strains revealed multiple pulsotypes. Vancomycin MIC creeps existed in both clinical MRSA isolates and colonized MRSA strains. Great diversity of PFGE typing was in both strains collected. There was no association between the clinical and colonized MRSA isolates with vancomycin MIC creep. Copyright © 2016. Published by Elsevier B.V.

  7. Comparative genome analysis of multiple vancomycin-resistant Enterococcus faecium isolated from two fatal cases.

    PubMed

    Lim, Shu Yong; Yap, Kien-Pong; Teh, Cindy Shuan Ju; Jabar, Kartini Abdul; Thong, Kwai Lin

    2017-04-01

    Enterococcus faecium is both a commensal of the human intestinal tract and an opportunistic pathogen. The increasing incidence of enterococcal infections is mainly due to the ability of this organism to develop resistance to multiple antibiotics, including vancomycin. The aim of this study was to perform comparative genome analyses on four vancomycin-resistant Enterococcus faecium (VRE fm ) strains isolated from two fatal cases in a tertiary hospital in Malaysia. Two sequence types, ST80 and ST203, were identified which belong to the clinically important clonal complex (CC) 17. This is the first report on the emergence of ST80 strains in Malaysia. Three of the studied strains (VREr5, VREr6, VREr7) were each isolated from different body sites of a single patient (patient Y) and had different PFGE patterns. While VREr6 and VREr7 were phenotypically and genotypically similar, the initial isolate, VREr5, was found to be more similar to VRE2 isolated from another patient (patient X), in terms of the genome contents, sequence types and phylogenomic relationship. Both the clinical records and genome sequence data suggested that patient Y was infected by multiple strains from different clones and the strain that infected patient Y could have derived from the same clone from patient X. These multidrug resistant strains harbored a number of virulence genes such as the epa locus and pilus-associated genes which could enhance their persistence. Apart from that, a homolog of E. faecalis bee locus was identified in VREr5 which might be involved in biofilm formation. Overall, our comparative genomic analyses had provided insight into the genetic relatedness, as well as the virulence potential, of the four clinical strains. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Vancomycin-Associated Cast Nephropathy

    PubMed Central

    Luque, Yosu; Louis, Kevin; Jouanneau, Chantal; Placier, Sandrine; Esteve, Emmanuel; Bazin, Dominique; Rondeau, Eric; Letavernier, Emmanuel; Wolfromm, Alice; Gosset, Clément; Boueilh, Anna; Burbach, Maren; Frère, Perrine; Verpont, Marie-Christine; Vandermeersch, Sophie; Langui, Dominique; Daudon, Michel; Frochot, Vincent

    2017-01-01

    Vancomycin is a widely prescribed antibiotic, but the exact nature of vancomycin-associated nephrotoxicity is unclear, in particular when considering the frequent coadministration of aminoglycosides. We describe here the initial case of a 56-year-old woman with normal renal function developing unexplained ARF without hypovolemia after administration of vancomycin without coadministration of aminoglycosides. Studying the patient’s renal biopsy specimen, we ascertained that obstructive tubular casts composed of noncrystal nanospheric vancomycin aggregates entangled with uromodulin explained the vancomycin-associated ARF. We developed in parallel a new immunohistologic staining technique to detect vancomycin in renal tissue and confirmed retrospectively that deleterious vancomycin-associated casts existed in eight additional patients with acute tubular necrosis in the absence of hypovolemia. Concomitant high vancomycin trough plasma levels had been observed in each patient. We also reproduced experimentally the toxic and obstructive nature of vancomycin-associated cast nephropathy in mice, which we detected using different in vivo imaging techniques. In conclusion, the interaction of uromodulin with nanospheric vancomycin aggregates represents a new mode of tubular cast formation, revealing the hitherto unsuspected mechanism of vancomycin-associated renal injury. PMID:28082518

  9. Vancomycin-Associated Cast Nephropathy.

    PubMed

    Luque, Yosu; Louis, Kevin; Jouanneau, Chantal; Placier, Sandrine; Esteve, Emmanuel; Bazin, Dominique; Rondeau, Eric; Letavernier, Emmanuel; Wolfromm, Alice; Gosset, Clément; Boueilh, Anna; Burbach, Maren; Frère, Perrine; Verpont, Marie-Christine; Vandermeersch, Sophie; Langui, Dominique; Daudon, Michel; Frochot, Vincent; Mesnard, Laurent

    2017-06-01

    Vancomycin is a widely prescribed antibiotic, but the exact nature of vancomycin-associated nephrotoxicity is unclear, in particular when considering the frequent coadministration of aminoglycosides. We describe here the initial case of a 56-year-old woman with normal renal function developing unexplained ARF without hypovolemia after administration of vancomycin without coadministration of aminoglycosides. Studying the patient's renal biopsy specimen, we ascertained that obstructive tubular casts composed of noncrystal nanospheric vancomycin aggregates entangled with uromodulin explained the vancomycin-associated ARF. We developed in parallel a new immunohistologic staining technique to detect vancomycin in renal tissue and confirmed retrospectively that deleterious vancomycin-associated casts existed in eight additional patients with acute tubular necrosis in the absence of hypovolemia. Concomitant high vancomycin trough plasma levels had been observed in each patient. We also reproduced experimentally the toxic and obstructive nature of vancomycin-associated cast nephropathy in mice, which we detected using different in vivo imaging techniques. In conclusion, the interaction of uromodulin with nanospheric vancomycin aggregates represents a new mode of tubular cast formation, revealing the hitherto unsuspected mechanism of vancomycin-associated renal injury. Copyright © 2017 by the American Society of Nephrology.

  10. Raising the Alarmone: Within-Host Evolution of Antibiotic-Tolerant Enterococcus faecium

    PubMed Central

    2017-01-01

    ABSTRACT Enterococci are ancient commensal bacteria that recently emerged as leading causes of antibiotic-resistant, hospital-acquired infection. Vancomycin-resistant enterococci (VRE) epitomize why drug-resistant enterococcal infections are a problem: VRE readily colonize the antibiotic-perturbed gastrointestinal (GI) tract where they amplify to large numbers, and from there, they infect other body sites, including the bloodstream, urinary tract, and surgical wounds. VRE are resistant to many antimicrobials and host defenses, which facilitates establishment at the site of infection and confounds therapeutic clearance. Having evolved to colonize the GI tract, VRE are comparatively ill adapted to the human bloodstream. A recent study by Honsa and colleagues (E. S. Honsa et al., mBio 8:e02124-16, 2017, https://doi.org/10.1128/mBio.02124-16) found that a strain of vancomycin-resistant Enterococcus faecium evolved antibiotic tolerance within the bloodstream of an immunocompromised host by activating the stringent response through mutation of relA. Precisely how VRE colonize and infect and the selective pressures that led to the outgrowth of relA mutants are the subjects of ongoing research. PMID:28223450

  11. Modeling the economic impact of linezolid versus vancomycin in confirmed nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus.

    PubMed

    Patel, Dipen A; Shorr, Andrew F; Chastre, Jean; Niederman, Michael; Simor, Andrew; Stephens, Jennifer M; Charbonneau, Claudie; Gao, Xin; Nathwani, Dilip

    2014-07-22

    We compared the economic impacts of linezolid and vancomycin for the treatment of hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA)-confirmed nosocomial pneumonia. We used a 4-week decision tree model incorporating published data and expert opinion on clinical parameters, resource use and costs (in 2012 US dollars), such as efficacy, mortality, serious adverse events, treatment duration and length of hospital stay. The results presented are from a US payer perspective. The base case first-line treatment duration for patients with MRSA-confirmed nosocomial pneumonia was 10 days. Clinical treatment success (used for the cost-effectiveness ratio) and failure due to lack of efficacy, serious adverse events or mortality were possible clinical outcomes that could impact costs. Cost of treatment and incremental cost-effectiveness per successfully treated patient were calculated for linezolid versus vancomycin. Univariate (one-way) and probabilistic sensitivity analyses were conducted. The model allowed us to calculate the total base case inpatient costs as $46,168 (linezolid) and $46,992 (vancomycin). The incremental cost-effectiveness ratio favored linezolid (versus vancomycin), with lower costs ($824 less) and greater efficacy (+2.7% absolute difference in the proportion of patients successfully treated for MRSA nosocomial pneumonia). Approximately 80% of the total treatment costs were attributed to hospital stay (primarily in the intensive care unit). The results of our probabilistic sensitivity analysis indicated that linezolid is the cost-effective alternative under varying willingness to pay thresholds. These model results show that linezolid has a favorable incremental cost-effectiveness ratio compared to vancomycin for MRSA-confirmed nosocomial pneumonia, largely attributable to the higher clinical trial response rate of patients treated with linezolid. The higher drug acquisition cost of linezolid was offset by lower treatment failure

  12. Population Genomics of Reduced Vancomycin Susceptibility in Staphylococcus aureus

    PubMed Central

    Rishishwar, Lavanya; Kraft, Colleen S.

    2016-01-01

    ABSTRACT The increased prevalence of vancomycin-intermediate Staphylococcus aureus (VISA) is an emerging health care threat. Genome-based comparative methods hold great promise to uncover the genetic basis of the VISA phenotype, which remains obscure. S. aureus isolates were collected from a single individual that presented with recurrent staphylococcal bacteremia at three time points, and the isolates showed successively reduced levels of vancomycin susceptibility. A population genomic approach was taken to compare patient S. aureus isolates with decreasing vancomycin susceptibility across the three time points. To do this, patient isolates were sequenced to high coverage (~500×), and sequence reads were used to model site-specific allelic variation within and between isolate populations. Population genetic methods were then applied to evaluate the overall levels of variation across the three time points and to identify individual variants that show anomalous levels of allelic change between populations. A successive reduction in the overall levels of population genomic variation was observed across the three time points, consistent with a population bottleneck resulting from antibiotic treatment. Despite this overall reduction in variation, a number of individual mutations were swept to high frequency in the VISA population. These mutations were implicated as potentially involved in the VISA phenotype and interrogated with respect to their functional roles. This approach allowed us to identify a number of mutations previously implicated in VISA along with allelic changes within a novel class of genes, encoding LPXTG motif-containing cell-wall-anchoring proteins, which shed light on a novel mechanistic aspect of vancomycin resistance. IMPORTANCE The emergence and spread of antibiotic resistance among bacterial pathogens are two of the gravest threats to public health facing the world today. We report the development and application of a novel population genomic

  13. Vancomycin heteroresistance in coagulase negative Staphylococcus blood stream infections from patients of intensive care units in Mansoura University Hospitals, Egypt.

    PubMed

    Mashaly, Ghada El-Saeed; El-Mahdy, Rasha Hassan

    2017-09-19

    Vancomycin heteroresistance in coagulase negative Staphylococci (CoNS) is a recent health concern especially in serious infections like bloodstream infections as it may lead to failure of therapy. Little information is available about the prevalence vancomycin heteroresistance in CoNS causing bloodstream infections in intensive care units (ICUs) patients of Mansoura University Hospitals (MUHs). This prospective study enrolled 743 blood samples collected from ICUs patients presented with clinical manifestations of bloodstream infections over the period extending from January 2014 to March 2016. Samples were processed, coagulase negative Staphylococci were identified by routine microbiological methods and the absence of coagulase activity. Species were identified by API Staph 32. Oxacillin resistant CoNS were identified by cefoxitin disc diffusion method. Susceptibility testing of isolated CoNS to vancomycin was carried out using vancomycin agar dilution method. Mec A gene detection by PCR was done for oxacillin resistant isolates. Screening for vancomycin heteroresistance was done on brain heart infusion (BHI) agar containing 4 μg/mL vancomycin. Confirmation of vancomycin heteroresistance was carried out by population analysis profile (PAP). A total of 58 isolates were identified as CoNS from patients of clinically suspected bloodstream infections. The identified species were 33 (56.9%) Staphylococcus epidermidis, 12 (20.7%) Staphylococcus capitis, 7 (12.1%) Staphylococcus haemolyticus, and 3 isolates (5.2%) Staphylococcus lugdunesis. Three isolates were unidentified by API Staph 32. Forty-four (75.9%) isolates were oxacillin resistant. Mec A gene was detected in all oxacillin resistant isolates. All isolates had susceptible vancomycin MICs by agar dilution. Nine isolates (15.5%) could grow on BHI agar containing 4 μg/mL vancomycin. These isolates showed heterogeneous profile of resistance to vancomycin by population analysis profile. Vancomycin heteroresistant

  14. Vancomycin: ligand recognition, dimerization and super-complex formation.

    PubMed

    Jia, ZhiGuang; O'Mara, Megan L; Zuegg, Johannes; Cooper, Matthew A; Mark, Alan E

    2013-03-01

    The antibiotic vancomycin targets lipid II, blocking cell wall synthesis in Gram-positive bacteria. Despite extensive study, questions remain regarding how it recognizes its primary ligand and what is the most biologically relevant form of vancomycin. In this study, molecular dynamics simulation techniques have been used to examine the process of ligand binding and dimerization of vancomycin. Starting from one or more vancomycin monomers in solution, together with different peptide ligands derived from lipid II, the simulations predict the structures of the ligated monomeric and dimeric complexes to within 0.1 nm rmsd of the structures determined experimentally. The simulations reproduce the conformation transitions observed by NMR and suggest that proposed differences between the crystal structure and the solution structure are an artifact of the way the NMR data has been interpreted in terms of a structural model. The spontaneous formation of both back-to-back and face-to-face dimers was observed in the simulations. This has allowed a detailed analysis of the origin of the cooperatively between ligand binding and dimerization and suggests that the formation of face-to-face dimers could be functionally significant. The work also highlights the possible role of structural water in stabilizing the vancomycin ligand complex and its role in the manifestation of vancomycin resistance. © 2013 The Authors Journal compilation © 2013 FEBS.

  15. Enterococci in foods--a conundrum for food safety.

    PubMed

    Franz, Charles M A P; Stiles, Michael E; Schleifer, Karl Heinz; Holzapfel, Wilhelm H

    2003-12-01

    Enterococci form part of the lactic acid bacteria (LAB) of importance in foods. They can spoil processed meats but they are on the other hand important for ripening and aroma development of certain traditional cheeses and sausages, especially those produced in the Mediterranean area. Enterococci are also used as human probiotics. However, they are important nosocomial pathogens that cause bacteraemia, endocarditis and other infections. Some strains are resistant to many antibiotics, but antibiotic resistance alone cannot explain the virulence of some of these bacteria. Virulence factors such as adhesins, invasins and haemolysin have been described. The role of enterococci in disease has raised questions on their safety for use in foods or as probiotics. Studies on the incidence of virulence traits among enterococcal strains isolated from food showed that some harbour virulence traits and generally, Enterococcus faecalis harbours more of them than Enterococcus faecium. Regulations in Europe stipulate that safety of probiotic or starter strains is the responsibility of the producer; therefore, each strain intended for such use should be carefully evaluated. For numerous questions, immediate answers are not fully available. It is therefore suggested that when considering an Enterococcus strain for use as a starter or probiotic culture, it is imperative that each particular strain should be carefully evaluated for the presence of all known virulence factors. Ideally, such strains should harbour no virulence determinants and should be sensitive to clinically relevant antibiotics. In general, E. faecium appears to pose a lower risk for use in foods, because these strains generally harbour fewer recognised virulence determinants than E. faecalis. Generally, the incidence of such virulence determinants among E. faecium strains is low, as compared to E. faecalis strains, probably as a result of the presence of pheromone-responsive plasmids.

  16. Combination of Vancomycin and β-Lactam Therapy for Methicillin-Resistant Staphylococcus aureus Bacteremia: A Pilot Multicenter Randomized Controlled Trial.

    PubMed

    Davis, Joshua S; Sud, Archana; O'Sullivan, Matthew V N; Robinson, James O; Ferguson, Patricia E; Foo, Hong; van Hal, Sebastiaan J; Ralph, Anna P; Howden, Benjamin P; Binks, Paula M; Kirby, Adrienne; Tong, Steven Y C; Tong, Steven; Davis, Joshua; Binks, Paula; Majumdar, Suman; Ralph, Anna; Baird, Rob; Gordon, Claire; Jeremiah, Cameron; Leung, Grace; Brischetto, Anna; Crowe, Amy; Dakh, Farshid; Whykes, Kelly; Kirkwood, Maria; Sud, Archana; Menon, Mahesh; Somerville, Lucy; Subedi, Shrada; Owen, Shirley; O'Sullivan, Matthew; Liu, Eunice; Zhou, Fei; Robinson, Owen; Coombs, Geoffrey; Ferguson, Patrician; Ralph, Anna; Liu, Eunice; Pollet, Simon; Van Hal, Sebastian; Foo, Hong; Van Hal, Sebastian; Davis, Rebecca

    2016-01-15

    In vitro laboratory and animal studies demonstrate a synergistic role for the combination of vancomycin and antistaphylococcal β-lactams for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Prospective clinical data are lacking. In this open-label, multicenter, clinical trial, adults with MRSA bacteremia received vancomycin 1.5 g intravenously twice daily and were randomly assigned (1:1) to receive intravenous flucloxacillin 2 g every 6 hours for 7 days (combination group) or no additional therapy (standard therapy group). Participants were stratified by hospital and randomized in permuted blocks of variable size. Randomization codes were kept in sealed, sequentially numbered, opaque envelopes. The primary outcome was the duration of MRSA bacteremia in days. We randomly assigned 60 patients to receive vancomycin (n = 29), or vancomycin plus flucloxacillin (n = 31). The mean duration of bacteremia was 3.00 days in the standard therapy group and 1.94 days in the combination group. According to a negative binomial model, the mean time to resolution of bacteremia in the combination group was 65% (95% confidence interval, 41%-102%; P = .06) that in the standard therapy group. There was no difference in the secondary end points of 28- and 90-day mortality, metastatic infection, nephrotoxicity, or hepatotoxicity. Combining an antistaphylococcal β-lactam with vancomycin may shorten the duration of MRSA bacteremia. Further trials with a larger sample size and objective clinically relevant end points are warranted. Australian New Zealand Clinical Trials Registry: ACTRN12610000940077 (www.anzctr.org.au). © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  17. Synergy of arbekacin-based combinations against vancomycin hetero-intermediate Staphylococcus aureus.

    PubMed

    Lee, Ji Young; Oh, Won Sup; Ko, Kwan Soo; Heo, Sang Taek; Moon, Chi Sook; Ki, Hyun Kyun; Kiem, Sungmin; Peck, Kyong Ran; Song, Jae Hoon

    2006-04-01

    This study was undertaken to evaluate the in vitro activities of arbekacin-based combination regimens against vancomycin hetero-intermediate Staphylococcus aureus (hetero-VISA). Combinations of arbekacin with vancomycin, rifampin, ampicillin-sulbactam, teicoplanin, or quinupristin-dalfopristin against seven hetero-VISA strains and two methicillin-resistant S. aureus strains were evaluated by the time-kill assay. The combinations of arbekacin with vancomycin, teicoplanin, or ampicillin-sulbactam showed the synergistic interaction against hetero-VISA strains. Data suggest that these arbekacin-based combination regimens may be useful candidates for treatment options of hetero-VISA infections.

  18. Synergy of Arbekacin-based Combinations Against Vancomycin Hetero-intermediate Staphylococcus aureus

    PubMed Central

    Lee, Ji-Young; Oh, Won Sup; Ko, Kwan Soo; Heo, Sang Taek; Moon, Chi Sook; Ki, Hyun Kyun; Kiem, Sungmin; Peck, Kyong Ran

    2006-01-01

    This study was undertaken to evaluate the in vitro activities of arbekacin-based combination regimens against vancomycin hetero-intermediate Staphylococcus aureus (hetero-VISA). Combinations of arbekacin with vancomycin, rifampin, ampicillin-sulbactam, teicoplanin, or quinipristin-dalfopristin against seven hetero-VISA strains and two methicillin-resistant S. aureus strains were evaluated by the time-kill assay. The combinations of arbekacin with vancomycin, teicoplanin, or ampicillin-sulbactam showed the synergistic interaction against hetero-VISA strains. Data suggest that these arbekacin-based combination regimens may be useful candidates for treatment options of hetero-VISA infections. PMID:16614499

  19. Complete Reconstitution of the Vancomycin-Intermediate Staphylococcus aureus Phenotype of Strain Mu50 in Vancomycin-Susceptible S. aureus

    PubMed Central

    Sekine, Miwa; Hishinuma, Tomomi; Aiba, Yoshifumi; Hiramatsu, Keiichi

    2016-01-01

    Complete reconstitution of the vancomycin-intermediate Staphylococcus aureus (VISA) phenotype of strain Mu50 was achieved by sequentially introducing mutations into six genes of vancomycin-susceptible S. aureus (VSSA) strain N315ΔIP. The six mutated genes were detected in VISA strain Mu50 but not in N315ΔIP. Introduction of the mutation Ser329Leu into vraS, encoding the sensor histidine kinase of the vraSR two-component regulatory (TCR) system, and another mutation, Glu146Lys, into msrR, belonging to the LytR-CpsA-Psr (LCP) family, increased the level of vancomycin resistance to that detected in heterogeneous vancomycin-intermediate S. aureus (hVISA) strain Mu3. Introduction of two more mutations, Asn197Ser into graR of the graSR TCR system and His481Tyr into rpoB, encoding the β subunit of RNA polymerase, converted the hVISA strain into a VISA strain with the same level of vancomycin resistance as Mu50. Surprisingly, however, the constructed quadruple mutant strain ΔIP4 did not have a thickened cell wall, a cardinal feature of the VISA phenotype. Subsequent study showed that cell wall thickening was an inducible phenotype in the mutant strain, whereas it was a constitutive one in Mu50. Finally, introduction of the Ala297Val mutation into fdh2, which encodes a putative formate dehydrogenase, or a 67-amino-acid sequence deletion into sle1 [sle1(Δ67aa)], encoding the hydrolase of N-acetylmuramyl-l-alanine amidase in the peptidoglycan, converted inducible cell wall thickening into constitutive cell wall thickening. sle1(Δ67aa) was found to cause a drastic decrease in autolysis activity. Thus, all six mutated genes required for acquisition of the VISA phenotype were directly or indirectly involved in the regulation of cell physiology. The VISA phenotype seemed to be achieved through multiple genetic events accompanying drastic changes in cell physiology. PMID:27067329

  20. Vancomycin-resistant Enterococcus in pediatric oncology patients: balancing infection prevention and family-centered care.

    PubMed

    Singh, Jasjit; Esparza, Samuel; Patterson, Melanie; Vogel, Kate; Patel, Bijal; Gornick, Wendi

    2013-04-01

    In February 2007, we experienced an abrupt 8-fold increase in vancomycin-resistant Enterococcus (VRE)-positive pediatric hematology/oncology patients in isolation per day, peaking at 12 patients in isolation per day in June 2007. We enforced and expanded infection prevention practices and initiated a rigorous 6-month clearance process. After noting an eventual decrease, we modified clearance to a 3-month process, maintaining <1 patient/day in isolation by June 2009, subjectively improving family and staff satisfaction after this 2-year process. VRE infection was relatively uncommon (7.8%), although continued VRE colonization portended an overall poorer prognosis.

  1. Block Copolymer Nanoparticles Remove Biofilms of Drug-Resistant Gram-Positive Bacteria by Nanoscale Bacterial Debridement.

    PubMed

    Li, Jianghua; Zhang, Kaixi; Ruan, Lin; Chin, Seow Fong; Wickramasinghe, Nirmani; Liu, Hanbin; Ravikumar, Vikashini; Ren, Jinghua; Duan, Hongwei; Yang, Liang; Chan-Park, Mary B

    2018-06-26

    Biofilms and the rapid evolution of multidrug resistance complicate the treatment of bacterial infections. Antibiofilm agents such as metallic-inorganic nanoparticles or peptides act by exerting antibacterial effects and, hence, do not combat biofilms of antibiotics-resistant strains. In this Letter, we show that the block copolymer DA95B5, dextran- block-poly((3-acrylamidopropyl) trimethylammonium chloride (AMPTMA)- co-butyl methacrylate (BMA)), effectively removes preformed biofilms of various clinically relevant multidrug-resistant Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE V583), and Enteroccocus faecalis (OG1RF). DA95B5 self-assembles into core-shell nanoparticles with a nonfouling dextran shell and a cationic core. These nanoparticles diffuse into biofilms and attach to bacteria but do not kill them; instead, they promote the gradual dispersal of biofilm bacteria, probably because the solubility of the bacteria-nanoparticle complex is enhanced by the nanoparticle dextran shell. DA95B5, when applied as a solution to a hydrogel pad dressing, shows excellent in vivo MRSA biofilm removal efficacy of 3.6 log reduction in a murine excisional wound model, which is significantly superior to that for vancomycin. Furthermore, DA95B5 has very low in vitro hemolysis and negligible in vivo acute toxicity. This new strategy for biofilm removal (nanoscale bacterial debridement) is orthogonal to conventional rapidly developing resistance traits in bacteria so that it is as effective toward resistant strains as it is toward sensitive strains and may have widespread applications.

  2. In vitro activity of flomoxef and cefazolin in combination with vancomycin.

    PubMed

    Simon, C; Simon, M

    1991-01-01

    207 clinical isolates from strains of patients from the University Children's Hospital of Kiel were investigated for their in vitro activity with the agar dilution method against flomoxef and cefazolin (alone and partially in combination with vancomycin). Staphylococci were also tested with other cephalosporins (cefoxitin, cefamandole, cefotaxime, cefotetan and latamoxef). Flomoxef and cefazolin always acted more vigorously on staphylococci than the other cephalosporins. Resistance of Staphylococcus aureus strains against flomoxef and cefazolin did not occur but was found in 15 and 5 of 98 Staphylococcus epidermidis strains, respectively. Enterococcus faecalis strains were always resistant against both drugs; Streptococcus faecium strains were only moderately sensitive. Combined testing of flomoxef or cefazolin with vancomycin showed synergism in almost all staphylococcal strains. Synergism was stronger when S. epidermidis strains were only weakly sensitive to or resistant against flomoxef and cefazolin in comparison to highly sensitive strains. Flomoxef (or cefazolin) acted synergistically in combination with vancomycin on E. faecalis and S. faecium with the exception of two strains of E. faecalis which showed an additive effect of both drugs.

  3. The Impact of AUC-Based Monitoring on Pharmacist-Directed Vancomycin Dose Adjustments in Complicated Methicillin-Resistant Staphylococcus aureus Infection.

    PubMed

    Stoessel, Andrew M; Hale, Cory M; Seabury, Robert W; Miller, Christopher D; Steele, Jeffrey M

    2018-01-01

    This study aimed to assess the impact of area under the curve (AUC)-based vancomycin monitoring on pharmacist-initiated dose adjustments after transitioning from a trough-only to an AUC-based monitoring method at our institution. A retrospective cohort study of patients treated with vancomycin for complicated methicillin-resistant Staphylococcus aureus (MRSA) infection between November 2013 and December 2016 was conducted. The frequency of pharmacist-initiated dose adjustments was assessed for patients monitored via trough-only and AUC-based approaches for trough ranges: 10 to 14.9 mg/L and 15 to 20 mg/L. Fifty patients were included: 36 in the trough-based monitoring and 14 in the AUC-based-monitoring group. The vancomycin dose was increased in 71.4% of patients when troughs were 10 to 14.9 mg/L when a trough-only approach was used and in only 25% of patients when using AUC estimation ( P = .048). In the AUC group, the dose was increased only when AUC/minimum inhibitory concentration (MIC) <400; unchanged regimens had an estimated AUC/MIC ≥400. The AUC-based monitoring did not significantly increase the frequency of dose reductions when trough concentrations were 15 to 20 mg/L (AUC: 33.3% vs trough: 4.6%; P = .107). The AUC-based monitoring resulted in fewer patients with dose adjustments when trough levels were 10 to 14.9 mg/L. The AUC-based monitoring has the potential to reduce unnecessary vancomycin exposure and warrants further investigation.

  4. Is Vancomycine Still a Choice for Chronic Osteomyelitis Empirical Therapy in Iran?

    PubMed Central

    Izadi, Morteza; Zamani, Mohammad Mahdi; Mousavi, Seyed Ahmad; Sadat, Seyed Mir Mostafa; Siami, Zeinab; Vais Ahmadi, Noushin; Jonaidi Jafari, Nematollah; Shirvani, Shahram; Majidi Fard, Mojgan; Imani Fooladi, Abbas Ali

    2012-01-01

    Background Pyogenic bacteria and especially Staphylococcus aurous (S. aurous) are the most common cause of chronic osteomyelitis. Not only treatment protocol of chronic osteomyelitis occasionally is amiss but also this malady responds to treatment difficultly. Objectives This study investigates antibiotic resistance pattern of S. aurous isolated from Iranian patients who suffer from chronic osteomyelitis by two methods: disk diffusion (Kirby bauyer) and E-test (Epsilometer test) to find Vancomycin susceptibility and MIC (Minimum inhibitory concentration). Patients and Methods One hundred and thirty one patients who suffer from chronic osteomyelitis which have been referred to both governmental and private hospitals at 2010 were tried out for culturing of osteomyelitis site (sites). Antibiotic susceptibility and MIC of isolated bacteria were investigated by Kirby bauyer and E-test respectively. Results Samples were collected from bone (73.4%), surrounding tissue (14.6%) and wound discharge (12%). S. aureus was isolated from 49.6% of the samples. According to disc diffusion, methicillin resistance S. aureus (MRSA) was 75% and Vancomycin resistance S. aurous (VRSA) was 0% and based on MIC, MRSA was 68.5% and VRSA was 0%. According to MIC experiments, maximum sensitivity was against to Vancomycin (90.2%) and ciprofloxacin (54.4%) respectively but based on disc diffusion, maximum sensitivity was against to Vancomycin (97.7%) and ciprofloxacin (43.2%), respectively (P = 0.001). E-test (9.8%) in comparison with Disc diffusion (2.3%) showed higher percent of intermediate susceptibility to Vancomycin (P = 0.017). Conclusions Comparison of antibiograms and MICs showed that Kirby bauyer technique especially for detection of VISA strains is not reliable comparison with E-test. Already VRSA strains have not detected in Iranian chronic osteomyelitis, Thus Vancomycin is the first choice for chronic osteomyelitis empirical therapy in Iran yet. PMID:23483042

  5. Antimicrobial resistance status of Enterococcus from Australian cattle populations at slaughter.

    PubMed

    Barlow, Robert S; McMillan, Kate E; Duffy, Lesley L; Fegan, Narelle; Jordan, David; Mellor, Glen E

    2017-01-01

    Antimicrobial agents are used in cattle production systems for the prevention and control of bacterial associated diseases. A consequence of their use is the potential development of antimicrobial resistance (AMR). Enterococcus faecium and Enterococcus faecalis that are resistant to antimicrobials are of increased concern to public health officials throughout the world as they may compromise the ability of various treatment regimens to control disease and infection in human medicine. Australia is a major exporter of beef; however it does not have an ongoing surveillance system for AMR in cattle or foods derived from these animals. This study examined 910 beef cattle, 290 dairy cattle and 300 veal calf faecal samples collected at slaughter for the presence of enterococci. Enterococcus were isolated from 805 (88.5%) beef cattle faeces, 244 (84.1%) dairy cattle faeces and 247 (82.3%) veal calf faeces with a total of 800 enterococci subsequently selected for AMR testing. The results of AMR testing identified high levels of resistance to antimicrobials that are not critically or highly important to human medicine with resistance to flavomycin (80.2%) and lincomycin (85.4-94.2%) routinely observed. Conversely, resistance to antibiotics considered critically or highly important to human medicine such as tigecycline, daptomycin, vancomycin and linezolid was not present in this study. There is minimal evidence that Australian cattle production practices are responsible for disproportionate contributions to AMR development and in general resistance to antimicrobials of critical and high importance in human medicine was low regardless of the isolate source. The low level of antimicrobial resistance in Enterococcus from Australian cattle is likely to result from comprehensive controls around the use of antimicrobials in food-production animals in Australia. Nevertheless, continued monitoring of the effects of all antimicrobial use is required to support Australia's reputation

  6. Antimicrobial resistance status of Enterococcus from Australian cattle populations at slaughter

    PubMed Central

    McMillan, Kate E.; Duffy, Lesley L.; Fegan, Narelle; Jordan, David; Mellor, Glen E.

    2017-01-01

    Antimicrobial agents are used in cattle production systems for the prevention and control of bacterial associated diseases. A consequence of their use is the potential development of antimicrobial resistance (AMR). Enterococcus faecium and Enterococcus faecalis that are resistant to antimicrobials are of increased concern to public health officials throughout the world as they may compromise the ability of various treatment regimens to control disease and infection in human medicine. Australia is a major exporter of beef; however it does not have an ongoing surveillance system for AMR in cattle or foods derived from these animals. This study examined 910 beef cattle, 290 dairy cattle and 300 veal calf faecal samples collected at slaughter for the presence of enterococci. Enterococcus were isolated from 805 (88.5%) beef cattle faeces, 244 (84.1%) dairy cattle faeces and 247 (82.3%) veal calf faeces with a total of 800 enterococci subsequently selected for AMR testing. The results of AMR testing identified high levels of resistance to antimicrobials that are not critically or highly important to human medicine with resistance to flavomycin (80.2%) and lincomycin (85.4–94.2%) routinely observed. Conversely, resistance to antibiotics considered critically or highly important to human medicine such as tigecycline, daptomycin, vancomycin and linezolid was not present in this study. There is minimal evidence that Australian cattle production practices are responsible for disproportionate contributions to AMR development and in general resistance to antimicrobials of critical and high importance in human medicine was low regardless of the isolate source. The low level of antimicrobial resistance in Enterococcus from Australian cattle is likely to result from comprehensive controls around the use of antimicrobials in food-production animals in Australia. Nevertheless, continued monitoring of the effects of all antimicrobial use is required to support Australia

  7. Rapid identification of enterococci.

    PubMed Central

    Brown, L H; Peterson, E M; de la Maza, L M

    1983-01-01

    Enterococci were identified in 4 h with bile esculin agar and the Autobac system (General Diagnostics, Warner-Lambert Co., Morris Plains, N.J.), which was used to incubate and monitor salt broth for growth. Of 86 group D streptococci tested, 41 enterococci grew in salt broth and were bile esculin positive within 4 h; none of 45 group D nonenterococcal streptococci exhibited growth in the salt broth, and only 38 of them were bile esculin positive within 4 h. PMID:6403579

  8. “Slow VISA,” a Novel Phenotype of Vancomycin Resistance, Found In Vitro in Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Strain Mu3

    PubMed Central

    Saito, Michie; Katayama, Yuki; Hishinuma, Tomomi; Iwamoto, Akira; Aiba, Yoshifumi; Kuwahara-Arai, Kyoko; Cui, Longzhu; Matsuo, Miki; Aritaka, Nanae

    2014-01-01

    Heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) clinical strain Mu3 spontaneously generates VISA strains at an extremely high frequency (≥1 × 10−6). The generated VISA strains usually grow more slowly than does the parent hVISA strain, but they form colonies on vancomycin-containing agar plates before 48 h of incubation. However, we noticed a curious group of VISA strains, designated “slow VISA” (sVISA), whose colonies appear only after 72 h of incubation. They have extremely prolonged doubling times but have vancomycin MICs of 8 to ∼24 mg/liter when determined after 72 to ∼144 h of incubation. We established strain Mu3-6R-P (6R-P), which has a vancomycin MIC of 16 mg/liter (at 72 h), as a representative sVISA strain. Its cell wall was thickened and autolytic activity was decreased compared to the respective qualities of the parent hVISA strain Mu3. Whole-genome sequencing of 6R-P revealed only one mutation, encoded by rpoB (R512P), which replaced the 512th arginine of the RNA polymerase β-subunit with proline. Its VISA phenotype was unstable, and the strain frequently reverted to hVISA with concomitant losses of pinpoint colony morphology and cell wall thickness and reduced autolytic activity. Sequencing of the rpoB genes of the phenotypic revertant strains revealed mutations affecting the 512th codon, where the proline of 6R-P was replaced with leucine, serine, or histidine. Slow VISA generated in the tissues of an infected patient serves as a temporary shelter for hVISA to survive vancomycin therapy. The sVISA strain spontaneously returns to hVISA when the threat of vancomycin is lifted. The rpoB(R512P) mutation may be regarded as a regulatory mutation that switches the reversible phenotype of sVISA on and off. PMID:24841271

  9. Novel quercetin glycosides as potent anti-MRSA and anti-VRE agents.

    PubMed

    Hossion, Abugafar M L; Sasaki, Kenji

    2013-12-01

    Each year in the United States, at least 2 million people become infected with bacteria that are resistant to antibiotics and at least 23,000 people die each year as a direct result of these infections (Threat report 2013). Vancomycin is an FDA approved antibiotic and is growing importance in the treatment of hospital infections, with particular emphasis on its value to fight against methicillin-resistant Staphylococcus aureus (MRSA). The increasing use of vancomycin to treat infections caused by the Gram-positive MRSA in the 1970s selected for drug-resistant enterococci, less potent than staphylococci but opportunistic in the space vacated by other bacteria and in patients with compromised immune systems. The dramatic rise of antibiotic-resistant bacteria over the past two decades has stressed the need for completely novel classes of antibacterial agents. This paper reports the recent patent review on the strategy for finding novel quercetinglycoside type antibacterial agents against vancomycin-resistant bacterial strains.

  10. Linezolid versus Vancomycin in Treatment of Complicated Skin and Soft Tissue Infections

    PubMed Central

    Weigelt, John; Itani, Kamal; Stevens, Dennis; Lau, William; Dryden, Matthew; Knirsch, Charles

    2005-01-01

    Skin and soft tissue infections (SSTIs) are a common cause of morbidity in both the community and the hospital. An SSTI is classified as complicated if the infection has spread to the deeper soft tissues, if surgical intervention is necessary, or if the patient has a comorbid condition hindering treatment response (e.g., diabetes mellitus or human immunodeficiency virus). The purpose of this study was to compare linezolid to vancomycin in the treatment of suspected or proven methicillin-resistant gram-positive complicated SSTIs (CSSTIs) requiring hospitalization. This was a randomized, open-label, comparator-controlled, multicenter, multinational study that included patients with suspected or proven methicillin-resistant Staphylococcus aureus (MRSA) infections that involved substantial areas of skin or deeper soft tissues, such as cellulitis, abscesses, infected ulcers, or burns (<10% of total body surface area). Patients were randomized (1:1) to receive linezolid (600 mg) every 12 h either intravenously (i.v.) or orally or vancomycin (1 g) every 12 h i.v. In the intent-to-treat population, 92.2% and 88.5% of patients treated with linezolid and vancomycin, respectively, were clinically cured at the test-of-cure (TOC) visit (P = 0.057). Linezolid outcomes (124/140 patients or 88.6%) were superior to vancomycin outcomes (97/145 patients or 66.9%) at the TOC visit for patients with MRSA infections (P < 0.001). Drug-related adverse events were reported in similar numbers in both the linezolid and the vancomycin arms of the trial. The results of this study demonstrate that linezolid therapy is well tolerated, equivalent to vancomycin in treating CSSTIs, and superior to vancomycin in the treatment of CSSTIs due to MRSA. PMID:15917519

  11. Phenotypic and genotypic characterization of vancomycin-resistant Enterococcus faecium clinical isolates from two hospitals in Mexico: First detection of VanB phenotype-vanA genotype.

    PubMed

    Bocanegra-Ibarias, Paola; Flores-Treviño, Samantha; Camacho-Ortiz, Adrián; Morfin-Otero, Rayo; Villarreal-Treviño, Licet; Llaca-Díaz, Jorge; Martínez-Landeros, Erik Alan; Rodríguez-Noriega, Eduardo; Calzada-Güereca, Andrés; Maldonado-Garza, Héctor Jesús; Garza-González, Elvira

    2016-01-01

    Enterococcus faecium has emerged as a multidrug-resistant nosocomial pathogen involved in outbreaks worldwide. Our aim was to determine the antimicrobial susceptibility, biofilm production, and clonal relatedness of vancomycin-resistant E. faecium (VREF) clinical isolates from two hospitals in Mexico. Consecutive clinical isolates (n=56) were collected in two tertiary care hospitals in Mexico from 2011 to 2014. VREF isolates were characterized by phenotypic and molecular methods including pulsed-field gel electrophoresis (PFGE). VREF isolates were highly resistant to vancomycin, erythromycin, norfloxacin, high-level streptomycin, and teicoplanin, and showed lower resistance to tetracycline, nitrofurantoin and quinupristin-dalfopristin. None of the isolates were resistant to linezolid. The vanA gene was detected in all isolates. Two VanB phenotype-vanA genotype isolates, highly resistant to vancomycin and susceptible to teicoplanin, were detected. Furthermore, 17.9% of the isolates were classified as biofilm producers, and the espfm gene was found in 98.2% of the isolates. A total of 37 distinct PFGE patterns and 6 clones (25% of the isolates as clone A, 5.4% as clone B, and 3.6% each as clone C, D, E, and F) were detected. Clone A was detected in 5 different wards of the same hospital during 14 months of surveillance. The high resistance to most antimicrobial agents and the moderate cross-transmission of VREF detected accentuates the need for continuous surveillance of E. faecium in the hospital setting. This is also the first reported incidence of the E. faecium VanB phenotype-vanA genotype in the Americas. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  12. Evaluation of contact precautions for methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus.

    PubMed

    Bardossy, Ana Cecilia; Alsafadi, Muhammad Yasser; Starr, Patricia; Chami, Eman; Pietsch, Jennifer; Moreno, Daniela; Johnson, Laura; Alangaden, George; Zervos, Marcus; Reyes, Katherine

    2017-12-01

    There are limited controlled data demonstrating contact precautions (CPs) prevent methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) infections in endemic settings. We evaluated changes in hospital-acquired MRSA and VRE infections after discontinuing CPs for these organisms. This is a retrospective study done at an 800-bed teaching hospital in urban Detroit. CPs for MRSA and VRE were discontinued hospital-wide in 2013. Data on MRSA and VRE catheter-associated urinary tract infections (CAUTIs), ventilator-associated pneumonia (VAP), central line-associated bloodstream infections (CLABSIs), surgical site infections (SSIs), and hospital-acquired MRSA bacteremia (HA-MRSAB) rates were compared before and after CPs discontinuation. There were 36,907 and 40,439 patients hospitalized during the two 12-month periods: CPs and no CPs. Infection rates in the CPs and no-CPs periods were as follows: (1) MRSA infections: VAP, 0.13 versus 0.11 (P = .84); CLABSI, 0.11 versus 0.19 (P = .45); SSI, 0 versus 0.14 (P = .50); and CAUTI, 0.025 versus 0.033 (P = .84); (2) VRE infections: CAUTI, 0.27 versus 0.13 (P = .19) and CLABSI, 0.29 versus 0.3 (P = .94); and (3) HA-MRSAB rates: 0.14 versus 0.11 (P = .55), respectively. Discontinuation of CPs did not adversely impact endemic MRSA and VRE infection rates. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  13. ANTIBACTERIAL ACTIVITY OF BONE ALLOGRAFTS: COMPARISON OF A NEW VANCOMYCIN-TETHERED ALLOGRAFT WITH ALLOGRAFT LOADED WITH ADSORBED VANCOMYCIN

    PubMed Central

    Ketonis, Constantinos; Barr, Stephanie; Shapiro, Irving M.; Parvizi, Javad; Adams, Christopher S.; Hickok, Noreen J.

    2010-01-01

    Bacterial contamination of bone allograft is a significant complication of orthopaedic surgery. To address this issue, we have engineered a method for covalently modifying bone allograft tissue with the antibiotic vancomycin. The goal of this investigation was to compare the biocidal properties of this new allograft material with those of vancomycin physisorbed onto graft material. The duration of antibiotic release from the vancomycin-modified allograft matrix was determined and no elution was observed. In contrast, the adsorbed antibiotic showed a peak elution at 24 h that then decreased over several days. We next used an S. aureus disk diffusion assay to measure the activity of the eluted vancomycin. Again we found that no active antibiotic was eluted from the covalently–modified allograft. Similarly, when the vancomycin-modified allograft morsel was used in the assay, no measurable elution was observed; amounts of antibiotic released from the adsorbed samples inhibited S. aureus growth for 4-7 days. Probably the most telling property of the allograft was that after two weeks, the tethered-allograft was able to resist bacterial colonization. Unlike the elution system in which vancomycin was depleted over the course of days-weeks, the antibiotic on the allograft was stably bound even after 300 days, while its biocidal activity remained undiminished for 60 days. This finding was in stark contrast to the antibiotic impregnated allograft which was readily colonized by bacteria. Finally we chose to evaluate three indicators of cell function: expression of a key transcription factor, expression of selected transcripts, and assessment of cell morphology. Since the tethered antibiotic appeared to have little or no effect on any of these activities, it was concluded that the stable, tethered antibiotic prevented bacterial infection while not modifying bone cell function. PMID:21035576

  14. Prevalence and antibiotic resistance of Enterococcus strains isolated from poultry.

    PubMed

    Stępień-Pyśniak, Dagmara; Marek, Agnieszka; Banach, Tomasz; Adaszek, Łukasz; Pyzik, Ewelina; Wilczyński, Jarosław; Winiarczyk, Stanisław

    2016-06-01

    The aim of this study was to evaluate the frequency of occurrence of bacteria of the genus Enterococcus in poultry, to identify them by means of matrixassisted laser desorption/ionisation time-of-flight mass spectrometry (MALDITOF MS), and to analyse the antimicrobial susceptibility of the isolated strains to the drugs most frequently used in poultry. The material for the bacteriological tests was obtained mainly from the heart (97%) of the birds investigated. Of a total of 2,970 samples tested, 911 (30.7%) tested positive for Enterococcus spp. Enterococci were detected in broilers (88.1%), laying hens (5.3%), turkeys (3.9%), breeding hens (2.2%), and geese (0.4%). The most commonly identified species were Enterococcus (E.) faecalis (74.7%), E. faecium (10.1%), E. gallinarum (5.5%), E. hirae (4.6%), and E. cecorum (4.1%). The most frequent resistance properties were resistance to sulphamethoxazole/trimethoprim (88%), tylosin (71.4%), enrofloxacin (69.4%), doxycycline (67.3%), and lincomycin/spectinomycin (56.1%). Only one vancomycin-resistant Enterococcus, E. cecorum from a broiler, was found.

  15. The evolution of vancomycin intermediate Staphylococcus aureus (VISA) and heterogenous-VISA.

    PubMed

    Howden, Benjamin P; Peleg, Anton Y; Stinear, Timothy P

    2014-01-01

    Resistance to new antimicrobials is generally recognized in Staphylococcus aureus soon after they are released for clinical use. In the case of vancomycin, which was first released in the 1950s, resistance was not reported until the mid 1990s, with the description of vancomycin-intermediate S. aureus (VISA), and heterogenous-VISA (hVISA). Unraveling the complex genetic and cell wall structural changes conferring low-level vancomycin resistance in S. aureus has proved challenging. However the recent advances in high throughput whole-genome sequencing has played a key role in determining the breadth of bacterial chromosomal changes linked with resistance. Diverse mutations in a small number of staphylococcal regulatory genes, in particular walKR, graRS, vraSR and rpoB, have been associated with hVISA and VISA. Only a small number of these mutations have been experimentally proven to confer the resistance phenotype and some of these only partially contribute to resistance. It also appears that the evolution of VISA from VSSA is a step-wise process. Transcriptomics studies, and analysis of host pathogen interactions, indicate that the evolution of vancomycin-susceptible S. aureus to VISA is associated not only with antibiotic resistance, but with other changes likely to promote persistent infection. These include predicted alterations in central metabolism, altered expression of virulence associated factors, attenuated virulence in vivo, and alterations in susceptibility to host innate immune responses, together with reduced susceptibility to other antibiotics. In fact, current data suggests that hVISA and VISA represent a bacterial evolutionary state favoring persistence in the face of not only antibiotics, but also the host environment. The additional knowledge of staphylococcal biology that has been uncovered during the study of hVISA and VISA is significant. The present review will detail the current understanding of the evolutionary process in the generation of h

  16. Clearance of Vancomycin-Resistant Enterococcus Concomitant With Administration of a Microbiota-Based Drug Targeted at Recurrent Clostridium difficile Infection.

    PubMed

    Dubberke, Erik R; Mullane, Kathleen M; Gerding, Dale N; Lee, Christine H; Louie, Thomas J; Guthertz, Harriet; Jones, Courtney

    2016-09-01

    Background.  Vancomycin-resistant Enterococcus (VRE) is a major healthcare-associated pathogen and a well known complication among transplant and immunocompromised patients. We report on stool VRE clearance in a post hoc analysis of the Phase 2 PUNCH CD study assessing a microbiota-based drug for recurrent Clostridium difficile infection (CDI). Methods.  A total of 34 patients enrolled in the PUNCH CD study received 1 or 2 doses of RBX2660 (microbiota suspension). Patients were requested to voluntarily submit stool samples at baseline and at 7, 30, and 60 days and 6 months after the last administration of RBX2660. Stool samples were tested for VRE using bile esculin azide agar with 6 µg/mL vancomycin and Gram staining. Vancomycin resistance was confirmed by Etest. Results.  VRE status (at least 1 test result) was available for 30 patients. All stool samples for 19 patients (63.3%, mean age 61.7 years, 68% female) tested VRE negative. Eleven patients (36.7%, mean age 75.5 years, 64% female) were VRE positive at the first test (baseline or 7-day follow-up). Of these patients, 72.7%, n = 8 converted to negative as of the last available follow-up (30 or 60 days or 6 months). Of the other 3: 1 died (follow-up data not available); 1 patient remained positive at all follow-ups; 1 patient retested positive at 6 months with negative tests during the interim. Conclusions.  Although based on a small sample size, this secondary analysis demonstrated the possibility of successfully converting a high percentage of VRE-positive patients to negative in a recurrent CDI population with RBX2660.

  17. Antimicrobial susceptibility testing of a clinical isolate of vancomycin-dependent enterococcus using D-alanine-D-alanine as a growth supplement.

    PubMed

    Sng, L H; Cornish, N; Knapp, C C; Ludwig, M D; Hall, G S; Washington, J A

    1998-04-01

    Bacteremia due to a vancomycin-dependent enterococcus (VDE) occurred during long-term vancomycin therapy in a renal transplant recipient with underlying pancreatitis and a vancomycin-resistant enterococcal (VRE) wound infection and bacteremia. The VDE was isolated from blood during vancomycin therapy and grew only in the presence of vancomycin and D-alanine-D-alanine (DADA), a substance required for cell-wall synthesis. Colonies beyond the periphery of growth of the VDE around a vancomycin disk contained vancomycin-independent revertant mutants after 48 hours of incubation. Pulsed-field gel electrophoresis of the VDE, revertant mutant, the initial blood culture isolate of VRE, and an autopsy isolate showed that the four strains were identical. Antimicrobial susceptibility testing was performed using standard macrobroth and microbroth dilution methods. DADA was used as a growth supplement for macrobroth dilution susceptibility testing of the VDE isolate. Minimum inhibitory concentrations (MICs) were similar for the VRE isolate and the VDE revertant, which were both resistant to ampicillin, high-level gentamicin, ciprofloxacin, imipenem, vancomycin, and daptomycin, and were susceptible to fusidic acid, high-level streptomycin, rifampin, and a quinupristin-dalfopristin combination. The MICs of teicoplanin were 2 microg/mL or less and 16 microg/mL for the clinical VRE isolate and the VDE revertant, respectively. The autopsy isolate was resistant to all antimicrobials tested and showed a fourfold increase in MICs for quinupristin-dalfopristin compared with that of the original blood isolate. The VDE was susceptible to all drugs tested except vancomycin.

  18. Antimicrobial resistance and virulence profile of enterococci isolated from poultry and cattle sources in Nigeria.

    PubMed

    Ngbede, Emmanuel Ochefije; Raji, Mashood Abiola; Kwanashie, Clara Nna; Kwaga, Jacob Kwada Paghi

    2017-03-01

    This study investigated the occurrence, antimicrobial resistance and virulence of Enterococcus from poultry and cattle farms. Three hundred and ninety samples: cloacal/rectal swabs (n = 260) and manure (n = 130] were processed for recovery of Enterococcus species. Standard bacteriological methods were used to isolate, identify and characterize Enterococcus species for antimicrobial susceptibility and expression of virulence traits. Detection of antibiotic resistance and virulence genes was carried out by polymerase chain reaction. Enterococcus was recovered from 167 (42.8%) of the 390 samples tested with a predominance of Enterococcus faecium (27.7%). Other species detected were Enterococcus gallinarum, Enterococcus faecalis, Enterococcus hirae, Enterococcus raffinosus, Enterococcus avium, Enterococcus casseliflavus, Enterococcus mundtii and Enterococcus durans. All the isolates tested were susceptible to vancomycin, but resistance to tetracycline, erythromycin, ampicillin and gentamicin was also observed among 61.0, 61.0, 45.1 and 32.7% of the isolates, respectively. Sixty (53.1%) of the isolates were multidrug resistant presenting as 24 different resistance patterns with resistance to gentamicin-erythromycin-streptomycin-tetracycline (CN-ERY-STR-TET) being the most common (n = 11) pattern. In addition to expression of virulence traits (haemolysin, gelatinase, biofilm production), antibiotic resistance (tetK, tetL, tetM, tetO and ermB) and virulence (asa1, gelE, cylA) genes were detected among the isolates. Also, in vitro transfer of resistance determinants was observed among 75% of the isolates tested. Our data revealed poultry, cattle and manure in this area are hosts to varying Enterococcus species harbouring virulence and resistance determinants that can be transferred to other organisms and also are important for causing nosocomial infection.

  19. Complete Genome Sequence of Staphylococcus aureus XN108, an ST239-MRSA-SCCmec III Strain with Intermediate Vancomycin Resistance Isolated in Mainland China

    PubMed Central

    Zhang, Xia; Xu, Xiaomeng; Yuan, Wenchang; Hu, Qiwen; Shang, Weilong; Hu, Xiaomei

    2014-01-01

    ST239-MRSA-SCCmec III (ST239, sequence type 239; MRSA, methicillin-resistant Staphylococcus aureus; SCCmec III, staphylococcal cassette chromosome mec type III) is the most predominant clone of hospital-acquired methicillin-resistant S. aureus in mainland China. We report here the complete genome sequence of XN108, the first vancomycin-intermediate S. aureus strain isolated from a steam-burned patient with a wound infection. PMID:25059856

  20. Inhibition of Staphylococcus epidermidis biofilms using polymerizable vancomycin derivatives.

    PubMed

    Lawson, McKinley C; Hoth, Kevin C; Deforest, Cole A; Bowman, Christopher N; Anseth, Kristi S

    2010-08-01

    Biofilm formation on indwelling medical devices is a ubiquitous problem causing considerable patient morbidity and mortality. In orthopaedic surgery, this problem is exacerbated by the large number and variety of material types that are implanted. Metallic hardware in conjunction with polymethylmethacrylate (PMMA) bone cement is commonly used. We asked whether polymerizable derivatives of vancomycin might be useful to (1) surface modify Ti-6Al-4V alloy and to surface/bulk modify PMMA bone cement to prevent Staphylococcus epidermidis biofilm formation and (2) whether the process altered the compressive modulus, yield strength, resilience, and/or fracture strength of cement copolymers. A Ti-6Al-4V alloy was silanized with methacryloxypropyltrimethoxysilane in preparation for subsequent polymer attachment. Surfaces were then coated with polymers formed from PEG(375)-acrylate or a vancomycin-PEG(3400)-PEG(375)-acrylate copolymer. PMMA was loaded with various species, including vancomycin and several polymerizable vancomycin derivatives. To assess antibiofilm properties of these materials, initial bacterial adherence to coated Ti-6Al-4V was determined by scanning electron microscopy (SEM). Biofilm dry mass was determined on PMMA coupons; the compressive mechanical properties were also determined. SEM showed the vancomycin-PEG(3400)-acrylate-type surface reduced adherent bacteria numbers by approximately fourfold when compared with PEG(375)-acrylate alone. Vancomycin-loading reduced all mechanical properties tested; in contrast, loading a vancomycin-acrylamide derivative restored these deficits but demonstrated no antibiofilm properties. A polymerizable, PEGylated vancomycin derivative reduced biofilm attachment but resulted in inferior cement mechanical properties. The approaches presented here may offer new strategies for developing biofilm-resistant orthopaedic materials. Specifically, polymerizable derivatives of traditional antibiotics may allow for direct

  1. Significance and survival of Enterococci during the house fly development.

    PubMed

    Ghosh, Anuradha; Akhtar, Mastura; Holderman, Chris; Zurek, Ludek

    2014-01-01

    House flies are among the most important nonbiting insect pests of medical and veterinary importance. Larvae develop in decaying organic substrates and their survival strictly depends on an active microbial community. House flies have been implicated in the ecology and transmission of enterococci, including multi-antibiotic-resistant and virulent strains of Enterococcus faecalis. In this study, eight American Type Culture Collection type strains of enterococci including Enterococcus avium, Enterococcus casseliflavus, Enterococcus durans, Enterococcus hirae, Enterococcus mundtii, Enterococcus gallinarum, Enterococcusfaecalis, and Enterococcusfaecium were evaluated for their significance in the development of house flies from eggs to adults in bacterial feeding assays. Furthermore, the bacterial colonization of the gut of teneral flies as well as the importance of several virulence traits of E. faecalis in larval mortality was assessed. Overall survival of house flies (egg to adult) was significantly higher when grown with typically nonpathogenic enterococcal species such as E. hirae (76.0% survival), E. durans (64.0%), and E. avium (64.0%) compared with that with clinically important species E. faecalis (24.0%) and E. faecium (36.0%). However, no significant differences in survival of house fly larvae were detected when grown with E. faecalis strains carrying various virulence traits, including isogenic mutants of the human clinical isolate E. faecalis V583 with in-frame deletions of gelatinase, serine protease, and capsular polysaccharide serotype C. Enterococci were commonly detected in fly puparia (range: 75-100%; concentration: 103-105 CFU/puparium);however, the prevalence of enterococci in teneral flies varied greatly: from 25.0 (E. casseliflavus) to 89.5% (E. hirae). In conclusion, depending on the species, enterococci variably support house fly larval development and colonize the gut of teneral adults. The human pathogenic species, E. faecalis and E. faecium

  2. Population Pharmacokinetics of Vancomycin in Patients Undergoing Allogeneic Hematopoietic Stem-Cell Transplantation.

    PubMed

    Okada, Akira; Kariya, Misato; Irie, Kei; Okada, Yutaka; Hiramoto, Nobuhiro; Hashimoto, Hisako; Kajioka, Ryosuke; Maruyama, Chika; Kasai, Hidefumi; Hamori, Mami; Nishimura, Asako; Shibata, Nobuhito; Fukushima, Keizo; Sugioka, Nobuyuki

    2018-05-15

    Vancomycin is a commonly used antimicrobial agent for patients undergoing allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Vancomycin has large inter- and intraindividual pharmacokinetic variability, which is mainly described by renal function; various studies have indicated that vancomycin pharmacokinetics are altered in special populations. However, little is known regarding vancomycin pharmacokinetics in patients undergoing allo-HSCT. Therefore, we aimed to develop a population pharmacokinetic (PopPK) model of vancomycin in patients undergoing allo-HSCT for effective and safe antimicrobial therapy and to develop a vancomycin dosing nomogram for a vancomycin optimal-dosing strategy. In total, 285 observations from 95 patients undergoing allo-HSCT were available. The final PopPK parameter estimates were central volume of distribution (V1, L), 39.2; clearance (L/h), 4.25; peripheral volume of distribution (V2, L), 56.1; and intercompartmental clearance (L/h), 1.95. The developed vancomycin model revealed an increase in V1 and V2 compared with those in the general population that consisted of patients with methicillin-resistant Staphylococcus aureus. Moreover, serum creatinine was reduced because of an increase in the plasma fraction because of destruction of hematopoietic stem cells accompanying allo-HSCT pretreatment, suggesting that the Cockcroft-Gault equation-based creatinine clearance value was overestimated. To our knowledge, this is the first PopPK study to develop a dosing nomogram for vancomycin in patients undergoing allo-HSCT and was proven to be useful in optimizing the dosage and dosing interval of vancomycin in these patients. This strategy will provide more useful information for vancomycin therapy with an evidence-based dose adjustment. © 2018, The American College of Clinical Pharmacology.

  3. Nosocomial infections and fever of unknown origin in pediatric hematology/oncology unit: a retrospective annual study.

    PubMed

    Al-Tonbary, Youssef A; Soliman, Othman E; Sarhan, Mohammed M; Hegazi, Moustafa A; El-Ashry, Rasha A; El-Sharkawy, Ashraf A; Salama, Osama S; Yahya, Raida

    2011-02-01

    pediatric hematology/oncology patients are faced with an increased risk of nosocomial infections (NIs) that vary in different populations and different institutions with considerable morbidity and mortality. This study was undertaken to assess the frequency and patterns of NIs in 1564 pediatric patients and to determine the prevalence of causative organisms and their antimicrobial sensitivity. a retrospective analysis was made in the patients admitted between January 2007 and January 2008 to the pediatric hematoloy/oncology unit of Mansoura University, Egypt. The 1564 patients showed 2084 admissions and 27 092 inpatient days. The Centers for Disease Control and Prevention criteria were used as a standard definition for NI. the overall rate of NIs in all patients and neutropenic patients was 8.6 and 25.3 per 1000 patient-days respectively. The frequent sites of NIs were blood stream (42.7%), the respiratory system (25.3%), the urinary system (22.2%) and the central nervous system (9.8%), whereas nosocomial fever of unknown origin constituted 52.9% of cases. The incidence of NIs was significantly higher during neutropenic days (P<0.001). Gram-positive organisms represented 64.5% of pathogens (Staphylococci 71.5%, Streptococci 16%, and pneumococci 7%), and Gram-negative organisms represented 30% (E. coli 48.6%, Klebsiella 15.7%, Pseudomonas 35.7%, and C. albicans 5.5%). Positive cultures were more frequent in summer (July to September). Susceptibility of isolated organisms was relatively low (cefoperazone/sulbactam 49.9%, amikacin 35.9%, imipenem/cilastin 34.4%, cefoperazone 33.6%, and vancomycin 36.5%). Methicillin-resistant S. aureus, extended spectrum beta lactamase and vancomycin resistant enterococci represented 30%, 45% and 75% of isolated S. aureus, Gram-negative organisms and Enterococci, respectively. blood stream infection and fever of unknown origin are the most common nosocomial infections in pediatric hematology/oncology patients with a higher risk during

  4. Mobile phones and computer keyboards: unlikely reservoirs of multidrug-resistant organisms in the tertiary intensive care unit.

    PubMed

    Smibert, O C; Aung, A K; Woolnough, E; Carter, G P; Schultz, M B; Howden, B P; Seemann, T; Spelman, D; McGloughlin, S; Peleg, A Y

    2018-03-02

    Few studies have used molecular epidemiological methods to study transmission links to clinical isolates in intensive care units. Ninety-four multidrug-resistant organisms (MDROs) cultured from routine specimens from intensive care unit (ICU) patients over 13 weeks were stored (11 meticillin-resistant Staphylococcus aureus (MRSA), two vancomycin-resistant enterococci and 81 Gram-negative bacteria). Medical staff personal mobile phones, departmental phones, and ICU keyboards were swabbed and cultured for MDROs; MRSA was isolated from two phones. Environmental and patient isolates of the same genus were selected for whole genome sequencing. On whole genome sequencing, the mobile phone isolates had a pairwise single nucleotide polymorphism (SNP) distance of 183. However, >15,000 core genome SNPs separated the mobile phone and clinical isolates. In a low-endemic setting, mobile phones and keyboards appear unlikely to contribute to hospital-acquired MDROs. Copyright © 2018 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  5. Contribution of Sand-Associated Enterococci to Dry Weather Water Quality

    PubMed Central

    2015-01-01

    Culturable enterococci and a suite of environmental variables were collected during a predominantly dry summer at a beach impacted by nonpoint source pollution. These data were used to evaluate sands as a source of enterococci to nearshore waters, and to assess the relationship between environmental factors and dry-weather enterococci abundance. Best-fit multiple linear regressions used environmental variables to explain more than half of the observed variation in enterococci in water and dry sands. Notably, during dry weather the abundance of enterococci in dry sands at the mean high-tide line was significantly positively related to sand moisture content (ranging from <1–4%), and the daily mean ENT in water could be predicted by a linear regression with turbidity alone. Temperature was also positively correlated with ENT abundance in this study, which may indicate an important role of seasonal warming in temperate regions. Inundation by spring tides was the primary rewetting mechanism that sustained culturable enterococci populations in high-tide sands. Tidal forcing modulated the abundance of enterococci in the water, as both turbidity and enterococci were elevated during ebb and flood tides. The probability of samples violating the single-sample maximum was significantly greater when collected during periods with increased tidal range: spring ebb and flood tides. Tidal forcing also affected groundwater mixing zones, mobilizing enterococci from sand to water. These data show that routine monitoring programs using discrete enterococci measurements may be biased by tides and other environmental factors, providing a flawed basis for beach closure decisions. PMID:25479559

  6. Contribution of sand-associated enterococci to dry weather water quality.

    PubMed

    Halliday, Elizabeth; Ralston, David K; Gast, Rebecca J

    2015-01-06

    Culturable enterococci and a suite of environmental variables were collected during a predominantly dry summer at a beach impacted by nonpoint source pollution. These data were used to evaluate sands as a source of enterococci to nearshore waters, and to assess the relationship between environmental factors and dry-weather enterococci abundance. Best-fit multiple linear regressions used environmental variables to explain more than half of the observed variation in enterococci in water and dry sands. Notably, during dry weather the abundance of enterococci in dry sands at the mean high-tide line was significantly positively related to sand moisture content (ranging from <1-4%), and the daily mean ENT in water could be predicted by a linear regression with turbidity alone. Temperature was also positively correlated with ENT abundance in this study, which may indicate an important role of seasonal warming in temperate regions. Inundation by spring tides was the primary rewetting mechanism that sustained culturable enterococci populations in high-tide sands. Tidal forcing modulated the abundance of enterococci in the water, as both turbidity and enterococci were elevated during ebb and flood tides. The probability of samples violating the single-sample maximum was significantly greater when collected during periods with increased tidal range: spring ebb and flood tides. Tidal forcing also affected groundwater mixing zones, mobilizing enterococci from sand to water. These data show that routine monitoring programs using discrete enterococci measurements may be biased by tides and other environmental factors, providing a flawed basis for beach closure decisions.

  7. Modulating activity of vancomycin and daptomycin on the expression of autolysis cell-wall turnover and membrane charge genes in hVISA and VISA strains.

    PubMed

    Cafiso, Viviana; Bertuccio, Taschia; Spina, Daniela; Purrello, Simona; Campanile, Floriana; Di Pietro, Cinzia; Purrello, Michele; Stefani, Stefania

    2012-01-01

    Glycopeptides are still the gold standard to treat MRSA (Methicillin Resistant Staphylococcus aureus) infections, but their widespread use has led to vancomycin-reduced susceptibility [heterogeneous Vancomycin-Intermediate-Staphylococcus aureus (hVISA) and Vancomycin-Intermediate-Staphylococcus aureus (VISA)], in which different genetic loci (regulatory, autolytic, cell-wall turnover and cell-envelope positive charge genes) are involved. In addition, reduced susceptibility to vancomycin can influence the development of resistance to daptomycin. Although the phenotypic and molecular changes of hVISA/VISA have been the focus of different papers, the molecular mechanisms responsible for these different phenotypes and for the vancomycin and daptomycin cross-resistance are not clearly understood. The aim of our study was to investigate, by real time RT-PCR, the relative quantitative expression of genes involved in autolysis (atl-lytM), cell-wall turnover (sceD), membrane charges (mprF-dltA) and regulatory mechanisms (agr-locus-graRS-walKR), in hVISA and VISA cultured with or without vancomycin and daptomycin, in order to better understand the molecular basis of vancomycin-reduced susceptibility and the modulating activity of vancomycin and daptomycin on the expression of genes implicated in their reduced susceptibility mechanisms. Our results show that hVISA and VISA present common features that distinguish them from Vancomycin-Susceptible Staphylococcus aureus (VSSA), responsible for the intermediate glycopeptide resistance i.e. an increased cell-wall turnover, an increased positive cell-wall charge responsible for a repulsion mechanism towards vancomycin and daptomycin, and reduced agr-functionality. Indeed, VISA emerges from hVISA when VISA acquires a reduced autolysis caused by a down-regulation of autolysin genes, atl/lytM, and a reduction of the net negative cell-envelope charge via dltA over-expression. Vancomycin and daptomycin, acting in a similar manner in h

  8. Biocide and antibiotic resistance of Enterococcus faecalis and Enterococcus faecium isolated from the swine meat chain.

    PubMed

    Rizzotti, Lucia; Rossi, Franca; Torriani, Sandra

    2016-12-01

    In this study nine strains of Enterococcus faecalis and 12 strains of Enterococcus faecium, isolated from different sample types in the swine meat chain and previously characterized for the presence of antibiotic resistance genes, were examined for phenotypic tolerance to seven biocides (chlorexidine, benzalkonium chloride, triclosan, sodium hypochlorite, 2-propanol, formaldehyde and hydrogen peroxide) and resistance to nine antibiotics (ampicillin, vancomycin, gentamicin, kanamycin, streptomycin, erythromycin, clindamycin, tetracycline and chloramphenicol). Moreover, the presence of efflux system encoding genes qacA/B, qacC, qacE, qacEΔ1, emeA, and stress response genes, sigV and gsp65, involved in the tolerance to biocides, was analysed. Most strains were not tolerant to the biocides, but showed minimum inhibitory concentrations (MICs) higher than the recommended cut-off values for all the antibiotics tested, except for vancomycin and chloramphenicol. Only weak correlations, if any, were found between biocide and antibiotic resistance data. One E. faecalis strain was tolerant to triclosan and one E. faecium strain, with higher tolerance to chlorexidine than the other strains tested, was found to carry a qacA/B gene. Our results indicated that phenotypic resistance to antibiotics is very frequent in enterococcal isolates from the swine meat chain, but phenotypic tolerance to biocides is not common. On the other hand, the gene qacA/B was found for the first time in the species E. faecium, an indication of the necessity to adopt measures suitable to control the spread of biocide resistance determinants among enterococci. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. The silver lining of disposable sporicidal privacy curtains in an intensive care unit.

    PubMed

    Kotsanas, Despina; Wijesooriya, W R P L I; Sloane, Tracy; Stuart, Rhonda L; Gillespie, Elizabeth E

    2014-04-01

    The environment is a well-known source of health care-acquired infection. Because of the known risk of contamination, patient privacy curtains require frequent changes to decrease the risk of spread from patients to curtain and visa versa. Fourteen disposable sporicidal privacy curtains were tested from December 2012 to June 2013 while hanging in a busy intensive care unit. Significant bacterial pathogens were identified and total bacteria enumerated as colony-forming units. Antimicrobial activity of curtain swatches was also tested against a range of bacteria in the laboratory. Measurements were recorded as zone of inhibition and contact inhibition. A cost analysis to replace standard curtains with disposable sporicidal curtains was also undertaken. Cultures grew low numbers of skin and environmental microorganisms with no methicillin-resistant Staphylococcus aureus, carbapenem-resistant Enterobacteriaceae, or Clostridium difficile detected. Vancomycin-resistant enterococci were recovered in very low numbers from 2 curtains where vancomycin-resistant enterococci-infected patients had been located. Privacy curtains demonstrated antimicrobial activity against C difficile and 13 additional bacterial pathogens. We conclude that disposable sporicidal privacy curtains are cost-effective and best replaced at 6 months in a high-risk area such as an intensive care unit. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

  10. Identification of Low-Level Vancomycin Resistance in Staphylococcus aureus in the Era of Informatics.

    PubMed

    Ford, Bradley A

    2016-04-01

    Vancomycin-intermediateStaphylococcus aureus(VISA) and heteroresistant VISA (hVISA) are pathogens for which accurate antimicrobial susceptibility testing (AST) would rule out standard treatment with vancomycin. Unfortunately, AST for vancomycin is relatively slow and standard methods are unable to reliably detect VISA and hVISA. An article in this issue (C. A. Mather, B. J. Werth, S. Sivagnanam, D. J. SenGupta, and S. M. Butler-Wu, J Clin Microbiol 54:883-890, 2016, doi:http://dx.doi.org/10.1128/JCM.02428-15) describes a rapid whole-cell matrix-assisted laser desorption ionization-time of flight proxy susceptibility method that highlights current innovations and challenges with rapid AST, VISA/hVISA identification, and clinical bioinformatics. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  11. Extracellular DNA Impedes the Transport of Vancomycin in Staphylococcus epidermidis Biofilms Preexposed to Subinhibitory Concentrations of Vancomycin

    PubMed Central

    Tseng, Boo Shan; Howlin, Robert P.; Deacon, Jill; Wharton, Julian A.; Thurner, Philipp J.; Gilmore, Brendan F.; Parsek, Matthew R.; Stoodley, Paul

    2014-01-01

    Staphylococcus epidermidis biofilm formation is responsible for the persistence of orthopedic implant infections. Previous studies have shown that exposure of S. epidermidis biofilms to sub-MICs of antibiotics induced an increased level of biofilm persistence. BODIPY FL-vancomycin (a fluorescent vancomycin conjugate) and confocal microscopy were used to show that the penetration of vancomycin through sub-MIC-vancomycin-treated S. epidermidis biofilms was impeded compared to that of control, untreated biofilms. Further experiments showed an increase in the extracellular DNA (eDNA) concentration in biofilms preexposed to sub-MIC vancomycin, suggesting a potential role for eDNA in the hindrance of vancomycin activity. Exogenously added, S. epidermidis DNA increased the planktonic vancomycin MIC and protected biofilm cells from lethal vancomycin concentrations. Finally, isothermal titration calorimetry (ITC) revealed that the binding constant of DNA and vancomycin was 100-fold higher than the previously reported binding constant of vancomycin and its intended cellular d-Ala-d-Ala peptide target. This study provides an explanation of the eDNA-based mechanism of antibiotic tolerance in sub-MIC-vancomycin-treated S. epidermidis biofilms, which might be an important factor for the persistence of biofilm infections. PMID:25267673

  12. Synthesis and study of antibacterial activities of antibacterial glycopeptide antibiotics conjugated with benzoxaboroles.

    PubMed

    Printsevskaya, S S; Reznikova, M I; Korolev, A M; Lapa, G B; Olsufyeva, E N; Preobrazhenskaya, M N; Plattner, J J; Zhang, Y K

    2013-04-01

    The ability of boron-containing compounds to undergo a number of novel binding interactions with drug target functional groups has recently been described. In an extension of this work, we have incorporated a boron-containing scaffold, the benzoxaborole, into several glycopeptides antibiotics. The aim of this work is to exploit the inherent reactivity of boron to gain additional interactions with the bacterial cell wall components to improve binding affinity and to thereby overcome resistance. Three antibacterial glycopeptides (vancomycin, eremomycin and teicoplanin aglycone) have been selected for the construction of a series of 12 new benzoxaborole-glycopeptide conjugates. The hybrid antibiotics, in which the benzoxaborole and glycopeptide moieties were separated by a linker, exhibited excellent antibacterial activity against Gram-positive bacteria, including those with intermediate susceptibility to glycopeptides. Some analogs also demonstrated activity against vancomycin-resistant enterococci. Conjugation of antibiotics with benzoxaborole derivatives provides antibiotics with new and useful properties. Teicoplanin aglycone-benzoxaborole derivatives overcome resistance of Gram-positive bacteria to vancomycin.

  13. Investigation of the Potential for Mutational Resistance to XF-73, Retapamulin, Mupirocin, Fusidic Acid, Daptomycin, and Vancomycin in Methicillin-Resistant Staphylococcus aureus Isolates during a 55-Passage Study ▿

    PubMed Central

    Farrell, David J.; Robbins, Marion; Rhys-Williams, William; Love, William G.

    2011-01-01

    XF-73 is a dicationic porphyrin drug with rapid Gram-positive antibacterial activity currently undergoing clinical trials for the nasal decolonization of Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA). In multistep (55-passage) resistance selection studies in the presence of subinhibitory concentrations of XF-73, retapamulin, mupirocin, fusidic acid, and vancomycin against four Network on Antimicrobial Resistance in Staphylococcus aureus MRSA strains, there was no >4-fold increase in the MIC for XF-73 after 55 passages. In contrast, there was an increase in the MICs for retapamulin (from 0.25 μg/ml to 4 to 8 μg/ml), for mupirocin (from 0.12 μg/ml to 16 to 512 μg/ml), for fusidic acid (from 0.12 μg/ml to 256 μg/ml), and for vancomycin (from 1 μg/ml to 8 μg/ml in two of the four strains tested). Further investigations using S. aureus NRS384 (USA300) and daptomycin demonstrated a 64-fold increase in the MIC after 55 passages (from 0.5 μg/ml to 32 μg/ml) with a >4-fold increase in the MIC obtained after only five passages. Sequencing analysis of selected isolates confirmed previously reported point mutations associated with daptomycin resistance. No cross-resistance to XF-73 was observed with the daptomycin-resistant strains, suggesting that whereas the two drugs act on the bacterial cell membrane, their specific site of action differs. XF-73 thus represents the first in a new class of antibacterial drugs, which (unlike the comparator antibiotics) after 55 passages exhibited a ≤4-fold increase in MIC against the strains tested. Antibacterial drugs with a low propensity for inducing bacterial resistance are much needed for the prevention and treatment of multidrug-resistant bacteria both within and outside the hospital setting. PMID:21149626

  14. Pore Water Transport of Enterococci out of Beach Sediments

    PubMed Central

    Phillips, Matthew C.; Solo-Gabriele, Helena M.; Reniers, Adrianus J. H. M.; Wang, John D.; Kiger, Russell T.; Abdel-Mottaleb, Noha

    2011-01-01

    Enterococci are used to evaluate the safety of beach waters and studies have identified beach sands as a source of these bacteria. In order to study and quantify the release of microbes from beach sediments, flow column systems were built to evaluate flow of pore water out of beach sediments. Results show a peak in enterococci (average of 10% of the total microbes in core) released from the sand core within one pore water volume followed by a marked decline to below detection. These results indicate that few enterococci are easily removed and that factors other than simple pore water flow control the release of the majority of enterococci within beach sediments. A significantly larger quantity and release of enterococci were observed in cores collected after a significant rain event suggesting the influx of fresh water can alter the release pattern as compared to cores with no antecedent rainfall. PMID:21945015

  15. Trovafloxacin in Combination with Vancomycin against Penicillin-Resistant Pneumococci in the Rabbit Meningitis Model

    PubMed Central

    Rodoni, Dina; Hänni, Fränzi; Gerber, Cynthia M.; Cottagnoud, Marianne; Neftel, Klaus; Täuber, Martin G.; Cottagnoud, Philippe

    1999-01-01

    Trovafloxacin, a new fluoroquinolone, produced bactericidal activity (−0.33 ± 0.13 Δlog10 CFU/ml · h; intravenously [i.v.] administered dose, 15 mg/kg) comparable to that of vancomycin (−0.39 ± 0.18 Δlog10 CFU/ml · h; i.v. administered dose, 20 mg/kg) in the treatment of experimental meningitis in rabbits due to a pneumococcal strain highly resistant to penicillin (MIC of penicillin G, 4 μg/ml). The combination of both drugs significantly increased (P < 0.05) the killing rate (−0.60 ± 0.23 Δlog10 CFU/ml · h) compared to that produced by either monotherapy. These results were also confirmed in vitro. PMID:10103211

  16. VraR Binding to the Promoter Region of agr Inhibits Its Function in Vancomycin-Intermediate Staphylococcus aureus (VISA) and Heterogeneous VISA.

    PubMed

    Dai, Yuanyuan; Chang, Wenjiao; Zhao, Changcheng; Peng, Jing; Xu, Liangfei; Lu, Huaiwei; Zhou, Shusheng; Ma, Xiaoling

    2017-05-01

    Acquisition of vancomycin resistance in Staphylococcus aureus is often accompanied by a reduction in virulence, but the mechanisms underlying this change remain unclear. The present study was undertaken to investigate this process in a clinical heterogeneous vancomycin-intermediate S. aureus (hVISA) strain, 10827; an hVISA reference strain, Mu3; and a VISA reference strain, Mu50, along with their respective series of vancomycin-induced resistant strains. In these strains, increasing MICs of vancomycin were associated with increased expression of the vancomycin resistance-associated regulator gene ( vraR ) and decreased expression of virulence genes ( hla , hlb , and coa ) and virulence-regulated genes (RNAIII, agrA , and saeR ). These results suggested that VraR might have a direct or indirect effect on virulence in S. aureus In electrophoretic mobility shift assays, VraR did not bind to promoter sequences of hla , hlb , and coa genes, but it did bind to the agr promoter region. In DNase I footprinting assays, VraR protected a 15-nucleotide (nt) sequence in the intergenic region between the agr P2 and P3 promoters. These results indicated that when S. aureus is subject to induction by vancomycin, expression of vraR is upregulated, and VraR binding inhibits the function of the Agr quorum-sensing system, causing reductions in the virulence of VISA/hVISA strains. Our results suggested that VraR in S. aureus is involved not only in the regulation of vancomycin resistance but also in the regulation of virulence. Copyright © 2017 American Society for Microbiology.

  17. Balancing vancomycin efficacy and nephrotoxicity: should we be aiming for trough or AUC/MIC?

    PubMed

    Patel, Karisma; Crumby, Ashley S; Maples, Holly D

    2015-04-01

    Sixty years later, the question that still remains is how to appropriately utilize vancomycin in the pediatric population. The Infectious Diseases Society of America published guidelines in 2011 that provide guidance for dosing and monitoring of vancomycin in adults and pediatrics. However, goal vancomycin trough concentrations of 15-20 μg/mL for invasive infections caused by methicillin-resistant Staphylococcus aureus were based primarily on adult pharmacokinetic and pharmacodynamic data that achieved an area under the curve to minimum inhibitory concentration ratio (AUC/MIC) of ≥400. Recent pediatric literature shows that vancomycin trough concentrations needed to achieve the target AUC/MIC are different than the adult goal troughs cited in the guidelines. This paper addresses several thoughts, including the role of vancomycin AUC/MIC in dosing strategies and safety monitoring, consistency in laboratory reporting, and future directions for calculating AUC/MIC in pediatrics.

  18. Occurrence of Multidrug-Resistant and Toxic-Metal Tolerant Enterococci in Fresh Feces from Urban Pigeons in Brazil

    PubMed Central

    da Silva, Vânia Lúcia; Caçador, Natália Cândido; dos Santos Fernandes da Silva, Carolina; Fontes, Cláudia Oliveira; Garcia, Gizele Duarte; Nicoli, Jacques Robert; Diniz, Cláudio Galuppo

    2012-01-01

    Enterococcus are emerging as important putative pathogens resistant to chemicals that are widely released into the environment, and urban pigeons might act as a natural reservoir contributing to the spread of resistant strains. This study aimed to evaluate the occurrence of Enterococcus in pigeon feces and their antimicrobial and toxic metal susceptibility. Bacteria were isolated and identified from 150 fresh feces by phenotypic and genetic techniques. Antimicrobial and toxic metal susceptibility was determined by the agar dilution method, and the multiple antibiotic resistance index (MAR) was calculated. Out of 120 isolates, no resistance was observed against penicillin and vancomycin, but was observed against gentamicin (55.8%), chloramphenicol (21.7%), tetracycline (13.3%), ciprofloxacin (8.4%) and rifampin (2.5%). 18.3% presented a MAR index ≥0.2, ranging between 0.14 to 0.57, indicating resistance to more than one antimicrobial. All samples were tolerant to >1024 μg mL−1 zinc and chromium. Minimal inhibitory concentration (MIC) of 1,024 μg mL−1 was observed for copper (100%) and nickel (71.4%). Mercury inhibited 88.4% at 32 μg mL−1 and the MIC for cadmium ranged from 0.125–128 μg mL−1. Since pigeons were found to harbor drug-resistant Enterococcus, our data support that their presence in the urban environment may contribute to the spread of resistance, with an impact on public health. PMID:22791051

  19. Extracellular DNA impedes the transport of vancomycin in Staphylococcus epidermidis biofilms preexposed to subinhibitory concentrations of vancomycin.

    PubMed

    Doroshenko, Natalya; Tseng, Boo Shan; Howlin, Robert P; Deacon, Jill; Wharton, Julian A; Thurner, Philipp J; Gilmore, Brendan F; Parsek, Matthew R; Stoodley, Paul

    2014-12-01

    Staphylococcus epidermidis biofilm formation is responsible for the persistence of orthopedic implant infections. Previous studies have shown that exposure of S. epidermidis biofilms to sub-MICs of antibiotics induced an increased level of biofilm persistence. BODIPY FL-vancomycin (a fluorescent vancomycin conjugate) and confocal microscopy were used to show that the penetration of vancomycin through sub-MIC-vancomycin-treated S. epidermidis biofilms was impeded compared to that of control, untreated biofilms. Further experiments showed an increase in the extracellular DNA (eDNA) concentration in biofilms preexposed to sub-MIC vancomycin, suggesting a potential role for eDNA in the hindrance of vancomycin activity. Exogenously added, S. epidermidis DNA increased the planktonic vancomycin MIC and protected biofilm cells from lethal vancomycin concentrations. Finally, isothermal titration calorimetry (ITC) revealed that the binding constant of DNA and vancomycin was 100-fold higher than the previously reported binding constant of vancomycin and its intended cellular d-Ala-d-Ala peptide target. This study provides an explanation of the eDNA-based mechanism of antibiotic tolerance in sub-MIC-vancomycin-treated S. epidermidis biofilms, which might be an important factor for the persistence of biofilm infections. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  20. Molecular Epidemiology of Vancomycin-Resistant Enterococcus faecium: a Prospective, Multicenter Study in South American Hospitals▿

    PubMed Central

    Panesso, Diana; Reyes, Jinnethe; Rincón, Sandra; Díaz, Lorena; Galloway-Peña, Jessica; Zurita, Jeannete; Carrillo, Carlos; Merentes, Altagracia; Guzmán, Manuel; Adachi, Javier A.; Murray, Barbara E.; Arias, Cesar A.

    2010-01-01

    Enterococcus faecium has emerged as an important nosocomial pathogen worldwide, and this trend has been associated with the dissemination of a genetic lineage designated clonal cluster 17 (CC17). Enterococcal isolates were collected prospectively (2006 to 2008) from 32 hospitals in Colombia, Ecuador, Perú, and Venezuela and subjected to antimicrobial susceptibility testing. Genotyping was performed with all vancomycin-resistant E. faecium (VREfm) isolates by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing. All VREfm isolates were evaluated for the presence of 16 putative virulence genes (14 fms genes, the esp gene of E. faecium [espEfm], and the hyl gene of E. faecium [hylEfm]) and plasmids carrying the fms20-fms21 (pilA), hylEfm, and vanA genes. Of 723 enterococcal isolates recovered, E. faecalis was the most common (78%). Vancomycin resistance was detected in 6% of the isolates (74% of which were E. faecium). Eleven distinct PFGE types were found among the VREfm isolates, with most belonging to sequence types 412 and 18. The ebpAEfm-ebpBEfm-ebpCEfm (pilB) and fms11-fms19-fms16 clusters were detected in all VREfm isolates from the region, whereas espEfm and hylEfm were detected in 69% and 23% of the isolates, respectively. The fms20-fms21 (pilA) cluster, which encodes a putative pilus-like protein, was found on plasmids from almost all VREfm isolates and was sometimes found to coexist with hylEfm and the vanA gene cluster. The population genetics of VREfm in South America appear to resemble those of such strains in the United States in the early years of the CC17 epidemic. The overwhelming presence of plasmids encoding putative virulence factors and vanA genes suggests that E. faecium from the CC17 genogroup may disseminate in the region in the coming years. PMID:20220167

  1. LIGHT-INDUCED PROCESSES AFFECTING ENTEROCOCCI IN AQUATIC ENVIRONMENTS

    EPA Science Inventory

    Fecal indicator bacteria such as enterococci have been used to assess contamination of freshwater and marine environments by pathogenic microorganisms. Various past studies have shown that sunlight plays an important role in reducing concentrations of culturable enterococci and ...

  2. vanA-positive multi-drug-resistant Enterococcus spp. isolated from surfaces of a US hospital laundry facility.

    PubMed

    Michael, K E; No, D; Roberts, M C

    2017-02-01

    Enterococcus spp. are a normal part of the gastrointestinal tract of humans and animals. They are also important pathogens, being responsible for 14% of US nosocomial infections from 2007 to 2010. To examine a laundry facility that processes clinical linens for the presence and seasonality of vancomycin-resistant Enterococcus spp. Surface samples were collected four times in 2015 from the dirty and clean areas of the laundry facility. Isolates were confirmed using biochemical assays, and antibiotic susceptibility testing was performed. Further investigations included molecular characterization by multi-locus sequence typing (MLST), detection of acquired vanA and vanB and/or intrinsic vanC1 genes by polymerase chain reaction, and eBURST analysis. Seventy-four vanA-positive multi-drug-resistant Enterococcus spp. were identified: 64/120 (53%) in the dirty area and 10/120 (8%) in the clean area. There were 14 ST types among the E. faecium isolates identified (ST16, 17, 18, 117, 186, 280, 324, 412, 584, 664, 665, 736, 750 and 1038). Both E. faecalis isolates were ST109. Isolation of vancomycin-resistant enterococci (VRE) isolates was significantly higher (53% vs 8%) in the dirty area of the facility compared with the clean area. This is the first study to examine an industrial laundry facility for the presence of VRE, and may be an unrecognized reservoir. Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  3. Influx of multidrug-resistant organisms by country-to-country transfer of patients.

    PubMed

    Mutters, Nico T; Günther, Frank; Sander, Anja; Mischnik, Alexander; Frank, Uwe

    2015-10-28

    Multidrug-resistant organisms (MDRO) are a worldwide problem. International migration and travel facilitate the spread of MDRO. Therefore the goal of our study was to assess the risk of influx of MDRO from patients transferred to one of Central Europe's largest hospitals from abroad. A mono-centre study was conducted. All patients transferred from other countries were screened; additional data was collected on comorbidities, etc. Presence of carbapenemases of multidrug-resistant Gram-negatives was confirmed by PCR. The association between length of stay, being colonized and/or infected by a MDRO, country of origin, diagnosis and other factors was assessed by binomial regression analyses. From 2012 to 2013, one fifth of all patients were colonized with MDRO (Methicillin-resistant Staphylococcus aureus [4.1 %], Vancomycin-resistant Enterococci [2.9 %], multidrug-resistant Gram-negatives [12.8 %] and extensively drug-resistant Gram-negatives [3.4 %]). The Gram-negatives carried a variety of carbapenemases including OXA, VIM, KPC and NDM. The length of stay was significantly prolonged by 77.2 % in patients colonized with a MDRO, compared to those not colonized (p<0.0001). Country-to-Country transfer of patients to European hospitals represents a high risk of introduction of MDRO and infection control specialists should endorse containment and screening measures.

  4. Vancomycin-induced thrombocytopenia in a 60-year-old man: a case report.

    PubMed

    Shah, Ravish A; Musthaq, Adnan; Khardori, Nancy

    2009-06-26

    Vancomycin, a glycopeptide antibiotic, is used to treat resistant gram-positive infections. There has been a 10- to 20-fold increase in its use over the past 25 years. Although ototoxicity and nephrotoxicity are well known side effects of vancomycin, it can also induce platelet reactive antibodies leading to life-threatening thrombocytopenia. Vancomycin is often clinically overlooked as a cause of thrombocytopenia, especially in a scenario of sepsis or when there is use of heparin. We report a proven case of vancomycin-induced thrombocytopenia and its reversal after discontinuation of vancomycin. A 60-year-old man with a history of hypertension, congestive heart failure and dyslipidemia was admitted for a right shoulder rotator cuff tear. He underwent right-shoulder arthroscopy and rotator cuff repair. About three weeks later, he developed pain, swelling and purulent drainage from his right shoulder. Arthroscopic irrigation and drainage was then performed. Intraoperative fluid revealed the presence of Methicillin susceptible Staphylococcus aureus, vancomycin-sensitive Enterococcus spp. and Serratia marcescens. The patient had no known allergies. After reviewing his antimicrobial susceptibility, he was started on vancomycin 1500 mgs intravenously every 12 hours (to treat both Staphylococcus aureus and Enterococcus spp) and ciprofloxacin 750 mgs by oral induction every 12 hours. The patient's condition improved following antibiotic treatment. He was discharged and allowed to go home on IV vancomycin and oral ciprofloxacin. The patient's platelet count on the day of starting vancomycin therapy was 253 x 10(3)/mm(3). At weeks one, two and three, the counts were 231 x 10(3)/mm(3), 272 x 10(3)/mm and 6 x 103/mm(3), respectively. The patient was admitted for further work-up of the thrombocytopenia. He was later shown to have vancomycin-induced platelet-reactive antibodies, causing significant thrombocytopenia, and then reversal after his vancomycin medication was

  5. A Decade-Long Commitment to Antimicrobial Resistance Surveillance in Portugal

    PubMed Central

    Marinho, Catarina M.; Santos, Tiago; Gonçalves, Alexandre; Poeta, Patrícia; Igrejas, Gilberto

    2016-01-01

    Antimicrobial resistance (AMR) is a worldwide problem with serious health and economic repercussions. Since the 1940s, underuse, overuse, and misuse of antibiotics have had a significant environmental downside. Large amounts of antibiotics not fully metabolized after use in human and veterinary medicine, and other applications, are annually released into the environment. The result has been the development and dissemination of antibiotic-resistant bacteria due to many years of selective pressure. Surveillance of AMR provides important information that helps in monitoring and understanding how resistance mechanisms develop and disseminate within different environments. Surveillance data is needed to inform clinical therapy decisions, to guide policy proposals, and to assess the impact of action plans to fight AMR. The Functional Genomics and Proteomics Unit, based at the University of Trás-os-Montes and Alto Douro in Vila Real, Portugal, has recently completed 10 years of research surveying AMR in bacteria, mainly commensal indicator bacteria such as enterococci and Escherichia coli from the microbiota of different animals. Samples from more than 75 different sources have been accessed, from humans to food-producing animals, pets, and wild animals. The typical microbiological workflow involved phenotypic studies followed by molecular approaches. Throughout the decade, 4,017 samples were collected and over 5,000 bacterial isolates obtained. High levels of AMR to several antimicrobial classes have been reported, including to β-lactams, glycopeptides, tetracyclines, aminoglycosides, sulphonamides, and quinolones. Multi-resistant strains, some relevant to human and veterinary medicine like extended-spectrum β-lactamase-producing E. coli and vancomycin-resistant enterococci, have been repeatedly isolated even in non-synanthropic animal species. Of particular relevance are reports of AMR bacteria in wildlife from natural reserves and endangered species. Future work

  6. Performance of Vitek 2 for Antimicrobial Susceptibility Testing of Staphylococcus spp. and Enterococcus spp.

    PubMed Central

    Bobenchik, April M.; Hindler, Janet A.; Giltner, Carmen L.; Saeki, Sandra

    2014-01-01

    Vitek 2 (bioMérieux, Inc., Durham, NC) is a widely used commercial antimicrobial susceptibility testing system. We compared MIC results obtained by Vitek 2 to those obtained by the Clinical and Laboratory Standards Institute (CLSI) broth microdilution (BMD) reference method for 134 staphylococcal and 84 enterococcal clinical isolates. Nineteen agents were evaluated, including all those available on Vitek 2 for testing staphylococci and enterococci. The resistance phenotypes tested included methicillin-resistant Staphylococcus aureus (MRSA) (n = 58), S. aureus with inducible clindamycin resistance (ICR) (n = 30), trimethoprim-sulfamethoxazole-resistant MRSA (n = 10), vancomycin-resistant Enterococcus (n = 37), high-level gentamicin-resistant Enterococcus (n = 15), linezolid-resistant Enterococcus (n = 5), and daptomycin-nonsusceptible Enterococcus faecalis (n = 6). For the staphylococci, there was 98.9% categorical agreement (CA). There was one very major error (VME) for gentamicin in a Staphylococcus hominis isolate, six VMEs for inducible clindamycin in S. aureus isolates, and two major errors (ME) for daptomycin in an S. aureus and a Staphylococcus epidermidis isolate. For enterococci, there was 97.3% CA. Two VMEs were observed for daptomycin in isolates of E. faecalis and 2 ME, 1 for high-level gentamicin resistance and 1 for nitrofurantoin, in E. faecium isolates. Overall, there was 98.3% CA and 99% essential agreement for the testing of staphylococci and enterococci by the Vitek 2. With the exception of detecting ICR in S. aureus, Vitek 2 performed reliably for antimicrobial susceptibility testing of staphylococci and enterococci. PMID:24478467

  7. AUC-Guided Vancomycin Dosing in Adolescent Patients With Suspected Sepsis.

    PubMed

    Lanke, Shankar; Yu, Tian; Rower, Joseph E; Balch, Alfred H; Korgenski, E Kent; Sherwin, Catherine M

    2017-01-01

    Vancomycin is a first-line treatment for β-lactam-resistant Gram-positive bacterial infections. Understanding the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of vancomycin in an adolescent population is of clinical importance in this often overlooked pediatric population. This retrospective study investigated vancomycin PK-PD in an adolescent cohort (12 to 18 years of age) of 463 patients (57% male, 81% white) admitted to the Intermountain Healthcare System between January 2006 and December 2013. Population PK modeling was performed in NONMEM 7.3. Vancomycin PK was well described with a 1-compartment model that identified both body weight (WT) and creatinine clearance (CRCL) as covariates significantly impacting vancomycin disposition. The model was then utilized to determine dosing strategies that achieved the targeted area under the 24-hour time curve vs minimum inhibitory concentration (AUC 0-24 /MIC) ratio of ≥400. Additionally, these data were correlated with minimum steady-state concentrations (C ss,min ) to find an acceptable target trough concentration range in adolescents. This analysis demonstrated that C ss,min ranging from 10 to 12.5 mg/L were highly predictive of achieving an AUC 0-24 /MIC ≥400 when the MIC was ≤1 mg/L. These results suggest that the target trough concentration for adolescents may be lower than that for adults. © 2016, The American College of Clinical Pharmacology.

  8. Biochemical and Genetic Characterization of the vanC-2 Vancomycin Resistance Gene Cluster of Enterococcus casseliflavus ATCC 25788

    PubMed Central

    Dutta, Ireena; Reynolds, Peter E.

    2002-01-01

    The vanC-2 cluster of Enterococcus casseliflavus ATCC 25788 consisted of five genes (vanC-2, vanXYC-2, vanTC-2, vanRC-2, and vanSC-2) and shared the same organization as the vanC cluster of E. gallinarum BM4174. The proteins encoded by these genes displayed a high degree of amino acid identity to the proteins encoded within the vanC gene cluster. The putative d,d-dipeptidase-d,d-carboxypeptidase, VanXYC-2, exhibited 81% amino acid identity to VanXYC, and VanTC-2 displayed 65% amino acid identity to the serine racemase, VanT. VanRC-2 and VanSC-2 displayed high degrees of identity to VanRC and VanSC, respectively, and contained the conserved residues identified as important to their function as a response regulator and histidine kinase, respectively. Resistance to vancomycin was expressed inducibly in E. casseliflavus ATCC 25788 and required an extended period of induction. Analysis of peptidoglycan precursors revealed that UDP-N-acetylmuramyl-l-Ala-δ-d-Glu-l-Lys-d-Ala-d-Ser could not be detected until several hours after the addition of vancomycin, and its appearance coincided with the resumption of growth. The introduction of additional copies of the vanTC-2 gene, encoding a putative serine racemase, and the presence of supplementary d-serine in the growth medium both significantly reduced the period before growth resumed after addition of vancomycin. This suggested that the availability of d-serine plays an important role in the induction process. PMID:12234834

  9. Distribution and persistence of fecal bacterial populations in liquid and dewatered sludge from a biological treatment plant.

    PubMed

    Vilanova, Xavier; Blanch, Anicet R

    2005-12-01

    The changes in composition and structure of fecal coliforms (FC) and enterococci (ENT) populations, as well as the elimination of spores of sulphite-reducing bacteria (SRB), were compared between municipal sewage and their derived sludge in a biological treatment plant in order to determine any selective reduction or adsorption to sludge during the treatment process. Additionally, the persistence of antibiotic-resistant enterococcal populations in two kinds of sludge was also considered to evaluate their potential elimination in the treatment process. Microbial indicators, vancomycin-resistant and erythromycin-resistant enterococci were enumerated. The structure and composition of FC and ENT populations were determined by biochemical fingerprinting and clustering analyses. Raw and treated sewage showed a concentration of FC 1 log unit higher than ENT and nearly 2 log units higher than spores of SRB. However, the three studied indicators showed similar concentrations in both types of sludge. Consequently, FC were eliminated in higher proportion than ENT and spores of SRB in sludge. FC and ENT populations showed high diversity and similarity population indexes for all kinds of samples. Antibiotic-resistant enterococci persisted in a similar proportion in respect to total enterococci not only in treated sewage but also in sludge. The persistence of antibiotic-resistant strains in sludge as well as in treated sewage should be considered if they are used for land disposal or for water reutilization, respectively.

  10. Predicting Maintenance Doses of Vancomycin for Hospitalized Patients Undergoing Hemodialysis.

    PubMed

    El Nekidy, Wasim S; El-Masri, Maher M; Umstead, Greg S; Dehoorne-Smith, Michelle

    2016-01-01

    Methicillin-resistant Staphylococcus aureus is a leading cause of death in patients undergoing hemodialysis. However, controversy exists about the optimal dose of vancomycin that will yield the recommended pre-hemodialysis serum concentration of 15-20 mg/L. To develop a data-driven model to optimize the accuracy of maintenance dosing of vancomycin for patients undergoing hemodialysis. A prospective observational cohort study was performed with 164 observations obtained from a convenience sample of 63 patients undergoing hemodialysis. All vancomycin doses were given on the floor after completion of a hemodialysis session. Multivariate linear generalized estimating equation analysis was used to examine independent predictors of pre-hemodialysis serum vancomycin concentration. Pre-hemodialysis serum vancomycin concentration was independently associated with maintenance dose ( B = 0.658, p < 0.001), baseline pre-hemodialysis serum concentration of the drug ( B = 0.492, p < 0.001), and interdialytic interval ( B = -2.133, p < 0.001). According to the best of 4 models that were developed, the maintenance dose of vancomycin required to achieve a pre-hemodialysis serum concentration of 15-20 mg/L, if the baseline serum concentration of the drug was also 15-20 mg/L, was 5.9 mg/kg with interdialytic interval of 48 h and 7.1 mg/kg with interdialytic interval of 72 h. However, if the baseline pre-hemodialysis serum concentration was 10-14.99 mg/L, the required dose increased to 9.2 mg/kg with an interdialytic interval of 48 h and 10.0 mg/kg with an interdialytic interval of 72 h. The maintenance dose of vancomycin varied according to baseline pre-hemodialysis serum concentration of the drug and interdialytic interval. The current practice of targeting a pre-hemodialysis concentration of 15-20 mg/L may be difficult to achieve for the majority of patients undergoing hemodialysis.

  11. Antibiotic susceptibility of enterococci isolated from traditional fermented meat products.

    PubMed

    Barbosa, J; Ferreira, V; Teixeira, P

    2009-08-01

    Antibiotic susceptibility was evaluated for 182 Enterococcus spp. isolated from Alheira, Chouriça de Vinhais and Salpicão de Vinhais, fermented meat products produced in the North of Portugal. Previously, a choice was made from a group of 1060 isolates, using phenotypic and genotypic tests. From these, 76 were previously identified as Enterococcus faecalis, 44 as Enterococcus faecium, one as Enterococcus casseliflavus and 61 as Enteroccocus spp. In order to encompass several of the known chemical and functional classes of antibiotics, resistance to ampicillin, penicillin G, ciprofloxacin, chloramphenicol, erythromycin, nitrofurantoin, rifampicin, tetracycline and vancomycin was evaluated. All the isolates were sensitive to antibiotics of clinical importance, such as penicillins and vancomycin. Some differences in Minimal Inhibitory Concentrations (MICs) of antibiotics, could be associated with the enterococcal species.

  12. Halloysite nanotubes as carriers of vancomycin in alginate-based wound dressing.

    PubMed

    Kurczewska, Joanna; Pecyna, Paulina; Ratajczak, Magdalena; Gajęcka, Marzena; Schroeder, Grzegorz

    2017-09-01

    The influence of an inorganic support - halloysite nanotubes - on the release rate and biological activity of the antibiotic encapsulated in alginate-based dressings was studied. The halloysite samples were loaded with approx. 10 wt.% of the antibiotic and then encapsulated in Alginate and Gelatin/Alginate gels. The material functionalized with aliphatic amine significantly extended the release of vancomycin from alginate-based gels as compared to that achieved when silica was used. After 24 h, the released amounts of the antibiotic immobilized at silica reached 70%, while for the drug immobilized at halloysite the released amount of vancomycin reached 44% for Alginate discs. The addition of gelatin resulted in even more prolonged sustained release of the drug. The antibiotic was released from the system with a double barrier with Higuchi kinetic model and Fickian diffusion mechanism. Only the immobilized drug encapsulated in Alginate gel demonstrated very good antimicrobial activity against various bacteria. The inhibition zones were greater than those of the standard discs for the staphylococci and enterococci bacteria tested. The addition of gelatin adversely affected the biological activity of the system. The inhibition zones were smaller than those of the reference samples. A reduction in the drug dose by half had no significant effect on changing the release rate and microbiological activity. The in vivo toxicity studies of the material with immobilized drug were carried out with Acutodesmus acuminatus and Daphnia magna . The material studied had no effect on the living organisms used in the bioassays. The proposed system with a double barrier demonstrated high storage stability.

  13. Genetic and molecular predictors of high vancomycin MIC in Staphylococcus aureus bacteremia isolates.

    PubMed

    Holmes, Natasha E; Turnidge, John D; Munckhof, Wendy J; Robinson, J Owen; Korman, Tony M; O'Sullivan, Matthew V N; Anderson, Tara L; Roberts, Sally A; Warren, Sanchia J C; Coombs, Geoffrey W; Tan, Hui-Leen; Gao, Wei; Johnson, Paul D R; Howden, Benjamin P

    2014-09-01

    An elevated vancomycin MIC is associated with poor outcomes in Staphylococcus aureus bacteremia (SAB) and is reported in patients with methicillin-susceptible S. aureus (MSSA) bacteremia in the absence of vancomycin treatment. Here, using DNA microarray and phenotype analysis, we investigated the genetic predictors and accessory gene regulator (agr) function and their relationship with elevated vancomycin MIC using blood culture isolates from a multicenter binational cohort of patients with SAB. Specific clonal complexes were associated with elevated (clonal complex 8 [CC8] [P < 0.001]) or low (CC22 [P < 0.001], CC88 [P < 0.001], and CC188 [P = 0.002]) vancomycin MIC. agr dysfunction (P = 0.014) or agr genotype II (P = 0.043) were also associated with an elevated vancomycin MIC. Specific resistance and virulence genes were also linked to an elevated vancomycin MIC, including blaZ (P = 0.002), sea (P < 0.001), clfA (P < 0.001), splA (P = 0.001), and the arginine catabolic mobile element (ACME) locus (P = 0.02). These data suggest that inherent organism characteristics may explain the link between elevated vancomycin MICs and poor outcomes in patients with SAB, regardless of the antibiotic treatment received. A consideration of clonal specificity should be included in future research when attempting to ascertain treatment effects or clinical outcomes. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  14. Health economic evaluation of patients treated for nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus: secondary analysis of a multicenter randomized clinical trial of vancomycin and linezolid.

    PubMed

    Niederman, Michael S; Chastre, Jean; Solem, Caitlyn T; Wan, Yin; Gao, Xin; Myers, Daniela E; Haider, Seema; Li, Jim Z; Stephens, Jennifer M

    2014-09-01

    Results from studies comparing health care resource use (HCRU), costs of treatment, and cost-effectiveness of linezolid compared with vancomycin therapy in the treatment of hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia are limited in the published literature. We therefore conducted an analysis to compare the HCRU, costs of treatment, and cost-effectiveness of linezolid compared with vancomycin in the treatment of hospitalized patients with MRSA nosocomial pneumonia using data from a Phase IV clinical trial. The economic effect of moderate to severe adverse events (MSAEs) and the development of renal failure were also evaluated. We performed a post hoc analysis of data from a Phase IV, double-blind, randomized, comparator-controlled, multicenter trial that compared linezolid and vancomycin treatment in patients with MRSA nosocomial pneumonia. HCRU and costs were compared based on treatment, development of MSAEs, and development of renal failure using data from the modified intent-to-treat population. Predictors of costs were evaluated using generalized linear models. A piggyback cost-effectiveness analysis was conducted to assess the incremental cost-effectiveness ratio of linezolid versus vancomycin, given the significantly higher clinical success of linezolid compared with vancomycin found in the trial. Overall, HCRU and costs were similar between the linezolid and vancomycin treatment groups; drug costs were significantly higher and dialysis costs significantly lower for linezolid- compared with vancomycin-treated patients. Total treatment costs were approximately $8000 higher (P = .046) for patients who developed renal failure compared with those who did not. Renal failure occurred more commonly in patients randomized to receive vancomycin (15%) compared with linezolid (4%; P < .001). Region, ventilator-associated pneumonia, clinical failure, and development of renal failure were associated with significantly

  15. Antimicrobial Resistance of Escherichia coli, Enterococci, Pseudomonas aeruginosa, and Staphylococcus aureus from Raw Fish and Seafood Imported into Switzerland.

    PubMed

    Boss, Renate; Overesch, Gudrun; Baumgartner, Andreas

    2016-07-01

    A total of 44 samples of salmon, pangasius (shark catfish), shrimps, and oysters were tested for the presence of Escherichia coli, enterococci, Pseudomonas aeruginosa, and Staphylococcus aureus, which are indicator organisms commonly used in programs to monitor antibiotic resistance. The isolated bacterial strains, confirmed by matrix-assisted laser desorption ionization time-of-flight mass spectroscopy, were tested against a panel of 29 antimicrobial agents to obtain MICs. Across the four sample types, Enterococcus faecalis (59%) was most common, followed by E. coli (55%), P. aeruginosa (27%), and S. aureus (9%). All bacterial species were resistant to some antibiotics. The highest rates of resistance were in E. faecalis to tetracycline (16%), in E. coli to ciprofloxacin (22%), and in S. aureus to penicillin (56%). Antibiotic resistance was found among all sample types, but salmon and oysters were less burdened than were shrimps and pangasius. Multidrug-resistant (MDR) strains were exclusively found in shrimps and pangasius: 17% of pangasius samples (MDR E. coli and S. aureus) and 64% of shrimps (MDR E. coli, E. faecalis, and S. aureus). Two of these MDR E. coli isolates from shrimps (one from an organic sample) were resistant to seven antimicrobial agents. Based on these findings, E. coli in pangasius, shrimps, and oysters, E. faecalis in pangasius, shrimps, and salmon, and P. aeruginosa in pangasius and shrimps are potential candidates for programs monitoring antimicrobial resistance. Enrichment methods for the detection of MDR bacteria of special public health concern, such as methicillin-resistant S. aureus and E. coli producing extended-spectrum β-lactamases and carbapenemases, should be implemented.

  16. Vancomycin-resistant enterococcus infection in the hematopoietic stem cell transplant recipient: an overview of epidemiology, management, and prevention

    PubMed Central

    Benamu, Esther; Deresinski, Stanley

    2018-01-01

    Vancomycin-resistant enterococcus (VRE) is now one of the leading causes of nosocomial infections in the United States. Hematopoietic stem cell transplantation (HSCT) recipients are at increased risk of VRE colonization and infection. VRE has emerged as a major cause of bacteremia in this population, raising important clinical questions regarding the role and impact of VRE colonization and infection in HSCT outcomes as well as the optimal means of prevention and treatment. We review here the published literature and scientific advances addressing these thorny issues and provide a rational framework for their approach. PMID:29333263

  17. Rapid and easy detection of low-level resistance to vancomycin in methicillin-resistant Staphylococcus aureus by matrix-assisted laser desorption ionization time-of-flight mass spectrometry.

    PubMed

    Asakura, Kota; Azechi, Takuya; Sasano, Hiroshi; Matsui, Hidehito; Hanaki, Hideaki; Miyazaki, Motoyasu; Takata, Tohru; Sekine, Miwa; Takaku, Tomoiku; Ochiai, Tomonori; Komatsu, Norio; Shibayama, Keigo; Katayama, Yuki; Yahara, Koji

    2018-01-01

    Vancomycin-intermediately resistant Staphylococcus aureus (VISA) and heterogeneous VISA (hVISA) are associated with treatment failure. hVISA contains only a subpopulation of cells with increased minimal inhibitory concentrations, and its detection is problematic because it is classified as vancomycin-susceptible by standard susceptibility testing and the gold-standard method for its detection is impractical in clinical microbiology laboratories. Recently, a research group developed a machine-learning classifier to distinguish VISA and hVISA from vancomycin-susceptible S. aureus (VSSA) according to matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) data. Nonetheless, the sensitivity of hVISA classification was found to be 76%, and the program was not completely automated with a graphical user interface. Here, we developed a more accurate machine-learning classifier for discrimination of hVISA from VSSA and VISA among MRSA isolates in Japanese hospitals by means of MALDI-TOF MS data. The classifier showed 99% sensitivity of hVISA classification. Furthermore, we clarified the procedures for preparing samples and obtaining MALDI-TOF MS data and developed all-in-one software, hVISA Classifier, with a graphical user interface that automates the classification and is easy for medical workers to use; it is publicly available at https://github.com/bioprojects/hVISAclassifier. This system is useful and practical for screening MRSA isolates for the hVISA phenotype in clinical microbiology laboratories and thus should improve treatment of MRSA infections.

  18. Rapid and easy detection of low-level resistance to vancomycin in methicillin-resistant Staphylococcus aureus by matrix-assisted laser desorption ionization time-of-flight mass spectrometry

    PubMed Central

    Asakura, Kota; Azechi, Takuya; Sasano, Hiroshi; Matsui, Hidehito; Hanaki, Hideaki; Miyazaki, Motoyasu; Takata, Tohru; Sekine, Miwa; Takaku, Tomoiku; Ochiai, Tomonori; Komatsu, Norio; Shibayama, Keigo

    2018-01-01

    Vancomycin-intermediately resistant Staphylococcus aureus (VISA) and heterogeneous VISA (hVISA) are associated with treatment failure. hVISA contains only a subpopulation of cells with increased minimal inhibitory concentrations, and its detection is problematic because it is classified as vancomycin-susceptible by standard susceptibility testing and the gold-standard method for its detection is impractical in clinical microbiology laboratories. Recently, a research group developed a machine-learning classifier to distinguish VISA and hVISA from vancomycin-susceptible S. aureus (VSSA) according to matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) data. Nonetheless, the sensitivity of hVISA classification was found to be 76%, and the program was not completely automated with a graphical user interface. Here, we developed a more accurate machine-learning classifier for discrimination of hVISA from VSSA and VISA among MRSA isolates in Japanese hospitals by means of MALDI-TOF MS data. The classifier showed 99% sensitivity of hVISA classification. Furthermore, we clarified the procedures for preparing samples and obtaining MALDI-TOF MS data and developed all-in-one software, hVISA Classifier, with a graphical user interface that automates the classification and is easy for medical workers to use; it is publicly available at https://github.com/bioprojects/hVISAclassifier. This system is useful and practical for screening MRSA isolates for the hVISA phenotype in clinical microbiology laboratories and thus should improve treatment of MRSA infections. PMID:29522576

  19. Survival of enterococci during hospital laundry processing.

    PubMed

    Orr, K E; Holliday, M G; Jones, A L; Robson, I; Perry, J D

    2002-02-01

    Much remains to be elucidated about the epidemiology of nosocomial enterococcal infections. Enterococci are, however, known to be relatively thermotolerant, and several studies have shown that under laboratory conditions many strains are able to survive the time/temperature combinations of the UK Department of Health recommendations for the decontamination of used linen (HSG(95)18). We therefore wished to investigate the efficacy of decontamination of enterococci from hospital linen in working hospital laundries. The thermotolerance of 40 strains of Enterococcus faecalis and Enterococcus faecium was first determined. Reduction by a factor of greater than 10(5) was achieved in only two of 40 strains after 3 min at 71 degrees C or 10 min at 65 degrees C, the time/temperature combinations specified by the Department of Health for the disinfection of used linen. During experimental challenge of 10 working hospital laundries, however, we demonstrated successful decontamination of laundry artificially contaminated with enterococci. This was shown to take place during the washing stage. Our study suggests that, despite the relative thermotolerance of enterococci, the time/temperature combinations specified in HSG(95)18 should be adequate for their decontamination in hospital laundries. Copyright 2002 The Hospital Infection Society.

  20. Prevalence and antimicrobial resistance of Enterococcus species of food animal origin from Beijing and Shandong Province, China.

    PubMed

    Liu, Y; Liu, K; Lai, J; Wu, C; Shen, J; Wang, Y

    2013-02-01

    To evaluate the prevalence and antimicrobial resistance of Enterococcus species from chickens and pigs in Beijing and Shandong Province, China. Swab samples were collected from four farms in Beijing and two in Shandong Province in 2009 and tested for Enterococcus. Minimum inhibitory concentrations of antimicrobial agents were determined using broth microdilution or agar screening methods. A total of 453 Enterococcus isolates were recovered, belonging to six different Enterococcus species. All isolates were sensitive to vancomycin. Resistance to tetracycline (92.5%), amikacin (89.4%), erythromycin (72.8%) and rifampin (58.1%), and high-level streptomycin resistance (HLSR, 50.3%) were prevalent, while resistance to penicillins (7.9% to penicillin and 4.2% to ampicillin) was rare. The resistance rates to phenicols (chloramphenicol and florfenicol) and enrofloxacin, and high-level gentamicin resistance (HLGR) were approximately 30%. The vast majority of the Enterococcus isolates were classified as multidrug-resistant organisms. Resistance of Enterococcus sp. to most antimicrobials was more prevalent in China than in European or other Asian countries. Our findings reveal a high level of antimicrobial resistance in Enterococcus isolates from food animals in China and underline the need for prudent use of antibiotics in chicken and pig production to minimize the spread of antibiotic-resistant enterococci. © 2012 The Society for Applied Microbiology.

  1. An economic model to compare linezolid and vancomycin for the treatment of confirmed methicillin-resistant Staphylococcus aureus nosocomial pneumonia in Germany.

    PubMed

    Patel, Dipen A; Michel, Andre; Stephens, Jennifer; Weber, Bertram; Petrik, Christian; Charbonneau, Claudie

    2014-01-01

    Across Europe, methicillin-resistant Staphylococcus aureus (MRSA) is considered to be the primary cause of nosocomial pneumonia (NP). In Germany alone, approximately 14,000 cases of MRSA-associated NP occur annually, which may have a significant impact on health care resource use and associated economic costs. The objective of this study was to investigate the economic impact of linezolid compared with that of vancomycin in the treatment of hospitalized patients with MRSA-confirmed NP in the German health care system. A 4-week decision tree model incorporated published data and expert opinion on clinical parameters, resource use, and costs (2012 euros) was constructed. The base case first-line treatment duration for patients with MRSA-confirmed NP was 10 days. Treatment success (survival), failure due to lack of efficacy, serious adverse events, and mortality were possible outcomes that could impact costs. Alternate scenarios were analyzed, such as varying treatment duration (7 or 14 days) or treatment switch due to a serious adverse event/treatment failure (at day 5 or 10). The model calculated total base case inpatient costs of €15,116 for linezolid and €15,239 for vancomycin. The incremental cost-effectiveness ratio favored linezolid (versus vancomycin), with marginally lower costs (by €123) and greater efficacy (+2.7% absolute difference in the proportion of patients successfully treated for MRSA NP). Approximately 85%-87% of the total treatment costs were attributed to hospital stay (primarily in the intensive care unit). Sensitivity analysis yielded similar results. The model results show that linezolid is a cost-effective alternative to vancomycin for MRSA-confirmed NP, largely attributable to the higher clinical response rate of patients treated with linezolid.

  2. Public Health Risks of Multiple-Drug-Resistant Enterococcus spp. in Southeast Asia

    PubMed Central

    Lee, Sui Mae; Rahman, Sadequr

    2015-01-01

    Enterococci rank as one of the leading causes of nosocomial infections, such as urinary tract infections, surgical wound infections, and endocarditis, in humans. These infections can be hard to treat because of the rising incidence of antibiotic resistance. Enterococci inhabiting nonhuman reservoirs appear to play a critical role in the acquisition and dissemination of antibiotic resistance determinants. The spread of antibiotic resistance has become a major concern in both human and veterinary medicine, especially in Southeast Asia, where many developing countries have poor legislation and regulations to control the supply and excessive use of antimicrobials. This review addresses the occurrence of antibiotic-resistant enterococci in Association of Southeast Asian Nations countries and proposes infection control measures that should be applied to limit the spread of multiple-drug-resistant enterococci. PMID:26150452

  3. PEGylated liposomal vancomycin: a glimmer of hope for improving treatment outcomes in MRSA pneumonia.

    PubMed

    Pumerantz, Andrew S

    2012-12-01

    Methicillin-resistant Staphylococcus aureus (MRSA) plays a significant role in the pandemic of multidrug resistant bacterial infections and is a major cause of hospital-acquired pneumonia. MRSA pneumonia carries a high morbidity and mortality rate especially in elderly diabetics with chronic kidney disease. S. aureus is highly virulent and successful respiratory pathogen. Vancomycin and linezolid are the only two antimicrobial agents FDA-approved to treat MRSA pneumonia. Standard vancomycin dosing is associated with high clinical failure rates and higher dosages are associated with increased nephrotoxicity. Pharmacokinetic and pharmacodynamic limitations are major contributors to poor outcomes with vancomycin. New agents are needed to improve treatment outcomes with MRSA pneumonia. Recently released antimicrobials with in vitro activity are not FDA-approved for treating MRSA pneumonia. Other novel agents are being investigated though none are in late-stage development. Pharmaceutical industry perception of low returns on investment, a Sisyphean regulatory environment, and obstacles to patentability have contributed to declining interest in both the development of novel antibiotics and the improvement of existing generic formulations. Despite decades of investigation into liposomal encapsulation as a drug delivery system that would increase efficacy and decrease toxicity, only liposomal amphotericin B and doxorubicin are commercially available. In this article, the pharmacokinetics and biodistribution of a novel PEGylated liposomal vancomycin formulation along with passive targeting and the enhanced permeability and retention effect of liposomal drug delivery; the pathogenesis of MRSA pneumonia; and recent patents of novel anti-MRSA agents, including inhalational liposomal vancomycin, are reviewed.

  4. AUC/MIC Pharmacodynamic Target Is Not a Good Predictor of Vancomycin Efficacy in Methicillin-Resistant Staphylococcus aureus Experimental Endocarditis

    PubMed Central

    Castañeda, Ximena; García-de-la-Mària, Cristina; Gasch, Oriol; Pericas, Juan M.; Armero, Yolanda; Soy, Dolors; García-González, Javier; Falces, Carlos; Ninot, Salvador; Almela, Manel; Ambrosioni, Juan; Quintana, Eduardo; Vidal, Barbara; Fuster, David; Llopis, Jaume; Soto, Sara; Moreno, Asuncion; Marco, Francesc

    2017-01-01

    ABSTRACT The aim of this in vivo study was to compare the efficacy of vancomycin at standard doses (VAN-SD) to that of VAN at adjusted doses (VAN-AD) in achieving a VAN area under the curve/MIC ratio (AUC/MIC) of ≥400 against three methicillin-resistant Staphylococcus aureus (MRSA) strains with different microdilution VAN MICs in an experimental endocarditis model. The valve vegetation bacterial counts after 48 h of VAN therapy were compared, and no differences were observed between the two treatment groups for any of the three strains tested. Overall, for VAN-SD and VAN-AD, the rates of sterile vegetations were 15/45 (33.3%) and 21/49 (42.8%) (P = 0.343), while the medians (interquartile ranges [IQRs]) for log10 CFU/g of vegetation were 2 (0 to 6.9) and 2 (0 to 4.5) (P = 0.384), respectively. In conclusion, this VAN AUC/MIC pharmacodynamic target was not a good predictor of vancomycin efficacy in MRSA experimental endocarditis. PMID:28373187

  5. AUC/MIC Pharmacodynamic Target Is Not a Good Predictor of Vancomycin Efficacy in Methicillin-Resistant Staphylococcus aureus Experimental Endocarditis.

    PubMed

    Castañeda, Ximena; García-de-la-Mària, Cristina; Gasch, Oriol; Pericas, Juan M; Armero, Yolanda; Soy, Dolors; García-González, Javier; Falces, Carlos; Ninot, Salvador; Almela, Manel; Ambrosioni, Juan; Quintana, Eduardo; Vidal, Barbara; Fuster, David; Llopis, Jaume; Soto, Sara; Moreno, Asuncion; Marco, Francesc; Miró, Jose M

    2017-06-01

    The aim of this in vivo study was to compare the efficacy of vancomycin at standard doses (VAN-SD) to that of VAN at adjusted doses (VAN-AD) in achieving a VAN area under the curve/MIC ratio (AUC/MIC) of ≥400 against three methicillin-resistant Staphylococcus aureus (MRSA) strains with different microdilution VAN MICs in an experimental endocarditis model. The valve vegetation bacterial counts after 48 h of VAN therapy were compared, and no differences were observed between the two treatment groups for any of the three strains tested. Overall, for VAN-SD and VAN-AD, the rates of sterile vegetations were 15/45 (33.3%) and 21/49 (42.8%) ( P = 0.343), while the medians (interquartile ranges [IQRs]) for log 10 CFU/g of vegetation were 2 (0 to 6.9) and 2 (0 to 4.5) ( P = 0.384), respectively. In conclusion, this VAN AUC/MIC pharmacodynamic target was not a good predictor of vancomycin efficacy in MRSA experimental endocarditis. Copyright © 2017 American Society for Microbiology.

  6. Heterogeneous resistance to vancomycin in Staphylococcus epidermidis, Staphylococcus haemolyticus and Staphylococcus warneri clinical strains: characterisation of glycopeptide susceptibility profiles and cell wall thickening.

    PubMed

    Nunes, Ana Paula Ferreira; Teixeira, Lúcia Martins; Iorio, Natália Lopes Pontes; Bastos, Carla Callegário Reis; de Sousa Fonseca, Leila; Souto-Padrón, Thaís; dos Santos, Kátia Regina Netto

    2006-04-01

    The population analysis profile (PAP) method as well as analysis of autolytic activity and cellular ultrastructure by transmission electron microscopy (TEM) were used to characterise Staphylococcus epidermidis, Staphylococcus haemolyticus and Staphylococcus warneri clinical strains with reduced susceptibility to glycopeptides. All strains showed heterogeneous profiles to vancomycin and teicoplanin by the PAP method. Subpopulations that grew in the presence of high concentrations of each drug were selected from the PAP as derivative strains. Their glycopeptide minimal inhibitory concentrations (MICs) were determined and subsequently all parental and derivative strains were grown in one-half of the MIC of vancomycin or teicoplanin. An increase in cell wall thickness of all derivative strains was seen by TEM, with statistically significant values (P<0.01) compared with their respective parental strains. In general, variable rates of autolysis among the strains were observed. Cell wall thickness is an important factor involved in glycopeptide resistance and, in association with PAP results, confirmed the Brazilian coagulase-negative staphylococci clinical isolates as being heteroresistant to glycopeptides. Detection of these heteroresistant organisms is important in order to achieve more judicious use of vancomycin and teicoplanin in hospitals.

  7. Influence of Age on Frequency of Vancomycin Dosing

    PubMed Central

    Legal, Michael; Wan, Marisa

    2010-01-01

    Background: Vancomycin is commonly prescribed at the authors’ institution because of a high prevalence of invasive infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in a generally younger population. The most commonly prescribed empiric dosing interval is every 12 h (q12h). However, observations have suggested that younger adult patients require more frequent dosing, such as every 8 h (q8h). Initial underdosing of vancomycin may increase the risk of antibiotic failure. Objective: To determine whether patients under 40 years of age are more likely than older patients to require q8h dosing of vancomycin and whether recommendations can be made to alter current prescribing practices. Methods: This retrospective unmatched case–control study involved patients who had received vancomycin for suspected or confirmed severe MRSA infections. The cases were patients who had been confirmed as requiring q8h dosing, and the controls were patients who had been confirmed as requiring q12h dosing (on the basis of target predose serum levels). The influence of age (the predictor variable) on outcome (the vancomycin regimen) was evaluated by logistic regression. Results: The odds ratio for patients under 40 years of age requiring q8h dosing was 3.1 (95% confidence interval 1.5–6.3) (p = 0.002). Sixty percent of patients under 40 ultimately required a q8h regimen to achieve target predose serum levels. Patients who required q8h dosing took longer to achieve their first therapeutic serum level than those with q12h dosing (median 6 versus 4 days; p < 0.001). Conclusions: In this patient population, age less than 40 years was a strong predictor for requiring more frequent dosing of vancomycin. The authors suggest that doses of 15 mg/kg IV q8h be used empirically for younger patients with severe infections and normal renal function. PMID:22478948

  8. Occurrence of airborne vancomycin- and gentamicin-resistant bacteria in various hospital wards in Isfahan, Iran

    PubMed Central

    Mirhoseini, Seyed Hamed; Nikaeen, Mahnaz; Khanahmad, Hossein; Hassanzadeh, Akbar

    2016-01-01

    Background: Airborne transmission of pathogenic resistant bacteria is well recognized as an important route for the acquisition of a wide range of nosocomial infections in hospitals. The aim of this study was to determine the prevalence of airborne vancomycin and gentamicin (VM and GM) resistant bacteria in different wards of four educational hospitals. Materials and Methods: A total of 64 air samples were collected from operating theater (OT), Intensive Care Unit (ICU), surgery ward, and internal medicine ward of four educational hospitals in Isfahan, Iran. Airborne culturable bacteria were collected using all glass impingers. Samples were analyzed for the detection of VM- and GM-resistant bacteria. Results: The average level of bacteria ranged from 99 to 1079 CFU/m3. The highest level of airborne bacteria was observed in hospital 4 (628 CFU/m3) and the highest average concentration of GM- and VM-resistant airborne bacteria were found in hospital 3 (22 CFU/m3). The mean concentration of airborne bacteria was the lowest in OT wards and GM- and VM-resistant airborne bacteria were not detected in this ward of hospitals. The highest prevalence of antibiotic-resistant airborne bacteria was observed in ICU ward. There was a statistically significant difference for the prevalence of VM-resistant bacteria between hospital wards (P = 0.012). Conclusion: Our finding showed that the relatively high prevalence of VM- and GM-resistant airborne bacteria in ICUs could be a great concern from the point of view of patients' health. These results confirm the necessity of application of effective control measures which significantly decrease the exposure of high-risk patients to potentially airborne nosocomial infections. PMID:27656612

  9. Occurrence of airborne vancomycin- and gentamicin-resistant bacteria in various hospital wards in Isfahan, Iran.

    PubMed

    Mirhoseini, Seyed Hamed; Nikaeen, Mahnaz; Khanahmad, Hossein; Hassanzadeh, Akbar

    2016-01-01

    Airborne transmission of pathogenic resistant bacteria is well recognized as an important route for the acquisition of a wide range of nosocomial infections in hospitals. The aim of this study was to determine the prevalence of airborne vancomycin and gentamicin (VM and GM) resistant bacteria in different wards of four educational hospitals. A total of 64 air samples were collected from operating theater (OT), Intensive Care Unit (ICU), surgery ward, and internal medicine ward of four educational hospitals in Isfahan, Iran. Airborne culturable bacteria were collected using all glass impingers. Samples were analyzed for the detection of VM- and GM-resistant bacteria. The average level of bacteria ranged from 99 to 1079 CFU/m(3). The highest level of airborne bacteria was observed in hospital 4 (628 CFU/m(3)) and the highest average concentration of GM- and VM-resistant airborne bacteria were found in hospital 3 (22 CFU/m(3)). The mean concentration of airborne bacteria was the lowest in OT wards and GM- and VM-resistant airborne bacteria were not detected in this ward of hospitals. The highest prevalence of antibiotic-resistant airborne bacteria was observed in ICU ward. There was a statistically significant difference for the prevalence of VM-resistant bacteria between hospital wards (P = 0.012). Our finding showed that the relatively high prevalence of VM- and GM-resistant airborne bacteria in ICUs could be a great concern from the point of view of patients' health. These results confirm the necessity of application of effective control measures which significantly decrease the exposure of high-risk patients to potentially airborne nosocomial infections.

  10. Biochemical and genetic characterization of the vanC-2 vancomycin resistance gene cluster of Enterococcus casseliflavus ATCC 25788.

    PubMed

    Dutta, Ireena; Reynolds, Peter E

    2002-10-01

    The vanC-2 cluster of Enterococcus casseliflavus ATCC 25788 consisted of five genes (vanC-2, vanXY(C-2), vanT(C-2), vanR(C-2), and vanS(C-2)) and shared the same organization as the vanC cluster of E. gallinarum BM4174. The proteins encoded by these genes displayed a high degree of amino acid identity to the proteins encoded within the vanC gene cluster. The putative D,D-dipeptidase-D,D-carboxypeptidase, VanXY(C-2), exhibited 81% amino acid identity to VanXY(C), and VanT(C-2) displayed 65% amino acid identity to the serine racemase, VanT. VanR(C-2) and VanS(C-2) displayed high degrees of identity to VanR(C) and VanS(C), respectively, and contained the conserved residues identified as important to their function as a response regulator and histidine kinase, respectively. Resistance to vancomycin was expressed inducibly in E. casseliflavus ATCC 25788 and required an extended period of induction. Analysis of peptidoglycan precursors revealed that UDP-N-acetylmuramyl-L-Ala-delta-D-Glu-L-Lys-D-Ala-D-Ser could not be detected until several hours after the addition of vancomycin, and its appearance coincided with the resumption of growth. The introduction of additional copies of the vanT(C-2) gene, encoding a putative serine racemase, and the presence of supplementary D-serine in the growth medium both significantly reduced the period before growth resumed after addition of vancomycin. This suggested that the availability of D-serine plays an important role in the induction process.

  11. Linking non-culturable (qPCR) and culturable enterococci densities with hydrometeorological conditions

    USGS Publications Warehouse

    Byappanahalli, Muruleedhara N.; Whitman, Richard L.; Shively, Dawn A.; Nevers, Meredith B.

    2010-01-01

    Quantitative polymerase chain reaction (qPCR) measurement of enterococci has been proposed as a rapid technique for assessment of beach water quality, but the response of qPCR results to environmental conditions has not been fully explored. Culture-based E. coli and enterococci have been used in empirical predictive models to characterize their responses to environmental conditions and to increase monitoring frequency and efficiency. This approach has been attempted with qPCR results only in few studies. During the summer of 2006, water samples were collected from two southern Lake Michigan beaches and the nearby river outfall (Burns Ditch) and were analyzed for enterococci by culture-based and non-culture-based (i.e., qPCR) methods, as well as culture-based E. coli. Culturable enterococci densities (log CFU/100 ml) for the beaches were significantly correlated with enterococci qPCR cell equivalents (CE) (R = 0.650, P N = 32). Enterococci CE and CFU densities were highest in Burns Ditch relative to the beach sites; however, only CFUs were significantly higher (P R = 0.565, P N = 32). Culturable E. coli and enterococci densities were significantly correlated (R = 0.682, P N = 32). Regression analyses suggested that enterococci CFU could be predicted by lake turbidity, Burns Ditch discharge, and wind direction (adjusted R2 = 0.608); enterococci CE was best predicted by Burns Ditch discharge and log-transformed lake turbidity × wave height (adjusted R2 = 0.40). In summary, our results show that analytically, the qPCR method compares well to the non-culture-based method for measuring enterococci densities in beach water and that both these approaches can be predicted by hydrometeorological conditions. Selected predictors and model results highlight the differences between the environmental responses of the two method endpoints and the potentially high variance in qPCR results

  12. Resistance mechanisms of linezolid-nonsusceptible enterococci in Korea: low rate of 23S rRNA mutations in Enterococcus faecium.

    PubMed

    Lee, Sae-Mi; Huh, Hee Jae; Song, Dong Joon; Shim, Hyang Jin; Park, Kyung Sun; Kang, Cheol-In; Ki, Chang-Seok; Lee, Nam Yong

    2017-12-01

    To investigate linezolid-resistance mechanisms in linezolid-nonsusceptible enterococci (LNSE) isolated from a tertiary hospital in Korea. Enterococcal isolates exhibiting linezolid MICs ≥4 mg l -1 that were isolated between December 2011 and May 2016 were investigated by PCR and sequencing for mutations in 23S rRNA or ribosomal proteins (L3, L4 and L22) and for the presence of cfr, cfr(B) and optrA genes.Results/Key findings. Among 135 LNSE (87 Enterococcus faecium and 48 Enterococcus faecalis isolates), 39.1 % (34/87) of E. faecium and 18.8 % (9/48) of E. faecalis isolates were linezolid-resistant. The optrA carriage was the dominant mechanism in E. faecalis: 13 isolates, including 10 E. faecalis [70 % (7/10) linezolid-resistant and 30 % (3/10) linezolid-intermediate] and three E. faecium [33.3 % (1/3) linezolid-resistant and 66.7 % (2/3) linezolid-intermediate], contained the optrA gene. G2576T mutations in the 23S rRNA gene were detected only in E. faecium [14 isolates; 71.4 % (10/14) linezolid-resistant and 28.6 % (4/14) linezolid-intermediate]. One linezolid-intermediate E. faecium harboured a L22 protein alteration (Ser77Thr). No isolates contained cfr or cfr(B) genes and any L3 or L4 protein alterations. No genetic mechanism of resistance was identified for 67.6 % (23/34) of linezolid-resistant E. faecium. A low rate of 23S rRNA mutations and the absence of known linezolid-resistance mechanisms in the majority of E. faecium isolates suggest regional differences in the mechanisms of linezolid resistance and the possibility of additional mechanisms.

  13. Outbreak of vancomycin-resistant enterococcus colonization among pediatric oncology patients.

    PubMed

    Nolan, Sheila M; Gerber, Jeffrey S; Zaoutis, Theoklis; Prasad, Priya; Rettig, Susan; Gross, Kimberly; McGowan, Karin L; Reilly, Anne F; Coffin, Susan E

    2009-04-01

    To detect the burden of vancomycin-resistant Enterococcus (VRE) colonization among pediatric oncology patients and to determine risk factors for VRE acquisition. Retrospective case-control study. The Children's Hospital of Philadelphia. Pediatric oncology patients hospitalized from June 2006 through December 2007. Prevalence surveys revealed an increased VRE burden among pediatric oncology patients. For the case-control study, the 16 case patients were pediatric oncology patients who had 1 stool sample negative for VRE at screening before having a stool sample positive for VRE at screening; the 62 control patients had 2 consecutive screenings in which stool samples were negative for VRE. Case and control patients were matched on the duration of the interval between screens. Analyses were performed to determine the association between multiple exposures and VRE acquisition. The prevalence survey revealed that 5 (9.6%) of 52 patients had unsuspected VRE colonization at the time of hospitalization. Multivariate analysis identified a lack of empirical contact precautions (odds ratio [OR], 17.16 [95% confidence interval {CI}, 1.49-198.21]; P= .02) and the presence of a gastrointestinal device (OR, 4.03 [95% CI, 1.04-15.56]; P= .04) as significant risk factors for acquisition of VRE. Observations in the interventional radiology department revealed that staff could not access the portions of the electronic medical record in which isolation precautions were documented. Simple interventions that granted access and that trained interventional radiology staff to review the need for precautions, coupled with enhanced infection control practices, interrupted ongoing transmission and reduced the proportion of VRE screens that were positive to 15 (1.2%) of 1,270. Inadequate communication with regard to infection control precautions can increase the risk of transmission of epidemiologically important organisms, particularly when patients receive care at multiple clinic locations

  14. Enterococci in the Environment

    EPA Science Inventory

    Enterococci are common, commensal members of gut communities in mammals and birds, yet they are also opportunistic pathogens that cause millions of human and animal infections annually. Because they are shed in human and animal feces, are readily culturable, and predict human hea...

  15. Antibiotic-resistant fecal bacteria, antibiotics, and mercury in surface waters of Oakland County, Michigan, 2005-2006

    USGS Publications Warehouse

    Fogarty, Lisa R.; Duris, Joseph W.; Crowley, Suzanne L.; Hardigan, Nicole

    2007-01-01

    Water samples collected from 20 stream sites in Oakland and Macomb Counties, Mich., were analyzed to learn more about the occurrence of cephalosporin-resistant Escherichia coli (E. coli) and vancomycin-resistant enterococci (VRE) and the co-occurrence of antibiotics and mercury in area streams. Fecal indicator bacteria concentrations exceeded the Michigan recreational water-quality standard of 300 E. coli colony forming units (CFU) per 100 milliliters of water in 19 of 35 stream-water samples collected in Oakland County. A gene commonly associated with enterococci from humans was detected in samples from Paint Creek at Rochester and Evans Ditch at Southfield, indicating that human fecal waste is a possible source of fecal contamination at these sites. E. coli resistant to the cephalosporin antibiotics (cefoxitin and/ or ceftriaxone) were found at all sites on at least one occasion. The highest percentages of E. coli isolates resistant to cefoxitin and ceftriaxone were 71 percent (Clinton River at Auburn Hills) and 19 percent (Sashabaw Creek near Drayton Plains), respectively. Cephalosporin-resistant E. coli was detected more frequently in samples from intensively urbanized or industrialized areas than in samples from less urbanized areas. VRE were not detected in any sample collected in this study. Multiple antibiotics (azithromycin, erythromycin, ofloxacin, sulfamethoxazole, and trimethoprim) were detected in water samples from the Clinton River at Auburn Hills, and tylosin (an antibiotic used in veterinary medicine and livestock production that belongs to the macrolide group, along with erythromycin) was detected in one water sample from Paint Creek at Rochester. Concentrations of total mercury were as high as 19.8 nanograms per liter (Evans Ditch at Southfield). There was no relation among percentage of antibiotic-resistant bacteria and measured concentrations of antibiotics or mercury in the water. Genetic elements capable of exchanging multiple antibiotic-resistance

  16. Search for Novel Antibacterial Compounds and Targets.

    PubMed

    Kuroda, Teruo; Ogawa, Wakano

    2017-01-01

    Drug-resistant bacteria including methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Pseudomonas aeruginosa, and vancomycin-resistant enterococci (VRE) have been spreading; however, the development of new antibacterial drugs has not progressed accordingly. Novel antibacterial drugs or their candidate seeds need to be developed for effective antibiotic therapy. Under these conditions, the search for novel compounds and novel targets is important. In Okayama University, as a part of the Drug Discovery for Intractable Infectious Diseases project, we are proceeding with the development of antibacterial drugs for the treatment of drug-resistant bacterial infections. We found that riccardin C (a natural product of liverwort) and 6,6'-dihydroxythiobinupharidine (from the crude drug Senkotsu) exhibited strong antibacterial activities, particularly against Gram-positive bacteria. We showed that riccardin C induced cell membrane leakage and that 6,6'-dihydroxythiobinupharidine inhibited DNA topoisomerase IV. Moreover, 6,6'-dihydroxythiobinupharidine exerted synergistic effects with already known anti-MRSA drugs as well as with vancomycin for VRE.

  17. A 1.5 hour procedure for identification of Enterococcus Species directly from blood cultures.

    PubMed

    Morgan, Margie A; Marlowe, Elizabeth; Novak-Weekly, Susan; Miller, J M; Painter, T M; Salimnia, Hossein; Crystal, Benjamin

    2011-02-10

    Enterococci are a common cause of bacteremia with E. faecalis being the predominant species followed by E. faecium. Because resistance to ampicillin and vancomycin in E. faecalis is still uncommon compared to resistance in E. faecium, the development of rapid tests allowing differentiation between enterococcal species is important for appropriate therapy and resistance surveillance. The E. faecalis OE PNA FISH assay (AdvanDx, Woburn, MA) uses species-specific peptide nucleic acid (PNA) probes in a fluorescence in situ hybridization format and offers a time to results of 1.5 hours and the potential of providing important information for species-specific treatment. Multicenter studies were performed to assess the performance of the 1.5 hour E. faecalis/OE PNA FISH procedure compared to the original 2.5 hour assay procedure and to standard bacteriology methods for the identification of enterococci directly from a positive blood culture bottle.

  18. A 1.5 Hour Procedure for Identification of Enterococcus Species Directly from Blood Cultures

    PubMed Central

    Morgan, Margie A.; Marlowe, Elizabeth; Novak-Weekly, Susan; Miller, J.M.; Painter, T.M.; Salimnia, Hossein; Crystal, Benjamin

    2011-01-01

    Enterococci are a common cause of bacteremia with E. faecalis being the predominant species followed by E. faecium. Because resistance to ampicillin and vancomycin in E. faecalis is still uncommon compared to resistance in E. faecium, the development of rapid tests allowing differentiation between enterococcal species is important for appropriate therapy and resistance surveillance. The E. faecalis OE PNA FISH assay (AdvanDx, Woburn, MA) uses species-specific peptide nucleic acid (PNA) probes in a fluorescence in situ hybridization format and offers a time to results of 1.5 hours and the potential of providing important information for species-specific treatment. Multicenter studies were performed to assess the performance of the 1.5 hour E. faecalis/OE PNA FISH procedure compared to the original 2.5 hour assay procedure and to standard bacteriology methods for the identification of enterococci directly from a positive blood culture bottle. PMID:21339730

  19. Resistance profiles and risk factors of resistant microorganisms in bacteraemia of abdominal origin.

    PubMed

    Martín Jaramago, J; Armero Ibáñez, R; Camarena Miñana, J J; Morales Suárez-Varela, M

    2017-11-01

    The presence of resistant microorganisms is a major cause of failure in initial empirical antimicrobial therapy. The objectives of this study are to determine the resistance profile of microorganisms that cause bacteraemia of abdominal origin and to identify whether the previous use of antibiotics and the place of acquisition of bacteraemia are risk factors associated with the presence of resistant organisms. A clinical, observational, epidemiological, retrospective cohort study was conducted with all the adult patients admitted to a university hospital from 2011-2013. Antimicrobial resistance profiles were described and a 95% confidence interval chi-square test was used to determine whether the variables studied were risk factors in the isolation of resistant microorganisms. Of the 1245 patients with bacteraemia, 212 (17%) presented bacteraemia of abdominal origin. The resistance profile highlights the incidence of methicillin resistant Staphylococcus aureus (50%), coagulase-negative staphylococci resistant to linezolid (20.58%), enterococci resistant to vancomycin (3.12%), Escherichia coli resistant to third-generation cephalosporins (9.9%) and fluoroquinolones (35.64%), Klebsiella pneumoniae resistant to third-generation cephalosporins (8.33%), Pseudomonas aeruginosa resistant to fluoroquinolones and carbapenem (25% and 25% respectively) and Acinetobacter baumanii resistant to fluoroquinolones and carbapenem (100% and 100% respectively), Candida albicans resistant to fluconazole (11.11%), single Candida krusei isolate resistant to fluconazole and Candida parapsilosis resistant to echinocandins (12.5%). In our study, previous use of antibiotics had a statistically significant association with the isolation of resistant microorganisms (P=.013) but not the place of acquisition of bacteraemia (P=.239). Establishing the incidence of resistant organisms can improve empirical antimicrobial therapy in patients with bacteraemia of abdominal origin. Previous use of

  20. Role of the transmembrane domain of the VanT serine racemase in resistance to vancomycin in Enterococcus gallinarum BM4174.

    PubMed

    Arias, C A; Peña, J; Panesso, D; Reynolds, P

    2003-03-01

    Enterococcus gallinarum BM4175 (a vancomycin-susceptible derivative of BM4174 obtained by insertional inactivation of vanC-1) was transformed with plasmid constructs pCA10 (containing the genes necessary for resistance, vanC-1-XYc-T), pJP1 (with a fragment lacking the DNA encoding the transmembrane region of VanT, -vanC-1-XYc-T((Delta))(2-322)-) and with plasmids containing fragments encoding either the transmembrane (mvanT(1-322)) or racemase (svanT(323-698)) domains of VanT under the control of a constitutive promoter. Accumulated peptidoglycan precursors were measured in all strains in the presence of L-Ser, D-Ser (50 mM) or in the absence of any growth supplement. Uptake of 0.1 mM L-[(14)C]serine was also determined in BM4174, BM4175 and BM4175/pCA10. Vancomycin resistance was restored in BM4175 transformed with pCA10(C-1-XYc-T), and the profile of peptidoglycan precursors was similar to wild-type E. gallinarum BM4174. Transformation of E. gallinarum BM4175 with plasmid pJP1(vanC-1-XYc-T((Delta))(2-322)) resulted in: (i) vancomycin MICs remaining within susceptible levels (< or =4 mg/L) in the absence of any growth supplement, but increasing to 8 mg/L when either L-Ser or D-Ser was added to the medium; and (ii) the relative amounts of accumulated UDP-MurNAc-pentapeptide[D-Ser] and tetrapeptide precursors decreasing substantially compared with BM4175/pCA10 and BM4174. The effect on the appearance of tetrapeptide appeared to be host dependent, since a substantial amount was present when the same plasmid construct pJP1(vanC-1-XYc-T((Delta))(2-322)) was electroporated into Enterococcus faecalis JH2-2. The uptake of L-[(14)C]Ser at 240 s was decreased by approximately 40% in BM4175 compared with BM4174. Plasmid pCA10(C-1-XY(C)-T) restored uptake of L-[(14)C]Ser at 180 and 240 s in BM4175. The results suggest that the transmembrane domain of VanT is likely to be involved in the transport of L-Ser, and that in its absence the resistance phenotype is compromised.

  1. Comparative analysis of the complete genome of an epidemic hospital sequence type 203 clone of vancomycin-resistant Enterococcus faecium

    PubMed Central

    2013-01-01

    Background In this report we have explored the genomic and microbiological basis for a sustained increase in bloodstream infections at a major Australian hospital caused by Enterococcus faecium multi-locus sequence type (ST) 203, an outbreak strain that has largely replaced a predecessor ST17 sequence type. Results To establish a ST203 reference sequence we fully assembled and annotated the genome of Aus0085, a 2009 vancomycin-resistant Enterococcus faecium (VREfm) bloodstream isolate, and the first example of a completed ST203 genome. Aus0085 has a 3.2 Mb genome, comprising a 2.9 Mb circular chromosome and six circular plasmids (2 kb–130 kb). Twelve percent of the 3222 coding sequences (CDS) in Aus0085 are not present in ST17 E. faecium Aus0004 and ST18 E. faecium TX16. Extending this comparison to an additional 12 ST17 and 14 ST203 E. faecium hospital isolate genomes revealed only six genomic regions spanning 41 kb that were present in all ST203 and absent from all ST17 genomes. The 40 CDS have predicted functions that include ion transport, riboflavin metabolism and two phosphotransferase systems. Comparison of the vancomycin resistance-conferring Tn1549 transposon between Aus0004 and Aus0085 revealed differences in transposon length and insertion site, and van locus sequence variation that correlated with a higher vancomycin MIC in Aus0085. Additional phenotype comparisons between ST17 and ST203 isolates showed that while there were no differences in biofilm-formation and killing of Galleria mellonella, ST203 isolates grew significantly faster and out-competed ST17 isolates in growth assays. Conclusions Here we have fully assembled and annotated the first ST203 genome, and then characterized the genomic differences between ST17 and ST203 E. faecium. We also show that ST203 E. faecium are faster growing and can out-compete ST17 E. faecium. While a causal genetic basis for these phenotype differences is not provided here, this study revealed conserved genetic

  2. Design, synthesis, and biological evaluation of a novel series of quercetin diacylglucosides as potent anti-MRSA and anti-VRE agents.

    PubMed

    Hossion, Abugafar M L; Otsuka, Nao; Kandahary, Rafiya K; Tsuchiya, Tomofusa; Ogawa, Wakano; Iwado, Akimasa; Zamami, Yoshito; Sasaki, Kenji

    2010-09-01

    A series of novel quercetin diacylglucosides were designed and first synthesized by Steglich esterification on the basis of MRSA strains inhibiting natural compound A. The in vitro inhibition of different multi-drug resistant bacterial strains and Escherichia coli DNA gyrase B was investigated. In the series, compound 10h was up to 128-fold more potent against vancomycin-resistant enterococci and more effective than A, which represents a promising new candidate as a potent anti-MRSA and anti-VRE agent. Copyright 2010. Published by Elsevier Ltd.

  3. The cost effectiveness of vancomycin for preventing infections after shoulder arthroplasty: a break-even analysis.

    PubMed

    Hatch, M Daniel; Daniels, Stephen D; Glerum, Kimberly M; Higgins, Laurence D

    2017-03-01

    Increasing methicillin resistance and recognition of Propionibacterium acnes as a cause of infection in shoulder arthroplasty has led to the adoption of local vancomycin powder application as a more effective method to prevent expensive periprosthetic infections. However, no study has analyzed the cost effectiveness of vancomycin powder for preventing infection after shoulder replacement. Cost data for infection-related care of 16 patients treated for deep periprosthetic shoulder infection was collected from our institution for the break-even analysis. An equation was developed and applied to the data to determine how effective vancomycin powder would need to be at reducing a baseline infection rate to make prophylactic use cost effective. The efficacy of vancomycin (absolute risk reduction [ARR]) was evaluated at different unit costs, baseline infection rates, and average costs of treating infection. We determined vancomycin to be cost effective if the initial infection rate decreased by 0.04% (ARR). Using the current costs of vancomycin reported in the literature (range: $2.50/1000 mg to $44/1000 mg), we determined vancomycin to be cost effective with an ARR range of 0.01% at a cost of $2.50/1000 mg to 0.19% at $44/1000 mg. Baseline infection rate does not influence the ARR obtained at any specific cost of vancomycin or the cost of treating infection. We have derived and used a break-even equation to assess efficacy of prophylactic antibiotics during shoulder surgery. We further demonstrated the prophylactic administration of local vancomycin powder during shoulder arthroplasty to be a highly cost-effective practice. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  4. Adjunctive vancomycin powder in pediatric spine surgery is safe.

    PubMed

    Gans, Itai; Dormans, John P; Spiegel, David A; Flynn, John M; Sankar, Wudbhav N; Campbell, Robert M; Baldwin, Keith D

    2013-09-01

    Therapeutic level II cohort study. To evaluate the safety of adjunctive local application of vancomycin powder (VP) for infection prophylaxis in posterior instrumented thoracic and lumbar spine wounds in pediatric patients weighing more than 25 kg. Spine surgeons have largely turned to vancomycin prophylaxis in an attempt to decrease the incidence of late surgical site infection and acute surgical site infection from methicillin-resistant Staphylococcus aureus. In adult patients, the adjunctive local application of VP with an intravenous cephalosporin has been shown to decrease postsurgical wound infection rates significantly; however, the safety of VP as an adjunct in pediatric spine surgery has not been reported. We reviewed data collected under a systematic protocol specifically designed to monitor the safety profile of VP. We measured changes in creatinine and systemic vancomycin levels after intrawound application of 500 mg of unreconstituted VP during spine deformity correction surgery in patients weighing more than 25 kg (patients also received routine intravenous cephalosporin prophylaxis). Laboratory values were measured preoperatively and on postoperative days 1 and 4. Any adverse reactions and infections through available follow-up (2-8 mo) were recorded. Eighty-seven consecutive pediatric patients with spinal deformity weighing more than 25 kg who received intraoperative VP during a 9-month period were identified. Sixty-three percent of the patients in this series had adolescent idiopathic scoliosis, 15% congenital scoliosis, 15% neuromuscular scoliosis, and 5% spondylolisthesis. The average change in creatinine levels between the preoperative and postoperative day 1 draw was -0.03 and between the preoperative and postoperative day 4 draw was -0.075. The postoperative systemic vancomycin levels remained undetectable. None of the patients experienced nephrotoxicity or red man syndrome. Three of the 87 patients developed a surgical site infection. In this

  5. Nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus treated with linezolid or vancomycin: A secondary economic analysis of resource use from a Spanish perspective.

    PubMed

    Rello, J; Nieto, M; Solé-Violán, J; Wan, Y; Gao, X; Solem, C T; De Salas-Cansado, M; Mesa, F; Charbonneau, C; Chastre, J

    2016-11-01

    Adopting a unique Spanish perspective, this study aims to assess healthcare resource utilization (HCRU) and the costs of treating nosocomial pneumonia (NP) produced by methicillin-resistant Staphylococcus aureus (MRSA) in hospitalized adults using linezolid or vancomycin. An evaluation is also made of the renal failure rate and related economic outcomes between study groups. An economic post hoc evaluation of a randomized, double-blind, multicenter phase 4 study was carried out. Nosocomial pneumonia due to MRSA in hospitalized adults. The modified intent to treat (mITT) population comprised 224 linezolid- and 224 vancomycin-treated patients. Costs and HCRU were evaluated between patients administered either linezolid or vancomycin, and between patients who developed renal failure and those who did not. Analysis of HCRU outcomes and costs. Total costs were similar between the linezolid- (€17,782±€9,615) and vancomycin-treated patients (€17,423±€9,460) (P=.69). The renal failure rate was significantly lower in the linezolid-treated patients (4% vs. 15%; P<.001). The total costs tended to be higher in patients who developed renal failure (€19,626±€10,840 vs. €17,388±€9,369; P=.14). Among the patients who developed renal failure, HCRU (days on mechanical ventilation: 13.2±10.7 vs. 7.6±3.6 days; P=.21; ICU stay: 14.4±10.5 vs. 9.9±6.6 days; P=.30; hospital stay: 19.5±9.5 vs. 16.1±11.0 days; P=.26) and cost (€17,219±€8,792 vs. €20,263±€11,350; P=.51) tended to be lower in the linezolid- vs. vancomycin-treated patients. There were no statistically significant differences in costs per patient-day between cohorts after correcting for mortality (€1000 vs. €1,010; P=.98). From a Spanish perspective, there were no statistically significant differences in total costs between the linezolid and vancomycin pneumonia cohorts. The drug cost corresponding to linezolid was partially offset by fewer renal failure adverse events. Copyright © 2016

  6. Mutations associated with reduced surotomycin susceptibility in Clostridium difficile and Enterococcus species.

    PubMed

    Adams, Hannah M; Li, Xiang; Mascio, Carmela; Chesnel, Laurent; Palmer, Kelli L

    2015-07-01

    Clostridium difficile infection (CDI) is an urgent public health concern causing considerable clinical and economic burdens. CDI can be treated with antibiotics, but recurrence of the disease following successful treatment of the initial episode often occurs. Surotomycin is a rapidly bactericidal cyclic lipopeptide antibiotic that is in clinical trials for CDI treatment and that has demonstrated superiority over vancomycin in preventing CDI relapse. Surotomycin is a structural analogue of the membrane-active antibiotic daptomycin. Previously, we utilized in vitro serial passage experiments to derive C. difficile strains with reduced surotomycin susceptibilities. The parent strains used included ATCC 700057 and clinical isolates from the restriction endonuclease analysis (REA) groups BI and K. Serial passage experiments were also performed with vancomycin-resistant and vancomycin-susceptible Enterococcus faecium and Enterococcus faecalis. The goal of this study is to identify mutations associated with reduced surotomycin susceptibility in C. difficile and enterococci. Illumina sequence data generated for the parent strains and serial passage isolates were compared. We identified nonsynonymous mutations in genes coding for cardiolipin synthase in C. difficile ATCC 700057, enoyl-(acyl carrier protein) reductase II (FabK) and cell division protein FtsH2 in C. difficile REA type BI, and a PadR family transcriptional regulator in C. difficile REA type K. Among the 4 enterococcal strain pairs, 20 mutations were identified, and those mutations overlap those associated with daptomycin resistance. These data give insight into the mechanism of action of surotomycin against C. difficile, possible mechanisms for resistance emergence during clinical use, and the potential impacts of surotomycin therapy on intestinal enterococci. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  7. Susceptibility Profile of Staphylococcus epidermidis and Staphylococcus haemolyticus Isolated from Blood Cultures to Vancomycin and Novel Antimicrobial Drugs over a Period of 12 Years.

    PubMed

    Pinheiro, Luiza; Brito, Carla Ivo; Pereira, Valéria Cataneli; Oliveira, Adilson; Bartolomeu, Ariane Rocha; Camargo, Carlos Henrique; Cunha, Maria Lourdes Ribeiro Souza

    2016-06-01

    The aim of this study was to evaluate the antimicrobial susceptibility profile of 85 Staphylococcus epidermidis and 84 Staphylococcus haemolyticus strains isolated from blood cultures to oxacillin, vancomycin, tigecycline, linezolid, daptomycin, and quinupristin/dalfopristin over a period of 12 years. S. epidermidis and S. haemolyticus isolated from blood cultures of inpatients, attended at a teaching hospital, were analyzed for the presence of the mecA gene and by SCCmec typing. The minimum inhibitory concentration (MIC) values of tigecycline, linezolid, daptomycin, quinupristin/dalfopristin, and vancomycin were determined. Isolates exhibiting vancomycin MICs of ≥2 μg/ml were typed by pulsed-field gel electrophoresis (PFGE). The rate of mecA positivity was 92.9% and 100% in S. epidermidis and S. haemolyticus, respectively. The most frequent SCCmec types were type III (53.2%) in S. epidermidis and type I (32.1%) in S. haemolyticus. All isolates were susceptible to linezolid and daptomycin, but 7.1% of S. haemolyticus and 2.3% of S. epidermidis isolates were resistant to tigecycline, and 1.2% each of S. haemolyticus and S. epidermidis were resistant and intermediately resistant to quinupristin/dalfopristin, respectively. S. epidermidis exhibited higher vancomycin MICs (40% with MIC of ≥2 μg/ml). Clonal typing of strains with vancomycin MIC of ≥2 μg/ml revealed the presence of different PFGE types of S. epidermidis and S. haemolyticus over a period of up to 4 years (2002-2004, 2005-2008, 2006-2009, 2010-2011). Despite the observation of a high prevalence of mecA, the clinical strains were fully susceptible to vancomycin and to the new drugs linezolid, daptomycin, tigecycline, and quinupristin/dalfopristin. The PFGE types with vancomycin MIC of ≥2 μg/ml exhibited a great diversity of SCCmec cassettes, demonstrating that S. epidermidis and S. haemolyticus may easily acquire these resistance-conferring genetic elements.

  8. Short- and long-term effects of oral vancomycin on the human intestinal microbiota

    PubMed Central

    Isaac, Sandrine; Scher, Jose U.; Djukovic, Ana; Jiménez, Nuria; Littman, Dan R.; Abramson, Steven B.; Pamer, Eric G.; Ubeda, Carles

    2017-01-01

    Background Oral vancomycin remains the mainstay of therapy for severe infections produced by Clostridium difficile, the most prevalent cause of healthcare-associated infectious diarrhoea in developed countries. However, its short- and long-term effects on the human intestinal microbiota remain largely unknown. Methods We utilized high-throughput sequencing to analyse the effects of vancomycin on the faecal human microbiota up to 22 weeks post-antibiotic cessation. The clinical relevance of the observed microbiota perturbations was studied in mice. Results During vancomycin therapy, most intestinal microbiota genera and operational taxonomic units (OTUs) were depleted in all analysed subjects, including all baseline OTUs from the phylum Bacteroidetes. This was accompanied by a vast expansion of genera associated with infections, including Klebsiella and Escherichia/Shigella. Following antibiotic cessation, marked differences in microbiota resilience were observed among subjects. While some individuals recovered a microbiota close to baseline composition, in others, up to 89% of abundant OTUs could no longer be detected. The clinical relevance of the observed microbiota changes was further demonstrated in mice, which developed analogous microbiota alterations. During vancomycin treatment, mice were highly susceptible to intestinal colonization by an antibiotic-resistant pathogen and, upon antibiotic cessation, a less-resilient microbiota allowed higher levels of pathogen colonization. Conclusions Oral vancomycin induces drastic and consistent changes in the human intestinal microbiota. Upon vancomycin cessation, the microbiota recovery rate varied considerably among subjects, which could influence, as validated in mice, the level of susceptibility to pathogen intestinal colonization. Our results demonstrate the negative long-term effects of vancomycin, which should be considered as a fundamental aspect of the cost–benefit equation for antibiotic prescription. PMID

  9. In vitro antibacterial activity of seven Indian spices against high level gentamicin resistant strains of enterococci

    PubMed Central

    Bipin, Chapagain; Chitra, Pai (Bhat); Minakshi, Bhattacharjee

    2015-01-01

    Introduction The aim of the study was to explore the in vitro antibacterial activity of seven ethanolic extracts of spices against high level gentamicin resistant (HLGR) enterococci isolated from human clinical samples. Material and methods Two hundred and fifteen enterococcal strains were isolated from clinical samples. High level gentamicin resistance in ethanolic extracts of cumin (Cuminum cyminum), cinnamon (Cinnamomum zeylanicum), ginger (Zingiber officinale), fenugreek (Trigonella foenum-graecum), cloves (Syzygium aromaticum), cardamom (Elettaria cardamomum Maton) and black pepper (Piper nigrum) were prepared using Soxhlet apparatus. The antibacterial effect of the extracts was studied using the well diffusion method. Statistical analysis was carried out by χ2 test using SPSS 17 software. Results Only cinnamon and ginger were found to have activity against all the isolates, whereas cumin and cloves had a variable effect on the strains. Fenugreek, black pepper and cardamom did not show any effect on the isolates. The zone diameter of inhibition obtained for cinnamon, ginger, cloves and cumin was in the range 31–34 mm, 27–30 mm, 25–26 mm and 19–20 mm respectively. Conclusions Cinnamomum zeylanicum and Z. officinale showed the maximum antibacterial activity against the enterococcal isolates followed by S. aromaticum and C. cyminum. The findings of the study show that spices used in the study can contribute to the development of potential antimicrobial agents for inclusion in the anti-enterococcal treatment regimen. PMID:26322099

  10. Healthcare-associated Staphylococcus aureus bacteremia in children: Evidence for reverse vancomycin creep and impact of vancomycin trough levels on outcome

    PubMed Central

    McNeil, J Chase; Kok, Eric Y; Forbes, Andrea; Lamberth, Linda; Hulten, Kristina G; Vallejo, Jesus G; Mason, Edward O; Kaplan, Sheldon L

    2015-01-01

    Introduction Elevated vancomycin MICs in S. aureus have been associated with worse clinical outcomes in adults. For invasive MRSA infections in adults, the IDSA recommends targeting vancomycin serum trough concentrations between 15–20 μg/ml. We evaluated trends in vancomycin MICs from healthcare-associated S. aureus bacteremia isolates in children in addition to correlating vancomycin serum trough levels with clinical outcomes. Methods Patients and isolates were identified from a prospective S. aureus surveillance study at Texas Children's Hospital (TCH). Healthcare-associated S. aureus bacteremia isolates from 2003–2013 were selected. Vancomycin MICs by E-test were determined and medical records were reviewed. Acute kidney injury (AKI) was defined as doubling of the baseline serum creatinine. Results 341 isolates met inclusion criteria. We observed a reverse vancomycin creep among MRSA isolates in the study period with a decline in the proportion of isolates with vancomycin MIC ≥ 2 μg/ml (from 32.7% to 5.6%, p<0.001). However, the proportion of MSSA isolates with MIC ≥ 2 μg/ml increased (from 2.9% to 9%, p=0.04). Among patients who had vancomycin troughs performed, there was no difference in duration of bacteremia or fever with vancomycin trough >15 μg/ml vs. < 15 μg/ml. A vancomycin trough > 15 μg/ml was, however, an independent risk factor for AKI. Conclusions Vancomycin MICs are shifting among healthcare-associated S. aureus bacteremia isolates with significant differences between MRSA and MSSA at TCH. Higher vancomycin troughs did not improve outcomes in pediatric healthcare-associated S. aureus bacteremia but were associated with increased nephrotoxicity. Further studies are needed to better understand optimal management of children with S. aureus bacteremia. PMID:26646549

  11. High prevalence of diverse vancomycin resistance Enterococcus faecium isolates in clinical and environmental sources in ICU wards in southwest of Iran.

    PubMed

    Arshadi, Maniya; Douraghi, Masoumeh; Shokoohizadeh, Leili; Moosavian, Seyed Mojtaba; Pourmand, Mohammad Reza

    2017-10-01

    This study aimed at determining the prevalence, antibiotic resistance patterns, and genetic linkage of Vancomycin Resistant Enterococcus faecium (VREfm) from different sources in the southwest of Iran. A total of 51 VREfm isolates were obtained and subjected to antibiotic susceptibility testing, carriage of virulence genes, and pulsed-field gel electrophoresis (PFGE) method. All the VRE isolates exhibited a high level of resistance to teicoplanin, ampicillin, erythromycin, ciprofloxacin, and gentamicin, also carried the vanA gene. A total of 59% and 34% of the VREfm strains harbored esp and hyl genes, respectively. The results from PFGE showed 31 PFGE patterns including 10 common types (CT) and 21 single types (ST) among the VRE isolates. Furthermore, isolates from different sources in each common type revealed cross transmission between clinical and environmental sources. Overall, the study showed a high prevalence of diverse VRE faecium strains with threatening resistance phenotypes in the environment and clinical sections among different ICU wards of Ahvaz hospitals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Comparative Analysis of the First Complete Enterococcus faecium Genome

    PubMed Central

    Lam, Margaret M. C.; Seemann, Torsten; Bulach, Dieter M.; Gladman, Simon L.; Chen, Honglei; Haring, Volker; Moore, Robert J.; Ballard, Susan; Grayson, M. Lindsay; Johnson, Paul D. R.; Howden, Benjamin P.

    2012-01-01

    Vancomycin-resistant enterococci (VRE) are one of the leading causes of nosocomial infections in health care facilities around the globe. In particular, infections caused by vancomycin-resistant Enterococcus faecium are becoming increasingly common. Comparative and functional genomic studies of E. faecium isolates have so far been limited owing to the lack of a fully assembled E. faecium genome sequence. Here we address this issue and report the complete 3.0-Mb genome sequence of the multilocus sequence type 17 vancomycin-resistant Enterococcus faecium strain Aus0004, isolated from the bloodstream of a patient in Melbourne, Australia, in 1998. The genome comprises a 2.9-Mb circular chromosome and three circular plasmids. The chromosome harbors putative E. faecium virulence factors such as enterococcal surface protein, hemolysin, and collagen-binding adhesin. Aus0004 has a very large accessory genome (38%) that includes three prophage and two genomic islands absent among 22 other E. faecium genomes. One of the prophage was present as inverted 50-kb repeats that appear to have facilitated a 683-kb chromosomal inversion across the replication terminus, resulting in a striking replichore imbalance. Other distinctive features include 76 insertion sequence elements and a single chromosomal copy of Tn1549 containing the vanB vancomycin resistance element. A complete E. faecium genome will be a useful resource to assist our understanding of this emerging nosocomial pathogen. PMID:22366422

  13. Effect of Protein Binding on the Activity of Penicillins in Combination with Gentamicin Against Enterococci

    PubMed Central

    Glew, Richard H.; Moellering, Robert C.

    1979-01-01

    To assess the effect of protein binding by human serum on the synergistic interaction of penicillins with gentamicin, time-kill curves were determined for four penicillins alone and in combination with gentamicin against 10 blood isolates of enterococci. Killing curves demonstrated synergism with penicillin G plus gentamicin against all 10 strains in either broth or 50% human serum. In broth the combinations of nafcillin plus gentamicin and oxacillin plus gentamicin were synergistic against 10 of 10 strains and 4 of 10 strains, respectively. However, in serum, nafcillin plus gentamicin was synergistically bactericidal against only two strains and oxacillin plus gentamicin against none. Methicillin plus gentamicin was synergistic against none of the enterococci in either medium. Thus, the semisynthetic, penicillinase-resistant penicillins are unlikely to be effective in the therapy of patients with enterococcal endocarditis. PMID:426508

  14. Clinical features and treatment outcomes of vancomycin-intermediate Staphylococcus aureus (VISA) and heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) in a tertiary care institution in Singapore.

    PubMed

    Fong, R K C; Low, J; Koh, T H; Kurup, A

    2009-08-01

    This retrospective case-control study was undertaken to review the clinical features associated with heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) and vancomycin-intermediate S. aureus (VISA) infections and the local impact they have on clinical outcome. Compared with vancomycin-susceptible S. aureus (n = 30), hVISA and VISA infections (n = 10) are found to be associated with a longer period of prior glycopeptide use (P = 0.01), bone/joint (P < 0.01) and prosthetic infections (P = 0.04), as well as treatment failure, as evidenced by longer bacteremic (P < 0.01) and culture positivity (P < 0.01) periods. This was observed to have resulted in longer hospital length of stay (P < 0.01) and total antibiotic therapy duration (P = 0.01). There was, however, no significant difference in the overall patient mortality or the hospitalization cost (P = 0.12) in both groups. Clinicians should be cognizant of the association between hVISA/VISA with high bacterial load deep-seated infections. We recommend targeted and even universal screening for hVISA/VISA in methicillin-resistant S. aureus (MRSA) infections.

  15. Clostridium difficile Infection and Patient-Specific Antimicrobial Resistance Testing Reveals a High Metronidazole Resistance Rate.

    PubMed

    Barkin, Jodie A; Sussman, Daniel A; Fifadara, Nimita; Barkin, Jamie S

    2017-04-01

    Clostridium difficile (CD) infection (CDI) causes marked morbidity and mortality, accounting for large healthcare expenditures annually. Current CDI treatment guidelines focus on clinical markers of patient severity to determine the preferred antibiotic regimen of metronidazole versus vancomycin. The antimicrobial resistance patterns for patients with CD are currently unknown. The aim of this study was to define the antimicrobial resistance patterns for CD. This study included all patients with stools sent for CD testing to a private laboratory (DRG Laboratory, Alpharetta, Georgia) in a 6-month period from across the USA. Patient data was de-identified, with only age, gender, and zip-code available per laboratory protocol. All samples underwent PCR testing followed by hybridization for CD toxin regions A and B. Only patients with CD-positive PCR were analyzed. Antimicrobial resistance testing using stool genomic DNA evaluated presence of imidazole- and vancomycin-resistant genes using multiplex PCR gene detection. Of 2743, 288 (10.5%) stool samples were positive for CD. Six were excluded per protocol. Of 282, 193 (69.4%) were women, and average age was 49.4 ± 18.7 years. Of 282, 62 were PCR positive for toxins A and B, 160 for toxin A positive alone, and 60 for toxin B positive alone. Antimicrobial resistance testing revealed 134/282 (47.5%) patients resistant to imidazole, 17 (6.1%) resistant to vancomycin, and 9 (3.2%) resistant to imidazole and vancomycin. CD-positive patients with presence of imidazole-resistant genes from stool DNA extract was a common phenomenon, while vancomycin resistance was uncommon. Similar to treatment of other infections, antimicrobial resistance testing should play a role in CDI clinical decision-making algorithms to enable more expedited and cost-effective delivery of patient care.

  16. Zunyimycins B and C, New Chloroanthrabenzoxocinones Antibiotics against Methicillin-Resistant Staphylococcus aureus and Enterococci from Streptomyces sp. FJS31-2.

    PubMed

    Lü, Yuhong; Shao, Meiyun; Wang, Yinyin; Qian, Shengyan; Wang, Miao; Wang, Yingquan; Li, Xiaoqian; Bao, Yuxin; Deng, Chengmin; Yue, Changwu; Liu, Daishun; Liu, Ning; Liu, Minghao; Huang, Ying; Chen, Zehui; Hu, Yonglin

    2017-02-08

    This study performed an optimization of the fermentation conditions to activate the expression of the zunyimycin family biosynthesis genes of the zunyimycin-producing streptomycetes strain Streptomyces sp. FJS31-2. Bioassay-guided isolation and purification by varied chromatographic methods yielded two new compounds of the zunyimycin derivatives, namely, 31-2-7 and 31-2-8, accompanied with three known anthrabenzoxocinones family members of zunyimycin A, BE24566B, and chloroanthrabenzoxocinone. Their structures were elucidated by NMR, HRESIMS, IR, UV, and CD. Results showed that these two compounds were structurally similar to the previously reported compound zunyimycin A but differed in positions and number of chlorine atom substitution. The two novel compounds were called zunyimycins B and C. Antibacterial activity assay indicated that zunyimycin C showed a good inhibitory effect on the methicillin-resistant Staphylococcus aureus and Enterococci .

  17. [Two cases of vancomycin-intermediate Staphylococcus aureus isolated from joint tissue or wound].

    PubMed

    Hong, Ki Ho; Park, Jeong Su; Kim, Eui-Chong

    2008-12-01

    Since its first isolation in 1997, vancomycin-intermediate Staphylococcus aureus (VISA) has been a clinical concern because it may lead to treatment failure. Up to the present, there were two reports of clinical VISA cases in Korea. We now report two additional cases of VISA with the minimum inhibitory concentration (MIC) of 4 microg/mL. The first patient was a 59 yr-old man who had undergone total hip replacement arthroplasty in 1999 due to avascular necrosis of femur heads. He had recurrent episodes of infected hip caused by methicillin-resistant Staphylococcus aureus (MRSA) and was treated with vancomycin. He underwent replacement operation of prosthesis. Cultures of joint fluid and joint tissue grew S. aureus. Vancomycin MIC as determined by a broth microdilution method was 4 microg/mL for the both isolates. The patient was treated with high enough doses of vancomycin to maintain serum trough concentrations at 20-25 microg/mL for 52 days and was discharged. The second patient was a 57 yr-old man with diabetes. He lost consciousness from drinking. After recovery of consciousness, he was diagnosed with aspiration pneumonia. MRSA and Acinetobacter baumannii were cultured from sputum and the patient was treated with vancomycin and meropenem. During hospitalization, bed sores developed in his ankle and back. A wound culture from the sore grew S. aureus with vancomycin MIC of 4 microg/mL. Since infection was localized, systemic antibiotics did not seem necessary, and the patient was transferred to another hospital for isolation and management.

  18. Lactobacillus reuteri and Escherichia coli in the human gut microbiota may predict weight gain associated with vancomycin treatment

    PubMed Central

    Million, M; Thuny, F; Angelakis, E; Casalta, J-P; Giorgi, R; Habib, G; Raoult, D

    2013-01-01

    Background: Antibiotics, used for 60 years to promote weight gain in animals, have been linked to obesity in adults and in children when administered during early infancy. Lactobacillus reuteri has been linked to obesity and weight gain in children affected with Kwashiorkor using ready-to-use therapeutic food. In contrast, Escherichia coli has been linked with the absence of obesity. Both of these bacteria are resistant to vancomycin. Objectives and methods: We assessed vancomycin-associated weight and gut microbiota changes, and tested whether bacterial species previously linked with body mass index (BMI) predict weight gain at 1 year. All endocarditis patients treated with vancomycin or amoxicillin in our center were included from January 2008 to December 2010. Bacteroidetes, Firmicutes, Lactobacillus and Methanobrevibacter smithii were quantified using real-time PCR on samples obtained during the 4–6 weeks antibiotic regimen. L. reuteri, L. plantarum, L. rhamnosus, Bifidobacterium animalis and E. coli were quantified on stool samples obtained during the first week of antibiotics. Results: Of the193 patients included in the study, 102 were treated with vancomycin and 91 with amoxicillin. Vancomycin was associated with a 10% BMI increase (odds ratio (OR) 14.1; 95% confidence interval (CI; 1.03–194); P=0.047) and acquired obesity (4/41 versus 0/56, P=0.01). In patients treated with vancomycin, Firmicutes, Bacteroidetes and Lactobacillus increased, whereas M. smithii decreased (P<0.05). The absence of E. coli was an independent predictor of weight gain (OR=10.7; 95% CI (1.4–82.0); P=0.02). Strikingly, a patient with an 18% BMI increase showed a dramatic increase of L. reuteri but no increase of E. coli. Conclusion: The acquired obesity observed in patients treated with vancomycin may be related to a modulation of the gut microbiota rather than a direct antibiotic effect. L. reuteri, which is resistant to vancomycin and produces broad bacteriocins, may have an

  19. Prediction of Vancomycin Dose for Recommended Trough Concentrations in Pediatric Patients With Cystic Fibrosis.

    PubMed

    Amin, Raid W; Guttmann, Rodney P; Harris, Quianna R; Thomas, Janesha W

    2018-05-01

    Vancomycin is a key antibiotic used in the treatment of multiple conditions including infections associated with cystic fibrosis and methicillin-resistant Staphylococcus aureus. The present study sought to develop a model based on empirical evidence of optimal vancomycin dose as judged by clinical observations that could accelerate the achievement of desired trough level in children with cystic fibrosis. Transformations of dose and trough were used to arrive at regression models with excellent fit for dose based on weight or age for a target trough. Results of this study indicate that the 2 proposed regression models are robust to changes in age or weight, suggesting that the daily dose on a per-kilogram basis is determined primarily by the desired trough level. The results show that to obtain a vancomycin trough level of 20 μg/mL, a dose of 80 mg/kg/day is needed. This analysis should improve the efficiency of vancomycin usage by reducing the number of titration steps, resulting in improved patient outcome and experience. © 2018, The American College of Clinical Pharmacology.

  20. Short- and long-term effects of oral vancomycin on the human intestinal microbiota.

    PubMed

    Isaac, Sandrine; Scher, Jose U; Djukovic, Ana; Jiménez, Nuria; Littman, Dan R; Abramson, Steven B; Pamer, Eric G; Ubeda, Carles

    2017-01-01

    Oral vancomycin remains the mainstay of therapy for severe infections produced by Clostridium difficile, the most prevalent cause of healthcare-associated infectious diarrhoea in developed countries. However, its short- and long-term effects on the human intestinal microbiota remain largely unknown. We utilized high-throughput sequencing to analyse the effects of vancomycin on the faecal human microbiota up to 22 weeks post-antibiotic cessation. The clinical relevance of the observed microbiota perturbations was studied in mice. During vancomycin therapy, most intestinal microbiota genera and operational taxonomic units (OTUs) were depleted in all analysed subjects, including all baseline OTUs from the phylum Bacteroidetes. This was accompanied by a vast expansion of genera associated with infections, including Klebsiella and Escherichia/Shigella. Following antibiotic cessation, marked differences in microbiota resilience were observed among subjects. While some individuals recovered a microbiota close to baseline composition, in others, up to 89% of abundant OTUs could no longer be detected. The clinical relevance of the observed microbiota changes was further demonstrated in mice, which developed analogous microbiota alterations. During vancomycin treatment, mice were highly susceptible to intestinal colonization by an antibiotic-resistant pathogen and, upon antibiotic cessation, a less-resilient microbiota allowed higher levels of pathogen colonization. Oral vancomycin induces drastic and consistent changes in the human intestinal microbiota. Upon vancomycin cessation, the microbiota recovery rate varied considerably among subjects, which could influence, as validated in mice, the level of susceptibility to pathogen intestinal colonization. Our results demonstrate the negative long-term effects of vancomycin, which should be considered as a fundamental aspect of the cost-benefit equation for antibiotic prescription. © The Author 2016. Published by Oxford

  1. [Enterocin typing of enterococci].

    PubMed

    Sedov, V I

    1978-09-01

    The author worked out a method of enterocinotyping on enterococci. A possibility of enterococcus typing by means of a set of enterocinogenic enterococcus strains was shown. A mobile enterococcus 4 (10 p) strain, possessing a high antagonistic activity, is suggested for enterococcus identification. Differentiation of enterococcus species by the enterocine sensitivity proved to be impossible.

  2. Persistence of bacterial pathogens, antibiotic resistance genes, and enterococci in tidal creek tributaries.

    PubMed

    Jones, Chance E; Maddox, Anthony; Hurley, Dorset; Barkovskii, Andrei L

    2018-05-19

    Intertidal creeks form the primary hydrologic link between estuaries and land-based activities on barrier islands. Fecal indicators Enterococcus spp. (Entero1), pathogens Shigella spp. (ipaH), Salmonella spp. (invA), E. coli of EHEC/EPEC groups (eaeA), E. coli of EAEC, EIEC, and UPEC groups (set1B), E. coli of STEC group (stx1); and tetracycline resistance genes (tet(B), tet(C), tet(D), tet(E), tet(K), tet(Q), tet(W), and tet(X); TRG) were detected in the headwater of Oakdale Creek (Sapelo Island, GA) receiving runoffs from Hog Hammock village. Excavation of drainage ditches around the village caused a high increase in the incidence of the above determinants. Water samples were collected from the headwater, transferred to diffusion chambers, submersed in the headwater, saltmarsh, and mouth of the creek; and the determinants were monitored for 3 winter months. With some exceptions, their persistence decreased in order headwater > saltmarsh > mouth. Genes associated with Enterococcus spp. were the most persistent at all the sites, following in the headwater with determinants for Salmonella spp. and E. coli of EAEC, EIEC, and UPEC groups. In the mouth, the most persistent gene was eaeA indicating EHEC, EPEC, and STEC. Tet(B) and tet(C) persisted the longest in headwater and saltmarsh. No TRG persisted after 11 days in the mouth. Most determinants revealed correlations with temperature and pH, and inverse correlations with dissolved oxygen. Decay rates of the above determinants varied in the range of -0.02 to -0.81/day, and were up to 40 folds higher in the saltmarsh and mouth than in the headwater. Our data demonstrated that water parameters could to some extent predict a general trend in the fate of virulence and antibiotic resistance determinants in tidal creek tributaries but strongly suggested that their persistence in these tributaries cannot be predicted from that of enterococci, or extrapolated from one biological contaminant to another. Copyright

  3. Antimicrobial Resistance of Enterococcus Species Isolated from Chicken in Turkey

    PubMed Central

    Sanlibaba, Pınar; Tezel, Basar Uymaz; Senturk, Esra

    2018-01-01

    Abstract The aim of the present work was to provide information about Enterococcus strains isolated from pre-packaged chicken samples in Ankara (Turkey), focusing on their prevalence, phenotypic and genotypic characteristics, and antibiotic resistance. We report the first study on the occurrence of antibiotic resistant enterococci in pre-packaged chicken samples in Ankara. A total of 97 suspicious enterococcal isolates were identified from 122 chicken samples. All isolates were identified to species level by phenotypic and molecular methods. In the 16S rDNA sequence analysis, Enterococcus faecium (61.85%) and Enterococcus faecalis (38.15%) were found to be the most frequently detected Enterococcus spp. Of the 97 isolates tested for hemolytic activity, 12.37% enterococcal strains were β-hemolytic. β-Hemolysin was most prevalent among E. faecium (58.33%) compared to E. faecalis (41.66%). Disk diffusion method was used for determining of antibiotic resistance. The analysis of the antimicrobial resistance of the 97 Enterococcus isolates revealed that the resistance to kanamycin (98.96%), rifampicin (80.41%) and ampicillin (60.82%) was most frequent. Furthermore, resistance to erythromycin (38.14%) and ciprofloxacin (34.02%) was also observed. The frequencies of resistance to tetracycline (9.27%), penicillin G (8.24%), and chloramphenicol (3.09%), gentamicin (2.06%) and streptomycin (1.03%) were low. None of the isolates was resistant to vancomycin. Multi-drug resistance was found in 97.93% of Enterococcus strains. E. faecium strains showed a more resistant phenotype than E. faecalis strains according to the antibiotic resistance levels. The results of this study indicated that chicken meat is a potential reservoir for the transmission of antibiotic resistance from animals to humans. PMID:29805287

  4. Outbreak of Vancomycin-Resistant Enterococcus Colonization Among Pediatric Oncology Patients

    PubMed Central

    Nolan, Sheila M.; Gerber, Jeffrey S.; Zaoutis, Theoklis; Prasad, Priya; Rettig, Susan; Gross, Kimberly; McGowan, Karin L.; Reilly, Anne F.; Coffin, Susan E.

    2010-01-01

    OBJECTIVE To detect the burden of vancomycin-resistant Enterococcus (VRE) colonization among pediatric oncology patients and to determine risk factors for VRE acquisition. DESIGN Retrospective case-control study. SETTING The Children’s Hospital of Philadelphia. PATIENTS Pediatric oncology patients hospitalized from June 2006 through December 2007. METHODS Prevalence surveys revealed an increased VRE burden among pediatric oncology patients. For the case-control study, the 16 case patients were pediatric oncology patients who had 1 stool sample negative for VRE at screening before having a stool sample positive for VRE at screening; the 62 control patients had 2 consecutive screenings in which stool samples were negative for VRE. Case and control patients were matched on the duration of the interval between screens. Analyses were performed to determine the association between multiple exposures and VRE acquisition. RESULTS The prevalence survey revealed that 5 (9.6%) of 52 patients had unsuspected VRE colonization at the time of hospitalization. Multivariate analysis identified a lack of empirical contact precautions (odds ratio [OR], 17.16 [95% confidence interval {CI}, 1.49–198.21]; P = .02) and the presence of a gastrointestinal device (OR, 4.03 [95% CI, 1.04–15.56]; P = .04) as significant risk factors for acquisition of VRE. Observations in the interventional radiology department revealed that staff could not access the portions of the electronic medical record in which isolation precautions were documented. Simple interventions that granted access and that trained interventional radiology staff to review the need for precautions, coupled with enhanced infection control practices, interrupted ongoing transmission and reduced the proportion of VRE screens that were positive to 15 (1.2%) of 1,270. CONCLUSIONS Inadequate communication with regard to infection control precautions can increase the risk of transmission of epidemiologically important organisms

  5. Attachment of Escherichia coli and enterococci to particles in runoff.

    PubMed

    Soupir, Michelle L; Mostaghimi, Saied; Dillaha, Theo

    2010-01-01

    Association of Escherichia coli and enterococci with particulates present in runoff from erodible soils has important implications for modeling the fate and transport of bacteria from agricultural sources and in the selection of management practices to reduce bacterial movement to surface waters. Three soils with different textures were collected from the Ap horizon (silty loam, silty clay loam, and loamy fine sand), placed in portable box plots, treated with standard cowpats, and placed under a rainfall simulator. Rainfall was applied to the plots until saturation-excess flow occurred for 30 min, and samples were collected 10, 20, and 30 min after initiation of the runoff event. The attachment of E. coli and enterococci to particles present in runoff was determined by a screen filtration and centrifugation procedure. Percentage of E. coli and enterococci attached to particulates in runoff ranged from 28 to 49%, with few statistically significant differences in attachment among the three soils. Similar partitioning release patterns were observed between E. coli and enterococci from the silty loam (r = 0.57) and silty clay loam soils (r = 0.60). At least 60% of all attached E. coli and enterococci were associated particles within an 8- to 62-microm particle size category. The results indicate that the majority of fecal bacteria attach to and are transported with manure colloids in sediment-laden flow regardless of the soil texture.

  6. High Prevalence of Multidrug-Resistant Bacteria in Libyan War Casualties Admitted to a Tertiary Care Hospital, Germany.

    PubMed

    Lohr, Benedikt; Pfeifer, Yvonne; Heudorf, Ursel; Rangger, Christoph; Norris, Douglas E; Hunfeld, Klaus-Peter

    2018-06-01

    The ongoing Libyan conflict constantly causes victims among the military and civilian population. Cross-border transfer of patients represents a high risk of introducing multidrug-resistant organisms (MDROs), for example, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci, and carbapenem-resistant gram-negative organisms (CROs), into the country of destination. This study assessed the MDRO status in Libyan war casualties (n = 67) admitted to Northwest Medical Centre in Frankfurt/Main, Germany, from August 2016 till January 2017. Identified multidrug-resistant nonfermenters and Enterobacteriaceae were subjected to molecular detection of β-lactamases and further mechanisms of resistance. All isolates were typed by enzymatic macrorestriction and subsequent pulsed-field gel electrophoresis. MDROs were found in 40 (60%) patients, including 25 (37%) positive for at least one CRO and 11 (16%) patients with MRSA. A total of 37 isolates of Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, Enterobacter cloacae, and Serratia marcescens produced carbapenemases: NDM (n = 17), OXA-48 (n = 15), and OXA-23 (n = 9) in addition to other β-lactamases (with bla CTX-M-group-1 being most frequent) and plasmid-mediated quinolone resistance genes (qnrB, aac(6')Ib-cr). Bacterial strain typing revealed the presence of various clones. This high MDRO rate in Libyan war casualties demands awareness, appropriate screening, and containment measures for medical institutions involved in medical care to avoid patient-to-patient transmission.

  7. Prevalence and antibiotic resistance of Enterococcus spp. isolated from retail cheese, ready-to-eat salads, ham, and raw meat.

    PubMed

    Pesavento, G; Calonico, C; Ducci, B; Magnanini, A; Lo Nostro, A

    2014-08-01

    Food specimens were analyzed in order to research Enterococcus spp.: 636 samples of raw meat (227 beef, 238 poultry, and 171 pork), 278 samples of cheese (110 fresh soft cheese and 168 mozzarella cheese), 214 samples of ready-to-eat salads, and 187 samples of ham. 312 strains of Enterococcus spp samples were isolated, then identified and submitted to susceptibility tests against 11 antimicrobial agents. The predominant species were Enterococcus faecalis in raw meat and Enterococcus faecium in retail products. Low percentages of microorganisms were resistant to vancomycin (3.53%), teicoplanin (2.24%), linezolid (0.32%), and amoxicillin in combination with clavulanic acid (0.32%). A high percentage of resistance was noted in E. faecalis at high level gentamicin (21.9%) and tetracycline (60.6%). In general, strains of E. faecalis were more resistant than E. faecium. Enterococci should be considered not only potential pathogens, but also a reservoir of genes encoding antibiotic resistance which can be transferred to other microorganisms. Continuous monitoring of their incidence and emerging resistance is important in order to identify foods which potentially represent a real risk to the population, and to ensure effective treatment of human enterococcal infections. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Determination of the Feasibility of Preparing Vancomycin Microparticles

    DTIC Science & Technology

    1997-01-01

    Maryland 21702-5012. 13. ABSTRACT (Maximum 200 The main objective of this project was to develop, prepare, and deliver 25 g of vancomycin microcapsules ...demonstrated that the BIOTEK vancomycin microcapsules met all the criteria stipulated in the contract. The microcapsules maintained a sustained release of...therapeutic levels of vancomycin and inhibited bacterial growth of Staphylococcus aureus for 19 days. The preparation of these vancomycin microcapsules

  9. Trend in vancomycin susceptibility and correlation with molecular characteristics of methicillin-resistant Staphylococcus aureus causing invasive infections in Taiwan: results from the Tigecycline in vitro Surveillance in Taiwan (TIST) study, 2006-2010.

    PubMed

    Tsao, Shin-Ming; Wang, Wei-Yao; Ko, Wen-Chien; Huang, Cheng-Hua; Lu, Chin-Te; Chuang, Yin-Ching; Liu, Chia-Ying; Liao, Chun-Hsing; Chen, Yao-Shen; Liu, Yung-Ching; Chen, Wei-Yu; Jang, Tsrang-Neng; Lin, Hsiu-Chen; Chen, Chih-Ming; Shi, Zhi-Yuan; Pan, Sung-Ching; Yang, Jia-Ling; Kung, Hsiang-Chi; Liu, Chun-Eng; Cheng, Yu-Jen; Liu, Jien-Wei; Sun, Wu; Wang, Lih-Shinn; Yu, Kwok-Woon; Chiang, Ping-Cherng; Lee, Ming-Hsun; Lee, Chun-Ming; Hsu, Gwo-Jong; Chen, Yen-Hsu; Lu, Po-Liang; Thomas, Chang-Yao Tsao; Hsueh, Po-Ren

    2014-10-01

    This study was intended to investigate the trend in vancomycin susceptibility and correlation with molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) causing invasive infections. A total of 670 MRSA isolates were collected from patients with invasive infections as part of bacterial collection in the Tigecycline in vitro Surveillance in Taiwan (TIST) from 2006 to 2010. MICs of the isolates to vancomycin were determined using the agar dilution method. Characteristics of staphylococcal cassette chromosome mec (SCCmec), mec-associated hypervariable region (dru), and accessory gene regulator (agr) of the isolates were identified by polymerase chain reaction methods. MRSA isolates with SCCmec types I, II, and III were molecularly defined as hospital-associated MRSA (HA-MRSA), and those with SCCmec types IV, V, and VT were assigned as community-associated MRSA (CA-MRSA). All but 1 MRSA isolates exhibited vancomycin MICs ≤1 mg/L. A declining trend in vancomycin MICs among MRSA isolates was noted, which was associated with the decline in proportion of HA-MRSA. The percentage of CA-MRSA increased from 25.6% in 2006 to 46.0% in 2010. An increase in the geometric mean of vancomycin MICs was found in MRSA with particular molecular types such as SCCmec types II and III, agr groups I and II, and dru10-14. A significant correlation among particular molecular types was found, including SCCmecII-agr group II-dru4, SCCmecIII-agr group I-dru11-14, SCCmecIV-agr group II-dru9, and SCCmecVT-agr group I-dru9 and dru11. There was no vancomycin creep among MRSA isolates, and the declining trend of vancomycin MIC against MRSA was attributed to the increasing prevalence of CA-MRSA over time. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Current and novel antibiotics against resistant Gram-positive bacteria.

    PubMed

    Perez, Federico; Salata, Robert A; Bonomo, Robert A

    2008-01-01

    The challenge posed by resistance among Gram-positive bacteria, epitomized by methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE) and vancomycin-intermediate and -resistant S. aureus (VISA and VRSA) is being met by a new generation of antimicrobials. This review focuses on the new β-lactams with activity against MRSA (ceftobiprole and ceftaroline) and on the new glycopeptides (oritavancin, dalbavancin, and telavancin). It will also consider the role of vancomycin in an era of existing alternatives such as linezolid, daptomycin and tigecycline. Finally, compounds in early development are described, such as iclaprim, friulimicin, and retapamulin, among others.

  11. Diversity of Tn1546 in vanA-positive Enterococcus faecium clinical isolates with VanA, VanB, and VanD phenotypes and susceptibility to vancomycin.

    PubMed

    Cha, J O; Yoo, J I; Kim, H K; Kim, H S; Yoo, J S; Lee, Y S; Jung, Y H

    2013-10-01

    To investigate diversity in the vanA cluster in Enterococcus faecium isolates from nontertiary hospitals. We identified 43 vanA-positive Ent. faecium isolates, including two vancomycin-susceptible isolates, from hospitals between 2003 and 2006. Of these isolates, >85% were resistant to ampicillin, erythromycin and ciprofloxacin. The vanA cluster was classified into six types using overlapping PCR, but the prototype transposon Tn1546 was not found. Most vanA-positive vancomycin-resistant Enterococcus (VRE) carried IS1216V and belonged to Type III (58·1%) or Type II (20·9%). vanY, vanZ and IS1216V were observed in the left and right ends of Type III with long-range PCR. IS1216V was also observed within vanS and vanX in the two vancomycin-susceptible isolates and in two vancomycin-resistant isolates. No VRE isolates with VanB and VanD phenotypes contained point mutations in vanS, unlike in previous reports. Sequence types (STs) of all isolates belonged to clonal complex 17, and ST78 was predominant. Insertion sequences, especially IS1216V, cause structural variation in the vanA cluster. We report the first observation of vanY and vanZ at the left end of Tn1546 in clinical isolates. This is the first report of the frequency of vancomycin resistance and diversity of Tn1546 in vanA-positive Ent. faecium isolates from nontertiary hospitals. © 2013 The Society for Applied Microbiology.

  12. Fosfomycin synergy in vitro with amoxicillin, daptomycin, and linezolid against vancomycin-resistant Enterococcus faecium from renal transplant patients with infected urinary stents.

    PubMed

    Descourouez, Jillian L; Jorgenson, Margaret R; Wergin, Justine E; Rose, Warren E

    2013-03-01

    Fosfomycin is a potential option for vancomycin-resistant enterococcus (VRE) infections despite limited in vitro and clinical data. In this study, 32 VRE isolates from renal transplant patients with urinary stent infections were susceptible to fosfomycin, daptomycin, and linezolid and resistant to amoxicillin, minocycline, and nitrofurantoin based on their MIC(50)s and MIC(90)s. Fosfomycin was bacteriostatic at 0.5 to 16× the MIC (32 to 2,048 μg/ml); synergy occurred when fosfomycin was combined with daptomycin (2.8 to 3.9 log(10) CFU/ml kill; P < 0.001) or amoxicillin (2.6 to 3.4; P < 0.05). These combinations may be potent options to treat VRE urinary infections pending investigation of clinical efficacy.

  13. A vancomycin drug use evaluation and economic analysis in a cancer treatment centre.

    PubMed

    Dranitsaris, G; Pilla, N J; McGreer, A

    1994-04-01

    Princess Margaret Hospital is a 140-bed university affiliated cancer treatment centre. Vancomycin was the only formulary agent available for the treatment of methicillin-resistant gram-positive organisms. The high cost and potential toxicity of this drug warranted a closer examination of its use. The purpose of this study was to evaluate vancomycin use and to determine the economic impact when it was used contrary to newly developed hospital guidelines. A sample of 100 vancomycin orders was randomly selected from all prescriptions filled in 1992. The indication, dose, and duration of therapy for each order were compared against the hospital guidelines. The cost savings associated with altering the sample of prescriptions to meet hospital guidelines were then determined. Nine percent of the prescriptions were for nonapproved indications. The actual dose used did not meet criteria in 32% of cases and the length of therapy was beyond the approved duration in 45% of the orders. If the cases had been altered to meet the guidelines then a total savings of $13,581 would have been realized. The projected savings for the entire year (1992) would have been $100,907. The critical problem areas in vancomycin prescribing were the duration of therapy and dose. The results have provided the impetus to initiate a hospital wide prospective Drug Utilization Evaluation (DUE) study to optimize vancomycin prescribing. The program costs would be easily covered by the expected savings.

  14. Combination of cephalosporins with vancomycin or teicoplanin enhances antibacterial effect of glycopeptides against heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) and VISA.

    PubMed

    Lai, Chih-Cheng; Chen, Chi-Chung; Chuang, Yin-Ching; Tang, Hung-Jen

    2017-01-31

    Eight heterogeneous vancomycin-intermediate S. aureus (h-VISA) and seven VISA clinical isolates confirmed by the population analysis profile/area under the curve ratio (PAP/AUC) were collected. We further performed the PAP/AUC, time-killing methods and MIC tests using vancomycin/teicoplanin alone or combination with susceptible breakpoint concentrations of cefazolin, cefmetazole, cefotaxime, and cefepime for these isolates. The PAP/AUC MIC curve shifted left after addition of cephalosporins with vancomycin or teicoplanin for both h-VISA and VISA isolates. With the combination of different cephalosporins with vancomycin or teicoplanin, the AUC/Mu3 AUC ratio decreased to <0.9 for the standard Mu3 isolate which are compatible with the definition of vancomycin susceptible S. aureus. These decreases ranged between 1.81-2.02 and 2.37-2.85-fold for h-VISA treated with cephalosporins and vancomycin or teicoplanin, and 2.05-4.59, and 2.93-4,89-fold for VISA treated with cephalosporins with vancomycin or teicoplanin. As measured by time-killing assays, the combinations of different cephalosporins with vancomycin concentrations at 1/2 and 1/4 MIC, exhibited a bactericidal and bacteriostatic effect in VISA. The mean fold of MIC decline for vancomycin base combinations ranged from 1.81-3.83 and 2.71-9.33 for h-VISA and VISA, respectively. Overall, this study demonstrated the enhanced antibacterial activity of vancomycin/teicoplanin after adding cephalosporins against clinical h-VISA/VISA isolates.

  15. Combination of cephalosporins with vancomycin or teicoplanin enhances antibacterial effect of glycopeptides against heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) and VISA

    PubMed Central

    Lai, Chih-Cheng; Chen, Chi-Chung; Chuang, Yin-Ching; Tang, Hung-Jen

    2017-01-01

    Eight heterogeneous vancomycin-intermediate S. aureus (h-VISA) and seven VISA clinical isolates confirmed by the population analysis profile/area under the curve ratio (PAP/AUC) were collected. We further performed the PAP/AUC, time-killing methods and MIC tests using vancomycin/teicoplanin alone or combination with susceptible breakpoint concentrations of cefazolin, cefmetazole, cefotaxime, and cefepime for these isolates. The PAP/AUC MIC curve shifted left after addition of cephalosporins with vancomycin or teicoplanin for both h-VISA and VISA isolates. With the combination of different cephalosporins with vancomycin or teicoplanin, the AUC/Mu3 AUC ratio decreased to <0.9 for the standard Mu3 isolate which are compatible with the definition of vancomycin susceptible S. aureus. These decreases ranged between 1.81–2.02 and 2.37–2.85-fold for h-VISA treated with cephalosporins and vancomycin or teicoplanin, and 2.05–4.59, and 2.93–4,89-fold for VISA treated with cephalosporins with vancomycin or teicoplanin. As measured by time-killing assays, the combinations of different cephalosporins with vancomycin concentrations at 1/2 and 1/4 MIC, exhibited a bactericidal and bacteriostatic effect in VISA. The mean fold of MIC decline for vancomycin base combinations ranged from 1.81–3.83 and 2.71–9.33 for h-VISA and VISA, respectively. Overall, this study demonstrated the enhanced antibacterial activity of vancomycin/teicoplanin after adding cephalosporins against clinical h-VISA/VISA isolates. PMID:28139739

  16. Oral care with vancomycin paste for reduction in incidence of alpha-hemolytic streptococcal sepsis.

    PubMed

    Barker, G J; Call, S K; Gamis, A S

    1995-05-01

    alpha-Hemolytic streptococcal (AHS) sepsis is increasing in oncology patients receiving myelosuppressive chemotherapy. In response to a high rate of AHS sepsis in this population at our institution, an oral care protocol was instituted, including vancomycin 0.5% in flavored methylcellulose (vanc paste) applied orally t.i.d. at the oncologists' discretion. A retrospective cohort study of 239 neutropenic episodes among 42 children receiving myelosuppressive chemotherapy between 1988 and 1991 compared the incidence of septicemia based on the prophylactic use of vanc paste. A total of 236 consecutive neutropenic episodes were evaluable, 121 with vanc paste and 115 without. AHS sepsis occurred in one child using vanc paste and in six children not using vanc paste (p = 0.06). Excluding staph-only positive blood cultures, which would not be reduced with a topical oral antibiotic drug, there were 6 and 13 positive blood cultures in the vanc-paste and nonvanc-paste patients, respectively (p = 0.09). There was no increase in incidence of gram-negative bacteremia among vanc-paste recipients. Vancomycin resistance was not encountered. This analysis suggests that vanc paste effectively reduces AHS sepsis, does not increase gram-negative bacteremia, and is not associated with vancomycin resistance. A multicentered, placebo-controlled, double-blind study is currently planned.

  17. Determination of antibiotic resistance of lactic acid bacteria isolated from traditional Turkish fermented dairy products.

    PubMed

    Erginkaya, Z; Turhan, E U; Tatlı, D

    2018-01-01

    In this study, the antibiotic resistance (AR) of lactic acid bacteria (LAB) isolated from traditional Turkish fermented dairy products was investigated. Yogurt, white cheese, tulum cheese, cokelek, camız cream and kefir as dairy products were collected from various supermarkets. Lactic acid bacteria such as Lactobacillus spp., Streptococcus spp., Bifidobacterium spp., and Enterecoccus spp. were isolated from these dairy products. Lactobacillus spp. were resistant to vancomycin (58%), erythromycin (10.8%), tetracycline (4.3%), gentamicin (28%), and ciprofloxacin (26%). Streptococcus spp. were resistant to vancomycin (40%), erythromycin (10%), chloramphenicol (10%), gentamicin (20%), and ciprofloxacin (30%). Bifidobacterium spp. were resistant to vancomycin (60%), E 15 (6.6%), gentamicin (20%), and ciprofloxacin (33%). Enterococcus spp. were resistant to vancomycin (100%), erythromycin (100%), rifampin (100%), and ciprofloxacin (100%). As a result, LAB islated from dairy products in this study showed mostly resistance to vancomycin.

  18. Vancomycin Injection

    MedlinePlus

    ... is in a class of medications called glycopeptide antibiotics. It works by killing bacteria that cause infections.Antibiotics such as vancomycin injection will not work for colds, flu, or other viral infections. Taking ...

  19. Pathogen occurrence and antimicrobial resistance trends among urinary tract infection isolates in the Asia-Western Pacific Region: report from the SENTRY Antimicrobial Surveillance Program, 1998-1999.

    PubMed

    Turnidge, John; Bell, Jan; Biedenbach, Douglas J; Jones, Ronald N

    2002-07-01

    Worldwide surveillance of antimicrobial resistance among urinary tract pathogens is useful to determine important trends and geographical variation for common Gram-positive and -negative species. The most common causative uropathogens often have intrinsic or acquired resistance mechanisms which include ESBL production among enteric bacilli, multi-drug resistant staphylococci and non-fermentative Gram-negative bacilli such as Pseudomonas aeruginosa and Acinetobacter spp. and vancomycin-resistant Enterococcus spp. This study evaluates pathogen frequency and the resistance rates among urinary tract infection (UTI) pathogens in 14 medical centres in the Asia-Pacific region between 1998 and 1999. The isolates were referred to a central monitor for reference NCCLS broth microdilution testing, identification confirmation and patient demographic analysis. Over 50% of the 958 pathogens were Escherichia coli and Klebsiella spp. followed by P. aeruginosa, Enterococcus spp. and Enterobacter spp. Susceptibility for the three enteric bacilli was high for carbapenems (100%), 'fourth-generation' cephalosporins (cefepime 94.9-98.6%) and amikacin (> or = 93.0%). Beta-lactamase inhibitor compounds were more active against E. coli (piperacillin/tazobactam; > 90% susceptible) than the other two enteric species and all other tested agents had a narrower spectra of activity. The rank order of anti-pseudomonal agents was amikacin (91.5% susceptible)> imipenem > piperacillin/tazobactam > tobramycin > ceftazidime and cefepime (77.4 and 76.4% susceptible, respectively). Susceptibility to quinolones for the P. aeruginosa isolates was only 63.2-67.0%. Only one vancomycin-intermediate Enterococcus spp. (van C phenotype) was detected among the 103 strains tested. Newer fluoroquinolones (gatifloxacin; MIC(50), mg/l) were more potent against enterococci than ciprofloxacin (MIC(50), 2 mg/l) and high-level resistance to aminoglycosides was common (41.7%). The data presented are compared to studies

  20. Genome Sequencing Reveals the Environmental Origin of Enterococci and Potential Biomarkers for Water Quality Monitoring

    EPA Science Inventory

    Enterococci are common members of the gut microbiome and frequent causative agents of nosocomial infection. Because of their enteric lifestyle and ease of culturing, enterococci have been used worldwide as indicators of fecal pollution of waters. However, enterococci were recentl...

  1. Vancomycin analogues containing monosaccharides exhibit improved antibiotic activity: a combined one-pot enzymatic glycosylation and chemical diversification strategy.

    PubMed

    Thayer, Desiree A; Wong, Chi-Huey

    2006-09-18

    Many natural products contain carbohydrate moieties that contribute to their biological activity. Manipulation of the carbohydrate domain of natural products through multiple glycosylations to identify new derivatives with novel biological activities has been a difficult and impractical process. We report a practical one-pot enzymatic approach with regeneration of cosubstrates to synthesize analogues of vancomycin that contain an N-alkyl glucosamine, which exhibited marked improvement in antibiotic activity against a vancomycin-resistant strain of Enterococcus.

  2. Daptomycin versus vancomycin for complicated skin and skin structure infections: clinical and economic outcomes.

    PubMed

    Davis, Susan L; McKinnon, Peggy S; Hall, Levi M; Delgado, George; Rose, Warren; Wilson, Robert F; Rybak, Michael J

    2007-12-01

    To assess the effect of daptomycin compared with vancomycin on the clinical and economic outcomes in patients with complicated skin and skin structure infections. Prospective, open-label study. Level 1 trauma center in Detroit, Michigan. Fifty-three adult patients with complicated skin and skin structure infections at risk for methicillin-resistant Staphylococcus aureus (MRSA) infection who were treated with daptomycin and a matched cohort of 212 patients treated with vancomycin. Patients in the prospective arm received intravenous daptomycin 4 mg/kg every 24 hours for at least 3 days but not more than 14 days. Historical controls received at least 3 days of vancomycin dosed to achieve trough concentrations of 5-20 microg/ml. Outcomes evaluated included blinded assessments of clinical resolution, duration of therapy, and costs. The most common diagnoses were cellulitis (31%), abscess (22%), and both cellulitis with abscess (37%). Microbiology differed significantly between groups, with S. aureus found in 27 patients (51%) in the daptomycin group and 167 patients (79%) in the vancomycin group and MRSA in 22 (42%) and 159 (75%), respectively (p<0.001). The proportions of patients with clinical improvement or resolution of their infections on days 3 and 5 were 90% versus 70% and 98% versus 81% in the daptomycin versus vancomycin groups, respectively (p<0.01 for both comparisons), and 100% at the end of therapy in both groups. Among patients with complete resolution of their infections (41 patients [77%] with daptomycin vs 89 patients [42%] with vancomycin, p<0.05), median duration of intravenous therapy was 4 and 7 days, respectively, (p<0.001), and hospital costs were $5027 and $7552 (p<0.001). Patients receiving daptomycin achieved more rapid resolution of symptoms and clinical cure and had a decreased duration of inpatient therapy compared with those receiving vancomycin. This study suggests that daptomycin is a cost-effective alternative to vancomycin for

  3. Preliminary survey of antibiotic-resistant fecal indicator bacteria and pathogenic Escherichia coli from river-water samples collected in Oakland County, Michigan, 2003

    USGS Publications Warehouse

    Fogarty, Lisa R.; Duris, Joseph W.; Aichele, Stephen S.

    2005-01-01

    A preliminary study was done in Oakland County, Michigan, to determine the concentration of fecal indicator bacteria (fecal coliform bacteria and enterococci), antibiotic resistance patterns of these two groups, and the presence of potentially pathogenic Escherichia coli (E. coli). For selected sites, specific members of these groups [E. coli, Enterococcus faecium (E. faecium) and Enterococcus faecalis (E. faecalis)] were isolated and tested for levels of resistance to specific antibiotics used to treat human infections by pathogens in these groups and for their potential to transfer these resistances. In addition, water samples from all sites were tested for indicators of potentially pathogenic E. coli by three assays: a growth-based assay for sorbitol-negative E. coli, an immunological assay for E. coli O157, and a molecular assay for three virulence and two serotype genes. Samples were also collected from two non-urbanized sites outside of Oakland County. Results from the urbanized Oakland County area were compared to those from these two non-urbanized sites. Fecal indicator bacteria concentrations exceeded State of Michigan recreational water-quality standards and (or) recommended U.S. Environmental Protection Agency (USEPA) standards in samples from all but two Oakland County sites. Multiple-antibiotic-resistant fecal coliform bacteria were found at all sites, including two reference sites from outside the county. Two sites (Stony Creek and Paint Creek) yielded fecal coliform isolates resistant to all tested antibiotics. Patterns indicative of extended-spectrum-β-lactamase (ESBL)- producing fecal coliform bacteria were found at eight sites in Oakland County and E. coli resistant to clinically significant antibiotics were recovered from the River Rouge, Clinton River, and Paint Creek. Vancomycin-resistant presumptive enterococci were found at six sites in Oakland County and were not found at the reference sites. Evidence of acquired antibiotic resistances was

  4. Membrane Filter Technique for Enumeration of Enterococci in Marine Waters

    PubMed Central

    Levin, M. A.; Fischer, J. R.; Cabelli, V. J.

    1975-01-01

    A membrane filter procedure is described for the enumeration of enterococci in marine waters. The procedure utilizes a highly selective and somewhat differential primary isolation medium followed by an in situ substrate test for identifying colonies of those organisms capable of hydrolyzing esculin. The procedure (mE) was evaluated with known streptococci strains and field samples with regard to its accuracy, sensitivity, selectivity, specificity, precision, and comparability to existing methods. Essentially quantitative recovery was obtained with seawater-stressed cells of Streptococcus faecalis and S. faccium. Neither S. bovis, S. equinus, S. mitis, nor S. salivarius grew on the medium. The selectivity of the medium was such that a 10,000-fold reduction in background organisms was obtained relative to a medium which contained no inhibitors and was incubated at 35 C. About 90% of those typical colonies designated as enterococci confirmed as such and about 12% of the colonies not so designated were, in fact, identified as enterococci. Plate to plate variability across samples approximated that expected by chance alone. Verified recoveries of enterococci from natural samples by the mE procedure, on the average, exceeded those by the KF method by one order of magnitude. PMID:807165

  5. Environmental Panels as a Proxy for Nursing Facility Patients With Methicillin-Resistant Staphylococcus Aure and Vancomycin-Resistant Enterococcus Colonization.

    PubMed

    Cassone, Marco; Mantey, Julia; Perri, Mary Beth; Gibson, Kristen; Lansing, Bonnie; McNamara, Sara; Patel, Payal K; Cheng, Vincent C C; Walters, Maroya S; Stone, Nimalie D; Zervos, Marcus J; Mody, Lona

    2018-05-02

    Most nursing facilities (NFs) lack methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) surveillance programs due to limited resources and high costs. We investigated the utility of environmental screening of high-touch surfaces in patient rooms as a way to circumvent these challenges. We compared MRSA and VRE culture data from high-touch surfaces in patients' rooms (14450 samples from 6 NFs) and ranked each site's performance in predicting patient colonization (7413 samples). The best-performing sites were included in a MRSA- and a VRE-specific panel that functioned as a proxy for patient colonization. Molecular typing was performed to confirm available concordant patient-environment pairs. We identified and validated a MRSA panel that consisted of the bed controls, nurse call button, bed rail, and TV remote control. The VRE panel included the toilet seat, bed controls, bed rail, TV remote control, and top of the side table. Panel colonization data tracked patient colonization. Negative predictive values were 89%-92% for MRSA and 82%-84% for VRE. Molecular typing confirmed a strong clonal type relationship in available concordant patient-environment pairs (98% for MRSA, 91% for VRE), pointing to common epidemiological patterns for environmental and patient isolates. Environmental panels used as a proxy for patient colonization and incorporated into facility surveillance protocols can guide decolonization strategies, improve awareness of MRSA and VRE burden, and inform efforts to reduce transmission. Targeted environmental screening may be a viable surveillance strategy for MRSA and VRE detection in NFs.

  6. TD-1792 versus Vancomycin for Treatment of Complicated Skin and Skin Structure Infections

    PubMed Central

    Potgieter, Peter D.; Li, Yu-Ping; Barriere, Steven L.; Churukian, Allan; Kingsley, Jeff; Corey, G. Ralph

    2012-01-01

    TD-1792 is a first-in-class glycopeptide-cephalosporin heterodimer that exhibits bactericidal activity against Gram-positive pathogens. We conducted a randomized, double-blind, active-control, phase II trial in patients with complicated skin and skin structure infections caused by suspected or confirmed Gram-positive organisms. Patients 18 to 65 years old were randomized to receive 7 to 14 days of either TD-1792 (2 mg/kg of body weight intravenously [i.v.] every 24 h [q24h]) or vancomycin (1 g i.v. q12h, with dosage regimens adjusted per site-specific procedures). A total of 197 patients were randomized and received at least one dose of study medication. Rates of clinical success at the test-of-cure evaluation were similar in all analysis populations. Among 170 clinically evaluable patients, cure rates were 91.7% and 90.7% in the TD-1792 and vancomycin groups, respectively (95% confidence interval [CI] of −7.9 to 9.7 for the difference). In microbiologically evaluable patients with methicillin-resistant Staphylococcus aureus at baseline (n = 75), cure rates were 94.7% in the TD-1792 group and 91.9% in the vancomycin group. Microbiological eradication of Gram-positive pathogens (n = 126) was achieved in 93.7% and 92.1% of patients in the TD-1792 and vancomycin groups, respectively. Seven patients were discontinued from study medication due to an adverse event (AE): 2 and 5 in the TD-1792 and vancomycin groups, respectively. AEs were of similar types and severities between the two groups, other than pruritus, which was more common in patients who received vancomycin. No patients in the TD-1792 group experienced a serious AE. This study supports further clinical development of TD-1792 in patients with Gram-positive infection. PMID:22869571

  7. Clinico-Microbiological Investigation of Catheter Associated Urinary Tract Infection by Enterococcus faecalis: vanA Genotype

    PubMed Central

    Padmavathy, Kesavaram; Madhavan, Radha; Krithika, Nagarajan; Kiruthiga, Alexander

    2015-01-01

    Prolonged hospitalization and exposure to third generation cephalosporins are reported to facilitate the acquisition and colonization of Vancomycin Resistant Enterococci (VRE). Though VRE is not uncommon in India, urinary tract infection with a vanA genotype is a cause of serious concern as VRE co-exhibit resistance to aminoglycosides. In India, majority of the VRE isolates recovered from hospitalized patients include Enterococcus faecium. We report a case of catheter associated urinary tract infection by an endogenous, multidrug resistant E. faecalis of vanA genotype following prolonged hospitalization, ICU stay, catheterisation and exposure to 3G cephalosporin and metronidazole. The patient responded to linezolid therapy. PMID:26435949

  8. Effect of subtherapeutic vs. therapeutic administration of macrolides on antimicrobial resistance in Mannheimia haemolytica and enterococci isolated from beef cattle

    PubMed Central

    Zaheer, Rahat; Cook, Shaun R.; Klima, Cassidy L.; Stanford, Kim; Alexander, Trevor; Topp, Edward; Read, Ron R.; McAllister, Tim A.

    2013-01-01

    Macrolides are the first-line treatment against bovine respiratory disease (BRD), and are also used to treat infections in humans. The macrolide, tylosin phosphate, is often included in the diet of cattle as a preventative for liver abscesses in many regions of the world outside of Europe. This study investigated the effects of administering macrolides to beef cattle either systemically through a single subcutaneous injection (therapeutic) or continuously in-feed (subtherapeutic), on the prevalence and antimicrobial resistance of Mannheimia haemolytica and Enterococcus spp. isolated from the nasopharynx and faeces, respectively. Nasopharyngeal and faecal samples were collected weekly over 28 days from untreated beef steers and from steers injected once with tilmicosin or tulathromycin or continuously fed tylosin phosphate at dosages recommended by manufacturers. Tilmicosin and tulathromycin were effective in lowering (P < 0.05) the prevalence of M. haemolytica, whereas subtherapeutic tylosin had no effect. M. haemolytica isolated from control- and macrolide-treated animals were susceptible to macrolides as well as to other antibiotics. Major bacteria co-isolated with M. haemolytica from the nasopharynx included Pasteurella multocida, Staphylococcus spp., Acinetobacter spp., Escherichia coli and Bacillus spp. With the exception of M. haemolytica and P. multocida, erythromycin resistance was frequently found in other isolated species. Both methods of macrolide administration increased (P < 0.05) the proportion of erythromycin resistant enterococci within the population, which was comprised almost exclusively of Enterococcus hirae. Injectable macrolides impacted both respiratory and enteric microbes, whereas orally administered macrolides only influenced enteric bacteria. PMID:23750157

  9. Pharmacist-led implementation of a vancomycin guideline across medical and surgical units: impact on clinical behavior and therapeutic drug monitoring outcomes

    PubMed Central

    Phillips, Cameron J; Gordon, David L

    2015-01-01

    Background Vancomycin is the antibiotic of choice for the treatment of serious infections such as methicillin-resistant Staphylococcus aureus (MRSA). Inappropriate prescribing of vancomycin can lead to therapeutic failure, antibiotic resistance, and drug toxicity. Objective To examine the effectiveness of pharmacist-led implementation of a clinical practice guideline for vancomycin dosing and monitoring in a teaching hospital. Methods An observational pre–post study design was undertaken to evaluate the implementation of the vancomycin guideline. The implementation strategy principally involved education, clinical vignettes, and provision of pocket guidelines to accompany release of the guideline to the hospital Intranet. The target cohort for clinical behavioral change was junior medical officers, as they perform the majority of prescribing and monitoring of vancomycin in hospitals. Assessment measures were recorded for vancomycin prescribing, therapeutic drug monitoring, and patient outcomes. Results Ninety-nine patients, 53 pre- and 46 post-implementation, were included in the study. Prescribing of a loading dose increased from 9% to 28% (P=0.02), and guideline adherence to starting maintenance dosing increased from 53% to 63% (P=0.32). Dose adjustment by doctors when blood concentrations were outside target increased from 53% to 71% (P=0.12), and correct timing of initial concentration measurement increased from 43% to 57% (P=0.23). Appropriately timed trough concentrations improved from 73% to 81% (P=0.08). Pre-dose (trough) concentrations in target range rose from 33% to 44% (P=0.10), while potentially toxic concentrations decreased from 32% to 21% (P=0.05) post-implementation. Infection cure rates for patients increased from 85% to 96% (P=0.11) after the guideline was implemented. Conclusion The implementation strategy employed in this study demonstrated potential effectiveness, and should prompt additional larger studies to optimize strategies that will

  10. FINGERPRINTING OF FECAL ENTEROCOCCI BY MATRIX ASSISTED LASER DESORPTION IONIZATION MASS SPECTROMETRY

    EPA Science Inventory

    The fecal enterococci group has been suggested as an indicator of fecal contamination in freshwater and marine water systems and as a potential target for bacterial source tracking of fecal pollution. While many studies have described the diversity of enterococci in environmenta...

  11. 21 CFR 862.3950 - Vancomycin test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862... diagnosis and treatment of vancomycin overdose and in monitoring the level of vancomycin to ensure...

  12. In Vitro Assessment of Electric Currents Increasing the Effectiveness of Vancomycin Against Staphylococcus epidermidis Biofilms.

    PubMed

    Haddad, Peter A; Mah, Thien-Fah; Mussivand, Tofy

    2016-08-01

    Biofilms are communities of bacteria that can cause infections which are resistant to the immune system and antimicrobial treatments, posing a significant threat for patients with implantable and indwelling medical devices. The purpose of our research was to determine if utilizing specific parameters for electric currents in conjunction with antibiotics could effectively treat a highly resistant biofilm. Our study evaluated the impact of 16 μg/mL of vancomycin with or without 22 or 333 μA of direct electric current (DC) generated by stainless steel electrodes against 24-, 48-, and 72-h-old Staphylococcus epidermidis biofilms formed on titanium coupons. An increase in effectiveness of vancomycin was observed with the combination of 333 μA of electric current against 48-h-old biofilms (P value = 0.01) as well as in combination with 22 μA of electric current against 72-h-old biofilms (P value = 0.04); 333 μA of electric current showed the most significant impact on the effectiveness of vancomycin against S. epidermidis biofilms demonstrating a bioelectric effect previously not observed against this strain of bacteria. © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  13. Enhanced Membrane Pore Formation through High-Affinity Targeted Antimicrobial Peptides

    PubMed Central

    Arnusch, Christopher J.; Pieters, Roland J.; Breukink, Eefjan

    2012-01-01

    Many cationic antimicrobial peptides (AMPs) target the unique lipid composition of the prokaryotic cell membrane. However, the micromolar activities common for these peptides are considered weak in comparison to nisin, which follows a targeted, pore-forming mode of action. Here we show that AMPs can be modified with a high-affinity targeting module, which enables membrane permeabilization at low concentration. Magainin 2 and a truncated peptide analog were conjugated to vancomycin using click chemistry, and could be directed towards specific membrane embedded receptors both in model membrane systems and whole cells. Compared with untargeted vesicles, a gain in permeabilization efficacy of two orders of magnitude was reached with large unilamellar vesicles that included lipid II, the target of vancomycin. The truncated vancomycin-peptide conjugate showed an increased activity against vancomycin resistant Enterococci, whereas the full-length conjugate was more active against a targeted eukaryotic cell model: lipid II containing erythrocytes. This study highlights that AMPs can be made more selective and more potent against biological membranes that contain structures that can be targeted. PMID:22768121

  14. Proteomic characterization of vanA-containing Enterococcus recovered from Seagulls at the Berlengas Natural Reserve, W Portugal.

    PubMed

    Radhouani, Hajer; Poeta, Patrícia; Pinto, Luís; Miranda, Júlio; Coelho, Céline; Carvalho, Carlos; Rodrigues, Jorge; López, María; Torres, Carmen; Vitorino, Rui; Domingues, Pedro; Igrejas, Gilberto

    2010-09-21

    Enterococci have emerged as the third most common cause of nosocomial infections, requiring bactericidal antimicrobial therapy. Although vancomycin resistance is a major problem in clinics and has emerged in an important extend in farm animals, few studies have examined it in wild animals. To determine the prevalence of vanA-containing Enterococcus strains among faecal samples of Seagulls (Larus cachinnans) of Berlengas Natural Reserve of Portugal, we developed a proteomic approach integrated with genomic data. The purpose was to detect the maximum number of proteins that vary in different enterococci species which are thought to be connected in some, as yet unknown, way to antibiotic resistance. From the 57 seagull samples, 54 faecal samples showed the presence of Enterococcus isolates (94.7%). For the enterococci, E. faecium was the most prevalent species in seagulls (50%), followed by E. faecalis and E. durans (10.4%), and E. hirae (6.3%). VanA-containing enterococcal strains were detected in 10.5% of the 57 seagull faecal samples studied. Four of the vanA-containing enterococci were identified as E. faecium and two as E. durans. The tet(M) gene was found in all five tetracycline-resistant vanA strains. The erm(B) gene was demonstrated in all six erythromycin-resistant vanA strains. The hyl virulence gene was detected in all four vanA-containing E. faecium isolates in this study, and two of them harboured the purK1 allele. In addition these strains also showed ampicillin and ciprofoxacin resistance. The whole-cell proteomic profile of vanA-containing Enterococcus strains was applied to evaluate the discriminatory power of this technique for their identification. The major differences among species-specific profiles were found in the positions corresponding to 97-45 kDa. Sixty individualized protein spots for each vanA isolate was identified and suitable for peptide mass fingerprinting measures by spectrometry measuring (MALDI/TOF MS) and their identification

  15. Proteomic characterization of vanA-containing Enterococcus recovered from Seagulls at the Berlengas Natural Reserve, W Portugal

    PubMed Central

    2010-01-01

    Background Enterococci have emerged as the third most common cause of nosocomial infections, requiring bactericidal antimicrobial therapy. Although vancomycin resistance is a major problem in clinics and has emerged in an important extend in farm animals, few studies have examined it in wild animals. To determine the prevalence of vanA-containing Enterococcus strains among faecal samples of Seagulls (Larus cachinnans) of Berlengas Natural Reserve of Portugal, we developed a proteomic approach integrated with genomic data. The purpose was to detect the maximum number of proteins that vary in different enterococci species which are thought to be connected in some, as yet unknown, way to antibiotic resistance. Results From the 57 seagull samples, 54 faecal samples showed the presence of Enterococcus isolates (94.7%). For the enterococci, E. faecium was the most prevalent species in seagulls (50%), followed by E. faecalis and E. durans (10.4%), and E. hirae (6.3%). VanA-containing enterococcal strains were detected in 10.5% of the 57 seagull faecal samples studied. Four of the vanA-containing enterococci were identified as E. faecium and two as E. durans. The tet(M) gene was found in all five tetracycline-resistant vanA strains. The erm(B) gene was demonstrated in all six erythromycin-resistant vanA strains. The hyl virulence gene was detected in all four vanA-containing E. faecium isolates in this study, and two of them harboured the purK1 allele. In addition these strains also showed ampicillin and ciprofoxacin resistance. The whole-cell proteomic profile of vanA-containing Enterococcus strains was applied to evaluate the discriminatory power of this technique for their identification. The major differences among species-specific profiles were found in the positions corresponding to 97-45 kDa. Sixty individualized protein spots for each vanA isolate was identified and suitable for peptide mass fingerprinting measures by spectrometry measuring (MALDI/TOF MS) and their

  16. Effects of Vancomycin Versus Nafcillin in Enhancing Killing of Methicillin-Susceptible Staphylococcus aureus Causing Bacteremia by Human Cathelicidin LL37

    PubMed Central

    Le, Jennifer; Dam, Quang; Schweizer, Marin; Thienphrapa, Wdee; Nizet, Victor; Sakoulas, George

    2016-01-01

    Recent studies have demonstrated that anti-staphylococcal beta-lactam antibiotics, like nafcillin, render methicillin-resistant Staphylococcus aureus (MRSA) more susceptible to killing by innate host defense peptides (HDPs), such as cathelicidin LL-37. We compared the effects of growth in 1/4 minimum inhibitory concentration (MIC) of nafcillin or vancomycin on LL-37 killing of 92 methicillin-susceptible S. aureus (MSSA) isolates. For three randomly selected strains among these, we examined the effects of nafcillin, vancomycin, daptomycin, or linezolid on LL-37 killing and autolysis. Growth in the presence of sub-inhibitory nafcillin significantly enhanced LL-37 killing of MSSA compared to vancomycin and antibiotic-free controls. Nafcillin also reduced MSSA production of the golden staphylococcal pigment staphyloxanthin in 39% of pigmented strains vs. 14% for vancomycin. Among antibiotics tested, only nafcillin resulted in significantly increased MSSA autolysis. These studies point to additional mechanisms of anti-staphylococcal activity of nafcillin beyond direct bactericidal activity, properties that vancomycin and other antibiotic classes do not exhibit. The ability of nafcillin to enhance sensitivity to innate host defense peptides may contribute to its superior effectiveness against MSSA as suggested by studies comparing clinical outcomes to vancomycin treatment. PMID:27234592

  17. Cost-effectiveness of telavancin versus vancomycin for treatment of complicated skin and skin structure infections.

    PubMed

    Laohavaleeson, Somvadee; Barriere, Steven L; Nicolau, David P; Kuti, Joseph L

    2008-12-01

    To determine the cost-effectiveness of telavancin versus vancomycin for the treatment of complicated skin and skin structure infections (cSSSIs). Pharmacoeconomic analysis conducted from the hospital's perspective using data from the Assessment of Telavancin in Complicated Skin and Skin Structure Infections (ATLAS) phase III clinical trial. One hundred twenty-nine hospitals in the United States and internationally. A total of 1044 clinically evaluable patients who were hospitalized with a cSSSI during the ATLAS trial and who received at least one dose of telavancin or vancomycin in the hospital. Diagnosis-related group-specific hospital bed costs, antibiotic acquisition prices, and cost of vancomycin monitoring were applied to the resource utilization data collected during the ATLAS trial. Infection-related length of stay (LOS(ir)) and hospitalization costs (COST(ir)) were compared between the telavancin (514 patients) and vancomycin (530 patients) groups. Incremental cost-effectiveness ratios (ICERs) were calculated for the total population and a subset of patients infected with methicillin-resistant Staphylococcus aureus (MRSA) by using a 25,000-sample bootstrap analysis. During sensitivity analyses, the daily acquisition price for telavancin was increased from the equivalent to vancomycin ($13.44) to $50, $100, $150, or $200, and the rate of MRSA acquisition was varied between 30% and 75%. The median (interquartile range) LOS(ir) was 8 days (6-12 days) for both telavancin and vancomycin (p=0.742), and median (interquartile range) COST(ir) was $8118 ($6291-11,758) and $8185 ($6474-11,405), respectively (p=0.560). Similar findings were observed for the MRSA subset. Telavancin cost-effectiveness was greater for the MRSA population versus the total population. During bootstrap analyses of the MRSA population, the ICER for telavancin ranged from dominant (-$9560) to $27,889 as acquisition price was increased. Telavancin LOS(ir) and total COST(ir) were similar to

  18. Transplacental transfer of vancomycin and telavancin

    PubMed Central

    NANOVSKAYA, Tatiana; PATRIKEEVA, Svetlana; ZHAN, Ying; FOKINA, Valentina; HANKINS, Gary DV; AHMED, Mahmoud S.

    2014-01-01

    Objectives Determine the bidirectional transfer and distribution of vancomycin and telavancin across the dually perfused term human placental lobule. Study design The technique of dually perfused placental lobule was used in its recirculating mode to determine the Maternal-to-Fetal (n=20) and Fetal-to-Maternal (n=18) transfer of each antibiotic which were co-perfused with their radioactive isotopes. The concentrations of drugs were determined by liquid scintillation spectrometry. Results In the Maternal-to-Fetal direction, the transfer of vancomycin (9.6 ± 4%) and telavancin (6.5 ± 2%) were low; however, telavancin retention by the perfused lobule was greater than that of vancomycin (p < 0.01). The normalized transplacental transfer of telavancin across the placental lobule in the F→M direction was higher than in the M→F direction (p < 0.01), suggesting the involvement of placental efflux transporters. Conclusions The ex vivo perfusion experiments revealed low transfer of vancomycin and telavancin to the fetal circuit. PMID:22867688

  19. Evaluation of body weight-based vancomycin therapy and the incidence of nephrotoxicity: a retrospective study in the northwest of China.

    PubMed

    Dong, Mo-Han; Wang, Jing-Wen; Wu, Yin; Chen, Bei-Yu; Yu, Min; Wen, Ai-Dong

    2015-08-01

    To identify specific risk factors of vancomycin-induced nephrotoxicity in China, as the relationship between vancomycin therapy (dosing and trough concentration monitoring) and nephrotoxicity has been the subject of critical debate. The cases of 90 critically ill patients who received vancomycin therapy in Xijing Hospital in the northwest of China between March 2014 and January 2015 were reviewed retrospectively. Vancomycin dosing, blood serum trough concentration, and other independent risk factors associated with nephrotoxicity were evaluated in a multivariable model. Among the 90 critically ill patients, 59 were males; mean age was 46.3 years. The indications for vancomycin use were methicillin-resistant Staphylococcus aureus-associated pneumonia, central nervous system infection, and bacteremia. Clinical pharmacists prescribed weight-based dosing, ranging from 20 to 45mg/kg/day. Fourteen (15.6%) patients developed nephrotoxicity, with serum creatinine elevated significantly from a mean (standard deviation) of 90.0 (18.8) μmol/l to 133.8 (63.2) μmol/l (p = 0.015). It was found that those with a vancomycin dosage >38mg/kg/day (50.0% vs. 11.3%, p = 0.004) and a vancomycin serum trough concentration >20mg/l (57.1% vs. 12.0%, p = 0.01) were more likely to develop nephrotoxicity. The data from this study indicate that a vancomycin dosage >38mg/kg/day and a serum trough level >20mg/l are both independent factors associated with the development of nephrotoxicity, suggesting that renal function should be monitored closely during vancomycin treatment. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. A Quasi-Experiment To Study the Impact of Vancomycin Area under the Concentration-Time Curve-Guided Dosing on Vancomycin-Associated Nephrotoxicity

    PubMed Central

    Finch, Natalie A.; Zasowski, Evan J.; Murray, Kyle P.; Mynatt, Ryan P.; Zhao, Jing J.; Yost, Raymond; Pogue, Jason M.

    2017-01-01

    ABSTRACT Evidence suggests that maintenance of vancomycin trough concentrations at between 15 and 20 mg/liter, as currently recommended, is frequently unnecessary to achieve the daily area under the concentration-time curve (AUC24) target of ≥400 mg · h/liter. Many patients with trough concentrations in this range have AUC24 values in excess of the therapeutic threshold and within the exposure range associated with nephrotoxicity. On the basis of this, the Detroit Medical Center switched from trough concentration-guided dosing to AUC-guided dosing to minimize potentially unnecessary vancomycin exposure. The primary objective of this analysis was to assess the impact of this intervention on vancomycin-associated nephrotoxicity in a single-center, retrospective quasi-experiment of hospitalized adult patients receiving intravenous vancomycin from 2014 to 2015. The primary analysis compared the incidence of nephrotoxicity between patients monitored by assessment of the AUC24 and those monitored by assessment of the trough concentration. Multivariable logistic and Cox proportional hazards regression examined the independent association between the monitoring strategy and nephrotoxicity. Secondary analysis compared vancomycin exposures (total daily dose, AUC, and trough concentrations) between monitoring strategies. Overall, 1,280 patients were included in the analysis. After adjusting for severity of illness, comorbidity, duration of vancomycin therapy, and concomitant receipt of nephrotoxins, AUC-guided dosing was independently associated with lower nephrotoxicity by both logistic regression (odds ratio, 0.52; 95% confidence interval [CI], 0.34 to 0.80; P = 0.003) and Cox proportional hazards regression (hazard ratio, 0.53; 95% CI, 0.35 to 0.78; P = 0.002). AUC-guided dosing was associated with lower total daily vancomycin doses, AUC values, and trough concentrations. Vancomycin AUC-guided dosing was associated with reduced nephrotoxicity, which appeared to be a

  1. A Quasi-Experiment To Study the Impact of Vancomycin Area under the Concentration-Time Curve-Guided Dosing on Vancomycin-Associated Nephrotoxicity.

    PubMed

    Finch, Natalie A; Zasowski, Evan J; Murray, Kyle P; Mynatt, Ryan P; Zhao, Jing J; Yost, Raymond; Pogue, Jason M; Rybak, Michael J

    2017-12-01

    Evidence suggests that maintenance of vancomycin trough concentrations at between 15 and 20 mg/liter, as currently recommended, is frequently unnecessary to achieve the daily area under the concentration-time curve (AUC 24 ) target of ≥400 mg · h/liter. Many patients with trough concentrations in this range have AUC 24 values in excess of the therapeutic threshold and within the exposure range associated with nephrotoxicity. On the basis of this, the Detroit Medical Center switched from trough concentration-guided dosing to AUC-guided dosing to minimize potentially unnecessary vancomycin exposure. The primary objective of this analysis was to assess the impact of this intervention on vancomycin-associated nephrotoxicity in a single-center, retrospective quasi-experiment of hospitalized adult patients receiving intravenous vancomycin from 2014 to 2015. The primary analysis compared the incidence of nephrotoxicity between patients monitored by assessment of the AUC 24 and those monitored by assessment of the trough concentration. Multivariable logistic and Cox proportional hazards regression examined the independent association between the monitoring strategy and nephrotoxicity. Secondary analysis compared vancomycin exposures (total daily dose, AUC, and trough concentrations) between monitoring strategies. Overall, 1,280 patients were included in the analysis. After adjusting for severity of illness, comorbidity, duration of vancomycin therapy, and concomitant receipt of nephrotoxins, AUC-guided dosing was independently associated with lower nephrotoxicity by both logistic regression (odds ratio, 0.52; 95% confidence interval [CI], 0.34 to 0.80; P = 0.003) and Cox proportional hazards regression (hazard ratio, 0.53; 95% CI, 0.35 to 0.78; P = 0.002). AUC-guided dosing was associated with lower total daily vancomycin doses, AUC values, and trough concentrations. Vancomycin AUC-guided dosing was associated with reduced nephrotoxicity, which appeared to be a result

  2. Outcomes associated with initial versus later vancomycin use in patients with complicated skin and skin-structure infections.

    PubMed

    Itani, Kamal M F; Akhras, Kasem S; Stellhorn, Robert; Quintana, Alvaro; Budd, David; Merchant, Sanjay

    2009-01-01

    Delayed coverage of pathogens including meticillin-resistant Staphylococcus aureus (MRSA) in pneumonia and bacteraemia has been associated with increased mortality and length of hospital stay (LOS). However, less is known about the impact of delayed appropriate coverage in complicated skin and skin-structure infections (cSSSIs). To evaluate the clinical and economic outcomes associated with early versus late use of vancomycin in the management of patients hospitalized for cSSSIs. Retrospective analysis was performed using an inpatient claims database of >500 US hospitals in 2005. Using prescription claims, patients with primary or secondary cSSSI admissions were classified into three groups: 1 = early vancomycin monotherapy; 2 = early vancomycin combination therapy; 3 = late vancomycin therapy. Outcomes studied included LOS and inpatient hospital costs. One-way analysis of variance was used for unadjusted analysis and multivariate regression methods were used to control for co-variates. A total of 34,942 patients (27.78% of all patients with cSSSIs) were treated with vancomycin. Mean age was 54.7 years and 54.3% of the patients were males. Mean unadjusted total LOS was 8.46, 9.44 and 13.2 days, and hospital costs in 2005 values were USD10 211.94, USD12 361.94 and USD18 344.00 for groups 1, 2 and 3, respectively. In-hospital mortality rate was highest in group 3 (4.18%) and lowest in group 1 (1.75%). Generalized linear models used to control for potential confounding variables between early versus late vancomycin use suggest that among cSSSI patients late vancomycin use is an independent predictor of higher LOS and costs. In this large inpatient database, later vancomycin use in patients with cSSSIs appears to be significantly associated with higher LOS and total costs.

  3. Identification of Risk Factors for Nephrotoxicity in Patients Receiving Extended-Duration, High-Trough Vancomycin Therapy

    PubMed Central

    Contreiras, Claire; Legal, Michael; Lau, Tim T Y; Thalakada, Rosanne; Shalansky, Stephen; Ensom, Mary H H

    2014-01-01

    Background: In the past, impurities in vancomycin formulations were thought to contribute to nephrotoxicity. In contrast, when current, purer formulations are dosed at conventional trough levels (i.e., 5–15 mg/L), the incidence of nephrotoxicity is relatively low. Recent guidelines have recommended targeting higher vancomycin trough levels in treatment of complicated methicillin-resistant Staphylococcus aureus infections. Dosing based on these higher trough levels may be associated with nephrotoxicity, so the potential risk factors for vancomycin-associated nephrotoxicity require clearer definition. Objectives: To determine the occurrence of nephrotoxicity in patients receiving more than 7 days of vancomycin therapy with high trough levels (15–20 mg/L) and to identify and evaluate specific risk factors related to development of vancomycin-associated nephrotoxicity (i.e., serum creatinine ≥ 44.2 μmol/L or increase ≥ 50% [i.e., ≥ 26.2 μmol/L] from baseline on 2 consecutive days). Methods: Health care records were reviewed for patients seen at 2 major teaching hospitals between January 2008 and March 2011. Patients who had attained high trough levels of vancomycin were screened for eligibility. Patients with unstable renal function, those undergoing hemodialysis, and those for whom dosage and/or sampling times were unclear were excluded. Univariate and multivariate analyses were performed to identify risk factors associated with nephrotoxicity. Univariate variables with p < 0.1 were included in the logistic regression model. Results: Of the 176 patients with high trough levels included in the analysis, 24 (14%) experienced nephrotoxicity. In univariate analysis, admission to a general medicine unit (the setting of care for 16 [67%] of the 24 patients with nephrotoxicity) and extended duration of vancomycin treatment were identified as risk factors for nephrotoxicity (p < 0.1). Other risk factors included gastrointestinal comorbidity (p = 0.056), malignancy

  4. Relationship between day 1 and day 2 Vancomycin area under the curve values and emergence of heterogeneous Vancomycin-intermediate Staphylococcus aureus (hVISA) by Etest® macromethod among patients with MRSA bloodstream infections: a pilot study.

    PubMed

    Martirosov, Dmitriy M; Bidell, Monique R; Pai, Manjunath P; Scheetz, Marc H; Rosenkranz, Susan L; Faragon, Corey; Malik, M; Mendes, R E; Jones, R N; McNutt, Louise-Anne; Lodise, Thomas P

    2017-08-02

    In vitro data suggests that suboptimal initial vancomycin exposure may select for heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) infections. However, no clinical studies have evaluated the relationship between initial vancomycin exposure and emergence of hVISA. This pilot study seeks to assess the relationship between day 1 and day 2 vancomycin area under the curve (AUC) and emergence of hVISA bloodstream infections (BSIs) by Etest® macromethod among patients with a non-hVISA BSI at baseline. This was a retrospective cohort study of patients with methicillin-resistant Staphylococcus aureus (MRSA) BSIs at Albany Medical Center Hospital (AMCH) between January 2005 and June 2009. The vancomycin AUC exposure variables on day 1 (AUC 0-24h ) and day 2 (AUC 24-48h ) were estimated using the maximal a posteriori probability (MAP) procedure in ADAPT 5. There were 238 unique episodes of MRSA BSIs during the study period, 119 of which met inclusion criteria. Overall, hVISA emerged in 7/119 (5.9%) of patients. All 7 cases of hVISA involved patients who did not achieve area under the curve over broth microdilution minimum inhibitory concentration (AUC 0-24h /MIC BMD ) ratio of 521 or an AUC 24-48h /MIC BMD ratio of 650. No associations between other day 1 and day 2 AUC variables and emergence of hVISA were noted. Although more data are needed to draw definitive conclusions, these findings suggest that hVISA emergence among patients with non-hVISA MRSA BSIs at baseline may be partially explained by suboptimal exposure to vancomycin in the first 1 to 2 days of therapy. At a minimum, these findings support further study of the relationship between initial vancomycin exposure and hVISA emergence among patients with MRSA BSIs in a well-powered, multi-center, prospective trial.

  5. Wild corvid birds colonized with vancomycin-resistant Enterococcus faecium of human origin harbor epidemic vanA plasmids.

    PubMed

    Oravcová, Veronika; Peixe, Luísa; Coque, Teresa M; Novais, Carla; Francia, Maria V; Literák, Ivan; Freitas, Ana R

    2018-06-02

    The most prevalent type of acquired vancomycin resistance in Enterococcus faecium (VREfm) is encoded by the vanA transposon Tn1546, mainly located on transferable plasmids. vanA plasmids have been characterized in VREfm from a variety of sources but not wild birds. The aim of this study was to analyse the genetic context of VREfm strains recovered from wild corvid birds and to compare their plasmid and strain characteristics with human strains. To achieve that, 75 VREfm isolates, including strains from wild birds recovered during wide surveillance studies performed in Europe, Canada and the United States (2010-2013), and clinical and wastewater strains from Czech Republic, a region lacking data about vanA plasmids, were analysed. Their population structure, presence of major putative virulence markers and characterization of vanA transposons and plasmids were established. VREfm from wild birds were mainly associated with major human lineages (ST18 and ST78) circulating in hospitals worldwide and were enriched in putative virulence markers that are highly associated with clinical E. faecium from human infections. They also carried plasmids of the same families usually found in the clinical setting [RCR, small theta plasmids, RepA_N (pRUM/pLG1) and Inc18]. The clinically widespread IS1251-carrying Tn1546 type "F" was predominant and Tn1546-vanA was mainly located on pRUM/Axe-Txe (USA) and Inc18- or pLG1-like (Europe) plasmids. VREfm from hospitals and wastewaters carried Tn1546-vanA in different plasmid types including mosaic pRUM-Inc18 plasmids, not identified in wild birds. This is the first characterization of vanA plasmids obtained from wild birds. A similar plasmid pool seems to exist in different clonal E. faecium backgrounds of humans and wild birds. The isolation of VREfm strains from wild birds that belong to human E. faecium adapted lineages and carry virulence genes, Tn1546 and plasmid variants widespread in the clinical setting is of concern and highlight

  6. Emerging Infectious Diseases, Antimicrobial Resistance and Millennium Development Goals: Resolving the Challenges through One Health.

    PubMed

    Asokan, G V; Kasimanickam, R K

    2013-01-01

    Most emerging infectious diseases are zoonoses, which could severely hamper reaching the targets of millennium development goals (MDG). Five out of the total eight MDG's are strongly associated with the Emerging Infectious Diseases (EIDs). Recent emergence and dissemination of drug-resistant pathogens has accelerated and prevent reaching the targets of MDG, with shrinking of therapeutic arsenal, mostly due to antimicrobial resistance (AMR). World Health Organization (WHO has identified AMR as 1 of the 3 greatest threats to global health. Until now, methicillin-resistant staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) have been observed in hospital-acquired infections. In India, within a span of three years, New Delhi metallo-β-lactamase prevalence has risen from three percent in hospitals to twenty- fifty percent and is found to be colistin resistant as well. Routine use of antimicrobials in animal husbandry accounts for more than 50% in tonnage of all antimicrobial production to promote growth and prophylaxis. This has consequences to human health and environmental contamination with a profound impact on the environmental microbiome, resulting in resistance. Antibiotic development is now considered a global health crisis. The average time required to receive regulatory approval is 7.2 years. Moreover, the clinical approval success is only 16%. To overcome resistance in antimicrobials, intersectoral partnerships among medical, veterinary, and environmental disciplines, with specific epidemiological, diagnostic, and therapeutic approaches are needed. Joint efforts under "One Health", beyond individual professional boundaries are required to stop antimicrobial resistance against zoonoses (EID) and reach the MDG.

  7. A dirty cause of vancomycin-mediated Henoch-Schonlein purpura: oxygen tubing is not a foley.

    PubMed

    Shah, Nikhil H; Kline, Kristopher P; Shukla, Manas K

    2017-06-20

    A 59-year-old male presented with methicillin-resistant Staphylococcus aureus bacteraemia from a prostatic abscess and was treated with vancomycin. Two weeks into his treatment course, he developed severe joint pains, abdominal pain with bloody, mucinous stools and a diffuse palpable purpuric rash on his extremities. Biopsy of the rash showed IgA immune-complex deposition consistent with Henoch-Schönlein purpura. After treatment with glucocorticoids, his symptoms resolved completely. Vancomycin is an extremely commonly used antibiotic with certain well-known adverse effects. Henoch-Schönlein purpura, a vasculitis involving abdominal pain, arthralgias and palpable purpura, is a much less common side effect, as seen in this patient. Given that vancomycin is widely used internationally, clinicians should be aware of the risks entailed by its use. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  8. Effect of swine manure application timing on the persistence and transport of antibiotic-resistant Enterococcus and resistance genes

    USDA-ARS?s Scientific Manuscript database

    Swine manure applied to agricultural fields may lead to the transport of antibiotic resistant bacteria and antibiotic resistance genes to freshwater systems. Enterococci were studied because they are fecal indicator bacteria associated with manure. Resistance genes include genes from live cells, dea...

  9. Auditory function after application of ototopical vancomycin and mupirocin solutions in a murine model.

    PubMed

    Rutherford, Kimberley D; Kavanagh, Katherine; Parham, Kourosh

    2011-03-01

    To determine whether mupirocin (440 µg/mL) and vancomycin otic drops (25 mg/mL) show evidence of ototoxicity in CBA/J mice immediately following a 7-day course of daily intratympanic (IT) injections and 1 month following treatment. Nonrandomized controlled trial. Academic hospital laboratory. Twenty CBA/J mice. Mean auditory brainstem response (ABR) thresholds increased in all drug- and saline-treated ears immediately after 7 days of IT injections but returned to baseline for most stimulus frequencies by 30 days later. This finding appeared to be correlated with the presence and subsequent resolution of tympanic membrane (TM) perforations and granulation tissue at the injection sites. Mupirocin-treated ears showed no significant difference in ABR thresholds compared to saline-treated ears. No significant differences were noted between vancomycin- and saline-treated ears, but there was a significant interaction between testing day and stimulus frequency (P < .001). Further analysis revealed that ABR thresholds at 32 kHz remained significantly elevated in vancomycin-treated mice despite the resolution of TM perforations and granulation tissue 30 days after completion of IT injections (95% confidence interval, -13.5 to -5.5, P < .01). Although IT application of mupirocin solution (440 µg/mL) caused no significant change in the ABR thresholds in a murine model, vancomycin solution (25 mg/mL) resulted in high-frequency threshold elevations in both the ear directly injected and the contralateral ear. Mupirocin solution may be beneficial in managing otitis externa and media caused by resistant pathogens. Further studies of ototopical vancomycin are needed to define parameters governing its safe use.

  10. Bullous dermatosis associated with vancomycin extravasation.

    PubMed

    Bohm, Nicole M; Wong, Jeffrey G

    2012-02-01

    Cutaneous side effects related to vancomycin therapy have been reported including histamine-related reactions, linear IgA bullous dermatosis, Stevens-Johnson syndrome, maculopapular rash and drug rash with eosinophilia and systemic symptoms. In all instances, these reports were due to the systemic administration of vancomycin and subsequent immunological reactions to the medication. Drug extravasation into soft tissues can result in a variety of clinical outcomes usually related to physiochemical properties of the drug extravasated and its diluents or pharmacologic effects on the vasculature and tissue. The authors report a patient who experienced vancomycin extravasation that resulted in a localized bullous eruption resembling linear IgA bullous dermatosis, a phenomenon not previously described in the literature.

  11. Role of Vancomycin as a Component of Oral Nonabsorbable Antibiotics for Microbial Suppression in Leukemic Patients

    PubMed Central

    Bender, John F.; Schimpff, Stephen C.; Young, Viola Mae; Fortner, Clarence L.; Brouillet, Mary D.; Love, Lillian J.; Wiernik, Peter H.

    1979-01-01

    A total of 38 adult patients with acute leukemia who were undergoing remission induction chemotherapy in regular patient rooms were randomly allocated to one of two oral nonabsorbable antibiotic regimens for infection prophylaxis (gentamicin, vancomycin, and nystatin [GVN] or gentamicin and nystatin [GN]) to evaluate whether vancomycin was a necessary component. The patient population in both groups were comparable. Tolerance to GVN was less than GN but compliance was approximately equal (>85% in both groups). Patients receiving vancomycin demonstrated greater overall alimentary tract microbial suppression; however, acquisition of potential pathogens was approximately equal in both groups. The incidence of bacteremia, as well as the overall incidence of infection as related to the number of days at various granulocyte levels, was also approximately equal in both groups. Group D Streptococcus species were poorly suppressed by GN compared with GVN, although no patient developed an infection with these organisms. Colonization by newly acquired gram-negative bacilli was significantly less in the GN group (GN, 3 colonizations; GVN, 13 colonizations; P < 0.01). It is concluded that vancomycin may be safely eliminated from the GVN regimen provided microbiological data is monitored to detect resistant organisms. PMID:464573

  12. Vancomycin-resistant Enterococcus faecium sequence type 796 - rapid international dissemination of a new epidemic clone.

    PubMed

    Mahony, Andrew A; Buultjens, Andrew H; Ballard, Susan A; Grabsch, Elizabeth A; Xie, Shirley; Seemann, Torsten; Stuart, Rhonda L; Kotsanas, Despina; Cheng, Allen; Heffernan, Helen; Roberts, Sally A; Coombs, Geoffrey W; Bak, Narin; Ferguson, John K; Carter, Glen C; Howden, Benjamin P; Stinear, Timothy P; Johnson, Paul D R

    2018-01-01

    Vancomycin-resistant Enterococcus faecium (VRE) is a leading cause of hospital-acquired infections. New, presumably better-adapted strains of VRE appear unpredictably; it is uncertain how they spread despite improved infection control. We aimed to investigate the relatedness of a novel sequence type (ST) of vanB E. faecium - ST796 - very near its time of origin from hospitals in three Australian states and New Zealand. Following near-simultaneous outbreaks of ST796 in multiple institutions, we gathered then tested colonization and bloodstream infection isolates' antimicrobial resistance (AMR) phenotypes, and phylogenomic relationships using whole genome sequencing (WGS). Patient meta-data was explored to trace the spread of ST796. A novel clone of vanB E. faecium (ST796) was first detected at one Australian hospital in late 2011, then in two New Zealand hospitals linked by inter-hospital transfers from separate Melbourne hospitals. ST796 also appeared in hospitals in South Australia and New South Wales and was responsible for at least one major colonization outbreak in a Neonatal Intensive Care Unit without identifiable links between centers. No exceptional AMR was detected in the isolates. While WGS analysis showed very limited diversity at the core genome, consistent with recent emergence of the clone, clustering by institution was observed. Evolution of new E. faecium clones, followed by recognized or unrecognized movement of colonized individuals then rapid intra-institutional cross-transmission best explain the multi-center, multistate and international outbreak we observed.

  13. Association between Vancomycin Day 1 Exposure Profile and Outcomes among Patients with Methicillin-Resistant Staphylococcus aureus Infective Endocarditis

    PubMed Central

    Casapao, Anthony M.; Lodise, Thomas P.; Davis, Susan L.; Claeys, Kimberly C.; Kullar, Ravina; Levine, Donald P.

    2015-01-01

    Given the critical importance of early appropriate therapy, a retrospective cohort (2002 to 2013) was performed at the Detroit Medical Center to evaluate the association between the day 1 vancomycin exposure profile and outcomes among patients with MRSA infective endocarditis (IE). The day 1 vancomycin area under the concentration-time curve (AUC0–24) and the minimum concentration at 24 h (Cmin 24) was estimated for each patient using the Bayesian procedure in ADAPT 5, an approach shown to accurately predict the vancomycin exposure with low bias and high precision with limited pharmacokinetic sampling. Initial MRSA isolates were collected and vancomycin MIC was determined by broth microdilution (BMD) and Etest. The primary outcome was failure, defined as persistent bacteremia (≥7 days) or 30-day attributable mortality. Classification and regression tree analysis (CART) was used to determine the vancomycin exposure variables associated with an increased probability of failure. In total, 139 patients met study criteria; 76.3% had right-sided IE, 16.5% had left-sided IE, and 7.2% had both left and right-sided IE. A total of 89/139 (64%) experienced failure by composite definition. In the CART analysis, failure was more pronounced in patients with an AUC0–24/MIC as determined by BMD of ≤600 relative to those with AUC0–24/MIC as determined by BMD of >600 (69.8% versus 54.7%, respectively, P = 0.073). In the logistic regression analysis, an AUC/MIC as determined by BMD of ≤600 (adjusted odds ratio, 2.3; 95% confidence interval, 1.01 to 5.37; P = 0.047) was independently associated with failure. Given the retrospective nature of the present study, further prospective studies are required but these data suggest that patients with an AUC0–24/MIC as determined by BMD of ≤600 present an increased risk of failure. PMID:25753631

  14. Red man syndrome caused by vancomycin powder.

    PubMed

    Nagahama, Yasunori; VanBeek, Marta J; Greenlee, Jeremy D W

    2018-04-01

    Red man syndrome (RMS) is a well-known hypersensitivity reaction caused by intravenous administration of vancomycin, with symptoms ranging from flushing, erythematous rash, pruritus, mild to profound hypotension, and even cardiac arrest. RMS has not previously been described from local application of vancomycin powder in a surgical wound, a technique increasingly utilized for infection prophylaxis in many surgical disciplines including neurosurgery. We describe the first reported case of RMS as a result of local intra-wound application of vancomycin powder for infection prophylaxis. A 73-year-old male with a history of Parkinson's disease underwent 2-stage deep brain stimulation implantation surgeries. Vancomycin powder was applied locally in the surgical wounds for infection prophylaxis during both of the surgeries. The patient developed a well-demarcated, geometric erythematous pruritic rash following the second surgery that was clinically diagnosed as RMS and resolved without sequelae. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. A novel injectable borate bioactive glass cement for local delivery of vancomycin to cure osteomyelitis and regenerate bone.

    PubMed

    Cui, Xu; Zhao, Cunju; Gu, Yifei; Li, Le; Wang, Hui; Huang, Wenhai; Zhou, Nai; Wang, Deping; Zhu, Yi; Xu, Jun; Luo, Shihua; Zhang, Changqing; Rahaman, Mohamed N

    2014-03-01

    Osteomyelitis (bone infection) is often difficult to cure. The commonly-used treatment of surgical debridement to remove the infected bone combined with prolonged systemic and local antibiotic treatment has limitations. In the present study, an injectable borate bioactive glass cement was developed as a carrier for the antibiotic vancomycin, characterized in vitro, and evaluated for its capacity to cure osteomyelitis in a rabbit tibial model. The cement (initial setting time = 5.8 ± 0.6 min; compressive strength = 25.6 ± 0.3 MPa) released vancomycin over ~25 days in phosphate-buffered saline, during which time the borate glass converted to hydroxyapatite (HA). When implanted in rabbit tibial defects infected with methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis, the vancomycin-loaded cement converted to HA and supported new bone formation in the defects within 8 weeks. Osteomyelitis was cured in 87 % of the defects implanted with the vancomycin-loaded borate glass cement, compared to 71 % for the defects implanted with vancomycin-loaded calcium sulfate cement. The injectable borate bioactive glass cement developed in this study is a promising treatment for curing osteomyelitis and for regenerating bone in the defects following cure of the infection.

  16. Antibiotic resistance and virulence traits in clinical and environmental Enterococcus faecalis and Enterococcus faecium isolates.

    PubMed

    Rathnayake, I U; Hargreaves, M; Huygens, F

    2012-07-01

    This study compared virulence and antibiotic resistance traits in clinical and environmental Enterococcus faecalis and Enterococcus faecium isolates. E. faecalis isolates harboured a broader spectrum of virulence determinants compared to E. faecium isolates. The virulence traits Cyl-A, Cyl-B, Cyl-M, gel-E, esp and acm were tested and environmental isolates predominantly harboured gel-E (80% of E. faecalis and 31.9% of E. faecium) whereas esp was more prevalent in clinical isolates (67.8% of E. faecalis and 70.4% of E. faecium). E. faecalis and E. faecium isolated from water had different antibiotic resistance patterns compared to those isolated from clinical samples. Linezolid resistance was not observed in any isolates tested and vancomycin resistance was observed only in clinical isolates. Resistance to other antibiotics (tetracycline, gentamicin, ciprofloxacin and ampicillin) was detected in both clinical and water isolates. Clinical isolates were more resistant to all the antibiotics tested compared to water isolates. Multi-drug resistance was more prevalent in clinical isolates (71.2% of E. faecalis and 70.3% of E. faecium) compared to water isolates (only 5.7% E. faecium). tet L and tet M genes were predominantly identified in tetracycline-resistant isolates. All water and clinical isolates resistant to ciprofloxacin and ampicillin contained mutations in the gyrA, parC and pbp5 genes. A significant correlation was found between the presence of virulence determinants and antibiotic resistance in all the isolates tested in this study (p<0.05). The presence of antibiotic resistant enterococci, together with associated virulence traits, in surface recreational water could be a public health risk. Copyright © 2012 Elsevier GmbH. All rights reserved.

  17. ANTI-ADHESIVE AND ANTI-BIOFILM ACTIVITIES IN VITRO OF LINEZOLID, VANCOMYCIN, TIGECYCLINE AND DAPTOMYCIN AGAINST STAPHYLOCOCCUS HAEMOLYTICUS.

    PubMed

    Juda, Marek; Helon, Pawel; Malm, Anna

    2016-11-01

    Biofilm may be formed on wide variety of surfaces, including indwelling medical devices, leading to several infectious diseases, e.g., bacteremia and sepsis. The most,important pathogens related with infections associated with medical devices are coagulase-negative staphylococci, including Staphylococcus haeinolyticus - bacterial species which express quite often the multidrug resistance. The four clinical multiresistant and methicillin-resistant S. haenzolyticus were included in the present study. The evaluation of drug susceptibility was performed by using disc-diffusion method and broth microdilution method according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. The biofilm formation on the Nelaton catheter and the effect of linezolid, vancomycin, tigecycline and daptomycin on the biofilm formation and disruption of mature structure was based on the method with TTC (2,3,5-triphenyltetrazolium chloride). The adhesion process of S. haenzolyticus to the Nelaton catheter was inhibited by antibiotics, as follows: line-zolid at concentration 0.25-0.5 x MIC, vancomycin - concentration 0.5 x MIC, tigecycline - concentration 0.25-4 x MIC and daptomycin - concentration 0.06-1 x MIC, depending on the isolate. Linezolid inhibited the biofilm formation at concentration between 0.5-1 x MIC, vancomycin - 1-2 x MIC, tigecycline - 0.5-4 x MIC and daptomycin - 0.06-2 x MIC. The concentration of linezolid eradicating the mature biofilm was found to be 1-2 x MIC, vancomycin - 2-8 x MIC, tigecycline - 2-4 x MIC and daptomycin - 0.06-2 x MIC. The most active antibiotic against S. haentolyticus biofilm formation and disruption of mature structure seems to be daptomycin.

  18. Glycopeptide antibiotic biosynthesis.

    PubMed

    Yim, Grace; Thaker, Maulik N; Koteva, Kalinka; Wright, Gerard

    2014-01-01

    Glycopeptides such as vancomycin, teicoplanin and telavancin are essential for treating infections caused by Gram-positive bacteria. Unfortunately, the dwindled pipeline of new antibiotics into the market and the emergence of glycopeptide-resistant enterococci and other resistant bacteria are increasingly making effective antibiotic treatment difficult. We have now learned a great deal about how bacteria produce antibiotics. This information can be exploited to develop the next generation of antimicrobials. The biosynthesis of glycopeptides via nonribosomal peptide assembly and unusual amino acid synthesis, crosslinking and tailoring enzymes gives rise to intricate chemical structures that target the bacterial cell wall. This review seeks to describe recent advances in our understanding of both biosynthesis and resistance of these important antibiotics.

  19. Major globally disseminated clonal complexes of antimicrobial resistant enterococci associated with infections in cancer patients in Brazil.

    PubMed

    Santos, Barbara A; Oliveira, Jéssica S; Cardoso, Nayara T; Barbosa, André V; Superti, Silvana V; Teixeira, Lúcia M; Neves, Felipe P G

    2017-11-01

    Cancer and hematological malignancies constitute major comorbidities in enterococcal infections, but little is known about the characteristics of enterococci affecting cancer patients. The aim of this study was to characterize 132 enterococcal clinical isolates obtained from cancer patients attending a Cancer Reference Center in Brazil between April 2013 and March 2014. Susceptibility to 17 antimicrobial agents was assessed by disk diffusion method. Resistance and virulence genes were investigated by PCR. Multilocus sequence typing (MLST) was performed for selected Enterococcus faecalis and Enterococcus faecium isolates. The predominant species was E. faecalis (108 isolates), followed by E. faecium (18), Enterococcus gallinarum (3), Enterococcus avium (2) and Enterococcus durans (1). Multidrug-resistant (MDR) isolates made up 44.7%, but all isolates were susceptible to fosfomycin, linezolid and glycopeptides. The most prevalent genes associated with erythromycin- and tetracycline-non susceptible isolates were erm(B) (47/71; 66.2%) and tet(M) (24/68; 35.3%), respectively. High-level resistance (HLR) to gentamicin was found in 22 (16.7%) isolates and 13 (59.1%) of them carried the aac(6')-Ie-aph(2″)-Ia gene. HLR to streptomycin was detected in 34 (25.8%) isolates, of which 15 (44.1%) isolates had the ant(6')-Ia gene. The most common virulence genes were gelE (48.9%), esp (30.5%) and asa1 (29.8%). MLST performed for 26 E. faecalis isolates revealed 18 different sequence-types (STs), with seven corresponding to novel STs (625, 626, 627, 628, 629, 630, and 635). On the other hand, nine of 10 E. faecium isolates analyzed by MLST belonged to a single clonal complex, comprised of mostly ST412, which emerged worldwide after mid-2000s, but also two novel STs (963 and 964). We detected major globally disseminated E. faecalis and E. faecium clonal complexes along with novel closely related STs, indicating the fitness and continuous evolution of these hospital

  20. Synthetic membrane-targeted antibiotics.

    PubMed

    Vooturi, S K; Firestine, S M

    2010-01-01

    Antimicrobial resistance continues to evolve and presents serious challenges in the therapy of both nosocomial and community-acquired infections. The rise of resistant strains like methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Staphylococcus aureus (VRSA) and vancomycin-resistant enterococci (VRE) suggests that antimicrobial resistance is an inevitable evolutionary response to antimicrobial use. This highlights the tremendous need for antibiotics against new bacterial targets. Agents that target the integrity of bacterial membrane are relatively novel in the clinical armamentarium. Daptomycin, a lipopeptide is a classical example of membrane-bound antibiotic. Nature has also utilized this tactic. Antimicrobial peptides (AMPs), which are found in all kingdoms, function primarily by permeabilizing the bacterial membrane. AMPs have several advantages over existing antibiotics including a broad spectrum of activity, rapid bactericidal activity, no cross-resistance with the existing antibiotics and a low probability for developing resistance. Currently, a small number of peptides have been developed for clinical use but therapeutic applications are limited because of poor bioavailability and high manufacturing cost. However, their broad specificity, potent activity and lower probability for resistance have spurred the search for synthetic mimetics of antimicrobial peptides as membrane-active antibiotics. In this review, we will discuss the different classes of synthetic membrane-bound antibiotics published since 2004.

  1. A multi-beach study of Staphylococcus aureus, MRSA, and enterococci in seawater and beach sand.

    PubMed

    Goodwin, Kelly D; McNay, Melody; Cao, Yiping; Ebentier, Darcy; Madison, Melissa; Griffith, John F

    2012-09-01

    Incidences of Staphylococcus aureus and methicillin resistant S. aureus (MRSA) have risen worldwide prompting a need to better understand routes of human exposure and whether standard bacterial water quality monitoring practices adequately account for this potential threat. Beach water and sand samples were analyzed during summer months for S. aureus, enterococci, and MRSA at three southern California beaches (Avalon, Doheny, Malibu Surfrider). S. aureus frequently was detected in samples of seawater (59%, n = 328) and beach sand (53%, n = 358). MRSA sometimes was detected in seawater (1.6%, n = 366) and sand (2.7%, n = 366) at relatively low concentrations. Site specific differences were observed, with Avalon Beach presenting the highest concentrations of S. aureus and Malibu Surfrider the lowest in both seawater and sand. S. aureus concentrations in seawater and sand were correlated to each other and to a variety of other parameters. Multiple linear regression on the combined beach data indicated that significant explanatory variables for S. aureus in seawater were S. aureus in sand, water temperature, enterococci in seawater, and the number of swimmers. In sand, S. aureus concentrations were related to S. aureus in seawater, water temperature, enterococci in seawater, and inversely to surf height classification. Only the correlation to water temperature held for individually analyzed beaches and for S. aureus concentrations in both seawater and sand. To provide context for these results, the prevalence of S. aureus in sand was compared to published fomite studies, and results suggested that beach prevalence was similar to that in homes. Published by Elsevier Ltd.

  2. A RAPID, SPECIFIC MEMBRANE FILTRATION PROCEDURE FOR ENUMERATION OF ENTEROCOCCI IN RECREATIONAL WATER

    EPA Science Inventory

    A two-step membrane filter (MP) method with mE medium, upon which the membrane must be incubated for 48 h and then transferred to a substrate medium to differentiate enterococci, is recommended by the U.S.Environmental Protection Agency to measure enterococci in fresh and marine ...

  3. Emerging treatment options for acute bacterial skin and skin structure infections: focus on intravenous delafloxacin

    PubMed Central

    Righi, Elda; Carnelutti, Alessia; Vena, Antonio; Bassetti, Matteo

    2018-01-01

    The increase in hospitalization due to acute bacterial skin and skin structure infections (ABSSSI) caused by resistant pathogens supports the need for new treatment options. Antimicrobial options for ABSSSI that provide broad-spectrum coverage, including gram-negative pathogens and multidrug-resistant gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), are limited. Delafloxacin is a novel fluoroquinolone available as intravenous and oral formulations and is characterized by an increased efficacy in acidic environments and activity on bacterial biofilm. Delafloxacin displays enhanced in vitro activity against MRSA, and enterococci, while maintaining efficacy against gram-negative pathogens and anaerobes. Delafloxacin has been studied for the treatment of ABSSSI and respiratory infections. Phase III studies have demonstrated noninferiority of delafloxacin compared to vancomycin, linezolid, tigecycline, and the combination of vancomycin plus aztreonam in the treatment of ABSSSI. Due to its favorable pharmacokinetic characteristics, the wide spectrum of action, and the potential for sequential therapy, delafloxacin represents a promising option in the empirical and targeted treatment of ABSSSI, both in hospital- and in community-based care. PMID:29670380

  4. Emerging treatment options for acute bacterial skin and skin structure infections: focus on intravenous delafloxacin.

    PubMed

    Righi, Elda; Carnelutti, Alessia; Vena, Antonio; Bassetti, Matteo

    2018-01-01

    The increase in hospitalization due to acute bacterial skin and skin structure infections (ABSSSI) caused by resistant pathogens supports the need for new treatment options. Antimicrobial options for ABSSSI that provide broad-spectrum coverage, including gram-negative pathogens and multidrug-resistant gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), are limited. Delafloxacin is a novel fluoroquinolone available as intravenous and oral formulations and is characterized by an increased efficacy in acidic environments and activity on bacterial biofilm. Delafloxacin displays enhanced in vitro activity against MRSA, and enterococci, while maintaining efficacy against gram-negative pathogens and anaerobes. Delafloxacin has been studied for the treatment of ABSSSI and respiratory infections. Phase III studies have demonstrated noninferiority of delafloxacin compared to vancomycin, linezolid, tigecycline, and the combination of vancomycin plus aztreonam in the treatment of ABSSSI. Due to its favorable pharmacokinetic characteristics, the wide spectrum of action, and the potential for sequential therapy, delafloxacin represents a promising option in the empirical and targeted treatment of ABSSSI, both in hospital- and in community-based care.

  5. Resistance surveillance program report for selected European nations (2011).

    PubMed

    Jones, Ronald N; Flonta, Mirela; Gurler, Nazahat; Cepparulo, Mario; Mendes, Rodrigo E; Castanheira, Mariana

    2014-04-01

    In the European component of the Regional Resistance Surveillance study for 2011, a total of 21 countries were monitored for antimicrobial resistance patterns including Belgium, Bulgaria (BU), Croatia, Czech Republic, France (F), Germany (GE), Greece (GR), Ireland (IR), Israel (IS), Italy (IT), Poland (PO), Portugal (PT), Romania (RO), Russia (RU), Slovakia (SK), Slovenia, Spain, Sweden (SW), Turkey (T), Ukraine, and United Kingdom. Results from testing 12,572 strains (100 [BU] to 1535 [F] per nation) were interpreted by contemporary published breakpoints. Samples from 47 hospitals were reference tested against agents such as amikacin (AMK), cefoperazone/sulbactam (C/S), colistin (COL), levofloxacin, linezolid (LZD), tigecycline (TIG), vancomycin (VAN), and 21 others. Among Staphylococcus aureus, LZD (MIC90, 2 μg/mL), TIG (MIC90, 0.12 μg/mL), and VAN (MIC90, 1 μg/mL) exhibited complete coverage and methicillin resistance rates among nations (average, 31%) ranged from 0.9% (SW) to 60.0-60.2% (PT, SK). Seven LZD-resistant coagulase-negative staphylococci (only 1.1% resistance overall) were noted in 5 nations, and a Staphylococcus simulans strain (MIC, 8 μg/mL from RO) had L3 mutations (N130D, G152A, F147S, A157R); also 6 LZD-resistant enterococci were detected in 3 countries (GE, IR, T). VAN-resistant enterococci (10% overall; 84% VanA) were found in 14 countries, highest in GE and IR (23.0%). The ESBL phenotype rate for Escherichia coli was 20.1% (range, 0.9% [SW] to 70.0-89.7% [BU, RU]), best inhibited by COL (100.0% S), TIG (100.0%), AMK (83.3-94.1%), C/S (81.0%), and carbapenems (>99.0%; resistant strains in IS and T). Klebsiella spp. had greater ESBL rates (45.7% overall, range 2.5-100.0%), as well as carbapenem resistance (8.3% overall, greatest in BU, GR, IS, IT, PO, RO, RU, T). Non-fermentative Gram-negative bacilli (Pseudomonas aeruginosa, Acinetobacter [ACB]) were generally less susceptible, except against COL (99.2-99.6% S) and TIG (95.0% inhibited at

  6. Effectiveness of local vancomycin powder to decrease surgical site infections: a meta-analysis.

    PubMed

    Chiang, Hsiu-Yin; Herwaldt, Loreen A; Blevins, Amy E; Cho, Edward; Schweizer, Marin L

    2014-03-01

    Some surgeons use systemic vancomycin to prevent surgical site infections (SSIs), but patients who do not carry methicillin-resistant Staphylococcus aureus have an increased risk of SSIs when given vancomycin alone for intravenous prophylaxis. Applying vancomycin powder to the wound before closure could increase the local tissue vancomycin level without significant systemic levels. However, the effectiveness of local vancomycin powder application for preventing SSIs has not been established. Our objective was to systematically review and evaluate studies on the effectiveness of local vancomycin powder for decreasing SSIs. Meta-analysis. We included observational studies, quasi-experimental studies, and randomized controlled trials of patients undergoing surgical procedures that involved vancomycin powder application to surgical wounds, reported SSI rates, and had a comparison group that did not use local vancomycin powder. The primary outcome was postoperative SSIs. The secondary outcomes included deep incisional SSIs and S. aureus SSIs. We performed systematic literature searches in PubMed, the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, the Cochrane Central Register of Controlled Trials via Wiley, Scopus (including EMBASE abstracts), Web of Science, ClinicalTrials.gov, BMC Proceedings, ProQuest Dissertation, and Thesis in Health and Medicine, and conference abstracts from IDWeek, the Interscience Conference on Antimicrobial Agents and Chemotherapy, the Society for Healthcare Epidemiology of America, and the American Academy of Orthopedic Surgeons annual meetings, and also the Scoliosis Research Society Annual Meeting and Course. We ran the searches from inception on May 9, 2013 with no limits on date or language. After reviewing 373 titles or abstracts and 22 articles in detail, we included 10 independent studies and used a random-effects model when pooling risk estimates to assess the effectiveness of local

  7. Vancomycin-Resistance Enterococci Infections in the Department of the Defense: Annual Report 2014

    DTIC Science & Technology

    2015-07-22

    change in 2014 as VRE continues to predominately affect elderly females and manifest as urinary tract infections ( UTIs ). In addition, antibiotic...urinary tract infections ( UTIs ). In addition, antibiotic susceptibility patterns did not substantially change in 2014. Daptomycin, linezolid and...the infection continues to predominately affect elderly females and manifest as UTIs . In addition, antibiotic susceptibility patterns did not

  8. Gene Expression Analysis Reveals New Possible Mechanisms of Vancomycin-Induced Nephrotoxicity and Identifies Gene Markers Candidates

    PubMed Central

    Dieterich, Christine; Puey, Angela; Lyn, Sylvia; Swezey, Robert; Furimsky, Anna; Fairchild, David; Mirsalis, Jon C.; Ng, Hanna H.

    2009-01-01

    Vancomycin, one of few effective treatments against methicillin-resistant Staphylococcus aureus, is nephrotoxic. The goals of this study were to (1) gain insights into molecular mechanisms of nephrotoxicity at the genomic level, (2) evaluate gene markers of vancomycin-induced kidney injury, and (3) compare gene expression responses after iv and ip administration. Groups of six female BALB/c mice were treated with seven daily iv or ip doses of vancomycin (50, 200, and 400 mg/kg) or saline, and sacrificed on day 8. Clinical chemistry and histopathology demonstrated kidney injury at 400 mg/kg only. Hierarchical clustering analysis revealed that kidney gene expression profiles of all mice treated at 400 mg/kg clustered with those of mice administered 200 mg/kg iv. Transcriptional profiling might thus be more sensitive than current clinical markers for detecting kidney damage, though the profiles can differ with the route of administration. Analysis of transcripts whose expression was changed by at least twofold compared with vehicle saline after high iv and ip doses of vancomycin suggested the possibility of oxidative stress and mitochondrial damage in vancomycin-induced toxicity. In addition, our data showed changes in expression of several transcripts from the complement and inflammatory pathways. Such expression changes were confirmed by relative real-time reverse transcription–polymerase chain reaction. Finally, our results further substantiate the use of gene markers of kidney toxicity such as KIM-1/Havcr1, as indicators of renal injury. PMID:18930951

  9. Gene expression analysis reveals new possible mechanisms of vancomycin-induced nephrotoxicity and identifies gene markers candidates.

    PubMed

    Dieterich, Christine; Puey, Angela; Lin, Sylvia; Lyn, Sylvia; Swezey, Robert; Furimsky, Anna; Fairchild, David; Mirsalis, Jon C; Ng, Hanna H

    2009-01-01

    Vancomycin, one of few effective treatments against methicillin-resistant Staphylococcus aureus, is nephrotoxic. The goals of this study were to (1) gain insights into molecular mechanisms of nephrotoxicity at the genomic level, (2) evaluate gene markers of vancomycin-induced kidney injury, and (3) compare gene expression responses after iv and ip administration. Groups of six female BALB/c mice were treated with seven daily iv or ip doses of vancomycin (50, 200, and 400 mg/kg) or saline, and sacrificed on day 8. Clinical chemistry and histopathology demonstrated kidney injury at 400 mg/kg only. Hierarchical clustering analysis revealed that kidney gene expression profiles of all mice treated at 400 mg/kg clustered with those of mice administered 200 mg/kg iv. Transcriptional profiling might thus be more sensitive than current clinical markers for detecting kidney damage, though the profiles can differ with the route of administration. Analysis of transcripts whose expression was changed by at least twofold compared with vehicle saline after high iv and ip doses of vancomycin suggested the possibility of oxidative stress and mitochondrial damage in vancomycin-induced toxicity. In addition, our data showed changes in expression of several transcripts from the complement and inflammatory pathways. Such expression changes were confirmed by relative real-time reverse transcription-polymerase chain reaction. Finally, our results further substantiate the use of gene markers of kidney toxicity such as KIM-1/Havcr1, as indicators of renal injury.

  10. Antibacterial activity of head-to-head bis-benzimidazoles.

    PubMed

    Moreira, Joao B; Mann, John; Neidle, Stephen; McHugh, Timothy D; Taylor, Peter W

    2013-10-01

    Symmetric bis-benzimidazole (BBZ) conjugates were profiled for activity against a range of Gram-positive and Gram-negative bacteria. para-Substituted ethoxy, amino and methoxy derivatives displayed potent bacteriostatic activity against meticillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, streptococci and Listeria monocytogenes. Moderate to good activity was also found against mycobacteria; two compounds were strongly active against logarithmic phase and hypoxia-induced latent Mycobacterium tuberculosis. No compound displayed significant activity towards Gram-negative bacteria. Only high concentrations of antibacterial BBZs showed cytotoxic effects towards fibroblasts, and the most active compound was well tolerated by zebrafish embryos. Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  11. Mortality in Kittens Is Associated with a Shift in Ileum Mucosa-Associated Enterococci from Enterococcus hirae to Biofilm-Forming Enterococcus faecalis and Adherent Escherichia coli

    PubMed Central

    Ghosh, Anuradha; Borst, Luke; Stauffer, Stephen H.; Suyemoto, Mitsu; Moisan, Peter; Zurek, Ludek

    2013-01-01

    Approximately 15% of foster kittens die before 8 weeks of age, with most of these kittens demonstrating clinical signs or postmortem evidence of enteritis. While a specific cause of enteritis is not determined in most cases, these kittens are often empirically administered probiotics that contain enterococci. The enterococci are members of the commensal intestinal microbiota but also can function as opportunistic pathogens. Given the complicated role of enterococci in health and disease, it would be valuable to better understand what constitutes a “healthy” enterococcal community in these kittens and how this microbiota is impacted by severe illness. In this study, we characterized the ileum mucosa-associated enterococcal community of 50 apparently healthy and 50 terminally ill foster kittens. In healthy kittens, Enterococcus hirae was the most common species of ileum mucosa-associated enterococci and was often observed to adhere extensively to the small intestinal epithelium. These E. hirae isolates generally lacked virulence traits. In contrast, non-E. hirae enterococci, notably Enterococcus faecalis, were more commonly isolated from the ileum mucosa of kittens with terminal illness. Isolates of E. faecalis had numerous virulence traits and multiple antimicrobial resistances. Moreover, the attachment of Escherichia coli to the intestinal epithelium was significantly associated with terminal illness and was not observed in any kitten with adherent E. hirae. These findings identify a significant difference in the species of enterococci cultured from the ileum mucosa of kittens with terminal illness compared to the species cultured from healthy kittens. In contrast to prior case studies that associated enteroadherent E. hirae with diarrhea in young animals, these controlled studies identified E. hirae as more often isolated from healthy kittens and adherence of E. hirae as more common and extensive in healthy kittens than in sick kittens. PMID:23966487

  12. In vitro activity of Tedizolid phosphate against multidrug-resistant Streptococcus pneumoniae isolates from Asian countries.

    PubMed

    Baek, Jin Yang; Kang, Cheol-In; Kim, So Hyun; Ko, Kwan Soo; Chung, Doo Ryeon; Peck, Kyong Ran; Hsueh, Po-Ren; Thamlikitkul, Visanu; So, Thomas Man-Kit; Lee, Nam Yong; Song, Jae-Hoon

    2016-06-01

    Tedizolid phosphate is a second-generation oxazolidinone prodrug that is potential activity against a wide range of Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus, penicillin-resistant streptococci, and vancomycin-resistant enterococci. The in vitro activity of tedizolid and other comparator agents against multidrug-resistant (MDR) pneumococci from various Asian countries were evaluated. Of the S. pneumoniae clinical pneumonia isolates collected during 2008 and 2009 from 8 Asian countries (Korea, Taiwan, Thailand, Hong Kong, Vietnam, Malaysia, Philippines, and Sri Lanka), 104 isolates of MDR pneumococci were included in this study. Antimicrobial susceptibility testing for 18 antimicrobial agents was performed by broth microdilution method. Tedizolid was highly active against pneumococci. All isolates tested were inhibited at a tedizolid minimum inhibitory concentration (MIC) value of ≤0.25μg/ml (ranged from ≤0.03μg/ml to 0.25μg/ml). The MIC50 and MIC90 of tedizolid against MDR pneumococci were both 0.12μg/ml, while MIC50 and MIC90 of linezolid were 0.5μg/ml and 1μg/ml, respectively. In addition, tedizolid maintained the activity against S. pneumoniae regardless of the extensively drug-resistant (XDR) phenotype of the isolates. The activity of tedizolid was excellent against all types of MDR pneumococci, exhibiting and maintaining at least 4-fold-greater potency compared to linezolid, regardless of resistance phenotypes to other commonly utilized agents. Tedizolid has the potential to be an agent to treat infections caused by MDR pneumococci in the Asia. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Microbiology and Outcomes of Peritonitis in Northern India

    PubMed Central

    Prasad, Kashi Nath; Singh, Kamini; Rizwan, Arshi; Mishra, Priyanka; Tiwari, Dinesh; Prasad, Narayan; Gupta, Amit

    2014-01-01

    ♦ Background: Peritoneal dialysis (PD) is an established treatment modality for end-stage renal disease (ESRD). Peritonitis remains a serious complication in PD patients and an important cause of drop-out from the program. Types of pathogens and their drug resistance patterns may determine the outcome of peritonitis. The present study was undertaken to determine the microbiology of peritonitis in PD patients, antibiotic resistance in commonly isolated bacterial pathogens and clinical outcomes. ♦ Method: We enrolled 211 patients with ESRD undergoing PD who developed peritonitis during 2002 to 2011. PD fluids were cultured and antibiotic susceptibility test of the bacterial isolates was performed. ♦ Result: A total of 303 peritonitis episodes with an overall incidence of 0.41 episodes per patient-year were recorded. Gram-positive, gram-negative, fungi, Mycobacterium tuberculosis and ≥ 2 organisms were isolated from 102 (33.7%), 89 (29.4%), 41 (13.5%), 11 (3.6%) and five (1.6%) episodes respectively; 55 (18.2%) episodes were culture negative. Coagulase-negative Staphylococcus spp. (CONS) was the most common isolate. Catheter loss and hospital admission in gram-negative peritonitis were significantly higher than in gram-positive peritonitis (36/89 (40.4%) vs 20/102 (19.6%), p < 0.001; and 56/89 (62.9%) vs 42/102 (41.2%), p = 0.004 respectively). Antibiotic susceptibility tests showed 54.3% of Enterobacteriaceae isolates were extended spectrum β-lactamase (ESBL) producers, 23.5% of Acinetobacter species and 11.5% of Pseudomonas aeruginosa were metallo-β-lactamase (MBL) producers; 15.4% of enterococci and 28.6% of staphylococci were resistant to vancomycin and methicillin respectively. Mortality was significantly higher in patients having peritonitis due to vancomycin-resistant enterococci, ESBL- and MBL-producing bacteria. ♦ Conclusion: Emerging antimicrobial resistance calls for prompt diagnosis and aggressive empiric therapy based on the local sensitivity

  14. Vancomycin and/or Multidrug-Resistant Citrobacter Freundii Altered the Metabolic Pattern of Soil Microbial Community

    PubMed Central

    Cycoń, Mariusz; Orlewska, Kamila; Markowicz, Anna; Żmijowska, Agnieszka; Smoleń-Dzirba, Joanna; Bratosiewicz-Wąsik, Jolanta; Wąsik, Tomasz J.; Piotrowska-Seget, Zofia

    2018-01-01

    Despite many studies, our knowledge on the impact of antibiotics and antibiotic-resistant bacteria on the metabolic activity of soil microbial communities is still limited. To ascertain this impact, the community level physiological profiles (CLPPs) and the activity of selected enzymes (dehydrogenase, urease, and phosphatases) in soils treated with vancomycin (VA) and/or multidrug resistant Citrobacter freundii were determined during a 90-day experiment. A multivariate analysis and the resistance (RS)/resilience (RL) concept were used to assess the potential of native microorganisms to maintain their catabolic activity under exposure of VA and/or a high level of C. freundii. In addition, the dissipation rate of VA was evaluated in non-sterile (nsS) and sterile (sS) soils. The results revealed a negative impact of VA on the metabolic activity of soil microorganisms on days 1, 15, and 30 as was showed by a decrease in the values of the CLPP indices (10–69%) and the enzyme activities (6–32%) for treated soils as compared to the control. These observations suggested a low initial resistance of soil microorganisms to VA and/or C. freundii but they were resilient in the long term. Considering the mean values of the RS index, the resistance of measured parameters was categorized in the following order: alkaline phosphatase (0.919) > acid phosphatase (0.899) > dehydrogenase (0.853) > the evenness index (0.840) > urease (0.833) > the Shannon-Wiener index (0.735) > substrate richness (0.485) > the AWCD (0.301). The dissipation process of VA was relatively fast and independent of the concentration used. The DT50 values for VA applied at both concentrations were about 16 days. In addition, the dissipation of VA in nsS was three times faster compared to the dissipation of antibiotic in sS. In conclusion, both CLPP and enzyme activities assays appeared to be useful tool for the determination of disturbances within soil microbial communities and used together may be helpful

  15. Molecular Basis for Lytic Bacteriophage Resistance in Enterococci.

    PubMed

    Duerkop, Breck A; Huo, Wenwen; Bhardwaj, Pooja; Palmer, Kelli L; Hooper, Lora V

    2016-08-30

    The human intestine harbors diverse communities of bacteria and bacteriophages. Given the specificity of phages for their bacterial hosts, there is growing interest in using phage therapies to combat the rising incidence of multidrug-resistant bacterial infections. A significant barrier to such therapies is the rapid development of phage-resistant bacteria, highlighting the need to understand how bacteria acquire phage resistance in vivo Here we identify novel lytic phages in municipal raw sewage that kill Enterococcus faecalis, a Gram-positive opportunistic pathogen that resides in the human intestine. We show that phage infection of E. faecalis requires a predicted integral membrane protein that we have named PIPEF (for phage infection protein from E. faecalis). We find that PIPEF is conserved in E. faecalis and harbors a 160-amino-acid hypervariable region that determines phage tropism for distinct enterococcal strains. Finally, we use a gnotobiotic mouse model of in vivo phage predation to show that the sewage phages temporarily reduce E. faecalis colonization of the intestine but that E. faecalis acquires phage resistance through mutations in PIPEF Our findings define the molecular basis for an evolutionary arms race between E. faecalis and the lytic phages that prey on them. They also suggest approaches for engineering E. faecalis phages that have altered host specificity and that can subvert phage resistance in the host bacteria. Bacteriophage therapy has received renewed attention as a potential solution to the rise in antibiotic-resistant bacterial infections. However, bacteria can acquire phage resistance, posing a major barrier to phage therapy. To overcome this problem, it is necessary to understand phage resistance mechanisms in bacteria. We have unraveled one such resistance mechanism in Enterococcus faecalis, a Gram-positive natural resident of the human intestine that has acquired antibiotic resistance and can cause opportunistic infections

  16. D-lactic acidosis mediated neuronal encephalopathy in acute lymphoblastic leukemia patient: an under diagnosis.

    PubMed

    Mendu, Damodara Rao; Fleisher, Martin; McCash, Samuel I; Pessin, Melissa S; Ramanathan, Lakshmi V

    2015-02-20

    D-lactic acidosis, also referred as D-lactate encephalopathy, has been reported in patients with short bowl syndrome (SBS). The neurologic symptoms include altered mental status, slurred speech, and ataxia. Onset of neurological symptoms is accompanied by metabolic acidosis and high anion gap. We present here a case of D-lactic acidosis in a patient with acute lymphoblastic leukemia (ALL) who developed severe neurological symptoms and metabolic acidosis due to vancomycin-resistant enterococci (VRE) infection, and elevated D-lactic acid. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Influence of Vancomycin Infusion Methods on Endothelial Cell Toxicity

    PubMed Central

    Drouet, Maryline; Chai, Feng; Barthélémy, Christine; Lebuffe, Gilles; Debaene, Bertrand; Odou, Pascal

    2014-01-01

    Peripheral intravenous therapy is frequently used in routine hospital practice and, due to various factors, its most common side effect is phlebitis. The infusion of vancomycin is particularly associated with phlebitis despite its widespread use. French guidelines recommend central intravenous infusion for high concentrations of vancomycin, but peripheral intravenous therapy is often preferred in intensive care units. Methods of vancomycin infusion are either intermittent infusion or continuous infusion. A comparison of these methods under in vitro conditions simulating clinical use could result in better infusion efficacy. Human umbilical vein endothelial cells (HUVECs) were therefore challenged with clinical doses of vancomycin over a 24- to 72-h period using these infusion methods. Cell death was measured with the alamarBlue test. Concentration-dependent and time-dependent vancomycin toxicity on HUVECs was noted with a 50% lethal dose at 5 mg/ml after 24 h, reaching 2.5 mg/ml after 72 h of infusion, simulating long-term infusion. This toxicity does not seem to be induced by acidic pH. In comparing infusion methods, we observed that continuous infusion induced greater cell toxicity than intermittent infusion at doses higher than 1 g/day. The increasing use of vancomycin means that new guidelines are required to avoid phlebitis. If peripheral intravenous therapy is used to reduce infusion time, along with intermittent infusion, vein irritation and localized phlebitis may be reduced. Further studies have to be carried out to explore the causes of vancomycin endothelial toxicity. PMID:25421476

  18. Are Vancomycin Trough Concentrations Adequate for Optimal Dosing?

    PubMed Central

    Youn, Gilmer; Jones, Brenda; Jelliffe, Roger W.; Drusano, George L.; Rodvold, Keith A.; Lodise, Thomas P.

    2014-01-01

    The current vancomycin therapeutic guidelines recommend the use of only trough concentrations to manage the dosing of adults with Staphylococcus aureus infections. Both vancomycin efficacy and toxicity are likely to be related to the area under the plasma concentration-time curve (AUC). We assembled richly sampled vancomycin pharmacokinetic data from three studies comprising 47 adults with various levels of renal function. With Pmetrics, the nonparametric population modeling package for R, we compared AUCs estimated from models derived from trough-only and peak-trough depleted versions of the full data set and characterized the relationship between the vancomycin trough concentration and AUC. The trough-only and peak-trough depleted data sets underestimated the true AUCs compared to the full model by a mean (95% confidence interval) of 23% (11 to 33%; P = 0.0001) and 14% (7 to 19%; P < 0.0001), respectively. In contrast, using the full model as a Bayesian prior with trough-only data allowed 97% (93 to 102%; P = 0.23) accurate AUC estimation. On the basis of 5,000 profiles simulated from the full model, among adults with normal renal function and a therapeutic AUC of ≥400 mg · h/liter for an organism for which the vancomycin MIC is 1 mg/liter, approximately 60% are expected to have a trough concentration below the suggested minimum target of 15 mg/liter for serious infections, which could result in needlessly increased doses and a risk of toxicity. Our data indicate that adjustment of vancomycin doses on the basis of trough concentrations without a Bayesian tool results in poor achievement of maximally safe and effective drug exposures in plasma and that many adults can have an adequate vancomycin AUC with a trough concentration of <15 mg/liter. PMID:24165176

  19. A Mutation in the PP2C Phosphatase Gene in a Staphylococcus aureus USA300 Clinical Isolate with Reduced Susceptibility to Vancomycin and Daptomycin

    PubMed Central

    Passalacqua, Karla D.; Satola, Sarah W.; Crispell, Emily K.

    2012-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) strains with reduced susceptibility to vancomycin (MIC of 4 to 8 μg/ml) are referred to as vancomycin-intermediate S. aureus (VISA). In this study, we characterized two isogenic USA300 S. aureus isolates collected sequentially from a single patient with endocarditis where the S. aureus isolate changed from being susceptible to vancomycin (VSSA) (1 μg/ml) to VISA (8 μg/ml). In addition, the VISA isolate lost beta-lactamase activity and showed increased resistance to daptomycin and linezolid. The two strains did not differ in growth rate, but the VISA isolate had a thickened cell wall and was less autolytic. Transcriptome sequencing (RNA-seq) analysis comparing the two isolates grown to late exponential phase showed significant differences in transcription of cell surface protein genes (spa, SBI [second immunoglobulin-binding protein of S. aureus], and fibrinogen-binding proteins), regulatory genes (agrBCA, RNAIII, sarT, and saeRS), and others. Using whole-genome shotgun resequencing, we identified 6 insertion/deletion mutations between the VSSA and VISA isolates. A protein phosphatase 2C (PP2C) family phosphatase had a 6-bp (nonframeshift) insertion mutation in a highly conserved metal binding domain. Complementation of the clinical VISA isolate with a wild-type copy of the PP2C gene reduced the vancomycin and daptomycin MICs and increased autolytic activity, suggesting that this gene contributed to the reduced vancomycin susceptibility phenotype acquired in vivo. Creation of de novo mutants from the VSSA strain resulted in different mutations, demonstrating that reduced susceptibility to vancomycin in USA300 strains can occur via multiple routes, highlighting the complex nature of the VISA phenotype. PMID:22850507

  20. Distribution of multi-resistant Gram-negative versus Gram-positive bacteria in the hospital inanimate environment.

    PubMed

    Lemmen, S W; Häfner, H; Zolldann, D; Stanzel, S; Lütticken, R

    2004-03-01

    We prospectively studied the difference in detection rates of multi-resistant Gram-positive and multi-resistant Gram-negative bacteria in the inanimate environment of patients harbouring these organisms. Up to 20 different locations around 190 patients were surveyed. Fifty-four patients were infected or colonized with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE) and 136 with multi-resistant Gram-negative bacteria. The environmental detection rate for MRSA or VRE was 24.7% (174/705 samples) compared with 4.9% (89/1827 samples) for multi-resistant Gram-negative bacteria (P<0.001). Gram-positive bacteria were isolated more frequently than Gram-negatives from the hands of patients (P<0.001) and hospital personnel (P=0.1145). Environmental contamination did not differ between the intensive care units (ICUs) and the general wards (GWs), which is noteworthy because our ICUs are routinely disinfected twice a day, whereas GWs are cleaned just once a day with detergent. Current guidelines for the prevention of spread of multi-resistant bacteria in the hospital setting do not distinguish between Gram-positive and Gram-negative isolates. Our results suggest that the inanimate environment serves as a secondary source for MRSA and VRE, but less so for Gram-negative bacteria. Thus, strict contact isolation in a single room with complete barrier precautions is recommended for MRSA or VRE; however, for multi-resistant Gram-negative bacteria, contact isolation with barrier precautions for close contact but without a single room seems sufficient. This benefits not only the patients, but also the hospital by removing some of the strain placed on already over-stretched resources.

  1. Blood culture contamination with Enterococci and skin organisms: implications for surveillance definitions of primary bloodstream infections.

    PubMed

    Freeman, Joshua T; Chen, Luke Francis; Sexton, Daniel J; Anderson, Deverick J

    2011-06-01

    Enterococci are a common cause of bacteremia but are also common contaminants. In our institution, approximately 17% of positive blood cultures with enterococci are mixed with skin organisms. Such isolates are probable contaminants. The specificity of the current definition of primary bloodstream infection could be increased by excluding enterococci mixed with skin organisms. Copyright © 2011 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

  2. Significant reduction in vancomycin-resistant enterococcus colonization and bacteraemia after introduction of a bleach-based cleaning-disinfection programme.

    PubMed

    Grabsch, E A; Mahony, A A; Cameron, D R M; Martin, R D; Heland, M; Davey, P; Petty, M; Xie, S; Grayson, M L

    2012-12-01

    Vancomycin-resistant enterococcus (VRE) colonization and infection have increased at our hospital, despite adherence to standard VRE control guidelines. We implemented a multi-modal, hospital-wide improvement programme including a bleach-based cleaning-disinfection programme ('Bleach-Clean'). VRE colonization, infection and environmental contamination were compared pre and post implementation. The programme included a new product (sodium hypochlorite 1000 ppm + detergent), standardized cleaning-disinfection practices, employment of cleaning supervisors, and modified protocols to rely on alcohol-based hand hygiene and sleeveless aprons instead of long-sleeved gowns and gloves. VRE was isolated using chromogenic agar and/or routine laboratory methods. Outcomes were assessed during the 6 months pre and 12 months post implementation, including proportions (per 100 patients screened) of VRE colonization in high-risk wards (HRWs: intensive care, liver transplant, renal, haematology/oncology); proportions of environmental contamination; and episodes of VRE bacteraemia throughout the entire hospital. Significant reductions in newly recognized VRE colonizations (208/1948 patients screened vs 324/4035, a 24.8% reduction, P = 0.001) and environmental contamination (66.4% reduction, P = 0.012) were observed, but the proportion of patients colonized on admission was stable. The total burden of inpatients with VRE in the HRWs also declined (median percentage of colonized inpatients per week, 19.4% vs 17.3%, P = 0.016). Hospital-wide VRE bacteraemia declined from 14/2935 patients investigated to 5/6194 (83.1% reduction; P < 0.001), but there was no change in vancomycin-susceptible enterococcal bacteraemia (P = 0.54). The Bleach-Clean programme was associated with marked reductions in new VRE colonizations in high-risk patients, and VRE bacteraemia across the entire hospital. These findings have important implications for VRE control in endemic healthcare settings. Copyright

  3. In vitro pharmacodynamics of human simulated exposures of ceftaroline and daptomycin against MRSA, hVISA, and VISA with and without prior vancomycin exposure.

    PubMed

    Bhalodi, Amira A; Hagihara, Mao; Nicolau, David P; Kuti, Joseph L

    2014-01-01

    The effects of prior vancomycin exposure on ceftaroline and daptomycin therapy against methicillin-resistant Staphylococcus aureus (MRSA) have not been widely studied. Humanized free-drug exposures of vancomycin at 1 g every 12 h (q12h), ceftaroline at 600 mg q12h, and daptomycin at 10 mg/kg of body weight q24h were simulated in a 96-h in vitro pharmacodynamic model against three MRSA isolates, including one heteroresistant vancomycin-intermediate S. aureus (hVISA) isolate and one VISA isolate. A total of five regimens were tested: vancomycin, ceftaroline, and daptomycin alone for the entire 96 h, and then sequential therapy with vancomycin for 48 h followed by ceftaroline or daptomycin for 48 h. Microbiological responses were measured by the changes in log10 CFU during 96 h from baseline. Control isolates grew to 9.16 ± 0.32, 9.13 ± 0.14, and 8.69 ± 0.28 log10 CFU for MRSA, hVISA, and VISA, respectively. Vancomycin initially achieved ≥3 log10 CFU reductions against the MRSA and hVISA isolates, followed by regrowth beginning at 48 h; minimal activity was observed against VISA. The change in 96-h log10 CFU was largest for sequential therapy with vancomycin followed by ceftaroline (-5.22 ± 1.2, P = 0.010 versus ceftaroline) and for sequential therapy with vancomycin followed by ceftaroline (-3.60 ± 0.6, P = 0.037 versus daptomycin), compared with daptomycin (-2.24 ± 1.0), vancomycin (-1.40 ± 1.8), and sequential therapy with vancomycin followed by daptomycin (-1.32 ± 1.0, P > 0.5 for the last three regimens). Prior exposure of vancomycin at 1 g q12h reduced the initial microbiological response of daptomycin, particularly for hVISA and VISA isolates, but did not affect the response of ceftaroline. In the scenario of poor vancomycin response for high-inoculum MRSA infection, a ceftaroline-containing regimen may be preferred.

  4. Susceptibility of vancomycin-resistant and -sensitive Enterococcus faecium obtained from Danish hospitals to benzalkonium chloride, chlorhexidine and hydrogen peroxide biocides.

    PubMed

    Alotaibi, Sulaiman M I; Ayibiekea, Alafate; Pedersen, Annemette Frøling; Jakobsen, Lotte; Pinholt, Mette; Gumpert, Heidi; Hammerum, Anette M; Westh, Henrik; Ingmer, Hanne

    2017-12-01

    In Danish hospitals, the number of infections caused by vancomycin-resistant Enterococcus faecium (VRE faecium) has dramatically increased in recent years. Hospital disinfectants are essential in eliminating pathogenic microorganisms, and reduced susceptibility may contribute to hospital-associated infections. We have addressed whether clinical VRE faecium display decreased biocide susceptibility when compared to vancomycin-sensitive Enterococcus faecium (VSE faecium) isolates. In total 12 VSE faecium and 37 VRE faecium isolates obtained from Danish hospitals over an extended time period were tested for susceptibility towards three commonly applied biocides, namely benzalkonium chloride, chlorhexidine and hydrogen peroxide. For benzalkonium chloride, 89 % of VRE faecium strains had a minimal inhibitory concentration (MIC) of 8 mg l -1 , whereas for VSE faecium, only 25 % of the strains had an MIC of 8 mg l -1 . For chlorhexidine, the MIC of 95 % of VRE faecium strains was 4 mg l -1 or higher, while only 33 % of VSE faecium strains displayed MIC values at the same level. In contrast, both VRE and VSE faecium displayed equal susceptibility to hydrogen peroxide, but a higher minimal bactericidal concentration (MBC) was found for the former. The efflux activity was also assessed, and this was generally higher for the VRE faecium strains compared to VSE faecium. VRE faecium from Danish hospitals demonstrated decreased susceptibility towards benzalkonium chloride and chlorhexidine compared to VSE faecium, where the use of chlorhexidine is particularly heavy in the hospital environment. These findings suggest that biocide tolerance may characterize VRE faecium isolated in Danish hospitals.

  5. Impact of Discontinuing Contact Precautions for Methicillin-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococcus: An Interrupted Time Series Analysis.

    PubMed

    Bearman, Gonzalo; Abbas, Salma; Masroor, Nadia; Sanogo, Kakotan; Vanhoozer, Ginger; Cooper, Kaila; Doll, Michelle; Stevens, Michael P; Edmond, Michael B

    2018-06-01

    OBJECTIVETo investigate the impact of discontinuing contact precautions among patients infected or colonized with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) on rates of healthcare-associated infection (HAI). Single-center, quasi-experimental study conducted between 2011 and 2016.METHODSWe employed an interrupted time series design to evaluate the impact of 7 horizontal infection prevention interventions across intensive care units (ICUs) and hospital wards at an 865-bed urban, academic medical center. These interventions included (1) implementation of a urinary catheter bundle in January 2011, (2) chlorhexidine gluconate (CHG) perineal care outside ICUs in June 2011, (3) hospital-wide CHG bathing outside of ICUs in March 2012, (4) discontinuation of contact precautions in April 2013 for MRSA and VRE, (5) assessments and feedback with bare below the elbows (BBE) and contact precautions in August 2014, (6) implementation of an ultraviolet-C disinfection robot in March 2015, and (7) 72-hour automatic urinary catheter discontinuation orders in March 2016. Segmented regression modeling was performed to assess the changes in the infection rates attributable to the interventions.RESULTSThe rate of HAI declined throughout the study period. Infection rates for MRSA and VRE decreased by 1.31 (P=.76) and 6.25 (P=.21) per 100,000 patient days, respectively, and the infection rate decreased by 2.44 per 10,000 patient days (P=.23) for device-associated HAI following discontinuation of contact precautions.CONCLUSIONThe discontinuation of contact precautions for patients infected or colonized with MRSA or VRE, when combined with horizontal infection prevention measures was not associated with an increased incidence of MRSA and VRE device-associated infections. This approach may represent a safe and cost-effective strategy for managing these patients.Infect Control Hosp Epidemiol 2018;39:676-682.

  6. Vancomycin AUC/MIC and Corresponding Troughs in a Pediatric Population

    PubMed Central

    Lardieri, Allison B.; Heil, Emily L.; Morgan, Jill A.

    2017-01-01

    OBJECTIVES Adult guidelines suggest an area under the curve/minimum inhibitory concentration (AUC/MIC) > 400 corresponds to a vancomycin trough serum concentration of 15 to 20 mg/L for methicillin-resistant Staphylococcus aureus infections, but obtaining these troughs in children are difficult. The primary objective of this study was to assess the likelihood that 15 mg/kg of vancomycin every 6 hours in a child achieves an AUC/MIC > 400. METHODS This retrospective chart review included pediatric patients >2 months to <18 years with a positive S aureus blood culture and documented MIC who received at least two doses of vancomycin with corresponding trough. Patients were divided into two groups: group 1 initially receiving ≥15 mg/kg every 6 hours, and group 2 initially receiving any other dosing ranges or intervals. AUCs were calculated four times using three pharmacokinetic methods. RESULTS A total of 36 patients with 99 vancomycin trough serum concentrations were assessed. Baseline characteristics were similar between groups. For troughs in group 1 (n = 55), the probability of achieving an AUC/MIC > 400 ranged from 16.4% to 90.9% with a median trough concentration of 11.4 mg/L, while in group 2 (n = 44) the probability of achieving AUC/MIC > 400 ranged from 15.9% to 54.5% with mean trough concentration of 9.2 mg/L. The AUC/MICs were not similar between the different pharmacokinetic methods used; however, a trapezoidal equation (Method A) yielded the highest correlation coefficient (r2 = 0.59). When dosing every 6 hours, an AUC/MIC of 400 correlated to a trough serum concentration of 11 mg/L. CONCLUSIONS The probability of achieving an AUC/MIC > 400 using only a trough serum concentration and an MIC with patients receiving 15 mg/kg every 6 hours is variable based on the method used to calculate the AUC. An AUC/MIC of 400 in children correlated to a trough concentration of 11 mg/L using a trapezoidal Method to calculate AUC. PMID:28337080

  7. Vancomycin AUC/MIC and Corresponding Troughs in a Pediatric Population.

    PubMed

    Kishk, Omayma A; Lardieri, Allison B; Heil, Emily L; Morgan, Jill A

    2017-01-01

    Adult guidelines suggest an area under the curve/minimum inhibitory concentration (AUC/MIC) > 400 corresponds to a vancomycin trough serum concentration of 15 to 20 mg/L for methicillin-resistant Staphylococcus aureus infections, but obtaining these troughs in children are difficult. The primary objective of this study was to assess the likelihood that 15 mg/kg of vancomycin every 6 hours in a child achieves an AUC/MIC > 400. This retrospective chart review included pediatric patients >2 months to <18 years with a positive S aureus blood culture and documented MIC who received at least two doses of vancomycin with corresponding trough. Patients were divided into two groups: group 1 initially receiving ≥15 mg/kg every 6 hours, and group 2 initially receiving any other dosing ranges or intervals. AUCs were calculated four times using three pharmacokinetic methods. A total of 36 patients with 99 vancomycin trough serum concentrations were assessed. Baseline characteristics were similar between groups. For troughs in group 1 (n = 55), the probability of achieving an AUC/MIC > 400 ranged from 16.4% to 90.9% with a median trough concentration of 11.4 mg/L, while in group 2 (n = 44) the probability of achieving AUC/MIC > 400 ranged from 15.9% to 54.5% with mean trough concentration of 9.2 mg/L. The AUC/MICs were not similar between the different pharmacokinetic methods used; however, a trapezoidal equation (Method A) yielded the highest correlation coefficient (r 2 = 0.59). When dosing every 6 hours, an AUC/MIC of 400 correlated to a trough serum concentration of 11 mg/L. The probability of achieving an AUC/MIC > 400 using only a trough serum concentration and an MIC with patients receiving 15 mg/kg every 6 hours is variable based on the method used to calculate the AUC. An AUC/MIC of 400 in children correlated to a trough concentration of 11 mg/L using a trapezoidal Method to calculate AUC.

  8. [Enterococcal endocarditis: a multicenter study of 76 cases].

    PubMed

    Martínez-Marcos, Francisco Javier; Lomas-Cabezas, José Manuel; Hidalgo-Tenorio, Carmen; de la Torre-Lima, Javier; Plata-Ciézar, Antonio; Reguera-Iglesias, José María; Ruiz-Morales, Josefa; Márquez-Solero, Manuel; Gálvez-Acebal, Juan; de Alarcón-González, Arístides

    2009-12-01

    Although enterococci occupy the third position among microorganisms producing infectious endocarditis (IE) following streptococci and Staphylococcus aureus, few multicenter studies have provided an in-depth analysis of enterococcal IE. Description of the characteristics of 76 cases of enterococcal left-sided infectious endocarditis (LSIE) (native: 59, prosthetic: 17) retrieved from the database of the Cardiovascular Infections Study Group of the Andalusian Society of Infectious Diseases, with emphasis on the comparison with non-enterococcal LSIE. Enterococci were the causal agent in 76 of the 696 episodes of LSIE (11%). Compared with non-enterococcal LSIE, enterococcal LSIE was more commonly seen in patients older than 65 (47.4% vs. 27.6%, P<0.0005), and those with chronic diseases (75% vs. 54.6%, P<0.001), calcified valves (18.6% vs. 10%, P<0.05), and previous urinary (30.3% vs. 2.1%, P<0.00001) or abdominal (10.5% vs. 3.1%, P<0.01) infections, and produced a higher rate of relapses (6.6% vs. 2.3%, P<0.05). Enterococcal LSIE was associated with fewer peripheral vascular or skin manifestations (14.5% vs. 27.1%, P<0.05) and fewer immunological phenomena (10.5% vs. 24%, P<0.01). Among the total of patients with enterococcal LSIE, 36.8% underwent valve surgery during hospitalization. In-hospital mortality was 32.9% for enterococcal LSIE, 9.3% for viridans group streptococci (VGS) LSIE and 48.6% for S. aureus LSIE (enterococci vs VGS: P<0.0001; enterococci vs S. aureus: P=0.02). Enterococcal LSIE patients treated with the combination of a penicillin or vancomycin plus an aminoglycoside (n=60) and those treated with ampicillin plus ceftriaxone (n=6) showed similar in-hospital mortality (26.7% vs 33.3%, P=0.66). High-level resistance to gentamicin was detected in 5 of 38 episodes of enterococcal LSIE (13.1%). Enterococcal LSIE appears in patients with well-defined clinical characteristics, and causes few peripheral vascular or skin manifestations and few immunological

  9. Comparative evaluation of two methods of enumerating enterococci in foods: collaborative study.

    PubMed

    Peterz, M; Steneryd, A C

    1993-05-01

    Two methods of enumerating enterococci in foods were compared in a collaborative study. Thirteen laboratories tested four blind duplicate samples containing different levels of enterococci and two negative control samples. Freeze-dried mixtures of bacteria were used as simulated food samples. The freeze-dried samples were reconstituted and either spread directly on the surface of Slanetz and Bartley medium (SB) and incubated at 44 degrees C for 48 h or preincubated in tryptone soya agar at 37 degrees C for 2 h before being overlaid by SB and incubated at 37 degrees C for a further 46 h. The numbers CFU of enterococci recovered by the two methods were not significantly different except for one sample where the 37 degrees C method gave a somewhat higher recovery. The 44 degrees C method was less time-consuming and less laborious.

  10. Elimination of Routine Contact Precautions for Endemic Methicillin-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococcus: A Retrospective Quasi-Experimental Study.

    PubMed

    Martin, Elise M; Russell, Dana; Rubin, Zachary; Humphries, Romney; Grogan, Tristan R; Elashoff, David; Uslan, Daniel Z

    2016-11-01

    OBJECTIVE To evaluate the impact of discontinuation of contact precautions (CP) for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) and expansion of chlorhexidine gluconate (CHG) use on the health system. DESIGN Retrospective, nonrandomized, observational, quasi-experimental study. SETTING Two California hospitals. PARTICIPANTS Inpatients. METHODS We compared hospital-wide laboratory-identified clinical culture rates (as a marker of healthcare-associated infections) 1 year before and after routine CP for endemic MRSA and VRE were discontinued and CHG bathing was expanded to all units. Culture data from patients and cost data on material utilization were collected. Nursing time spent donning personal protective equipment was assessed and quantified using time-driven activity-based costing. RESULTS Average positive culture rates before and after discontinuing CP were 0.40 and 0.32 cultures/100 admissions for MRSA (P=.09), and 0.48 and 0.40 cultures/100 admissions for VRE (P=.14). When combining isolation gown and CHG costs, the health system saved $643,776 in 1 year. Before the change, 28.5% intensive care unit and 19% medicine/surgery beds were on CP for MRSA/VRE. On the basis of average room entries and donning time, estimated nursing time spent donning personal protective equipment for MRSA/VRE before the change was 45,277 hours/year (estimated cost, $4.6 million). CONCLUSION Discontinuing routine CP for endemic MRSA and VRE did not result in increased rates of MRSA or VRE after 1 year. With cost savings on materials, decreased healthcare worker time, and no concomitant increase in possible infections, elimination of routine CP may add substantial value to inpatient care delivery. Infect Control Hosp Epidemiol 2016;1-8.

  11. Vancomycin tolerance in clinical and laboratory Streptococcus pneumoniae isolates depends on reduced enzyme activity of the major LytA autolysin or cooperation between CiaH histidine kinase and capsular polysaccharide.

    PubMed

    Moscoso, Miriam; Domenech, Mirian; García, Ernesto

    2010-08-01

    Vancomycin is frequently added to standard therapy for pneumococcal meningitis. Although vancomycin-resistant Streptococcus pneumoniae strains have not been isolated, reports on the emergence of vancomycin-tolerant pneumococci are a cause of concern. To date, the molecular basis of vancomycin tolerance in S. pneumoniae is essentially unknown. We examined two vancomycin-tolerant clinical isolates, i.e. a purported autolysin negative (LytA(-)), serotype 23F isolate (strain S3) and the serotype 14 strain 'Tupelo', which is considered a paradigm of vancomycin tolerance. S3 was characterized here as carrying a frameshift mutation in the lytA gene encoding the main pneumococcal autolysin. The vancomycin tolerance of strain S3 was abolished by transformation to the autolysin-proficient phenotype. The original Tupelo strain was discovered to be a mixture: a strain showing a vancomycin-tolerant phenotype (Tupelo_VT) and a vancomycin-nontolerant strain (Tupelo_VNT). The two strains differed only in terms of a single mutation in the ciaH gene present in the VT strain. Most interestingly, although the vancomycin tolerance of Tupelo_VT could be overcome by increasing the LytA dosage upon transformation by a multicopy plasmid or by externally adding the autolysin, we show that vancomycin tolerance in S. pneumoniae requires the simultaneous presence of a mutated CiaH histidine kinase and capsular polysaccharide. © 2010 Blackwell Publishing Ltd.

  12. Discovery of novel piperonyl derivatives as diapophytoene desaturase inhibitors for the treatment of methicillin-, vancomycin- and linezolid-resistant Staphylococcus aureus infections.

    PubMed

    Wei, Hanwen; Mao, Fei; Ni, Shuaishuai; Chen, Feifei; Li, Baoli; Qiu, Xiaoxia; Hu, Linghao; Wang, Manjiong; Zheng, Xinyu; Zhu, Jin; Lan, Lefu; Li, Jian

    2018-02-10

    Inhibition of S. aureus diapophytoene desaturase (CrtN) could serve as an alternative approach for addressing the tricky antibiotic resistance by blocking the biosynthesis of carotenoid pigment which shields the bacterium from host oxidant killing. In this study, we designed and synthesized 44 derivatives with piperonyl scaffold targeting CrtN and the structure-activity relationships (SARs) were examined extensively to bring out the discovery of 21b with potent efficacy and better hERG safety profile compared to the first class CrtN inhibitor benzocycloalkane derivative 2. Except the excellent pigment inhibitory activity against wild-type S. aureus, 21b also showed excellent pigment inhibition against four pigmented MRSA strains. In addition, H 2 O 2 killing and human whole blood killing assays proved 21b could sensitize S. aureus to be killed under oxidative stress conditions. Notably, the murine study in vivo validated the efficacy of 21b against pigmented S. aureus Newman, vancomycin-intermediate S. aureus Mu50 and linezolid-resistant S. aureus NRS271. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  13. Comparative in vitro study of the antimicrobial activities of different commercial antibiotic products of vancomycin

    PubMed Central

    2011-01-01

    Background One of the most critical problems about antimicrobial therapy is the increasing resistance to antibiotics. Previous studies have shown that there is a direct relation between erroneous prescription, dosage, route, duration of the therapy and the antibiotics resistance. Other important point is the uncertainty about the quality of the prescribed medicines. Some physicians believe that generic drugs are not as effective as innovator ones, so it is very important to have evidence that shows that all commercialized drugs are suitable for therapeutic use. Methods Microbial assays were used to establish the potency, the Minimal Inhibitory Concentrations (MICs), the Minimal Bactericidal Concentration (MBCs), the critical concentrations, and the production of spontaneous mutants that are resistant to vancomycin. Results The microbial assay was validated in order to determine the Vancomycin potency of the tasted samples. All the products showed that have potency values between 90 - 115% (USP requirement). The products behave similarly because the MICs, The MBCs, the critical concentrations, the critical concentrations ratios between standard and samples, and the production of spontaneous mutants don't have significant differences. Conclusions All products analyzed by microbiological tests, show that both trademarks and generics do not have statistical variability and the answer of antimicrobial activity Show also that they are pharmaceutical equivalents. PMID:21777438

  14. Comparative in vitro study of the antimicrobial activities of different commercial antibiotic products of vancomycin.

    PubMed

    Diaz, Jorge A; Silva, Edelberto; Arias, Maria J; Garzón, María

    2011-07-21

    One of the most critical problems about antimicrobial therapy is the increasing resistance to antibiotics. Previous studies have shown that there is a direct relation between erroneous prescription, dosage, route, duration of the therapy and the antibiotics resistance. Other important point is the uncertainty about the quality of the prescribed medicines. Some physicians believe that generic drugs are not as effective as innovator ones, so it is very important to have evidence that shows that all commercialized drugs are suitable for therapeutic use. Microbial assays were used to establish the potency, the Minimal Inhibitory Concentrations (MICs), the Minimal Bactericidal Concentration (MBCs), the critical concentrations, and the production of spontaneous mutants that are resistant to vancomycin. The microbial assay was validated in order to determine the Vancomycin potency of the tasted samples. All the products showed that have potency values between 90 - 115% (USP requirement). The products behave similarly because the MICs, The MBCs, the critical concentrations, the critical concentrations ratios between standard and samples, and the production of spontaneous mutants don't have significant differences. All products analyzed by microbiological tests, show that both trademarks and generics do not have statistical variability and the answer of antimicrobial activity Show also that they are pharmaceutical equivalents.

  15. Impact of an oil-based lubricant on the effectiveness of the sterilization processes .

    PubMed

    Rutala, William A; Gergen, Maria F; Weber, David J

    2008-01-01

    Surgical instruments, including hinged instruments, were inoculated with test microorganisms (ie, methicillin-resistant Staphylococcus aureus, approximately 2 x 10(6) colony-forming units [cfu]; Pseudomonas aeruginosa, approximately 3 x 10(6) cfu; Escherichia coli, approximately 2 x 10(5) cfu; vancomycin-resistant enterococci, 1 x 10(5) cfu; Geobacillus stearothermophilus spores, 2 x 10(5) cfu or more; or Bacillus atrophaeus spores, 9 x 10(4) cfu or more), coated with an oil-based lubricant (hydraulic fluid), subjected to a sterilization process, and then samples from the instruments were cultured. We found that the oil-based lubricant did not alter the effectiveness of the sterilization process because high numbers of clinically relevant bacteria and standard test spores (which are relatively resistant to the sterilization process) were inactivated.

  16. The Relationship Between Vancomycin Trough Concentrations and AUC/MIC Ratios in Pediatric Patients: A Qualitative Systematic Review.

    PubMed

    Tkachuk, Stacey; Collins, Kyle; Ensom, Mary H H

    2018-04-01

    In adults, the area under the concentration-time curve (AUC) divided by the minimum inhibitory concentration (MIC) is associated with better clinical and bacteriological response to vancomycin in patients with methicillin-resistant Staphylococcus aureus who achieve target AUC/MIC ≥ 400. This target is often extrapolated to pediatric patients despite the lack of similar evidence. The impracticalities of calculating the AUC in practice means vancomycin trough concentrations are used to predict the AUC/MIC. This review aimed to determine the relationship between vancomycin trough concentrations and AUC/MIC in pediatric patients. We searched the MEDLINE and Embase databases, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials using the medical subject heading (MeSH) terms vancomycin and AUC and pediatric* or paediatric*. Articles were included if they were published in English and reported a relationship between vancomycin trough concentrations and AUC/MIC. Of 122 articles retrieved, 11 met the inclusion criteria. One trial reported a relationship between vancomycin trough concentrations, AUC/MIC, and clinical outcomes but was likely underpowered. Five studies found troughs 6-10 mg/l were sufficient to attain an AUC/MIC > 400 in most general hospitalized pediatric patients. One study in patients undergoing cardiothoracic surgery found a trough of 18.4 mg/l achieved an AUC/MIC > 400. Two oncology studies reported troughs ≥ 15 mg/l likely attained an AUC/MIC ≥ 400. In critical care patients: one study found a trough of 9 mg/l did not attain the AUC/MIC target; another found 7 mg/l corresponded to an AUC/MIC of 400. Potential vancomycin targets varied based on the population studied but, for general hospitalized pediatric patients, troughs of 6-10 mg/l are likely sufficient to achieve AUC/MIC ≥ 400. For MIC ≥ 2 mg/l, higher troughs are likely necessary to achieve an AUC/MIC ≥ 400. More

  17. Estimation of Enterococci Input from Bathers and Animals on A Recreational Beach Using Camera Images

    PubMed Central

    D, Wang John; M, Solo-Gabriele Helena; M, Abdelzaher Amir; E, Fleming Lora

    2010-01-01

    Enterococci, are used nationwide as a water quality indicator of marine recreational beaches. Prior research has demonstrated that enterococci inputs to the study beach site (located in Miami, FL) are dominated by non-point sources (including humans and animals). We have estimated their respective source functions by developing a counting methodology for individuals to better understand their non-point source load impacts. The method utilizes camera images of the beach taken at regular time intervals to determine the number of people and animal visitors. The developed method translates raw image counts for weekdays and weekend days into daily and monthly visitation rates. Enterococci source functions were computed from the observed number of unique individuals for average days of each month of the year, and from average load contributions for humans and for animals. Results indicate that dogs represent the larger source of enterococci relative to humans and birds. PMID:20381094

  18. Fate and transport of veterinary antibiotics, antibiotic-resistant bacteria, and antibiotic resistance gene from fields receiving poultry manure during storm events

    USDA-ARS?s Scientific Manuscript database

    Antimicrobials are used in production agriculture to treat disease and promote animal growth, but the presence of antibiotics in the environment raises concern about widespread antibiotic resistance. This study documents the occurrence and transport of tylosin, tetracycline, enterococci resistant to...

  19. What happens in hospitals does not stay in hospitals: antibiotic-resistant bacteria in hospital wastewater systems.

    PubMed

    Hocquet, D; Muller, A; Bertrand, X

    2016-08-01

    Hospitals are hotspots for antimicrobial-resistant bacteria (ARB) and play a major role in both their emergence and spread. Large numbers of these ARB will be ejected from hospitals via wastewater systems. In this review, we present quantitative and qualitative data of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli, vancomycin-resistant enterococci and Pseudomonas aeruginosa in hospital wastewaters compared to community wastewaters. We also discuss the fate of these ARB in wastewater treatment plants and in the downstream environment. Published studies have shown that hospital effluents contain ARB, the burden of these bacteria being dependent on their local prevalence. The large amounts of antimicrobials rejected in wastewater exert a continuous selective pressure. Only a few countries recommend the primary treatment of hospital effluents before their discharge into the main wastewater flow for treatment in municipal wastewater treatment plants. Despite the lack of conclusive data, some studies suggest that treatment could favour the ARB, notably ESBL-producing E. coli. Moreover, treatment plants are described as hotspots for the transfer of antibiotic resistance genes between bacterial species. Consequently, large amounts of ARB are released in the environment, but it is unclear whether this release contributes to the global epidemiology of these pathogens. It is reasonable, nevertheless, to postulate that it plays a role in the worldwide progression of antibiotic resistance. Antimicrobial resistance should now be seen as an 'environmental pollutant', and new wastewater treatment processes must be assessed for their capability in eliminating ARB, especially from hospital effluents. Copyright © 2016. Published by Elsevier Ltd.

  20. Diversity, distribution and antibiotic resistance of Enterococcus spp. recovered from tomatoes, leaves, water and soil on U.S. Mid-Atlantic farms.

    PubMed

    Micallef, Shirley A; Goldstein, Rachel E Rosenberg; George, Ashish; Ewing, Laura; Tall, Ben D; Boyer, Marc S; Joseph, Sam W; Sapkota, Amy R

    2013-12-01

    Antibiotic-resistant enterococci are important opportunistic pathogens and have been recovered from retail tomatoes. However, it is unclear where and how tomatoes are contaminated along the farm-to-fork continuum. Specifically, the degree of pre-harvest contamination with enterococci is unknown. We evaluated the prevalence, diversity and antimicrobial susceptibilities of enterococci collected from tomato farms in the Mid-Atlantic United States. Tomatoes, leaves, groundwater, pond water, irrigation ditch water, and soil were sampled and tested for enterococci using standard methods. Antimicrobial susceptibility testing was performed using the Sensititre microbroth dilution system. Enterococcus faecalis isolates were characterized using amplified fragment length polymorphism to assess dispersal potential. Enterococci (n = 307) occurred in all habitats and colonization of tomatoes was common. Seven species were identified: Enterococcus casseliflavus, E. faecalis, Enterococcus gallinarum, Enterococcus faecium, Enterococcus avis, Enterococcus hirae and Enterococcus raffinosus. E. casseliflavus predominated in soil and on tomatoes and leaves, and E. faecalis predominated in pond water. On plants, distance from the ground influenced presence of enterococci. E. faecalis from samples within a farm were more closely related than those from samples between farms. Resistance to rifampicin, quinupristin/dalfopristin, ciprofloxacin and levofloxacin was prevalent. Consumption of raw tomatoes as a potential exposure risk for antibiotic-resistant Enterococcus spp. deserves further attention. Copyright © 2013 Elsevier Ltd. All rights reserved.