[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.

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

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.

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.

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

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.

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

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

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.

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.

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

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.

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

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.

[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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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

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.

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

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.

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.

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.

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).

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.

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.

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

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

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

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

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.

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.

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.

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

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.

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.

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

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

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

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

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

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

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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

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

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 ...

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.

[Studies for the development of novel anti-MRSA/VRE drugs].

PubMed

Hashizume, Hideki

2012-01-01

The widespread emergence of multidrug-resistant Gram-positive pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) is a high threat for human health. In the course of screening for active compounds against the above drug-resistant bacteria from microbial metabolites, we discovered three kinds of novel compounds designated tripropeptins, pargamicin, and amycolamicin. Tripropeptin C (TPPC), major component of tripropeptins, is the most promising compound because it is efficacious against MRSA and VRE both in vitro and in a mouse septicemia model, and shows no cross-resistance to available drugs including vancomycin. Studies of incorporation of radioactive macromolecular precursors and accumulation of UDP-MurNAc-pentapeptide in the cytoplasm in S. aureus Smith revealed that TPPC is a cell wall synthesis inhibitor. Antimicrobial activity of TPPC was weakened by addition of prenylpyrophosphates but not with prenylphosphates, UDP-linked sugars, or the pentapeptide of peptidoglycan. Direct interaction between TPPC and undecaprenyl pyrophosphate (C(55)-PP) was observed by mass spectrometry and thin layer chromatography, and TPPC inhibits C(55)-PP phosphatase, which plays a crucial role in peptidoglycan synthesis at an IC(50) of 0.03-0.1 µM in vitro. From the analysis of accumulation of lipid carrier-related compounds, TPPC caused accumulation of C(55)-PP in situ, leading to the accumulation of a glycine-added lipid intermediate, suggesting a distinct mode of action from that of clinically important drugs such as vancomycin, daptomycin, and bacitracin. TPPC might represent a promising novel class of antibiotic against MRSA and VRE infections.

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.

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

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.

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

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.

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

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

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.

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 ...

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.

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

Annual Surveillance Summary: Vancomycin-Resistant Enterococci (VRE) Infections in the Military Health System (MHS), 2016

DTIC Science & Technology

2017-06-01

to assess prescription practices, the Standard Inpatient Data Record (SIDR) to determine healthcare-associated exposures, Defense Manpower Data...1 Results ...limitations were applied to this annual summary. As such, this report presents analytical results and discussion of CY 2016 data for VRE infections in the

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.

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.

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.

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.

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.

A Discrete Event Simulation Model of Patient Flow in a General Hospital Incorporating Infection Control Policy for Methicillin-Resistant Staphylococcus Aureus (MRSA) and Vancomycin-Resistant Enterococcus (VRE).

PubMed

Shenoy, Erica S; Lee, Hang; Ryan, Erin E; Hou, Taige; Walensky, Rochelle P; Ware, Winston; Hooper, David C

2018-02-01

Hospitalized patients are assigned to available staffed beds based on patient acuity and services required. In hospitals with double-occupancy rooms, patients must be additionally matched by gender. Patients with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) must be bedded in single-occupancy rooms or cohorted with other patients with similar MRSA/VRE flags. We developed a discrete event simulation (DES) model of patient flow through an acute care hospital. Patients are matched to beds based on acuity, service, gender, and known MRSA/VRE colonization. Outcomes included time to bed arrival, length of stay, patient-bed acuity mismatches, occupancy, idle beds, acuity-related transfers, rooms with discordant MRSA/VRE colonization, and transmission due to discordant colonization. Observed outcomes were well-approximated by model-generated outcomes for time-to-bed arrival (6.7 v. 6.2 to 6.5 h) and length of stay (3.3 v. 2.9 to 3.0 days), with overlapping 90% coverage intervals. Patient-bed acuity mismatches, where patient acuity exceeded bed acuity and where patient acuity was lower than bed acuity, ranged from 0.6 to 0.9 and 8.6 to 11.1 mismatches per h, respectively. Values for observed occupancy, total idle beds, and acuity-related transfers compared favorably to model-predicted values (91% v. 86% to 87% occupancy, 15.1 v. 14.3 to 15.7 total idle beds, and 27.2 v. 22.6 to 23.7 transfers). Rooms with discordant colonization status and transmission due to discordance were modeled without an observed value for comparison. One-way and multi-way sensitivity analyses were performed for idle beds and rooms with discordant colonization. We developed and validated a DES model of patient flow incorporating MRSA/VRE flags. The model allowed for quantification of the substantial impact of MRSA/VRE flags on hospital efficiency and potentially avoidable nosocomial transmission.

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.

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.

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

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

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.

Defining the Role of the Environment in the Emergence and Persistence of vanA Vancomycin-Resistant Enterococcus (VRE) in an Intensive Care Unit: A Molecular Epidemiological Study.

PubMed

Lee, Andie S; White, Elizabeth; Monahan, Leigh G; Jensen, Slade O; Chan, Raymond; van Hal, Sebastiaan J

2018-06-01

OBJECTIVETo describe the transmission dynamics of the emergence and persistence of vanA vancomycin-resistant enterococcus (VRE) in an intensive care unit (ICU) using whole-genome sequencing of patient and environmental isolates.DESIGNRetrospective cohort study.SETTINGICU in a tertiary referral center.PARTICIPANTSPatients admitted to the ICU over an 11-month period.METHODS VanA VRE isolated from patients (n=31) were sequenced using the Illumina MiSeq platform. Environmental samples from bed spaces, equipment, and waste rooms were collected. All vanA VRE-positive environmental samples (n=14) were also sequenced. Data were collected regarding patient ward and bed movements.RESULTSThe 31 patient vanA VRE isolates were from screening (n=19), urine (n=4), bloodstream (n=3), skin/wound (n=3), and intra-abdominal (n=2) sources. The phylogeny from sequencing data confirmed several VRE clusters, with 1 group accounting for 38 of 45 isolates (84%). Within this cluster, cross-transmission was extensive and complex across the ICU. Directionality indicated that colonized patients contaminated environmental sites. Similarly, environmental sources not only led to patient colonization but also to infection. Notably, shared equipment acted as a conduit for transmission between different ICU areas. Infected patients, however, were not linked to further VRE transmission.CONCLUSIONSGenomic sequencing confirmed a predominantly clonal outbreak of VRE with complex transmission dynamics. The environmental reservoir, particularly from shared equipment, played a key role in ongoing VRE spread. This study provides evidence to support the use of multifaceted strategies, with an emphasis on measures to reduce bacterial burden in the environment, for successful VRE control.Infect Control Hosp Epidemiol 2018;39:668-675.

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

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

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

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

Action mechanism of 6, 6'-dihydroxythiobinupharidine from Nuphar japonicum, which showed anti-MRSA and anti-VRE activities.

PubMed

Okamura, Shinya; Nishiyama, Eri; Yamazaki, Tomohiro; Otsuka, Nao; Taniguchi, Shoko; Ogawa, Wakano; Hatano, Tsutomu; Tsuchiya, Tomofusa; Kuroda, Teruo

2015-06-01

Multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin resistant enterococci (VRE), cause serious infections at clinical sites, for which the development of new drugs is necessary. We screened candidates for new antibiotics and investigated its action mechanism. An antimicrobial compound was isolated from an extract of Nuphar japonicum. Its chemical structure was determined by NMR, MS, and optical rotation. We measured its minimum inhibitory concentration (MIC) using the microdilution method. The effects of the compound on DNA gyrase and DNA topoisomerase IV were investigated with DNA supercoiling, decatenation, and cleavage assay. We isolated and identified 6,6'-dihydroxythiobinupharidine as the antimicrobial compound. The MIC of this compound was 1-4 μg/mL against various MRSA and VRE strains. We also demonstrated that this compound inhibited DNA topoisomerase IV (IC50 was 10-15 μM), but not DNA gyrase in S. aureus, both of which are known to be the targets of quinolone antibiotics and necessary for DNA replication. However, this compound only exhibited slight cross-resistance to norfloxacin-resistant S. aureus, which indicated that DTBN might inhibit other targets besides topoisomerase IV. These results suggest that 6,6'-dihydroxythiobinupharidine may be a potent candidate or seed for novel antibacterial agents. DTBN from N. japonicum showed anti-MRSA and anti-VRE activities. DTBN might be involved in the inhibition of DNA topoisomerase IV. DTBN might be useful as a seed compound. The information on the inhibition mechanism of DTBN will be useful for the modification of DTBN towards developing novel anti-MRSA and anti-VRE drug. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

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.

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.

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.

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

[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.

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

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.

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

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.

Postdischarge decontamination of MRSA, VRE, and Clostridium difficile isolation rooms using 2 commercially available automated ultraviolet-C-emitting devices.

PubMed

Wong, Titus; Woznow, Tracey; Petrie, Mike; Murzello, Elena; Muniak, Allison; Kadora, Amin; Bryce, Elizabeth

2016-04-01

Two ultraviolet-C (UVC)-emitting devices were evaluated for effectiveness in reducing methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and Clostridium difficile (CD). Six surfaces in rooms previously occupied by patients with MRSA, VRE, or CD were cultured before and after cleaning and after UVC disinfection. In a parallel laboratory study, MRSA and VRE suspended in trypticase soy broth were inoculated onto stainless steel carriers in triplicate, placed in challenging room areas, subjected to UVC, and subcultured to detect growth. Sixty-one rooms and 360 surfaces were assessed. Before cleaning, MRSA was found in 34.4%, VRE was found in 29.5%, and CD was found in 31.8% of rooms. Cleaning reduced MRSA-, VRE-, and CD-contaminated rooms to 27.9%, 29.5%, and 22.7%, respectively (not statistically significant). UVC disinfection further reduced MRSA-, VRE-, and CD-contaminated rooms to 3.3% (P = .0003), 4.9% (P = .0003), and 0% (P = .0736), respectively. Surface colony counts (excluding floors) decreased from 88.0 to 19.6 colony forming units (CFU) (P < .0001) after manual cleaning; UVC disinfection further reduced it to 1.3 CFU (P = .0013). In a multivariable model of the carrier study, the odds of detecting growth in broth suspensions after UVC disinfection were 7 times higher with 1 machine (odds ratio, 6.96; 95% confidence interval, 3.79-13.4) for a given organism, surface, and concentration. UVC devices are effective adjuncts to manual cleaning but vary in their ability to disinfect high concentrations of organisms in the presence of protein. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

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.

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

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.

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

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.

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.

Vancomycin-Resistant Enterococcus Colonization and Bacteremia and Hematopoietic Stem Cell Transplantation Outcomes.

PubMed

Ford, Clyde D; Gazdik, Michaela A; Lopansri, Bert K; Webb, Brandon; Mitchell, Birgitta; Coombs, Jana; Hoda, Daanish; Petersen, Finn Bo

2017-02-01

The association between pre-hematopoietic stem cell transplantation (HSCT) vancomycin-resistant Enterococcus (VRE) colonization, HSCT-associated VRE bacteremia, and HSCT mortality is disputed. We studied 161 consecutive patients with acute leukemia who underwent HSCT at our hospital between 2006 and 2014, of whom 109 also received leukemia induction/consolidation on our unit. All inpatients had weekly VRE stool surveillance. Pre-HSCT colonization was not associated with increases in HSCT mortality but did identify a subgroup of HSCT recipients with a higher risk for VRE bacteremia and possibly bacteremia from other organisms. The major risk factor for pre-HSCT colonization was the number of hospital inpatient days between initial admission for leukemia and HSCT. One-third of evaluable patients colonized before HSCT were VRE-culture negative on admission for HSCT; these patients had an increased risk for subsequent VRE stool surveillance positivity but not VRE bacteremia. Molecular typing of VRE isolates obtained before and after HSCT showed that VRE strains frequently change. Postengraftment VRE bacteremia was associated with a much higher mortality than pre-engraftment VRE bacteremia. Pre-engraftment bacteremia from any organism was associated with an alternative donor and resulted in an increase in hospital length of stay and cost. Mortality was similar for pre-engraftment VRE bacteremia and pre-engraftment bacteremia due to other organisms, but mortality associated with post-engraftment VRE bacteremia was higher and largely explained by associated severe graft-versus-host disease and relapsed leukemia. These data emphasize the importance of distinguishing between VRE colonization before HSCT and at HSCT, between pre-engraftment and postengraftment VRE bacteremia, and between VRE bacteremia and bacteremia from other organisms. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

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 �

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.

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.

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

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.

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.

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

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.

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.

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.

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.

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.

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

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

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.

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.

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

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.

Comparison of risk factors and outcomes of daptomycin-susceptible and -nonsusceptible vancomycin-resistant Enterococcus faecium infections in liver transplant recipients.

PubMed

Lewis, J D; Barros, A J; Sifri, C D

2018-02-10

Vancomycin-resistant Enterococcus faecium (VRE) infections are common in liver transplant recipients (LTRs). Daptomycin (DAP) is an important treatment for such infections; however, DAP-nonsusceptible VRE (DNS-VRE) are increasingly frequent. The purpose of this study was to compare clinical characteristics and outcomes of LTRs with infections due to DNS-VRE and DAP-susceptible VRE (DS-VRE). A single center, retrospective review of patients who underwent liver transplantation between January 1, 2010 and December 31, 2015 and developed infections due to DS-VRE or DNS-VRE post transplant was performed. Patients with DNS-VRE and DS-VRE infections were compared using univariate and logistic regression analysis. Fourteen LTRs developed DNS-VRE and 20 LTRs developed DS-VRE infection post-transplantation. No significant differences were observed in demographics, model for end-stage liver disease (MELD) scores, causes of end-stage liver disease, or rate of pre-transplant perirectal VRE colonization between groups. Bleeding complications and renal replacement therapy were more common in the DNS-VRE group than in the DS-VRE group. The duration of transplant hospitalization and post-transplant intensive care unit (ICU) admission was longer in the DNS-VRE group than in the DS-VRE group. The 30-day and 6-month mortality rate associated with DNS-VRE infection was similar to that associated with DS-VRE infection. Liver transplant recipients who develop DNS-VRE infection have higher bleeding complications and longer, more complex hospitalizations compared to those who develop DS-VRE infection post transplantation; however, mortality at 30 days and 6 months is not significantly worse. Further study is needed to determine optimal strategies for the prevention and treatment of DNS-VRE infections in LTRs. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

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.

Influence of an independent quarterly audit on publicly reported vancomycin-resistant enterocococi bacteremia data in Ontario, Canada.

PubMed

Prematunge, Chatura; Policarpio, Michelle E; Johnstone, Jennie; Adomako, Kwaku; Nadolny, Emily; Lam, Freda; Li, Ye; Brown, Kevin A; Garber, Gary

2018-04-13

All Ontario hospitals are mandated to self-report vancomycin-resistant enterocococi (VRE) bacteremias to Ontario's Ministry of Health and Long-term Care for public reporting purposes. Independent quarterly audits of publicly reported VRE bacteremias between September 2013 and June 2015 were carried out by Public Health Ontario. VRE bacteremia case-reporting errors between January 2009 and August 2013 were identified by a single retrospective audit. Employing a quasiexperimental pre-post study design, the relative risk of VRE bacteremia reporting errors before and after quarterly audits were modeled using Poisson regression adjusting for hospital type, case counts reported to the Ministry of Health and Long-term Care, and autocorrelation via generalized estimating equation. Overall, 24.5% (126 out of 514) of VRE bacteremias were reported in error; 114 out of 367 (31%) VRE bacteremias reported before quarterly audits and 12 out of 147 (8.1%) reported after audits were found to be incorrect. In adjusted analysis, quarterly audits of VRE bacteremias were associated with significant reductions in reporting errors when compared with before quarterly auditing (relative risk, 0.17; 95% confidence interval, 0.05-0.63). Risk of reporting errors among community hospitals were greater than acute teaching hospitals of the region (relative risk, 4.39; 95% CI, 3.07-5.70). This study found independent quarterly audits of publicly reported VRE bacteremias to be associated with significant reductions in reporting errors. Public reporting systems should consider adopting routine data audits and hospital-targeted training to improve data accuracy. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

Optimization of the central linker of dicationic bis-benzimidazole anti-MRSA and anti-VRE agents.

PubMed

Hu, Laixing; Kully, Maureen L; Boykin, David W; Abood, Norman

2009-07-01

A series of bis-benzimidazole diamidine compounds containing different central linkers has been synthesized and evaluated for in vitro antibacterial activities, including drug-resistant bacterial strains. Seven compounds have shown potent antibacterial activities. The anti-MRSA and anti-VRE activities of compound 1h were more potent than that of the lead compound 1a and vancomycin.

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.

Synthesis and in vitro activity of dicationic bis-benzimidazoles as a new class of anti-MRSA and anti-VRE agents.

PubMed

Hu, Laixing; Kully, Maureen L; Boykin, David W; Abood, Norman

2009-03-01

A new class of novel bis-benzimidazole diamidine compounds have been synthesized and evaluated for in vitro antibacterial activities, including drug-resistant bacterial strains. Anti-MRSA and anti-VRE activities of the most potent compound 1 were more active than Vancomycin. The mechanism of action for this class of compounds appears to be different from existing antibiotics. Bis-benzimidazole diamidine compounds have potential for further investigation as a new class of potent anti-MRSA and anti-VRE agents.

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.

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

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.

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.

[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.

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

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.

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.

Co-colonization of vanA and vanB Enterococcus faecium of clonal complex 17 in a patient with bacteremia due to vanA E. faecium.

PubMed

Seol, Chang Ahn; Park, Jeong Su; Sung, Heungsup; Kim, Mi-Na

2014-06-01

A 53-year-old Vietnamese man with liver cirrhosis was transferred from a Vietnamese hospital to our tertiary care hospital in Korea in order to undergo a liver transplantation. Bacteremia due to vanA Enterococcus faecium was diagnosed, and stool surveillance cultures for vancomycin-resistant enterococci (VRE) were positive for both vanA and vanB E. faecium. Pulsed-field gel electrophoresis analysis revealed that the 2 vanA VRE isolates from the blood and stool were clonal, but the vanB VRE was unrelated to the vanA VRE. vanA and vanB VRE were ST64 and ST18, single-allele variations of clonal complex 17, respectively. This is the first case report of vanA VRE bacteremia in a Vietnamese patient and demonstrates the reemergence of vanB VRE since a single outbreak occurred 15years ago in Korea. The reemergence of vanB VRE emphasizes the importance of VRE genotyping to prevent the spread of new VRE strains. Copyright © 2014 Elsevier Inc. All rights reserved.

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

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

Room contamination, patient colonization pressure, and the risk of vancomycin-resistant Enterococcus colonization on a unit dedicated to the treatment of hematologic malignancies and hematopoietic stem cell transplantation.

PubMed

Ford, Clyde D; Lopansri, Bert K; Gazdik, Michaela A; Webb, Brandon; Snow, Gregory L; Hoda, Daanish; Adams, Barbara; Petersen, Finn Bo

2016-10-01

Contaminated surfaces and colonization pressure are risk factors for vancomycin-resistant Enterococcus (VRE) colonization in intensive care units (ICUs). Whether these apply to modern units dedicated to the care of hematologic malignancies and hematopoietic stem cell transplant (HSCT) procedures is unknown. We reviewed the records of 780 consecutive admissions for acute leukemia, autologous HSCT, or allogeneic HSCT in which the patient was at risk for hospital-acquired VRE and underwent weekly surveillance. We also obtained staff and room cultures, observed staff behavior, and performed VRE molecular strain typing on selected isolates. The overall rate of VRE colonization was 11.4 cases/1,000 patient days. Cultures of room surfaces revealed VRE isolates in 10% of terminally cleaned rooms. A prior VRE-colonized room occupant did not increase risk, and paired isolates from 20 patients and prior occupants were indistinguishable on molecular typing in only 1 pair. VRE colonization pressure was significantly associated with acquisition. Cultures of unit personnel and shared equipment were negative except for weighing scales. Observation of unit clinical personnel showed high compliance for hand sanitation and but less so for gowns. Conversely, ancillary staff showed poor compliance. Transmission of VRE from room surfaces seems to be an infrequent event. Encouraging adherence to surveillance, disinfection, and contact isolation protocols may decrease VRE colonization rates. Copyright © 2016. Published by Elsevier Inc.

Duration of exposure to multiple antibiotics is associated with increased risk of VRE bacteraemia: a nested case-control study.

PubMed

Gouliouris, Theodore; Warne, Ben; Cartwright, Edward J P; Bedford, Luke; Weerasuriya, Chathika K; Raven, Kathy E; Brown, Nick M; Török, M Estée; Limmathurotsakul, Direk; Peacock, Sharon J

2018-03-13

VRE bacteraemia has a high mortality and continues to defy control. Antibiotic risk factors for VRE bacteraemia have not been adequately defined. We aimed to determine the risk factors for VRE bacteraemia focusing on duration of antibiotic exposure. A retrospective matched nested case-control study was conducted amongst hospitalized patients at Cambridge University Hospitals NHS Foundation Trust (CUH) from 1 January 2006 to 31 December 2012. Cases who developed a first episode of VRE bacteraemia were matched 1:1 to controls by length of stay, year, specialty and ward type. Independent risk factors for VRE bacteraemia were evaluated using conditional logistic regression. Two hundred and thirty-five cases were compared with 220 controls. Duration of exposure to parenteral vancomycin, fluoroquinolones and meropenem was independently associated with VRE bacteraemia. Compared with patients with no exposure to vancomycin, those who received courses of 1-3 days, 4-7 days or >7 days had a stepwise increase in risk of VRE bacteraemia [conditional OR (cOR) 1.2 (95% CI 0.4-3.8), 3.8 (95% CI 1.2-11.7) and 6.6 (95% CI 1.9-22.8), respectively]. Other risk factors were: presence of a central venous catheter (CVC) [cOR 8.7 (95% CI 2.6-29.5)]; neutropenia [cOR 15.5 (95% CI 4.2-57.0)]; hypoalbuminaemia [cOR 8.5 (95% CI 2.4-29.5)]; malignancy [cOR 4.4 (95% CI 1.6-12.0)]; gastrointestinal disease [cOR 12.4 (95% CI 4.2-36.8)]; and hepatobiliary disease [cOR 7.9 (95% CI 2.1-29.9)]. Longer exposure to vancomycin, fluoroquinolones or meropenem was associated with VRE bacteraemia. Antimicrobial stewardship interventions targeting high-risk antibiotics are required to complement infection control procedures against VRE bacteraemia.

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.

Money and transmission of bacteria

PubMed Central

2013-01-01

Money is one of the most frequently passed items in the world. The aim of this study was to ascertain the survival status of bacteria including Staphylococcus aureus, Escherichia coli, and Vancomycin- Resistant Enterococci (VRE) on banknotes from different countries and the transmission of bacteria to people who come in contact with the banknotes. The survival rate was highest for the Romanian Leu yielding all three microorganisms used after both three and six hours of drying. Furthermore, the Leu was the only banknote to yield VRE after one day of drying. Other currencies either enabled the survival of Extended-Spectrum Beta-Lactamases (ESBL) and VRE (e.g. Euro), but not of MRSA, or the other way round (e.g. US Dollar). While a variety of factors such as community hygiene levels, people’s behaviour, and antimicrobial resistance rates at community level obviously have influence on the transmission of resistant microorganisms, the type of banknote-paper may be an additional variable to consider. PMID:23985137

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

Epidemiology of Resistant Microbial Strains Among Different Groups of People (Healthy, Infected and Exposed to Animals)

ClinicalTrials.gov

2017-11-10

ESBL Producing E.Coli; ESBL Producing K.Pneumoniae; Multidrug Resistant P.Aeruginosa; Carbapenem Resistant P.Aeruginosa; Methicillin Resistant Staphylococcus Aureus (MRSA); Vancomycin (Glycopeptide) Resistant Enterococcus (VRE)

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.

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.

New Acquisition of Antibiotic-Resistant Organisms in Skilled Nursing Facilities

PubMed Central

Fisch, Jay; Lansing, Bonnie; Wang, Linda; Symons, Kathleen; Cherian, Kay; McNamara, Sara

2012-01-01

The epidemiology of new acquisition of antibiotic-resistant organisms (AROs) in community-based skilled nursing facilities (SNFs) is not well studied. To define the incidence, persistence of, and time to new colonization with methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and ceftazidime-resistant (CAZr) and ciprofloxacin-resistant (CIPr) Gram-negative bacteria (GNB) in SNFs, SNF residents were enrolled and specimens from the nares, oropharynx, groin, perianal area, and wounds were prospectively cultured monthly. Standard microbiological tests were used to identify MRSA, VRE, and CAZr and CIPr GNB. Residents with at least 3 months of follow-up were included in the analysis. Colonized residents were categorized as having either preexisting or new acquisition. The time to colonization for new acquisition of AROs was calculated. Eighty-two residents met the eligibility criteria. New acquisition of AROs was common. For example, of the 59 residents colonized with CIPr GNB, 28 (47%) were colonized with CIPr GNB at the start of the study (96% persistent and 4% intermittent), and 31 (53%) acquired CIPr GNB at the facility (61% persistent). The time to new acquisition was shortest for CIPr GNB, at a mean of 75.5 days; the time to new acquisition for MRSA was 126.6 days (P = 0.007 versus CIPr GNB), that for CAZr was 176.0 days (P = 0.0001 versus CIPr GNB), and that for VRE was 186.0 days (P = 0.0004 versus CIPr GNB). Functional status was significantly associated with new acquisition of AROs (odds ratio [OR], 1.24; P = 0.01). New acquisition of AROs, in particular CIPr GNB and MRSA, is common in SNFs. CIPr GNB are acquired rapidly. Additional longitudinal studies to investigate risk factors for ARO acquisition are required. PMID:22378900

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.

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

Multiresistant Bacteria Isolated from Chicken Meat in Austria

PubMed Central

Zarfel, Gernot; Galler, Herbert; Luxner, Josefa; Petternel, Christian; Reinthaler, Franz F.; Haas, Doris; Kittinger, Clemens; Grisold, Andrea J.; Pless, Peter; Feierl, Gebhard

2014-01-01

Multidrug resistant bacteria (MDR bacteria), such as extended spectrum beta-lactamase (ESBL) Enterobacteriaceae, methicillin resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococci (VRE), pose a challenge to the human health care system. In recent years, these MDR bacteria have been detected increasingly outside the hospital environment. Also the contamination of food with MDR bacteria, particularly of meat and meat products, is a concern. The aim of the study was to evaluate the occurrence of MDR bacteria in chicken meat on the Austrian market. For this study, 50 chicken meat samples were analysed. All samples originated from chickens slaughtered in Austrian slaughterhouses and were marked as produced in Austria. Samples were analysed for the presence of ESBL Enterobacteriaceae, methicillin resistant Staphylococci and VRE. Resistance genes of the isolated bacteria were characterised by PCR and sequencing. In the present study 26 ESBL producing E. coli, five mecA gene harbouring Staphylococci (but no MRSA), and four VRE were detected in chicken meat samples of Austrian origin. In 24 (48%) of the samples no ESBL Enterobacteriaceae, MRSA, methicillin resistant coagulase negative Staphylococcus (MRCNS) or VRE could be detected. None of the samples contained all three types of investigated multiresistant bacteria. In concordance to previous studies, CTX-M-1 and SHV-12 were the dominant ESBL genes. PMID:25485979

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

Intestinal Translocation of Clinical Isolates of Vancomycin-Resistant Enterococcus faecalis and ESBL-Producing Escherichia coli in a Rat Model of Bacterial Colonization and Liver Ischemia/Reperfusion Injury

PubMed Central

van der Heijden, Karin M.; van der Heijden, Inneke M.; Galvao, Flavio H.; Lopes, Camila G.; Costa, Silvia F.; Abdala, Edson; D’Albuquerque, Luiz A.; Levin, Anna S.

2014-01-01

The objectives of this study were to develop a rat model of gastrointestinal colonization with vancomycin-resistant Enterococcus faecalis (VRE) and extended-spectrum beta-lactamase (ESBL)-producing E. coli and to evaluate intestinal translocation to blood and tissues after total and partial hepatic ischemia. Methods - We developed a model of rat colonization with VRE and ESBL-E coli. Then we studied four groups of colonized rats: Group I (with hepatic pedicle occlusion causing complete liver ischemia and intestinal stasis); Group II (with partial liver ischemia without intestinal stasis); Group III (surgical manipulation without hepatic ischemia or intestinal stasis); Group IV (anesthetized without surgical manipulation). After sacrifice, portal and systemic blood, large intestine, small intestine, spleen, liver, lungs, and cervical and mesenteric lymph nodes were cultured. Endotoxin concentrations in portal and systemic blood were determined. Results – The best inocula were: VRE: 2.4×1010 cfu and ESBL-E. coli: 1.12×1010 cfu. The best results occurred 24 hours after inoculation and antibiotic doses of 750 µg/mL of water for vancomycin and 2.1 mg/mL for ceftriaxone. There was a significantly higher proportion of positive cultures for ESBL-E. coli in the lungs in Groups I, II and III when compared with Group IV (67%; 60%; 75% and 13%, respectively; p:0.04). VRE growth was more frequent in mesenteric lymph nodes for Groups I (67%) and III (38%) than for Groups II (13%) and IV (none) (p:0.002). LPS was significantly higher in systemic blood of Group I (9.761±13.804 EU/mL−p:0.01). No differences for endotoxin occurred in portal blood. Conclusion –We developed a model of rats colonized with resistant bacteria useful to study intestinal translocation. Translocation occurred in surgical procedures with and without hepatic ischemia-reperfusion and probably occurred via the bloodstream. Translocation was probably lymphatic in the ischemia-reperfusion groups

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.

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.

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

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

Vancomycin-resistant Enterococcus faecium bacteraemia as a complication of Kayexalate (sodium polystyrene sulfonate, SPS) in sorbitol-induced ischaemic colitis.

PubMed

Cerrud-Rodriguez, Roberto Christian; Alcaraz-Alvarez, Diego; Chiong, Brian Bobby; Ahmed, Abdurhman

2017-11-09

We present the case report of an 80-year-old woman with chronic kidney disease stage G5 admitted to the hospital with fluid overload and hyperkalaemia. Sodium polystyrene sulfonate (SPS, Kayexalate) in sorbitol suspension was given orally to treat her hyperkalaemia, which precipitated an episode of SPS in sorbitol-induced ischaemic colitis with the subsequent complication of vancomycin-resistant Enterococcus (VRE) bacteraemia. SPS (Kayexalate) in sorbitol suspension has been implicated in the development of intestinal necrosis. Sorbitol, which is added as a cathartic agent to decrease the chance of faecal impaction, may be primarily responsible through several proposed mechanisms. The gold standard of diagnosis is the presence of SPS crystals in the colon biopsy. On a MEDLINE search, no previous reports of a VRE bacteraemia as a complication of biopsy-confirmed SPS in sorbitol ischaemic colitis were found. To the best of our knowledge, ours would be the first such case ever reported. © 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.

Frequency, risk factors, and outcomes of vancomycin-resistant Enterococcus colonization and infection in patients with newly diagnosed acute leukemia: different patterns in patients with acute myelogenous and acute lymphoblastic leukemia.

PubMed

Ford, Clyde D; Lopansri, Bert K; Haydoura, Souha; Snow, Greg; Dascomb, Kristin K; Asch, Julie; Bo Petersen, Finn; Burke, John P

2015-01-01

OBJECTIVE To determine the frequency, risk factors, and outcomes for vancomycin-resistant Enterococcus (VRE) colonization and infection in patients with newly diagnosed acute leukemia. DESIGN Retrospective clinical study with VRE molecular strain typing. SETTING A regional referral center for acute leukemia. PATIENTS Two hundred fourteen consecutive patients with newly diagnosed acute leukemia between 2006 and 2012. METHODS All patients had a culture of first stool and weekly surveillance for VRE. Clinical data were abstracted from the Intermountain Healthcare electronic data warehouse. VRE molecular typing was performed utilizing the semi-automated DiversiLab System. RESULTS The rate of VRE colonization was directly proportional to length of stay and was higher in patients with acute lymphoblastic leukemia. Risk factors associated with colonization include administration of corticosteroids (P=0.004) and carbapenems (P=0.009). Neither a colonized prior room occupant nor an increased unit colonization pressure affected colonization risk. Colonized patients with acute myelogenous leukemia had an increased risk of VRE bloodstream infection (BSI, P=0.002). Other risk factors for VRE BSI include severe neutropenia (P=0.04) and diarrhea (P=0.008). Fifty-eight percent of BSI isolates were identical or related by molecular typing. Eighty-nine percent of bloodstream isolates were identical or related to stool isolates identified by surveillance cultures. VRE BSI was associated with increased costs (P=0.0003) and possibly mortality. CONCLUSIONS VRE colonization has important consequences for patients with acute myelogenous leukemia undergoing induction therapy. For febrile neutropenic patients with acute myelogenous leukemia, use of empirical antibiotic regimens that avoid carbapenems and include VRE coverage may be helpful in decreasing the risks associated with VRE BSI.

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.

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.

MiBAlert-a new information tool to fight multidrug-resistant bacteria in the hospital setting.

PubMed

Olesen, Bente; Anhøj, Jacob; Rasmussen, Kenneth Palle; Mølbak, Kåre; Voldstedlund, Marianne

2016-11-01

Although the timely isolation of patients is an essential intervention to limit spread of drug-resistant bacteria, information about the colonization status is often unavailable or lost when patients are readmitted or transferred between hospitals. Therefore, carriers of drug resistant bacteria are not recognized sufficiently early, and proper and timely isolation precautions are not taken. Consequently, resistant bacteria of public health concerns including vancomycin resistant enterococci (VRE) and methicillin resistant Staphylococcus aureus (MRSA) can spread epidemically. To ensure timely identification and proper isolation of such patients we developed an automatic real-time alert of carriers of drug resistant bacteria. The aim of this paper is to describe the system, called MiBAlert, and share the initial experiences in connection with an outbreak of VRE in the greater Copenhagen area (the Capital region), Denmark. We obtained data on cases of VRE from hospitals in Copenhagen during the period when the first version of MiBAlert was implemented and log-data on the use of MiBAlert. Furthermore, a survey was conducted among 88 staff members to investigate their experiences of MiBAlert. The alert is a tool directed toward healthcare personnel accessing the electronic health record (EHR) and those further involved in the care and treatment of the patient. It is based on a web service using data from the national microbiological database, MiBa. MiBAlert is a real-time electronic non-intrusive alert generated automatically in the header of the EHR each time record is accessed. On February 15, 2015 a pilot version of MiBAlert was launched. All positive tests for VRE throughout 1year were shown with alert status by MiBAlert visible to all medical staff with access to EHR. The alert system was automatically updated directly in the EHR across the five hospitals in the Capital region. We found that the system performed satisfactorily, being operational 24/7 all 135 trial

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.

Presence, distribution and molecular epidemiology of multi-drug-resistant Gram-negative bacilli from medical personnel of intensive care units in Tianjin, China, 2007-2015.

PubMed

Liu, H; Fei, C N; Zhang, Y; Liu, G W; Liu, J; Dong, J

2017-06-01

Multi-drug-resistant Gram-negative bacteria (MDRGNB) have become an important cause of nosocomial infection in intensive care units (ICUs). To investigate the molecular epidemiology of MDRGNB isolated from medical personnel (MP) and non-medical personnel (NMP) at 69 ICUs in Tianjin, China. From April 2007 to October 2015, 2636 nasal and hand swab samples from 1185 MP and 133 NMP were cultured for GNB (including MDRGNB), meticillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). The susceptibilities of GNB to 14 antimicrobial agents were determined, and 80 MDRGNB were characterized using pulsed-field gel electrophoresis (PFGE) and dendrogram analysis. In total, 301 GNB were identified in 269 MP, including 109 MDRGNB isolates in 104 MP. Forty-two GNB were isolated from 39 NMP, which included 20 NMP with MDRGNB. Overall, 8.8% of MP were colonized with MDRGNB, which greatly exceeded colonization rates with MRSA (0.9%) and VRE (0.1%). Three pairs of Klebsiella pneumoniae and one pair of Enterobacter aerogenes were indistinguishable from each other, but the majority of isolate tests had distinct PFGE profiles. The prevalence of MDRGNB was high among ICU MP in Tianjin, and greatly exceeded that of VRE and MRSA. There was no difference in the rates of nasal carriage of MDRGNB between MP and NMP, but NMP were significantly more likely to have hand colonization with MDRGNB. PFGE profiles showed that there was only limited sharing of strains of MDR E. aerogenes and K. pneumoniae between personnel. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

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.

Assessment of materials commonly utilized in health care: implications for bacterial survival and transmission.

PubMed

Lankford, Mary G; Collins, Susan; Youngberg, Larry; Rooney, Denise M; Warren, John R; Noskin, Gary A

2006-06-01

Contaminated environmental surfaces, equipment, and health care workers' hands have been linked to outbreaks of infection or colonization because of vancomycin-resistant enterococci (VRE) and Pseudomonas aeruginosa (PSAE). Upholstery, walls, and flooring may enhance bacterial survival, providing infectious reservoirs. Investigate recovery of VRE and PSAE, determine efficacy of disinfection, and evaluate VRE transmission from surfaces. Upholstery, flooring, and wall coverings were inoculated with VRE and PSAE and assessed for recovery at 24 hours, 72 hours, and 7 days. Inoculated surfaces were cleaned utilizing manufacturers' recommendations of natural, commercial, or hospital-approved products and methods, and samples were obtained. To assess potential for transmission, volunteers touched VRE-inoculated surfaces and imprinted palms onto contact-impression plates. Twenty-four hours following inoculation, all surfaces had recovery of VRE; 13 (92.9%) of 14 surfaces had persistent PSAE. After cleaning, VRE was recovered from 7 (50%) surfaces, PSAE from 5 (35.7%) surfaces. After inoculation followed by palmar contact, VRE was recovered from all surfaces touched. Bacteria commonly encountered in hospitals are capable of prolonged survival and may promote cross transmission. Selection of surfaces for health care environments should include product application and complexity of manufacturers' recommendations for disinfection. Recovery of organisms on surfaces and hands emphasizes importance of hand hygiene compliance prior to patient contact.

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.

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.

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.

Epidemiology and molecular typing of VRE bloodstream isolates in an Irish tertiary care hospital.

PubMed

Ryan, L; O'Mahony, E; Wrenn, C; FitzGerald, S; Fox, U; Boyle, B; Schaffer, K; Werner, G; Klare, I

2015-10-01

Ireland has the highest rate of vancomycin-resistant Enterococcus faecium (VREfm) isolated from blood of nosocomial patients in Europe, which rose from 33% (110/330) in 2007 to 45% (178/392) in 2012. No other European country had a VREfm rate from blood cultures of >25%. Our aim was to elucidate the reasons for this significantly higher rate in Ireland. The epidemiology and molecular typing of VRE from bloodstream infections (BSIs) was examined in a tertiary care referral hospital and isolates were compared with those from other tertiary care referral centres in the region. The most common source of VRE BSIs was intra-abdominal sepsis, followed by line-related infection and febrile neutropenia. Most of the isolates were positive for vanA; 52% (43/83) possessed the esp gene and 12% (10/83) possessed the hyl gene. Genotyping by SmaI macrorestriction analysis (PFGE) of isolates revealed clonal relatedness between bloodstream isolates and environmental isolates. VRE BSI isolates from two other tertiary care hospitals in the Dublin region showed relatedness by PFGE analysis. MLST revealed four STs (ST17, ST18, ST78 and ST203), all belonging to the clonal complex of hospital-associated strains. Irish VRE BSI isolates have virulence factor profiles as previously reported from Europe. Typing analysis shows the spread of individual clones within the hospital and between regional tertiary care hospitals. Apart from transmission of VRE within the hospital and transfer of colonized patients between Irish hospitals, no other explanation for the persistently high VREfm BSI rate in Ireland has been found. © The Author 2015. 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.

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.

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.

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.

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

Feasibility, efficacy, and adverse effects of outpatient antibacterial prophylaxis in children with acute myeloid leukemia

PubMed Central

Inaba, Hiroto; Gaur, Aditya H; Cao, Xueyuan; Flynn, Patricia M; Pounds, Stanley B; Avutu, Viswatej; Marszal, Lindsay N; Howard, Scott C; Pui, Ching-Hon; Ribeiro, Raul C; Hayden, Randall T; Rubnitz, Jeffrey E

2014-01-01

BACKGROUND Intensive chemotherapy for pediatric acute myeloid leukemia (AML) incurs the risk of infectious complications, but the benefits of antibiotic prophylaxis remain unclear. METHODS In 103 children treated on the AML02 protocol between October 2002 and October 2008 at St. Jude Children’s Research Hospital, we retrospectively assessed the effect of antibiotic prophylaxis on the frequency of febrile neutropenia, clinically or microbiologically confirmed infections (including bacteremia), and antibiotic resistance, and on the results of nasal and rectal surveillance cultures. Initially, patients received no prophylaxis or oral cephalosporin (Group A). Then the protocol was amended to give intravenous cefepime alone or intravenous vancomycin plus either oral cephalosporin, oral ciprofloxacin, or intravenous cefepime (Group B). RESULTS There were 334 infectious episodes. Group A had a significantly greater frequency of documented infections and bacteremia (both P < .0001) (including gram-positive and gram-negative bacteremia, P = .0003 and .001, respectively) than Group B, especially viridans streptococcal bacteremia (P = .001). The incidence of febrile neutropenia without documented infection was not different between the two groups. Five cases of bacteremia with vancomycin-resistant enterococci (VRE) occurred in group B (vs. none in Group A), without related mortality. Two of these cases were preceded by positive VRE rectal surveillance cultures. CONCLUSIONS Outpatient intravenous antibiotic prophylaxis is feasible in children with AML and reduces the frequency of documented infection but not of febrile neutropenia. Despite emergence of VRE bacteremia, the benefits favor antibiotic prophylaxis. Creative approaches to shorten the duration of prophylaxis and thereby minimize resistance should be explored. PMID:24677028

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.

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.

Reduction of Clostridium Difficile and vancomycin-resistant Enterococcus contamination of environmental surfaces after an intervention to improve cleaning methods

PubMed Central

Eckstein, Brittany C; Adams, Daniel A; Eckstein, Elizabeth C; Rao, Agam; Sethi, Ajay K; Yadavalli, Gopala K; Donskey, Curtis J

2007-01-01

Background Contaminated environmental surfaces may play an important role in transmission of some healthcare-associated pathogens. In this study, we assessed the adequacy of cleaning practices in rooms of patients with Clostridium difficile-associated diarrhea (CDAD) and vancomycin-resistant Enterococcus (VRE) colonization or infection and examined whether an intervention would result in improved decontamination of surfaces. Methods During a 6-week period, we cultured commonly touched surfaces (i.e. bedrails, telephones, call buttons, door knobs, toilet seats, and bedside tables) in rooms of patients with CDAD and VRE colonization or infection before and after housekeeping cleaning, and again after disinfection with 10% bleach performed by the research staff. After the housekeeping staff received education and feedback, additional cultures were collected before and after housekeeping cleaning during a 10-week follow-up period. Results Of the 17 rooms of patients with VRE colonization or infection, 16 (94%) had one or more positive environmental cultures before cleaning versus 12 (71%) after housekeeping cleaning (p = 0.125), whereas none had positive cultures after bleach disinfection by the research staff (p < 0.001). Of the 9 rooms of patients with CDAD, 100% had positive cultures prior to cleaning versus 7 (78%) after housekeeping cleaning (p = 0.50), whereas only 1 (11%) had positive cultures after bleach disinfection by research staff (p = 0.031). After an educational intervention, rates of environmental contamination after housekeeping cleaning were significantly reduced. Conclusion Our findings provide additional evidence that simple educational interventions directed at housekeeping staff can result in improved decontamination of environmental surfaces. Such interventions should include efforts to monitor cleaning and disinfection practices and provide feedback to the housekeeping staff. PMID:17584935

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

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

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

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.

Mechanism of Honey Bacteriostatic Action Against MRSA and VRE Involves Hydroxyl Radicals Generated from Honey's Hydrogen Peroxide.

PubMed

Brudzynski, Katrina; Lannigan, Robert

2012-01-01

It has been recently reported that honey hydrogen peroxide in conjunction with unknown honey components produced cytotoxic effects resulting in bacterial growth inhibition and DNA degradation. The objective of this study was twofold: (a) to investigate whether the coupling chemistry involving hydrogen peroxide is responsible for a generation of hydroxyl radicals and (b) whether (•)OH generation affects growth of multi-drug resistant clinical isolates. The susceptibility of five different strains of methicillin-resistant Staphylococcus aureus (MRSA) and four strains of vancomycin-resistant Enterococcus faecium (VRE) isolates from infected wounds to several honeys was evaluated using broth microdilution assay. Isolates were identified to genus and species and their susceptibility to antibiotics was confirmed using an automated system (Vitek(®), Biomérieux(®)). The presence of the mec(A) gene, nuc gene and van(A) and (B) genes were confirmed by polymerase chain reaction. Results showed that no clinical isolate was resistant to selected active honeys. The median difference in honeys MICs against these strains ranged between 12.5 and 6.25% v/v and was not different from the MIC against standard Escherichia coli and Bacillus subtilis. Generation of (•)OH during bacteria incubation with honeys was analyzed using 3'-(p-aminophenyl) fluorescein (APF) as the (•)OH trap. The (•)OH participation in growth inhibition was monitored directly by including APF in broth microdilution assay. The growth of MRSA and VRE was inhibited by (•)OH generation in a dose-dependent manner. Exposure of MRSA and VRE to honeys supplemented with Cu(II) augmented production of (•)OH by 30-fold and increased honey bacteriostatic potency from MIC(90) 6.25 to MIC(90)< 0.78% v/v. Pretreatment of honeys with catalase prior to their supplementation with Cu ions fully restored bacterial growth indicating that hydroxyl radicals were produced from H(2)O(2) via the Fenton-type reaction. In

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

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

Mechanism of Honey Bacteriostatic Action Against MRSA and VRE Involves Hydroxyl Radicals Generated from Honey’s Hydrogen Peroxide

PubMed Central

Brudzynski, Katrina; Lannigan, Robert

2012-01-01

It has been recently reported that honey hydrogen peroxide in conjunction with unknown honey components produced cytotoxic effects resulting in bacterial growth inhibition and DNA degradation. The objective of this study was twofold: (a) to investigate whether the coupling chemistry involving hydrogen peroxide is responsible for a generation of hydroxyl radicals and (b) whether •OH generation affects growth of multi-drug resistant clinical isolates. The susceptibility of five different strains of methicillin-resistant Staphylococcus aureus (MRSA) and four strains of vancomycin-resistant Enterococcus faecium (VRE) isolates from infected wounds to several honeys was evaluated using broth microdilution assay. Isolates were identified to genus and species and their susceptibility to antibiotics was confirmed using an automated system (Vitek®, Biomérieux®). The presence of the mec(A) gene, nuc gene and van(A) and (B) genes were confirmed by polymerase chain reaction. Results showed that no clinical isolate was resistant to selected active honeys. The median difference in honeys MICs against these strains ranged between 12.5 and 6.25% v/v and was not different from the MIC against standard Escherichia coli and Bacillus subtilis. Generation of •OH during bacteria incubation with honeys was analyzed using 3′-(p-aminophenyl) fluorescein (APF) as the •OH trap. The •OH participation in growth inhibition was monitored directly by including APF in broth microdilution assay. The growth of MRSA and VRE was inhibited by •OH generation in a dose-dependent manner. Exposure of MRSA and VRE to honeys supplemented with Cu(II) augmented production of •OH by 30-fold and increased honey bacteriostatic potency from MIC90 6.25 to MIC90< 0.78% v/v. Pretreatment of honeys with catalase prior to their supplementation with Cu ions fully restored bacterial growth indicating that hydroxyl radicals were produced from H2O2 via the Fenton-type reaction. In conclusion, we have

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.

Cleaning the grey zones of hospitals: A prospective, crossover, interventional study.

PubMed

Semret, Makeda; Dyachenko, Alina; Ramman-Haddad, Leila; Belzile, Eric; McCusker, Jane

2016-12-01

Environmental cleaning is a fundamental principle of infection prevention in hospitals, but its role in reducing transmission of health care-acquired pathogens has been difficult to prove experimentally. In this study we analyze the influence of cleaning previously uncleaned patient care items, grey zones (GZ), on health care-acquired transmission rates. The intervention consisted of specific GZ cleaning by an extra cleaner (in addition to routine cleaning) on 2 structurally different acute care medical wards for a period of 6 months each, in a crossover design. Data on health care-acquired transmissions of vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus, and Clostridium difficile were collected during both periods. Adjusted incidence rate ratios (IRRs) using Poisson regression were calculated to compare transmission of pathogens between both periods on both wards. During the intervention VRE transmission was significantly decreased (2-fold) on the ward where patients had fewer roommates; cleaning of GZ did not have any effect on the ward with multiple-occupancy rooms. There was no impact on methicillin-resistant S aureus transmission and only a nonsignificant decrease in transmission of C difficile. Our data provide evidence that targeted cleaning interventions can reduce VRE transmission when rooming conditions are optimized; such interventions can be cost-effective when the burden of VRE is significant. Enhanced cleaning interventions are less beneficial in the context of room sharing where many other factors contribute to transmission of pathogens. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

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...

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

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 ...

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.

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.

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

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

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.

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.

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.

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...

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

[Effect of tigecycline on selected multiresistant bacteria].

PubMed

Kolár, Milan; Hanulík, Vojtech; Chromá, Magdalena

2009-02-01

Currently, one of the most serious problems in medicine is the increasing resistance of pathogenic bacteria to antimicrobial drugs. Bacterial resistance may potentially be solved in particular by decreasing the consumption of antibiotics and increasing the quality of their use. Equally important, however, is the development of new antimicrobial drugs and their use in clinical practice. One of the new antibiotic agents is tigecycline of the glycylcycline group. The presented work aimed at assessing its in vitro effect on selected multiresistant bacteria. Clinical samples were collected from patients hospitalized in the University Hospital Olomouc to isolate ESBL- and AmpC beta-lactamase-producing enterobacteria, methicillin-resistant Staphylococcus aureus (MRSA) strains and vancomycin-resistant enterococci (VRE). In the isolates, susceptibility to tigecycline was determined by the standard microdilution method. A total of 350 isolates were tested (100 MRSA, 10 0 VRE, 100 ESBL-positive and 50 AmpC-positive enterobacteria). In the cases of VRE and MRSA, no resistance to tigecycline was detected and the minimum inhibitory concentrations (MIC) did not exceed 0.25 mg/l and 0.5 mg/l, respectively. In ESBL-positive enterobacteria, 97% susceptibility (MIC range = or <0.06 to 4 mg/l) was detected; in AmpC-positive enterobacteria, the MIC range was = or <0.03-2 mg/l and susceptibility reached 98 %. Tigecycline may be considered a suitable alternative in the treatment of infections caused by the above-mentioned multiresistant strains.

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.

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.

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.

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.

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.

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

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.

Effectiveness of cleaning-disinfection wipes and sprays against multidrug-resistant outbreak strains.

PubMed

Kenters, Nikki; Huijskens, Elisabeth G W; de Wit, Sophie C J; van Rosmalen, Joost; Voss, Andreas

2017-08-01

Hospital rooms play an important role in the transmission of several health care-associated pathogens. During the last few years, a number of innovative cleaning-disinfecting products have been brought to market. In this study, commercially available products combining cleaning and disinfection were compared, using 2 different application methods. The aim was to determine which product was most effective in simultaneous cleaning and disinfection of surfaces. Seven cleaning-disinfecting wipes and sprays based on different active ingredients were tested for their efficacy in removal of microbial burden and proteins. Efficacy was tested with known Dutch outbreak strains: vancomycin-resistant enterococci (VRE), Klebsiella pneumoniae OXA-48, or Acinetobacter baumannii. For all bacteria, ready-to-use cleaning-disinfecting products reduced the microbial count with a log 10 reduction >5 with a 5-minute exposure time, with the exception of a spray based on hydrogen peroxide. Omitting the aforementioned hydrogen peroxide spray, there were no significant differences between use of a wipe or spray in bacterial load reduction. Using adenosine triphosphate (ATP) measurements, a significant difference in log 10 relative light units (RLU) reduction between various bacteria (P ≤ .001) was observed. In general, a >5 log 10 reduction of colony forming units (CFU) for tested wipes and sprays was obtained for all tested bacteria strains, with exception of hydrogen peroxide spray and VRE. Although ATP may show a difference between pre- and postcleaning, RLU reduction does not correlate with actual CFU reductions. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Susceptibility rates in Latin American nations: report from a regional resistance surveillance program (2011).

PubMed

Jones, Ronald N; Guzman-Blanco, Manuel; Gales, Ana C; Gallegos, Belisario; Castro, Aura Lucia Leal; Martino, Marines Dalla Valle; Vega, Silvio; Zurita, Jeannete; Cepparulo, Mario; Castanheira, Mariana

2013-01-01

To establish a resistance (R) surveillance program monitoring antimicrobial susceptibility patterns in Latin America (LATAM; Argentina [ARG], Brazil [BRA], Chile, Colombia [CBA], Costa Rica, Ecuador [ECU], Guatemala [GUA], Mexico [MEX], Panama [PAN], Peru, and Venezuela [VEN]). In 2011, 4979 organisms were collected from 11 nations (20 laboratories) for susceptibility testing in a central laboratory design. Antimicrobials were tested by CLSI methods and results interpreted by CLSI and EUCAST breakpoints. Most common Gram-positive (Staphylococcus aureus [SA, 921], other staphylococci [CoNS; 299], enterococci [218], Streptococcus pneumoniae [SPN; 182], β-haemolytic streptococci [115]) and Gram-negative (E. coli [EC; 644], Klebsiella spp. [KSP; 517], Enterobacters [272], Pseudomonas aeruginosa [PSA; 586], Acinetobacters [ACB; 494]) pathogens were analyzed against linezolid (LZD), vancomycin (VAN), tigecycline (TIG), colistin (COL), cefoperazone/sulbactam (C/S), and amikacin (AMK). MRSA rates varied from 29% (CBA, BRA) to 79% (Peru); but LZD (MIC90, 2mg/L), TIG (MIC90, 0.12mg/L) and VAN (MIC90, 1mg/L) covered all strains. Enterococci showed a 14% VRE rate, highest in BRA and MEX; all inhibited by TIG and daptomycin, but not LZD (three non-susceptible with G2576T mutations or cfr). Penicillin-R among SPN and viridans streptococci was 51.6 and 41.1%, respectively. LZD overall R against Gram-positives was 0.3%. High ESBL rates were observed in EC (54-71%) and KSP (≥50%) from GUA, MEX and Peru, and six nations, respectively. Carbapenem-R in KSP was 9%, highest rates associated with KPC in BRA, CBA, ECU, PAN and VEN; also a NDM-1 in KSP from CBA. AMK, TIG, C/S and carbapenems were the broadest-spectrum agents tested against Enterobacteriaceae. Only COL inhibited >90% of PSA; COL and TIG (≤2mg/L) covered ≥85% of ACB. LATAM nations demonstrated variable levels of antimicrobial R especially among Enterobacteriaceae (β-lactamase-mediated), PSA and ACB. MRSA (48%), VRE

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).

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.

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

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.

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

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.

Hand-hygiene compliance does not predict rates of resistant infections in critically ill surgical patients.

PubMed

Jayaraman, Sudha P; Klompas, Michael; Bascom, Molli; Liu, Xiaoxia; Piszcz, Regina; Rogers, Selwyn O; Askari, Reza

2014-10-01

Our institution had a major outbreak of multi-drug-resistant Acinetobacter (MDRA) in its general surgical and trauma intensive care units (ICUs) in 2011, requiring implementation of an aggressive infection-control response. We hypothesized that poor hand-hygiene compliance (HHC) may have contributed to the outbreak of MDRA. A response to the outbreak including aggressive environmental cleaning, cohorting, and increased hand hygiene compliance monitoring may have led to an increase in HHC after the outbreak and to a consequent decrease in the rates of infection by the nosocomial pathogens methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and Clostridium difficile. Hand-hygiene compliance, tracked in monthly audits by trained and anonymous observers, was abstracted from an infection control database. The incidences of nosocomial MRSA, VRE, and C. difficile were calculated from a separate prospectively collected data base for 6 mo before and 12 mo after the 2011 outbreak of MDRA in the institution's general surgical and trauma ICUs, and data collected prospectively from two unaffected ICUs (the thoracic surgical ICU and medical intensive care unit [MICU]). We created a composite endpoint of "any resistant pathogen," defined as MRSA, VRE, or C. difficile, and compared incidence rates over time, using the Wilcoxon signed rank test and Pearson product-moment correlation coefficient to measure the correlations among these rates. Rates of HHC before and after the outbreak of MDRA were consistently high in both the general surgical (median rates: 100% before and 97.6% after the outbreak, p=0.93) and trauma ICUs (median rates: 90% before and 96.75% after the outbreak, p=0.14). In none of the ICUs included in the study did the rates of HHC increase in response to the outbreak of MDRA. The incidence of "any resistant pathogen" decreased in the general surgical ICU after the outbreak (from 6.7/1,000 patient-days before the outbreak to 2

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.

Epidemiology of multidrug resistant bacterial organisms and Clostridium difficile in German hospitals in 2014: Results from a nationwide one-day point prevalence of 329 German hospitals.

PubMed

Huebner, Nils-Olaf; Dittmann, Kathleen; Henck, Vivien; Wegner, Christian; Kramer, Axel

2016-09-02

One important aspect in combatting resistance to antibiotics is to increase the awareness and knowledge by epidemiological studies. We therefore conducted a German-wide point-prevalence survey for multidrug resistant bacterial organisms (MDROs) and Clostridium difficile (CD) to assess the epidemiology and structure quality of infection control in German hospitals. 1550 hospitals were asked to participate and to report surveillance data on the prevalence of Methicillin-resistant and Vancomycin resistant Staphylococcus aureus (MRSA, VRSA/GRSA), Vancomycin resistant Enterococcus faecalis/faecium (VRE), multiresistant strains of Escherichia coli (EC), Klebsiella spp. (KS), Enterobacter spp. (ES), Acinetobacter spp. (AB) and Pseudomonas spp. (PS). as well as CD infections. Surveys from 73,983 patients from 329 hospitals were eligible for analysis. MRSA was the most often reported pathogen (prevalence: 1.64 % [CI95: 1.46-1.82]), followed by 3 multidrug resistant EC (3MRGN-EC) (0.75 % [CI95: 0.60-0.89]), CD (0.74 % [CI95: 0.60-0.88]), VRE (0.25 % [CI95: 0.13-0.37]) und 3MRGN-KS (0.22 % [CI95: [0.15-0.29]). The majority of hospitals met the German recommendations for staffing with infection control personnel. The continuing increase in participating hospitals in this third survey in a row indicates a growing awareness to MDROs and our pragmatic approach. Our results confirm that MRSA, 3MRGN-EC, VRE and 3MRGN-KS remain the most prevalent MDROs in German hospitals.

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.

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.

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

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.

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.

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

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.

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

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.

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.

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

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

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

First UK trial of Xenex PX-UV, an automated ultraviolet room decontamination device in a clinical haematology and bone marrow transplantation unit.

PubMed

Beal, A; Mahida, N; Staniforth, K; Vaughan, N; Clarke, M; Boswell, T

2016-06-01

There is growing interest in the use of no-touch automated room decontamination devices within healthcare settings. Xenex PX-UV is an automated room disinfection device using pulsed ultraviolet (UV) C radiation with a short cycle time. To investigate the microbiological efficacy of this device when deployed for terminal decontamination of isolation rooms within a clinical haematology unit. The device was deployed in isolation rooms in a clinical haematology unit. Contact plates were applied to common touch points to determine aerobic total colony counts (TCCs) and samples collected using Polywipe™ sponges for detection of vancomycin-resistant enterococci (VRE). The device was easy to transport, easy to use, and it disinfected rooms rapidly. There was a 76% reduction in the TCCs following manual cleaning, with an additional 14% reduction following UV disinfection, resulting in an overall reduction of 90% in TCCs. There was a 38% reduction in the number of sites where VRE was detected, from 26 of 80 sites following manual cleaning to 16 of 80 sites with additional UV disinfection. The Xenex PX-UV device can offer a simple and rapid additional decontamination step for terminal disinfection of patient rooms. However, the microbiological efficacy against VRE was somewhat limited. Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

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.

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

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

Rectal swab screening assays of public health importance in molecular diagnostics: Sample adequacy control.

PubMed

Glisovic, Sanja; Eintracht, Shaun; Longtin, Yves; Oughton, Matthew; Brukner, Ivan

Rectal swabs are routinely used by public health authorities to screen for multi-drug resistant enteric bacteria including vancomycin-resistant enterococci (VRE) and carbapenem-resistant enterobacteriaceae (CRE). Screening sensitivity can be influenced by the quality of the swabbing, whether performed by the patient (self-swabbing) or a healthcare practitioner. One common exclusion criterion for rectal swabs is absence of "visible soiling" from fecal matter. In our institution, this criterion excludes almost 10% of rectal swabs received in the microbiology laboratory. Furthermore, over 30% of patients in whom rectal swabs are cancelled will not be re-screened within the next 48h, resulting in delays in removing infection prevention measures. We describe two quantitative polymerase chain reaction (qPCR)-based assays, human RNAse P and eubacterial 16S rDNA, which might serve as suitable controls for sampling adequacy. However, lower amounts of amplifiable human DNA make the 16s rDNA assay a better candidate for sample adequacy control. Copyright © 2017. Published by Elsevier Ltd.

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.

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.

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.

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.

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).

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.

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

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.

Intestinal microbiome disruption in patients in a long-term acute care hospital: A case for development of microbiome disruption indices to improve infection prevention.

PubMed

Halpin, Alison Laufer; de Man, Tom J B; Kraft, Colleen S; Perry, K Allison; Chan, Austin W; Lieu, Sung; Mikell, Jeffrey; Limbago, Brandi M; McDonald, L Clifford

2016-07-01

Composition and diversity of intestinal microbial communities (microbiota) are generally accepted as a risk factor for poor outcomes; however, we cannot yet use this information to prevent adverse outcomes. Stool was collected from 8 long-term acute care hospital patients experiencing diarrhea and 2 fecal microbiota transplant donors; 16S rDNA V1-V2 hypervariable regions were sequenced. Composition and diversity of each sample were described. Stool was also tested for Clostridium difficile, vancomycin-resistant enterococci (VRE), and carbapenem-resistant Enterobacteriaceae. Associations between microbiota diversity and demographic and clinical characteristics, including antibiotic use, were analyzed. Antibiotic exposure and Charlson Comorbidity Index were inversely correlated with diversity (Spearman = -0.7). Two patients were positive for VRE; both had microbiomes dominated by Enterococcus faecium, accounting for 67%-84% of their microbiome. Antibiotic exposure correlated with diversity; however, other environmental and host factors not easily obtainable in a clinical setting are also known to impact the microbiota. Therefore, direct measurement of microbiome disruption by sequencing, rather than reliance on surrogate markers, might be most predictive of adverse outcomes. If and when microbiome characterization becomes a standard diagnostic test, improving our understanding of microbiome dynamics will allow for interpretation of results to improve patient outcomes. Published by Elsevier Inc.

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.

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

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.

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.

In Vitro Assessment of the Antimicrobial Efficacy of Optimized Nitroglycerin-Citrate-Ethanol as a Nonantibiotic, Antimicrobial Catheter Lock Solution for Prevention of Central Line-Associated Bloodstream Infections

PubMed Central

Reitzel, Ruth A.; Hirsh-Ginsberg, Cheryl; Murray, Kimberly; Chaftari, Anne-Marie; Hachem, Ray; Raad, Issam

2016-01-01

The rapid, broad-spectrum, biofilm-eradicating activity of the combination of 0.01% nitroglycerin, 7% citrate, and 20% ethanol and its potential as a nonantibiotic, antimicrobial catheter lock solution (ACLS) were previously reported. Here, a nitroglycerin-citrate-ethanol (NiCE) ACLS optimized for clinical assessment was developed by reducing the nitroglycerin and citrate concentrations and increasing the ethanol concentration. Biofilm-eradicating activity was sustained when the ethanol concentration was increased from 20 to 22% which fully compensated for reducing the citrate concentration from 7% to 4% as well as the nitroglycerin concentration from 0.01% to 0.0015% or 0.003%. The optimized formulations demonstrated complete and rapid (2 h) eradication of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate Staphylococcus aureus (VISA), methicillin-resistant Staphylococcus epidermidis (MRSE), vancomycin-resistant enterococci (VRE), multidrug-resistant (MDR) Pseudomonas aeruginosa, MDR Klebsiella pneumoniae, MDR Enterobacter cloacae, MDR Acinetobacter baumannii, MDR Escherichia coli, MDR Stenotrophomonas maltophilia, Candida albicans, and Candida glabrata biofilms. The optimized NiCE lock solutions demonstrated anticoagulant activities comparable to those of heparin lock solutions. NiCE lock solution was significantly more effective than taurolidine-citrate-heparin lock solution in eradicating biofilms of Staphylococcus aureus and Candida glabrata. The optimized, nonantibiotic, heparin-free NiCE lock solution demonstrates rapid broad-spectrum biofilm eradication as well as effective anticoagulant activity, making NiCE a high-quality ACLS candidate for clinical assessment. PMID:27297475

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.

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.

Prevalence of Multidrug-Resistant Organisms in Hospitalized Pediatric Refugees in an University Children's Hospital in Germany 2015-2016.

PubMed

Tenenbaum, Tobias; Becker, Klaus-Peter; Lange, Bettina; Martin, Anka; Schäfer, Peter; Weichert, Stefan; Schroten, Horst

2016-11-01

OBJECTIVE To determine the prevalence of multidrug-resistant organisms (MDROs) colonizing in pediatric refugees admitted to a University Children Hospital in Germany. DESIGN Retrospective observational study. SETTING General pediatric and pediatric surgery units. PATIENTS In Germany, recommendations for MDRO screening of pediatric refugees were recently published. According to these and institutional recommendations, all hospitalized pediatric refugees were screened for MDROs between October 2015 and March 2016. METHODS Using electronic surveillance data, we performed a chart review to identify the prevalence of MDROs among and the clinical diagnoses of pediatric refugees. RESULTS Among 325 patients hospitalized for various causes, most frequently gastroenteritis (30.9%), MDROs were detected in 33.8%. Most of these patients were colonized with multidrug-resistant Gram-negative (MRGN) bacteria (113 isolates), mostly 2MRGN/ESBL (87 isolates); some patients were colonized with methicillin-resistant Staphylococcus aureus (MRSA, 22 isolates); and 1 patient was colonized with vancomycin-resistant enterococci (VRE). Among 110 refugee patients, we detected single colonization with an MDRO in 84 patients (76.4%), co-colonization with 2 pathogens in 23 patients (20.9%), and triple colonization in 3 patients (2.7%). However, infections with MDROs occurred in only 3.6% of pediatric refugees. The peak of positive MDRO screening results in 2015 correlated with an increased hospitalization rate. CONCLUSION Implementation of infection control measures among pediatric refugees is challenging. Due to the high frequency of MDROs in these patients, current screening, isolation, and treatment strategies may have to be adapted. Infect Control Hosp Epidemiol 2016;1-5.

Probing the role of the vancomycin e-ring aryl chloride: selective divergent synthesis and evaluation of alternatively substituted E-ring analogues.

PubMed

Pinchman, Joseph R; Boger, Dale L

2013-05-23

The selective functionalization of vancomycin aglycon derivatives through conversion of the E-ring aryl chloride to a reactive boronic acid and its use in the synthesis of a systematic series of vancomycin E-ring analogues are described. The series was used to examine the E-ring chloride impact in binding d-Ala-d-Ala and on antimicrobial activity. In contrast to the reduced activity of the unsubstituted E-ring derivatives, hydrophobic and relatively nonpolar substituents approach or match the chloro-substituted vancomycin and were insensitive to the electronic character of the substituent (e.g., Cl vs CN/OMe), whereas highly polar substituents fail to provide the enhancements. Moreover, the active permethylated vancomycin aglycon derivatives exhibit VanB VRE antimicrobial activity at levels that approach (typically within 2-fold) their activity against sensitive bacteria. The robust borylation reaction also enabled the functionalization of a minimally protected vancomycin aglycon (N-Boc-vancomycin aglycon) and provides a direct method for the preparation of previously inaccessible analogues.

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

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

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...

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.

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

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 ...

A polyclonal outbreak of bloodstream infections by Enterococcus faecium in patients with hematologic malignancies.

PubMed

Alatorre-Fernández, Pamela; Mayoral-Terán, Claudia; Velázquez-Acosta, Consuelo; Franco-Rodríguez, Cecilia; Flores-Moreno, Karen; Cevallos, Miguel Ángel; López-Vidal, Yolanda; Volkow-Fernández, Patricia

2017-03-01

Enterococcus faecium causes bloodstream infection (BSI) in patients with hematologic malignancies (HMs). We studied the clinical features and outcomes of patients with HM with vancomycin-sensitive E faecium (VSE) and vancomycin-resistant E faecium (VRE) BSI and determined the genetic relatedness of isolates and circumstances associated with the upsurge of E faecium BSI. Case-control study of patients with HM and E faecium-positive blood culture from January 2008-December 2012; cases were patients with VRE and controls were VSE isolates. The strains were tested for Van genes by polymerase chain reaction amplification and we performed pulsed-field gel electrophoresis to determine genetic relatedness. Fifty-eight episodes of E faecium BSI occurred: 35 sensitive and 23 resistant to vancomycin. Mortality was 46% and 57%, attributable 17% and 40%, respectively. Early stage HM was associated with VSE (P = .044), whereas an episode of BSI within the 3 months before the event (P = .039), prophylactic antibiotics (P = .013), and vancomycin therapy during the previous 3 months (P = .001) was associated with VRE. The VanA gene was identified in 97% of isolates studied. E faecium isolates were not clonal. E faecium BSI was associated with high mortality. This outbreak of VRE was not clonal; it was associated with antibiotic-use pressure and highly myelosuppressive chemotherapy. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

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

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

Novel anti-infective compounds from marine bacteria.

PubMed

Rahman, Hafizur; Austin, Brian; Mitchell, Wilfrid J; Morris, Peter C; Jamieson, Derek J; Adams, David R; Spragg, Andrew Mearns; Schweizer, Michael

2010-03-05

As a result of the continuous evolution of microbial pathogens towards antibiotic-resistance, there have been demands for the development of new and effective antimicrobial compounds. Since the 1960s, the scientific literature has accumulated many publications about novel pharmaceutical compounds produced by a diverse range of marine bacteria. Indeed, marine micro-organisms continue to be a productive and successful focus for natural products research, with many newly isolated compounds possessing potentially valuable pharmacological activities. In this regard, the marine environment will undoubtedly prove to be an increasingly important source of novel antimicrobial metabolites, and selective or targeted approaches are already enabling the recovery of a significant number of antibiotic-producing micro-organisms. The aim of this review is to consider advances made in the discovery of new secondary metabolites derived from marine bacteria, and in particular those effective against the so called "superbugs", including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin resistant enterococci (VRE), which are largely responsible for the increase in numbers of hospital acquired, i.e., nosocomial, infections.

The prevention and management of infections due to multidrug resistant organisms in haematology patients

PubMed Central

Trubiano, Jason A; Worth, Leon J; Thursky, Karin A; Slavin, Monica A

2015-01-01

Infections due to resistant and multidrug resistant (MDR) organisms in haematology patients and haematopoietic stem cell transplant recipients are an increasingly complex problem of global concern. We outline the burden of illness and epidemiology of resistant organisms such as gram-negative pathogens, vancomycin-resistant Enterococcus faecium (VRE), and Clostridium difficile in haematology cohorts. Intervention strategies aimed at reducing the impact of these organisms are reviewed: infection prevention programmes, screening and fluoroquinolone prophylaxis. The role of newer therapies (e.g. linezolid, daptomycin and tigecycline) for treatment of resistant and MDR organisms in haematology populations is evaluated, in addition to the mobilization of older agents (e.g. colistin, pristinamycin and fosfomycin) and the potential benefit of combination regimens. PMID:24341410

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

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.

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.

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

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

Cold air plasma to decontaminate inanimate surfaces of the hospital environment.

PubMed

Cahill, Orla J; Claro, Tânia; O'Connor, Niall; Cafolla, Anthony A; Stevens, Niall T; Daniels, Stephen; Humphreys, Hilary

2014-03-01

The hospital environment harbors bacteria that may cause health care-associated infections. Microorganisms, such as multiresistant bacteria, can spread around the patient's inanimate environment. Some recently introduced biodecontamination approaches in hospitals have significant limitations due to the toxic nature of the gases and the length of time required for aeration. This study evaluated the in vitro use of cold air plasma as an efficient alternative to traditional methods of biodecontamination of hospital surfaces. Cultures of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli, and Acinetobacter baumannii were applied to different materials similar to those found in the hospital environment. Artificially contaminated sections of marmoleum, mattress, polypropylene, powder-coated mild steel, and stainless steel were then exposed to a cold air pressure plasma single jet for 30 s, 60 s, and 90 s, operating at approximately 25 W and 12 liters/min flow rate. Direct plasma exposure successfully reduced the bacterial load by log 3 for MRSA, log 2.7 for VRE, log 2 for ESBL-producing E. coli, and log 1.7 for A. baumannii. The present report confirms the efficient antibacterial activity of a cold air plasma single-jet plume on nosocomial bacterially contaminated surfaces over a short period of time and highlights its potential for routine biodecontamination in the clinical environment.

Quantitative proteomic view associated with resistance to clinically important antibiotics in Gram-positive bacteria: a systematic review

PubMed Central

Lee, Chang-Ro; Lee, Jung Hun; Park, Kwang Seung; Jeong, Byeong Chul; Lee, Sang Hee

2015-01-01

The increase of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) poses a worldwide and serious health threat. Although new antibiotics, such as daptomycin and linezolid, have been developed for the treatment of infections of Gram-positive pathogens, the emergence of daptomycin-resistant and linezolid-resistant strains during therapy has now increased clinical treatment failures. In the past few years, studies using quantitative proteomic methods have provided a considerable progress in understanding antibiotic resistance mechanisms. In this review, to understand the resistance mechanisms to four clinically important antibiotics (methicillin, vancomycin, linezolid, and daptomycin) used in the treatment of Gram-positive pathogens, we summarize recent advances in studies on resistance mechanisms using quantitative proteomic methods, and also examine proteins playing an important role in the bacterial mechanisms of resistance to the four antibiotics. Proteomic researches can identify proteins whose expression levels are changed in the resistance mechanism to only one antibiotic, such as LiaH in daptomycin resistance and PrsA in vancomycin resistance, and many proteins simultaneously involved in resistance mechanisms to various antibiotics. Most of resistance-related proteins, which are simultaneously associated with resistance mechanisms to several antibiotics, play important roles in regulating bacterial envelope biogenesis, or compensating for the fitness cost of antibiotic resistance. Therefore, proteomic data confirm that antibiotic resistance requires the fitness cost and the bacterial envelope is an important factor in antibiotic resistance. PMID:26322035

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.

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.

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.

Antimicrobial Resistance Surveillance among Intensive Care Units of a Tertiary Care Hospital in Southern India

PubMed Central

Moolchandani, Kailash; Deepashree, R; Sistla, Sujatha; Harish, BN; Mandal, Jharna

2017-01-01

Introduction Hospital Acquired Infections (HAIs) are the rising threat in the health care facilities across the globe. As most Intesive Care Unit (ICU) patients are frequently on broad spectrum antimicrobials, this induces selective antibiotic pressure which leads to development of Antimicrobial Resistance (AMR) among the microorganisms of ICUs. Aim To study the occurrence of different types of HAIs in patients admitted to various ICUs of JIPMER and the AMR pattern of the bacterial pathogens isolated from them. Materials and Methods The record based retrospective data of culture reports of the patients admitted to all the ICUs of JIPMER during the period from April 2015 to March 2016 were collected. A total of 3,090 isolates were obtained from the clinical specimens of 1,244 patients. Data on various factors like demographic characters, type of ICU, infecting organism, site of infection, type of HAI’s and AMR including co-resistance were collected and analysed using Microsoft Excel. Results Most common culture positive clinical specimen received was tracheal aspirate (29.9%) followed by exudate (22.7%). Acinetobacter spp from tracheal aspirate and Pseudomonas spp from blood specimens were the most common organisms isolated; whereas Escherichia coli was the predominant organism found in urine, exudate and sterile fluid specimens. About 22.2% infections were HAIs, out of which pneumonia (6.24%) was the most common. Analysis of antimicrobial susceptibility pattern revealed that most of Gram-Negative Bacilli (GNB) was Multi Drug Resistant (MDR) i.e., resistant to three or more class of antibiotics such as cephalosporins, carbapenems, aminoglycosides, tetracyclines and fluoroquinolones. The prevalence of Methicillin- resistant Staphylococcus aureus (MRSA) and Vancomycin- resistant Enterococci (VRE) were found to be 40.6% and 11.9% respectively. Conclusion The increasing trend AMR among the hospital acquired pathogens such as MDR-GNBs, MRSA and VRE pose a great threat

In Vitro Assessment of the Antimicrobial Efficacy of Optimized Nitroglycerin-Citrate-Ethanol as a Nonantibiotic, Antimicrobial Catheter Lock Solution for Prevention of Central Line-Associated Bloodstream Infections.

PubMed

Reitzel, Ruth A; Rosenblatt, Joel; Hirsh-Ginsberg, Cheryl; Murray, Kimberly; Chaftari, Anne-Marie; Hachem, Ray; Raad, Issam

2016-09-01

The rapid, broad-spectrum, biofilm-eradicating activity of the combination of 0.01% nitroglycerin, 7% citrate, and 20% ethanol and its potential as a nonantibiotic, antimicrobial catheter lock solution (ACLS) were previously reported. Here, a nitroglycerin-citrate-ethanol (NiCE) ACLS optimized for clinical assessment was developed by reducing the nitroglycerin and citrate concentrations and increasing the ethanol concentration. Biofilm-eradicating activity was sustained when the ethanol concentration was increased from 20 to 22% which fully compensated for reducing the citrate concentration from 7% to 4% as well as the nitroglycerin concentration from 0.01% to 0.0015% or 0.003%. The optimized formulations demonstrated complete and rapid (2 h) eradication of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate Staphylococcus aureus (VISA), methicillin-resistant Staphylococcus epidermidis (MRSE), vancomycin-resistant enterococci (VRE), multidrug-resistant (MDR) Pseudomonas aeruginosa, MDR Klebsiella pneumoniae, MDR Enterobacter cloacae, MDR Acinetobacter baumannii, MDR Escherichia coli, MDR Stenotrophomonas maltophilia, Candida albicans, and Candida glabrata biofilms. The optimized NiCE lock solutions demonstrated anticoagulant activities comparable to those of heparin lock solutions. NiCE lock solution was significantly more effective than taurolidine-citrate-heparin lock solution in eradicating biofilms of Staphylococcus aureus and Candida glabrata The optimized, nonantibiotic, heparin-free NiCE lock solution demonstrates rapid broad-spectrum biofilm eradication as well as effective anticoagulant activity, making NiCE a high-quality ACLS candidate for clinical assessment. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

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

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.

A treatment plant receiving waste water from multiple bulk drug manufacturers is a reservoir for highly multi-drug resistant integron-bearing bacteria.

PubMed

Marathe, Nachiket P; Regina, Viduthalai R; Walujkar, Sandeep A; Charan, Shakti Singh; Moore, Edward R B; Larsson, D G Joakim; Shouche, Yogesh S

2013-01-01

The arenas and detailed mechanisms for transfer of antibiotic resistance genes between environmental bacteria and pathogens are largely unclear. Selection pressures from antibiotics in situations where environmental bacteria and human pathogens meet are expected to increase the risks for such gene transfer events. We hypothesize that waste-water treatment plants (WWTPs) serving antibiotic manufacturing industries may provide such spawning grounds, given the high bacterial densities present there together with exceptionally strong and persistent selection pressures from the antibiotic-contaminated waste. Previous analyses of effluent from an Indian industrial WWTP that processes waste from bulk drug production revealed the presence of a range of drugs, including broad spectrum antibiotics at extremely high concentrations (mg/L range). In this study, we have characterized the antibiotic resistance profiles of 93 bacterial strains sampled at different stages of the treatment process from the WWTP against 39 antibiotics belonging to 12 different classes. A large majority (86%) of the strains were resistant to 20 or more antibiotics. Although there were no classically-recognized human pathogens among the 93 isolated strains, opportunistic pathogens such as Ochrobactrum intermedium, Providencia rettgeri, vancomycin resistant Enterococci (VRE), Aerococcus sp. and Citrobacter freundii were found to be highly resistant. One of the O. intermedium strains (ER1) was resistant to 36 antibiotics, while P. rettgeri (OSR3) was resistant to 35 antibiotics. Class 1 and 2 integrons were detected in 74/93 (80%) strains each, and 88/93 (95%) strains harbored at least one type of integron. The qPCR analysis of community DNA also showed an unprecedented high prevalence of integrons, suggesting that the bacteria living under such high selective pressure have an appreciable potential for genetic exchange of resistance genes via mobile gene cassettes. The present study provides insight into

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.

Chlorhexidine bathing for the prevention of colonization and infection with multidrug-resistant microorganisms in a hematopoietic stem cell transplantation unit over a 9-year period

PubMed Central

Mendes, Elisa Teixeira; Ranzani, Otavio T.; Marchi, Ana Paula; da Silva, Mariama Tomaz; Filho, José Ulysses Amigo; Alves, Tânia; Guimarães, Thais; Levin, Anna S.; Costa, Silvia Figueiredo

2016-01-01

Abstract Health care associated infections (HAIs) are currently among the major challenges to the care of hematopoietic stem cell transplantation (HSCT) patients. The objective of the present study was to evaluate the impact of 2% chlorhexidine (CHG) bathing on the incidence of colonization and infection with vancomycin-resistant Enterococcus (VRE), multidrug-resistant (MDR) gram-negative pathogens, and to evaluate their CHG minimum inhibitory concentration (MIC) after the intervention. A quasi-experimental study with duration of 9 years was conducted. VRE colonization and infection, HAI rates, and MDR gram-negative infection were evaluated by interrupted time series analysis. The antibacterial susceptibility profile and mechanism of resistance to CHG were analyzed in both periods by the agar dilution method in the presence or absence of the efflux pump inhibitor carbonyl cyanide-m-chlorophenyl hydrazone (CCCP) and presence of efflux pumps (qacA/E, qacA, qacE, cepA, AdeA, AdeB, and AdeC) by polymerase chain reaction (PCR). The VRE colonization and infection rates were significantly reduced in the postintervention period (P = 0.001). However, gram-negative MDR rates in the unit increased in the last years of the study. The CHG MICs for VRE increased during the period of exposure to the antiseptic. A higher MIC at baseline period was observed in MDR gram-negative strains. The emergence of a monoclonal Pseudomonas aeruginosa clone was observed in the second period. Concluding, CHG bathing was efficient regarding VRE colonization and infection, whereas no similar results were found with MDR gram-negative bacteria. PMID:27861350

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

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

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.

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.

Assessment of Environmental Contamination with Pathogenic Bacteria at a Hospital Laundry Facility.

PubMed

Michael, Karen E; No, David; Daniell, William E; Seixas, Noah S; Roberts, Marilyn C

2017-11-10

Little is known about exposure to pathogenic bacteria among industrial laundry workers who work with soiled clinical linen. To study worker exposures, an assessment of surface contamination was performed at an industrial laundry facility serving hospitals in Seattle, WA, USA. Surface swab samples (n = 240) from the environment were collected during four site visits at 3-month intervals. These samples were cultured for Clostridium difficile, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE). Voluntary participation of 23 employees consisted of nasal swabs for detection of MRSA, observations during work, and questionnaires. Contamination with all three pathogens was observed in both dirty (laundry handling prior to washing) and clean areas (subsequent to washing). The dirty area had higher odds of overall contamination (≥1 pathogen) than the clean area (odds ratio, OR = 18.0, 95% confidence interval 8.9-36.5, P < 0.001). The odds of contamination were high for each individual pathogen: C. difficile, OR = 15.5; MRSA, OR = 14.8; and VRE, OR = 12.6 (each, P < 0.001). The highest odds of finding surface contamination occurred in the primary and secondary sort areas where soiled linens were manually sorted by employees (OR = 63.0, P < 0.001). The study substantiates that the laundry facility environment can become contaminated by soiled linens. Workers who handle soiled linen may have a higher risk of exposure to C. difficile, MRSA, and VRE than those who handle clean linens. Improved protocols for prevention and reduction of environmental contamination were implemented because of this study. © The Author 2017. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

MRJP1-containing glycoproteins isolated from honey, a novel antibacterial drug candidate with broad spectrum activity against multi-drug resistant clinical isolates

PubMed Central

Brudzynski, Katrina; Sjaarda, Calvin; Lannigan, Robert

2015-01-01

The emergence of extended- spectrum β-lactamase (ESBL) is the underlying cause of growing antibiotic resistance among Gram-negative bacteria to β-lactam antibiotics. We recently reported the discovery of honey glycoproteins (glps) that exhibited a rapid, concentration-dependent antibacterial activity against both Gram-positive Bacillus subtilis and Gram-negative Escherichia coli that resembled action of cell wall-active β-lactam drugs. Glps showed sequence identity with the Major Royal Jelly Protein 1 (MRJP1) precursor that harbors three antimicrobial peptides: Jelleins 1, 2, and 4. Here, we used semi-quantitative radial diffusion assay and broth microdilution assay to evaluate susceptibility of a number of multi-drug resistant (MDR) clinical isolates to the MRJP1-contaning honey glycoproteins. The MDR bacterial strains comprised three methicillin-resistant Staphylococcus aureus (MRSA), four Pseudomonas aeruginosa, two Klebsiella pneumoniae, two vancomycin-resistant Enterococci (VRE), and five ESBL identified as one Proteus mirabilis, three E. coli, and one E. coli NDM. Their resistance to different classes of antibiotics was confirmed using automated system Vitek 2. MDR isolates differed in their susceptibility to glps with MIC90 values ranging from 4.8 μg/ml against B. subtilis to 14.4 μg/ml against ESBL K. pneumoniae, Klebsiella spp. ESBL and E. coli and up to 33 μg/ml against highly resistant strains of P. aeruginosa. Glps isolated from different honeys showed a similar ability to overcome bacterial resistance to β-lactams suggesting that (a) their mode of action is distinct from other classes of β-lactams and that (b) the common glps structure was the lead structure responsible for the activity. The results of the current study together with our previous evidence of a rapid bactericidal activity of glps demonstrate that glps possess suitable characteristics to be considered a novel antibacterial drug candidate. PMID:26217333

Blood pressure cuffs as a vector for transmission of multi-resistant organisms: colonisation rates and effects of disinfection.

PubMed

Grewal, Harjeet; Varshney, Kavita; Thomas, Lee C; Kok, Jen; Shetty, Amith

2013-06-01

Blood pressure (BP) cuffs are potential vectors for transmission of multi-resistant organisms (MROs). The present study aims to determine MRO colonisation rates in BP cuffs from areas of high patient flow as an assessment of the quality of disinfection and infection control practices. BP cuffs in the ED, high dependency unit (HDU) and operating theatres (OT) were prospectively examined after routine disinfection procedures. Swabs collected from the inner and outer surfaces of BP cuffs during inter-patient intervals were plated onto replicate organism detection and counting, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) chromogenic agar plates to detect rates of bacterial, MRSA and VRE colonisation, respectively. High bacterial colonisation rates were detected in BP cuffs from all three areas. BP cuffs from OT were significantly less colonised compared with cuffs from HDU and ED; 76% versus 96% and 100% (P < 0.0001) for inner surfaces and 86% versus 98% and 100% (P < 0.0001) for outer surfaces, respectively. Equivalent or higher bacterial growth was observed on the inner surface compared with outer surface in 54%, 84% and 86% of BP cuffs from OT, HDU and ED, respectively. MRSA was detected in 3 of 150 (2%) swabs collected, but no VRE was detected. Although MRSA and VRE were infrequently isolated, current disinfection and infection control protocols need to be improved given the greater recovery of organisms from the inner compared with outer surfaces of BP cuffs. © 2013 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

A decade of genomic history for healthcare-associated Enterococcus faecium in the United Kingdom and Ireland

PubMed Central

Raven, Kathy E.; Reuter, Sandra; Reynolds, Rosy; Brodrick, Hayley J.; Russell, Julie E.; Török, M. Estée; Parkhill, Julian; Peacock, Sharon J.

2016-01-01

Vancomycin-resistant Enterococcus faecium (VREfm) is an important cause of healthcare-associated infections worldwide. We undertook whole-genome sequencing (WGS) of 495 E. faecium bloodstream isolates from 2001–2011 in the United Kingdom and Ireland (UK&I) and 11 E. faecium isolates from a reference collection. Comparison between WGS and multilocus sequence typing (MLST) identified major discrepancies for 17% of isolates, with multiple instances of the same sequence type (ST) being located in genetically distant positions in the WGS tree. This confirms that WGS is superior to MLST for evolutionary analyses and is more accurate than current typing methods used during outbreak investigations. E. faecium has been categorized as belonging to three clades (Clades A1, hospital-associated; A2, animal-associated; and B, community-associated). Phylogenetic analysis of our isolates replicated the distinction between Clade A (97% of isolates) and Clade B but did not support the subdivision of Clade A into Clade A1 and A2. Phylogeographic analyses revealed that Clade A had been introduced multiple times into each hospital referral network or country, indicating frequent movement of E. faecium between regions that rarely share hospital patients. Numerous genetic clusters contained highly related vanA-positive and -negative E. faecium, which implies that control of vancomycin-resistant enterococci (VRE) in hospitals also requires consideration of vancomycin-susceptible E. faecium. Our findings reveal the evolution and dissemination of hospital-associated E. faecium in the UK&I and provide evidence for WGS as an instrument for infection control. PMID:27527616

A decade of genomic history for healthcare-associated Enterococcus faecium in the United Kingdom and Ireland.

PubMed

Raven, Kathy E; Reuter, Sandra; Reynolds, Rosy; Brodrick, Hayley J; Russell, Julie E; Török, M Estée; Parkhill, Julian; Peacock, Sharon J

2016-10-01

Vancomycin-resistant Enterococcus faecium (VREfm) is an important cause of healthcare-associated infections worldwide. We undertook whole-genome sequencing (WGS) of 495 E. faecium bloodstream isolates from 2001-2011 in the United Kingdom and Ireland (UK&I) and 11 E. faecium isolates from a reference collection. Comparison between WGS and multilocus sequence typing (MLST) identified major discrepancies for 17% of isolates, with multiple instances of the same sequence type (ST) being located in genetically distant positions in the WGS tree. This confirms that WGS is superior to MLST for evolutionary analyses and is more accurate than current typing methods used during outbreak investigations. E. faecium has been categorized as belonging to three clades (Clades A1, hospital-associated; A2, animal-associated; and B, community-associated). Phylogenetic analysis of our isolates replicated the distinction between Clade A (97% of isolates) and Clade B but did not support the subdivision of Clade A into Clade A1 and A2. Phylogeographic analyses revealed that Clade A had been introduced multiple times into each hospital referral network or country, indicating frequent movement of E. faecium between regions that rarely share hospital patients. Numerous genetic clusters contained highly related vanA-positive and -negative E. faecium, which implies that control of vancomycin-resistant enterococci (VRE) in hospitals also requires consideration of vancomycin-susceptible E. faecium Our findings reveal the evolution and dissemination of hospital-associated E. faecium in the UK&I and provide evidence for WGS as an instrument for infection control. © 2016 Raven et al.; Published by Cold Spring Harbor Laboratory Press.

Bromomethylthioindole Inspired Carbazole Hybrids as Promising Class of Anti-MRSA Agents.

PubMed

Cheng, Chia-Yi; Chang, Chun-Ping; Lauderdale, Tsai-Ling Yang; Yu, Guann-Yi; Lee, Jinq-Chyi; Jhang, Yi-Wun; Wu, Chien-Huang; Ke, Yi-Yu; Sadani, Amit A; Yeh, Ching-Fang; Huang, I-Wen; Kuo, Yi-Ping; Tsai, De-Jiun; Yeh, Teng-Kuang; Tseng, Chen-Tso; Song, Jen-Shin; Liu, Yu-Wei; Tsou, Lun K; Shia, Kak-Shan

2016-12-08

Series of N -substituted carbazole analogues bearing an indole ring were synthesized as anti-methicillin-resistant Staphylococcus aureus (MRSA) agents from a molecular hybridization approach. The representative compound 19 showed an MIC = 1 μg/mL against a panel of MRSA clinical isolates as it possessed comparable in vitro activities to that of vancomycin. Moreover, compound 19 also exhibited MIC = 1 μg/mL activities against a recent identified Z172 MRSA strain (vancomycin-intermediate and daptomycin-nonsusceptible phenotype) and the vancomycin-resistant Enterococcus faecalis (VRE) strain. In a mouse model with lethal infection of MRSA (4N216), a 75% survival rate was observed after a single dose of compound 19 was intravenously administered at 20 mg/kg. In light of their equipotent activities against different MRSA isolates and VRE strain, the data underscore the importance of designed hybrid series for the development of new N -substituted carbazoles as potential anti-MRSA agents.

Bromomethylthioindole Inspired Carbazole Hybrids as Promising Class of Anti-MRSA Agents

PubMed Central

2016-01-01

Series of N-substituted carbazole analogues bearing an indole ring were synthesized as anti-methicillin-resistant Staphylococcus aureus (MRSA) agents from a molecular hybridization approach. The representative compound 19 showed an MIC = 1 μg/mL against a panel of MRSA clinical isolates as it possessed comparable in vitro activities to that of vancomycin. Moreover, compound 19 also exhibited MIC = 1 μg/mL activities against a recent identified Z172 MRSA strain (vancomycin-intermediate and daptomycin-nonsusceptible phenotype) and the vancomycin-resistant Enterococcus faecalis (VRE) strain. In a mouse model with lethal infection of MRSA (4N216), a 75% survival rate was observed after a single dose of compound 19 was intravenously administered at 20 mg/kg. In light of their equipotent activities against different MRSA isolates and VRE strain, the data underscore the importance of designed hybrid series for the development of new N-substituted carbazoles as potential anti-MRSA agents. PMID:27994762

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.

[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.

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.

Double-Serine Fluoroquinolone Resistance Mutations Advance Major International Clones and Lineages of Various Multi-Drug Resistant Bacteria.

PubMed

Fuzi, Miklos; Szabo, Dora; Csercsik, Rita

2017-01-01

The major international sequence types/lineages of methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae and ESBL-producing E. coli were demonstrated to have been advanced by favorable fitness balance associated with high-level resistance to fluoroquinolones. The paper shows that favorable fitness in the major STs/lineages of these pathogens was principally attained by the capacity of evolving mutations in the fluoroquinolone-binding serine residues of both the DNA gyrase and topoisomerase IV enzymes. The available information on fitness balance incurred by individual and various combinations of mutations in the enzymes is reviewed in multiple species. Moreover, strong circumstantial evidence is presented that major STs/lineages of other multi-drug resistant bacteria, primarily vancomycin-resistant Enterococcus faecium (VRE), emerged by a similar mechanism. The reason(s) why the major ST/lineage strains of various pathogens proved more adept at evolving favorable mutations than most isolates of the same species remains to be elucidated.

Double-Serine Fluoroquinolone Resistance Mutations Advance Major International Clones and Lineages of Various Multi-Drug Resistant Bacteria

PubMed Central

Fuzi, Miklos; Szabo, Dora; Csercsik, Rita

2017-01-01

The major international sequence types/lineages of methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae and ESBL-producing E. coli were demonstrated to have been advanced by favorable fitness balance associated with high-level resistance to fluoroquinolones. The paper shows that favorable fitness in the major STs/lineages of these pathogens was principally attained by the capacity of evolving mutations in the fluoroquinolone-binding serine residues of both the DNA gyrase and topoisomerase IV enzymes. The available information on fitness balance incurred by individual and various combinations of mutations in the enzymes is reviewed in multiple species. Moreover, strong circumstantial evidence is presented that major STs/lineages of other multi-drug resistant bacteria, primarily vancomycin-resistant Enterococcus faecium (VRE), emerged by a similar mechanism. The reason(s) why the major ST/lineage strains of various pathogens proved more adept at evolving favorable mutations than most isolates of the same species remains to be elucidated. PMID:29250038

Synthesis and In Vitro Activity of Polyhalogenated 2-phenylbenzimidazoles as a New Class of anti-MRSA and Anti-VRE Agents.

PubMed

Göker, Hakan; Karaaslan, Cigdem; Püsküllü, Mustafa Orhan; Yildiz, Sulhiye; Duydu, Yalcin; Üstündağ, Aylin; Yalcin, Can Özgür

2016-01-01

A series of novel polyhalogenated 2-phenylbenzimidazoles have been synthesized and evaluated for in vitro antistaphylococcal activity against drug-resistant bacterial strains (methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus faecium. Certain compounds inhibit bacterial growth perfectly. 11 was active than vancomycin (0.78 μg/mL) with the lowest MIC values with 0.19 μg/mL against methicillin-resistant Staphylococcus aureus, 8 and 35 exhibited best inhibitory activity against vancomycin-resistant Enterococcus faecium (1.56 μg/mL). The mechanism of action for this class of compounds appears to be different than clinically used antibiotics. These polyhalogenated benzimidazoles have potential for further investigation as a new class of potent anti-methicillin-resistant Staphylococcus aureus and anti-vancomycin-resistant Enterococcus faecium agents. © 2015 John Wiley & Sons A/S.

Methicillin-resistant Staphylococcus aureus: clinical manifestations and antimicrobial therapy.

PubMed

Cunha, B A

2005-07-01

Methicillin-resistant Staphylococcus aureus (MRSA) is a common skin coloniser and less commonly causes infection. MRSA colonisation should be contained by infection control measures and not treated. MRSA infections cause the same spectrum of infection as MSSA infections, i.e., skin/soft tissue infections, bone/joint infections, central IV line infections, and acute bacterial endocarditis (native valve/prosthetic valve). There is a discrepancy between in-vitro sensitivity and in-vivo effectiveness with MRSA. To treat MRSA infections, clinicians should select an MRSA drug with proven in-vivo effectiveness, i.e., daptomycin. Linezolid, quinupristin/dalfopristin, minocycline, or vancomycin, and not rely on in-vitro susceptibility data. For MRSA, doxycycline cannot be substituted for minocycline. Linezolid and minocycline are available for oral administration and both are also effective in treating MRSA CNS infections. Vancomycin is being used less due to side effects, (increasing MICs/resistance, VISA/VRSA), and increased VRE prevalence. The most potent anti-MRSA drug at the present time is daptomycin. Daptomycin is useful when rapid/effective therapy of MRSA bacteraemia/endocarditis is necessary. Daptomycin is also useful to treat persistent MRSA bacteraemias/MRSA treatment failures with other drugs, i.e., vancomycin. There is no difference in virulence between MSSA and MRSA infections if treatment is started early and with an agent that has in-vivo effectiveness.

Improving hospital hygiene to reduce the impact of multidrug-resistant organisms in health care--a prospective controlled multicenter study.

PubMed

Gerlich, Miriam G; Piegsa, Jens; Schäfer, Christian; Hübner, Nils-Olaf; Wilke, Florian; Reuter, Susanne; Engel, Georg; Ewert, Ralf; Claus, Franziska; Hübner, Claudia; Ried, Walter; Flessa, Steffen; Kramer, Axel; Hoffmann, Wolfgang

2015-10-22

Nosocomial infections are the most common complication during inpatient hospital care. An increasing proportion of these infections are caused by multidrug-resistant organisms (MDROs). This report describes an intervention study which was designed to address the practical problems encountered in trying to avoid and treat infections caused by MDROs. The aim of the HARMONIC (Harmonized Approach to avert Multidrug-resistant Organisms and Nosocomial Infections) study is to provide comprehensive support to hospitals in a defined study area in north-east Germany, to meet statutory requirements. To this end, a multimodal system of hygiene management was implemented in the participating hospitals. HARMONIC is a controlled intervention study conducted in eight acute care hospitals in the 'Health Region Baltic Sea Coast' in Germany. The intervention measures include the provision of written recommendations on methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE) and multi-resistant Gram-negative bacteria (MRGN), supplemented by regional recommendations for antibiotic prescriptions. In addition, there is theoretical and practical training of health care workers (HCWs) in the prevention and handling of MDROs, as well as targeted and critically gauged applications of antibiotics. The main outcomes of the implementation and analysis of the HARMONIC study are: (i) screening rates for MRSA, VRE and MRGN in high-risk patients, (ii) the frequency of MRSA decolonization, (iii) the level of knowledge of HCWs concerning MDROs, and (iv) specific types and amounts of antibiotics used. The data are predominantly obtained by paper-based questionnaires and documentation sheets. A computer-assisted workflow-based documentation system was developed in order to provide support to the participating facilities. The investigation includes three nested studies on risk profiles of MDROs, health-related quality of life, and cost analysis. A six-month follow

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.

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

Novel Compounds From Shark and Stingray Epidermal Mucus With Antimicrobial Activity Against Wound Infection Pathogens

DTIC Science & Technology

2014-03-01

Micrococcus sp., Enterococcus faecalis, Enterococcus faecium, Vancomycin resistant Enterococcus, and Escherichia coli). During the second Quarter of...mm) 803 D10 Rhinoptera bonasus MRSA (9.5) MSSA (4.5) Bacillus cereus (6) Listeria monocytogenes (6) MRSA (2) Micrococcus sp (7) VRE (2) 803...E6 Rhinoptera bonasus MRSA (7.5) MSSA (8.5) VRE (4.5) Bacillus subtilis (10) MRSA (10) MRSA (10) Micrococcus (16) Listeria monocytogenes (13

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.

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

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

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.

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

Intervention to Reduce Transmission of Resistant Bacteria in Intensive Care

PubMed Central

Huskins, W. Charles; Huckabee, Charmaine M.; O’Grady, Naomi P.; Murray, Patrick; Kopetskie, Heather; Zimmer, Louise; Walker, Mary Ellen; Sinkowitz-Cochran, Ronda L.; Jernigan, John A.; Samore, Matthew; Wallace, Dennis; Goldmann, Donald A.

2012-01-01

BACKGROUND Intensive care units (ICUs) are high-risk settings for the transmission of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE). METHODS In a cluster-randomized trial, we evaluated the effect of surveillance for MRSA and VRE colonization and of the expanded use of barrier precautions (intervention) as compared with existing practice (control) on the incidence of MRSA or VRE colonization or infection in adult ICUs. Surveillance cultures were obtained from patients in all participating ICUs; the results were reported only to ICUs assigned to the intervention. In intervention ICUs, patients who were colonized or infected with MRSA or VRE were assigned to care with contact precautions; all the other patients were assigned to care with universal gloving until their discharge or until surveillance cultures obtained at admission were reported to be negative. RESULTS During a 6-month intervention period, there were 5434 admissions to 10 intervention ICUs, and 3705 admissions to 8 control ICUs. Patients who were colonized or infected with MRSA or VRE were assigned to barrier precautions more frequently in intervention ICUs than in control ICUs (a median of 92% of ICU days with either contact precautions or universal gloving [51% with contact precautions and 43% with universal gloving] in intervention ICUs vs. a median of 38% of ICU days with contact precautions in control ICUs, P<0.001). In intervention ICUs, health care providers used clean gloves, gowns, and hand hygiene less frequently than required for contacts with patients assigned to barrier precautions; when contact precautions were specified, gloves were used for a median of 82% of contacts, gowns for 77% of contacts, and hand hygiene after 69% of contacts, and when universal gloving was specified, gloves were used for a median of 72% of contacts and hand hygiene after 62% of contacts. The mean (±SE) ICU-level incidence of events of colonization or infection

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.

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

A Treatment Plant Receiving Waste Water from Multiple Bulk Drug Manufacturers Is a Reservoir for Highly Multi-Drug Resistant Integron-Bearing Bacteria

PubMed Central

Walujkar, Sandeep A.; Charan, Shakti Singh; Moore, Edward R. B.; Larsson, D. G. Joakim; Shouche, Yogesh S.

2013-01-01

The arenas and detailed mechanisms for transfer of antibiotic resistance genes between environmental bacteria and pathogens are largely unclear. Selection pressures from antibiotics in situations where environmental bacteria and human pathogens meet are expected to increase the risks for such gene transfer events. We hypothesize that waste-water treatment plants (WWTPs) serving antibiotic manufacturing industries may provide such spawning grounds, given the high bacterial densities present there together with exceptionally strong and persistent selection pressures from the antibiotic-contaminated waste. Previous analyses of effluent from an Indian industrial WWTP that processes waste from bulk drug production revealed the presence of a range of drugs, including broad spectrum antibiotics at extremely high concentrations (mg/L range). In this study, we have characterized the antibiotic resistance profiles of 93 bacterial strains sampled at different stages of the treatment process from the WWTP against 39 antibiotics belonging to 12 different classes. A large majority (86%) of the strains were resistant to 20 or more antibiotics. Although there were no classically-recognized human pathogens among the 93 isolated strains, opportunistic pathogens such as Ochrobactrum intermedium, Providencia rettgeri, vancomycin resistant Enterococci (VRE), Aerococcus sp. and Citrobacter freundii were found to be highly resistant. One of the O. intermedium strains (ER1) was resistant to 36 antibiotics, while P. rettgeri (OSR3) was resistant to 35 antibiotics. Class 1 and 2 integrons were detected in 74/93 (80%) strains each, and 88/93 (95%) strains harbored at least one type of integron. The qPCR analysis of community DNA also showed an unprecedented high prevalence of integrons, suggesting that the bacteria living under such high selective pressure have an appreciable potential for genetic exchange of resistance genes via mobile gene cassettes. The present study provides insight into

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

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.

Nurses’ uniforms: How many bacteria do they carry after one shift?

PubMed Central

Sanon, Marie-Anne; Watkins, Sally

2013-01-01

This pilot study investigated the pathogens that nurses are potentially bringing into the public and their home when they wear work uniforms outside of the work environment. To achieve this, sterilized uniforms were distributed to 10 nurses at a local hospital in Washington State at the beginning of their shift. Worn uniforms were collected at the end of the shifts and sent to a laboratory for analysis. Four tests were conducted: 1) a heterotrophic growth plate count, 2) methicillin-resistant Staphylococcus aureus (MRSA) growth, 3) vancomycin-resistant Enterococci (VRE), and 4) identification of the heterotrophic plate counts. Each participant completed a questionnaire and a survey. The results showed that the average bacteria colony growth per square inch was 1,246 and 5,795 for day and night shift, respectively. After 48 h, MRSA positives were present on 4 of the day shift and 3 of the night shift uniforms. Additional bacteria identified include: Bacillus sp., Micrococcus luteus, Staphylococcus aureus, Staphylococcus epidermidis, and Micrococcus roseus. The significant presence of bacteria on the uniforms 48 h after the shift ended necessitates further study, discussions and policy consideration regarding wearing health care uniforms outside of the work environment. PMID:25285235

Nurses' uniforms: How many bacteria do they carry after one shift?

PubMed

Sanon, Marie-Anne; Watkins, Sally

2012-12-01

This pilot study investigated the pathogens that nurses are potentially bringing into the public and their home when they wear work uniforms outside of the work environment. To achieve this, sterilized uniforms were distributed to 10 nurses at a local hospital in Washington State at the beginning of their shift. Worn uniforms were collected at the end of the shifts and sent to a laboratory for analysis. Four tests were conducted: 1) a heterotrophic growth plate count, 2) methicillin-resistant Staphylococcus aureus (MRSA) growth, 3) vancomycin-resistant Enterococci (VRE), and 4) identification of the heterotrophic plate counts. Each participant completed a questionnaire and a survey. The results showed that the average bacteria colony growth per square inch was 1,246 and 5,795 for day and night shift, respectively. After 48 h, MRSA positives were present on 4 of the day shift and 3 of the night shift uniforms. Additional bacteria identified include: Bacillus sp., Micrococcus luteus, Staphylococcus aureus, Staphylococcus epidermidis, and Micrococcus roseus. The significant presence of bacteria on the uniforms 48 h after the shift ended necessitates further study, discussions and policy consideration regarding wearing health care uniforms outside of the work environment.

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.

Application of WHONET in the Antimicrobial Resistance Surveillance of Uropathogens: A First User Experience from Nepal

PubMed Central

Ghosh, A.N.; Bhatta, D.R.; Ansari, M.T.; Tiwari, H.K.; Mathuria, J.P.; Gaur, A.; Supram, H.S.; Gokhale, S.

2013-01-01

Introduction: WHONET is a freely downloadable, Windows-based database software which is used for the management and analysis of microbiology data, with a special focus on the analysis of antimicrobial susceptibility test results. Urinary Tract Infections (UTI) are a common medical problem and they are responsible for notable morbidity among young and sexually active women. Objectives: The major objective of this study was the utilization and application of the WHONET program for the Antimicrobial Resistance (AMR) surveillance of uropathogens. Methods: A total of 3209 urine samples were collected from patients who visited Manipal Teaching Hospital with a clinical suspicion of UTI, during December 2010 to July 2011. The isolation and characterization of the isolates were done by conventional methods. Antimicrobial Susceptibility Testing (AST) was performed by Kirby Bauer’s disc diffusion method. The data entry and analysis were done by using the WHONET 5.6 software. Results: Out of the 3209 specimens, 497 bacterial isolates were obtained and they were subjected to AST. Escherichia coli (66.2%) was the commonest bacterial isolate, followed by Enterococcus species (9.3%), Staphylococcus aureus (5.0%), and Klebsiella pneumoniae (4.2%). Among the gram-negative enteric bacilli, a high prevalence of resistance was observed against ampicillin and ciprofloxacin. The gram negative nonfermenters exhibited a high degree of resistance to ceftazidime. Staphylococcus species. showed a moderately high resistance to co-trimoxazole. One isolate was Vancomycin Resistant Enterococci (VRE). Conclusion: This study, a first of its kind which was done in Nepal, was carried out by using the WHONET software to monitor, analyze and share the antimicrobial susceptibility data at various levels. This study was also aimed at building a surveillance network in Nepal, with the National Public Health Laboratory, Nepal, acting as a nodal centre. This would help in the formulation of antibiotic

Application of WHONET in the Antimicrobial Resistance Surveillance of Uropathogens: A First User Experience from Nepal.

PubMed

Ghosh, A N; Bhatta, D R; Ansari, M T; Tiwari, H K; Mathuria, J P; Gaur, A; Supram, H S; Gokhale, S

2013-05-01

WHONET is a freely downloadable, Windows-based database software which is used for the management and analysis of microbiology data, with a special focus on the analysis of antimicrobial susceptibility test results. Urinary Tract Infections (UTI) are a common medical problem and they are responsible for notable morbidity among young and sexually active women. The major objective of this study was the utilization and application of the WHONET program for the Antimicrobial Resistance (AMR) surveillance of uropathogens. A total of 3209 urine samples were collected from patients who visited Manipal Teaching Hospital with a clinical suspicion of UTI, during December 2010 to July 2011. The isolation and characterization of the isolates were done by conventional methods. Antimicrobial Susceptibility Testing (AST) was performed by Kirby Bauer's disc diffusion method. The data entry and analysis were done by using the WHONET 5.6 software. Out of the 3209 specimens, 497 bacterial isolates were obtained and they were subjected to AST. Escherichia coli (66.2%) was the commonest bacterial isolate, followed by Enterococcus species (9.3%), Staphylococcus aureus (5.0%), and Klebsiella pneumoniae (4.2%). Among the gram-negative enteric bacilli, a high prevalence of resistance was observed against ampicillin and ciprofloxacin. The gram negative nonfermenters exhibited a high degree of resistance to ceftazidime. Staphylococcus species. showed a moderately high resistance to co-trimoxazole. One isolate was Vancomycin Resistant Enterococci (VRE). This study, a first of its kind which was done in Nepal, was carried out by using the WHONET software to monitor, analyze and share the antimicrobial susceptibility data at various levels. This study was also aimed at building a surveillance network in Nepal, with the National Public Health Laboratory, Nepal, acting as a nodal centre. This would help in the formulation of antibiotic policies and in identifying hospital and community outbreaks

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

[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.

Antimicrobial Susceptibility Patterns of Enterococcus faecalis and Enterococcus faecium Isolated from Poultry Flocks in Germany.

PubMed

Maasjost, J; Mühldorfer, K; Cortez de Jäckel S; Hafez, H M

2015-03-01

Between 2010 and 2011, 145 Enterococcus isolates (Enterococcus faecalis, n = 127; Enterococcus faecium, n = 18) were collected during routine bacteriologic diagnostics from broilers, layers, and fattening turkeys in Germany showing various clinical signs. The susceptibility to 24 antimicrobial agents was investigated by broth microdilution test to determine minimum inhibitory concentrations (MICs). All E. faecalis isolates (n = 127) were susceptible to the beta-lactam antibiotics ampicillin, amoxicillin-clavulanic acid, and penicillin. Corresponding MIC with 50% inhibition (MIC50) and MIC with 90% inhibition (MIC90) values of these antimicrobial agents were at the lower end of the test range (≤ 4 μg/ml). In addition, no vancomycin-resistant enterococci (VRE) were found. High resistance rates were identified in both Enterococcus species for lincomycin (72%-99%) and tetracycline (67%-82%). Half or more than half of Enterococcus isolates were resistant to gentamicin (54%-72%) and the macrolide antibiotics erythromycin (44%-61%) and tylosin-tartate (44%-56%). Enterococcus faecalis isolated from fattening turkeys showed the highest prevalence of antimicrobial resistance compared to other poultry production systems. Eighty-nine out of 145 Enterococcus isolates were resistant to three or more antimicrobial classes. Again, turkeys stood out with 42 (8 1%) multiresistant isolates. The most-frequent resistance patterns of E. faecalis were gentamicin, lincomycin, and tetracycline in all poultry production systems.

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

Impact of pulsed xenon ultraviolet light on hospital-acquired infection rates in a community hospital.

PubMed

Vianna, Pedro G; Dale, Charles R; Simmons, Sarah; Stibich, Mark; Licitra, Carmelo M

2016-03-01

The role of contaminated environments in the spread of hospital-associated infections has been well documented. This study reports the impact of a pulsed xenon ultraviolet no-touch disinfection system on infection rates in a community care facility. This study was conducted in a community hospital in Southern Florida. Beginning November 2012, a pulsed xenon ultraviolet disinfection system was implemented as an adjunct to traditional cleaning methods on discharge of select rooms. The technology uses a xenon flashlamp to generate germicidal light that damages the DNA of organisms in the hospital environment. The device was implemented in the intensive care unit (ICU), with a goal of using the pulsed xenon ultraviolet system for disinfecting all discharges and transfers after standard cleaning and prior to occupation of the room by the next patient. For all non-ICU discharges and transfers, the pulsed xenon ultraviolet system was only used for Clostridium difficile rooms. Infection data were collected for methicillin-resistant Staphylococcus aureus, C difficile, and vancomycin-resistant Enterococci (VRE). The intervention period was compared with baseline using a 2-sample Wilcoxon rank-sum test. In non-ICU areas, a significant reduction was found for C difficile. There was a nonsignificant decrease in VRE and a significant increase in methicillin-resistant S aureus. In the ICU, all infections were reduced, but only VRE was significant. This may be because of the increased role that environment plays in the transmission of this pathogen. Overall, there were 36 fewer infections in the whole facility and 16 fewer infections in the ICU during the intervention period than would have been expected based on baseline data. Implementation of pulsed xenon ultraviolet disinfection is associated with significant decreases in facility-wide and ICU infection rates. These outcomes suggest that enhanced environmental disinfection plays a role in the risk mitigation of hospital

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

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.

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

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.

Antibody-Based Therapy for Enterococcal Catheter-Associated Urinary Tract Infections.

PubMed

Flores-Mireles, Ana L; Walker, Jennifer N; Potretzke, Aaron; Schreiber, Henry L; Pinkner, Jerome S; Bauman, Tyler M; Park, Alyssa M; Desai, Alana; Hultgren, Scott J; Caparon, Michael G

2016-10-25

Gram-positive bacteria in the genus Enterococcus are a frequent cause of catheter-associated urinary tract infection (CAUTI), a disease whose treatment is increasingly challenged by multiantibiotic-resistant strains. We have recently shown that E. faecalis uses the Ebp pilus, a heteropolymeric surface fiber, to bind the host protein fibrinogen as a critical step in CAUTI pathogenesis. Fibrinogen is deposited on catheters due to catheter-induced inflammation and is recognized by the N-terminal domain of EbpA (EbpA NTD ), the Ebp pilus's adhesin. In a murine model, vaccination with EbpA NTD confers significant protection against CAUTI. Here, we explored the mechanism of protection using passive transfer of immune sera to show that antisera blocking EbpA NTD -fibrinogen interactions not only is prophylactic but also can act therapeutically to reduce bacterial titers of an existing infection. Analysis of 55 clinical CAUTI, bloodstream, and gastrointestinal isolates, including E. faecalis, E. faecium, and vancomycin-resistant enterococci (VRE), revealed a diversity of levels of EbpA expression and fibrinogen-binding efficiency in vitro Strikingly, analysis of 10 strains representative of fibrinogen-binding diversity demonstrated that, irrespective of EbpA levels, EbpA NTD antibodies were universally protective. The results indicate that, despite diversity in levels of fibrinogen binding, strategies that target the disruption of EbpA NTD -fibrinogen interactions have considerable promise for treatment of CAUTI. Urinary catheterization is a routine medical procedure, and it has been estimated that 30 million Foley catheters are used annually in the United States. Importantly, placement of a urinary catheter renders the patient susceptible to developing a catheter-associated urinary tract infection, accounting for 1 million cases per year. Additionally, these infections can lead to serious complications, including bloodstream infection and death. Enterococcus strains

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

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

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

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

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.

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.

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.

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.

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.

Controlling Hospital-Acquired Infection: Focus on the Role of the Environment and New Technologies for Decontamination

PubMed Central

2014-01-01

SUMMARY There is increasing interest in the role of cleaning for managing hospital-acquired infections (HAI). Pathogens such as vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA), multiresistant Gram-negative bacilli, norovirus, and Clostridium difficile persist in the health care environment for days. Both detergent- and disinfectant-based cleaning can help control these pathogens, although difficulties with measuring cleanliness have compromised the quality of published evidence. Traditional cleaning methods are notoriously inefficient for decontamination, and new approaches have been proposed, including disinfectants, steam, automated dispersal systems, and antimicrobial surfaces. These methods are difficult to evaluate for cost-effectiveness because environmental data are not usually modeled against patient outcome. Recent studies have reported the value of physically removing soil using detergent, compared with more expensive (and toxic) disinfectants. Simple cleaning methods should be evaluated against nonmanual disinfection using standardized sampling and surveillance. Given worldwide concern over escalating antimicrobial resistance, it is clear that more studies on health care decontamination are required. Cleaning schedules should be adapted to reflect clinical risk, location, type of site, and hand touch frequency and should be evaluated for cost versus benefit for both routine and outbreak situations. Forthcoming evidence on the role of antimicrobial surfaces could supplement infection prevention strategies for health care environments, including those targeting multidrug-resistant pathogens. PMID:25278571