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Sample records for multi-drug resistant serotype

  1. [Travellers and multi-drug resistance bacteria].

    PubMed

    Takeshita, Nozomi

    2012-02-01

    The number of international travellers has increased. There is enormous diversity in medical backgrounds, purposes of travel, and travelling styles among travellers. Travellers are hospitalized abroad because of exotic and common diseases via medical tourism. This is one way of transporting and importing human bacteria between countries, including multi-drug resistant organisms. In developing countries, the antimicrobial resistance in Shigella sp. and Salmonella sp. have been a problem, because of this trend, the first choice of antibiotics has changed in some countries. Community acquired infections as well as hospital acquired infections with MRSA, multi-drug resistance (MDR) Pseudomonas aeruginosa, and ESBL have been a problem. This review will discuss the risk of MDR bacterial infectious diseases for travellers.

  2. Evaluation of the potential antimicrobial resistance transfer from a multi-drug resistant Escherichia coli to Salmonella in dairy calves

    USDA-ARS?s Scientific Manuscript database

    Previous research conducted by our laboratory investigated the incidence of multi-drug resistant (MDR) Salmonella in dairy cattle and reported that individual cattle, and most often calves, shed multiple Salmonella serotypes that vary in the degree of antibiotic resistance. More recently, we invest...

  3. Combination Approaches to Combat Multi-Drug Resistant Bacteria

    PubMed Central

    Worthington, Roberta J.; Melander, Christian

    2013-01-01

    The increasing prevalence of infections caused by multi-drug resistant bacteria is a global health problem that is exacerbated by the dearth of novel classes of antibiotics entering the clinic over the past 40 years. Herein we describe recent developments toward combination therapies for the treatment of multi-drug resistant bacterial infections. These efforts include antibiotic-antibiotic combinations, and the development of adjuvants that either directly target resistance mechanisms such as the inhibition of β-lactamase enzymes, or indirectly target resistance by interfering with bacterial signaling pathways such as two-component systems. We also discuss screening of libraries of previously approved drugs to identify non-obvious antimicrobial adjuvants. PMID:23333434

  4. The challenges of multi-drug-resistance in hepatology.

    PubMed

    Fernández, Javier; Bert, Frédéric; Nicolas-Chanoine, Marie-Hélène

    2016-11-01

    Antimicrobial resistance has become a major global public health security problem that needs coordinated approaches at regional, national and international levels. Antibiotic overuse and the failure of control measures to prevent the spread of resistant bacteria in the healthcare environment have led to an alarming increase in the number of infections caused by resistant bacteria, organisms that resist many (multi-drug and extensively drug-resistant strains), if not all (pan-drug-resistant bacteria) currently available antibiotics. While Gram-positive cocci resistance (methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci) shows a heterogeneous geographical distribution, extended-spectrum β-lactamase-producing Enterobacteriaceae and carbapenem-resistant Enterobacteriaceae have become pandemic worldwide and endemic in some parts of the world, respectively. Moreover, currently available therapeutic options for resistant bacteria are very limited, with very few new agents in development. Antimicrobial resistance is especially relevant in decompensated cirrhosis. Firstly, cirrhotic patients are highly susceptible to develop infections caused by resistant bacteria as risk factors of multiresistance concentrate in this population (mainly repeated hospitalizations and antibiotic exposure). Secondly, inappropriate empirical antibiotic schedules easily translate into increased morbidity (acute kidney injury, acute-on-chronic liver failure, septic shock) and hospital mortality in advanced cirrhosis. Therefore, hepatologists must face nowadays a complex clinical scenario that requires new empirical antibiotic strategies that may further spread resistance. Global, regional and local preventive measures should therefore be implemented to combat antimicrobial resistance in cirrhosis including the restriction of antibiotic prophylaxis to high-risk populations, investigation on non-antibiotic prophylaxis, stewardship programs on adequate antibiotic

  5. Lethal neonatal meningoencephalitis caused by multi-drug resistant, highly virulent Escherichia coli.

    PubMed

    Iqbal, Junaid; Dufendach, Kevin R; Wellons, John C; Kuba, Maria G; Nickols, Hilary H; Gómez-Duarte, Oscar G; Wynn, James L

    2016-01-01

    Neonatal meningitis is a rare but devastating condition. Multi-drug resistant (MDR) bacteria represent a substantial global health risk. This study reports on an aggressive case of lethal neonatal meningitis due to a MDR Escherichia coli (serotype O75:H5:K1). Serotyping, MDR pattern and phylogenetic typing revealed that this strain is an emergent and highly virulent neonatal meningitis E. coli isolate. The isolate was resistant to both ampicillin and gentamicin; antibiotics currently used for empiric neonatal sepsis treatment. The strain was also positive for multiple virulence genes including K1 capsule, fimbrial adhesion fimH, siderophore receptors iroN, fyuA and iutA, secreted autotransporter toxin sat, membrane associated proteases ompA and ompT, type II polysaccharide synthesis genes (kpsMTII) and pathogenicity-associated island (PAI)-associated malX gene. The presence of highly-virulent MDR organisms isolated in neonates underscores the need to implement rapid drug resistance diagnostic methods and should prompt consideration of alternate empiric therapy in neonates with Gram negative meningitis.

  6. Autophagy and Transporter-Based Multi-Drug Resistance

    PubMed Central

    Kumar, Priyank; Zhang, Dong-Mei; Degenhardt, Kurt; Chen, Zhe-Sheng

    2012-01-01

    All the therapeutic strategies for treating cancers aim at killing the cancer cells via apoptosis (programmed cell death type I). Defective apoptosis endow tumor cells with survival. The cell can respond to such defects with autophagy. Autophagy is a cellular process by which cytoplasmic material is either degraded to maintain homeostasis or recycled for energy and nutrients in starvation. A plethora of evidence has shown that the role of autophagy in tumors is complex. A lot of effort is needed to underline the functional status of autophagy in tumor progression and treatment, and elucidate how to tweak autophagy to treat cancer. Furthermore, during the treatment of cancer, the limitation for the cure rate and survival is the phenomenon of multi drug resistance (MDR). The development of MDR is an intricate process that could be regulated by drug transporters, enzymes, anti-apoptotic genes or DNA repair mechanisms. Reports have shown that autophagy has a dual role in MDR. Furthermore, it has been reported that activation of a death pathway may overcome MDR, thus pointing the importance of other death pathways to regulate tumor cell progression and growth. Therefore, in this review we will discuss the role of autophagy in MDR tumors and a possible link amongst these phenomena. PMID:24710490

  7. Demonstrating a Multi-drug Resistant Mycobacterium tuberculosis Amplification Microarray

    PubMed Central

    Linger, Yvonne; Kukhtin, Alexander; Golova, Julia; Perov, Alexander; Qu, Peter; Knickerbocker, Christopher; Cooney, Christopher G.; Chandler, Darrell P.

    2014-01-01

    Simplifying microarray workflow is a necessary first step for creating MDR-TB microarray-based diagnostics that can be routinely used in lower-resource environments. An amplification microarray combines asymmetric PCR amplification, target size selection, target labeling, and microarray hybridization within a single solution and into a single microfluidic chamber. A batch processing method is demonstrated with a 9-plex asymmetric master mix and low-density gel element microarray for genotyping multi-drug resistant Mycobacterium tuberculosis (MDR-TB). The protocol described here can be completed in 6 hr and provide correct genotyping with at least 1,000 cell equivalents of genomic DNA. Incorporating on-chip wash steps is feasible, which will result in an entirely closed amplicon method and system. The extent of multiplexing with an amplification microarray is ultimately constrained by the number of primer pairs that can be combined into a single master mix and still achieve desired sensitivity and specificity performance metrics, rather than the number of probes that are immobilized on the array. Likewise, the total analysis time can be shortened or lengthened depending on the specific intended use, research question, and desired limits of detection. Nevertheless, the general approach significantly streamlines microarray workflow for the end user by reducing the number of manually intensive and time-consuming processing steps, and provides a simplified biochemical and microfluidic path for translating microarray-based diagnostics into routine clinical practice. PMID:24796567

  8. Demonstrating a multi-drug resistant Mycobacterium tuberculosis amplification microarray.

    PubMed

    Linger, Yvonne; Kukhtin, Alexander; Golova, Julia; Perov, Alexander; Qu, Peter; Knickerbocker, Christopher; Cooney, Christopher G; Chandler, Darrell P

    2014-04-25

    Simplifying microarray workflow is a necessary first step for creating MDR-TB microarray-based diagnostics that can be routinely used in lower-resource environments. An amplification microarray combines asymmetric PCR amplification, target size selection, target labeling, and microarray hybridization within a single solution and into a single microfluidic chamber. A batch processing method is demonstrated with a 9-plex asymmetric master mix and low-density gel element microarray for genotyping multi-drug resistant Mycobacterium tuberculosis (MDR-TB). The protocol described here can be completed in 6 hr and provide correct genotyping with at least 1,000 cell equivalents of genomic DNA. Incorporating on-chip wash steps is feasible, which will result in an entirely closed amplicon method and system. The extent of multiplexing with an amplification microarray is ultimately constrained by the number of primer pairs that can be combined into a single master mix and still achieve desired sensitivity and specificity performance metrics, rather than the number of probes that are immobilized on the array. Likewise, the total analysis time can be shortened or lengthened depending on the specific intended use, research question, and desired limits of detection. Nevertheless, the general approach significantly streamlines microarray workflow for the end user by reducing the number of manually intensive and time-consuming processing steps, and provides a simplified biochemical and microfluidic path for translating microarray-based diagnostics into routine clinical practice.

  9. Multi drug resistance in strong biofilm forming clinical isolates of Staphylococcus epidermidis.

    PubMed

    Sahal, Gulcan; Bilkay, Isil Seyis

    2014-01-01

    Staphylococcus epidermidis which exists in healthy human skin as a commensal inhabitant is also an important pathogen forming biofilms on many surfaces and recently, increased resistance traits were suggested to be acquired in biofilm environments. In this study; clinical Prevalences, antibiotic resistances and biofilm formations of S. epidermidis strains were determined and comparison of all these findings with each other was carried out in order to take precautions against them and figure out if high biofilm forming S. epidermidis strains display multi drug resistance. According to our results; samples of wound and blood were the most S. epidermidis isolated clinical materials (40%; 35%) and cardiothoracic surgery was the most S. epidermidis observed service unit. All of these strains were sensitive to vancomycin, however 65% of them showed resistance to all β-lactam antibiotics (Penicillin, Oxacillin, Amoxicilin/Clavulonic acid), used in this study and 60% of all S. epidermidis strains were found as multi drug resistant. When the results of strong biofilm forming S. epidermidis strains are examined; they were isolated from sample of blood and service unit of cardiovascular surgery in highest frequency and 80% of them were β-lactam resistant whereas 100% of them were multi drug resistant. One of these multi drug resistant strains which was resistant to maximum amount of different antimicrobial classes, was also observed as maximum biofilm forming strain among all the other S. epidermidis isolates. Multi drug resistance in strong biofilm forming strains shows that; biofilms play a role in antimicrobial resistance traits of S. epidermidis.

  10. Hospital costs of nosocomial multi-drug resistant Pseudomonas aeruginosa acquisition.

    PubMed

    Morales, Eva; Cots, Francesc; Sala, Maria; Comas, Mercè; Belvis, Francesc; Riu, Marta; Salvadó, Margarita; Grau, Santiago; Horcajada, Juan P; Montero, Maria Milagro; Castells, Xavier

    2012-05-23

    We aimed to assess the hospital economic costs of nosocomial multi-drug resistant Pseudomonas aeruginosa acquisition. A retrospective study of all hospital admissions between January 1, 2005, and December 31, 2006 was carried out in a 420-bed, urban, tertiary-care teaching hospital in Barcelona (Spain). All patients with a first positive clinical culture for P. aeruginosa more than 48 h after admission were included. Patient and hospitalization characteristics were collected from hospital and microbiology laboratory computerized records. According to antibiotic susceptibility, isolates were classified as non-resistant, resistant and multi-drug resistant. Cost estimation was based on a full-costing cost accounting system and on the criteria of clinical Activity-Based Costing methods. Multivariate analyses were performed using generalized linear models of log-transformed costs. Cost estimations were available for 402 nosocomial incident P. aeruginosa positive cultures. Their distribution by antibiotic susceptibility pattern was 37.1% non-resistant, 29.6% resistant and 33.3% multi-drug resistant. The total mean economic cost per admission of patients with multi-drug resistant P. aeruginosa strains was higher than that for non-resistant strains (15,265 vs. 4,933 Euros). In multivariate analysis, resistant and multi-drug resistant strains were independently predictive of an increased hospital total cost in compared with non-resistant strains (the incremental increase in total hospital cost was more than 1.37-fold and 1.77-fold that for non-resistant strains, respectively). P. aeruginosa multi-drug resistance independently predicted higher hospital costs with a more than 70% increase per admission compared with non-resistant strains. Prevention of the nosocomial emergence and spread of antimicrobial resistant microorganisms is essential to limit the strong economic impact.

  11. Hospital costs of nosocomial multi-drug resistant Pseudomonas aeruginosa acquisition

    PubMed Central

    2012-01-01

    Background We aimed to assess the hospital economic costs of nosocomial multi-drug resistant Pseudomonas aeruginosa acquisition. Methods A retrospective study of all hospital admissions between January 1, 2005, and December 31, 2006 was carried out in a 420-bed, urban, tertiary-care teaching hospital in Barcelona (Spain). All patients with a first positive clinical culture for P. aeruginosa more than 48 h after admission were included. Patient and hospitalization characteristics were collected from hospital and microbiology laboratory computerized records. According to antibiotic susceptibility, isolates were classified as non-resistant, resistant and multi-drug resistant. Cost estimation was based on a full-costing cost accounting system and on the criteria of clinical Activity-Based Costing methods. Multivariate analyses were performed using generalized linear models of log-transformed costs. Results Cost estimations were available for 402 nosocomial incident P. aeruginosa positive cultures. Their distribution by antibiotic susceptibility pattern was 37.1% non-resistant, 29.6% resistant and 33.3% multi-drug resistant. The total mean economic cost per admission of patients with multi-drug resistant P. aeruginosa strains was higher than that for non-resistant strains (15,265 vs. 4,933 Euros). In multivariate analysis, resistant and multi-drug resistant strains were independently predictive of an increased hospital total cost in compared with non-resistant strains (the incremental increase in total hospital cost was more than 1.37-fold and 1.77-fold that for non-resistant strains, respectively). Conclusions P. aeruginosa multi-drug resistance independently predicted higher hospital costs with a more than 70% increase per admission compared with non-resistant strains. Prevention of the nosocomial emergence and spread of antimicrobial resistant microorganisms is essential to limit the strong economic impact. PMID:22621745

  12. Diverse and abundant multi-drug resistant E. coli in Matang mangrove estuaries, Malaysia.

    PubMed

    Ghaderpour, Aziz; Ho, Wing Sze; Chew, Li-Lee; Bong, Chui Wei; Chong, Ving Ching; Thong, Kwai-Lin; Chai, Lay Ching

    2015-01-01

    E.coli, an important vector distributing antimicrobial resistance in the environment, was found to be multi-drug resistant, abundant, and genetically diverse in the Matang mangrove estuaries, Malaysia. One-third (34%) of the estuarine E. coli was multi-drug resistant. The highest antibiotic resistance prevalence was observed for aminoglycosides (83%) and beta-lactams (37%). Phylogenetic groups A and B1, being the most predominant E. coli, demonstrated the highest antibiotic resistant level and prevalence of integrons (integron I, 21%; integron II, 3%). Detection of phylogenetic group B23 downstream of fishing villages indicates human fecal contamination as a source of E. coli pollution. Enteroaggregative E. coli (1%) were also detected immediately downstream of the fishing village. The results indicated multi-drug resistance among E. coli circulating in Matang estuaries, which could be reflective of anthropogenic activities and aggravated by bacterial and antibiotic discharges from village lack of a sewerage system, aquaculture farms and upstream animal husbandry.

  13. ACSSuT Multi-Drug Resistance Among Salmonella Isolates of Animal Origin

    USDA-ARS?s Scientific Manuscript database

    BACKGROUND: Multi-drug resistant (MDR) Salmonella Typhimurium DT104 (DT104) emerged in the mid-1990’s in humans and animals with infection resulting in increased morbidity and mortality. DT104 was characterized by resistance to Ampicillin, Chloramphenicol, Streptomycin, Sulfa, and Tetracycline (AC...

  14. Outbreak of mastitis in sheep caused by multi-drug resistant Enterococcus faecalis in Sardinia, Italy.

    PubMed

    Sanciu, G; Marogna, G; Paglietti, B; Cappuccinelli, P; Leori, G; Rappelli, P

    2013-03-01

    An outbreak of infective mastitis due to Enterococcus faecalis occurred in an intensive sheep farm in north Sardinia (Italy). E. faecalis, which is only rarely isolated from sheep milk, was unexpectedly found in 22·3% of positive samples at microbiological examination. Forty-five out of the 48 E. faecalis isolates showed the same multi-drug resistance pattern (cloxacillin, streptomycin, kanamycin, clindamycin, oxytetracycline). E. faecalis isolates were analysed by pulsed-field gel electrophoresis, and all 45 multi-drug resistant strains showed an indistinguishable macrorestiction profile, indicating their clonal origin. To our knowledge, this is the first report of an outbreak of mastitis in sheep caused by E. faecalis.

  15. [Multi-drug resistant bacteria, a complex mechanism].

    PubMed

    Hilaire, Jean-Christophe

    2013-01-01

    Bacteria are said to be multidrug resistant when they are only sensitive to a small number of antibiotics used as treatments. This problem of resistance appeared in hospitals soon after antibiotics were first used. In the 1960s, strains of staphylococcus became resistant to penicillin.

  16. [Psychological impacts of being a carrier of multi-drug resistant bacteria].

    PubMed

    Pires, Elisabete; Frange, Pierre; Henry, Benoît; Lortholary, Olivier; Reichert, Catherine

    2015-01-01

    Learning that they are a carrier of multi-drug resistant bacteria and being placed in isolation to prevent transmission has significant psychological repercussions for the patient and their families. Through therapeutic education, caregivers adapt their support to the patient's experience, raising their awareness of prevention. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  17. Recycling antibiotics into GUMBOS: A new combination strategy to combat multi-drug resistant bacteria

    USDA-ARS?s Scientific Manuscript database

    The emergence of multi-drug resistant bacteria, coupled with the lack of new antibiotics in development, is fast evolving into a global crisis. New strategies utilizing existing antibacterial agents are urgently needed. We propose one such strategy in which four outmoded ß-lactam antibiotics (amp...

  18. [Caring for a patient carrying multi-drug resistant bacteria at home].

    PubMed

    Kereun, François

    2015-01-01

    Private practice health professionals play a role in the fight against healthcare-associated infections. The management of the home care of a patient carrying multi-drug resistant bacteria reveals the weaknesses in the community-hospital link. Providing care in complete safety for the caregiver as well as the patient is a major challenge. A private practice nurse shares his experience.

  19. Establishment and identification of the human multi-drug-resistant cholangiocarcinoma cell line QBC939/ADM.

    PubMed

    Liu, Zhi-Hua; He, Yan-Ping; Zhou, Yukun; Zhang, Peng; Qin, Huanlong

    2011-06-01

    In this study, we aim to establish the human multi-drug-resistant cholangiocarcinoma cell line QBC939/ADM which can be grow and passaged steadily in 1 μg/ml concentration of adriamycin in appropriate medium. The human multi-drug-resistant cholangiocarcinoma cell line QBC939/ADM was established using the method of exposure to medium with adriamycin alternated between high and low concentration with gradually increasing concentration. Furthermore, QBC939 and QBC939/ADM were both treated with adriamycin, mitomycin and vindesine, and then detected by MTT assay, respectively. Growth cycle and intra-cellular concentrations of ADM within cells of each group were determined by flow cytometry. Expression levels of P-glycoprotein were detected by Western bolt and real-time PCR. Results showed that, compared with QBC939, the inhibitive rates of adriamycin, mitomycin and vindesine to QBC939/ADM were lower. Content of ADM in the QBC939/ADM was lower. Western bolt and real time PCR showed that P-glycoprotein in the QBC939/ADM group was over expressed. Therefore, QBC939/ADM was establish and identified as the multi-drug-resistant cell line, which can grow and be passaged steadily in 1 μg/ml concentration adriamycin in appropriate medium. And the multi-drug-resistant character of QBC939/ADM was indicated to be related to the over expression of P-glycoprotein induced by chemotherapeutic drugs.

  20. [The risk of infection with patients with multi-drug resistant bacteria in the operating room].

    PubMed

    Latroche, Marie-France; Roche, Géraldine; Velardo, Danielle

    2015-01-01

    The risk of infection in the operating theatre is constant and multifactorial. It can be contained through a prevention process. The organisation, implementation, monitoring and the results of the patient pathway are all sources for the analysis of practices, quality and professional progress in order to limit the risks of transmitting multi-drug or highly resistant bacteria.

  1. Cooperative Antibiotic Resistance in a Multi-Drug Environment

    NASA Astrophysics Data System (ADS)

    Yurtsev, Eugene; Dai, Lei; Gore, Jeff

    2013-03-01

    The emergence of antibiotic resistance in bacteria is a significant health concern. A frequent mechanism of antibiotic resistance involves the production of an enzyme which inactivates the antibiotic. By inactivating the antibiotic, resistant cells can ``share'' their resistance with other cells in the bacterial population, suggesting that it may be possible to observe cooperation between strains that inactivate different antibiotics. Here, we experimentally track the population dynamics of two E. coli strains in the presence of two different antibiotics. We find that together the strains are able to grow in antibiotic concentrations that inhibit growth of either of the strains individually. We observe that even when there is stable coexistence between the two strains, the population size of each strain can undergo large oscillations. We expect that our results will provide insight into the evolution of antibiotic resistance and the evolutionary origin of phenotypic diversity and cooperative behaviors.

  2. Diverse and abundant multi-drug resistant E. coli in Matang mangrove estuaries, Malaysia

    PubMed Central

    Ghaderpour, Aziz; Ho, Wing Sze; Chew, Li-Lee; Bong, Chui Wei; Chong, Ving Ching; Thong, Kwai-Lin; Chai, Lay Ching

    2015-01-01

    E.coli, an important vector distributing antimicrobial resistance in the environment, was found to be multi-drug resistant, abundant, and genetically diverse in the Matang mangrove estuaries, Malaysia. One-third (34%) of the estuarine E. coli was multi-drug resistant. The highest antibiotic resistance prevalence was observed for aminoglycosides (83%) and beta-lactams (37%). Phylogenetic groups A and B1, being the most predominant E. coli, demonstrated the highest antibiotic resistant level and prevalence of integrons (integron I, 21%; integron II, 3%). Detection of phylogenetic group B23 downstream of fishing villages indicates human fecal contamination as a source of E. coli pollution. Enteroaggregative E. coli (1%) were also detected immediately downstream of the fishing village. The results indicated multi-drug resistance among E. coli circulating in Matang estuaries, which could be reflective of anthropogenic activities and aggravated by bacterial and antibiotic discharges from village lack of a sewerage system, aquaculture farms and upstream animal husbandry. PMID:26483759

  3. Type 2 diabetes and multi-drug resistant tuberculosis

    PubMed Central

    Fisher-Hoch, Susan P.; Whitney, Erin; McCormick, Joseph B.; Crespo, Gonzalo; Smith, Brian; Rahbar, Mohammad H.; Restrepo, Blanca I.

    2010-01-01

    The association between tuberculosis (TB) and diabetes is re-emerging with the epidemic of type 2 diabetes (T2DM). We analyzed retrospective data from 2,878 TB patients across the Texas/Mexico border. Overall 161/2878 (5.6%) patients had MDR TB (resistance to rifampin and isoniazid): Texas 49/1442 (3.4%) and Mexico 112/1436 (7.8%). In Texas MDR TB was significantly associated with T2DM (OR 2.1 95% CI 1.1–4.2) when adjusted for age, gender, drug and alcohol abuse, HIV infection and history of previous episode of TB, and in Mexico (OR 1.80 95% CI 1.1–2.9) when adjusted for age and gender. Patients with T2DM were consistently more likely to be compliant with DOTS therapy (OR 2.4 95% CI 1.1–5.4) than patients without T2DM. In Texas, all but 3 of the T2DM patients with MDR TB were resistant at their first culture at the time of diagnosis. It is possible that impaired immunity in T2DM increases susceptibility to infection with resistant strains. PMID:18728934

  4. Transfer between an Algerian and a French hospital of four multi-drug resistant bacterial strains together via a single patient

    PubMed Central

    Moissenet, Didier; Richard, Patrick; Granados, Maria; Mérens, Audrey; Fournier, Damien; Fines-Guyon, Marguerite; Arlet, Guillaume; Vu-Thien, Hoang

    2015-01-01

    A 5 years-old girl, seriously burnt with fire, was first hospitalized during four days in an hospital at Alger, and then transferred to our hospital at Paris. Admitted in our intensive care burns unit, she was third degree burnt on 78% of total body surface area, already treated with imipenem and vancomycin at her arrival. Clinical aggravation was rapidly observed and death occurred within 24 hours. Cultures of blood and multiple wound swabs yielded 3 multi-drug resistant bacterial strains: Acinetobacter baumannii with carbapenemase OXA-23, Pseudomonas aeruginosa serotype O11 with metallo-ß-lactamase VIM-4 and Klebsiella pneumoniae with CTX-M-15 extended-spectrum ß-lactamase. Culture of a rectal swab showed colonization by Enterococcus faecium with vanA glycopeptides resistance. Patients colonized with one or two multi-drug-resistant strains were not rare in our burns unit, especially those transferred from Algeria, but this case of a single patient harboring four multi-drug-resistant strains is exceptional. PMID:26550534

  5. Bacteriophages: biosensing tools for multi-drug resistant pathogens.

    PubMed

    Tawil, N; Sacher, E; Mandeville, R; Meunier, M

    2014-03-21

    Pathogen detection is of utmost importance in many sectors, such as in the food industry, environmental quality control, clinical diagnostics, bio-defence and counter-terrorism. Failure to appropriately, and specifically, detect pathogenic bacteria can lead to serious consequences, and may ultimately be lethal. Public safety, new legislation, recent outbreaks in food contamination, and the ever-increasing prevalence of multidrug-resistant infections have fostered a worldwide research effort targeting novel biosensing strategies. This review concerns phage-based analytical and biosensing methods targeted towards theranostic applications. We discuss and review phage-based assays, notably phage amplification, reporter phage, phage lysis, and bioluminescence assays for the detection of bacterial species, as well as phage-based biosensors, including optical (comprising SPR sensors and fiber optic assays), electrochemical (comprising amperometric, potentiometric, and impedimetric sensors), acoustic wave and magnetoelastic sensors.

  6. Xenopus laevis oocytes infected with multi-drug-resistant bacteria: implications for electrical recordings.

    PubMed

    O'Connell, Denice; Mruk, Karen; Rocheleau, Jessica M; Kobertz, William R

    2011-08-01

    The Xenopus laevis oocyte has been the workhorse for the investigation of ion transport proteins. These large cells have spawned a multitude of novel techniques that are unfathomable in mammalian cells, yet the fickleness of the oocyte has driven many researchers to use other membrane protein expression systems. Here, we show that some colonies of Xenopus laevis are infected with three multi-drug-resistant bacteria: Pseudomonas fluorescens, Pseudomonas putida, and Stenotrophomonas maltophilia. Oocytes extracted from infected frogs quickly (3-4 d) develop multiple black foci on the animal pole, similar to microinjection scars, which render the extracted eggs useless for electrical recordings. Although multi-drug resistant, the bacteria were susceptible to amikacin and ciprofloxacin in growth assays. Supplementing the oocyte storage media with these two antibiotics prevented the appearance of the black foci and afforded oocytes suitable for whole-cell recordings. Given that P. fluorescens associated with X. laevis has become rapidly drug resistant, it is imperative that researchers store the extracted oocytes in the antibiotic cocktail and not treat the animals harboring the multi-drug-resistant bacteria.

  7. Comparative Genomics Study of Multi-Drug-Resistance Mechanisms in the Antibiotic-Resistant Streptococcus suis R61 Strain

    PubMed Central

    Zhang, Anding; Wu, Jiayan; Chen, Bo; Hua, Yafeng; Yu, Jun; Chen, Huanchun; Xiao, Jingfa; Jin, Meilin

    2011-01-01

    Background Streptococcus suis infections are a serious problem for both humans and pigs worldwide. The emergence and increasing prevalence of antibiotic-resistant S. suis strains pose significant clinical and societal challenges. Results In our study, we sequenced one multi-drug-resistant S. suis strain, R61, and one S. suis strain, A7, which is fully sensitive to all tested antibiotics. Comparative genomic analysis revealed that the R61 strain is phylogenetically distinct from other S. suis strains, and the genome of R61 exhibits extreme levels of evolutionary plasticity with high levels of gene gain and loss. Our results indicate that the multi-drug-resistant strain R61 has evolved three main categories of resistance. Conclusions Comparative genomic analysis of S. suis strains with diverse drug-resistant phenotypes provided evidence that horizontal gene transfer is an important evolutionary force in shaping the genome of multi-drug-resistant strain R61. In this study, we discovered novel and previously unexamined mutations that are strong candidates for conferring drug resistance. We believe that these mutations will provide crucial clues for designing new drugs against this pathogen. In addition, our work provides a clear demonstration that the use of drugs has driven the emergence of the multi-drug-resistant strain R61. PMID:21966396

  8. Bloodstream infections caused by multi-drug resistant Proteus mirabilis: Epidemiology, risk factors and impact of multi-drug resistance.

    PubMed

    Korytny, Alexander; Riesenberg, Klaris; Saidel-Odes, Lisa; Schlaeffer, Fransisc; Borer, Abraham

    2016-01-01

    The prevalence of antimicrobial co-resistance among ESBL-producing Enterobactereaceae is extremely high in Israel. Multidrug-resistant Proteus mirabilis strains (MDR-PM), resistant to almost all antibiotic classes have been described. The aim was to determine the risk factors for bloodstream infections caused by MDR-PM and clinical outcomes. A retrospective case-control study. Adult patients with PM bacteremia during 7 years were identified retrospectively and their files reviewed for demographics, underlying diseases, Charlson Comorbidity Index, treatment and outcome. One hundred and eighty patients with PM-bloodstream infection (BSI) were included; 90 cases with MDR-PM and 90 controls with sensitive PM (S-PM). Compared to controls, cases more frequently were from nursing homes, had recurrent hospital admissions in the past year and received antibiotic therapy in the previous 3 months, were bedridden and suffered from peripheral vascular disease and peptic ulcer disease (p < 0.001). Two-thirds of the MDR-PM isolates were ESBL-producers vs 4.4% of S-PM isolates (p < 0.001, OR = 47.6, 95% CI = 15.9-142.6). In-hospital crude mortality rate of patients with MDR-PM BSI was 37.7% vs 23.3% in those with S-PM BSI (p = 0.0359, OR = 2, 95% CI = 1.4-3.81). PM bacteremia in elderly and functionally-dependent patients is likely to be caused by nearly pan-resistant PM strains in the institution; 51.8% of the patients received inappropriate empiric antibiotic treatment. The crude mortality rate of patients with MDR-PM BSI was significantly higher than that of patients with S-PM BSI.

  9. Antimicrobial resistance and serotype distribution of Streptococcus pneumoniae isolates from Crete, Greece.

    PubMed

    Maraki, S; Christidou, A; Tselentis, Y

    2001-06-01

    Susceptibility to 14 antibiotics was determined for 125 clinical isolates of Streptococcus pneumoniae collected over a 3-year period in Crete, Greece. Twenty-three isolates (18.4%) showed intermediate resistance and 15 (12%) high-level resistance to penicillin. Erythromycin, chloramphenicol, tetracycline, trimethoprim-sulphamethoxazole and sparfloxacin resistance rates were 16.8, 10.4, 19.2, 24.8 and 9.6%, respectively. Multiple resistance was observed in 22 strains. Vancomycin and levofloxacin were the most active agents tested. The most prevalent serotype among penicillin-susceptible pneumococci was 14, followed by 9, 7 and 1, while among penicillin-intermediate or -resistant strains serotype 23 was predominant followed by 19 and 9. These results show that as well as a high level of penicillin resistance in this region, some strains are also resistant to other antibiotics and may show multi-drug resistance.

  10. Identification of New Drug Targets in Multi-Drug Resistant Bacterial Infections

    DTIC Science & Technology

    2014-10-01

    Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT: A. baumannii is a gram -negative bacillus (GNB) known to cause health-care associated...24! 2 W81XWH-11-2-0218 Annual Report October 2014 Introduction& A. baumannii is a gram -negative bacillus (GNB...approach to drug target discovery in multi-drug resistant gram negative bacilli. Future Microbiology. Posters April 2014. K.M. Armbruster

  11. [Home intravenous antimicrobial therapy in multi-drug resistant microorganism infections].

    PubMed

    Pérez-López, Jordi; Pardos-Gea, José; San José Laporte, Antonio; Almirante Gragera, Benito; Marian Oltean, Dan; Vilardell Tarrés, Miquel

    2012-05-12

    Although home intravenous antimicrobial infusion therapy (HIVAIT) has proved its safety and efficacy in a great number of common infections, there are few published studies about its role in the treatment of infections caused by multi-drug resistant microorganisms. Our objectives are to study clinical and epidemiological characteristics of patients with multi-drug resistant microorganism infections treated with HIVAIT, and its usefulness in this type of infections. We analyzed all patients diagnosed of infections requiring HIVAIT and admitted to our Hospital at Home Unit (HHU) from March 2007 to February 2010. Subjects were divided into two groups: patients with multi-drug resistant microorganism infections as a study group, and the remaining patients as a control group. A total of 487 patients were included, 82 in the study group. Comorbidity and physical dependence were higher in this group than in the control group (p=0.000 and p=0.002 respectively). The majority of patients were discharged because of a satisfactory clinical evolution. However, 17 (20.7%) patients in the study group required readmission to hospital during treatment and another 22 (26.8%) were re-admitted to hospital 3 months after discharge from HHU. There were significant differences between the results from the control group in clinical readmissions. Patients with multi-drug resistant microorganism infections and HIVAIT have higher comorbidity, physical dependence, and frequency of hospital readmissions. However, HIVAIT is useful in this kind of infections if the patients are appropriately selected. Copyright © 2011 Elsevier España, S.L. All rights reserved.

  12. Genomic Analysis Reveals Multi-Drug Resistance Clusters in Group B Streptococcus CC17 Hypervirulent Isolates Causing Neonatal Invasive Disease in Southern Mainland China

    PubMed Central

    Campisi, Edmondo; Rosini, Roberto; Ji, Wenjing; Guidotti, Silvia; Rojas-López, Maricarmen; Geng, Guozhu; Deng, Qiulian; Zhong, Huamin; Wang, Weidong; Liu, Haiying; Nan, Cassandra; Margarit, Immaculada; Rinaudo, C. D.

    2016-01-01

    Neonatal invasive disease caused by group B Streptococcus (GBS) represents a significant public health care concern globally. However, data related to disease burden, serotype distribution, and molecular epidemiology in China and other Asian countries are very few and specifically relative to confined regions. The aim of this study was to investigate the genetic characteristics of GBS isolates recovered from neonates with invasive disease during 2013–2014 at Guangzhou and Changsha hospitals in southern mainland China. We assessed the capsular polysaccharide type, pilus islands (PIs) distribution and hvgA gene presence in a panel of 26 neonatal clinical isolates, of which 8 were recovered from Early Onset Disease and 18 from Late Onset Disease (LOD). Among 26 isolates examined, five serotypes were identified. Type III was the most represented (15 cases), particularly among LOD strains (n = 11), followed by types Ib (n = 5), V (n = 3), Ia (n = 2) and II (n = 1). We performed whole-genome sequencing analysis and antimicrobial susceptibility testing on the 14 serotype III isolates belonging to the hypervirulent Clonal Complex 17 (serotype III-CC17). The presence of PI-2b alone was associated with 13 out of 14 serotype III-CC17 strains. Genome analysis led us to identify two multi-drug resistance gene clusters harbored in two new versions of integrative and conjugative elements (ICEs), carrying five or eight antibiotic resistance genes, respectively. These ICEs replaced the 16 kb-locus that normally contains the PI-1 operon. All isolates harboring the identified ICEs showed multiple resistances to aminoglycoside, macrolide, and tetracycline antibiotic classes. In conclusion, we report the first whole-genome sequence analysis of 14 GBS serotype III-CC17 strains isolated in China, representing the most prevalent lineage causing neonatal invasive disease. The acquisition of newly identified ICEs conferring multiple antibiotic resistance could in part explain the spread

  13. Combined therapy for multi-drug-resistant Acinetobacter baumannii infection--is there evidence outside the laboratory?

    PubMed

    Tuon, Felipe F; Rocha, Jaime L; Merlini, Alexandre B

    2015-09-01

    Acinetobacter are among the most common bacteria isolated in hospital infections, especially in developing countries. Multi-drug, extended-drug or pan-drug resistance makes treatment a real medical challenge. In the present review, the authors describe clinical and experimental data in order to present different current and potential future strategies to treat infections caused by multi-drug-resistant Acinetobacter. The therapeutic options for carbapenem-resistant Acinetobacter are scarce, and the current options have poor pharmacokinetic aspects and several side effects. Combined therapy has been an alternative for multi-drug-resistant Acinetobacter. However, this issue is always controversial. In some studies combined therapy has shown superiority for some strains of Acinetobacter in animal models and in vitro studies. However, studies with humans are scarce and too poor quality to suggest the best approach for the treatment of infections caused by multi-drug-resistant Acinetobacter baumannii.

  14. [Diagnostic accuracy of three technologies for the diagnosis of multi-drug resistant tuberculosis].

    PubMed

    Alvis-Zakzuk, Nelson José; Carrasquilla, María De Los Ángeles; Gómez, Verónica Jhajaira; Robledo, Jaime; Alvis-Guzmán, Nelson Rafael; Hernández, José Mauricio

    2017-09-01

    Multi-drug resistant (MDR-TB) and extensively drug-resistant (XDR-TB) tuberculoses are a global public health problem. Their timely detection might reduce the burden of the disease and the economic impact on health systems worldwide. To conduct a literature review of the diagnostic accuracy of three molecular tests to detect multi-drug resistant and extensively drug-resistant tuberculoses. A systematic literature review following Cochrane methodology was carried out to study the diagnostic accuracy of three molecular tests to detect MDR-TB and XDR-TB in previous studies among immunocompetent population. Articles indexed in Medline and Embase were reviewed starting in 2007. Diagnostic accuracy was reported by sensitivity, specificity, and positive and negative predictive values of each test. In total, 8, 12 and 13 studies were included to assess the diagnostic accuracy of GeneXpert MTB/RIF®, GenoType MTBDRplus® and GenoType MTBDRsl®, respectively. The specificity of GeneXpert MTB/RIF® ranged between 91 and 100%, and its sensitivity between 33.3 and 100%. The sensitivity of GenoType® MTBDRplus® ranged between 88 and 100%. The sensitivity and specificity of GenoType MTBDRsl® to evaluate drug resistance ranged between 56 and 100% and 21 and 100%, respectively. The three diagnostic tests evaluated have shown an adequate diagnostic accuracy to detect MDR and XDR tuberculoses.

  15. Efficacy of fresh Aloe vera gel against multi-drug resistant bacteria in infected leg ulcers.

    PubMed

    Banu, Asima; Sathyanarayana, Bc; Chattannavar, Goura

    2012-01-01

    Infected leg ulcers are major health problems resulting in morbidity and disability and are usually chronic and refractory to antimicrobial treatment. The present study is aimed at determining the bacteria involved in leg ulcers and their resistance patterns to commonly used antibiotics as well as to determine whether Aloe Vera has antibacterial activity against multi-drug resistant organisms and promotes wound healing. A total of 30 cases with leg ulcers infected with multi-drug resistant organisms were treated with topical aloe vera gel and 30 age and sex-matched controls were treated with topical antibiotics. Culture and sensitivity was done from the wounds on alternate days and the ulcer was clinically and microbiologically assessed after 10 days. The results were compiled and statistically analysed. Cultures of the study group who were using aloe vera dressings showed no growth by the fifth day in 10 (33.3%) cases, seventh day in another 16 (53.3%) and ninth day in two of the remaining four cases (6.7%) while in two (6.7%) cases there was no decrease in the bacterial count. This means that of the 30 cases, 28 showed no growth by the end of 11 days while two cases showed no decrease in bacterial count. Growth of bacteria in study group is decreased from 100% (30 cases) to 6.7% (2 cases) by day 11 with P<0.001. Cultures of the control group did not show any decrease in the bacterial growth by day 11. Aloe vera gel preparation is cheap and was effective even against multi-drug resistant organisms as compared to the routinely used topical anti-microbial agents.

  16. Anti-mycobacterial activity of garlic (Allium sativum) against multi-drug resistant and non-multi-drug resistant mycobacterium tuberculosis.

    PubMed

    Hannan, Abdul; Ikram Ullah, Muhammad; Usman, Muhammad; Hussain, Shahid; Absar, Muhammad; Javed, Khursheed

    2011-01-01

    Emergence of multi-drug resistant (MDR) and extensively drug resistant (XDR) TB throughout the developing world is very disturbing in the present scenario of TB management. There is a fundamental need to explore alternative anti-TB agents. Hence natural plants should be investigated to understand their antimicrobial properties and safety. Garlic (Allium sativum) is one of natural plant which possesses variety of biological properties like anti-tumor, anti-hyperlipedemic and anti-microbial etc. The present study was evaluated for anti-bacterial activity of garlic against non-MDR and MDR isolates of M. tuberculosis. A total of 20 clinical isolates of MTB including 15 MDR and 5 non-MDR were investigated. Ethanolic extract of garlic was prepared by maceration method. Minimum inhibitory concentration (MIC) was performed by using 7H9 middle brook broth dilution technique. MIC of garlic extract was ranged from 1 to 3 mg/ml; showing inhibitory effects of garlic against both non-MDR and MDR M. tuberculosis isolates. Alternate medicine practices with plant extracts including garlic should be considered to decrease the burden of drug resistance and cost in the management of diseases. The use of garlic against MDR-TB may be of great importance regarding public health.

  17. Genetic characteristics of one highly multi-drug-resistant strain of Klebsiella ozaenae.

    PubMed

    Huang, Jiansheng; Li, Xirong; Zhu, Naishuo; Li, Guoxiong

    2012-09-01

    One highly multi-drug-resistant, mucus-producing and foul-smelling strain of Klebsiella ozaenae was isolated from a patient in the ICU of a Chinese tertiary hospital. MICs of several clinical antimicrobials against the strain were obtained using the Vitek-2 Compact System with AST-GN13 cards and resistance genes were evaluated by PCR and gene sequencing. The strain was resistant to most of the β-lactams and quinolones tested and carried several antibiotic resistance genes, including bla(KPC-2), bla(TEM-98), bla(CTX-M-3), bla(SHV-26) and qnrS. To our knowledge, this is the first report of β-lactam and quinolone resistance genes co-existing in a K. ozaenae strain in China.

  18. Multi drug resistance and Extended Spectrum Beta Lactamases in clinical isolates of Shigella: A study from New Delhi, India.

    PubMed

    Aggarwal, Prabhav; Uppal, Beena; Ghosh, Roumi; Krishna Prakash, S; Chakravarti, Anita; Jha, Arun Kumar; Rajeshwari, Krishnan

    2016-01-01

    Shigella is an important cause of gastroenteritis in local Indian population, as well as of traveler's diarrhea in the international visitors to India. These patients often require appropriate antimicrobial therapy; however, rapid development of antimicrobial resistance poses a major hurdle in achieving this goal. A prospective study was conducted during 2009-12 in New Delhi, India, including 6339 stool samples from gastroenteritis patients. 121 Shigella strains were identified on the basis of colony morphology, biochemical reactions, serotyping and ipaH gene based PCR. Antimicrobial susceptibility testing by disc diffusion, MIC determination by Vitek(®) 2 and phenotypic tests for ESBL/AmpC production were done. Nineteen percent strains (23/121) were found to be resistant to third generation cephalosporins and all were phenotypically confirmed to be ESBL producers; one strain was positive for AmpC. ESBL producing strains were also found to be significantly more resistant (p < 0.05) to several other antimicrobials agents in comparison to ESBL non-producers, [ampicillin (100% vs. 62.2%), ampicillin/sulbactam (100% vs. 30.6%), cotrimoxazole (100% vs. 77.6%), ciprofloxacin (87.0% vs. 49.0%), ofloxacin (87.0% vs. 52.0%) and gentamicin (30.4% vs. 7.1%)]. Multidrug resistance was seen in 76% strains. Inappropriate use of antimicrobial agents puts high selection pressure on the higher-end antibiotics. Multi-drug resistance and high rates of ESBL production by Shigella is a matter of concern for the local population as well as international travelers. Therefore, better national level antimicrobial management programs are the priority needs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Multi-drug resistant tuberculosis in Chuuk State Federated States of Micronesia, 2008-2009.

    PubMed

    Fred, D; Desai, M; Song, R; Bamrah, S; Pavlin, B I; Heetderks, A; Ekiek, M J

    2010-04-01

    Multi-drug resistant tuberculosis (MDR TB) is a growing public health concern, particularly for the Pacific, where rates of tuberculosis infection are extremely high. In May 2008, a cluster of patients with MDR TB were identified in Chuuk State, Federated States of Micronesia. A multi-agency investigation led to the eventual discovery of 21 cases, and over 100 latent TB infections. Incomplete implementation of Directly Observed Therapy (DOT) and contact investigation were major contributors to the outbreak. The problem of MDR TB in Chuuk was controlled only after a concerted effort on the part of multiple agencies coupled with the highest level of political commitment.

  20. Overcoming drug resistance in multi-drug resistant cancers and microorganisms: a conceptual framework.

    PubMed

    Avner, Benjamin S; Fialho, Arsenio M; Chakrabarty, Ananda M

    2012-01-01

    Resistance development against multiple drugs is a common feature among many pathogens--including bacteria such as Pseudomonas aeruginosa, viruses, and parasites--and also among cancers. The reasons are two-fold. Most commonly-used rationally-designed small molecule drugs or monoclonal antibodies, as well as antibiotics, strongly inhibit a key single step in the growth and proliferation of the pathogen or cancer cells. The disease agents quickly change or switch off this single target, or activate the efflux mechanisms to pump out the drug, thereby becoming resistant to the drug. A second problem is the way drugs are designed. The pharmaceutical industry chooses to use, by high-throughput screening, compounds that are maximally inhibitory to the key single step in the growth of the pathogen or cancer, thereby promoting selective pressure. An ideal drug would be one that inhibits multiple steps in the disease progression pathways with less stringency in these steps. Low levels of inhibition at multiple steps provide cumulative strong inhibitory effect, but little incentives or ability on the part of the pathogen/cancer to develop resistance. Such intelligent drug design involving multiple less stringent inhibitory steps is beyond the scope of the drug industry and requires evolutionary wisdom commonly possessed by bacteria. This review surveys assessments of the current clinical situation with regard to drug resistance in P. aeruginosa, and examines tools currently employed to limit this trend. We then provide a conceptual framework in which we explore the similarities between multi-drug resistance in pathogens and in cancers. We summarize promising work on anti-cancer drugs derived from the evolutionary wisdom of bacteria such as P. aeruginosa, and how such strategies can be the basis for how to look for candidate protein/peptide antibiotic drugs from bioengineered bugs. Such multi-domain proteins, unlike diffusible antibiotics, are not diffusible because of their

  1. Antitubercular and antibacterial activity of quinonoid natural products against multi-drug resistant clinical isolates.

    PubMed

    Dey, Diganta; Ray, Ratnamala; Hazra, Banasri

    2014-07-01

    Multi-drug resistant Mycobacterium tuberculosis and other bacterial pathogens represent a major threat to human health. In view of the critical need to augment the current drug regime, we have investigated therapeutic potential of five quinonoids, viz. emodin, diospyrin, plumbagin, menadione and thymoquinone, derived from natural products. The antimicrobial activity of quinonoids was evaluated against a broad panel of multi-drug and extensively drug-resistant tuberculosis (M/XDR-TB) strains, rapid growing mycobacteria and other bacterial isolates, some of which were producers of β-lactamase, Extended-spectrum β-lactamase (ESBL), AmpC β-lactamase, metallo-beta-lactamase (MBL) enzymes, as well as their drug-sensitive ATCC counterparts. All the tested quinones exhibited antimycobacterial and broad spectrum antibacterial activity, particularly against M. tuberculosis (lowest MIC 0.25 µg/mL) and Gram-positive bacteria (lowest MIC <4 µg/mL) of clinical origin. The order of antitubercular activity of the tested quinonoids was plumbagin > emodin ~ menadione ~ thymoquinone > diospyrin, whereas their antibacterial efficacy was plumbagin > menadione ~ thymoquinone > diospyrin > emodin. Furthermore, this is the first evaluation performed on these quinonoids against a broad panel of drug-resistant and drug-sensitive clinical isolates, to the best of our knowledge.

  2. [Establishment and biological characteristics of a multi-drug resistant cell line A549/Gem.].

    PubMed

    Wang, Weixia; Liu, Xiaoqing; Liu, Guangxian; Lin, Li; Zheng, Xiaoling; Zhu, Yunfeng; Li, Xiaobing

    2008-02-20

    Multi-drug resistance is one of the most important reason why the survival time of non-small cell lung cancer patients is so short. The aim of this study is to establish multi-drug resistant cell line A549/Gem and discuss its biological characters so as to elaborate the possible mechanisms of gemcitabine resistance. Human gemcitabine-resistant non-small cell lung cancer cell line A549/Gem was established by repeated clinical serous peak concentration then low but gradually increasing concentration of gemcitabine from its parental cell human lung adenocarcinoma cell line A549 which is sensitive to gemcitabine. During the course of inducement, monitored its morphology, checked its resistance index and resistant pedigree by MTT method, gathered its growth curve and calculated its doubling time, examined its DNA contents and cell cycles by flow cytometry; at the same time, measured its expression of P53, EGFR, c-erb-B-2, PTEN, PCNA, c-myc, VEGF, MDR-1, Bcl-2, nm23, MMP-9, TIMP-1, CD44v6 Proteins, and RRM1 mRNA. The resistance index of A549/Gem' to gemcitabine was 163.228, and the cell line also exhibited cross-resistance to vinorelbine, taxotere, fluorouraci, etoposide and cisplatin, but kept sensitivity to paclitaxol and oxaliplatin. The doubling time of it was shorter and figures in G0-G1 phase were increased than A549. Compared with A549, A549/Gem' achieved EGFR and c-myc protein expression, nm23 protein expression enhanced, p53, Cerb-B-2 and bcl-2 protein expression reduced, PTEN, PCNA and MDR-1 protein expression vanished, but that of MMP-9, VEGF, CD44v6 and TIMP-1 protein changed trivially. Meanwhile, the expression of RRM1 mRNA was augmented markedly. The resistance index of A549/Gem to gemcitabine was 129.783, and the cell line also held cross-resistance to vinorelbine, taxotere, etoposide, cisplatin and sensitivity to paclitaxol. But the resistance to fluorouracil and sensitivity to oxaliplatin vanished. And the expression of RRM1 mRNA decreased visibly. The

  3. Molecular serotyping and antimicrobial resistance profiles of Actinobacillus pleuropneumoniae isolated from pigs in South Korea.

    PubMed

    Kim, Boram; Hur, Jin; Lee, Ji Yeong; Choi, Yoonyoung; Lee, John Hwa

    2016-09-01

    Actinobacillus pleuropneumoniae (APP) causes porcine pleuropneumonia (PP). Serotypes and antimicrobial resistance patterns in APP isolates from pigs in Korea were examined. Sixty-five APP isolates were genetically serotyped using standard and multiplex PCR (polymerase chain reaction). Antimicrobial susceptibilities were tested using the standardized disk-agar method. PCR was used to detect β-lactam, gentamicin and tetracycline-resistance genes. The random amplified polymorphic DNA (RAPD) patterns were determined by PCR. Korean pigs predominantly carried APP serotypes 1 and 5. Among 65 isolates, one isolate was sensitive to all 12 antimicrobials tested in this study. Sixty-two isolates was resistant to tetracycline and 53 isolates carried one or five genes including tet(B), tet(A), tet(H), tet(M)/tet(O), tet(C), tet(G) and/or tet(L)-1 markers. Among 64 strains, 9% and 26.6% were resistance to 10 and three or more antimicrobials, respectively. Thirteen different antimicrobial resistance patterns were observed and RAPD analysis revealed a separation of the isolates into two clusters: cluster II (6 strains resistant to 10 antimicrobials) and cluster I (the other 59 strains). Results show that APP serotypes 1 and 5 are the most common in Korea, and multi-drug resistant strains are prevalent. RAPD analysis demonstrated that six isolates resistant to 10 antimicrobials belonged to the same cluster.

  4. Honeydew honey as a potent antibacterial agent in eradication of multi-drug resistant Stenotrophomonas maltophilia isolates from cancer patients.

    PubMed

    Majtan, Juraj; Majtanova, Lubica; Bohova, Jana; Majtan, Viktor

    2011-04-01

    Multi-drug resistance in nosocomial pathogens is a continually evolving and alarming problem in health care units. Since ancient times, honey has been used successfully for the treatment of a broad spectrum of infections with no risk of resistance development. This study investigated the antibacterial activity of two natural honeys, namely honeydew and manuka, against 20 nosocomial multi-drug resistant Stenotrophomonas maltophilia (S. maltophilia) isolates from cancer patients. An antibiotic susceptibility test was carried out using the disk diffusion method with 20 antibiotic disks. The antibacterial activity of honey was determined using a broth dilution method. The concentration of honey used in the study was within the range of 3.75% to 25% (w/v). All 20 clinical isolates were multi-drug resistant against 11 to 19 antibiotics. The MICs for honeydew honey ranged from 6.25% to 17.5%, while those for active manuka honey ranged from 7.5% to 22.5%. Honeydew honey had lower MICs than manuka honey against 16 of the tested isolates. This study showed that Slovak honeydew honey has exceptional antibacterial activity against multi-drug resistant S. maltophilia isolates and was more efficient than manuka honey (UMF 15+). Honeydew honey with strong antibacterial activity could be used as a potential agent to eradicate multi-drug resistant clinical isolates.

  5. Existence of multiple-stable equilibria for a multi-drug-resistant model of Mycobacterium tuberculosis.

    PubMed

    Gumel, Abba B; Song, Baojun

    2008-07-01

    The resurgence of multi-drug-resistant tuberculosis in some parts of Europe and North America calls for a mathematical study to assess the impact of the emergence and spread of such strain on the global effort to effectively control the burden of tuberculosis. This paper presents a deterministic compartmental model for the transmission dynamics of two strains of tuberculosis, a drug-sensitive (wild) one and a multi-drug-resistant strain. The model allows for the assessment of the treatment of people infected with the wild strain. The qualitative analysis of the model reveals the following. The model has a disease-free equilibrium, which is locally asymptotically stable if a certain threshold, known as the effective reproduction number, is less than unity. Further, the model undergoes a backward bifurcation, where the disease-free equilibrium coexists with a stable endemic equilibrium. One of the main novelties of this study is the numerical illustration of tri-stable equilibria, where the disease-free equilibrium coexists with two stable endemic equilibrium when the aforementioned threshold is less than unity, and a bi-stable setup, involving two stable endemic equilibria, when the effective reproduction number is greater than one. This, to our knowledge, is the first time such dynamical features have been observed in TB dynamics. Finally, it is shown that the backward bifurcation phenomenon in this model arises due to the exogenous re-infection property of tuberculosis.

  6. Antibiotic Restriction Might Facilitate the Emergence of Multi-drug Resistance.

    PubMed

    Obolski, Uri; Stein, Gideon Y; Hadany, Lilach

    2015-06-01

    High antibiotic resistance frequencies have become a major public health issue. The decrease in new antibiotics' production, combined with increasing frequencies of multi-drug resistant (MDR) bacteria, cause substantial limitations in treatment options for some bacterial infections. To diminish overall resistance, and especially the occurrence of bacteria that are resistant to all antibiotics, certain drugs are deliberately scarcely used--mainly when other options are exhausted. We use a mathematical model to explore the efficiency of such antibiotic restrictions. We assume two commonly used drugs and one restricted drug. The model is examined for the mixing strategy of antibiotic prescription, in which one of the drugs is randomly assigned to each incoming patient. Data obtained from Rabin medical center, Israel, is used to estimate realistic single and double antibiotic resistance frequencies in incoming patients. We find that broad usage of the hitherto restricted drug can reduce the number of incorrectly treated patients, and reduce the spread of bacteria resistant to both common antibiotics. Such double resistant infections are often eventually treated with the restricted drug, and therefore are prone to become resistant to all three antibiotics. Thus, counterintuitively, a broader usage of a formerly restricted drug can sometimes lead to a decrease in the emergence of bacteria resistant to all drugs. We recommend re-examining restriction of specific drugs, when multiple resistance to the relevant alternative drugs already exists.

  7. Antibiotic Restriction Might Facilitate the Emergence of Multi-drug Resistance

    PubMed Central

    Obolski, Uri; Stein, Gideon Y.; Hadany, Lilach

    2015-01-01

    High antibiotic resistance frequencies have become a major public health issue. The decrease in new antibiotics' production, combined with increasing frequencies of multi-drug resistant (MDR) bacteria, cause substantial limitations in treatment options for some bacterial infections. To diminish overall resistance, and especially the occurrence of bacteria that are resistant to all antibiotics, certain drugs are deliberately scarcely used—mainly when other options are exhausted. We use a mathematical model to explore the efficiency of such antibiotic restrictions. We assume two commonly used drugs and one restricted drug. The model is examined for the mixing strategy of antibiotic prescription, in which one of the drugs is randomly assigned to each incoming patient. Data obtained from Rabin medical center, Israel, is used to estimate realistic single and double antibiotic resistance frequencies in incoming patients. We find that broad usage of the hitherto restricted drug can reduce the number of incorrectly treated patients, and reduce the spread of bacteria resistant to both common antibiotics. Such double resistant infections are often eventually treated with the restricted drug, and therefore are prone to become resistant to all three antibiotics. Thus, counterintuitively, a broader usage of a formerly restricted drug can sometimes lead to a decrease in the emergence of bacteria resistant to all drugs. We recommend re-examining restriction of specific drugs, when multiple resistance to the relevant alternative drugs already exists. PMID:26110266

  8. Antiplasmid activity of 1'-acetoxychavicol acetate from Alpinia galanga against multi-drug resistant bacteria.

    PubMed

    Latha, C; Shriram, Varsha D; Jahagirdar, Sheetal S; Dhakephalkar, Prashant K; Rojatkar, Supada R

    2009-06-25

    Alpinia galanga (L.) Swartz is traditionally used in the treatment of various ailments across India, China, and Southeast Asian countries. In India it is a reputed drug in indigenous system of medicine and largely used as antibacterial and antiseptic. In southern India the rhizomes has been used as a domestic remedy against bacterial infections. To identify a potential antiplasmid compound from Alpinia galanga against multi-drug resistant bacteria. The crude rhizome extract of Alpinia galanga was prepared in acetone. Antibacterial activity was checked by MIC and antiplasmid activity was checked by SIC. The principal compound responsible for the antiplasmid activity, in the crude extract, was identified by bioassay guided fractionation using hexane-acetone. Antibiotic resistance profile of plasmid harboring strains and plasmid cured strains was determined by disc diffusion method. The crude acetone extract of the rhizomes of Alpinia galanga exhibited antiplasmid activity against Salmonella typhi, Escherichia coli and vancomycin resistant Enterococcus faecalis with an efficiency of 92%, 82% and 8% respectively at 400 microg/ml SIC. The principal compound responsible for the activity was identified as 1'-acetoxychavicol acetate. 1'-Acetoxychavicol acetate demonstrated the ability to cure plasmid encoded antibiotic resistance in various multi-drug resistant bacterial strains of clinical isolates such as Enterococcus faecalis, Salmonella typhi, Pseudomonas aeruginosa, Escherichia coli and Bacillus cereus with curing efficiency of 66%, 75%, 70%, 32% and 6% respectively at SIC of 400-800 microg/ml. 1'-Acetoxychavicol acetate mediated R-plasmid curing significantly reduced the minimal inhibitory concentration of antibiotics required to inhibit growth of bacteria, thus making the antibiotic treatment more effective.

  9. Detection of multi-drug resistant Escherichia coli in the urban waterways of Milwaukee, WI

    PubMed Central

    Kappell, Anthony D.; DeNies, Maxwell S.; Ahuja, Neha H.; Ledeboer, Nathan A.; Newton, Ryan J.; Hristova, Krassimira R.

    2015-01-01

    Urban waterways represent a natural reservoir of antibiotic resistance which may provide a source of transferable genetic elements to human commensal bacteria and pathogens. The objective of this study was to evaluate antibiotic resistance of Escherichia coli isolated from the urban waterways of Milwaukee, WI compared to those from Milwaukee sewage and a clinical setting in Milwaukee. Antibiotics covering 10 different families were utilized to determine the phenotypic antibiotic resistance for all 259 E. coli isolates. All obtained isolates were determined to be multi-drug resistant. The E. coli isolates were also screened for the presence of the genetic determinants of resistance including ermB (macrolide resistance), tet(M) (tetracycline resistance), and β-lactamases (blaOXA, blaSHV, and blaPSE). E. coli from urban waterways showed a greater incidence of antibiotic resistance to 8 of 17 antibiotics tested compared to human derived sources. These E. coli isolates also demonstrated a greater incidence of resistance to higher numbers of antibiotics compared to the human derived isolates. The urban waterways demonstrated a greater abundance of isolates with co-occurrence of antibiotic resistance than human derived sources. When screened for five different antibiotic resistance genes conferring macrolide, tetracycline, and β-lactam resistance, clinical E. coli isolates were more likely to harbor ermB and blaOXA than isolates from urban waterway. These results indicate that Milwaukee’s urban waterways may select or allow for a greater incidence of multiple antibiotic resistance organisms and likely harbor a different antibiotic resistance gene pool than clinical sources. The implications of this study are significant to understanding the presence of resistance in urban freshwater environments by supporting the idea that sediment from urban waterways serves as a reservoir of antibiotic resistance. PMID:25972844

  10. Detection of multi-drug resistant Escherichia coli in the urban waterways of Milwaukee, WI.

    PubMed

    Kappell, Anthony D; DeNies, Maxwell S; Ahuja, Neha H; Ledeboer, Nathan A; Newton, Ryan J; Hristova, Krassimira R

    2015-01-01

    Urban waterways represent a natural reservoir of antibiotic resistance which may provide a source of transferable genetic elements to human commensal bacteria and pathogens. The objective of this study was to evaluate antibiotic resistance of Escherichia coli isolated from the urban waterways of Milwaukee, WI compared to those from Milwaukee sewage and a clinical setting in Milwaukee. Antibiotics covering 10 different families were utilized to determine the phenotypic antibiotic resistance for all 259 E. coli isolates. All obtained isolates were determined to be multi-drug resistant. The E. coli isolates were also screened for the presence of the genetic determinants of resistance including ermB (macrolide resistance), tet(M) (tetracycline resistance), and β-lactamases (bla OXA, bla SHV, and bla PSE). E. coli from urban waterways showed a greater incidence of antibiotic resistance to 8 of 17 antibiotics tested compared to human derived sources. These E. coli isolates also demonstrated a greater incidence of resistance to higher numbers of antibiotics compared to the human derived isolates. The urban waterways demonstrated a greater abundance of isolates with co-occurrence of antibiotic resistance than human derived sources. When screened for five different antibiotic resistance genes conferring macrolide, tetracycline, and β-lactam resistance, clinical E. coli isolates were more likely to harbor ermB and bla OXA than isolates from urban waterway. These results indicate that Milwaukee's urban waterways may select or allow for a greater incidence of multiple antibiotic resistance organisms and likely harbor a different antibiotic resistance gene pool than clinical sources. The implications of this study are significant to understanding the presence of resistance in urban freshwater environments by supporting the idea that sediment from urban waterways serves as a reservoir of antibiotic resistance.

  11. Control of a Multi-Drug-Resistant Acinetobacter baumannii Outbreak after Orthopedics Department Relocation

    PubMed Central

    Gogou, Vasiliki; Meletis, Georgios; Tsitouras, Dimosthenis

    2013-01-01

    Acinetobacter baumannii clinical isolates have the ability to survive in the hospital niche for prolonged time periods and to develop resistance against multiple antimicrobial agents. Therefore, A. baumannii has emerged as an important cause of nosocomial outbreaks worldwide, especially in critical-care environments such as intensive care units. In the present communication, we report a multi-drug-resistant A. baumannii outbreak that occurred in an orthopedics department in Greece after the admission of a patient previously hospitalized in the intensive care unit of a Greek tertiary care hospital. Despite the implementation of infection control measures, 29 patients were infected, significantly raising their hospitalization periods and treatment costs. Interestingly, the outbreak was put under control after the department’s previously programmed relocation. PMID:27694769

  12. Population genetics of multi-drug resistant (MDR) IncA/C plasmid in Salmonella enterica isolated from animals

    USDA-ARS?s Scientific Manuscript database

    Food animals harboring Multi-Drug Resistant (MDR) Salmonella enterica are a potential source for acquisition of zoonotic pathogens. Plasmids (small, self-replicating, extra-chromosomal DNA) are often associated with antimicrobial resistance and plasmids carrying MDR genes have been found to be a maj...

  13. Molecular Epidemiology of Multi-Drug Resistant Acinetobacter baumannii Isolated in Shandong, China

    PubMed Central

    Jiang, Meijie; Liu, Lijuan; Ma, Yunhua; Zhang, Zhijun; Li, Ning; Zhang, Fusen; Zhao, Shuping

    2016-01-01

    Acinetobacter baumannii is an emerging nosocomial pathogen prevalent in hospitals worldwide. In order to understand the molecular epidemiology of multi-drug resistant (MDR) A. baumannii, we investigated the genotypes of A. baumannii isolated from 10 hospitals in Shandong, China, from August 2013 to December 2013, by pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Antimicrobial resistance genes were analyzed by PCR and DNA sequencing. By PFGE analysis, we discovered 11 PFGE types in these 10 hospitals. By MLST, we assigned these isolates to 12 sequence types (STs), 10 of which belong to the cloning complex CC92, including the prevalent ST369, ST208, ST195, and ST368. Two new STs, namely ST794 and ST809, were detected only in one hospital. All isolates of the MDR A. baumannii were resistant to carbapenem, except 2 isolates, which did not express the blaOXA-23 carbapenemase gene, indicating blaOXA-23 is the major player for carbapenem resistance. We also discovered armA is likely to be responsible for amikacin resistance, and may play a role in gentamicin and tobramycin resistance. aac(3)-I is another gene responsible for gentamicin and tobramycin resistance. In summary, we discovered that the majority of the isolates in Shandong, China, were the STs belonging to the CC92. Besides, two new STs were detected in one hospital. These new STs should be further investigated for prevention of outbreaks caused by A. baumannii. PMID:27818659

  14. Bacterial recombination promotes the evolution of multi-drug-resistance in functionally diverse populations

    PubMed Central

    Perron, Gabriel G.; Lee, Alexander E. G.; Wang, Yun; Huang, Wei E.; Barraclough, Timothy G.

    2012-01-01

    Bacterial recombination is believed to be a major factor explaining the prevalence of multi-drug-resistance (MDR) among pathogenic bacteria. Despite extensive evidence for exchange of resistance genes from retrospective sequence analyses, experimental evidence for the evolutionary benefits of bacterial recombination is scarce. We compared the evolution of MDR between populations of Acinetobacter baylyi in which we manipulated both the recombination rate and the initial diversity of strains with resistance to single drugs. In populations lacking recombination, the initial presence of multiple strains resistant to different antibiotics inhibits the evolution of MDR. However, in populations with recombination, the inhibitory effect of standing diversity is alleviated and MDR evolves rapidly. Moreover, only the presence of DNA harbouring resistance genes promotes the evolution of resistance, ruling out other proposed benefits for recombination. Together, these results provide direct evidence for the fitness benefits of bacterial recombination and show that this occurs by mitigation of functional interference between genotypes resistant to single antibiotics. Although analogous to previously described mechanisms of clonal interference among alternative beneficial mutations, our results actually highlight a different mechanism by which interactions among co-occurring strains determine the benefits of recombination for bacterial evolution. PMID:22048956

  15. Emergence of multi drug resistance among soil bacteria exposing to insecticides.

    PubMed

    Rangasamy, Kirubakaran; Athiappan, Murugan; Devarajan, Natarajan; Parray, Javid A

    2017-04-01

    Impacts of pesticide exposure on the soil microbial flora and cross resistance to antibiotics have not been well documented. Development of antibiotic resistance is a common issue among soil bacteria which are exposing to pesticides continuously at sub-lethal concentration. The present study was focused to evaluate the correlation between pesticide exposures and evolution of multi drug resistance among isolates collected from soil applied with insecticides. Twenty five insecticide (Monochrotophos) degrading bacteria were isolated from contaminated agricultural soil. The bacterial isolates Bacillus Sps, Bacillus cereus, Bacillus firmus and Bacillus thuringiensis were found to be resistant against chloramphenical, monochrotophos, ampicillin, cefotaxime, streptomycin and tetracycline antibiotics used. Involvement of plasmid in drug as well as insecticide resistant was confirmed through plasmid curing among selected bacterial strains. Bacillus Sps (MK-07), Bacillus cereus (MK-11), Bacillus firmus (MK-13) and Bacillus thuringiensis (MK-24) lost their resistant against insecticides and antibiotics once after removal of plasmid by exposing to 2% sodium dodecyl sulphate. The plasmid was transformed back to bacteria which produced similar derivatives when cultured in Minimal Salt medium (pH 7.0) supplemented with 0.4% of insecticide. Homology modeling was used to prove that organophosphorus hydrolase and able to metabolize all the antibiotics showed positive interaction with high docking score. The present study revealed that persistent of insecticides in the agricultural soil may lead to increasing development of multidrug resistance among soil bacteria. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Prevalence and risk factors for carriage of multi-drug resistant Staphylococci in healthy cats and dogs.

    PubMed

    Gandolfi-Decristophoris, Paola; Regula, Gertraud; Petrini, Orlando; Zinsstag, Jakob; Schelling, Esther

    2013-01-01

    We investigated the distribution of commensal staphylococcal species and determined the prevalence of multi-drug resistance in healthy cats and dogs. Risk factors associated with the carriage of multi-drug resistant strains were explored. Isolates from 256 dogs and 277 cats were identified at the species level using matrix-assisted laser desorption ionisation-time of flight mass spectrometry. The diversity of coagulase-negative Staphylococci (CNS) was high, with 22 species in dogs and 24 in cats. Multi-drug resistance was frequent (17%) and not always associated with the presence of the mecA gene. A stay in a veterinary clinic in the last year was associated with an increased risk of colonisation by multi-drug resistant Staphylococci (OR = 2.4, 95% CI: 1.1~5.2, p value LRT = 0.04). When identifying efficient control strategies against antibiotic resistance, the presence of mechanisms other than methicillin resistance and the possible role of CNS in the spread of resistance determinants should be considered.

  17. Molecular approaches for detection of the multi-drug resistant tuberculosis (MDR-TB) in Bangladesh.

    PubMed

    Aurin, Tafsina Haque; Munshi, Saurab Kishore; Kamal, S M Mostofa; Rahman, Md Mostafizur; Hossain, Md Shamim; Marma, Thaythayhla; Rahman, Farjana; Noor, Rashed

    2014-01-01

    The principal obstacles in the treatment of tuberculosis (TB) are delayed and inaccurate diagnosis which often leads to the onset of the drug resistant TB cases. To avail the appropriate treatment of the patients and to hinder the transmission of drug-resistant TB, accurate and rapid detection of resistant isolates is critical. Present study was designed to demonstrate the efficacy of molecular techniques inclusive of line probe assay (LPA) and GeneXpert MTB/RIF methods for the detection of multi-drug resistant (MDR) TB. Sputum samples from 300 different categories of treated and new TB cases were tested for the detection of possible mutation in the resistance specific genes (rpoB, inhA and katG) through Genotype MTBDRplus assay or LPA and GeneXpert MTB/RIF tests. Culture based conventional drug susceptibility test (DST) was also carried out to measure the efficacy of the molecular methods employed. Among 300 samples, 191 (63.7%) and 193 (64.3%) cases were found to be resistant against rifampicin in LPA and GeneXpert methods, respectively; while 189 (63%) cases of rifampicin resistance were detected by conventional DST methods. On the other hand, 196 (65.3%) and 191 (63.7%) isolates showed isoniazid resistance as detected by LPA and conventional drug susceptibility test (DST), respectively. Among the drug resistant isolates (collectively 198 in LPA and 193 in conventional DST), 189 (95.6%) and 187 (96.9%) were considered to be MDR as examined by LPA and conventional DST, respectively. Category-II and -IV patients encountered higher frequency of drug resistance compared to those from category-I and new cases. Considering the higher sensitivity, specificity and accuracy along with the required time to results significantly shorter, our study supports the adoption of LPA and GeneXpert assay as efficient tools in detecting drug resistant TB in Bangladesh.

  18. Persistence of Multi-Drug Resistance Plasmids in Sterile Water under Very Low Concentrations of Tetracycline

    PubMed Central

    Bien, Thi Lan Thanh; Sato-Takabe, Yuki; Ogo, Mitsuko; Usui, Masaru; Suzuki, Satoru

    2015-01-01

    The persistence of the multi-drug resistance plasmids pAQU1 and IncFIB was examined in bacterial populations under very low selective pressure. We herein demonstrated that these plasmids stably remained not only in the original host, but also in a transconjugant, even after being in a non-culturable state. In seawater microcosms containing Photobacterium damselae 04Ya311 possessing pAQU1, no significant loss of pAQU1 was observed during a 30-d starvation period. The copy numbers of pAQU1 and IncFIB in E. coli were constant. The results of the present study suggest that these plasmids have the ability to remain among various bacteria under oligotrophic conditions with low antibiotic selection pressure. PMID:26639579

  19. Multi-drug-resistant hypertension caused by severe aortic coarctation presenting in late adulthood.

    PubMed

    Meller, Stephanie M; Fahey, John T; Setaro, John F; Forrest, John K

    2015-04-01

    Aortic coarctation, a congenital narrowing in the region of the ligamentum arteriosium, is a rare etiology for multi-drug-resistant hypertension in adulthood; however, advances in stenting modalities may offer long-term improvements in morbidity and possibly even cure. We report on a female patient in her late 50s presenting with refractory hypertension and severely elevated renin levels, ultimately diagnosed with aortic coarctation and treated with percutaneous stent implantation, which resulted in successful blood pressure control with verapamil monotherapy. This case highlights the efficacy of endovascular stent implantation for the treatment of coarctation and the need for clinicians to consider this disease entity in the differential diagnosis of refractory hypertension even in late adulthood.

  20. Circumvention of multi-drug resistance of cancer cells by Chinese herbal medicines

    PubMed Central

    2010-01-01

    Multi-drug resistance (MDR) of cancer cells severely limits therapeutic outcomes. A proposed mechanism for MDR involves the efflux of anti-cancer drugs from cancer cells, primarily mediated by ATP-binding cassette (ABC) membrane transporters including P-glycoprotein. This article reviews the recent progress of using active ingredients, extracts and formulae from Chinese medicine (CM) in circumventing ABC transporters-mediated MDR. Among the ABC transporters, Pgp is the most extensively studied for its role in MDR reversal effects. While other MDR reversal mechanisms remain unclear, Pgp inhibition is a criterion for further mechanistic study. More mechanistic studies are needed to fully establish the pharmacological effects of potential MDR reversing agents. PMID:20653978

  1. Diabetic Foot Gangrene Patient with Multi-drug Resistant Pseudomonas Putida Infection in Karawaci District, Indonesia

    PubMed Central

    Hardjo Lugito, Nata Pratama; Nawangsih, Cucu; Moksidy, Jevany Claudia; Kurniawan, Andree; Tjiang, Margaret Merlyn

    2015-01-01

    Pseudomonas putida is a rod-shaped, non fermenting Gram-negative organism frequently found in the environment that utilizes aerobic metabolism, previously thought to be of low pathogenicity. It had been reported as cause of skin and soft tissue infection, especially in immunocompromised patients. A female green grocer, 51 year-old came to internal medicine out-patient clinic with gangrene and osteomyelitis on her 1st, 2nd and 3rd digit and wound on the sole of the right foot since 1 month prior. The patient had history of uncontrolled diabetes since a year ago. She was given ceftriaxone 2 grams b.i.d, metronidazole 500 mg t.i.d empirically and then amikacin 250 mg b.i.d, followed by amputation of the digits and wound debridement. The microorganism's culture from pus revealed multi drug resistant Pseudomonas putida. She recovered well after antibiotics and surgery. PMID:25722620

  2. Association of interleukins genes polymorphisms with multi-drug resistant tuberculosis in Ukrainian population.

    PubMed

    Butov, Dmytro O; Kuzhko, Mykhaylo M; Makeeva, Natalia I; Butova, Tetyana S; Stepanenko, Hanna L; Dudnyk, Andrii B

    2016-01-01

    Multi-drug resistant tuberculosis (MDR TB) is a significant health problem in some parts of the world. Three major cytokines involved in TB immunopathogenesis include IL-2, IL-4 and IL-10. The susceptibility to MDR TB may be genetically determined. The aim of the study was to assess the association of IL-2, IL-4, IL-10 gene polymorphisms with multi-drug resistant tuberculosis (MDR TB) in Ukrainian population. We observed 140 patients suffering from infiltrative pulmonary tuberculosis (PT) and 30 apparently healthy subjects. The patients were assigned to two groups whether they suffer or do not suffer from pulmonary MDR TB. Interleukin gene (IL) polymorphisms, particularly T330G polymorphism in the IL-2 gene, C589T polymorphism in the IL-4 gene and G1082A polymorphism in the IL-10 gene were studied through polymerase chain reaction. Circulating levels of IL-2, IL-4 and IL-10 in venous blood were estimated using ELISA. Prior to treatment, patients with PT showed significant increase of IL-2 levels and decrease of IL-4 and IL-10 levels compared to apparently healthy subjects. Circulating IL-4 and IL-10 levels were significantly decreased whilst serum IL-2 level was significantly increased in patients with MDR TB compared to non-MDR TB. Low IL-4 and IL-10 secretion and considerable IL-2 alterations were shown to be significantly associated with mutations of homozygous and heterozygous genotypes affecting C589T polymorphism in the IL-4 gene, G1082A polymorphism in the IL-10 gene and T330G polymorphism in the IL-2 gene in patients with PT. Heterozygous genotype and mutations homozygous genotypes gene in polymorphisms determining specified cytokines' production is a PT risk factor and may lead to disease progression into chronic phase. Heterozygous genotype of aforementioned cytokine genetic polymorphisms was significantly the most frequent in patients with MDR TB.

  3. Multi-drug-resistant Enterococcus faecalis among Egyptian patients with urinary tract infection.

    PubMed

    Abdelkareem, Mohammad Z; Sayed, Mohamed; Hassuna, Noha A; Mahmoud, Mahmoud S; Abdelwahab, Sayed F

    2017-04-01

    The prevalence of Enterococcus faecalis (E. faecalis) infections among Egyptians with urinary tract infection (UTI), their antimicrobial susceptibility and mechanisms of resistance are under investigated. In this study, 300 urine samples were collected from UTI patients to identify E. faecalis. Antimicrobial susceptibility to 18 antimicrobial agents was tested. The presence of aac(6)-Ie-aph(2)Ia, erm(B) and mef(A/E) genes was examined by PCR. Fifty-seven (19%) isolates were identified as E. faecalis. All isolates were sensitive to teicoplanin and were completely resistant to nalidixic acid, cefotaxime and cefadroxil. Multi-drug-resistant (MDR) was found to be 100% with 45 different antibiotypes. The aac(6)Ia-aph(2)Ia gene was found in 100 and 90% of the isolates resistant to gentamicin at concentrations of 120 and 10 μg, respectively. erm(B) and mef(A/E) genes were present in 92.5% (37/40) and 2.5% (1/40) of erythromycin-resistant isolates, respectively. We conclude that there is a high prevalence of E. faecalis in UTI cases with a 100% MDR rate indicating a serious problem in treating infections by this organism in Egypt.

  4. Emerging resistant serotypes of invasive Streptococcus pneumoniae

    PubMed Central

    Elshafie, Sittana; Taj-Aldeen, Saad J

    2016-01-01

    Background Streptococcus pneumoniae is the leading cause of meningitis and sepsis. The aim of the study was to analyze the distribution, vaccine serotype coverage, and antibiotic resistance of S. pneumoniae serotypes isolated from patients with invasive diseases, after the introduction of pneumococcal 7-valent conjugated vaccine (PCV-7). Methods A total of 134 isolates were collected from blood and cerebrospinal fluid specimens at Hamad Hospital during the period from 2005 to 2009. Isolate serotyping was done using the Quellung reaction. The prevaccination period was considered before 2005. Results The most common serotypes for all age groups were 3 (12.70%), 14 (11.90%), 1 (11.90%), 19A (9.00%), 9V (5.20%), 23F (5.20%), and 19F (4.50%). Coverage rates for infant <2 years for PCV-7, the 10-valent conjugated vaccine (PCV-10), and the 13-valent conjugated vaccine (PCV-13) were 34.78%, 52.17%, and 78.26%, respectively. Coverage rates of these vaccines were 50%, 67.86%, and 75% for the 2–5 years age group; 27.12%, 40.68%, and 64.41% for the age group 6–64 years; and 25%, 33.33%, and 66.67% for the ≥65 years age group, respectively. The percentage of nonsusceptible isolates to penicillin, cefotaxime, and erythromycin were 43.86%, 16.66%, and 22.81%, respectively. Thirty-seven isolates (32.46%) were multidrug resistant (MDR) and belonged to serotypes 14, 19A, 19F, 23F, 1, 9V, 12F, 4, 6B, 3, and 15A. Compared to previous results before the introduction of PCV-7, there was a significant reduction in penicillin-nonsusceptable S. pneumoniae from 66.67% to 43.86%, and a slight insignificant reduction in erythromycin nonsusceptible strains from 27.60% to 22.8%, while there was a significant increase in cefotaxime nonsusceptible strains from 3.55% to 16.66%. Conclusion Invasive pneumococcal strains and the emergence of MDR serotypes is a global burden that must be addressed through multiple strategies, including vaccination, antibiotic stewardship, and continuous

  5. Genotypic characterization of multi-drug-resistant Mycobacterium tuberculosis isolates in Myanmar.

    PubMed

    Aye, Khin Saw; Nakajima, Chie; Yamaguchi, Tomoyuki; Win, Min Min; Shwe, Mu Mu; Win, Aye Aye; Lwin, Thandar; Nyunt, Wint Wint; Ti, Ti; Suzuki, Yasuhiko

    2016-03-01

    The number of multi-drug-resistant tuberculosis (MDR-TB) cases is rising worldwide. As a countermeasure against this situation, the implementation of rapid molecular tests to identify MDR-TB would be effective. To develop such tests, information on the frequency and distribution of mutations associating with phenotypic drug resistance in Mycobacterium tuberculosis is required in each country. During 2010, the common mutations in the rpoB, katG and inhA of 178 phenotypically MDR M. tuberculosis isolates collected by the National Tuberculosis Control Program (NTP) in Myanmar were investigated by DNA sequencing. Mutations affecting the 81-bp rifampicin (RIF) resistance-determining region (RRDR) of the rpoB were identified in 127 of 178 isolates (71.3%). Two of the most frequently affected codons were 531 and 526, with percentages of 48.3% and 14.0% respectively. For isoniazid (INH) resistance, 114 of 178 MDR-TB isolates (64.0%) had mutations in the katG in which a mutation-conferring amino acid substitution at codon 315 from Ser to Thr was the most common. Mutations in the inhA regulatory region were also detected in 20 (11.2%) isolates, with the majority at position -15. Distinct mutation rate and pattern from surrounding countries might suggest that MDR-TB has developed and spread domestically in Myanmar.

  6. Antimicrobial activity of various ethanolic plant extracts against pathogenic multi drug resistant Candida spp.

    PubMed

    Khan, Shaista; Imran, Mohd; Imran, Mohammed; Pindari, Nuzhat

    2017-01-01

    A total of 50 Candida isolates were isolated and identified from clinical specimens and these were tested for resistance to various antifungal drugs. It was observed multi-drug resistance in all candida isolates by 84%, 62%, 60%, 76%, 46, 30%, and 22% against fluconazole, clotrimazole, Amphotericin B, itraconazole, ketoconazole, miconazole and nystatin tested respectively. The isolates, which were found to be resistant to antifungal drugs were selected and subjected to antifungal testing against six ethanolic plants, extract namely Azadiracta indica, Allium sativum, Cordia dichotoma Ocimum sanctum, Syzygium cumini and Trigonella foenum grecum. All the plant extracts tested were found to effective against all MDR Candida isolates with inhibition zone ranging from 10- 18mm in diameter. Ethanolic extract of Allium sativum was observed most effective against the isolates among all the plants extracts tested. The minimum inhibitory concentration (MIC) of all ethanolic plant extract was recorded ranging from 1.56-25mg/ml against MDR candida isolates. Phytochemical analysis of the alcoholic plant extracts revealed the presence of alkaloid, flavanoid, glycosoid, phenol; phenol, tannins, saponins in all the plants studied. The present study may be successful in identifying the plants with different antimicrobial activity. These plants containing various phytochemicals may be exploited in the treatment of infectious diseases caused by drug-resistant microorganisms.

  7. Antimicrobial activity of various ethanolic plant extracts against pathogenic multi drug resistant Candida spp.

    PubMed Central

    Khan, Shaista; Imran, Mohd; Imran, Mohammed; Pindari, Nuzhat

    2017-01-01

    A total of 50 Candida isolates were isolated and identified from clinical specimens and these were tested for resistance to various antifungal drugs. It was observed multi-drug resistance in all candida isolates by 84%, 62%, 60%, 76%, 46, 30%, and 22% against fluconazole, clotrimazole, Amphotericin B, itraconazole, ketoconazole, miconazole and nystatin tested respectively. The isolates, which were found to be resistant to antifungal drugs were selected and subjected to antifungal testing against six ethanolic plants, extract namely Azadiracta indica, Allium sativum, Cordia dichotoma Ocimum sanctum, Syzygium cumini and Trigonella foenum grecum. All the plant extracts tested were found to effective against all MDR Candida isolates with inhibition zone ranging from 10- 18mm in diameter. Ethanolic extract of Allium sativum was observed most effective against the isolates among all the plants extracts tested. The minimum inhibitory concentration (MIC) of all ethanolic plant extract was recorded ranging from 1.56-25mg/ml against MDR candida isolates. Phytochemical analysis of the alcoholic plant extracts revealed the presence of alkaloid, flavanoid, glycosoid, phenol; phenol, tannins, saponins in all the plants studied. The present study may be successful in identifying the plants with different antimicrobial activity. These plants containing various phytochemicals may be exploited in the treatment of infectious diseases caused by drug-resistant microorganisms. PMID:28584446

  8. [The role of CCLINs in the event of an epidemic of multi-drug and highly resistant bacteria].

    PubMed

    Landriu, Danièle

    2015-01-01

    The management of epidemics of multi-drug and highly resistant bacteria must be based on a structured organisation. Within each region it requires the expertise of centres for the interregional coordination of nosocomial infection control (CCLINs) and their regional branches of nosocomial infection control (Arlin) which support hospitals in reporting these types of epidemics.

  9. Cefazolin loaded chitosan nanoparticles to cure multi drug resistant Gram-negative pathogens.

    PubMed

    Jamil, Bushra; Habib, Huma; Abbasi, Shahid; Nasir, Habib; Rahman, Abdur; Rehman, Asma; Bokhari, Habib; Imran, Muhammad

    2016-01-20

    Antibiotic resistance against Gram-negative microbes is considered as an alarming phenomenon that needs to be addressed urgently to develop better therapeutic solutions. The aim of the present research work was to investigate and develop cefazolin loaded chitosan nanoparticles (CSNPs) as a potential tool against multidrug resistant pathogens. Empty and drug loaded CSNPs were prepared by ionic gelation method. It was observed by Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM) based studies that CSNPs were less than 100 nm in size and displayed homogeneity both in shape and size. Encapsulation of cefazolin has not increased the size of nano systems. Zeta sizer results revealed that both systems have positive zeta potential of more or less +50 mV, thus contributing towards a stable formulation. Encapsulation efficiency was directly proportional to the increase in the concentration of antibiotic (28-62%). Furthermore, growth kinetics study had demonstrated excellent antimicrobial potential of cefazolin loaded CSNPs against multi drug resistant Klebsiella pneumoniae, Pseudomonas aeroginosa and Extended Spectrum Beta Lactamase (ESBL) positive Escherichia coli. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Recycling antibiotics into GUMBOS: a new combination strategy to combat multi-drug-resistant bacteria.

    PubMed

    Cole, Marsha R; Hobden, Jeffery A; Warner, Isiah M

    2015-04-10

    The emergence of multi-drug-resistant bacteria, coupled with the lack of new antibiotics in development, is fast evolving into a global crisis. New strategies utilizing existing antibacterial agents are urgently needed. We propose one such strategy in which four outmoded β-lactam antibiotics (ampicillin, carbenicillin, cephalothin and oxacillin) and a well-known antiseptic (chlorhexidine di-acetate) were fashioned into a group of uniform materials based on organic salts (GUMBOS) as an alternative to conventional combination drug dosing strategies. The antibacterial activity of precursor ions (e.g., chlorhexidine diacetate and β-lactam antibiotics), GUMBOS and their unreacted mixtures were studied with 25 clinical isolates with varying antibiotic resistance using a micro-broth dilution method. Acute cytotoxicity and therapeutic indices were determined using fibroblasts, endothelial and cervical cell lines. Intestinal permeability was predicted using a parallel artificial membrane permeability assay. GUMBOS formed from ineffective β-lactam antibiotics and cytotoxic chlorhexidine diacetate exhibited unique pharmacological properties and profound antibacterial activity at lower concentrations than the unreacted mixture of precursor ions at equivalent stoichiometry. Reduced cytotoxicity to invasive cell types commonly found in superficial and chronic wounds was also observed using GUMBOS. GUMBOS show promise as an alternative combination drug strategy for treating wound infections caused by drug-resistant bacteria.

  11. Multi-drug-resistant enterotoxigenic and enterohemorrhagic Escherichia coli isolated from children with diarrhea.

    PubMed

    Zeighami, Habib; Haghi, Fakhri; Hajiahmadi, Fahimeh; Kashefiyeh, Mehdi; Memariani, Mojtaba

    2015-06-01

    Multi-drug-resistant (MDR) diarrheagenic Escherichia coli (DEC) has rapidly spread worldwide and represents the most serious threat to the management of diarrhea in developing countries. During the period from March 2011 to January 2012, a total of 450 stool samples of diarrheal children aged 0-60 months were studied. In order to detect enterotoxigenic E. coli (ETEC) and enterohemorrhagic E. coli (EHEC) simultaneously, a mixture of four primer pairs specific for eltB, estA, vt1, and vt2 genes was used in a multiplex PCR. Antimicrobial susceptibility testing was performed as the Clinical and Laboratory Standards Institute (CLSI) guidelines. A total of 140 (31·1%) DEC were isolated from 450 stool samples. Diarrheagenic E. coli exhibited high-level resistance to aztreonam (80·7%), amoxicillin (74·4%), and tetracycline (69·3%). Also, 86·4% of E. coli isolates were resistant to at least three different classes of antimicrobial agents and considered as MDR. The frequency of ETEC and EHEC pathotypes was 46·4 and 12·1%, respectively and all of these isolates were MDR. In conclusion, MDR ETEC continues to be an important agent associated with diarrhea in children from Tabriz, Iran.

  12. Role of wild birds as carriers of multi-drug resistant Escherichia coli and Escherichia vulneris.

    PubMed

    Shobrak, Mohammed Y; Abo-Amer, Aly E

    2014-01-01

    Emergence and distribution of multi-drug resistant (MDR) bacteria in environments pose a risk to human and animal health. A total of 82 isolates of Escherichia spp. were recovered from cloacal swabs of migrating and non-migrating wild birds. All bacterial isolates were identified and characterized morphologically and biochemically. 72% and 50% of isolates recovered from non-migrating and migrating birds, respectively, showed positive congo red dye binding (a virulence factor). Also, hemolysin production (a virulence factor) was showed in 8% of isolates recovered from non-migrating birds and 75% of isolates recovered from migrating birds. All isolates recovered from non-migrating birds were found resistant to Oxacillin while all isolates recovered from migrating birds demonstrated resistance to Oxacillin, Chloramphenicol, Oxytetracycline and Lincomycin. Some bacterial isolates recovered from non-migrating birds and migrating birds exhibited MDR phenotype. The MDR isolates were further characterized by API 20E and 16S rRNA as E. coli and E. vulneris. MDR Escherichia isolates contain ~1-5 plasmids of high-molecular weights. Accordingly, wild birds could create a potential threat to human and animal health by transmitting MDR bacteria to water streams and other environmental sources through their faecal residues, and to remote regions by migration.

  13. Role of wild birds as carriers of multi-drug resistant Escherichia coli and Escherichia vulneris

    PubMed Central

    Shobrak, Mohammed Y.; Abo-Amer, Aly E.

    2014-01-01

    Emergence and distribution of multi-drug resistant (MDR) bacteria in environments pose a risk to human and animal health. A total of 82 isolates of Escherichia spp. were recovered from cloacal swabs of migrating and non-migrating wild birds. All bacterial isolates were identified and characterized morphologically and biochemically. 72% and 50% of isolates recovered from non-migrating and migrating birds, respectively, showed positive congo red dye binding (a virulence factor). Also, hemolysin production (a virulence factor) was showed in 8% of isolates recovered from non-migrating birds and 75% of isolates recovered from migrating birds. All isolates recovered from non-migrating birds were found resistant to Oxacillin while all isolates recovered from migrating birds demonstrated resistance to Oxacillin, Chloramphenicol, Oxytetracycline and Lincomycin. Some bacterial isolates recovered from non-migrating birds and migrating birds exhibited MDR phenotype. The MDR isolates were further characterized by API 20E and 16S rRNA as E. coli and E. vulneris. MDR Escherichia isolates contain ~1–5 plasmids of high-molecular weights. Accordingly, wild birds could create a potential threat to human and animal health by transmitting MDR bacteria to water streams and other environmental sources through their faecal residues, and to remote regions by migration. PMID:25763023

  14. Multi-drug resistant tuberculous spondylitis: A review of the literature

    PubMed Central

    Kizilbash, Quratulain Fatima; Seaworth, Barbara Joyce

    2016-01-01

    While tuberculous vertebral osteomyelitis is an ancient scourge, multi-drug resistant-tuberculosis (MDR-TB) is a modern major public health concern. The objective of this study was to review and summarize the data available on MDR-TB spondylitis. An extensive search of the PubMed database was conducted for articles in English relevant to MDR-TB spondylitis by December 2015. Tuberculous spondylitis accounts for 0.5–1% of all TB cases, and it is estimated that there are probably 5000 MDR-TB spondylitis cases each year worldwide. The diagnosis of MDR-TB spondylitis requires a high index of suspicion based on epidemiologic, clinical, and radiologic features. Cultures and susceptibility testing remain the gold standard for the diagnosis of MDR-TB, but this can take several weeks to obtain. Medical treatment is the mainstay of therapy, and ideally, it should be based on drug susceptibility testing. If empiric treatment is necessary, it should be based on drug exposure history, contact history, epidemiology, and local drug resistance data, if available. The total duration of treatment should not be <18–24 months. Clinical, radiographic, and if possible, bacteriologic improvement should be used to assess the treatment success. Surgery should be reserved for neurologic deterioration, significant kyphosis, spinal instability, severe pain, and failure of medical management. PMID:27803747

  15. Chloramphenicol – A Potent Armament Against Multi-Drug Resistant (MDR) Gram Negative Bacilli?

    PubMed Central

    2016-01-01

    Introduction Multidrug-resistant gram-negative bacteria cause infections which are hard to treat and cause high morbidity and mortality. Due to limited therapeutic options there is a renewed interest upon older antimicrobials which had fallen into disuse as a result of toxic side effects. One such antibiotic is chloramphenicol which was sidelined due to reports linking its use with the development of aplastic anaemia. Aim A study was conducted to evaluate the susceptibility of chloramphenicol in light of the emerging problem of multi-drug resistant gram negative bacteria (MDR GNB). Materials and Methods A total of 483 MDR GNB of the 650 consecutive Gram Negative Bacteria isolated from various clinical samples of patients admitted at a tertiary care hospital in Jaipur between January-June 2014 were screened for chloramphenicol susceptibility by the disc diffusion method as per CLSI guidelines. Results The MDR GNB isolates were obtained from 217 (45%) urine, 163 (34%) from respiratory samples, 52(11%) from pus, 42 (9%) from blood and 9 (2%) from body fluids. A 68% of the MDR GNB isolates were found to be sensitive to chloramphenicol. Conclusion Clinicians should always check for the local susceptibility of Gram-negative bacteria to chloramphenicol. This antibiotic has a potential to play a role in the therapeutic management of infections due to MDR GNB pathogens. PMID:27042458

  16. Multi-drug resistant Pseudomonas aeruginosa keratitis and its effective treatment with topical colistimethate

    PubMed Central

    Chatterjee, Samrat; Agrawal, Deepshikha

    2016-01-01

    The purpose was to evaluate the clinical outcome in multi-drug resistant Pseudomonas aeruginosa (MDR-PA) bacterial keratitis and report the successful use of an alternative antibiotic, topical colistimethate in some of them. The medical records of 12 culture-proven MDR-PA keratitis patients, all exhibiting in vitro resistance by Kirby–Bauer disc diffusion method to ≥ three classes of routinely used topical antibiotics were reviewed. Eight patients were treated with 0.3% ciprofloxacin or ofloxacin, 1 patient with 5% imipenem/cilastatin and 3 patients with 1.6% colistimethate. The outcomes in 8 eyes treated with only fluoroquinolones were evisceration in 4 eyes, therapeutic corneal graft in 1 eye, phthisis bulbi in 1 eye, and no improvement in 2 eyes. The eye treated with imipenem/cilastin required a therapeutic corneal graft. All the three eyes treated with 1.6% colistimethate healed. Colistimethate may prove to be an effective alternative antibiotic in the treatment of MDR-PA keratitis. PMID:27050354

  17. Multi-drug resistant tuberculous spondylitis: A review of the literature.

    PubMed

    Kizilbash, Quratulain Fatima; Seaworth, Barbara Joyce

    2016-01-01

    While tuberculous vertebral osteomyelitis is an ancient scourge, multi-drug resistant-tuberculosis (MDR-TB) is a modern major public health concern. The objective of this study was to review and summarize the data available on MDR-TB spondylitis. An extensive search of the PubMed database was conducted for articles in English relevant to MDR-TB spondylitis by December 2015. Tuberculous spondylitis accounts for 0.5-1% of all TB cases, and it is estimated that there are probably 5000 MDR-TB spondylitis cases each year worldwide. The diagnosis of MDR-TB spondylitis requires a high index of suspicion based on epidemiologic, clinical, and radiologic features. Cultures and susceptibility testing remain the gold standard for the diagnosis of MDR-TB, but this can take several weeks to obtain. Medical treatment is the mainstay of therapy, and ideally, it should be based on drug susceptibility testing. If empiric treatment is necessary, it should be based on drug exposure history, contact history, epidemiology, and local drug resistance data, if available. The total duration of treatment should not be <18-24 months. Clinical, radiographic, and if possible, bacteriologic improvement should be used to assess the treatment success. Surgery should be reserved for neurologic deterioration, significant kyphosis, spinal instability, severe pain, and failure of medical management.

  18. Association of Multi-Drug Resistance Gene Polymorphisms with Pancreatic Cancer Outcome

    PubMed Central

    Tanaka, Motofumi; Okazaki, Taro; Suzuki, Hideo; Abbruzzese, James L.; Li, Donghui

    2010-01-01

    BACKGROUND The purpose of this study was to identify single nucleotide polymorphisms (SNPs) of multi-drug resistance genes that are associated with clinical outcome in patients with potentially resectable pancreatic adenocarcinoma who were treated with preoperative gemcitabine-based chemoradiotherapy at M.D. Anderson Cancer Center. METHODS We selected 8 SNPs of 7 drug resistance genes; MDR1 (ABCB1), MRP1-5 (ABCC1-5), and BCRP (ABCG2), which have been reported to be important in mediating drug resistance. Genotype was determined by the Taqman method. The associations of genotype with tumor response to therapy and overall survival (OS) were evaluated using log-rank test, Cox regression, and logistic regression models. RESULTS MRP5 A-2G AA genotype showed significant association with OS (log-rank P =.010). The hazard ratio (95% confidence interval) was 1.65 (1.11-2.45) after adjusting for clinical predictors. The MRP2 G40A GG genotype had a weak association with reduced OS (log-rank P =.097). A combined effect of the two genotypes on OS was observed. Patients with none of the adverse genotypes had a median survival time (MST) of 34.0 months, and those with 1-2 deleterious alleles had a significantly lower MST of 20.7 months, respectively (log-rank P =.006). MRP2 G40A GG genotype was also significantly associated with poor histological response to chemoradiotherapy (P =.028). CONCLUSIONS These observations suggest a potential role of polymorphic variants of drug resistance genes to predict a therapeutic efficacy and survival of patients with potentially resectable pancreatic cancer. PMID:20922799

  19. Clonal Diversity in Multi Drug Resistant (MDR) Enterococci Isolated from Fecal Normal Flora

    PubMed Central

    Hasannejad Bibalan, Meysam; Eshaghi, Morteza; Sadeghi, Javad; Asadian, Mahla; Narimani, Tahmineh; Talebi, Malihe

    2015-01-01

    Enterococci are Gram positive and catalase- negative cocci that are found in the gastrointestinal tract of mammals and birds, and are readily isolated from soil, surface and waters. The aim of this study was to discriminate between Enterococcus isolates based on repetitive element sequence based –PCR (Rep-PCR) with the BOXA2R primer and their antibiotics profile. Enterococci isolates were obtained from 180 fecal samples. The isolates were identified by biochemical reaction and specific identification was confirmed by PCR with species specific primers. All isolates were subjected to Rep typing and antimicrobial susceptibility tests. Rep-PCR analysis of 180 isolates revealed 93 REP types with forty-five single types (ST1 to ST45) and forty-eight common types (CT1 to 48). Antibiotic susceptibility tests exhibited that 53 (29.4%), 43 (23.8%), 11 (6.1%) and 9 (5%) were resistant to erythromycin, tetracycline, gentamicin and ciprofloxacin respectively but among the isolates, sixteen were multi drug resistant (MDR). These MDR isolates showed 11 Rep types with seven single types and four common types. In addition, 81.2% of MDR isolates were from male subjects and the average age of these persons was more than fifty years. This study showed that 56.2% of MDR isolates were homogeneous with 95 % similarity, and high rate of resistance to tetracycline and erythromycin (81.2%) were observed in these isolates. The concern about these normal flora isolates are the pathogenic potential of these bacteria through the horizontal transfer of antibiotic resistance and virulence genes. PMID:27014649

  20. Clonal Diversity in Multi Drug Resistant (MDR) Enterococci Isolated from Fecal Normal Flora.

    PubMed

    Hasannejad Bibalan, Meysam; Eshaghi, Morteza; Sadeghi, Javad; Asadian, Mahla; Narimani, Tahmineh; Talebi, Malihe

    2015-01-01

    Enterococci are Gram positive and catalase- negative cocci that are found in the gastrointestinal tract of mammals and birds, and are readily isolated from soil, surface and waters. The aim of this study was to discriminate between Enterococcus isolates based on repetitive element sequence based -PCR (Rep-PCR) with the BOXA2R primer and their antibiotics profile. Enterococci isolates were obtained from 180 fecal samples. The isolates were identified by biochemical reaction and specific identification was confirmed by PCR with species specific primers. All isolates were subjected to Rep typing and antimicrobial susceptibility tests. Rep-PCR analysis of 180 isolates revealed 93 REP types with forty-five single types (ST1 to ST45) and forty-eight common types (CT1 to 48). Antibiotic susceptibility tests exhibited that 53 (29.4%), 43 (23.8%), 11 (6.1%) and 9 (5%) were resistant to erythromycin, tetracycline, gentamicin and ciprofloxacin respectively but among the isolates, sixteen were multi drug resistant (MDR). These MDR isolates showed 11 Rep types with seven single types and four common types. In addition, 81.2% of MDR isolates were from male subjects and the average age of these persons was more than fifty years. This study showed that 56.2% of MDR isolates were homogeneous with 95 % similarity, and high rate of resistance to tetracycline and erythromycin (81.2%) were observed in these isolates. The concern about these normal flora isolates are the pathogenic potential of these bacteria through the horizontal transfer of antibiotic resistance and virulence genes.

  1. Preliminary survey of local bacteriophages with lytic activity against multi-drug resistant bacteria.

    PubMed

    Latz, Simone; Wahida, Adam; Arif, Assuda; Häfner, Helga; Hoß, Mareike; Ritter, Klaus; Horz, Hans-Peter

    2016-10-01

    Bacteriophages (phages) represent a potential alternative for combating multi-drug resistant bacteria. Because of their narrow host range and the ever emergence of novel pathogen variants the continued search for phages is a prerequisite for optimal treatment of bacterial infections. Here we performed an ad hoc survey in the surroundings of a University hospital for the presence of phages with therapeutic potential. To this end, 16 aquatic samples of different origins and locations were tested simultaneously for the presence of phages with lytic activity against five current, but distinct strains each from the ESKAPE-group (i.e., Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae). Phages could be isolated for 70% of strains, covering all bacterial species except S. aureus. Apart from samples from two lakes, freshwater samples were largely devoid of phages. By contrast, one liter of hospital effluent collected at a single time point already contained phages active against two-thirds of tested strains. In conclusion, phages with lytic activity against nosocomial pathogens are unevenly distributed across environments with the prime source being the immediate hospital vicinity. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Viper metalloproteinase (Agkistrodon halys pallas) with antimicrobial activity against multi-drug resistant human pathogens.

    PubMed

    Samy, Ramar Perumal; Gopalakrishnakone, Ponnampalam; Chow, Vincent T K; Ho, Bow

    2008-07-01

    Metalloproteinases are abundant enzymes in crotalidae and viperidae snake venoms. Snake venom metalloproteinases (SVMPs) comprise a family of zinc-dependent enzymes, which display many different biological activities. A 23.1 kDa protein was isolated from Agkistrodon halys (pallas, Chinese viper) snake venom. The toxin is a single chain polypeptide with a molecular weight of 23146.61 and an N-terminal sequence (MIQVLLVTICLAVFPYQGSSIILES) relatively similar to that of other metalloprotein-like proteases isolated from the snake venoms of the Viperidae family. The antibacterial effect of Agkistrodon halys metalloproteinase (AHM) on Burkholderia pseudomallei (strains TES and KHW), Escherichia coli, Enterobacter aerogenes, Proteus vulgaris, Proteus mirabilis, Pseudomonas aeruginosa (Gram-negative bacteria) and Staphylococcus aureus (Gram-positive bacterium) was studied at a concentration 120 microM. Interestingly, we found that the metalloproteinase exhibited antibacterial properties and was more active against S. aureus, P. vulgaris, P. mirabilis and multi-drug resistant B. pseudomallei (strain KHW) bacteria. AHM variants with high bacteriostatic activity (MIC 1.875-60 microM) also tended to be less cytotoxic against U-937 human monocytic cells up to 1 mM concentrations. These results suggest that this metalloprotein exerts its antimicrobial effect by altering membrane packing and inhibiting mechanosensitive targets. (c) 2008 Wiley-Liss, Inc.

  3. Antimicrobial potential of Halophilic actinomycetes against multi drug resistant (MDR) ventilator associated pneumonia causing bacterial pathogens.

    PubMed

    Aslam, Sana; Sajid, Imran

    2016-03-01

    A collection of forty halophilic actinomycetes isolated from water and mud samples of the saline lake at Kalar Kahar, salt range, Pakistan, was screened to investigate their antimicrobial potential against multi drug resistant (MDR) ventilator associated pneumonia causing bacterial pathogens. The isolates exhibited significant tolerance to alkaline conditions and grew well at pH 9-11. The taxonomic status of the isolated strains was determined by morphological, biochemical and physiological characterization and by 16s rRNA gene sequencing. The results revealed that majority of the isolates (90%) belong to the genus Streptomyces. Most of the isolates exhibited remarkable antimicrobial activity up to 20mm zone of inhibition against MDR ventilator associated pneumonia causing bacteria including Staphylococcus aureus, Pseudomonas aeruginosa, Proteus vulgaris, Klebsiella pneumoniae, Escherichia coli, Enterobacter and Acinetobacter spp. Additionally the isolates showed moderate to high cytotoxicity in the range of 40 to 80% larval mortality against Artemia salina in a micro well cytotoxicity assay. The chemical screening or the so called metabolic fingerprinting of the methanolic extracts of each isolate, by thin layer chromatography (TLC) using various staining reagents and by high performance liquid chromatography (HPLC-UV), indicated an impressive diversity of the compounds produced by these strains. The study reveals that these halophilic actinomycetes are a promising source of bioactive compounds. The preparative scale fermentation, isolation, purification and structure elucidation of the compounds produced by them may yield novel antimicrobial or chemotherapeutic agents.

  4. Anesthesia in patients with infectious disease caused by multi-drug resistant bacteria.

    PubMed

    Einav, Sharon; Wiener-Well, Yonit

    2017-06-01

    Up to 50% of specific bacterial strains in healthcare admission facilities are multi-drug resistant organisms (MDROs). Involvement of anesthesiologists in management of patients carrying/at risk of carrying MDROs may decrease transmission in the Operating Room (OR). Anesthesiologists, their work area and tools have all been implicated in MDRO outbreaks. Causes include contamination of external ventilation circuits and noncontribution of filters to prevention, inappropriate decontamination procedures for nondisposable equipment (e.g. laryngoscopes, bronchoscopes and stethoscopes) and the anesthesia workplace (e.g. external surfaces of cart and anesthesia machine, telephones and computer keyboards) during OR cleaning and lack of training in sterile drug management. Discussions regarding the management of potential MDRO carriers must include anesthesia providers to optimize infection control interventions as well as the anesthesia method, the location of surgery and recovery and the details of patient transport. Anesthesia staff must learn to identify patients at risk for MDRO infection. Antibiotic prophylaxis, although not evidence based, should adhere to known best practices. Adjuvant therapies (e.g. intranasal Mupirocin and bathing with antiseptics) should be considered. Addition of nonmanual OR cleaning methods such as ultraviolet irradiation or gaseous decontamination is encouraged. Anesthesiologists must undergo formal training in sterile drug preparation and administration.

  5. First report of multi-drug resistant tuberculosis in a systemic lupus erythematosus patient.

    PubMed

    Dorjee, Kunchok; Dierberg, Kerry L; Sadutshang, Tsetan D; Reingold, Arthur L

    2015-08-06

    Treatment of a multi-drug resistant tuberculosis (MDR-TB) patient is clinically challenging, requiring a minimum of 18 months of therapy. Its occurrence in a systemic lupus erythromatosus (SLE) patient may complicate management of both MDR-TB and SLE. This is the first descriptive report of MDR-TB in an SLE patient. A 19-year old female receiving long-term prednisolone for SLE was diagnosed with MDR-TB. She was started on MDR-TB treatment regimen and prednisolone was replaced with azathioprine. After an initial response to therapy, patient experienced a flare of lupus symptoms. Imaging studies revealed avascular necrosis of right femoral head. She was then treated with intravenous methyl-prednisolone, followed by maintenance corticosteroid. Azathioprine was discontinued due to hematological toxicity and failure to control SLE. Her symptoms of lupus regressed and did not re-occur for the duration of her MDR-TB treatment. Patient was declared cured of MDR-TB after 18 months of ATT. She is currently scheduled for a total hip replacement surgery. This case highlights the challenges of simultaneously managing MDR-TB and SLE in a patient due to their over-lapping signs and symptoms, drug-drug interactions, and the need for use of immunomodulatory agents in the absence of standard guidelines and documented previous experiences. Our experience underscores the importance of appropriate selection of treatment regimens for both MDR-TB and SLE.

  6. Active screening of multi-drug resistant bacteria effectively prevent and control the potential infections.

    PubMed

    Ren, Yuguo; Ma, Guoliang; Peng, Lin; Ren, Yufeng; Zhang, Fengmei

    2015-03-01

    Our objective is to determine if actively screen the multi-drug resistant bacteria (MDRB) infection in intensive care unit (ICU) to prevent, control, and decrease the infection rate and transmission of MDRB. The patients admitted in ICU of one hospital in 2013 were analyzed. The throat swab, blood, defecation, and urine of patients were actively collected for bacteria cultures to screen Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, and Acinetobacter baumannii in patients. All patients received screening of MDRB infection and colonization within 2 days and after 2 days of admission, the results showed that there were 418 infectious bacterial strains in total and P. aeruginosa was the main bacterium. The asymptomatic infection rates of P. aeruginosa, K. pneumonia, E. coli, S. aureus, and A. baumannii were 39.02, 24.74, 44.00, 29.17, and 33.33 %, respectively; the symptomatic infection rates were 60.98, 75.26, 56.00, 70.83, and 66.67 %. 59.70 % patients received antibiotics treatment, 27.45 % patients received trachea cannula, 32.95 % patients received mechanism ventilation, 2.27 % patients received arterial cannula or venous cannula and 4.00 % patients received indwelling urinary catheters. The main MDRB in ICU is P. aeruginosa. The active screening of MDRB infection and colonization can provide the opportunity to take the life-saving measure against MDRB and treat patients. This can decrease the infection risk and the nosocomial transmission of MDRB.

  7. Characterization of site-specific glycosylation of secreted proteins associated with multi-drug resistance of gastric cancer

    PubMed Central

    Li, Ting; Cheng, Kai; Dong, Jiaqiang; Tian, Miaomiao; Chai, Na; Guo, Hao; Li, Jinjing; You, Xin; Dong, Mingming; Ye, Mingliang; Nie, Yongzhan; Zou, Hanfa; Fan, Daiming

    2016-01-01

    Multi-drug resistance (MDR) remains a great obstacle to effective chemotherapy for gastric cancer. A number of secreted glycoproteins have been reported to be involved in the development of MDR in gastric cancer. However, whether glycosylation of secreted glycoproteins changes during MDR of gastric cancer is unclear. Our present work manifested that N-glycosites and site-specific glycoforms of secreted proteins in drug-resistant cell lines were distinctly different from those in the parental cell line for the first time. Further characterization highlighted the significance of some aberrantly glycosylated secretory proteins in MDR, suggesting that manipulating the glycosylation of specific glycoproteins could be a potential target for overcoming multi-drug resistance in gastric cancer. PMID:27015365

  8. Multi-drug resistant tuberculosis burden and risk factors: an update.

    PubMed

    Marahatta, S B

    2010-01-01

    Multi-drug resistant (MDR) tuberculosis is defined as disease caused by Mycobacterium tuberculosis with resistance to at least two anti-tubercular drugs Isoniazid and Rifampicin. Recent surveillance data have revealed that prevalence of the drug resistant tuberculosis has risen to the highest rate ever recorded in the history. Drug resistant tuberculosis generally arises through the selection of mutated strains by inadequate therapy. The most powerful predictor of the presence of MDR-TB is a history of treatment of TB. Shortage of drugs has been one of the most common reasons for the inadequacy of the initial anti-TB regimen, especially in resource poor settings. Other major issues significantly contributing to the higher complexity of the treatment of MDR-TB is the increased cost of treatment. Other factors also play important role in the development of MDR-TB such as poor administrative control on purchase and distribution of the drugs with no proper mechanism on quality control and bioavailability tests. Tuberculosis control program implemented in past has also partially contributed to the development of drug resistance due to poor follow up and infrastructure. The association known for centuries between TB and poverty also applies to MDR-TB, a rather significant inverse association with MDR-TB. Various treatment strategies have been employed, including the use of standardised treatment regimens based upon representative local susceptibility patterns, empirical treatment based upon previous treatment history and local Drug Susceptibility Test (DST) patterns, and individualised treatment designed on the basis of individual DST results.Treatment outcomes among MDR-TB cases have varied widely; a recent survey of five Green Line Committee (GLC) approved sites in resource-limited countries found treatment success rates of 70%. Treatment continues to be limited in the resource poor countries where the demand is high. The ultimate strategy to control multidrug

  9. Evaluation of a Commercial Multiplex PCR for Rapid Detection of Multi Drug Resistant Gram Negative Infections.

    PubMed

    Chavada, Ruchir; Maley, Michael

    2015-01-01

    Community and healthcare associated infections caused by multi-drug resistant gram negative organisms (MDR GN) represent a worldwide threat. Nucleic Acid Detection tests are becoming more common for their detection; however they can be expensive requiring specialised equipment and local expertise. This study was done to evaluate the utility of a commercial multiplex tandem (MT) PCR for detection of MDR GN. The study was done on stored laboratory MDR GN isolates from sterile and non-sterile specimens (n=126, out of stored 567 organisms). Laboratory validation of the MT PCR was done to evaluate sensitivity, specificity and agreement with the current phenotypic methods used in the laboratory. Amplicon sequencing was also done on selected isolates for assessing performance characteristics. Workflow and cost implications of the MT PCR were evaluated. The sensitivity and specificity of the MT PCR were calculated to be 95% and 96.7% respectively. Agreement with the phenotypic methods was 80%. Major lack of agreement was seen in detection of AmpC beta lactamase in enterobacteriaceae and carbapenemase in non-fermenters. Agreement of the MT PCR with another multiplex PCR was found to be 87%. Amplicon sequencing confirmed the genotype detected by MT PCR in 94.2 % of cases tested. Time to result was faster for the MT PCR but cost per test was higher. This study shows that with carefully chosen targets for detection of resistance genes in MDR GN, rapid and efficient identification is possible. MT PCR was sensitive and specific and likely more accurate than phenotypic methods.

  10. Evaluation of a Commercial Multiplex PCR for Rapid Detection of Multi Drug Resistant Gram Negative Infections

    PubMed Central

    Chavada, Ruchir; Maley, Michael

    2015-01-01

    Introduction: Community and healthcare associated infections caused by multi-drug resistant gram negative organisms (MDR GN) represent a worldwide threat. Nucleic Acid Detection tests are becoming more common for their detection; however they can be expensive requiring specialised equipment and local expertise. This study was done to evaluate the utility of a commercial multiplex tandem (MT) PCR for detection of MDR GN. Methods: The study was done on stored laboratory MDR GN isolates from sterile and non-sterile specimens (n=126, out of stored 567 organisms). Laboratory validation of the MT PCR was done to evaluate sensitivity, specificity and agreement with the current phenotypic methods used in the laboratory. Amplicon sequencing was also done on selected isolates for assessing performance characteristics. Workflow and cost implications of the MT PCR were evaluated. Results: The sensitivity and specificity of the MT PCR were calculated to be 95% and 96.7% respectively. Agreement with the phenotypic methods was 80%. Major lack of agreement was seen in detection of AmpC beta lactamase in enterobacteriaceae and carbapenemase in non-fermenters. Agreement of the MT PCR with another multiplex PCR was found to be 87%. Amplicon sequencing confirmed the genotype detected by MT PCR in 94.2 % of cases tested. Time to result was faster for the MT PCR but cost per test was higher. Conclusion: This study shows that with carefully chosen targets for detection of resistance genes in MDR GN, rapid and efficient identification is possible. MT PCR was sensitive and specific and likely more accurate than phenotypic methods. PMID:26464612

  11. A Novel Submicron Emulsion System Loaded with Doxorubicin Overcome Multi-Drug Resistance in MCF-7/ADR Cells

    PubMed Central

    Zhou, W. P.; Hua, H. Y.; Sun, P. C.; Zhao, Y. X.

    2015-01-01

    The purpose of the present study was to develop the Solutol HS15-based doxorubicin submicron emulsion with good stability and overcoming multi-drug resistance. In this study, we prepared doxorubicin submicron emulsion, and examined the stability after autoclaving, the in vitro cytotoxic activity, the intracellular accumulation and apoptpsis of doxorubicin submicron emulsion in MCF-7/ADR cells. The physicochemical properties of doxorubicin submicron emulsion were not significantly affected after autoclaving. The doxorubicin submicron emulsion significantly increased the intracellular accumulation of doxorubicin submicron emulsion and enhanced cytotoxic activity and apoptotic effects of doxorubicin. These results may be correlated to doxorubicin submicron emulsion inhibitory effects on efflux pumps through the progressive release of intracellular free Solutol HS15 from doxorubicin submicron emulsion. Furthermore, these in vitro results suggest that the Solutol HS15-based submicron emulsion may be a potentially useful drug delivery system to circumvent multi-drug resistance of tumor cells. PMID:26664069

  12. Multi-drug resistant E.coli urosepsis in physicians following transrectal ultrasound guided prostate biopsies--three cases including one death.

    PubMed

    Carlson, William H; Bell, David G; Lawen, Joseph G; Rendon, Ricardo A

    2010-04-01

    Three male physicians underwent transrectal ultrasound guided prostate biopsies for elevated prostate-specific antigen levels or irregular digital rectal exam findings. All three of these patients developed urosepsis secondary to multi-drug resistant organisms despite antibiotic prophylaxis. There are increasing reports of infectious complications following prostate biopsy caused by multi-drug resistant organisms. These cases highlight the potentially lethal risks to healthcare workers who are more likely to harbor multi-drug resistant organisms than the general population. Further research into preoperative assessment and appropriate antibiotic prophylaxis in all potentially high risk patients is warranted.

  13. In vitro activity of moxalactam and mecillinam, singly and in combination, against multi-drug-resistant Enterobacteriaceae and Pseudomonas species.

    PubMed Central

    Fass, R J

    1982-01-01

    The in vitro interaction of moxalactam and mecillinam against multi-drug-resistant gram-negative enteric bacilli was studied by checkerboard microdilution susceptibility tests and by killing curve kinetics. Against Enterobacteriaceae, the combination was unpredictable; the frequencies of synergy, indifference, and antagonism were 11, 76, and 13%, respectively. Against Pseudomonas sp., the two drugs were consistently indifferent. Overall, the combination of moxalactam and mecillinam was no more active than moxalactam alone. PMID:6282206

  14. In vitro and in vivo analysis of antimicrobial agents alone and in combination against multi-drug resistant Acinetobacter baumannii

    PubMed Central

    He, Songzhe; He, Hui; Chen, Yi; Chen, Yueming; Wang, Wei; Yu, Daojun

    2015-01-01

    Objective: To investigate the in vitro and in vivo antibacterial activities of tigecycline and other 13 common antimicrobial agents, alone or in combination, against multi-drug resistant Acinetobacter baumannii. Methods: An in vitro susceptibility test of 101 A. baumannii was used to detect minimal inhibitory concentrations (MICs). A mouse lung infection model of multi-drug resistant A. baumannii, established by the ultrasonic atomization method, was used to define in vivo antimicrobial activities. Results: Multi-drug resistant A. baumannii showed high sensitivity to tigecycline (98% inhibition), polymyxin B (78.2% inhibition), and minocycline (74.2% inhibition). However, the use of these antimicrobial agents in combination with other antimicrobial agents produced synergistic or additive effects. In vivo data showed that white blood cell (WBC) counts in drug combination groups C (minocycline + amikacin) and D (minocycline + rifampicin) were significantly higher than in groups A (tigecycline) and B (polymyxin B) (P < 0.05), after administration of the drugs 24 h post-infection. Lung tissue inflammation gradually increased in the model group during the first 24 h after ultrasonic atomization infection; vasodilation, congestion with hemorrhage were observed 48 h post infection. After 3 days of anti-infective therapy in groups A, B, C, and D, lung tissue inflammation in each group gradually recovered with clear structures. The mortality rates in drug combination groups(groups C and D) were much lower than in groups A and B. Conclusion: The combination of minocycline with either rifampicin or amikacin is more effective against multi-drug resistant A. baumannii than single-agent tigecycline or polymyxin B. In addition, the mouse lung infection by ultrasonic atomization is a suitable model for drug screening and analysis of infection mechanism. PMID:26074898

  15. Cytotoxicity of 15 Cameroonian medicinal plants against drug sensitive and multi-drug resistant cancer cells.

    PubMed

    Kuete, Victor; Djeussi, Doriane E; Mbaveng, Armelle T; Zeino, Maen; Efferth, Thomas

    2016-06-20

    Cameroonian medicinal plants are traditionally used to treat many ailments, including cancer and related diseases. Cancer is characterized as a condition with complex signs and symptoms. It has been recommended that ethnopharmacological usages such as immune and skin disorders, inflammatory, infectious, parasitic and viral diseases should be taken into account when selecting plants for anticancer screenings, since these reflect disease states bearing relevance to cancer or cancer-like symptoms. The present study aims at investigating 20 methanol extracts from 15 Cameroonian medicinal plants on a panel of human cancer cell lines, including various drug-resistant phenotypes. Possible modes of action of the of the most active plant were analyzed. Methanol extracts from different plant parts (leaves, bark, roots, fruits or whole plant) were evaluated for their cytotoxicity using resazurin reduction assay on a panel of nine sensitive and multi-drug resistant (MDR) cancer cell lines. Cell cycle, apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) were measured by flow cytometry. Prescreening of extracts at 80µg/mL showed that 6 extracts out of 20 inhibited more than 50% proliferation of leukemia CCRF-CEM cells; these include extracts from Anthocleista schweinfurthii fruits (ASF; 48.28%), Morus mesozygia bark (MMB; 42.76%), Nauclea latifolia bark (NLB; 38.75%), Tridesmostemon omphalocarpoides bark (TOB; 38.53%), Nauclea latifolia leaves (NLL; 35.17%) and Erythrina sigmoidea bark (ESB; 33.77%). Subsequent investigations revealed IC50 values below or around 20µg/mL for extracts from MMB, NLB, NLL and ESB towards sensitive CCRF-CEM cells and its resistant P-glycoprotein over-expressing subline CEM/ADR5000. The best extract, ESB also displayed IC50 values below 20µg/mL colon carcinoma HCT116 (p53(+/+)) cells with an IC50 value of 19.63µg/mL and it resistant p53 knockout subline HCT116 (p53(-)(/-)) with an IC50 value of 16.22µg

  16. The relationship between pneumococcal serotypes and antibiotic resistance.

    PubMed

    Song, Jae-Hoon; Dagan, Ron; Klugman, Keith P; Fritzell, Bernard

    2012-04-05

    Streptococcus pneumoniae (SP) causes significant burden of disease, including invasive pneumococcal disease and noninvasive diseases such as pneumonia and acute otitis media. SP has at least 93 different capsular serotypes, with the various serotypes having different propensities for producing disease or developing antibiotic resistance. An increase in the prevalence of antibiotic-resistant SP serotypes has been observed globally. The objective of this paper was to examine the relationship between antibiotic resistance and SP serotypes, with a primary focus on studies published in the past 10 years. Changing trends in antibiotic resistance and serotype distribution during this time, including those before and after the introduction of 7-valent pneumococcal conjugate vaccine (PCV7), were analyzed. Factors that influence the prevalence of antibiotic-resistant serotypes include antibiotic selection pressure, the use of PCV7, and the emergence and spread of antibiotic-resistant clones. The emergence of multidrug resistant serotype 19A is of particular concern. Antibiotic-resistant SP is a global problem that must be addressed through multiple strategies, including national vaccination programs, antibiotic control programs, and ongoing surveillance.

  17. Chemosensitizing effects of synthetic curcumin analogs on human multi-drug resistance leukemic cells.

    PubMed

    Mapoung, Sariya; Pitchakarn, Pornsiri; Yodkeeree, Supachai; Ovatlarnporn, Chitchamai; Sakorn, Natee; Limtrakul, Pornngarm

    2016-01-25

    Curcumin analogs were synthesized and their multi-drug resistance (MDR) reversing properties were determined in human MDR leukemic (K562/Adr) cells. Four analogs, 1,7-bis-(3,4-dimethoxy-phenyl)-hepta-1,6-diene-3,5-dione (1J), 2,6-bis-(4-hydroxy-3-methoxy-benzylidene)-cyclohexanone (2A), 2,6-bis-(3,4-dihydroxy-benzylidene)-cyclohexanone (2F) and 2,6-bis-(3,4-dimethoxy-benzylidene)-cyclohexanone (2J) markedly increased the sensitivity of K562/Adr cells to paclitaxel (PTX) for 8-, 2-, 8- and 16- folds, respectively and vinblastine (Vin) for 5-, 3-, 12- and 30- folds, respectively. The accumulation of P-gp substrates, Calcein-AM, Rhodamine 123 and Doxorubicin, was significantly increased by 1J (up to 6-, 11- and 22- folds, respectively) and 2J (up to 7-, 12- and 17- folds, respectively). Besides 2A, 2F and 2J dramatically decreased P-gp expression in K562/Adr cells. These results could be summarized in the following way. Analog 1J inhibited only P-gp function, while 2A and 2F inhibited only P-gp expression. Interestingly, 2J exerts inhibition of both P-gp function and expression. The combination index (CI) of combination between 2J and PTX (0.09) or Vin (0.06) in K562/Adr cells indicated strong synergistic effects, which likely due to its MDR reversing activity. Moreover, these analogs showed less cytotoxicity to peripheral mononuclear cells (human) and red blood cells (human and rat) suggesting the safety of analogs for further animal and clinical studies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Diversity of multi-drug resistant Acinetobacter baumannii population in a major hospital in Kuwait

    PubMed Central

    Vali, Leila; Dashti, Khadija; Opazo-Capurro, Andrés F.; Dashti, Ali A.; Al Obaid, Khaled; Evans, Benjamin A.

    2015-01-01

    Acinetobacter baumannii is one of the most important opportunistic pathogens that causes serious health care associated complications in critically ill patients. In the current study we report on the diversity of the clinical multi-drug resistant (MDR) A. baumannii in Kuwait by molecular characterization. One hundred A. baumannii were isolated from one of the largest governmental hospitals in Kuwait. Following the identification of the isolates by molecular methods, the amplified blaOXA-51-like gene product of one isolate (KO-12) recovered from blood showed the insertion of the ISAba19 at position 379 in blaOXA-78. Of the 33 MDR isolates, 28 (85%) contained blaOXA-23, 2 (6%) blaOXA-24 and 6 (18%) blaPER-1 gene. We did not detect blaOXA-58, blaVIM, blaIMP, blaGES, blaVEB, and blaNDM genes in any of the tested isolates. In three blaPER-1 positive isolates the genetic environment of blaPER-1 consisted of two copies of ISPa12 (tnpiA1) surrounding the blaPER-1 gene on a highly stable plasmid of ca. 140-kb. Multilocus-sequence typing (MLST) analysis of the 33 A. baumannii isolates identified 20 different STs, of which six (ST-607, ST-608, ST-609, ST-610, ST-611, and ST-612) were novel. Emerging STs such as ST15 (identified for the first time in the Middle East), ST78 and ST25 were also detected. The predominant clonal complex was CC2. Pulsed-field gel electrophoresis and MLST defined the MDR isolates as multi-clonal with diverse lineages. Our results lead us to believe that A. baumannii is diverse in clonal origins and/or is undergoing clonal expansion continuously while multiple lineages of MDR A. baumannii circulate in hospital ward simultaneously. PMID:26257720

  19. Preclinical study and clinical trial of a novel therapeutic vaccine against multi-drug resistant tuberculosis.

    PubMed

    Okada, Masaji; Kita, Yoko; Hashimoto, Satomi; Nakatani, Hitoshi; Nishimastu, Shiho; Kioka, Yumiko; Takami, Yasuko

    2017-02-01

    [Purpose] Multi-drug resistant (MDR), Mycobacterium tuberculosis (TB) is a big problem in the world. We have developed novel TB therapeutic vaccine (HVJ-E/HSP65 DNA +IL-12 DNA). [Methods and Results] DNA vaccine expressing TB heat shock protein 65 and IL-12 was delivered by the hemagglutinating virus of Japan (HVJ)-envelope. This vaccine provided remarkable protective efficacy and strong therapeutic efficacy against MDR-TB and XDR-TB in murine models. Furthermore, this vaccine provided therapeutic efficacy of prolongation of survival time of TB infected monkeys and augmented the immune responses. Therefore, the preclinical tests were studied for clinical trial. The injection of 100 μg of the vaccine /mouse i.m. three times in two weeks induced significantly strong production of IFN-γ and IL-2. 100 μg and 200 μg DNA vaccine/mouse i.m. augmented the production of these cytokines compared with 25 μg DNA vaccine/mouse i.m.. The ratio of 100 μg pDNA to 1AU HVJ-E enhanced the production of IFN-γ and IL-2. The decrease in the number of M. tuberculosis in liver of mice was observed by the vaccination of 100μg pDNA. By using these conditions, safety pharmacology study and toxicology test is being studied in monkeys administered by GMP level DNA vaccines. By the toxicology test using monkeys, high dose GMP level vaccine/ monkey is administrated. Safety pharmacological study of repeated administration is also being investigated in GLP level. Furthermore, we have planned to do clinical phase I trial. Targets are human patients with MDR-TB. The safety and tolerability of the vaccine will be evaluated. [Conclusion and recommendations] These data indicate that our novel vaccine might be useful against tuberculosis including XDR-TB and MDR-TB for human therapeutic clinical applications.

  20. The Multi-Drug Resistant Tuberculosis Diagnosis and Treatment Cascade in Bangladesh

    PubMed Central

    Hossain, Sarder Tanzir; Isaakidis, Petros; Sagili, Karuna D.; Islam, Shayla; Islam, Md Akramul; Shewade, Hemant Deepak; Kamal, S. M. Mostofa; Husain, Ashaque

    2015-01-01

    Objectives To determine, in areas supported by BRAC, Bangladesh i) the pre-diagnosis and pre-treatment attrition among presumptive and confirmed Multi-Drug Resistant Tuberculosis (MDR-TB) patients and ii) factors associated with attrition. Methods This was a retrospective cohort study involving record review. Presumptive MDR-TB patients from peripheral microscopy centres serving 60% of the total population of Bangladesh were included in the study. Attrition and turnaround time for MDR-TB diagnosis by Xpert MTB/RIF and treatment initiation were calculated between July 2012 and June 2014. Results Of 836 presumptive MDR-TB patients referred from 398 peripheral microscopy centres, 161 MDR-TB patients were diagnosed. The number of diagnosed MDR-TB patients was less than country estimates of MDR-TB patients (2000 cases) during the study period. Among those referred, pre-diagnosis and pre-treatment attrition was 17% and 21% respectively. Median turnaround time for MDR-TB testing, result receipt and treatment initiation was four, zero and five days respectively. Farmers (RR=2.3, p=0.01) and daily wage laborers (RR=2.1, p=0.04) had twice the risk of having pre-diagnosis attrition. Poor record-keeping and unreliable upkeep of presumptive MDR-TB patient databases were identified as challenges at the peripheral microscopy centres. Conclusion There was a low proportion of pre-diagnosis and pre-treatment attrition in patients with presumptive and confirmed MDR-TB under programmatic conditions. However, the recording and reporting system did not detect all presumptive MDR-TB patients, highlighting the need to improve the system in order to prevent morbidity, mortality and transmission of MDR-TB in the community. PMID:26110273

  1. The making of a public health problem: multi-drug resistant tuberculosis in India.

    PubMed

    Engel, Nora C

    2013-07-01

    This paper examines how actors construct the public problem of multi-drug resistant tuberculosis (MDR-TB) in India. MDR-TB has been framed by the World Health Organization as a pressing, global public health problem. The responses to MDR-TB are complicated as treatment takes longer and is more expensive than routine TB treatment. This is particularly problematic in countries, such as India, with high patient loads, a large and unregulated private sector, weak health systems and potentially high numbers of MDR-TB cases. This paper analyses how actors struggle for control over ownership, causal theories and political responsibility of the public problem of MDR-TB in India. It combines Gusfield's theory on the construction of public problems with insights from literature on the social construction of diseases and on medical social control. It highlights that there are flexible definitions of public problems, which are negotiated among actor groups and which shift over time. The Indian government has shifted its policy in recent years and acknowledged that MDR-TB needs to be dealt with within the TB programme. The study results reveal how the policy shift happened, why debates on the construction of MDR-TB as a public problem in India continue, and why actors with alternative theories than the government do not succeed in their lobbying efforts. Two main arguments are put forward. First, the construction of the public problem of MDR-TB in India is a social and political process. The need for representative data, international influence and politics define what is controllable. Second, the government seems to be anxious to control the definition of India's MDR-TB problem. This impedes an open, critical and transparent discussion on the definition of the public problem of MDR-TB, which is important in responding flexibly to emerging public health challenges.

  2. Antimicrobial resistance determinant microarray for analysis of multi-drug resistant isolates

    NASA Astrophysics Data System (ADS)

    Taitt, Chris Rowe; Leski, Tomasz; Stenger, David; Vora, Gary J.; House, Brent; Nicklasson, Matilda; Pimentel, Guillermo; Zurawski, Daniel V.; Kirkup, Benjamin C.; Craft, David; Waterman, Paige E.; Lesho, Emil P.; Bangurae, Umaru; Ansumana, Rashid

    2012-06-01

    The prevalence of multidrug-resistant infections in personnel wounded in Iraq and Afghanistan has made it challenging for physicians to choose effective therapeutics in a timely fashion. To address the challenge of identifying the potential for drug resistance, we have developed the Antimicrobial Resistance Determinant Microarray (ARDM) to provide DNAbased analysis for over 250 resistance genes covering 12 classes of antibiotics. Over 70 drug-resistant bacteria from different geographic regions have been analyzed on ARDM, with significant differences in patterns of resistance identified: genes for resistance to sulfonamides, trimethoprim, chloramphenicol, rifampin, and macrolide-lincosamidesulfonamide drugs were more frequently identified in isolates from sources in Iraq/Afghanistan. Of particular concern was the presence of genes responsible for resistance to many of the last-resort antibiotics used to treat war traumaassociated infections.

  3. Horizontal gene transfer and antibiotic resistance plasmids in multi-drug resistant Salmonella enterica serovars

    USDA-ARS?s Scientific Manuscript database

    Antibiotic resistant foodborne pathogens pose serious public health concerns and increase the burden of disease treatment. Antibiotic resistance genes can reside on the bacterial chromosome or on other self-replicating DNA molecules such as plasmids. The resistance genes/DNA can be transferred int...

  4. Diversity of Multi-Drug Resistant Avian Pathogenic Escherichia coli (APEC) Causing Outbreaks of Colibacillosis in Broilers during 2012 in Spain.

    PubMed

    Solà-Ginés, Marc; Cameron-Veas, Karla; Badiola, Ignacio; Dolz, Roser; Majó, Natalia; Dahbi, Ghizlane; Viso, Susana; Mora, Azucena; Blanco, Jorge; Piedra-Carrasco, Nuria; González-López, Juan José; Migura-Garcia, Lourdes

    2015-01-01

    Avian pathogenic Escherichia coli (APEC) are the major cause of colibacillosis in poultry production. In this study, a total of 22 E. coli isolated from colibacillosis field cases and 10 avian faecal E. coli (AFEC) were analysed. All strains were characterised phenotypically by susceptibility testing and molecular typing methods such as pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). The presence of 29 virulence genes associated to APEC and human extraintestinal pathogenic E. coli (ExPEC) was also evaluated. For cephalosporin resistant isolates, cephalosporin resistance genes, plasmid location and replicon typing was assessed. Avian isolates belonged to 26 O:H serotypes and 24 sequence types. Out of 22 APEC isolates, 91% contained the virulence genes predictors of APEC; iutA, hlyF, iss, iroN and ompT. Of all strains, 34% were considered ExPEC. PFGE analysis demonstrated a high degree of genetic polymorphism. All strains were multi-resistant, including those isolated from healthy animals. Eleven strains were resistant to cephalosporins; six contained blaCTX-M-14, two blaSHV-12, two blaCMY-2 and one blaSHV-2. Two strains harboured qnrA, and two qnrA together with aac(6')-Ib-cr. Additionally, the emergent clone O25b:H4-B2-ST131 was isolated from a healthy animal which harboured blaCMY-2 and qnrS genes. Cephalosporin resistant genes were mainly associated to the presence of IncK replicons. This study demonstrates a very diverse population of multi-drug resistant E. coli containing a high number of virulent genes. The E. coli population among broilers is a reservoir of resistance and virulence-associated genes that could be transmitted into the community through the food chain. More epidemiological studies are necessary to identify clonal groups and resistance mechanisms with potential relevance to public health.

  5. Diversity of Multi-Drug Resistant Avian Pathogenic Escherichia coli (APEC) Causing Outbreaks of Colibacillosis in Broilers during 2012 in Spain

    PubMed Central

    Solà-Ginés, Marc; Cameron-Veas, Karla; Badiola, Ignacio; Dolz, Roser; Majó, Natalia; Dahbi, Ghizlane; Viso, Susana; Mora, Azucena; Blanco, Jorge; Piedra-Carrasco, Nuria; González-López, Juan José; Migura-Garcia, Lourdes

    2015-01-01

    Avian pathogenic Escherichia coli (APEC) are the major cause of colibacillosis in poultry production. In this study, a total of 22 E. coli isolated from colibacillosis field cases and 10 avian faecal E. coli (AFEC) were analysed. All strains were characterised phenotypically by susceptibility testing and molecular typing methods such as pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). The presence of 29 virulence genes associated to APEC and human extraintestinal pathogenic E. coli (ExPEC) was also evaluated. For cephalosporin resistant isolates, cephalosporin resistance genes, plasmid location and replicon typing was assessed. Avian isolates belonged to 26 O:H serotypes and 24 sequence types. Out of 22 APEC isolates, 91% contained the virulence genes predictors of APEC; iutA, hlyF, iss, iroN and ompT. Of all strains, 34% were considered ExPEC. PFGE analysis demonstrated a high degree of genetic polymorphism. All strains were multi-resistant, including those isolated from healthy animals. Eleven strains were resistant to cephalosporins; six contained blaCTX-M-14, two blaSHV-12, two blaCMY-2 and one blaSHV-2. Two strains harboured qnrA, and two qnrA together with aac(6’)-Ib-cr. Additionally, the emergent clone O25b:H4-B2-ST131 was isolated from a healthy animal which harboured blaCMY-2 and qnrS genes. Cephalosporin resistant genes were mainly associated to the presence of IncK replicons. This study demonstrates a very diverse population of multi-drug resistant E. coli containing a high number of virulent genes. The E. coli population among broilers is a reservoir of resistance and virulence-associated genes that could be transmitted into the community through the food chain. More epidemiological studies are necessary to identify clonal groups and resistance mechanisms with potential relevance to public health. PMID:26600205

  6. Phytochemical Screening and Antimicrobial Activity of Some Medicinal Plants Against Multi-drug Resistant Bacteria from Clinical Isolates.

    PubMed

    Dahiya, Praveen; Dahiya, P; Purkayastha, Sharmishtha

    2012-09-01

    The in vitro antibacterial activity of various solvents and water extracts of aloe vera, neem, bryophyllum, lemongrass, tulsi, oregano, rosemary and thyme was assessed on 10 multi-drug resistant clinical isolates from both Gram-positive and Gram-negative bacteria and two standard strains including Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922. The zone of inhibition as determined by agar well diffusion method varied with the plant extract, the solvent used for extraction, and the organism tested. Klebsiella pneumoniae 2, Escherichia coli 3 and Staphylococcus aureus 3 were resistant to the plant extracts tested. Moreover, water extracts did not restrain the growth of any tested bacteria. Ethanol and methanol extracts were found to be more potent being capable of exerting significant inhibitory activities against majority of the bacteria investigated. Staphylococcus aureus 1 was the most inhibited bacterial isolate with 24 extracts (60%) inhibiting its growth whereas Escherichia coli 2 exhibited strong resistance being inhibited by only 11 extracts (28%). The results obtained in the agar diffusion plates were in fair correlation with that obtained in the minimum inhibitory concentration tests. The minimum inhibitory concentration of tulsi, oregano, rosemary and aloe vera extracts was found in the range of 1.56-6.25 mg/ml for the multi-drug resistant Staphylococcus aureus isolates tested whereas higher values (6.25-25 mg/ml) were obtained against the multi-drug resistant isolates Klebsiella pneumoniae 1 and Escherichia coli 1 and 2. Qualitative phytochemical analysis demonstrated the presence of tannins and saponins in all plants tested. Thin layer chromatography and bioautography agar overlay assay of ethanol extracts of neem, tulsi and aloe vera indicated flavonoids and tannins as major active compounds against methicillin-resistant Staphylococcus aureus.

  7. Phytochemical Screening and Antimicrobial Activity of Some Medicinal Plants Against Multi-drug Resistant Bacteria from Clinical Isolates

    PubMed Central

    Dahiya, Praveen; Purkayastha, Sharmishtha

    2012-01-01

    The in vitro antibacterial activity of various solvents and water extracts of aloe vera, neem, bryophyllum, lemongrass, tulsi, oregano, rosemary and thyme was assessed on 10 multi-drug resistant clinical isolates from both Gram-positive and Gram-negative bacteria and two standard strains including Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922. The zone of inhibition as determined by agar well diffusion method varied with the plant extract, the solvent used for extraction, and the organism tested. Klebsiella pneumoniae 2, Escherichia coli 3 and Staphylococcus aureus 3 were resistant to the plant extracts tested. Moreover, water extracts did not restrain the growth of any tested bacteria. Ethanol and methanol extracts were found to be more potent being capable of exerting significant inhibitory activities against majority of the bacteria investigated. Staphylococcus aureus 1 was the most inhibited bacterial isolate with 24 extracts (60%) inhibiting its growth whereas Escherichia coli 2 exhibited strong resistance being inhibited by only 11 extracts (28%). The results obtained in the agar diffusion plates were in fair correlation with that obtained in the minimum inhibitory concentration tests. The minimum inhibitory concentration of tulsi, oregano, rosemary and aloe vera extracts was found in the range of 1.56-6.25 mg/ml for the multi-drug resistant Staphylococcus aureus isolates tested whereas higher values (6.25-25 mg/ml) were obtained against the multi-drug resistant isolates Klebsiella pneumoniae 1 and Escherichia coli 1 and 2. Qualitative phytochemical analysis demonstrated the presence of tannins and saponins in all plants tested. Thin layer chromatography and bioautography agar overlay assay of ethanol extracts of neem, tulsi and aloe vera indicated flavonoids and tannins as major active compounds against methicillin-resistant Staphylococcus aureus. PMID:23716873

  8. Serotypes and Antimicrobial Resistance in Salmonella enterica Recovered from Clinical Samples from Cattle and Swine in Minnesota, 2006 to 2015.

    PubMed

    Hong, Samuel; Rovira, Albert; Davies, Peter; Ahlstrom, Christina; Muellner, Petra; Rendahl, Aaron; Olsen, Karen; Bender, Jeff B; Wells, Scott; Perez, Andres; Alvarez, Julio

    2016-01-01

    Salmonellosis remains one of the leading causes of foodborne disease worldwide despite preventive efforts at various stages of the food production chain. The emergence of multi-drug resistant (MDR) non-typhoidal Salmonella enterica represents an additional challenge for public health authorities. Food animals are considered a major reservoir and potential source of foodborne salmonellosis; thus, monitoring of Salmonella strains in livestock may help to detect emergence of new serotypes/MDR phenotypes and to gain a better understanding of Salmonella epidemiology. For this reason, we analyzed trends over a nine-year period in serotypes, and antimicrobial resistance, of Salmonella isolates recovered at the Minnesota Veterinary Diagnostic Laboratory (MVDL) from swine (n = 2,537) and cattle (n = 1,028) samples. Prevalence of predominant serotypes changed over time; in swine, S. Typhimurium and S. Derby decreased and S. Agona and S. 4,5,12:i:- increased throughout the study period. In cattle, S. Dublin, S. Montevideo and S. Cerro increased and S. Muenster became less frequent. Median minimum inhibitory concentration (MIC) values and proportion of antibiotic resistant isolates were higher for those recovered from swine compared with cattle, and were particularly high for certain antibiotic-serotype combinations. The proportion of resistant swine isolates was also higher than observed in the NARMS data, probably due to the different cohort of animals represented in each dataset. Results provide insight into the dynamics of antimicrobial resistant Salmonella in livestock in Minnesota, and can help to monitor emerging trends in antimicrobial resistance.

  9. Serotypes and Antimicrobial Resistance in Salmonella enterica Recovered from Clinical Samples from Cattle and Swine in Minnesota, 2006 to 2015

    PubMed Central

    Hong, Samuel; Rovira, Albert; Davies, Peter; Ahlstrom, Christina; Muellner, Petra; Rendahl, Aaron; Olsen, Karen; Bender, Jeff B.; Wells, Scott; Perez, Andres

    2016-01-01

    Salmonellosis remains one of the leading causes of foodborne disease worldwide despite preventive efforts at various stages of the food production chain. The emergence of multi-drug resistant (MDR) non-typhoidal Salmonella enterica represents an additional challenge for public health authorities. Food animals are considered a major reservoir and potential source of foodborne salmonellosis; thus, monitoring of Salmonella strains in livestock may help to detect emergence of new serotypes/MDR phenotypes and to gain a better understanding of Salmonella epidemiology. For this reason, we analyzed trends over a nine-year period in serotypes, and antimicrobial resistance, of Salmonella isolates recovered at the Minnesota Veterinary Diagnostic Laboratory (MVDL) from swine (n = 2,537) and cattle (n = 1,028) samples. Prevalence of predominant serotypes changed over time; in swine, S. Typhimurium and S. Derby decreased and S. Agona and S. 4,5,12:i:- increased throughout the study period. In cattle, S. Dublin, S. Montevideo and S. Cerro increased and S. Muenster became less frequent. Median minimum inhibitory concentration (MIC) values and proportion of antibiotic resistant isolates were higher for those recovered from swine compared with cattle, and were particularly high for certain antibiotic-serotype combinations. The proportion of resistant swine isolates was also higher than observed in the NARMS data, probably due to the different cohort of animals represented in each dataset. Results provide insight into the dynamics of antimicrobial resistant Salmonella in livestock in Minnesota, and can help to monitor emerging trends in antimicrobial resistance. PMID:27936204

  10. Population dynamics and antimicrobial resistance of the most prevalent poultry-associated Salmonella serotypes.

    PubMed

    Shah, Devendra H; Paul, Narayan C; Sischo, Willium C; Crespo, Rocio; Guard, Jean

    2017-03-01

    Salmonella spp. is the most predominant bacterial cause of foodborne gastroenteritis in humans. Due to the risk of human infection associated with poultry products and the prevalence of antimicrobial resistance, Salmonella also poses a significant challenge to commercial poultry production. During the last decade (2002 to 2012), the 12 most prevalent poultry-associated Salmonella serotypes (MPPSTs) were frequently and consistently isolated from poultry products in the United States. These MPPSTs and their percent prevalence in poultry products include Kentucky (4%), Enteritidis (2%) Heidelberg (2%), Typhimurium (2%), S. I 4,[5],12:i:- (0.31%), Montevideo (0.20%), Infantis (0.16%) Schwarzengrund (0.15%), Hadar (0.15%), Mbandaka (0.13%), Thompson (0.12%), and Senftenberg (0.04%). All MPPSTs except Kentucky are among the top 30 clinically significant serotypes that cause human illnesses in the United States. However with the exception of a few widely studied serotypes such as S. Enteritidis and Typhimurium, the ecology and epidemiology of the majority of MPPSTs still remain poorly investigated. Published data from the United States suggests that MPPSTs such as Heidelberg, Typhimurium, Kentucky, and Sentfenberg are more likely to be multi-drug resistant (MDR, ≥3 antimicobial classes) whereas Enteritidis, Montevideo, Schwarzengrund, Hadar, Infantis, Thompson, and Mbandaka are generally pan-susceptible or display resistance to fewer antimicobials. In contrast, the majority of MPPSTs isolated globally have been reported to display MDR phenotype. There also appears to be an international spread of a few MDR serotypes including Kentucky, Schwarzengrund, Hadar, Thomson, Sentfenberg, and Enteritidis, which may pose significant challenges to the public health. The current knowledge gaps on the ecology, epidemiology, and antimicrobial resistance of MPPSTs are discussed. © 2016 Poultry Science Association Inc.

  11. Prevalence of multi drug resistant Acinetobacter baumannii in the clinical samples from Tertiary Care Hospital in Islamabad, Pakistan.

    PubMed

    Begum, Shahzeera; Hasan, Fariha; Hussain, Shagufta; Ali Shah, Aamer

    2013-09-01

    Acinetobacter baumannii can cause a wide range of infections, including bacteremia, pneumonia, urinary tract infection, peritonitis, etc. This organism is becoming resistant to a large group of antibiotics, especially β-lactam antibiotics. The reason for multi-drug resistance may be the production of extended- spectrum β-lactamses (ESBLs), carbapenemases/metallo β-lactamases or AmpC β-lactamases. The aim of the present study was to determine the prevalence of multi-drug resistant Acinetobacter baumannii isolated from the patients in Surgical Intensive Care Units (SICUs) of Pakistan Institute of Medical Sciences (PIMS), Islamabad, Pakistan. A total of 91 A. baumanni isolates were collected from PIMS during the period from February 2011 to December 2011. The antibiotic susceptibility testing was performed by standard disc diffusion method as recommended by CLSI. Combination disc method, Modified Hodge test, EDTA disc synergy test and AmpC disc test were performed for detection of ESBLs, carbapenemases, metallo β-lactamases, and AmpC β-lactamases, respectively. The prevalence of MDRs was reported 100% among A. baumannii. The antibiotic susceptibility profile showed that minocycline and tigecycline were the most effective drugs against A. baumannii. Almost all of A. baumannii isolates were carbapenemase and metallo β-lactamase producers. AmpC prevalence was observed in 41.76%, while none of the isolates was ESBL producer. Antibiogram and minimal inhibitory concentrations (MICs) indicated tetracycline is relatively effective against A. baumanii. Increased frequency of multi-drug resistance supports the need for continuous surveillance to determine prevalence and evolution of these enzymes in Pakistan.

  12. [Orphanin FQ combined with adriamycin reverses multi-drug resistance of K562/ADM and its molecular mechanism].

    PubMed

    Wang, Xiao-Xia; Liu, Xiao-Qin; Zhang, Wei; Chen, Xuan; Zhao, Li

    2012-06-01

    Our study have confirmed that orphanin FQ (OFQ) alone can reverse the multi-drug resistance of K562/ADM at the cellular level. Thus, this study was purposed to investigate the molecular mechanism of OFQ combined with ADM that reverses multi-drug resistance of K562/ADM, as well as its correlation with the expression of MDR1 mRNA and P-glycoprotein (P-gp). MTT method was used to detect the proliferation ability of K562/ADM treated with OFQ and ADM alone and their combination; flow cytometry was performed to measure the cell apoptosis rate; real time-PCR was applied to detect the MDR1 mRAN expression; Western blot was used to determine the P-gp expression. The results showed that OFQ (0.1 µmol/L) combined with ADM (15 mg/L) significantly inhibited the cell proliferation of K562/ADM, compared with ADM group; the date gained at 48 h was statistically significant (P < 0.05), and cell apoptosis rate was significantly raised (P < 0.01); MDR1 mRNA and P-gp expression levels of OFR combined with ADM were significantly lower than that of ADM alone, and were time-dependent within 48 h. It is concluded that OFQ combined with ADM can reverse the multi-drug resistance of K562/ADM in time-dependent manner, and the 48 h after treatment with these 2 drugs is the best reverse time, which may be related with down regulating the expression of MDR1 mRNA and P-gp.

  13. Comparison of the multi-drug resistant human hepatocellular carcinoma cell line Bel-7402/ADM model established by three methods

    PubMed Central

    2010-01-01

    Background To compare the biological characteristics of three types of human hepatocellular carcinoma multi-drug resistant cell sub-lines Bel-7402/ADM models established by three methods. Methods Established human hepatocellular carcinoma adriamycin (ADM) multi-drug resistant cell sub-lines models Bel-7402/ADMV, Bel-7402/ADML and Bel-7402/ADMS by three methods of in vitro concentration gradient increased induction, nude mice liver-implanted induction and subcutaneous-implanted induction respectively. Phase contrast microscopy was used to observe the cells and the MTT (methyl thiazolyl tetrazolium) method was used to detect drug resistance of the three different sub-lines of cells. Results The three groups of drug resistant cells, Bel-7402/ADMV, Bel-7402/ADML and Bel-7402/ADMS generated cross-resistance to ADM and CDDP (cis-Diaminedichloroplatinum), but showed a significant difference in resistance to Bel-7402 IC50 value (P < 0.01). The doubling times were significantly extended compared to the parent cell line (39 h) and were 65 h (Bel-7402/ADMV), 46 h (Bel-7402/ADML), and 45 h (Bel-7402/ADMS). The excretion rates of ADM were significantly increased compared with the parent cell (34.14%) line and were 81.06% (Bel-7402/ADMV), 66.56% (Bel-7402/ADML) and 61.56% (Bel-7402/ADMS). Expression of P-gp and MRP in the three groups of resistant cells was significantly enhanced (P < 0.01). There was no significant variation in the expression of GSH/GST (P > 0.05). Conclusions Stable resistance was involved in the resistant cell line model established by the above three methods. Liver implantation was a good simulation of human hepatocellular and proved to be an ideal model with characteristics similar to human hepatocellular biology and the pharmacokinetics of anticancer drugs. PMID:20727186

  14. Comparison of the multi-drug resistant human hepatocellular carcinoma cell line Bel-7402/ADM model established by three methods.

    PubMed

    Zhong, Xingguo; Xiong, Maoming; Meng, Xiangling; Gong, Renhua

    2010-08-20

    To compare the biological characteristics of three types of human hepatocellular carcinoma multi-drug resistant cell sub-lines Bel-7402/ADM models established by three methods. Established human hepatocellular carcinoma adriamycin (ADM) multi-drug resistant cell sub-lines models Bel-7402/ADMV, Bel-7402/ADML and Bel-7402/ADMS by three methods of in vitro concentration gradient increased induction, nude mice liver-implanted induction and subcutaneous-implanted induction respectively. Phase contrast microscopy was used to observe the cells and the MTT (methyl thiazolyl tetrazolium) method was used to detect drug resistance of the three different sub-lines of cells. The three groups of drug resistant cells, Bel-7402/ADMV, Bel-7402/ADML and Bel-7402/ADMS generated cross-resistance to ADM and CDDP (cis-Diaminedichloroplatinum), but showed a significant difference in resistance to Bel-7402 IC50 value (P < 0.01). The doubling times were significantly extended compared to the parent cell line (39 h) and were 65 h (Bel-7402/ADMV), 46 h (Bel-7402/ADML), and 45 h (Bel-7402/ADMS). The excretion rates of ADM were significantly increased compared with the parent cell (34.14%) line and were 81.06% (Bel-7402/ADMV), 66.56% (Bel-7402/ADML) and 61.56% (Bel-7402/ADMS). Expression of P-gp and MRP in the three groups of resistant cells was significantly enhanced (P < 0.01). There was no significant variation in the expression of GSH/GST (P > 0.05). Stable resistance was involved in the resistant cell line model established by the above three methods. Liver implantation was a good simulation of human hepatocellular and proved to be an ideal model with characteristics similar to human hepatocellular biology and the pharmacokinetics of anticancer drugs.

  15. [Correlations of integrons and resistance gene cassettes in Gram-negative bacteria with multi-drug resistance].

    PubMed

    Li, Jiao; Ma, Yun-xia; Zhang, Quan-bin; Zhou, Yong-an; Shang, Run-ping; Li, Peng-li; Hao, Zi-qi

    2013-12-01

    To explore the correlations of integrons, gene cassettes and drug resistance phenotypes in 90 multi-drug resistant Gram-negative bacteria. Class I/II/III integron and variable region of positive strains of 90 Gram-negative bacteria were amplified by PCR and types of integron variable region gene cassettes analyzed by DNA sequence. And the resistant rates of integron positive and negative strains were tested by drug susceptibility. The detection rate of integron was 81.1% (73/90) in 90 Gram-negative bacteria. The integron types were class I (n = 70), class II (n = 3) and class III (n = 0). Based on the BLAST analysis by GenBank database, in the amplified fragments of Class I integron positive strains variable region gene ranging from 730 to 3300 bp, 8 types of integron structure were identified. And there were aadB (n = 11), aac (6')-II (n = 7), aadA5 (n = 10), dfrA17-aadA5 (n = 14), dfrA12-OrfF-aadA2(n = 1), aacA4-catB8-aadA1(n = 24), aacC1-OrfA-OrfB-aadA1 (n = 3), catB3-aadB-dhfrV-aacA4-nit1-nit2 (n = 1), in which catB3-aadB-dhfrV-aacA4-nit1-nit2 was a new resistance gene cassette; the variable region fragment of class II integron positive strain was 1600 bp, with 3 carrier strains of sat2-aadA1 gene cassette.Susceptibility testing showed that the antimicrobial resistance rate of integron positive strains to aminoglycosides and sulfa were significantly higher than those of integron negative strains and accorded with the results of integration variable region gene cassettes; the positive strains were more sensitive to amikacin with a resistance rate of 32.9% (24/73); and the drug resistance rates of all beta-lactam strains were ≥ 80%. There is a higher carrier rates of classI integron in Gram-negative bacteria. And the resistant phenotype is related with the types of resistance gene cassettes of integron variable region.

  16. Insights into the mechanism of drug resistance. X-ray structure analysis of multi-drug resistant HIV-1 protease ritonavir complex

    SciTech Connect

    Liu, Zhigang; Yedidi, Ravikiran S.; Wang, Yong; Dewdney, Tamaria G.; Reiter, Samuel J.; Brunzelle, Joseph S.; Kovari, Iulia A.; Kovari, Ladislau C.

    2013-01-08

    Ritonavir (RTV) is a first generation HIV-1 protease inhibitor with rapidly emerging drug resistance. Mutations at residues 46, 54, 82 and 84 render the HIV-1 protease drug resistant against RTV. We report the crystal structure of multi-drug resistant (MDR) 769 HIV-1 protease (carrying resistant mutations at residues 10, 36, 46, 54, 62, 63, 71, 82, 84 and 90) complexed with RTV and the in vitro enzymatic IC50 of RTV against MDR HIV-1 protease. The structural and functional studies demonstrate significant drug resistance of MDR HIV-1 protease against RTV, arising from reduced hydrogen bonds and Van der Waals interactions between RTV and MDR HIV-1 protease.

  17. Clinical response and outcome of pneumonia due to multi-drug resistant Acinetobacter baumannii in critically ill patients

    PubMed Central

    Shojaei, Lida; Mohammadi, Mostafa; Beigmohammadi, Mohammad-Taghi; Doomanlou, Mahsa; Abdollahi, Alireza; Feizabadi, Mohammad Mehdi; Khalili, Hossein

    2016-01-01

    Background and Objectives: The frequency of multi-drug resistant Acinetobacter spp. infections is increasing in Iran. Considering availability of limited therapeutic options, clinical response and outcome of ventilator-associated pneumonia due to multi-drug resistant A.baumannii were evaluated in critically ill patients. Materials and Methods: In this prospective study, 29 patients with carbapenem resistance A. baumannii ventilator-associated pneumonia were enrolled. Endotracheal aspirate specimens were analyzed according to the clinical and laboratory standard institute instructions in the hospital’s microbiology laboratory. Demographics, clinical, microbiological and laboratory findings were collected for each patient during the treatment course. Therapeutic empirical regimen, change in antibiotic regimen following receiving antibiogram results, clinical and microbiological responses, duration of ICU stay and outcome were collected for each recruited individual. Results: All of A. baumanii isolates were resistant to pipracillin-tazobactam, ceftriaxon, amikacin and ciprofloxacin. The resistance rate of A. baumanii species was 41.4% for ampicillin/sulbactabm and 93.1% for meropenem. Patients received either meropenem/colistin (51.7%) or meropenem/ampicillin-sulbactam (48.3%) as the treatment regimens based on the antimicrobial susceptibility patterns of isolates. Ventilator-associated pneumonia clinical response, improvement and failure achieved in 15 (51.7%), 8 (27.6%) and 6 (20.7%) of the patients respectively. Microbiological eradication and intermediate status were observed in 9/29 (31%) and 11/29 (37.9%) of patients, respectively Conclusion: The antibiotic regimens showed comparable efficacy in treatment of VAP due to MDR A. baumannii but mortality rate was high. Considering widespread and high mortality rates associated with MDR infections, applying infection control and antibiotic stewardship programs in hospitals are essential. PMID:28149487

  18. Novel Levofloxacin-Resistant Multidrug-Resistant Streptococcus pneumoniae Serotype 11A Isolates, South Korea

    PubMed Central

    Park, Miey; Kim, Hyun Soo; Kim, Han-Sung; Park, Ji Young; Song, Wonkeun; Cho, Hyoun Chan

    2016-01-01

    Of 608 Streptococcus pneumoniae clinical strains isolated at a hospital in South Korea during 2009–2014, sixteen (2.6%) were identified as levofloxacin resistant. The predominant serotype was 11A (9 isolates). Two novel sequence types of multidrug-resistant S. pneumoniae with serotype 11A were identified, indicating continuous diversification of resistant strains. PMID:27767906

  19. Multi drug resistant Pseudomonas aeruginosa: Pathogen burden and associated antibiogram in a tertiary care hospital of Pakistan.

    PubMed

    Ullah, Waheed; Qasim, Muhammad; Rahman, Hazir; Bari, Fazli; Khan, Saadullah; Rehman, Zia Ur; Khan, Zahid; Dworeck, Tamara; Muhammad, Noor

    2016-08-01

    Pseudomonas aeruginosa is an important pathogen of both community and hospital acquired infections, and a major threat to public health for continuous emergence of multi-drug resistance. Current prevalence and pattern of multidrug resistance in the clinical isolates of P. aeruginosa is reported here. Samples were collected from September 2013 to January 2014 tertiary care hospital, Peshawar. Samples were subjected to phenotypic and molecular based detection of P. aeruginosa and were further processed for multidrug resistance pattern. Out of 3700 samples, 102 were identified as MDR P. aeruginosa. Prevalence of MDR isolates were found in pus (34.3%), wounds (28.4%), urine (19.6%), blood (14.7%) and sputum (2.9%) respectively. Isolates were more resistant to Sulphamethoxazole/Trimethoprim (98.04%), Amoxycillin/Clavulanic acid, Doxycycline and Chloramphenicol (95.1%) each, while least resistant to Imipenem (43.1%), Cefoperazone/Sulbactam (50.98%) and Amikacin (53.9%). Extensive MDR pattern was observed in P. aeruginosa was found as (n = 17, 16.6%) isolates were resistant to all four classes of antibiotics. Increased burden of MDR P. aeruginosa was documented in the study. Moreover, some isolates were even resistant to four classes of antibiotics. Findings of the study will be helpful to devise an appropriate antibiotic treatment strategy against MDR P. aeruginosa to cope the chances of evolving resistant pathogens. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Effect and mechanism of nociceptin/orphanin FQ reversing multi-drug resistance in K562/ADM cell.

    PubMed

    Li, Zhao; Zhou, Lan-Xia; Zhang, Bao-Hong; Yan, Xiang; Li, Juan; Peng, Ya-Li; Chang, Min; Dong, Shou-Liang; Wang, Rui

    2008-09-01

    To investigate the effect and mechanism of nociceptin/orphanin FQ (OFQ) reversing multi-drug resistance of K562/ADM cells in vitro. MTT assay, Wright staining, flow cytometry, transmission electron microscope and gel electrophoresis were used to evaluate the effect and mechanism of OFQ in reversing multi-drug resistance of K562/ADM cells. OFQ could time-dependently reverse the ADM resistance of K562/ADM cell. After treatment with OFQ (1 x 10(-7) mol x L(-1)), K562/ADM cells were cultured for 24, 48 and 72 h. The reversal index (RI) was 1.33, 1.42 and 1.53, respectively. Furthermore, OFQ significantly increased the intracellular accumulation of ADM in K562/ADM cells and percentage apoptosis in K562/ADM cells. OFQ down-regulated the level of P-gp time-dependently, while the level of Fas and FasL were up-regulated. There were evidently significant differences compared with the control (P < 0.01). After treating K562/ADM cells with OFQ (1 x 10(-7) mol x L(-1)) and ADM (20 microg x ml(-1)) for 48 hours, the cells showed apoptotic nuclear fragmentation, which was characterized by the appearance of a DNA ladder pattern in genomic DNA gel electrophoresis. OFQ can reverse the ADM resistance of K562/ADM cells. The mechanism involves OFQ up-regulating the expression of Fas/FasL, down-regulating the level of P-gp, and decreasing the intracellular level of calcium in K562/ADM cells.

  1. Biosurfactins production by Bacillus amyloliquefaciens R3 and their antibacterial activity against multi-drug resistant pathogenic E. coli.

    PubMed

    Chi, Zhe; Rong, Yan-Jun; Li, Yang; Tang, Mei-Juan; Chi, Zhen-Ming

    2015-05-01

    In this work, the anti-Escherichia coli activity of the bioactive substances produced by Bacillus amyloliquefaciens R3 was examined. A new and cheap medium for production of the anti-E. coli substances which contained 20.0 g L(-1) soybean powder, 20.0 g L(-1) wheat flour, pH 6.0 was developed. A crude surfactant concentration of 0.48 mg mL(-1) was obtained after 27 h of 10-L fermentation, and the diameter of the clear zone on the plate seeded with the pathogenic E. coli 2# was 23.3 mm. A preliminary characterization suggested that the anti-E. coli substances produced by B. amyloliquefaciens R3 were the biosurfactins (F1, F2, F3, F4, and F5) with amino acids (GLLVDLL) and hydroxy fatty acids (of 12-15 carbons in length). It was found that all the strains of the pathogenic E. coli showed resistance to several different antibiotics, suggesting that they were the multi-drug resistance and all the strains of the pathogenic E. coli were sensitive to the biosurfactins, indicating that the biosurfactins produced by B. amyloliquefaciens R3 had a broad spectrum of antibacterial activity against the pathogenic E. coli with multi-drug resistant profiles. After the treatment with the purified biosurfactin (F1), the cell membrane of both the whole cells and protoplasts of the E. coli 2# was damaged and the whole cells of the bacterium were broken.

  2. Antibiotic Resistance of Escherichia coli Serotypes from Cochin Estuary

    PubMed Central

    Sukumaran, Divya P.; Durairaj, Srinivasan; Abdulla, Mohamed Hatha

    2012-01-01

    This study aimed at detecting the prevalence of antibiotic-resistant serotypes of Escherichia coli in Cochin estuary, India. E. coli strains were isolated during the period January 2010–December 2011 from five different stations set at Cochin estuary. Water samples from five different stations in Cochin estuary were collected on a monthly basis for a period of two years. Isolates were serotyped, antibiogram-phenotyped for twelve antimicrobial agents, and genotyped by polymerase chain reaction for uid gene that codes for β-D-glucuronidase. These E. coli strains from Cochin estuary were tested against twelve antibiotics to determine the prevalence of multiple antibiotic resistance among them. The results revealed that more than 53.33% of the isolates were multiple antibiotic resistant. Thirteen isolates showed resistance to sulphonamides and two of them contained the sul 1 gene. Class 1 integrons were detected in two E. coli strains which were resistant to more than seven antibiotics. In the present study, O serotyping, antibiotic sensitivity, and polymerase chain reaction were employed with the purpose of establishing the present distribution of multiple antibiotic-resistant serotypes, associated with E. coli isolated from different parts of Cochin estuary. PMID:23008708

  3. 4H-Chromene-based anticancer agents towards multi-drug resistant HL60/MX2 human leukemia: SAR at the 4th and 6th positions.

    PubMed

    Puppala, Manohar; Zhao, Xinghua; Casemore, Denise; Zhou, Bo; Aridoss, Gopalakrishnan; Narayanapillai, Sreekanth; Xing, Chengguo

    2016-03-15

    4H-Chromene-based compounds, for example, CXL017, CXL035, and CXL055, have a unique anticancer potential that they selectively kill multi-drug resistant cancer cells. Reported herein is the extended structure-activity relationship (SAR) study, focusing on the ester functional group at the 4th position and the conformation at the 6th position. Sharp SARs were observed at both positions with respect to cellular cytotoxic potency and selectivity between the parental HL60 and the multi-drug resistant HL60/MX2 cells. These results provide critical guidance for future medicinal optimization. Copyright © 2016. Published by Elsevier Ltd.

  4. Antimicrobial activity of Nigella sativa L. seed oil against multi-drug resistant Staphylococcus aureus isolated from diabetic wounds.

    PubMed

    Emeka, Lorina Badger; Emeka, Promise Madu; Khan, Tahir Mehmood

    2015-11-01

    Microbial resistance to existing antibiotics has led to an increase in the use of medicinal plants that show beneficial effects for various infectious diseases. The study evaluates the susceptibility of multidrug resistant Staphylococcus aureus to Nigella sativa oil. Staphylococcus aureus was isolated from 34 diabetic patient's wounds attending the Renaissance hospital, Nsukka, Southeast Nigeria. The isolates were characterized and identified using standard microbiological techniques. Isolates were cultured and a comparative In vitro antibiotic susceptibility test was carried out using the disk diffusion method. Of the 34 samples collected, 19(56%) showed multidrug resistance to the commonly used antibiotics. Nigella sativa oil was then studied for antibacterial activity against these multidrug resistant isolates of Staphylococcus aureus in varying concentration by well diffusion method. The oil showed pronounced dose dependent antibacterial activity against the isolates. Out of 19 isolates, 8(42%) were sensitive to undiluted oil sample; 4(21%) of these showed sensitivity at 200 mg/ml, 400 mg/ml and 800 mg/ml respectively. Eleven (58%) of the isolates were completely resistant to all the oil concentrations. The present study, reports the isolation of multi-drug resistant S. aureus from diabetic wounds and that more than half of isolates were susceptible to different concentrations N. sativa oil.

  5. Identification and Antibacterial Activity of Bacteria Isolated from Marine Sponge Haliclona (Reniera) sp. against Multi-Drug Resistant Human Pathogen

    NASA Astrophysics Data System (ADS)

    Ardhanu Asagabaldan, Meezan; Ayuningrum, D.; Kristiana, R.; Sabdono, A.; Radjasa, O. K.; Trianto, A.

    2017-02-01

    The marine sponge Haliclona (Reniera) sp. was a potential source of natural bioactive compounds. This sponge widely distributed along the coast of Panjang Island, Jepara, Indonesia. The aims of this research were to isolate the associated bacteria with Haliclona (Reniera) sp. and to screen the antibacterial activity against Multi-Drug Resistant (MDR) bacteria. Amount five bacteria were isolated using media selective for bacteria. The antibacterial activities of bacteria were performed by overlay methods. The bacteria strain PSP. 39-04 had the best activity against Pseudomonas aeruginosa, Staphylococcus aureus, Acinetobacter baumannii, and Enterobacter cloaceae. Based on colony morphology and phylogenetic characterization using 16S rRNA gene sequencing, PSP 39-04 was closely related with Chromohalobacter salixigens strain DSM3043.

  6. Multi-drugs resistant acne rosacea in a child affected by Ataxia-Telangiectasia: successful treatment with Isotretinoin.

    PubMed

    Cantarutti, Nicoletta; Claps, Alessia; Angelino, Giulia; Chessa, Luciana; Callea, Francesco; El Hachem, May; Diociaiuti, Andrea; Finocchi, Andrea

    2015-03-28

    Ataxia-Telangiectasia is a rare multisystem autosomal recessive disorder [OMIM 208900], caused by mutations in Ataxia-Telangiectasia Mutated gene. It is characterized by neurological, immunological and cutaneous involvement. Granulomas have been previously reported in Ataxia-Telangiectasia patients, even if acne rosacea has not been described.We report a case of a young Ataxia-Telangiectasia patient with a severe immunological and neurological involvement, who developed granulomatous skin lesions diagnosed by skin biopsy as acne rosacea. Considering the severe clinical picture and the lack of improvement to multiple topic and systemic therapies, treatment with Isotretinoin was started and the skin lesions disappeared after five months. However the therapy was stopped due to drug-hepatotoxicity.Systemic treatment with Isotretinoin should be carefully considered in patient with Ataxia-Telangiectasia for the treatment of multi-drug resistant acne rosacea, however its toxicity may limit long-term use and the risk/benefit ratio of the treatment should be evaluated.

  7. A rare case of typhoid presenting with fever, ascites, hyponatremia, thrombocytopenia, mesenteric lymphadenitis, and multi-drug resistance

    PubMed Central

    Margaret, A. Priya; Solomon, P. John; Lohith, Harita

    2015-01-01

    A rare case of typhoid presenting with thrombocytopenia, hyponatremia, ascites mesenteric adenitis, and multi-drug resistance is being presented in this article. An 8-year-old girl was admitted with a history of fever, vomiting, abdominal pain and loose stools. Clinical examination revealed fever and hepatosplenomegaly. Investigations showed leucopenia, thrombocytopenia and hyponatremia. Blood Widal was positive, and blood culture grew Salmonella typhi. Ultrasound abdomen revealed ascites, hepatosplenomegaly, mesenteric lymphadenopathy and thickening of the gall bladder. She was treated with ciprofloxacin intravenously for 6 days and when the fever persisted injection ceftriaxone was added. Ciprofloxacin was given intravenously for a total of 15 days and injection ceftriaxone was given for 12 days. Even then, the fever persisted and hence oral azithromycin was added. Fever subsided completely in 3 days with azithromycin and she became asymptomatic without fever, loose stools, abdominal pain or anything on follow-up after 3 months. PMID:26015752

  8. Identification of new surfaces of cofilin that link mitochondrial function to the control of multi-drug resistance.

    PubMed

    Kotiadis, Vassilios N; Leadsham, Jane E; Bastow, Emma L; Gheeraert, Aline; Whybrew, Jennafer M; Bard, Martin; Lappalainen, Pekka; Gourlay, Campbell W

    2012-05-01

    ADF/cofilin family proteins are essential regulators of actin cytoskeletal dynamics. Recent evidence also implicates cofilin in the regulation of mitochondrial function. Here, we identify new functional surfaces of cofilin that are linked with mitochondrial function and stress responses in the budding yeast Saccharomyces cerevisiae. Our data link surfaces of cofilin that are involved in separable activities of actin filament disassembly or stabilisation, to the regulation of mitochondrial morphology and the activation status of Ras, respectively. Importantly, charge alterations to conserved surfaces of cofilin that do not interfere with its actin regulatory activity lead to a dramatic increase in respiratory function that triggers a retrograde signal to upregulate a battery of ABC transporters and concurrent metabolic changes that support multi-drug resistance. We hypothesise that cofilin functions within a bio-sensing system that connects the cytoskeleton and mitochondrial function to environmental challenge.

  9. The potential role of garlic (Allium sativum) against the multi-drug resistant tuberculosis pandemic: a review.

    PubMed

    Dini, Catia; Fabbri, Alessia; Geraci, Andrea

    2011-01-01

    Worldly data show the increasing incidence of Mycobacterium tuberculosis (MTB) and particularly of multi-drug resistant tuberculosis (MDR-TB). In developing countries, TB control programmes are overwhelmed by the complexity of treating MDR-TB infected people, as current tools and therapies are inadequate. MDR-TB could become the main form of TB. Risk factors that make South Africa into one of the main epicentres are analysed. A review of the studies carried out about antitubercular properties of Allium sativum both in vitro and in vivo is provided. The researches about the garlic extracts effectiveness against clinical isolates of MDR-TB are of scientific importance. Allium sativum offers a hope for developing alternative drugs. The involvement of traditional healers (TH) in the TB health management could facilitate the administration of garlic extracts to the infected patients.

  10. A Review of the Evidence for Using Bedaquiline (TMC207) to Treat Multi-Drug Resistant Tuberculosis.

    PubMed

    Fox, Gregory J; Menzies, Dick

    2013-12-01

    Existing therapies for multi-drug resistant tuberculosis (MDR-TB) have substantial limitations, in terms of their effectiveness, side-effect profile, and complexity of administration. Bedaquiline is a novel diarylquinoline antibiotic that has recently been investigated as an adjunct to existing therapies for MDR-TB. Currently, limited clinical data are available to evaluate the drug's safety and effectiveness. In two small randomized-controlled clinical studies, bedaquiline given for 8 or 24 weeks has been shown to improve surrogate microbiological markers of treatment response, but trials have not yet evaluated its impact on clinical failure and relapse. Safety concerns include an increased mortality in the bedaquiline arm of one study, an increased incidence of QT segment prolongation on electrocardiogram, and hepatotoxicity. Until further research data are available, the use of bedaquiline should be confined to settings where carefully selected patients can be closely monitored.

  11. Identification of new surfaces of cofilin that link mitochondrial function to the control of multi-drug resistance

    PubMed Central

    Kotiadis, Vassilios N.; Leadsham, Jane E.; Bastow, Emma L.; Gheeraert, Aline; Whybrew, Jennafer M.; Bard, Martin; Lappalainen, Pekka; Gourlay, Campbell W.

    2012-01-01

    ADF/cofilin family proteins are essential regulators of actin cytoskeletal dynamics. Recent evidence also implicates cofilin in the regulation of mitochondrial function. Here, we identify new functional surfaces of cofilin that are linked with mitochondrial function and stress responses in the budding yeast Saccharomyces cerevisiae. Our data link surfaces of cofilin that are involved in separable activities of actin filament disassembly or stabilisation, to the regulation of mitochondrial morphology and the activation status of Ras, respectively. Importantly, charge alterations to conserved surfaces of cofilin that do not interfere with its actin regulatory activity lead to a dramatic increase in respiratory function that triggers a retrograde signal to upregulate a battery of ABC transporters and concurrent metabolic changes that support multi-drug resistance. We hypothesise that cofilin functions within a bio-sensing system that connects the cytoskeleton and mitochondrial function to environmental challenge. PMID:22344251

  12. 5-Episinuleptolide Decreases the Expression of the Extracellular Matrix in Early Biofilm Formation of Multi-Drug Resistant Acinetobacter baumannii

    PubMed Central

    Tseng, Sung-Pin; Hung, Wei-Chun; Huang, Chiung-Yao; Lin, Yin-Shiou; Chan, Min-Yu; Lu, Po-Liang; Lin, Lin; Sheu, Jyh-Horng

    2016-01-01

    Nosocomial infections and increasing multi-drug resistance caused by Acinetobacter baumannii have been recognized as emerging problems worldwide. Moreover, A. baumannii is able to colonize various abiotic materials and medical devices, making it difficult to eradicate and leading to ventilator-associated pneumonia, and bacteremia. Development of novel molecules that inhibit bacterial biofilm formation may be an alternative prophylactic option for the treatment of biofilm-associated A. baumannii infections. Marine environments, which are unlike their terrestrial counterparts, harbor an abundant biodiversity of marine organisms that produce novel bioactive natural products with pharmaceutical potential. In this study, we identified 5-episinuleptolide, which was isolated from Sinularia leptoclados, as an inhibitor of biofilm formation in ATCC 19606 and three multi-drug resistant A. baumannii strains. In addition, the anti-biofilm activities of 5-episinuleptolide were observed for Gram-negative bacteria but not for Gram-positive bacteria, indicating that the inhibition mechanism of 5-episinuleptolide is effective against only Gram-negative bacteria. The mechanism of biofilm inhibition was demonstrated to correlate to decreased gene expression from the pgaABCD locus, which encodes the extracellular polysaccharide poly-β-(1,6)-N-acetylglucosamine (PNAG). Scanning electron microscopy (SEM) indicated that extracellular matrix of the biofilm was dramatically decreased by treatment with 5-episinuleptolide. Our study showed potentially synergistic activity of combination therapy with 5-episinuleptolide and levofloxacin against biofilm formation and biofilm cells. These data indicate that inhibition of biofilm formation via 5-episinuleptolide may represent another prophylactic option for solving the persistent problem of biofilm-associated A. baumannii infections. PMID:27483290

  13. Cost-effectiveness of Newer Antiretroviral Drugs in Treatment-Experienced Patients with Multi-drug Resistant HIV Disease

    PubMed Central

    Bayoumi, Ahmed M.; Barnett, Paul G.; Joyce, Vilija R.; Griffin, Susan C.; Sun, Huiying; Bansback, Nick J.; Holodniy, Mark; Sanders, Gillian; Brown, Sheldon T.; Kyriakides, Tassos C.; Angus, Brian; Cameron, D. William; Anis, Aslam H.; Sculpher, Mark; Owens, Douglas K.

    2014-01-01

    Objective Newer antiretroviral drugs provide substantial benefits but are expensive. We determined the cost-effectiveness of using antiretroviral drugs in combination for patients with multi-drug resistant HIV disease. Design We built a cohort state-transition model representing treatment-experienced patients with low CD4 counts, high viral load levels, and multi-drug resistant virus. We estimated the effectiveness of newer drugs (those approved in 2005 or later) from published randomized trials. We estimated other parameters from a randomized trial and from the literature. The model had a lifetime time horizon and used the perspective of an ideal insurer in the United States. The interventions were combination antiretroviral therapy, consisting of two newer drugs and one conventional drug, compared to three conventional drugs. Outcome measures were life-years, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness. Results Substituting newer antiretroviral drugs increased expected survival by 3.9 years in advanced HIV disease. The incremental cost-effectiveness ratio of newer, compared to conventional, antiretroviral drugs was $75,556/QALY gained. Sensitivity analyses showed that substituting only one newer antiretroviral drug cost $54,559 to $68,732/QALY, depending on assumptions about efficacy. Substituting three newer drugs cost $105,956 to $117,477/QALY. Cost-effectiveness ratios were higher if conventional drugs were not discontinued. Conclusions In treatment-experienced patients with advanced HIV disease, use of newer antiretroviral agents can be cost effective, given a cost-effectiveness threshold in the range of $50,000 to $75,000 per QALY gained. Newer antiretroviral agents should be used in carefully selected patients for whom less expensive options are clearly inferior. PMID:24129369

  14. Antibacterial activities of Beilschmiedia obscura and six other Cameroonian medicinal plants against multi-drug resistant Gram-negative phenotypes.

    PubMed

    Fankam, Aimé G; Kuiate, Jules R; Kuete, Victor

    2014-07-14

    The rapid spread of bacteria expressing multi-drug resistance propels the search for new antibacterial agents. The present study was designed to evaluate the antibacterial activities of the methanol extracts from Beilschmiedia obscura and six other Cameroonian plants against a panel of twenty nine Gram-negative bacteria including Multi-drug resistant (MDR) phenotypes. The phytochemical investigations of the extracts were carried out according to the standard methods and the liquid micro-dilution assay was used for all antibacterial assays. Phytochemical analysis showed the presence of alkaloids in all studied extracts. Other chemical classes of secondary metabolites such as anthocyanines, anthraquinones flavonoids, saponins, tannins, sterols and triterpenes were selectively detected in the extracts. The extract from the fruits of Beilschmiedia obscura, Pachypodanthium staudtii leaves and Peperomia fernandopoiana (whole plant) displayed the best spectrum of activity with MIC values ranging from 16 to 1024 μg/mL against at least 65% and above of the tested bacteria. The extract from Beilschmiedia obscura was the most active with MIC values below 100 μg/mL against ten of the tested bacteria. This extract also showed MBC values below 1024 μg/mL against 55.17% of the studied microorganisms. Phenylalanine arginine β-naphthylamide (PAβN) significantly modulated the activities of extracts from the leaves and fruits of Pachypodanthium staudtii and Beilschmiedia obscura respectively, by increasing their inhibitory activity against Klebsiella pneumoniae KP55 strain at least four fold. The overall results of the present investigation provide information for the possible use of the methanol extracts of the studied plant species, especially B. obscura to fight infectious diseases caused by Gram-negative bacteria including MDR phenotypes.

  15. Antibacterial activities of Beilschmiedia obscura and six other Cameroonian medicinal plants against multi-drug resistant Gram-negative phenotypes

    PubMed Central

    2014-01-01

    Background The rapid spread of bacteria expressing multi-drug resistance propels the search for new antibacterial agents. The present study was designed to evaluate the antibacterial activities of the methanol extracts from Beilschmiedia obscura and six other Cameroonian plants against a panel of twenty nine Gram-negative bacteria including Multi-drug resistant (MDR) phenotypes. Methods The phytochemical investigations of the extracts were carried out according to the standard methods and the liquid micro-dilution assay was used for all antibacterial assays. Results Phytochemical analysis showed the presence of alkaloids in all studied extracts. Other chemical classes of secondary metabolites such as anthocyanines, anthraquinones flavonoids, saponins, tannins, sterols and triterpenes were selectively detected in the extracts. The extract from the fruits of Beilschmiedia obscura, Pachypodanthium staudtii leaves and Peperomia fernandopoiana (whole plant) displayed the best spectrum of activity with MIC values ranging from 16 to 1024 μg/mL against at least 65% and above of the tested bacteria. The extract from Beilschmiedia obscura was the most active with MIC values below 100 μg/mL against ten of the tested bacteria. This extract also showed MBC values below 1024 μg/mL against 55.17% of the studied microorganisms. Phenylalanine arginine β-naphthylamide (PAβN) significantly modulated the activities of extracts from the leaves and fruits of Pachypodanthium staudtii and Beilschmiedia obscura respectively, by increasing their inhibitory activity against Klebsiella pneumoniae KP55 strain at least four fold. Conclusion The overall results of the present investigation provide information for the possible use of the methanol extracts of the studied plant species, especially B. obscura to fight infectious diseases caused by Gram-negative bacteria including MDR phenotypes. PMID:25023038

  16. A comparison of membrane properties and composition between cell lines selected and transfected for multi-drug resistance.

    PubMed Central

    Callaghan, R.; van Gorkom, L. C.; Epand, R. M.

    1992-01-01

    Cell lines selected (CHRC5) and transfected (LR-73-1A) for multi-drug resistance have total lipid compositions which are indistinguishable between resistant and parental cells. Lipid composition was evaluated by 1H NMR and the total fatty acid content by GLC. No change in surface hydrophobicity, as measured with the fluorescent probe dansyl-PE, was observed as a result of transfection of CHO cells with the mdr1 gene. However, the selected cell line, CHRC5, showed a decreased surface hydrophobicity. This decreased surface hydrophobicity was indicated by an 8 nm increase in the fluorescence emission of dansyl-PE in the CHRC5 cell line compared with the AB1. Both resistant cell lines showed an increase in the polarisation of the fluorescent probe, TMA-DPH in the plasma membranes corresponding to a 14% and a 24% change in fluorescence polarisation for the selected and transfected cell lines, respectively. This is indicative of reduced mobility of the acyl chains in the resistant cell lines. Both the CHRC5 and the transfected cell lines showed almost a 2-fold increase in the initial rate of membrane cycling. The membrane cycling could be inhibited by a known bilayer stabiliser, the N-carbobenzoxy-D-Phe-L-Phe-Gly. These results indicate that the properties of the plasma membrane from resistant cells are altered compared with their parental cell line. PMID:1358166

  17. Baseline resistance and Cross resistance among fluoroquinolones in Multi Drug Resistant Mycobacterium tuberculosis Isolates at a national reference laboratory.

    PubMed

    H G, Mamatha; Shanthi, V

    2017-09-05

    Pre-existing fluoroquinolone (FQ) resistance in Multiple Drug Resistant Tuberculosis (MDR TB) patients is a major threat in treating MDR TB. This study was conducted to assess the percentage of FQ resistance among MDR TB patients and to determine whether there is complete cross-resistance between FQs (ofloxacin, levofloxacin and moxifloxacin) used as second line drugs in TB treatment. Among 879 MDR TB suspects tested, 68 were confirmed to be MDRTB and mono rifampicin resistant. They were further analyzed for FQ drug resistance by DST using MGIT. The minimal inhibitory concentrations (MIC) were also determined for ofloxacin, levofloxacin and moxifloxacin. Out of 879 MDR TB suspects, rifampicin resistance was observed in 70 patients (8%). Among which pre-existing FQ resistance was detected in 32% of patients. 88% of isolates exhibited a similar DST pattern for all three FQs tested. Cross resistance among FQs was not complete in 8 isolates. MIC of moxifloxacin was found to be much lower than MICs of ofloxacin and levofloxacin. A huge proportion of MDR TB strains (32%) exhibiting ofloxacin resistance prior treatment with second line anti TB drugs raises major concern. Baseline drug resistance detection in TB patients helps in cutting down transmission of drug resistant TB. The MIC for Ofloxacin was higher than its critical concentration indicating the prevalence of baseline resistance to FQs due to irrational use of the drug. Copyright © 2017. Published by Elsevier Ltd.

  18. Horizontal Transfer of a Multi-Drug Resistance Plasmid between Coliform Bacteria of Human and Bovine Origin in a Farm Environment

    PubMed Central

    Oppegaard, Hanne; Steinum, Terje M.; Wasteson, Yngvild

    2001-01-01

    Multi-drug-resistant coliform bacteria were isolated from feces of cattle exposed to antimicrobial agents and humans associated with the animals. Isolates from both cattle and humans harbored an R plasmid of 65 kb (pTMS1) that may have been transferred between them due to selective antibiotic pressure in the farm environment. PMID:11472956

  19. Clinical study on cluster care to prevent multi-drug resistant infection in ICU patients with severe encephalopathy

    PubMed Central

    Qiong, Liu; Hui, Zhu

    2016-01-01

    The value of clinical cluster nursing in the prevention of multi-drug resistant (MDR) infection in patients with severe encephalopathy in ICU was evaluated. ICU patients (n=129) diagnosed with severe encephalopathy between 2012 and 2014 were selected as the study group, while 106 cases of ICU patients diagnosed with severe encephalopathy between 2010 and 2012 were retrospectively selected as the control group. Control group patients were offered conventional integrated nursing care, while the study group patients were offered cluster nursing care. The differences in infection rate, colony and quantity, infection time, number, mortality rate and hospital stays between the two groups were compared and analyzed. Observations on the infection rate, diagnosis time, total number of infection, mortality rate caused by infection and hospital stays were lower in the study group patients than in controls (P<0.05). The patients in the study group had a much lower drug-resistant infection rate than that in the control group (P<0.05). In the patient groups there were infections with methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli, although the quantities of the above pathogenic microbe colonies in the study group were notably less than those in the control group (P<0.05). In conclusion, cluster nursing care effectively prevents MDR infections of ICU patients with severe encephalopathy and reduces the mortality rate, thus having an excellent clinical significance. PMID:28105127

  20. Characterization of Multi-Drug Resistant Enterococcus faecalis Isolated from Cephalic Recording Chambers in Research Macaques (Macaca spp.)

    PubMed Central

    Lebreton, Francois; Trowel, Elise; de la Fuente-Núñez, César; Dzink-Fox, Joanne; Gilmore, Michael S.; Fox, James G.

    2017-01-01

    Nonhuman primates are commonly used for cognitive neuroscience research and often surgically implanted with cephalic recording chambers for electrophysiological recording. Aerobic bacterial cultures from 25 macaques identified 72 bacterial isolates, including 15 Enterococcus faecalis isolates. The E. faecalis isolates displayed multi-drug resistant phenotypes, with resistance to ciprofloxacin, enrofloxacin, trimethoprim-sulfamethoxazole, tetracycline, chloramphenicol, bacitracin, and erythromycin, as well as high-level aminoglycoside resistance. Multi-locus sequence typing showed that most belonged to two E. faecalis sequence types (ST): ST 4 and ST 55. The genomes of three representative isolates were sequenced to identify genes encoding antimicrobial resistances and other traits. Antimicrobial resistance genes identified included aac(6’)-aph(2”), aph(3’)-III, str, ant(6)-Ia, tetM, tetS, tetL, ermB, bcrABR, cat, and dfrG, and polymorphisms in parC (S80I) and gyrA (S83I) were observed. These isolates also harbored virulence factors including the cytolysin toxin genes in ST 4 isolates, as well as multiple biofilm-associated genes (esp, agg, ace, SrtA, gelE, ebpABC), hyaluronidases (hylA, hylB), and other survival genes (ElrA, tpx). Crystal violet biofilm assays confirmed that ST 4 isolates produced more biofilm than ST 55 isolates. The abundance of antimicrobial resistance and virulence factor genes in the ST 4 isolates likely relates to the loss of CRISPR-cas. This macaque colony represents a unique model for studying E. faecalis infection associated with indwelling devices, and provides an opportunity to understand the basis of persistence of this pathogen in a healthcare setting. PMID:28081148

  1. Whole-Genome Sequencing Analysis of Serially Isolated Multi-Drug and Extensively Drug Resistant Mycobacterium tuberculosis from Thai Patients

    PubMed Central

    Faksri, Kiatichai; Tan, Jun Hao; Disratthakit, Areeya; Xia, Eryu; Prammananan, Therdsak; Suriyaphol, Prapat; Khor, Chiea Chuen; Teo, Yik-Ying; Ong, Rick Twee-Hee; Chaiprasert, Angkana

    2016-01-01

    Multi-drug and extensively drug-resistant tuberculosis (MDR and XDR-TB) are problems that threaten public health worldwide. Only some genetic markers associated with drug-resistant TB are known. Whole-genome sequencing (WGS) is a promising tool for distinguishing between re-infection and persistent infection in isolates taken at different times from a single patient, but has not yet been applied in MDR and XDR-TB. We aim to detect genetic markers associated with drug resistance and distinguish between reinfection and persistent infection from MDR and XDR-TB patients based on WGS analysis. Samples of Mycobacterium tuberculosis (n = 7), serially isolated from 2 MDR cases and 1 XDR-TB case, were retrieved from Siriraj Hospital, Bangkok. The WGS analysis used an Illumina Miseq sequencer. In cases of persistent infection, MDR-TB isolates differed at an average of 2 SNPs across the span of 2–9 months whereas in the case of reinfection, isolates differed at 61 SNPs across 2 years. Known genetic markers associated with resistance were detected from strains susceptible to streptomycin (2/7 isolates), p-aminosalicylic acid (3/7 isolates) and fluoroquinolone drugs. Among fluoroquinolone drugs, ofloxacin had the highest phenotype-genotype concordance (6/7 isolates), whereas gatifloxcain had the lowest (3/7 isolates). A putative candidate SNP in Rv2477c associated with kanamycin and amikacin resistance was suggested for further validation. WGS provided comprehensive results regarding molecular epidemiology, distinguishing between persistent infection and reinfection in M/XDR-TB and potentially can be used for detection of novel mutations associated with drug resistance. PMID:27518818

  2. Characterization of Multi-Drug Resistant Enterococcus faecalis Isolated from Cephalic Recording Chambers in Research Macaques (Macaca spp.).

    PubMed

    Woods, Stephanie E; Lieberman, Mia T; Lebreton, Francois; Trowel, Elise; de la Fuente-Núñez, César; Dzink-Fox, Joanne; Gilmore, Michael S; Fox, James G

    2017-01-01

    Nonhuman primates are commonly used for cognitive neuroscience research and often surgically implanted with cephalic recording chambers for electrophysiological recording. Aerobic bacterial cultures from 25 macaques identified 72 bacterial isolates, including 15 Enterococcus faecalis isolates. The E. faecalis isolates displayed multi-drug resistant phenotypes, with resistance to ciprofloxacin, enrofloxacin, trimethoprim-sulfamethoxazole, tetracycline, chloramphenicol, bacitracin, and erythromycin, as well as high-level aminoglycoside resistance. Multi-locus sequence typing showed that most belonged to two E. faecalis sequence types (ST): ST 4 and ST 55. The genomes of three representative isolates were sequenced to identify genes encoding antimicrobial resistances and other traits. Antimicrobial resistance genes identified included aac(6')-aph(2"), aph(3')-III, str, ant(6)-Ia, tetM, tetS, tetL, ermB, bcrABR, cat, and dfrG, and polymorphisms in parC (S80I) and gyrA (S83I) were observed. These isolates also harbored virulence factors including the cytolysin toxin genes in ST 4 isolates, as well as multiple biofilm-associated genes (esp, agg, ace, SrtA, gelE, ebpABC), hyaluronidases (hylA, hylB), and other survival genes (ElrA, tpx). Crystal violet biofilm assays confirmed that ST 4 isolates produced more biofilm than ST 55 isolates. The abundance of antimicrobial resistance and virulence factor genes in the ST 4 isolates likely relates to the loss of CRISPR-cas. This macaque colony represents a unique model for studying E. faecalis infection associated with indwelling devices, and provides an opportunity to understand the basis of persistence of this pathogen in a healthcare setting.

  3. Multi-Drug Resistance among Salmonella spp. Isolated from Food Animals

    USDA-ARS?s Scientific Manuscript database

    Introduction: Since the early 1990’s there has been increasing awareness and concern regarding the development of antimicrobial resistance among bacteria of public health significance. Of particular concern starting in 2000, was the emergence of multiple drug resistant (MDR) Salmonella Newport. How...

  4. Multi-Drug Resistance Mediated by Class 1 Integrons in Aeromonas Isolated from Farmed Freshwater Animals

    PubMed Central

    Deng, Yuting; Wu, Yali; Jiang, Lan; Tan, Aiping; Zhang, Ruiquan; Luo, Li

    2016-01-01

    Aeromonas is regarded as an important pathogen of freshwater animals but little is known about the genetics of its antimicrobial resistance in Chinese aquaculture. The aim of this study was to investigate the presence of integrons and characterize multidrug resistant Aeromonas spp. isolated from diseased farmed freshwater animals. These animal samples included fish, ornamental fish, shrimp, turtles, and amphibians which were collected from 64 farms in Guangdong province of South China. One hundred and twelve Aeromonas spp. isolates were examined for antimicrobial resistance phenotypes and the presence of class 1 integron sequences. Twenty-two (19.6%) of these isolates carried a class 1 integron comprising six different gene insertion cassettes including drfA12-orfF-aadA2, drfA12-orfF, aac(6′)-II-blaOXA-21-cat3, catB3, arr-3, and dfrA17. Among these, drfA12-orfF-aadA2 was the dominant gene cassette array (63.6%, 14/22) and this is the first report of aac(6′)-II-blaOXA-21-cat3 in an Aeromonas hydrophila isolate from a Chinese giant salamander (Andrias davidianus). All the integron-positive strains were resistant to more than five agents and 22 contained other resistance genes including blaCTX-M-3, blaTEM-1, aac(6′)-Ib-cr, and tetA. All integron-positive isolates also contained mutations in the quinolone resistance determining regions (QRDR). Our investigation demonstrates that freshwater animals can serve as a reservoir for pathogenic Aeromonas strains containing multiple drug-resistance integrons. This data suggests that surveillance for antimicrobial resistance of animal origin and a prudent and responsible use of antimicrobials in aquaculture is necessary in these farms. PMID:27379065

  5. [Evaluation of GenoType MTBDRplus for the detection of multi-drug-resistant Mycobacterium tuberculosis strains].

    PubMed

    Chikamatsu, Kinuyo; Mizuno, Kazue; Aono, Akio; Yamada, Hiroyuki; Sugamoto, Tetsuhiro; Nishiyama, Hiroyuki; Mitarai, Satoshi

    2011-07-01

    To evaluate GenoType MTBDRplus (Hain Lifescience, Germany) for its capacity to detect the resistance of rifampicin (RFP) and isoniazid (INH). A total of 44 confirmed multi-drug resistant (MDR) and 67 susceptible M. tuberculosis strains were tested for susceptibility to RFP and INH by GenoType MTBDR plus. The core 81bp region of the rpoB gene and the 322bp region of the katG gene and the inhA gene (248bp of which included the promoter and the ORF of the 379bp inhA) were directly sequenced for both MDR-TB and susceptible M. tuberculosis strains, and the mutations were confirmed. Susceptibility was tested by standard proportion method with 1% Ogawa medium. The sensitivities of GenoType MTBDRplus for RFP and INH resistance were 97.7% and 65.9%, respectively. The specificity for RFP and INH was 100%. The sensitivity of GenoType MTBDRplus was almost equivalent to the sequencing method for RFP, but that for INH was slightly inferior to the sequencing without significant difference. Geno Type MTBDRplus detected 97.7% of the mutations of rpoB compared with the direct sequencing. It also detected 24 katG MUT1 (S315T1) (54.5%) and 5 inhA MUT1 (C15T) mutations (11.4%), while the direct sequencing detected an additional 2 (4.5%) katG mutants. The accuracy of GenoType MTBDRplus for the detection of RFP resistance was confirmed to be comparable to that of DST using conventional culture-based methods, while it was less accurate for detection of INH resistance. GenoType MTBDRplus is useful for early diagnosis and infection control for MDR-TB because it has a short turnaround time of approximately 6 hours.

  6. Prediction of multi-drug resistance transporters using a novel sequence analysis method [version 2; referees: 2 approved

    SciTech Connect

    McDermott, Jason E.; Bruillard, Paul; Overall, Christopher C.; Gosink, Luke; Lindemann, Stephen R.

    2015-03-09

    There are many examples of groups of proteins that have similar function, but the determinants of functional specificity may be hidden by lack of sequencesimilarity, or by large groups of similar sequences with different functions. Transporters are one such protein group in that the general function, transport, can be easily inferred from the sequence, but the substrate specificity can be impossible to predict from sequence with current methods. In this paper we describe a linguistic-based approach to identify functional patterns from groups of unaligned protein sequences and its application to predict multi-drug resistance transporters (MDRs) from bacteria. We first show that our method can recreate known patterns from PROSITE for several motifs from unaligned sequences. We then show that the method, MDRpred, can predict MDRs with greater accuracy and positive predictive value than a collection of currently available family-based models from the Pfam database. Finally, we apply MDRpred to a large collection of protein sequences from an environmental microbiome study to make novel predictions about drug resistance in a potential environmental reservoir.

  7. Prediction of multi-drug resistance transporters using a novel sequence analysis method [version 2; referees: 2 approved

    DOE PAGES

    McDermott, Jason E.; Bruillard, Paul; Overall, Christopher C.; ...

    2015-03-09

    There are many examples of groups of proteins that have similar function, but the determinants of functional specificity may be hidden by lack of sequencesimilarity, or by large groups of similar sequences with different functions. Transporters are one such protein group in that the general function, transport, can be easily inferred from the sequence, but the substrate specificity can be impossible to predict from sequence with current methods. In this paper we describe a linguistic-based approach to identify functional patterns from groups of unaligned protein sequences and its application to predict multi-drug resistance transporters (MDRs) from bacteria. We first showmore » that our method can recreate known patterns from PROSITE for several motifs from unaligned sequences. We then show that the method, MDRpred, can predict MDRs with greater accuracy and positive predictive value than a collection of currently available family-based models from the Pfam database. Finally, we apply MDRpred to a large collection of protein sequences from an environmental microbiome study to make novel predictions about drug resistance in a potential environmental reservoir.« less

  8. Eradication of Multi-drug Resistant Bacteria by Ni Doped ZnO Nanorods: Structural, Raman and optical characteristics

    NASA Astrophysics Data System (ADS)

    Jan, Tariq; Iqbal, Javed; Ismail, Muhammad; Mansoor, Qaisar; Mahmood, Arshad; Ahmad, Amaar

    2014-07-01

    In this paper, ZnO nanorods doped with varying amounts of Ni have been prepared by chemical co-precipitation technique. Structural investigations provide the evidence that Ni is successfully doped into ZnO host matrix without having any secondary phases. Scanning electron microscopy (SEM) images reveal the formation of rodlike structure of undoped ZnO with average length and diameter of 1 μm and 80 nm, respectively. Raman spectroscopy results show that the E1LO phonons mode band shifts to the higher values with Ni doping, which is attributed to large amount of crystal defects. Ni doping is also found to greatly influence the optical properties of ZnO nanorods. The influence of Ni doping on antibacterial characteristics of ZnO nanorods have been studied by measuring the growth curves of Escherichia coli (E. coli), Methicillin-resistant Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) bacteria in the presence of prepared nanorods. ZnO nanorods antibacterial potency is found to increase remarkably with Ni doping against S. aureus and P. aeruginosa microbials, which might possibly be due to the increase in reactive oxygen species (ROS) generation. Interestingly, it is observed that Ni doped ZnO nanorods completely eradicates these multi-drug resistant bacteria.

  9. Antibacterial and antibiotic-modulation activity of six Cameroonian medicinal plants against Gram-negative multi-drug resistant phenotypes.

    PubMed

    Djeussi, Doriane E; Noumedem, Jaurès A K; Ngadjui, Bonaventure T; Kuete, Victor

    2016-05-04

    Bacterial Infections involving multi-drug resistant (MDR) phenotypes constitute a worldwide health concern. The present work was designed to assess the antibacterial properties of the methanol extracts of six medicinal plants (Anthocleista schweinfurthii, Nauclea latifolia, Boehmeria platyphylla, Caucalis melanantha, Erigeron floribundus and Zehneria scobra) and the effects of their associations with antibiotics on MDR Gram-negative bacteria over-expressing active efflux pumps. The antibacterial activities and the ability to potentiate antibiotic effects of the methanol extracts the tested plants were evaluated in vitro against twenty eight Gram-negative bacteria expressing MDR phenotypes, using broth microdilution method. The phytochemical screening of these extracts was also performed using standard methods. All tested extracts displayed moderate to low antibacterial activity on at least 14.3 % of the 28 tested bacteria, with MIC values ranged from 128 to 1024 μg/mL. The best antibacterial spectrum was observed with Naulcea latifolia bark extract. Extracts from A. schweinfurthii fruits, N. latifolia stem bark, Z. scobra and N. latifolia leaves showed synergistic effects with many antibiotics against MDR bacteria. The overall results of the present study provide information for the possible use of the studied plants, especially Nauclea latifolia in the control of Gram-negative bacterial infections including MDR species as antibacterials as well as resistance modulators.

  10. Euphorbiasteroid reverses P-glycoprotein-mediated multi-drug resistance in human sarcoma cell line MES-SA/Dx5.

    PubMed

    Choi, Jung Sook; Kang, Nam Sook; Min, Yong Ki; Kim, Seong Hwan

    2010-07-01

    In this study, we evaluated whether euphorbiasteroid isolated from Euphorbia lathyris has the potential to reverse P-glycoprotein (P-gp)-mediated multi-drug resistance (MDR) by using the drug-sensitive human sarcoma cell line MES-SA and its MDR counterpart MES-SA/Dx5. Interestingly, even at low concentrations of euphorbiasteroid (1-3 microM), it efficiently restored the toxicities of anticancer drugs including vinblastine, taxol and doxorubicin in MES-SA/Dx5 cells. Additionally, the computational Bayesian model for predicting potential P-gp substrates or inhibitors revealed that euphorbiasteroid showed 97% probability for substrate likeness having similar molecular features with 50 P-gp substrates. Consistent with this result, the substrate likeness of euphorbiasteroid was also experimentally confirmed by P-gp ATPase activity assay. In conclusion, our finding suggested that euphorbiasteroid could be a transport substrate for P-gp that can effectively inhibit P-gp-mediated drug transport and reverse resistance to anticancer drugs in MES-SA/Dx5 cells.

  11. Antibacterial activity of herbal extracts against multi-drug resistant Escherichia coli recovered from retail chicken meat.

    PubMed

    Shaheen, Arfat Yousaf; Sheikh, Ali Ahmad; Rabbani, Masood; Aslam, Asim; Bibi, Tasra; Liaqat, Fakhra; Muhammad, Javed; Rehmani, Shafqat Fatima

    2015-07-01

    Increasing incidence rate of multiple drug resistance in Escherichia coli (E. coli) due to extensive uses of antibiotics is a serious challenge to disease treatment. Contaminated retail chicken meat is one of the major sources of spread of multi drug resistant (MDR) E. coli. Current study has been conducted to study the prevalence of MDR E. coli in retail chicken meat samples from Lahore city of Pakistan and it was found that 73.86% of E. coli isolates have MDR pattern. In vitro evaluation of antibacterial activity of crude ethanolic extracts of six herbs against MDR E. coli phenotypes has revealed that clove and cinnamon have maximum zones of inhibition as compared to other herbal extracts. Mint and coriander gave the intermediate results while garlic and kalonji showed the least antibacterial activity against the MDR E. coli phenotypes using the agar well diffusion technique. Average Minimum Inhibitory Concentrations (MICs) for clove, mint, cinnamon, coriander, kalonji and garlic extracts were 1.15, 1.38, 0.5, 1.99, 2.41, 8.60 mg/mL respectively using the broth micro dilution method. The results obtained in present study were revealed that crude ethanol extracts of selected herbs have had significant antibacterial activity. Hence they can be used as promising alternatives of antimicrobials against MDR E. coli species and can be used for cooked food preservation.

  12. Detection of multi drug resistant bacteria in major hospitals in Kano, North-West, Nigeria.

    PubMed

    Yusuf, I; Arzai, A H; Haruna, M; Sharif, A A; Getso, M I

    2014-01-01

    Two major hospitals in Kano, North West Nigeria have recorded increasing resistance of clinical pathogens to broad spectrum β lactams, mediated by extended spectrum β-lactamase (ESβL) and non ESBLs. A study was therefore undertaken to determine the occurrence and prevalence of plasmid and chromosomal mediated AmpC βL and carbapenemase in addition to already known ESBL due to increasing resistance of pathogens from the two hospitals to carbapenems, cephamycins and flouroquinolones. Antibiogram tests and ESBL, AmpC and carbapenemase production tests were performed on all the isolates. AmpC and carbapenemase producers were further screened for AmpC inducibility and metallo beta lactamase production respectively. Majority of the isolates (> 80%) were resistant to both β-lactam and non β-lactam antibiotics. Reduced susceptibility to levofloxacin, nitrofurantoin, nalidixic acid and ofloxacin among the isolates were observed with the exception of P. aeruginosa which is totally resistant to imipenem and levofloxacin. An overall prevalence of 14.4%, 11.9% and 11.9.3% for ESβL, AmpC and carbapenemase was observed respectively. About 7.9% of the AmpC producers can over expressed the chromosomally mediated AmpC and 85.8% of the carbapenemase producers require metal for their action. Co-production of either of two and/or all of the enzymes was observed in E. coli, P. mirabilis and P. aeruginosa. Antibiotic resistance among isolates from the two hospitals is increasing and the major cause of this resistance in the pathogens studied are production of AmpC, carbapenemase (especially Metallo β-lactamase) in addition to already known ESBL enzymes by the pathogens. Some of the isolates also possess the capacity to elaborate two or more of the enzymes concurrently, which would renders them resistant to a multitude of antibiotics.

  13. Detection of multi drug resistant bacteria in major hospitals in Kano, North-West, Nigeria

    PubMed Central

    Yusuf, I.; Arzai, A.H.; Haruna, M.; Sharif, A.A.; Getso, M.I.

    2014-01-01

    Two major hospitals in Kano, North West Nigeria have recorded increasing resistance of clinical pathogens to broad spectrum β lactams, mediated by extended spectrum β-lactamase (ESβL) and non ESBLs. A study was therefore undertaken to determine the occurrence and prevalence of plasmid and chromosomal mediated AmpC βL and carbapenemase in addition to already known ESBL due to increasing resistance of pathogens from the two hospitals to carbapenems, cephamycins and flouroquinolones. Antibiogram tests and ESBL, AmpC and carbapenemase production tests were performed on all the isolates. AmpC and carbapenemase producers were further screened for AmpC inducibility and metallo beta lactamase production respectively. Majority of the isolates (> 80%) were resistant to both β-lactam and non β-lactam antibiotics. Reduced susceptibility to levofloxacin, nitrofurantoin, nalidixic acid and ofloxacin among the isolates were observed with the exception of P. aeruginosa which is totally resistant to imipenem and levofloxacin. An overall prevalence of 14.4%, 11.9% and 11.9.3% for ESβL, AmpC and carbapenemase was observed respectively. About 7.9% of the AmpC producers can over expressed the chromosomally mediated AmpC and 85.8% of the carbapenemase producers require metal for their action. Co-production of either of two and/or all of the enzymes was observed in E. coli, P. mirabilis and P. aeruginosa. Antibiotic resistance among isolates from the two hospitals is increasing and the major cause of this resistance in the pathogens studied are production of AmpC, carbapenemase (especially Metallo β-lactamase) in addition to already known ESBL enzymes by the pathogens. Some of the isolates also possess the capacity to elaborate two or more of the enzymes concurrently, which would renders them resistant to a multitude of antibiotics. PMID:25477909

  14. Development of Cefotaxime Impregnated Chitosan as Nano-antibiotics: De Novo Strategy to Combat Biofilm Forming Multi-drug Resistant Pathogens

    PubMed Central

    Jamil, Bushra; Habib, Huma; Abbasi, Shahid A.; Ihsan, Ayesha; Nasir, Habib; Imran, Muhammad

    2016-01-01

    Frequent incidents of antibiotic-resistant biofilm forming pathogens in community-associated and hospital-acquired infections have become a global concern owing to failure of conventional therapies. Nano-antibiotics (NABs) are de novo tools to overcome the multi-drug resistant mechanisms employed by the superbugs. Inhibition of biofilm formation is one of those strategies to curb multi drug resistance phenomenon. In the current study, the anti-biofilm and antibacterial potential of newly synthesized cefotaxime loaded chitosan based NABs have been investigated. Both bare and cefotaxime loaded NABs were prepared by ionotropic gelation method. They were found carrying positive zeta potential of more than +50 mV, indicating highly stable nano-dispersion. Moreover, microscopic studies revealed their size as less than 100 nm. NABs were tested against clinical isolates of multi drug resistant Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and methicillin resistant Staphylococcus aureus and wherein they demonstrated broad-spectrum anti-biofilm and anti-pathogenic activity. Thus, in vitro synergistic action of cephalosporin drugs and chitosan polymer at nano-scale in contrast to free antibiotics can be an improved broad-spectrum strategy to thwart resistance mechanisms in both Gram-positive and Gram-negative resistant pathogens. PMID:27047457

  15. Multi-drug resistant gram-negative enteric bacteria isolated from flies at Chengdu Airport, China.

    PubMed

    Liu, Yang; Yang, Yu; Zhao, Feng; Fan, Xuejun; Zhong, Wei; Qiao, Dairong; Cao, Yi

    2013-11-01

    We collected flies from Chengdu Shuangliu International Airport to examine for the presence of bacteria and to determine the sensitivity patterns of those bacteria. A total of 1,228 flies were collected from 6 sites around Chengdu Shuangliu International Airport from April to September 2011. The predominant species was Chrysomya megacephala (n=276, 22.5%). Antimicrobial-resistant gram-negative enteric bacteria (n=48) were isolated from flies using MacConkey agar supplemented with cephalothin (20 microg/ml). These were identified as Escherichia coli (n=37), Klebsiella pneumoniae (n=6), Pseudomonas aeruginosa (n=3) and Aeromonas hydrophila (n=2). All isolated bacteria were tested for resistance to 21 commonly used antimicrobials: amoxicillin (100%), ticarcillin (100%), cephalothin (100%), cefuroxime (100%), ceftazidime 1 (93.8%), piperacillin (93.8%), cefotaxime (89.6%), ticarcillin-clavulanate (81.3%), trimethoprim-sulfamethoxazole (62.5%), ciprofloxacin (54.2%), gentamicin (45.8%), cefepime (39.6%), tobramycin (39.6%), ceftazidime (22.9%), cefoxitin (16.7%), amikacin (16.7%), netilmicin (14.6%), amoxicillin-clavulanate (6.3%) and piperacillin-tazobactam (2.1%). No resistance to meropenem or imipenem was observed. Antibiotic resistance genes among the isolated bacteria were analyzed for by polymerase chain reaction. Thirty of the 48 bacteria with resistance (62.5%) possessed the blaTEM gene.

  16. A Mouse Model of Multi-Drug Resistant Staphylococcus aureus-induced Ocular Disease

    PubMed Central

    Broekema, Nicole M.; Larsen, Inna V.; Naruzawa, Erika S.; Filutowicz, Marcin; Kolb, Aaron W.; Teixeira, Leandro B. C.; Brandt, Curtis R.

    2016-01-01

    Staphylococcus aureus infection of the cornea is a significant threat to vision. The percentage of bacterial isolates resistant to antibiotics is increasing as is the percentage of infections caused by methicillin resistant isolates. There is a critical need for additional therapeutic approaches and their development will require the use of animal models to test efficacy. Two mouse models of S. aureus keratitis have been described but only quantified stromal keratitis (corneal clouding and perforation). We have extended these models using the methicillin resistant S. aureus USA300 LAC strain and show that eyelid inflammation and swelling (blepharitis) and corneal neovascularization can be quantified. This expanded model should prove useful in assessing additional effects of antibacterial therapies and additional pathological mechanisms involved in bacterial ocular infection. PMID:27896297

  17. Molecular Analysis and Expression of bap Gene in Biofilm-Forming Multi-Drug-Resistant Acinetobacter baumannii

    PubMed Central

    Azizi, Omid; Shahcheraghi, Fereshteh; Salimizand, Himen; Modarresi, Farzan; Shakibaie, Mohammad Reza; Mansouri, Shahla; Ramazanzadeh, Rashid; Badmasti, Farzad; Nikbin, Vajihe

    2016-01-01

    Background: Acinetobacter baumannii is commonly resistant to nearly all antibiotics due to presence of antibiotic resistance genes and biofilm formation. In this study we determined the presence of certain antibiotic-resistance genes associated with biofilm production and the influence of low iron concentration on expression of the biofilm-associated protein gene (bap) in development of biofilm among multi-drug-resistant A. baumannii (MDRAB) Methods: Sixty-five MDRAB isolates from clinical samples were collected. Molecular typing was carried out by random amplified polymorphism DNA polymerase chain reaction (RAPD-PCR). Biofilm formation was assayed by the microtiter method. Results: The sequence of bap was determined and deposited in the GenBank database (accession no. KR080550.1). Expression of bap in the presence of low iron was analyzed by relative quantitative real time PCR (rqRT-PCR). Nearly half of the isolates belonged to RAPD-types A and B remaining were either small clusters or singleton. The results of biofilm formation revealed that 23 (35.4%), 18 (27.7%), 13 (20%), and 11 (16.9%) of the isolates had strong, moderate, weak, and no biofilm activities, respectively. ompA and csuE genes were detected in all, while bap and blaPER-1 were detected in 43 (66%) and 42 (64%) of the isolates that showed strong and moderate biofilm activities (p ≤ 0.05), respectively. Analysis of bap expression by rqRT-PCR revealed five isolates with four-fold bap overexpression in the presence of low iron concentration (20 µM). Conclusion: The results suggest that bap overexpression may influence biofilm formation in presence of low iron concentration PMID:28070537

  18. Characterization of 13 multi-drug resistant Salmonella serovars from different broiler chickens associated with those of human isolates.

    PubMed

    Chiu, Lan-Ho; Chiu, Cheng-Hsun; Horn, Yan-Ming; Chiou, Chien-Shun; Lee, Chien-Yu; Yeh, Chia-Ming; Yu, Chang-You; Wu, Chean-Ping; Chang, Chao-Chin; Chu, Chishih

    2010-03-23

    Salmonella are frequently isolated from chickens and their products. Prevalent serogroups and serovars of Salmonella as well as their genotypes and antibiograms were determined for cloacal samples from 1595 chickens. To understand the possible serovar and H antigens for transmission between chicken and human, serovars and their H antigens of 164 chicken and 5314 human isolates were compared. Prevalence of Salmonella differed among chicken lines and ages. Chicken and human isolates belonged mainly to serogroup B, C1, C2-C3, D, and E. 13 serovars and 66 serovars were identified for chicken and human isolates respectively. The common serovars for chicken and human isolates were S. Typhimurium, S. Enteritidis, S. Albany, S. Derby, and S. Anatum and shared common H1 antigens "g complex; i; e,h; and z4,z24" and H2 antigens "1 complex and -". In human isolates, H1 antigen "i" and H2 antigen "-" were common in all serogroups. In chicken, antimicrobial susceptibility differed among serogroups, serovars and three counties. All isolates were susceptible to cefazolin and ceftriaxone, but highly resistant to ampicillin, chloramphenicol, flumequine, streptomycin, sulfamethoxazole-trimethoprim, and tetracycline. Except those isolates of serogroup C1 of Chick group and serogroup G, all isolates were multi-drug resistance. Only S. Kubacha, S. Typhimurium, S. Grampian, and S. Mons were resistant to ciprofloxacin and/or enrofloxacin. In chicken, prevalent serogroups and serovars were associated with chicken ages, lines and regions; and flouroquinolone-resistant and MDR isolates emerged. H1 antigens "g complex and i" and H2 antigens "1 complex and -" might be important for transmission of Salmonella between chicken and human.

  19. Characterization of 13 multi-drug resistant Salmonella serovars from different broiler chickens associated with those of human isolates

    PubMed Central

    2010-01-01

    Background Salmonella are frequently isolated from chickens and their products. Prevalent serogroups and serovars of Salmonella as well as their genotypes and antibiograms were determined for cloacal samples from 1595 chickens. To understand the possible serovar and H antigens for transmission between chicken and human, serovars and their H antigens of 164 chicken and 5314 human isolates were compared. Results Prevalence of Salmonella differed among chicken lines and ages. Chicken and human isolates belonged mainly to serogroup B, C1, C2-C3, D, and E. 13 serovars and 66 serovars were identified for chicken and human isolates respectively. The common serovars for chicken and human isolates were S. Typhimurium, S. Enteritidis, S. Albany, S. Derby, and S. Anatum and shared common H1 antigens "g complex; i; e,h; and z4,z24" and H2 antigens "1 complex and -". In human isolates, H1 antigen "i" and H2 antigen "-" were common in all serogroups. In chicken, antimicrobial susceptibility differed among serogroups, serovars and three counties. All isolates were susceptible to cefazolin and ceftriaxone, but highly resistant to ampicillin, chloramphenicol, flumequine, streptomycin, sulfamethoxazole-trimethoprim, and tetracycline. Except those isolates of serogroup C1 of Chick group and serogroup G, all isolates were multi-drug resistance. Only S. Kubacha, S. Typhimurium, S. Grampian, and S. Mons were resistant to ciprofloxacin and/or enrofloxacin. Conclusion In chicken, prevalent serogroups and serovars were associated with chicken ages, lines and regions; and flouroquinolone-resistant and MDR isolates emerged. H1 antigens "g complex and i" and H2 antigens "1 complex and -" might be important for transmission of Salmonella between chicken and human. PMID:20307324

  20. Peptidoglycan hydrolase enzyme fusions are uniquely suited for treating multi-drug resistant pathogens

    USDA-ARS?s Scientific Manuscript database

    Pathogens with resistance to multiple antibiotics are a world-wide concern for human and animal health. Bacteriophage lytic enzymes are a potent new source of antimicrobials for treating these pathogens. Phage are viruses that infect bacteria. Survival of the phage relies on phage encoded endoly...

  1. Prevalence of multi-drug resistant Salmonella on comercial dairies utilizing a single heifer raising facility

    USDA-ARS?s Scientific Manuscript database

    The objectives of the current research were two-fold: 1) Determine the prevalence of multiple drug resistant (MDR) Salmonella in the various classes of dairy cattle; and 2) Determine if co-mingling of calves from multiple farms at a heifer feedlot serves as a transmission vector for Salmonella back ...

  2. Mouse ATP-Binding Cassette (ABC) Transporters Conferring Multi-Drug Resistance.

    PubMed

    Li, Shuaizhang; Zhang, Wen; Yin, Xuejiao; Xing, Shilai; Xie, Heidi Qunhui; Cao, Zhengyu; Zhao, Bin

    2015-01-01

    The ABC (ATP-binding cassette) transporter is one of the largest and most ancient protein families with members functioning from protozoa to human. The resistance of cancer and tumor cells to anticancer drugs is due to the over-expression of some ABC transporters, which may finally lead to chemotherapy failure. The mouse ABC transporters are classified into seven subfamilies by phylogenetic analysis. The mouse ABC transporter gene, alias, chromosomal location and function have been determined. Within the ABC super-family, the MDR transporters (Abcb1, Abcc1, Abcg2) in mouse models have been proved to be valuable to investigate the biochemistry and physiological functions. This review concentrates on the multidrug resistance of mouse ABC transporters in cancer and tumor cells.

  3. Mouse ATP-Binding Cassette (ABC) Transporters Conferring Multi-Drug Resistance

    PubMed

    Shuaizhang, L I; Zhang, Wen; Yin, Xuejiao; Xing, Shilai; Xie, Qunhui; Cao, Zhengyu; Zhao, Bin

    2015-04-28

    The ABC (ATP-binding cassette) transporter is one of the largest and most ancient protein families with members functioning from protozoa to human. The resistance of cancer and tumor cells to anticancer drugs is due to the over-expression of some ABC transporters, which may finally lead to chemotherapy failure. The mouse ABC transporters are classified into seven subfamilies by phylogenetic analysis. The mouse ABC transporter gene, alias, chromosomal location and function have been determined. Within the ABC super-family, the MDR transporters (Abcb1, Abcc1, Abcg2) in mouse models have been proved to be valuable to investigate the biochemistry and physiological functions. This review concentrates on the multidrug resistance of mouse ABC transporters in cancer and tumor cells.

  4. The function of the thyroid gland in patients with multi-drug resistant tuberculosis.

    PubMed

    Matveyeva, S L; Shevchenko, O S; Pogorelova, O O

    2017-01-01

    Multidrug-resistant tuberculosis (MDRTB) remains a health problem for many countries in the world. The share of MDRTB is 10-30% among newly diagnosed cases and 20-70% among relapses and treatment failure. The aim of the study is to define the side effects of second line drugs used in the treatment of MDRTB on thyroid function. In 30 patients with multidrug resistant tuberculosis, echostructure of thyroid was studied by ultrasound imaging method. Indices of thyroid function: plasma levels of free thyroxin, thyroid stimulating hormone were studied before chemotherapy initiated, at the end of intensive phase and after the treatment finished. Decreasing of thyroid function under antituberculosis chemotherapy was approved. Monitoring and correction of thyroid function during antituberculosis chemotherapy was suggested. Patients with MDRTB taking ethionamide and PAS are at increased risk for hypothyroidism and goiter, and therefore require monitoring of thyroid function at all stages of antituberculosis chemotherapy for its timely correction.

  5. Bedaquiline: a new hope to treat multi-drug resistant tuberculosis.

    PubMed

    Patel, Rahul V; Riyaz, S D; Park, Se Won

    2014-01-01

    Each year, a huge number of new cases accounts of TB with added problems due to multidrug resistant TB varieties. Globally, TB is one of the top causes of loss of life among people living with HIV who are more likely than others to get TB infection. Current TB treatment includes long term administration of cocktail of drugs; hence, the development of an alternative armamentarium against TB is the primary requirement. In fact, new drugs with novel activity against mycobacteria are of significant importance in order to combat existing levels of resistance. The present report covers the discovery of a diarylquinoline TB drug, bedaquiline, its antituberculosis effects and mode of action. Clinical studies conducted on bedaquiline which brought it to the accelerated FDA acceptance have been described. This report is of great attention for therapeutic apothecaries working in TB medication growth in terms of creating further diarylquinoline applicants with a wide variety of antimycobacterial results.

  6. Natural History of Multi-Drug Resistant Organisms in a New Military Medical Facility

    DTIC Science & Technology

    2013-12-01

    are provided to hospital cleaning and infection control staff. 15. SUBJECT TERMS none provided 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...the genetic relatedness of any multidrug-resistant (MDR) target organism isolated from the environment to those isolated from clinical infections in...isolated from clinical infections from inpatients at the facility. Methods The study was undertaken as a quality improvement, patient safety project

  7. The burden of transmitted multi-drug resistance among epidemics of tuberculosis: A transmission model

    PubMed Central

    Kendall, Emily A.; Fofana, Mariam O.; Dowdy, David W.

    2015-01-01

    Background Multidrug-resistant tuberculosis (MDR-TB) can be acquired through de novo mutation during TB treatment or through transmission from other individuals with active MDR-TB. Understanding the balance between these two mechanisms is essential when allocating resources for MDR-TB. Methods We constructed a dynamic transmission model of an MDR-TB epidemic, allowing for both treatment-related acquisition and person-to-person transmission of resistance. We used national TB notification data to inform Bayesian estimates of the fraction of each country’s 2013 MDR-TB incidence that resulted from MDR transmission rather than treatment-related MDR acquisition. Findings Global estimates of 3·5% MDR-TB prevalence among new TB notifications and 20·5% among retreatment notifications translate into an estimate that resistance transmission rather than acquisition accounts for a median 96% (95% UR: 68–100%) of all incident MDR-TB, and 61% (16–95%) of incident MDR-TB in previously-treated individuals. The estimated percentage of MDR-TB resulting from transmission varied substantially with different countries’ notification data; for example, we estimated this percentage at 48% (30–75%) of MDR-TB in Bangladesh, versus 99% (91–100%) in Uzbekistan. Estimates were most sensitive to estimates of the transmissibility of MDR strains, the probability of acquiring MDR during tuberculosis treatment, and the responsiveness of MDR TB to first-line treatment. Interpretation Notifications of MDR prevalence from most high-burden settings are most consistent with the vast majority of incident MDR-TB resulting from transmission rather than new treatment-related acquisition of resistance. Merely improving the treatment of drug-susceptible TB is unlikely to greatly reduce future MDR-TB incidence. Improved diagnosis and treatment of MDR-TB – including new tests and drug regimens – should be highly prioritized. PMID:26597127

  8. Antibacterial and antibiotic-resistance modifying activity of the extracts and compounds from Nauclea pobeguinii against Gram-negative multi-drug resistant phenotypes.

    PubMed

    Seukep, Jackson A; Sandjo, Louis P; Ngadjui, Bonaventure T; Kuete, Victor

    2016-07-07

    Multi-drug resistance of Gram-negative bacteria constitutes a major obstacle in the antibacterial fight worldwide. The discovery of new and effective antimicrobials and/or resistance modulators is necessary to combat the spread of resistance or to reverse the multi-drug resistance. In this study, we investigated the antibacterial and antibiotic-resistance modifying activities against 29 Gram-negative bacteria including multi-drug resistant (MDR) phenotypes of the methanol extracts from Nauclea pobeguiinii leaves (NPL), Nauclea pobeguiinii bark (NPB) and six compounds from the bark extract, identified as 3-acetoxy-11-oxo-urs-12-ene (1), p-coumaric acid (2), citric acid trimethyl ester (3), resveratrol (4), resveratrol β- D -glucopyranoside (5) and strictosamide (6). The broth microdilution method was used to determine the minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC) of crude extracts and compounds as well as the antibiotic-resistance modifying effects of MPB and 4. MIC determinations indicate values ranging from 32-1024 μg/mL for NPB and NPL on 89.7 % and 69.0 % of the tested bacterial strains respectively. MIC values below 100 μg/mL were obtained with NPB against Escherichia coli ATCC10536, AG100 and Enterobacter aerogenes CM64 strains. The lowest MIC value for crude extracts of 32 μg/mL was obtained with NPB against E. coli ATCC10536. Compound 4 was active all tested bacteria, whilst 1, 3 and 6 displayed weak and selective inhibitory effects. The corresponding MIC value (16 μg/mL) was obtained with 4 against Klebsiella pneumoniae KP55 strain. Synergistic effects of the combination of NPB with chloramphenicol (CHL), kanamycin (KAN) as well as that of compound 4 with streptomycin (STR) and ciprofloxacin (CIP) were observed. The present study provides information on the possible use of Nauclea pobeguinii and compound 4 in the control of Gram-negative bacterial infections including MDR phenotypes. It also indicates

  9. Antibacterial effect of mango (Mangifera indica Linn.) leaf extract against antibiotic sensitive and multi-drug resistant Salmonella typhi.

    PubMed

    Hannan, Abdul; Asghar, Samra; Naeem, Tahir; Ikram Ullah, Muhammad; Ahmed, Ijaz; Aneela, Syeda; Hussain, Shabbir

    2013-07-01

    Alternative herbal medicine has been used to treat various infections from centuries. Natural plants contain phytoconstituents having similar chemical properties as of synthetic antibiotics. Typhoid fever is a serious infection and failure of its treatment emerged multi-drug resistant (MDR) bugs of Salmonella typhi. Due to multiple and repeated issues with antibiotics efficacy, it became essential to evaluate biological properties of plants from different geographical origins. Mango leaves have been Reported for various medicinal effects like antioxidant, antimicrobial, antihelminthic, antidiabetic and antiallergic etc. Objective of present study was to investigate anti-typhoid properties of acetone mango leaf extract (AMLE) against antibiotic sensitive and MDR S. typhi isolates. A total of 50 isolates of S. typhi including MDR (n=30) and antibiotic sensitive (n=20) were investigated. Staphylococcus aureus (ATCC 25923) and Salmonella typhimurium (ATCC14028) were used as quality control strains. AMLE was prepared and its antibacterial activity was evaluated by agar well diffusion screening method and minimum inhibitory concentration (MIC), by agar dilution technique. Zone of inhibition (mm) of AMLE against MDR and antibiotic sensitive isolates was 18±1.5mm (Mean±S.D). Zone of S. aureus (ATCC 25923) and S. typhimurium (ATCC14028) was 20±1.5mm (Mean±S.D). MIC of AMLE was Reported in range from 10-50 mg/ml. The present study described the inhibitory effects of mango leaves against S. typhi.

  10. The uptake of hydroxypropyl methacrylamide based homo, random and block copolymers by human multi-drug resistant breast adenocarcinoma cells

    PubMed Central

    Barz, Matthias; Luxenhofer, Robert; Zentel, Rudolf; Kabanov, Alexander V.

    2011-01-01

    A series of well defined, fluorescently labelled homopolymers, random and block copolymers based on N-(2-hydroxypropyl)-methacrylamide was prepared by reversible addition-fragmentation chain transfer polymerization (RAFT-polymerization). The polydispersity indexes for all polymers were in the range of 1.2 to 1.3 and the number average of the molar mass (Mn) for each polymer was set to be in the range of 15 kDa to 30 kDa. The cellular uptake of these polymers was investigated in the human multi-drug resistant breast adenocarcinoma cell line MCF7/ADR. The uptake greatly depended on the polymer molecular mass and structure. Specifically, smaller polymers (approx. 15 kDa) were taken up by the cells at much lower concentrations than larger polymers (approx. 30 kDa). Furthermore, for polymers of the same molar mass, the random copolymers were more easily internalized in cells than block copolymers or homopolymers. This is attributed to the fact that random copolymers form micelle-like aggregates by intra- and interchain interactions, which are smaller and less stable than the block copolymer structures in which the hydrophobic domain is buried and thus prevented from unspecific interaction with the cell membrane. Our findings underline the need for highly defined polymeric carriers and excipients for future applications in the field of nanomedicine. PMID:19631373

  11. Colistin combination therapy improves microbiologic cure in critically ill patients with multi-drug resistant gram-negative pneumonia.

    PubMed

    Parchem, N L; Bauer, K A; Cook, C H; Mangino, J E; Jones, C D; Porter, K; Murphy, C V

    2016-09-01

    Currently, in vitro synergy with colistin has not translated into improved clinical outcomes. This study aimed to compare colistin combination therapy to colistin monotherapy in critically ill patients with multi-drug resistant gram-negative (MDR-GN) pneumonia. This was a retrospective analysis of critically ill adult patients receiving intravenous colistin for MDR-GN pneumonia comparing colistin combination therapy to colistin monotherapy with a primary endpoint of clinical cure. Combination therapy was defined by administration of another antibiotic to which the MDR-GN pathogen was reported as susceptible or intermediate. Ninety patients were included for evaluation (41 combination therapy and 49 monotherapy). Baseline characteristics were similar between groups. No difference in clinical cure was observed between combination therapy and monotherapy in univariate analysis, nor when adjusted for APACHE II score and time to appropriate antibiotic therapy (57.1 vs. 63.4 %, adjusted OR 1.15, p = 0.78). Microbiological cure was significantly higher for combination therapy (87 vs. 35.5 %, p < 0.001). Colistin combination therapy was associated with a significant improvement in microbiological cure, without improvement in clinical cure. Based on the in vitro synergy and improvement in microbiological clearance, colistin combination therapy should be prescribed for MDR-GN pneumonia. Further research is warranted to determine if in vitro synergy with colistin translates into improved clinical outcomes.

  12. Antibacterial efficacy of silver nanoparticles against multi-drug resistant clinical isolates from post-surgical wound infections.

    PubMed

    Kasithevar, Muthupandi; Periakaruppan, Prakash; Muthupandian, Saravanan; Mohan, Mahalakshmi

    2017-06-01

    In order to investigate new effective and inexpensive nano-therapeutic approach for P. aeruginosa, staphylococcus aureus and coagulase negative staphylococci (CoNS), the present study reports an eco-friendly process for rapid synthesis of silver nanoparticles (Ag-NPs) using aqueous leaf extract of Corchorus Capsularis (CRCP). Formation of stable Ag-NPs at different time intervals gives mostly spherical particles with diameters ranging from 5 to 45 nm. The resulting Ag-NPs were characterized using Ultraviolet visible (UV-Vis) spectroscopy, Fourier Transform Infrared (FT-IR) spectroscopy, X-Ray Diffraction (XRD) analysis, Transmission Electron Microscopy (TEM) and Energy Dispersive X-ray analysis (EDX). XRD study shows that the particles are crystalline in nature with face centered cubic geometry. TEM studies show the formation of Ag-NPs with average size of 20.52 nm. The antimicrobial activity of the synthesized Ag-NPs was investigated against multi drug resistant (MDR) P. aeruginosa, Staphylococcus aureus and CoNS isolates from post-surgical wound infections. The present study suggests that Ag-NPs synthesized from aqueous leaf extract of CRCP shows significant antibacterial potential against MDR isolates from post-surgical wound infections. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Reasons for Non-Enrollment in Treatment among Multi-Drug Resistant Tuberculosis Patients in Hunan Province, China

    PubMed Central

    Xiao, Tao; Li, Yanhong; Yang, Kunyun; Tang, Yi; Bai, Liqiong

    2017-01-01

    In 2015, only 49% of notified multi-drug resistant tuberculosis (MDR-TB) patients in China were estimated to have initiated treatment, compared with 90% of those worldwide. A case-control study was conducted to identify the reasons for non-enrollment in treatment among MDR-TB patients in Hunan province, China. All detected MDR-TB patients registered in designated MDR-TB hospitals in Hunan province from 2011 to 2014 were included and followed until June 2015 to determine their treatment status. Approximately 33.8% (482/1425) of patients were not enrolled in standardized treatment. Factors associated with lower enrollment rate were: age greater than 60 years, living in rural area, unemployed or occupation unreported. Of those who were not enrolled in MDR-TB treatment, the primary reasons for non-enrollment included economic hardship (23.0%), out-migration for work (18.0%), concerns about work and studies (13.7%), and the belief that they were cured after undergoing drug-sensitive TB treatment (12.4%). Therefore, comprehensive strategies targeting priority populations, especially those enhancing treatment affordability and availability, need to be implemented to improve MDR-TB control. PMID:28114320

  14. Host-Directed Therapies for Tackling Multi-Drug Resistant Tuberculosis: Learning From the Pasteur-Bechamp Debates.

    PubMed

    Zumla, Alimuddin; Maeurer, Markus

    2015-11-01

    Tuberculosis remains a global emergency causing an estimated 1.5 million deaths annually. For several decades the major focus of tuberculosis treatment has been on antibiotic development targeting Mycobacterium tuberculosis. The lengthy tuberculosis treatment duration and poor treatment outcomes associated with multi-drug resistant tuberculosis (MDR-TB) are of major concern. The sparse new tuberculosis drug pipeline and widespread emergence of MDR-TB signal an urgent need for more innovative interventions to improve treatment outcomes. Building on the historical Pasteur-Bechamp debates on the role of the "microbe" vs the "host internal milieu" in disease causation, we make the case for parallel investments into host-directed therapies (HDTs). A range of potential HDTs are now available which require evaluation in randomized controlled clinical trials as adjunct therapies for shortening the duration of tuberculosis therapy and improving treatment outcomes for drug-susceptible tuberculosis and MDR-TB. Funder initiatives that may enable further research into HDTs are described.

  15. MMP1 expression is activated by Slug and enhances multi-drug resistance (MDR) in breast cancer

    PubMed Central

    Chen, Chien-Chung; Chen, Ming-Jenn

    2017-01-01

    High matrix metalloproteinase 1 (MMP1) expression is associated with enhanced breast cancer growth and metastasis and also might predict poor prognosis. In this study, we further investigated the functional role of MMP1 and how it is upregulated in multi-drug resistant (MDR) breast cancer cells. By retrieving microarray data in GEO datasets and the survival data in the Kaplan Meier plotter, we observed that MMP1 is significantly upregulated in MCF-7/ADR cells compared to the parental MCF-7 cells, while high MMP1 expression is associated with worse overall survival (OS) and recurrence free survival (RFS) in breast cancer patients after systematic therapy. Functional studies showed that MMP1 overexpression significantly reduced the drug sensitivity in MCF-7 cells, while MMP1 knockdown substantially enhanced the sensitivity in MCF-7/ADR cells. By performing western blotting and immunofluorescent staining, we confirmed that MCF-7/ADR cells had enhanced mesenchymal properties than MCF-7 cells. In MCF-7 cells, enforced Slug expression resulted in significant MMP1 upregulation, while in MCF-7/ADR cells, Slug knockdown led to reduced MMP1 expression. By performing bioinformatic analysis, we observed that the promoter of MMP1 has three putative Slug binding sites. The following dual luciferase assay and ChIP-qPCR verified these three binding sites. Therefore, we infer that Slug enhances MMP1 transcription via directly binding to the promoter region in breast cancer cells, which is a previously unrecognized mechanism in the development of MDR. PMID:28334049

  16. Snail-Induced Epithelial-to-Mesenchymal Transition Enhances P-gp-Mediated Multi Drug Resistance in HCC827 Cells.

    PubMed

    Tomono, Takumi; Yano, Kentaro; Ogihara, Takuo

    2017-03-17

    Overexpression and/or activation of P-glycoprotein (P-gp), which mediates efflux transport of various anti-cancer drugs in cancer cells, are associated with multi-drug resistance (MDR). On the other hand, malignant cancer cells frequently undergo epithelial-to-mesenchymal transition (EMT), thereby acquiring high migratory mobility and invasive ability. Snail is a transcriptional factor that represses multiple other factors, and its overexpression is a trigger of EMT. Since both P-gp and Snail are involved in malignant evolution of cancer, in this work, we evaluated whether or not EMT induced by overexpression of Snail influences P-gp expression and/or activity. Snail-overexpressing cells showed downregulation of epithelial markers, E-cadherin, occludin and claudin-1, and upregulation of mesenchymal markers, vimenin and ZEB1. Although Western blot analysis showed that P-gp expression levels were similar in Mock and Snail-overexpressing cells, the results of P-gp functional assays with P-gp substrates rhodamine123 and paclitaxel indicated that P-gp is activated in Snail-overexpressing cells. Indeed, Snail-overexpressing cells showed greater viability than Mock cells in the presence of paclitaxel. We observed caveolin-1 dephosphorylation and decreased GRB2 expression in Snail-overexpressing cells. These findings suggest a novel pathway leading to cancer MDR, in which Snail induces EMT concomitantly with a decrease of GRB2-mediated caveolin-1 phosphorylation, resulting in activation of P-gp.

  17. Turning the gun on cancer: Utilizing lysosomal P-glycoprotein as a new strategy to overcome multi-drug resistance.

    PubMed

    Seebacher, Nicole; Lane, Darius J R; Richardson, Des R; Jansson, Patric J

    2016-07-01

    Oxidative stress plays a role in the development of drug resistance in cancer cells. Cancer cells must constantly and rapidly adapt to changes in the tumor microenvironment, due to alterations in the availability of nutrients, such as glucose, oxygen and key transition metals (e.g., iron and copper). This nutrient flux is typically a consequence of rapid growth, poor vascularization and necrosis. It has been demonstrated that stress factors, such as hypoxia and glucose deprivation up-regulate master transcription factors, namely hypoxia inducible factor-1α (HIF-1α), which transcriptionally regulate the multi-drug resistance (MDR), transmembrane drug efflux transporter, P-glycoprotein (Pgp). Interestingly, in addition to the established role of plasma membrane Pgp in MDR, a new paradigm of intracellular resistance has emerged that is premised on the ability of lysosomal Pgp to transport cytotoxic agents into this organelle. This mechanism is enabled by the topological inversion of Pgp via endocytosis resulting in the transporter actively pumping agents into the lysosome. In this way, classical Pgp substrates, such as doxorubicin (DOX), can be actively transported into this organelle. Within the lysosome, DOX becomes protonated upon acidification of the lysosomal lumen, causing its accumulation. This mechanism efficiently traps DOX, preventing its cytotoxic interaction with nuclear DNA. This review discusses these effects and highlights a novel mechanism by which redox-active and protonatable Pgp substrates can utilize lysosomal Pgp to gain access to this compartment, resulting in catastrophic lysosomal membrane permeabilization and cell death. Hence, a key MDR mechanism that utilizes Pgp (the "gun") to sequester protonatable drug substrates safely within lysosomes can be "turned on" MDR cancer cells to destroy them from within. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Honokiol Enhances Paclitaxel Efficacy in Multi-Drug Resistant Human Cancer Model through the Induction of Apoptosis

    PubMed Central

    Wang, Xu; Beitler, Jonathan J.; Wang, Hong; Lee, Michael J.; Huang, Wen; Koenig, Lydia; Nannapaneni, Sreenivas; Amin, A. R. M. Ruhul; Bonner, Michael; Shin, Hyung Ju C.; Chen, Zhuo Georgia; Arbiser, Jack L.; Shin, Dong M.

    2014-01-01

    Resistance to chemotherapy remains a major obstacle in cancer therapy. This study aimed to evaluate the molecular mechanism and efficacy of honokiol in inducing apoptosis and enhancing paclitaxel chemotherapy in pre-clinical multi-drug resistant (MDR) cancer models, including lineage-derived human MDR (KB-8-5, KB-C1, KB-V1) and their parental drug sensitive KB-3-1 cancer cell lines. In vitro analyses demonstrated that honokiol effectively inhibited proliferation in KB-3-1 cells and the MDR derivatives (IC50 ranging 3.35±0.13 µg/ml to 2.77±0.22 µg/ml), despite their significant differences in response to paclitaxel (IC50 ranging 1.66±0.09 ng/ml to 6560.9±439.52 ng/ml). Honokiol induced mitochondria-dependent and death receptor-mediated apoptosis in MDR KB cells, which was associated with inhibition of EGFR-STAT3 signaling and downregulation of STAT3 target genes. Combined treatment with honokiol and paclitaxel synergistically augmented cytotoxicity in MDR KB cells, compared with treatment with either agent alone in vitro. Importantly, the combined treatment significantly inhibited in vivo growth of KB-8-5 tumors in a subcutaneous model. Tumor tissues from the combination group displayed a significant inhibition of Ki-67 expression and an increase in TUNEL-positive cells compared with the control group. These results suggest that targeting multidrug resistance using honokiol in combination with chemotherapy drugs may provide novel therapeutic opportunities. PMID:24586249

  19. Honokiol enhances paclitaxel efficacy in multi-drug resistant human cancer model through the induction of apoptosis.

    PubMed

    Wang, Xu; Beitler, Jonathan J; Wang, Hong; Lee, Michael J; Huang, Wen; Koenig, Lydia; Nannapaneni, Sreenivas; Amin, A R M Ruhul; Bonner, Michael; Shin, Hyung Ju C; Chen, Zhuo Georgia; Arbiser, Jack L; Shin, Dong M

    2014-01-01

    Resistance to chemotherapy remains a major obstacle in cancer therapy. This study aimed to evaluate the molecular mechanism and efficacy of honokiol in inducing apoptosis and enhancing paclitaxel chemotherapy in pre-clinical multi-drug resistant (MDR) cancer models, including lineage-derived human MDR (KB-8-5, KB-C1, KB-V1) and their parental drug sensitive KB-3-1 cancer cell lines. In vitro analyses demonstrated that honokiol effectively inhibited proliferation in KB-3-1 cells and the MDR derivatives (IC50 ranging 3.35 ± 0.13 µg/ml to 2.77 ± 0.22 µg/ml), despite their significant differences in response to paclitaxel (IC50 ranging 1.66 ± 0.09 ng/ml to 6560.9 ± 439.52 ng/ml). Honokiol induced mitochondria-dependent and death receptor-mediated apoptosis in MDR KB cells, which was associated with inhibition of EGFR-STAT3 signaling and downregulation of STAT3 target genes. Combined treatment with honokiol and paclitaxel synergistically augmented cytotoxicity in MDR KB cells, compared with treatment with either agent alone in vitro. Importantly, the combined treatment significantly inhibited in vivo growth of KB-8-5 tumors in a subcutaneous model. Tumor tissues from the combination group displayed a significant inhibition of Ki-67 expression and an increase in TUNEL-positive cells compared with the control group. These results suggest that targeting multidrug resistance using honokiol in combination with chemotherapy drugs may provide novel therapeutic opportunities.

  20. Penicillin resistance and serotyping of Streptococcus pneumoniae in Latin America.

    PubMed

    Camargos, Paulo; Fischer, Gilberto Bueno; Mocelin, Helena; Dias, Cícero; Ruvinsky, Raúl

    2006-09-01

    Streptococcus pneumoniae (Strep. pneumoniae) is the main cause of bacterial pneumonia in children less than 5 years of age, with high mortality rates in developing countries. In 1993, the Regional System for Vaccines Group (SIREVA) of the pan-American Health Organisation (PAHO) began a study involving six Latin American countries to identify serotypes and their representativity in the new conjugated vaccines, and to determine the degree of resistance to penicillin. Serotypes 14 (highest resistance level), 5, 1, 6A/B, 23F, 7F, 9V, 19F, 18C, 19A, 9N, were prevalent in the region, with some differences among countries. Although resistance to penicillin ranged from 2% (Brazil) to 21.1% (Mexico), studies have shown that pneumonia caused by Strep. pneumoniae with diminished sensitivity to penillin can be treated with this antibiotic. Only 58% of the serotypes isolated in the region studied were represented in the seven-valent vaccine. Continual surveillance is essential to determine which formulation of conjugated vaccine will be suitable for use in Latin America.

  1. Antibacterial and antibiotic resistance modifying activity of the extracts from Allanblackia gabonensis, Combretum molle and Gladiolus quartinianus against Gram-negative bacteria including multi-drug resistant phenotypes.

    PubMed

    Fankam, Aimé G; Kuiate, Jules R; Kuete, Victor

    2015-06-30

    Bacterial resistance to antibiotics is becoming a serious problem worldwide. The discovery of new and effective antimicrobials and/or resistance modulators is necessary to tackle the spread of resistance or to reverse the multi-drug resistance. We investigated the antibacterial and antibiotic-resistance modifying activities of the methanol extracts from Allanblackia gabonensis, Gladiolus quartinianus and Combretum molle against 29 Gram-negative bacteria including multi-drug resistant (MDR) phenotypes. The broth microdilution method was used to determine the minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC) of the samples meanwhile the standard phytochemical methods were used for the preliminary phytochemical screening of the plant extracts. Phytochemical analysis showed the presence of alkaloids, flavonoids, phenols and tannins in all studied extracts. Other chemical classes of secondary metabolites were selectively presents. Extracts from A. gabonensis and C. molle displayed a broad spectrum of activity with MICs varying from 16 to 1024 μg/mL against about 72.41% of the tested bacteria. The extract from the fruits of A. gabonensis had the best activity, with MIC values below 100 μg/mL on 37.9% of tested bacteria. Percentages of antibiotic-modulating effects ranging from 67 to 100% were observed against tested MDR bacteria when combining the leaves extract from C. molle (at MIC/2 and MIC/4) with chloramphenicol, kanamycin, streptomycin and tetracycline. The overall results of the present study provide information for the possible use of the studied plant, especially Allanblackia gabonensis and Combretum molle in the control of Gram-negative bacterial infections including MDR species as antibacterials as well as resistance modulators.

  2. Antimicrobial Action of Water-Soluble β-Chitosan against Clinical Multi-Drug Resistant Bacteria

    PubMed Central

    Park, Seong-Cheol; Nam, Joung-Pyo; Kim, Jun-Ho; Kim, Young-Min; Nah, Jae-Woon; Jang, Mi-Kyeong

    2015-01-01

    Recently, the number of patients infected by drug-resistant pathogenic microbes has increased remarkably worldwide, and a number of studies have reported new antibiotics from natural sources. Among them, chitosan, with a high molecular weight and α-conformation, exhibits potent antimicrobial activity, but useful applications as an antibiotic are limited by its cytotoxicity and insolubility at physiological pH. In the present study, the antibacterial activity of low molecular weight water-soluble (LMWS) α-chitosan (α1k, α5k, and α10k with molecular masses of 1, 5, and 10 kDa, respectively) and β-chitosan (β1k, β5k, and β10k) was compared using a range of pathogenic bacteria containing drug-resistant bacteria isolated from patients at different pH. Interestingly, β5k and β10k exhibited potent antibacterial activity, even at pH 7.4, whereas only α10k was effective at pH 7.4. The active target of β-chitosan is the bacterial membrane, where the leakage of calcein is induced in artificial PE/PG vesicles, bacterial mimetic membrane. Moreover, scanning electron microscopy showed that they caused significant morphological changes on the bacterial surfaces. An in vivo study utilizing a bacteria-infected mouse model found that LMWS β-chitosan could be used as a candidate in anti-infective or wound healing therapeutic applications. PMID:25867474

  3. Multi-Drug-Resistant Klebsiella pneumoniae Pancreatitis: A New Challenge in a Serious Surgical Infection

    PubMed Central

    Tugal, Derin; Lynch, Melanie; Hujer, Andrea M.; Rudin, Susan; Perez, Federico

    2015-01-01

    Abstract Background: Klebsiella pneumoniae is an important cause of nosocomial infections, but its role in severe acute pancreatitis (SAP) is not well defined. Few cases of K. pneumoniae associated SAP have been reported. Due to the emergence of extended-spectrum beta-lactamases (ESBLs) and carbapenemases, treatment of multidrug-resistant (MDR) K. pneumoniae presents a challenge. Tigecycline and colistin have gained recent attention for their broad-spectrum antimicrobial activity. Methods: We describe a case of SAP due to K. pneumoniae bearing K. pneumoniae carbapenemase (KPC) treated successfully with colistin plus tigecycline and offer a review of similar experiences published in the literature. Results: The case reported herein required surgical drainage of multiple pancreatic abscesses and treatment with tigecycline and colistin. Our comparative analysis revealed a number of unique features associated with SAP due to K. pneumoniae: 1) underlying pancreatic injury, 2) multiple drug resistance determinants and virulence factors that complicate treatment, and 3) surgical debridement as a requirement for cure. Conclusion: As the prevalence of K. pneumoniae bearing KPC continues to increase in the healthcare setting, SAP caused by this MDR pathogen will become more common. Tigecycline plus colistin was a successful antibiotic regimen for the treatment of SAP due to K. pneumoniae bearing KPC. PMID:24850293

  4. Whole animal automated platform for drug discovery against multi-drug resistant Staphylococcus aureus.

    PubMed

    Rajamuthiah, Rajmohan; Fuchs, Beth Burgwyn; Jayamani, Elamparithi; Kim, Younghoon; Larkins-Ford, Jonah; Conery, Annie; Ausubel, Frederick M; Mylonakis, Eleftherios

    2014-01-01

    Staphylococcus aureus, the leading cause of hospital-acquired infections in the United States, is also pathogenic to the model nematode Caenorhabditis elegans. The C. elegans-S. aureus infection model was previously carried out on solid agar plates where the bacteriovorous C. elegans feeds on a lawn of S. aureus. However, agar-based assays are not amenable to large scale screens for antibacterial compounds. We have developed a high throughput liquid screening assay that uses robotic instrumentation to dispense a precise amount of methicillin resistant S. aureus (MRSA) and worms in 384-well assay plates, followed by automated microscopy and image analysis. In validation of the liquid assay, an MRSA cell wall defective mutant, MW2ΔtarO, which is attenuated for killing in the agar-based assay, was found to be less virulent in the liquid assay. This robust assay with a Z'-factor consistently greater than 0.5 was utilized to screen the Biomol 4 compound library consisting of 640 small molecules with well characterized bioactivities. As proof of principle, 27 of the 30 clinically used antibiotics present in the library conferred increased C. elegans survival and were identified as hits in the screen. Surprisingly, the antihelminthic drug closantel was also identified as a hit in the screen. In further studies, we confirmed the anti-staphylococcal activity of closantel against vancomycin-resistant S. aureus isolates and other Gram-positive bacteria. The liquid C. elegans-S. aureus assay described here allows screening for anti-staphylococcal compounds that are not toxic to the host.

  5. Whole Animal Automated Platform for Drug Discovery against Multi-Drug Resistant Staphylococcus aureus

    PubMed Central

    Rajamuthiah, Rajmohan; Fuchs, Beth Burgwyn; Jayamani, Elamparithi; Kim, Younghoon; Larkins-Ford, Jonah; Conery, Annie; Ausubel, Frederick M.; Mylonakis, Eleftherios

    2014-01-01

    Staphylococcus aureus, the leading cause of hospital-acquired infections in the United States, is also pathogenic to the model nematode Caenorhabditis elegans. The C. elegans-S. aureus infection model was previously carried out on solid agar plates where the bacteriovorous C. elegans feeds on a lawn of S. aureus. However, agar-based assays are not amenable to large scale screens for antibacterial compounds. We have developed a high throughput liquid screening assay that uses robotic instrumentation to dispense a precise amount of methicillin resistant S. aureus (MRSA) and worms in 384-well assay plates, followed by automated microscopy and image analysis. In validation of the liquid assay, an MRSA cell wall defective mutant, MW2ΔtarO, which is attenuated for killing in the agar-based assay, was found to be less virulent in the liquid assay. This robust assay with a Z’-factor consistently greater than 0.5 was utilized to screen the Biomol 4 compound library consisting of 640 small molecules with well characterized bioactivities. As proof of principle, 27 of the 30 clinically used antibiotics present in the library conferred increased C. elegans survival and were identified as hits in the screen. Surprisingly, the antihelminthic drug closantel was also identified as a hit in the screen. In further studies, we confirmed the anti-staphylococcal activity of closantel against vancomycin-resistant S. aureus isolates and other Gram-positive bacteria. The liquid C. elegans – S. aureus assay described here allows screening for anti-staphylococcal compounds that are not toxic to the host. PMID:24586584

  6. Molecular detection assay of five Salmonella serotypes of public interest: Typhimurium, Enteritidis, Newport, Heidelberg, and Hadar.

    PubMed

    Bugarel, M; Tudor, A; Loneragan, G H; Nightingale, K K

    2017-03-01

    Foodborne illnesses due to Salmonella represent an important public-health concern worldwide. In the United States, a majority of Salmonella infections are associated with a small number of serotypes. Furthermore, some serotypes that are overrepresented among human disease are also associated with multi-drug resistance phenotypes. Rapid detection of serotypes of public-health concern might help reduce the burden of salmonellosis cases and limit exposure to multi-drug resistant Salmonella. We developed a two-step real-time PCR-based rapid method for the identification and detection of five Salmonella serotypes that are either overrepresented in human disease or frequently associated with multi-drug resistance, including serotypes Enteritidis, Typhimurium, Newport, Hadar, and Heidelberg. Two sets of four markers were developed to detect and differentiate the five serotypes. The first set of markers was developed as a screening step to detect the five serotypes; whereas, the second set was used to further distinguish serotypes Heidelberg, Newport and Hadar. The utilization of these markers on a two-step investigation strategy provides a diagnostic specificity of 97% for the detection of Typhimurium, Enteritidis, Heidelberg, Infantis, Newport and Hadar. The diagnostic sensitivity of the detection makers is >96%. The availability of this two-step rapid method will facilitate specific detection of Salmonella serotypes that contribute to a significant proportion of human disease and carry antimicrobial resistance. Published by Elsevier B.V.

  7. [Immunotherapy for MDR-TB (multi-drug resistant tuberculosis)--its feasibility].

    PubMed

    Tsuyuguchi, I

    1999-06-01

    MDR-TB is known to be man-made-disease. Inappropriate treatment of tuberculosis is responsible for the development of MDR-TB. MDR-TB is often accompanied with the immunosuppression of the host. Given that we are unable to develop another potent anti-TB drug in near future, immunotherapy directed at combating immunosuppression and enhancing the host's own immune response is an attractive approach to supplement conventional chemotherapy for MDR-TB. Patients with AIDS and patients with abnormalities of macrophage function have frequent problems with TB. This is suggesting that the host defenses involved in protection against mycobacteria include T-cell and monocyte/macrophage functions. That is cell-mediated immunity. Diverse cytokines are known to play an important role in anti-TB cell-mediated immunity, including IL-2, IL-12, IL-18 and IFN-gamma. Various animal experiments are indicating that administration of these cytokine (s) did recover the suppressed immunity and rescued the host from death by tuberculous infection. However, we have to keep it in mind that the results obtained from animal model of mycobacterial infection on the study of pathogenesis and immune responses in TB is not always applicable to the understanding of human TB. Clinical trial of inhalation therapy with IFN-gamma showed some improvement for drug-resistant TB. Cytokine treatment, however, often gave some deleterious side effects such as high fever, malaise, general edema and even the death of the host. Clinical trials with M. vaccae have been extensively conducted by UK group. The mechanisms underlying its possible therapeutic action remain to be clarified, but when administered at an appropriate dose, it has been shown to elicit a strong Th1 immune response. From the practical view point of immunotherapy for TB, surrogate markers of disease eradication and protective immunity are urgently required. Such markers would facilitate clinical trials by providing early evidence that test

  8. Risk Factors for Multi-Drug Resistant Pathogens and Failure of Empiric First-Line Therapy in Acute Cholangitis

    PubMed Central

    Reuken, Philipp A.; Torres, Dorian; Baier, Michael; Löffler, Bettina; Lübbert, Christoph; Lippmann, Norman; Stallmach, Andreas; Bruns, Tony

    2017-01-01

    Background Acute cholangitis (AC) requires the immediate initiation of antibiotic therapy in addition to treatment for biliary obstruction. Against a background of an increasing prevalence of multi-drug resistant (MDR) bacteria, the risk factors for the failure of empiric therapy must be defined. Methods Using a pathogen-based approach, 1764 isolates from positive bile duct cultures were retrospectively analyzed to characterize the respective pathogen spectra in two German tertiary centers. Using a patient-based approach, the clinical and laboratory data for 83 patients with AC were assessed to identify risk factors for AC with pathogens resistant to the applied empiric therapy. Results Bile cultures were predominantly polymicrobial, and empiric antibiotic therapies did not cover the full biliary pathogen spectrum in 78% of cases. MDR bacteria were isolated from the bile of 24/83 (29%) patients. The univariate risk factors for biliary MDR bacteria were male sex, nosocomial AC, prior antibiotic exposure and prior biliary stenting, of which biliary stenting was the only independent risk factor according to multivariate analysis (OR = 3.8; 95% CI 1.3–11.0, P = 0.013). Although there were no significant differences in survival or hospital stay in AC patients with and without detected biliary MDR pathogens, the former more often had a concomitant bloodstream infection (58% vs. 24%; P = 0.019), including those involving MDR pathogens or fungi (21% vs. 2%; P = 0.007). Conclusion Patients with biliary stents who develop AC should receive empiric therapy covering enterococci and extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. These patients are at an increased risk for bloodstream infections by MDR pathogens or fungi. PMID:28076388

  9. Synergistic effect of Myrtus communis L. essential oils and conventional antibiotics against multi-drug resistant Acinetobacter baumannii wound isolates.

    PubMed

    Aleksic, Verica; Mimica-Dukic, Neda; Simin, Natasa; Nedeljkovic, Natasa Stankovic; Knezevic, Petar

    2014-10-15

    Acinetobacter baumannii is a rapidly emerging, highly resistant clinical pathogen with increasing prevalence. In recent years, the limited number of antimicrobial agents available for treatment of infections with multi-drug resistant (MDR) strains reinforced tendency for discovery of novel antimicrobial agents or treatment strategies. The aim of the study was to determine antimicrobial effectiveness of three Myrtus communis L. essential oils, both alone and in combination with conventional antibiotics, against MDR A. baumannii wound isolates. The results obtained highlighted the occurrence of good antibacterial effect of myrtle oils when administered alone. Using checkerboard method, the combinations of subinhibitory concentrations of myrtle essential oils and conventional antibiotics, i.e. polymixin B and ciprofloxacine were examined. The results proved synergism among M. communis L. essential oils and both antibiotics against MDR A. baumannii wound isolates, with a FIC index under or equal 0.50. Combination of subinhibitory concentrations of essential oils and ciprofloxacin most frequently reduced bacterial growth in synergistic manner. The similar has been shown for combination with polymyxin B; furthermore, the myrtle essential oil resulted in re-sensitization of the MDR wound isolates, i.e. MICs used in combination were below the cut off for the sensitivity to the antibiotic. Time-kill curve method confirmed efficacy of myrtle essential oil and polymyxin B combination, with complete reduction of bacterial count after 6h. The detected synergy offers an opportunity for future development of treatment strategies for potentially lethal wound infections caused by MDR A. baumannii. Copyright © 2014 Elsevier GmbH. All rights reserved.

  10. Molecular and cytogenetic changes in multi-drug resistant cancer cells and their influence on new compounds testing.

    PubMed

    Podolski-Renić, Ana; Jadranin, Milka; Stanković, Tijana; Banković, Jasna; Stojković, Sonja; Chiourea, Maria; Aljančić, Ivana; Vajs, Vlatka; Tešević, Vele; Ruždijić, Sabera; Gagos, Sarantis; Tanić, Nikola; Pešić, Milica

    2013-09-01

    Multi-drug resistance (MDR) is a major obstacle to successful cancer treatment. Therefore, in vitro models are necessary for the investigation of the phenotypic changes provoked by cytotoxic agents and more importantly for preclinical testing of new anticancer drugs. We analyzed chromosomal, numerical, and structural changes after development of MDR, alterations in p53 and PTEN, single nucleotide polymorphisms (SNPs) in the mdr1 gene and corresponding protein expression of P-glycoprotein (P-gp) in three human MDR cancer cell lines: non-small cell lung carcinoma NCI-H460/R, colorectal carcinoma DLD1-TxR, and glioma U87-TxR. In addition, we explored how these molecular and phenotypic alterations influence the anticancer effect of new drugs. Cytogenetic analysis showed polyploidy reduction after development of MDR in U87-TxR. Losses of 6q in all resistant cancer cell lines and inactivation of p53 in U87-TxR and PTEN in DLD1-TxR were also revealed. Overexpression of P-gp was observed in all MDR cancer cell lines. We evaluated the anticancer activities and MDR reversal potential of Akt inhibitor GSK690693, Ras inhibitor Tipifarnib, and two P-gp inhibitors (jatrophane diterpenoids). Their effects vary due to the cell-type differences, existence of MDR phenotype, presence of mdr1 SNP, and tumor suppressors' alterations. Tipifarnib and jatrophane diterpenoids significantly sensitized MDR cancer cells to paclitaxel. In conclusion, investigated MDR cancer cells obtained new molecular and cytogenetic characteristics that may serve as potential clinical prognostic markers. In addition, these MDR cancer cell lines present a valuable model for preclinical evaluation of new anticancer agents.

  11. Phage therapy: An alternative to antibiotics in the age of multi-drug resistance

    PubMed Central

    Lin, Derek M; Koskella, Britt; Lin, Henry C

    2017-01-01

    The practice of phage therapy, which uses bacterial viruses (phages) to treat bacterial infections, has been around for almost a century. The universal decline in the effectiveness of antibiotics has generated renewed interest in revisiting this practice. Conventionally, phage therapy relies on the use of naturally-occurring phages to infect and lyse bacteria at the site of infection. Biotechnological advances have further expanded the repertoire of potential phage therapeutics to include novel strategies using bioengineered phages and purified phage lytic proteins. Current research on the use of phages and their lytic proteins, specifically against multidrug-resistant bacterial infections, suggests phage therapy has the potential to be used as either an alternative or a supplement to antibiotic treatments. Antibacterial therapies, whether phage- or antibiotic-based, each have relative advantages and disadvantages; accordingly, many considerations must be taken into account when designing novel therapeutic approaches for preventing and treating bacterial infections. Although much is still unknown about the interactions between phage, bacteria, and human host, the time to take phage therapy seriously seems to be rapidly approaching. PMID:28828194

  12. Phage therapy: An alternative to antibiotics in the age of multi-drug resistance.

    PubMed

    Lin, Derek M; Koskella, Britt; Lin, Henry C

    2017-08-06

    The practice of phage therapy, which uses bacterial viruses (phages) to treat bacterial infections, has been around for almost a century. The universal decline in the effectiveness of antibiotics has generated renewed interest in revisiting this practice. Conventionally, phage therapy relies on the use of naturally-occurring phages to infect and lyse bacteria at the site of infection. Biotechnological advances have further expanded the repertoire of potential phage therapeutics to include novel strategies using bioengineered phages and purified phage lytic proteins. Current research on the use of phages and their lytic proteins, specifically against multidrug-resistant bacterial infections, suggests phage therapy has the potential to be used as either an alternative or a supplement to antibiotic treatments. Antibacterial therapies, whether phage- or antibiotic-based, each have relative advantages and disadvantages; accordingly, many considerations must be taken into account when designing novel therapeutic approaches for preventing and treating bacterial infections. Although much is still unknown about the interactions between phage, bacteria, and human host, the time to take phage therapy seriously seems to be rapidly approaching.

  13. Bicalutamide failure in prostate cancer treatment: involvement of Multi Drug Resistance proteins.

    PubMed

    Colabufo, Nicola Antonio; Pagliarulo, Vincenzo; Berardi, Francesco; Contino, Marialessandra; Inglese, Carmela; Niso, Mauro; Ancona, Patrizia; Albo, Giancarlo; Pagliarulo, Arcangelo; Perrone, Roberto

    2008-12-28

    Prolonged bicalutamide treatment induced pathology regression although relapses with a more aggressive form of prostate cancer have been observed. This failure could be due to androgen receptor mutation. In the present work we hypothesized an alternative mechanism responsible for bicalutamide failure involving activity of ATP-binding cassette (ABC) pumps such as P-glycoprotein, Breast Cancer Receptor Protein (BCRP), and Multi Resistant Proteins (MRPs) that extrude the androgen antagonist from the cell membrane. As experimental models androgen-dependent (LnCap) and androgen-independent (PC-3) prostate cancer cell lines have been employed. Bicalutamide has been tested in the cell lines mentioned above in the absence and in the presence of MC18, our potent P-glycoprotein/BCRP/MRP1 inhibitor. The results displayed that bicalutamide antiproliferative effect at 72 h was ameliorated in LnCap cells (EC(50) from 51.9+/-6.1 microM to 17.8+/-2.6 microM in the absence and in the presence of MC18, respectively) and restored in PC-3 cells (EC(50) from 150+/-2.4 microM to 60+/-3.5 microM in the absence and in the presence of MC18, respectively). Moreover, we established the contribution of each transporter employing stable transfected cells (MDCK) overexpressing P-glycoprotein or BCRP or MRP1 pump. The results displayed that P-glycoprotein and BCRP were involved in bicalutamide efflux while MRP1 was unable to bind the antiandrogen drug.

  14. Clinical importance and cost of bacteremia caused by nosocomial multi drug resistant acinetobacter baumannii.

    PubMed

    Gulen, Tugba Arslan; Guner, Rahmet; Celikbilek, Nevreste; Keske, Siran; Tasyaran, Mehmet

    2015-09-01

    A. baumannii is an important nosocomial pathogen associated with high mortality, morbidity and medical cost. The aim of this study was to investigate risk factors for MDR A. baumannii bacteremia and also evaluate cost of hospitalization of these patients. Study was conducted in Ankara Atatürk Training and Research Hospital. Patients who were hospitalized in ICU and diagnosed for nosocomial blood stream infection (BSI) between January 2007 and December 2010 were checked retrospectively. Patients with nosocomial BSI caused by multidrug resistant A. baumannii were compared with the patients who had BSI caused by other Gram-negative microorganisms in terms of risk factors, mortality and medical costs. In multivariate analysis previous use of carbapenem, quinolone and metronidazole, and SAPS II score were found as independent risk factors. In case group; immunosupression, SAPS II score, and hospital stay until infection were independently associated with mortality in multivariate analysis. Our results suggest that the occurrence of MDR A.baumannii bacteremia was related with the usage of the wide spectrum antibiotics, and mortality rates were increased in patients that high SAPS II scores, long term hospitalization. Infection control procedures and limited antibiotic usage are very important for prevent nosocomial infections. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Antibacterial activity and mechanism of action of auranofin against multi-drug resistant bacterial pathogens

    PubMed Central

    Thangamani, Shankar; Mohammad, Haroon; Abushahba, Mostafa F. N.; Sobreira, Tiago J. P.; Hedrick, Victoria E.; Paul, Lake N.; Seleem, Mohamed N.

    2016-01-01

    Traditional methods employed to discover new antibiotics are both a time-consuming and financially-taxing venture. This has led researchers to mine existing libraries of clinical molecules in order to repurpose old drugs for new applications (as antimicrobials). Such an effort led to the discovery of auranofin, a drug initially approved as an anti-rheumatic agent, which also possesses potent antibacterial activity in a clinically achievable range. The present study demonstrates auranofin’s antibacterial activity is a complex process that involves inhibition of multiple biosynthetic pathways including cell wall, DNA, and bacterial protein synthesis. We also confirmed that the lack of activity of auranofin observed against Gram-negative bacteria is due to the permeability barrier conferred by the outer membrane. Auranofin’s ability to suppress bacterial protein synthesis leads to significant reduction in the production of key methicillin-resistant Staphylococcus aureus (MRSA) toxins. Additionally, auranofin is capable of eradicating intracellular MRSA present inside infected macrophage cells. Furthermore, auranofin is efficacious in a mouse model of MRSA systemic infection and significantly reduces the bacterial load in murine organs including the spleen and liver. Collectively, this study provides valuable evidence that auranofin has significant promise to be repurposed as a novel antibacterial for treatment of invasive bacterial infections. PMID:26936660

  16. The therapeutic potential of targeting ABC transporters to combat multi-drug resistance.

    PubMed

    Bugde, Piyush; Biswas, Riya; Merien, Fabrice; Lu, Jun; Liu, Dong-Xu; Chen, Mingwei; Zhou, Shufeng; Li, Yan

    2017-05-01

    Most disseminated cancers remain fatal despite the availability of a variety of conventional and novel treatments including surgery, chemotherapy, radiotherapy, immunotherapy, and biologically targeted therapy. A major factor responsible for the failure of chemotherapy in the treatment of cancer is the development of multidrug resistance (MDR). The overexpression of various ABC transporters in cancer cells can efficiently remove the anticancer drug from the cell, thus causing the drug to lose its effect. Areas covered: In this review, we summarised the ongoing research related to the mechanism, function, and regulation of ABC transporters. We integrated our current knowledge at different levels from molecular biology to clinical trials. We also discussed potential therapeutic strategies of targeting ABC transporters to reverse MDR in cancer cells. Expert opinion: Involvement of various ABC transporters to cancer MDR lays the foundation for developing tailored therapies that can overcome MDR. An ideal MDR reversal agent should have broad-spectrum ABC-transporter inhibitory activity, be potent, have good pharmacokinetics, have no trans-stimulation effects, and have low or no toxicity. Alternatively, nanotechnology-based drug delivery systems containing both the cytotoxic drug and reversing agent may represent a useful approach to reversing MDR with minimal off-target toxicity.

  17. Lessons from history of socioeconomic improvements: a new approach to treating multi-drug-resistant tuberculosis.

    PubMed

    Holloway, K L; Staub, K; Rühli, F; Henneberg, M

    2014-09-01

    This study investigated the trends in tuberculosis mortality through time in Switzerland. Information on the decline in mortality before chemotherapies were introduced may be useful in developing countries where drug-resistant tuberculosis is now becoming a major problem. Swiss data were collected from historical records and comparative data were obtained from the literature for England and Wales, New York, Japan, Brazil and Sierra Leone. Logistic curves were fitted to examine the rate of decline before introduction of pharmacotherapies and these show that the decline would have continued without the introduction of chemical therapies, including antibiotics. In Switzerland, England and Wales and New York, the decline had occurred long before the introduction of specific anti-tuberculosis agents. In Brazil and Japan, chemical therapy was co-incident with the decline in tuberculosis mortality rates. Overall, it is suggested that the effective control of tuberculosis can be achieved through a combination of chemical interventions, conservative therapy (rest, good nutrition, ventilation, etc.) as well as public health interventions addressing hygiene, nutrition, reducing exposure to infections and educating the population about tuberculosis.

  18. Antimicrobial and antibiofilm potential of biosurfactants isolated from lactobacilli against multi-drug-resistant pathogens

    PubMed Central

    2014-01-01

    Background Biosurfactants (BS) are amphiphilic compounds produced by microbes, either on the cell surface or secreted extracellularly. BS exhibit strong antimicrobial and anti-adhesive properties, making them good candidates for applications used to combat infections. In this study, our goal was to assess the in vitro antimicrobial, anti-adhesive and anti-biofilm abilities of BS produced by Lactobacillus jensenii and Lactobacillus rhamnosus against clinical Multidrug Resistant (MDR) strains of Acinetobacter baumannii, Escherichia coli, and Staphylococcus aureus (MRSA). Cell-bound BS from both L. jensenii and L. rhamnosus were extracted and isolated. The surface activities of crude BS samples were evaluated using an oil spreading assay. The antimicrobial, anti-adhesive and anti-biofilm activities of both BS against the above mentioned MDR pathogens were determined. Results Surface activities for both BS ranged from 6.25 to 25 mg/ml with clear zones observed between 7 and 11 cm. BS of both L. jensenii and L. rhamnosus showed antimicrobial activities against A. baumannii, E. coli and S. aureus at 25-50 mg/ml. Anti-adhesive and anti-biofilm activities were also observed for the aforementioned pathogens between 25 and 50 mg/ml. Finally, analysis by electron microscope indicated that the BS caused membrane damage for A. baumannii and pronounced cell wall damage in S. aureus. Conclusion Our results indicate that BS isolated from two Lactobacilli strains has antibacterial properties against MDR strains of A. baumannii, E. coli and MRSA. Both BS also displayed anti-adhesive and anti-biofilm abilities against A. baumannii, E. coli and S. aureus. Together, these capabilities may open up possibilities for BS as an alternative therapeutic approach for the prevention and/or treatment of hospital-acquired infections. PMID:25124936

  19. Identification of efflux-mediated multi-drug resistance in bacterial clinical isolates by two simple methods.

    PubMed

    Martins, Marta; Couto, Isabel; Viveiros, Miguel; Amaral, Leonard

    2010-01-01

    Two simple, instrument-free, user-friendly methods that can readily be implemented by a routine microbiology laboratory are described for the detection of multi-drug-resistant (MDR) isolates that overexpress efflux pump (EP) systems responsible for the MDR phenotype. The first method employs the universal EP substrate ethidium bromide (EB) at varying concentrations in agar-containing plates upon which the contents of an overnight culture are swabbed as spokes of a wheel. In this method, named the EB-agar cartwheel method, it is assumed that the smallest concentration of EB that produces fluorescence of the bacterial mass represents the highest concentration of EB that the bacteria can exclude. Consequently, as the efflux system(s) of a given MDR clinical bacterial isolate is overexpressed relative to that of a reference strain, the minimal concentration of EB producing fluorescence is significantly greater. A simple formula is provided which affords the ranking of MDR clinical isolates with respect to the degree of their efflux capacity. The second method, which can be used after the first one, determines whether the MDR phenotype is based upon an overexpressed efflux system. This method employs a 24-well microplate with separate wells containing or lacking an efflux pump inhibitor (EPI) and Kirby-Bauer discs that correspond to the antibiotics to which the MDR strain is resistant. After the wells are inoculated with the MDR clinical isolate, the plate is incubated overnight and each well is evaluated by eye for evidence of growth. Comparison of growth to the relevant control enables the observer to determine the following outcomes: no growth produced by the EPI-antibiotic combination (i.e., reversal of antibiotic resistance); reduced growth produced by the EPI-antibiotic combination; no difference in growth, i.e., EPI does not affect the resistance to the given antibiotic. If the first method showed that there was a significant difference between the minimum

  20. The Widespread Multidrug-Resistant Serotype O12 Pseudomonas aeruginosa Clone Emerged through Concomitant Horizontal Transfer of Serotype Antigen and Antibiotic Resistance Gene Clusters.

    PubMed

    Thrane, Sandra Wingaard; Taylor, Véronique L; Freschi, Luca; Kukavica-Ibrulj, Irena; Boyle, Brian; Laroche, Jérôme; Pirnay, Jean-Paul; Lévesque, Roger C; Lam, Joseph S; Jelsbak, Lars

    2015-09-22

    The O-specific antigen (OSA) in Pseudomonas aeruginosa lipopolysaccharide is highly varied by sugar identity, side chains, and bond between O-repeats. These differences classified P. aeruginosa into 20 distinct serotypes. In the past few decades, O12 has emerged as the predominant serotype in clinical settings and outbreaks. These serotype O12 isolates exhibit high levels of resistance to various classes of antibiotics. Here, we explore how the P. aeruginosa OSA biosynthesis gene clusters evolve in the population by investigating the association between the phylogenetic relationships among 83 P. aeruginosa strains and their serotypes. While most serotypes were closely linked to the core genome phylogeny, we observed horizontal exchange of OSA biosynthesis genes among phylogenetically distinct P. aeruginosa strains. Specifically, we identified a "serotype island" ranging from 62 kb to 185 kb containing the P. aeruginosa O12 OSA gene cluster, an antibiotic resistance determinant (gyrA(C248T)), and other genes that have been transferred between P. aeruginosa strains with distinct core genome architectures. We showed that these genes were likely acquired from an O12 serotype strain that is closely related to P. aeruginosa PA7. Acquisition and recombination of the "serotype island" resulted in displacement of the native OSA gene cluster and expression of the O12 serotype in the recipients. Serotype switching by recombination has apparently occurred multiple times involving bacteria of various genomic backgrounds. In conclusion, serotype switching in combination with acquisition of an antibiotic resistance determinant most likely contributed to the dissemination of the O12 serotype in clinical settings. Infection rates in hospital settings by multidrug-resistant (MDR) Pseudomonas aeruginosa clones have increased during the past decades, and serotype O12 is predominant among these epidemic strains. It is not known why the MDR phenotype is associated with serotype

  1. The enriched fraction of Elephantopus scaber Triggers apoptosis and inhibits multi-drug resistance transporters in human epithelial cancer cells

    PubMed Central

    Beeran, Asmy Appadath; Maliyakkal, Naseer; Rao, Chamallamudi Mallikarjuna; Udupa, Nayanabhirama

    2015-01-01

    Background: Medicinal plants have played an important role in the development of clinically useful anticancer agents. Elephantopus scaber (Asteraceae) (ES) is widely used in Indian traditional system of medicine for the treatment of various ailments including cancer. Objective: To investigate anticancer effects of ES in human epithelial cancer cells. Materials and Methods: Cytotoxicity of ethanolic extract of ES (ES-ET) and its fractions, such as ES Petroleum ether fraction (ES-PET), ES Dichloromethane fraction (ES DCM), n Butyl alcohol fraction (ES-BT), and ES-Rest (ES-R) were assessed in human epithelial cancer cell lines using sulforhodamine B (SRB) assay. Acridine orange/ethidium bromide assay and Hoechst 33342 assays were used to gauge induction of apoptosis. Cell cycle analysis and micronuclei assay were used to assess cell cycle specific pharmacological effects and drug induced genotoxicty. Further, the ability of ES to inhibit multi drug resistant (MDR) transporters (ABC-B1 and ABC-G2) was determined by Rhodamine (Rho) and Mitoxantrone (MXR) efflux assays. Results: The enriched fraction of ES (ES DCM) possessed dose-dependent potent cytotoxicity in human epithelial cancer cells. Further, treatment of cancer cells (HeLa, A549, MCF-7, and Caco-2) with ES DCM showed hall mark properties of apoptosis (membrane blebbing, nuclear condensation etc.). Similarly, ES DCM caused enhanced sub G0 content and micronuclei formation indicating the induction of apoptosis and drug induced genotoxicity in cancer cells, respectively. Interestingly, ES DCM inhibited MDR transporters (ABC B1 and ABC G2) in cancer cells. Conclusion: The enriched fraction of ES imparted cytotoxic effects, triggered apoptosis, induced genotoxicity, and inhibited MDR transporters in human epithelial cancer cells. Thus, ES appears to be potential anticancer agent. PMID:25829763

  2. Outcome of neurological early rehabilitation patients carrying multi-drug resistant bacteria: results from a German multi-center study.

    PubMed

    Rollnik, J D; Bertram, M; Bucka, C; Hartwich, M; Jöbges, M; Ketter, G; Leineweber, B; Mertl-Rötzer, M; Nowak, D A; Platz, T; Scheidtmann, K; Thomas, R; von Rosen, F; Wallesch, C W; Woldag, H; Peschel, P; Mehrholz, J; Pohl, M

    2017-03-20

    Colonization or infection with multi-drug resistant (MDR) bacteria is considered detrimental to the outcome of neurological and neurosurgical early rehabilitation patients. In a German multi-center study, 754 neurological early rehabilitation patients were enrolled and and reviewed in respect to MDR status, length of stay (LOS) and the following outcome variables: Barthel Index (BI), Early Rehabilitation Index (ERI), Glasgow Outcome Score Extended (GOSE), Coma Remission Scale (CRS), Functional Ambulation Categories (FAC). The mean age of the study population was 68.0 ± 14.8 years. Upon admission, the following prevalence for MDRs was observed: MRSA (methicillin resistant staphylococcus aureus) 7.0% (53/754), ESBL- (extended spectrum beta-lactamase) producing bacteria strains 12.6% (95/754), VRE (vancomycin resistant enterococci) 2.8% (21/754). Patients colonized or infected with MDR bacteria (MDR+) were significantly more frequently diagnosed with a critical illness polyneuropathy - CIP - than non-colonized (MDR-) patients: 29.0% vs. 14.8%. In addition, they were more frequently mechanically ventilated (MDR+: 55/138, 39.9%; MDR- 137/616, 22.2%). MDR+ patients were referred to rehabilitation earlier, had a longer LOS in early rehabilitation, lower BI on admission and at discharge, lower ERI on admission and lower CRS at discharge than MDR- patients. There was a highly significant correlation of the BI upon admission with the BI at discharge (rs = 0.492, p < 0.001). GOSE at discharge differed significantly between both groups (χ (2)-test, p < 0.01). Perhaps of greatest importance, mortality among MDR+ was higher in comparison to MDR- (18.1% vs. 7.6%). The outcome of neurological early rehabilitation patients colonized or infected with MDR bacteria including MRSA or ESBL producing strains is significantly poorer than by non-colonized patients. There is some evidence that the poor outcome could be related to the higher morbidity and lower functional

  3. Anti-candidal activity of essential oils alone and in combination with amphotericin B or fluconazole against multi-drug resistant isolates of Candida albicans.

    PubMed

    Khan, Mohd Sajjad Ahmad; Malik, Abida; Ahmad, Iqbal

    2012-01-01

    Therapy for candidiasis is becoming problematic due to the toxicities of currently available antifungal agents and the increasing prevalence of resistance among the etiologic agents. Therefore, new antifungals and alternative approaches are needed. In this study, 20 fluconazole-resistant strains of Candida albicans were found to have varying levels of resistance to other azoles, i.e., itraconazole (MIC of 4-128 μg/ml) and ketoconazole (2-256 μg/ml). In addition, 13 of these isolates appeared resistant to amphotericin B (32-128 μg/ml). A total of 21 plant essential oils were screened for their antifungal activity against these multi-drug resistant isolates. The oils of Cymbopogon martini, i.e., citral and cinnamaldehyde, exhibited strong inhibitory activity with minimum inhibitory concentrations (MIC(50)) ranging from 90-100 μg/ml. The test oils were more effective than fluconazole and amphotericin B in inhibiting azole- and amphotericin B-resistant, as well as amphotericin B-susceptible isolates. The test oils and especially eugenol, exhibited significant synergy with fluconazole or amphotericin B against the test isolates. These findings suggest the possible effective use of certain oils alone or in combination with fluconazole or amphotericin B, against multi-drug resistant isolates of C. albicans.

  4. Detection of Low Frequency Multi-Drug Resistance and Novel Putative Maribavir Resistance in Immunocompromised Pediatric Patients with Cytomegalovirus.

    PubMed

    Houldcroft, Charlotte J; Bryant, Josephine M; Depledge, Daniel P; Margetts, Ben K; Simmonds, Jacob; Nicolaou, Stephanos; Tutill, Helena J; Williams, Rachel; Worth, Austen J J; Marks, Stephen D; Veys, Paul; Whittaker, Elizabeth; Breuer, Judith

    2016-01-01

    Human cytomegalovirus (HCMV) is a significant pathogen in immunocompromised individuals, with the potential to cause fatal pneumonitis and colitis, as well as increasing the risk of organ rejection in transplant patients. With the advent of new anti-HCMV drugs there is therefore considerable interest in using virus sequence data to monitor emerging resistance to antiviral drugs in HCMV viraemia and disease, including the identification of putative new mutations. We used target-enrichment to deep sequence HCMV DNA from 11 immunosuppressed pediatric patients receiving single or combination anti-HCMV treatment, serially sampled over 1-27 weeks. Changes in consensus sequence and resistance mutations were analyzed for three ORFs targeted by anti-HCMV drugs and the frequencies of drug resistance mutations monitored. Targeted-enriched sequencing of clinical material detected mutations occurring at frequencies of 2%. Seven patients showed no evidence of drug resistance mutations. Four patients developed drug resistance mutations a mean of 16 weeks after starting treatment. In two patients, multiple resistance mutations accumulated at frequencies of 20% or less, including putative maribavir and ganciclovir resistance mutations P522Q (UL54) and C480F (UL97). In one patient, resistance was detected 14 days earlier than by PCR. Phylogenetic analysis suggested recombination or superinfection in one patient. Deep sequencing of HCMV enriched from clinical samples excluded resistance in 7 of 11 subjects and identified resistance mutations earlier than conventional PCR-based resistance testing in 2 patients. Detection of multiple low level resistance mutations was associated with poor outcome.

  5. Evolution of multi-drug resistant HCV clones from pre-existing resistant-associated variants during direct-acting antiviral therapy determined by third-generation sequencing

    NASA Astrophysics Data System (ADS)

    Takeda, Haruhiko; Ueda, Yoshihide; Inuzuka, Tadashi; Yamashita, Yukitaka; Osaki, Yukio; Nasu, Akihiro; Umeda, Makoto; Takemura, Ryo; Seno, Hiroshi; Sekine, Akihiro; Marusawa, Hiroyuki

    2017-03-01

    Resistance-associated variant (RAV) is one of the most significant clinical challenges in treating HCV-infected patients with direct-acting antivirals (DAAs). We investigated the viral dynamics in patients receiving DAAs using third-generation sequencing technology. Among 283 patients with genotype-1b HCV receiving daclatasvir + asunaprevir (DCV/ASV), 32 (11.3%) failed to achieve sustained virological response (SVR). Conventional ultra-deep sequencing of HCV genome was performed in 104 patients (32 non-SVR, 72 SVR), and detected representative RAVs in all non-SVR patients at baseline, including Y93H in 28 (87.5%). Long contiguous sequences spanning NS3 to NS5A regions of each viral clone in 12 sera from 6 representative non-SVR patients were determined by third-generation sequencing, and showed the concurrent presence of several synonymous mutations linked to resistance-associated substitutions in a subpopulation of pre-existing RAVs and dominant isolates at treatment failure. Phylogenetic analyses revealed close genetic distances between pre-existing RAVs and dominant RAVs at treatment failure. In addition, multiple drug-resistant mutations developed on pre-existing RAVs after DCV/ASV in all non-SVR cases. In conclusion, multi-drug resistant viral clones at treatment failure certainly originated from a subpopulation of pre-existing RAVs in HCV-infected patients. Those RAVs were selected for and became dominant with the acquisition of multiple resistance-associated substitutions under DAA treatment pressure.

  6. Development and evaluation of a novel vaccine against prevalent invasive multi-drug resistant strains of Streptococcus pneumoniae

    PubMed Central

    Bahy, Rehab H.; Hamouda, Hayam M.; Shahat, Amal S.; Amin, Magdy A.

    2016-01-01

    Streptococcus pneumoniae is a pathogen that causes serious invasive infections, such as septicemia, meningitis and pneumonia in addition to mild upper respiratory tract infections. Protection from pneumococcal diseases is thought to be mediated mainly by serotype-specific antibodies to capsular antigens. Pneumococcal conjugate vaccine consists of sugars (polysaccharides) from the capsule of the bacterium S. pneumoniae that are conjugated to a carrier protein. Three pneumococcal conjugated vaccines, each directed against a group of serotypes, are registered in Egypt; however, local vaccine production is required to cover the most prevalent serotypes. In this work, capsular polysaccharide from the most current and prevalent serotypes in Egypt were extracted, purified and conjugated to bovine serum albumin (BSA). The polysaccharide protein conjugate was purified through ultrafiltration technique and molecular size distribution was compared to an available vaccine. The immunogenicity of the prepared vaccine was examined via two methods: First, by measuring the levels of the elicited antibodies in the sera of the vaccinated mice; second, by challenging the vaccinated groups of mice with approximately 107 CFU of each specific serotype and determining the degree of protection the developled vaccine offers. Our results show that the developed conjugated capsular polysaccharide vaccine is highly immunogenic and protective in mice. This finding illustrates the importance of tracking the most recent and predominant peneumococcal serotypes to generate effective vaccines, instead of using expensive imported vaccines with large number of serotypes which might not be even present in the community. PMID:27917323

  7. Multi-drug resistance gene (MDR-1) and risk of brain metastasis in epithelial ovarian, fallopian tube, and peritoneal cancer

    PubMed Central

    Matsuo, Koji; Eno, Michele L.; Ahn, Edward H.; Shahzad, Mian M.K.; Im, Dwight D.; Rosenshein, Neil B.; Sood, Anil K.

    2011-01-01

    Background To evaluate risk factors that predict brain metastasis in epithelial ovarian, fallopian tube, and peritoneal cancer. Methods All patients with FIGO stage I to IV who underwent initial cytoreductive surgery between January 1995 and January 2009 were evaluated. The tumor samples were evaluated for 7 markers including multi-drug resistance gene (MDR-1), DNA aneuploidity and S-phase fraction, human epidermal growth factor receptor 2, estrogen receptor, progesterone receptor, p53 mutation, epidermal growth factor receptor, and CD31. Biomarker expression was evaluated as a predictor of hematogenous metastasis to the following locations: (i) liver and spleen, (ii) lung, and (iii) brain. Results There were 309 cases identified during the period. Of those, five (1.6%, 95%CI 0.2-3.0%) women developed brain metastasis. Time to onset of brain metastasis was significantly longer than for other recurrent sites (median time to recurrence after initial cytoreduction, brain vs lung vs liver, 21.4 vs 12.6 vs 11.0 months, p<0.05). Significantly increased expression of MDR-1 was seen in tumors from women who developed brain metastasis (brain vs non-brain sites, 80% vs 4.2-24.3%, p=0.004). In multivariate analysis, MDR-1 was the only significant variable associated with the risk of brain metastasis. MDR-1 expression predicted brain metastasis (Receiver-operator-characteristic curve analysis, AUC 0.808, p=0.018), and with a 10% positive expression of MDR-1 as the cutoff value, sensitivity, specificity, positive predictive value, negative predictive value, accuracy of prediction of brain metastasis were 80%, 86.1%, 15.4%, 99.3%, and 85.9%, respectively (odds ratio 24.7, 95%CI 2.64-232, p=0.002). Conclusions Increased expression of MDR-1 in the tumor tissue obtained at initial cytoreduction is associated with increased risk of developing brain metastases in women with epithelial ovarian, fallopian tube, or peritoneal cancer. PMID:20921883

  8. Detection of Low Frequency Multi-Drug Resistance and Novel Putative Maribavir Resistance in Immunocompromised Pediatric Patients with Cytomegalovirus

    PubMed Central

    Houldcroft, Charlotte J.; Bryant, Josephine M.; Depledge, Daniel P.; Margetts, Ben K.; Simmonds, Jacob; Nicolaou, Stephanos; Tutill, Helena J.; Williams, Rachel; Worth, Austen J. J.; Marks, Stephen D.; Veys, Paul; Whittaker, Elizabeth; Breuer, Judith

    2016-01-01

    Human cytomegalovirus (HCMV) is a significant pathogen in immunocompromised individuals, with the potential to cause fatal pneumonitis and colitis, as well as increasing the risk of organ rejection in transplant patients. With the advent of new anti-HCMV drugs there is therefore considerable interest in using virus sequence data to monitor emerging resistance to antiviral drugs in HCMV viraemia and disease, including the identification of putative new mutations. We used target-enrichment to deep sequence HCMV DNA from 11 immunosuppressed pediatric patients receiving single or combination anti-HCMV treatment, serially sampled over 1–27 weeks. Changes in consensus sequence and resistance mutations were analyzed for three ORFs targeted by anti-HCMV drugs and the frequencies of drug resistance mutations monitored. Targeted-enriched sequencing of clinical material detected mutations occurring at frequencies of 2%. Seven patients showed no evidence of drug resistance mutations. Four patients developed drug resistance mutations a mean of 16 weeks after starting treatment. In two patients, multiple resistance mutations accumulated at frequencies of 20% or less, including putative maribavir and ganciclovir resistance mutations P522Q (UL54) and C480F (UL97). In one patient, resistance was detected 14 days earlier than by PCR. Phylogenetic analysis suggested recombination or superinfection in one patient. Deep sequencing of HCMV enriched from clinical samples excluded resistance in 7 of 11 subjects and identified resistance mutations earlier than conventional PCR-based resistance testing in 2 patients. Detection of multiple low level resistance mutations was associated with poor outcome. PMID:27667983

  9. Serotype and antimicrobial resistance patterns of Salmonella isolates from commercial birds and poultry environment in Mississippi.

    PubMed

    Pulido-Landínez, Martha; Washington, Paul; Thornton, Jay Kay; Zhang, Yi; Sánchez-Ingunza, Roxana; Banda, Alejandro; Guard, Jean; Nascimento, Vladimir P; Magee, Danny L; Mauel, Michael J

    2014-03-01

    To obtain information about Salmonella from commercial birds and poultry environments within Mississippi, 50 Salmonella enterica isolates were collected and characterized by intergenic sequence ribotyping (ISR) serotyping and by determining antimicrobial resistance. ISR assigned serotype to all 50 Salmonella enterica isolates whereas the Kauffman-White-LeMinor antibody-based scheme assigned serotype to 48. Agreement between both methods was K = 89.58. Within the set, 12 serotypes were detected. The antimicrobial resistance patterns (ARP) of 12 serotypes, namely Enteritidis, Typhimurium, Kentucky, Bredeney, Mbandaka, Saintpaul, Montevideo, Cubana, Lille, Senftenberg, Johannesburg, and one serotype UN0094, were determined using minimum inhibitory concentration values. The antibiograms demonstrated differences between Salmonella serotypes and among isolates of the same serotype. All isolates were 100% susceptible to enrofloxacin and trimethoprim/sulfamethoxazole. The number of antimicrobials to which the isolates were resistant ranged from two to nine. Twenty-two different ARPs were identified and ARP1, with resistance to spectinomycin and sulfadimethoxine, was most frequently observed. Forty isolates (80%) were resistant to three or more antimicrobials and were thus designated multidrug resistant. Detection of a unique serotype, and variation in antibiograms within the set, demonstrates that it is important to survey isolates periodically from a region to follow epidemiologic trends.

  10. Occurrence of extended spectrum beta (b)-lactamases in multi-drug resistant Escherichia coli isolated from a clinical setting in Jimma University Specialized Hospital, Jimma, southwest Ethiopia.

    PubMed

    Mulualem, Yohannes; Kasa, Tesfaye; Mekonnen, Zeleke; Suleman, Sultan

    2012-06-01

    Resistance to antibiotics has grave consequences leading to treatment failure and increased health care costs. This public health risk has become a global problem with some countries like Ethiopia seriously affected. Members of the family enterobacteriaceae, including E. coli, are among the most important human pathogens accounting for the majority of bacterial strains isolated from clinical patient samples. Moreover, there is insufficient data regarding Extended-spectrum Beta-lactamase (ESBL) prevalence among Escherichia coli strains from Ethiopia. Thus, the objective was to determine the production of ESBL among clinical isolates and assess the in vitro susceptibility of the E. coli to the routinely used selected antibiotics. We collected a total of 359 clinical specimens (56 urine, 116 sputum, 72 stool and 15 wound swabs) from in- and outpatients at Jimma University Specialised Hospital, Jimma zone, southwest Ethiopia. E. coli was isolated from 67 (18.66%) clinical specimens, of which 24 (36%) isolates were ESBL producers. The resistance pattern to the tested antibiotics was: penicillin (97%), amoxacillin and ampicillin (86.6% each), tetracycline (73.1%), amoxacillin-clavulanate (70.1%), co-trimoxazole (56.7%), chloramphenicol (35.8%), ciprofloxacine (20.9%), norfloxacine (16.4%), cefotaxime (9%), ceftazidime (6%), gentamicin (3%). All the isolates tested showed resistance to two or more drugs, and were considered to be multi-drug resistant. A higher rate (46%) of ESBL production and multi-drug resistance was seen among isolates from inpatients as compared to outpatients (33%) at the hospital.

  11. Cholera outbreaks (2012) in three districts of Nepal reveal clonal transmission of multi-drug resistant Vibrio cholerae O1

    PubMed Central

    2014-01-01

    Background Although endemic cholera causes significant morbidity and mortality each year in Nepal, lack of information about the causal bacterium often hinders cholera intervention and prevention. In 2012, diarrheal outbreaks affected three districts of Nepal with confirmed cases of mortality. This study was designed to understand the drug response patterns, source, and transmission of Vibrio cholerae associated with 2012 cholera outbreaks in Nepal. Methods V. cholerae (n = 28) isolated from 2012 diarrhea outbreaks {n = 22; Kathmandu (n = 12), Doti (n = 9), Bajhang (n = 1)}, and surface water (n = 6; Kathmandu) were tested for antimicrobial response. Virulence properties and DNA fingerprinting of the strains were determined by multi-locus genetic screening employing polymerase chain reaction, DNA sequencing, and pulsed-field gel electrophoresis (PFGE). Results All V. cholerae strains isolated from patients and surface water were confirmed to be toxigenic, belonging to serogroup O1, Ogawa serotype, biotype El Tor, and possessed classical biotype cholera toxin (CTX). Double-mismatch amplification mutation assay (DMAMA)-PCR revealed the V. cholerae strains to possess the B-7 allele of ctx subunit B. DNA sequencing of tcpA revealed a point mutation at amino acid position 64 (N → S) while the ctxAB promoter revealed four copies of the tandem heptamer repeat sequence 5'-TTTTGAT-3'. V. cholerae possessed all the ORFs of the Vibrio seventh pandemic island (VSP)-I but lacked the ORFs 498–511 of VSP-II. All strains were multidrug resistant with resistance to trimethoprim-sulfamethoxazole (SXT), nalidixic acid (NA), and streptomycin (S); all carried the SXT genetic element. DNA sequencing and deduced amino acid sequence of gyrA and parC of the NAR strains (n = 4) revealed point mutations at amino acid positions 83 (S → I), and 85 (S → L), respectively. Similar PFGE (NotI) pattern revealed the Nepalese V. cholerae to be clonal

  12. Cholera outbreaks (2012) in three districts of Nepal reveal clonal transmission of multi-drug resistant Vibrio cholerae O1.

    PubMed

    Dixit, Sameer M; Johura, Fatema-Tuz; Manandhar, Sulochana; Sadique, Abdus; Rajbhandari, Rajesh M; Mannan, Shahnewaj B; Rashid, Mahamud-Ur; Islam, Saiful; Karmacharya, Dibesh; Watanabe, Haruo; Sack, R Bradley; Cravioto, Alejandro; Alam, Munirul

    2014-07-15

    Although endemic cholera causes significant morbidity and mortality each year in Nepal, lack of information about the causal bacterium often hinders cholera intervention and prevention. In 2012, diarrheal outbreaks affected three districts of Nepal with confirmed cases of mortality. This study was designed to understand the drug response patterns, source, and transmission of Vibrio cholerae associated with 2012 cholera outbreaks in Nepal. V. cholerae (n = 28) isolated from 2012 diarrhea outbreaks {n = 22; Kathmandu (n = 12), Doti (n = 9), Bajhang (n = 1)}, and surface water (n = 6; Kathmandu) were tested for antimicrobial response. Virulence properties and DNA fingerprinting of the strains were determined by multi-locus genetic screening employing polymerase chain reaction, DNA sequencing, and pulsed-field gel electrophoresis (PFGE). All V. cholerae strains isolated from patients and surface water were confirmed to be toxigenic, belonging to serogroup O1, Ogawa serotype, biotype El Tor, and possessed classical biotype cholera toxin (CTX). Double-mismatch amplification mutation assay (DMAMA)-PCR revealed the V. cholerae strains to possess the B-7 allele of ctx subunit B. DNA sequencing of tcpA revealed a point mutation at amino acid position 64 (N → S) while the ctxAB promoter revealed four copies of the tandem heptamer repeat sequence 5'-TTTTGAT-3'. V. cholerae possessed all the ORFs of the Vibrio seventh pandemic island (VSP)-I but lacked the ORFs 498-511 of VSP-II. All strains were multidrug resistant with resistance to trimethoprim-sulfamethoxazole (SXT), nalidixic acid (NA), and streptomycin (S); all carried the SXT genetic element. DNA sequencing and deduced amino acid sequence of gyrA and parC of the NAR strains (n = 4) revealed point mutations at amino acid positions 83 (S → I), and 85 (S → L), respectively. Similar PFGE (NotI) pattern revealed the Nepalese V. cholerae to be clonal, and related closely with V. cholerae associated with cholera in

  13. Antimicrobial resistance genes in multi-drug resistant Salmonella enterica serovars isolated most frequently from animals, retail meat, and humans in the U.S. and Canada

    PubMed Central

    Glenn, LaShanda M.; Lindsey, Rebecca L.; Folster, Jason P.; Whichard, Jean M.; Pecic, Gary; Boerlin, Patrick; Gilmour, Mathew W.; McDermott, Patrick F.; Harbottle, Heather; Fedorka-Cray, Paula J.; Frye, Jonathan G.

    2015-01-01

    Salmonella enterica is a prevalent food-borne pathogen which can carry multi-drug resistance (MDR) and could pose a threat to human health. Identifying the genetic elements associated with MDR in Salmonella isolated from animals, food, and humans can help determine the sources of MDR in food animals and their impact on human health. Representatives of MDR S. enterica serovars most frequently isolated from healthy animals, retail meat, and human infections in the U.S. and Canada were subjected to detailed genetic analysis (n=56). These included U.S. slaughter (n=12), retail (n=9), and human (9) isolates, and Canadian slaughter (n=9), retail (n=9), and human (n=8) isolates. These isolates were assayed by microarray for antimicrobial resistance and MDR plasmid genes. Genes detected encoded resistance to aminoglycosides (alleles of aac, aad, aph, strA/B); beta-lactams (blaTEM, blaCMY, blaPSE-1); chloramphenicol (cat, flo, cmlA); sulfamethoxazole (sulI); tetracycline (tet(A, B, C, D) and tetR); and trimethoprim (dfrA). Similar resistance genes were detected regardless of serovar, source, or location. Hybridization with IncA/C plasmid gene probes indicated that 27/56 isolates carried a member of this plasmid family; however these plasmids differed in several highly variable regions. Cluster analysis based on genes detected separated most of the isolates into two groups, one with IncA/C plasmids and one without IncA/C plasmids. Other plasmid replicons were detected in all but one isolate, and included I1 (25/56), N (23/56) and FIB (10/56). The presence of different mobile elements along with similar resistance genes suggest that these genetic elements may acquire similar resistance cassettes, and serve as multiple sources for MDR in Salmonella from food animals, retail meat, and human infections. PMID:23350745

  14. Comparison of Multi-Drug Resistant Environmental Methicillin-Resistant Staphylococcus aureus Isolated from Recreational Beaches and High Touch Surfaces in Built Environments

    PubMed Central

    Roberts, Marilyn C.; Soge, Olusegun O.; No, David

    2013-01-01

    Over the last decade community-acquired methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a major cause of disease in the general population with no health care exposure or known classical risk factors for MRSA infections. The potential community reservoirs have not been well defined though certain strains such as ST398 and USA300 have been well studied in some settings. MRSA has been isolated from recreational beaches, high-touch surfaces in homes, universities, and other community environmental surfaces. However, in most cases the strains were not characterized to determine if they are related to community-acquired or hospital-acquired clinical strains. We compared 55 environmental MRSA from 805 samples including sand, fresh, and marine water samples from local marine and fresh water recreational beaches (n = 296), high touch surfaces on the University of Washington campus (n = 294), surfaces in UW undergraduate housing (n = 85), and the local community (n = 130). Eleven USA300, representing 20% of the isolates, were found on the UW campus surfaces, student housing surfaces, and on the community surfaces but not in the recreational beach samples from the Northwest USA. Similarly, the predominant animal ST133 was found in the recreational beach samples but not in the high touch surface samples. All USA300 isolates were multi-drug resistant carrying two to six different antibiotic resistance genes coding for kanamycin, macrolides and/or macrolides-lincosamides-streptogramin B, and tetracycline, with the majority (72%) carrying four to six different antibiotic resistance genes. A surprising 98% of the 55 MRSA isolates were resistant to other classes of antibiotics and most likely represent reservoirs for these genes in the environment. PMID:23577006

  15. Comparison of Multi-Drug Resistant Environmental Methicillin-Resistant Staphylococcus aureus Isolated from Recreational Beaches and High Touch Surfaces in Built Environments.

    PubMed

    Roberts, Marilyn C; Soge, Olusegun O; No, David

    2013-01-01

    Over the last decade community-acquired methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a major cause of disease in the general population with no health care exposure or known classical risk factors for MRSA infections. The potential community reservoirs have not been well defined though certain strains such as ST398 and USA300 have been well studied in some settings. MRSA has been isolated from recreational beaches, high-touch surfaces in homes, universities, and other community environmental surfaces. However, in most cases the strains were not characterized to determine if they are related to community-acquired or hospital-acquired clinical strains. We compared 55 environmental MRSA from 805 samples including sand, fresh, and marine water samples from local marine and fresh water recreational beaches (n = 296), high touch surfaces on the University of Washington campus (n = 294), surfaces in UW undergraduate housing (n = 85), and the local community (n = 130). Eleven USA300, representing 20% of the isolates, were found on the UW campus surfaces, student housing surfaces, and on the community surfaces but not in the recreational beach samples from the Northwest USA. Similarly, the predominant animal ST133 was found in the recreational beach samples but not in the high touch surface samples. All USA300 isolates were multi-drug resistant carrying two to six different antibiotic resistance genes coding for kanamycin, macrolides and/or macrolides-lincosamides-streptogramin B, and tetracycline, with the majority (72%) carrying four to six different antibiotic resistance genes. A surprising 98% of the 55 MRSA isolates were resistant to other classes of antibiotics and most likely represent reservoirs for these genes in the environment.

  16. Evolution of multi-drug resistant HCV clones from pre-existing resistant-associated variants during direct-acting antiviral therapy determined by third-generation sequencing

    PubMed Central

    Takeda, Haruhiko; Ueda, Yoshihide; Inuzuka, Tadashi; Yamashita, Yukitaka; Osaki, Yukio; Nasu, Akihiro; Umeda, Makoto; Takemura, Ryo; Seno, Hiroshi; Sekine, Akihiro; Marusawa, Hiroyuki

    2017-01-01

    Resistance-associated variant (RAV) is one of the most significant clinical challenges in treating HCV-infected patients with direct-acting antivirals (DAAs). We investigated the viral dynamics in patients receiving DAAs using third-generation sequencing technology. Among 283 patients with genotype-1b HCV receiving daclatasvir + asunaprevir (DCV/ASV), 32 (11.3%) failed to achieve sustained virological response (SVR). Conventional ultra-deep sequencing of HCV genome was performed in 104 patients (32 non-SVR, 72 SVR), and detected representative RAVs in all non-SVR patients at baseline, including Y93H in 28 (87.5%). Long contiguous sequences spanning NS3 to NS5A regions of each viral clone in 12 sera from 6 representative non-SVR patients were determined by third-generation sequencing, and showed the concurrent presence of several synonymous mutations linked to resistance-associated substitutions in a subpopulation of pre-existing RAVs and dominant isolates at treatment failure. Phylogenetic analyses revealed close genetic distances between pre-existing RAVs and dominant RAVs at treatment failure. In addition, multiple drug-resistant mutations developed on pre-existing RAVs after DCV/ASV in all non-SVR cases. In conclusion, multi-drug resistant viral clones at treatment failure certainly originated from a subpopulation of pre-existing RAVs in HCV-infected patients. Those RAVs were selected for and became dominant with the acquisition of multiple resistance-associated substitutions under DAA treatment pressure. PMID:28361915

  17. Polysaccharide-capped silver Nanoparticles inhibit biofilm formation and eliminate multi-drug-resistant bacteria by disrupting bacterial cytoskeleton with reduced cytotoxicity towards mammalian cells

    NASA Astrophysics Data System (ADS)

    Sanyasi, Sridhar; Majhi, Rakesh Kumar; Kumar, Satish; Mishra, Mitali; Ghosh, Arnab; Suar, Mrutyunjay; Satyam, Parlapalli Venkata; Mohapatra, Harapriya; Goswami, Chandan; Goswami, Luna

    2016-04-01

    Development of effective anti-microbial therapeutics has been hindered by the emergence of bacterial strains with multi-drug resistance and biofilm formation capabilities. In this article, we report an efficient green synthesis of silver nanoparticle (AgNP) by in situ reduction and capping with a semi-synthetic polysaccharide-based biopolymer (carboxymethyl tamarind polysaccharide). The CMT-capped AgNPs were characterized by UV, DLS, FE-SEM, EDX and HR-TEM. These AgNPs have average particle size of ~20–40 nm, and show long time stability, indicated by their unchanged SPR and Zeta-potential values. These AgNPs inhibit growth and biofilm formation of both Gram positive (B. subtilis) and Gram negative (E. coli and Salmonella typhimurium) bacterial strains even at concentrations much lower than the minimum inhibitory concentration (MIC) breakpoints of antibiotics, but show reduced or no cytotoxicity against mammalian cells. These AgNPs alter expression and positioning of bacterial cytoskeletal proteins FtsZ and FtsA. CMT-capped AgNPs can effectively block growth of several clinical isolates and MDR strains representing different genera and resistant towards multiple antibiotics belonging to different classes. We propose that the CMT-capped AgNPs can have potential bio-medical application against multi-drug-resistant microbes with minimal cytotoxicity towards mammalian cells.

  18. Polysaccharide-capped silver Nanoparticles inhibit biofilm formation and eliminate multi-drug-resistant bacteria by disrupting bacterial cytoskeleton with reduced cytotoxicity towards mammalian cells

    PubMed Central

    Sanyasi, Sridhar; Majhi, Rakesh Kumar; Kumar, Satish; Mishra, Mitali; Ghosh, Arnab; Suar, Mrutyunjay; Satyam, Parlapalli Venkata; Mohapatra, Harapriya; Goswami, Chandan; Goswami, Luna

    2016-01-01

    Development of effective anti-microbial therapeutics has been hindered by the emergence of bacterial strains with multi-drug resistance and biofilm formation capabilities. In this article, we report an efficient green synthesis of silver nanoparticle (AgNP) by in situ reduction and capping with a semi-synthetic polysaccharide-based biopolymer (carboxymethyl tamarind polysaccharide). The CMT-capped AgNPs were characterized by UV, DLS, FE-SEM, EDX and HR-TEM. These AgNPs have average particle size of ~20–40 nm, and show long time stability, indicated by their unchanged SPR and Zeta-potential values. These AgNPs inhibit growth and biofilm formation of both Gram positive (B. subtilis) and Gram negative (E. coli and Salmonella typhimurium) bacterial strains even at concentrations much lower than the minimum inhibitory concentration (MIC) breakpoints of antibiotics, but show reduced or no cytotoxicity against mammalian cells. These AgNPs alter expression and positioning of bacterial cytoskeletal proteins FtsZ and FtsA. CMT-capped AgNPs can effectively block growth of several clinical isolates and MDR strains representing different genera and resistant towards multiple antibiotics belonging to different classes. We propose that the CMT-capped AgNPs can have potential bio-medical application against multi-drug-resistant microbes with minimal cytotoxicity towards mammalian cells. PMID:27125749

  19. EGF reverses multi-drug resistance via the p-ERK pathway in HepG2/ADM and SMMC7721/ADM hepatocellular carcinoma models.

    PubMed

    Yan, Feng; Bai, Li-Ping; Gao, Hua; Zhu, Chang-Ming; Lin, Li; Kang, Xiang-Peng

    2014-01-01

    To investigate signaling pathways for reversal of EGF-mediated multi-drug resistance (MDR) in hepatocellular carcinoma (HCC) models. HCC MDR cell strain HepG2/adriamycin (ADM) and SMMC7721/ADM models were established using a method of exposure to medium with ADM between low and high concentration with gradually increasing concentration. Drug sensitivity and reversal of multi-drug resistance by EGF were determined and the cell cycle distribution and apoptosis were analyzed by flow cytometry. Phosphorylation of ERK1, ERK2, ERK5 and expression of Bim were detected by Western blotting. The results showed that HepG2/ADM and SMMC7721/ADM cells were resistant not only to ADM, but also to multiple anticancer drugs. When used alone, EGF had no anti-tumor activity in HepG2/ADM and SMMC7721/ADM cells in vitro, while it increased the cytotoxicity of ADM. EGF induced cell apoptosis and G0/G1 phase cell cycle arrest in HepG2/ADM And SMMC7721/ADM cells, while enhancing activity of p-ERKs and up-regulated expression of BimEL. EGF might enhance the chemosensitivity of HepG2/ADM and SMMC7721/ADM cells via up-regulating p-ERKs and BimEL protein.

  20. Use of GeneXpert Mycobacterium tuberculosis/rifampicin for rapid detection of rifampicin resistant Mycobacterium tuberculosis strains of clinically suspected multi-drug resistance tuberculosis cases.

    PubMed

    Guenaoui, Kheira; Harir, Noria; Ouardi, Aissa; Zeggai, Soumia; Sellam, Feriel; Bekri, Farid; Cherif Touil, Sakina

    2016-05-01

    Multi-drug resistance (MDR) TB is defined as tuberculosis (TB) disease caused by a strain of Mycobacterium tuberculosis (MTB) that was resistant to at least isoniazid and rifampicin (RIF). Emerging Multidrug-Resistant TB is one of the major concerns of health policy and rapid detection of M. tuberculosis and detection of RIF resistance in infected patients are essential for disease management. The aim of this study was to evaluate patterns of RIF resistance in cases of sputum positive pulmonary TB by using GeneXpert MTB/RIF and comparing between phenotypic and genotypic testing of RIF resistance in MTB strains of clinically suspected MDR-TB isolated cases in western Algeria. In this study 50 sputum positive cases of pulmonary TB who were potential MDR suspect were included. Their sputum samples were collected and subjected to sputum smear microscopy, culture and conventional MTB/RIF test followed by GeneXpert MTB/RIF assay. Of total 50 cases included in this study, MTB was detected in all patients (100%) by GeneXpert MTB/RIF. However, RIF's resistance was detected in only 21 cases (42%) by GeneXpert MTB/RIF. All RIF resistant strains detected by GeneXpert MTB/RIF were phenotypically confirmed as MDR strains. 42.85% of cases were retreatment failure cases, retreatment cases smear positive at 4 months were 23.82%. While 19.05% of cases were retreatment cases smear positive at diagnosis, and 14.28% patient had history of contact with MDR-TB. Sensitivity, specificity, positive predictive value and negative predictive value of Xpert MTB/RIF to detect RIF resistance in comparison to conventional phenotypic drug susceptibility technique were found equal to the rates of 100%, 100%, 100% and 100%, respectively. GeneXpert MTB/RIF assay is efficient and reliable technique for the rapid diagnostic of TB. It's simplicity, high sensitivity and specificity for RIF resistance detection make this technique a very attractive tool for diagnostic of MTB and RIF resistance in MDR cases.

  1. Reversal of multi-drug resistance by pSUPER-shRNA-mdr1 in vivo and in vitro

    PubMed Central

    Pan, Guang-Dong; Yang, Jian-Qing; Yan, Lv-Nan; Chu, Guang-Ping; Liu, Qiang; Xiao, Yi; Yuan, Lin

    2009-01-01

    AIM: To explore the possibility of reversing multi-drug resistance (MDR) to HepG2/mdr1 in vitro and in vivo with RNA interference (RNAi). METHODS: HepG2/mdr1 was obtained by cloning the whole gene mdr1 into HepG2 cells. shRNA targeting sequence was designed to be homologous to the P-gp encoding MDR1 mRNA consensus sequence. pSUPER-shRNA/mdr1 was constructed using the enzyme-digested technique. HepG2/mdr1 cells were transfected with vectors of pSUPER-shRNA/mdr1 to measure their efficacy by real-time PCR for mdr1 mRNA, flow cytometry (FCM) for P-gp expression, and Rhodamine efflux, MTT method for HepG2/mdr1 function, respectively. In vivo, mice tumors were treated by injecting pSUPER-shRNA/mdr1 in situ and into intra-abdominal cavity. Tumors were collected to create cell suspension and cryosections after chemothearpy with adiramycin and mytomycin. The cell suspension was incubated in RPMI-1640 supplemented with G418 to screen stable cells for appreciating the reversal of MDR. Cryosections were treated with immunohistochemistry technique to show the effectiveness of transfection and the expression of P-gp. RESULTS: pSUPER-shRNA/mdr1 was successfully constructed, which was confirmed by sequencing. The MDR phenotype of HepG2/mdr1 was decreased significantly in vitro transfection. HepG2/mdr1 showing its MDR was reversed notably in P-gp expression (11.0% vs 98.2%, P < 0.01). Real-time PCR showed that mRNA/mdr1 was lower in test groups than in control groups (18.73 ± 1.33 vs 68.03 ± 2.21, P < 0.001). Compared with HepG2, the sensitivity of HepG2/mdr1 and HepG2/mdr1-dsRNA cells to ADM was decreased by 1.64 times and 15.6 times, respectively. The accumulation of DNR in positive groups was decreased evidently. In vivo, the p-gp expression in positive groups was significantly lower than that in control groups (65.1% vs 94.1%, P < 0.05). The tumor suppressing rate in test groups was 57.8%. After chemotherapy, the growth rate in test groups was lower than that in control

  2. Prevalence of antibiotic resistance in multi-drug resistant coagulase-negative staphylococci isolated from invasive infection in very low birth weight neonates in two Polish NICUs

    PubMed Central

    2013-01-01

    Background Multi-drug resistant coagulaso-negative staphylococci (CNS) have become an increasing problem in nosocomial infections connected with the presence of medical devices. The paper aimed to analyze the prevalence of antibiotic resistance in CNS isolated from invasive infection in very low birth weight (VLBW) neonates. Methods Continuous prospective target surveillance of infections was conducted in 2009 at two Polish NICUs that participated in the Polish Neonatology Surveillance Network (PNSN). The study covered 386 neonates with VLBW (≤1500 g), among which 262 cases of invasive infection were detected with predominance of CNS (123; 47%). Altogether, 100 CNS strains were analyzed. The resistance phenotypes were determined according to EUCAST. Resistance genes: mecA, ermA, ermB, ermC, msrA, aac(6')/aph(2''), ant(4')-Ia and aph(3')-IIIa were detected using multiplex PCR. Results The most common species was S. epidermidis (63%), then S. haemolyticus (28%) and other CNS (9%). Among S. epidermidis, 98% of isolates were resistant to methicillin, 90% to erythromycin, 39% to clindamycin, 95% to gentamicin, 60% to amikacin, 36% to ofloxacin, 2% to tigecycline, 3% to linezolid and 13% to teicoplanin. Among S. haemolyticus isolates, 100% were resistant to methicillin, erythromycin and gentamicin, 18% to clindamycin, 50% to amikacin, 86% to ofloxacin, 14% to tigecycline and 4% to teicoplanin. No resistance to linezolid was detected for S. haemolyticus isolates. Moreover, all isolates of S. epidermidis and S. haemolyticus were susceptible to vancomycin. The mecA gene was detected in 98% of S. epidermidis isolates and all of S. haemolyticus ones. Among macrolide resistance isolates, the ermC was most common in S. epidermidis (60%) while msrA was prevalent in S. haemolyticus (93%). The ermC gene was indicated in all isolates with cMLSB, whereas mrsA was found in isolates with MSB phenotype. Of the aminoglycoside resistance genes, aac(6')/aph(2'') were present alone in

  3. Prevalence of antibiotic resistance in multi-drug resistant coagulase-negative staphylococci isolated from invasive infection in very low birth weight neonates in two Polish NICUs.

    PubMed

    Brzychczy-Wloch, Monika; Borszewska-Kornacka, Maria; Gulczynska, Ewa; Wojkowska-Mach, Jadwiga; Sulik, Malgorzata; Grzebyk, Monika; Luchter, Malgorzata; Heczko, Piotr B; Bulanda, Malgorzata

    2013-12-20

    Multi-drug resistant coagulaso-negative staphylococci (CNS) have become an increasing problem in nosocomial infections connected with the presence of medical devices. The paper aimed to analyze the prevalence of antibiotic resistance in CNS isolated from invasive infection in very low birth weight (VLBW) neonates. Continuous prospective target surveillance of infections was conducted in 2009 at two Polish NICUs that participated in the Polish Neonatology Surveillance Network (PNSN). The study covered 386 neonates with VLBW (≤1500 g), among which 262 cases of invasive infection were detected with predominance of CNS (123; 47%). Altogether, 100 CNS strains were analyzed. The resistance phenotypes were determined according to EUCAST. Resistance genes: mecA, ermA, ermB, ermC, msrA, aac(6')/aph(2''), ant(4')-Ia and aph(3')-IIIa were detected using multiplex PCR. The most common species was S. epidermidis (63%), then S. haemolyticus (28%) and other CNS (9%). Among S. epidermidis, 98% of isolates were resistant to methicillin, 90% to erythromycin, 39% to clindamycin, 95% to gentamicin, 60% to amikacin, 36% to ofloxacin, 2% to tigecycline, 3% to linezolid and 13% to teicoplanin. Among S. haemolyticus isolates, 100% were resistant to methicillin, erythromycin and gentamicin, 18% to clindamycin, 50% to amikacin, 86% to ofloxacin, 14% to tigecycline and 4% to teicoplanin. No resistance to linezolid was detected for S. haemolyticus isolates. Moreover, all isolates of S. epidermidis and S. haemolyticus were susceptible to vancomycin. The mecA gene was detected in 98% of S. epidermidis isolates and all of S. haemolyticus ones. Among macrolide resistance isolates, the ermC was most common in S. epidermidis (60%) while msrA was prevalent in S. haemolyticus (93%). The ermC gene was indicated in all isolates with cMLSB, whereas mrsA was found in isolates with MSB phenotype. Of the aminoglycoside resistance genes, aac(6')/aph(2'') were present alone in 83% of S. epidermidis

  4. Capsular serotype and antibiotic resistance of Streptococcus pneumoniae isolates in Malaysia.

    PubMed

    Le, Cheng-Foh; Palanisamy, Navindra Kumari; Mohd Yusof, Mohd Yasim; Sekaran, Shamala Devi

    2011-01-01

    Streptococcus pneumoniae is a major causative agent of severe infections, including sepsis, pneumonia, meningitis, and otitis media, that has since become a major public health concern. In this study, the serotypes distribution of pneumococcal isolates was investigated to predict the efficacy of the 7-valent pneumococcal conjugate vaccine (PCV7) among the Malaysian populations. A total of 151 clinical isolates were serotyped using multiplex PCR assays. Out of them, there were 21.2% penicillin-resistant, 29.1% penicillin-intermediate, and 49.7% penicillin-susceptible S. pneumoniae strains. Serotypes detected among the Malaysian isolates were 1, 3, 10A, 11A/11D, 12F/12A, 14, 15A, 15B/15C, 16F, 18C/18B/18A/18F, 19A, 19F, 23F, 35B, 35F/47F, 6A/6B, 7C/7B/40, 7F/7A, 9V/9A, and 34. Serotype 19F and 23F were the two most prevalent serotypes detected. Serotypes are highly associated with invasiveness of isolates (p = 0.001) and penicillin susceptibility (p<0.001). Serotype 19F was observed to have increased resistance against penicillin while serotype 19A has high invasive tendency. Age of patients was an important factor underlying the pneumococcal serotypes (p = 0.03) and clinical sites of infections (p<0.001). High prevalence of pneumococcal isolates were detected among children <5 years old at nasopharyngeal sites while elderly adults ≥60 years old were at increased risk for pneumococcal bacteremia. Current study revealed that a number of serotypes, especially those associated with high penicillin resistance, have been formulated in the PCV7. Therefore, the protections expected from the routine use of PCV7 would be encouraging for the Malaysian. However, it is not possible to predict serotypes that might become predominant in the future and hence continued surveillance of circulating serotypes will be needed.

  5. Overcoming intrinsic multi-drug resistance in melanoma by blocking the mitochondrial respiratory chain of slow-cycling JARID1Bhigh cells

    PubMed Central

    Roesch, Alexander; Vultur, Adina; Bogeski, Ivan; Wang, Huan; Zimmermann, Katharina M.; Speicher, David; Körbel, Christina; Laschke, Matthias W.; Gimotty, Phyllis A.; Philipp, Stephan E.; Krause, Elmar; Pätzold, Sylvie; Villanueva, Jessie; Krepler, Clemens; Fukunaga-Kalabis, Mizuho; Hoth, Markus; Bastian, Boris; Vogt, Thomas; Herlyn, Meenhard

    2013-01-01

    Summary Despite success with BRAFV600E–inhibitors, therapeutic responses in patients with metastatic melanoma are short-lived because of the acquisition of drug resistance. We identified a mechanism of intrinsic multi-drug resistance based on the survival of a tumor cell subpopulation. Treatment with various drugs, including cisplatin and vemurafenib, uniformly leads to enrichment of slow-cycling, long-term tumor-maintaining melanoma cells expressing the H3K4-demethylase JARID1B/KDM5B/PLU-1. Proteome-profiling revealed an upregulation in enzymes of mitochondrial oxidative-ATP-synthesis (OXPHOS) in this subpopulation. Inhibition of mitochondrial respiration blocked the emergence of the JARID1Bhigh subpopulation and sensitized melanoma cells to therapy, independent of their genotype. Our findings support a two-tiered approach combining anti-cancer agents that eliminate rapidly proliferating melanoma cells with inhibitors of the drug-resistant slow-cycling subpopulation. PMID:23764003

  6. Serotypes and Antimicrobial Resistance of Human Nontyphoidal Isolates of Salmonella enterica from Crete, Greece.

    PubMed

    Maraki, Sofia; Papadakis, Ioannis S

    2014-01-01

    We report on the serotype distribution and the antimicrobial resistance patterns to 20 different antimicrobials of 150 Salmonella enterica strains isolated from stools of diarrhoeal patients on the island of Crete over the period January 2011-December 2012. Among the S. enterica serotypes recovered, Enteritidis was the most prevalent (37.3%), followed by Typhimurium (28.7%) and Newport (8.7%). No resistance was detected to extended-spectrum cephalosporins and carbapenems. Rates of resistance to ampicillin, amoxicillin/clavulanic acid, chloramphenicol, tetracycline, and cotrimoxazole were 9.3%, 4%, 2%, 15.3%, and 8.7%, respectively. Resistance to ≥4 antibiotics was primarily observed for serotypes Typhimurium and Hadar. Enteritidis remains the predominant serotype in Crete. Although low resistance to most antimicrobials was detected, continued surveillance of susceptibility is needed due to the risk of resistance.

  7. Suspected nosocomial infections with multi-drug resistant E. coli, including extended-spectrum beta-lactamase (ESBL)-producing strains, in an equine clinic.

    PubMed

    Walther, Birgit; Lübke-Becker, Antina; Stamm, Ivonne; Gehlen, Heidrun; Barton, Ann Kristin; Janssen, Traute; Wieler, Lothar H; Guenther, Sebastian

    2014-01-01

    Enterobacteriaceae such as Escherichia coli are common commensals as well as opportunistic and obligate pathogens. They cause a broad spectrum of infectious diseases in various hosts, including hospital-associated infections. In recent years, the rise of extended spectrum beta-lactamase (ESBL)-producing E. coli in companion animals (dogs, cats and horses) has been striking. However, reports on nosocomial infections are mostly anecdotic. Here we report on the suspected nosocomial spread of both ESBL-producing and non-ESBL-producing multi-drug resistant E. coli isolates in three equine patients within an equine clinic. Unlike easy-to-clean hospitalization opportunities available for small animal settings like boxes and cages made of ceramic floor tiles or stainless steel, clinical settings for horses are challenging environments for infection control programs due to unavoidable extraneous material including at least hay and materials used for horse bedding. The development of practice-orientated recommendations is needed to improve the possibilities for infection control to prevent nosocomial infections with multi-drug resistant and other transmissible pathogens in equine clinical settings.

  8. Sunlight mediated synthesis of silver nanoparticles by a novel actinobacterium (Sinomonas mesophila MPKL 26) and its antimicrobial activity against multi drug resistant Staphylococcus aureus.

    PubMed

    Manikprabhu, Deene; Cheng, Juan; Chen, Wei; Sunkara, Anil Kumar; Mane, Sunilkumar B; Kumar, Ram; das, Mousumi; N Hozzein, Wael; Duan, Yan-Qing; Li, Wen-Jun

    2016-05-01

    Synthesis of silver nanoparticles using microorganism are many, but there are only scanty reports using actinobacteria. In the present study, the actinobacterium of the genus Sinomonas was reported to synthesis silver nanoparticles for the first time. A photo-irradiation based method was developed for the synthesis of silver nanoparticles, which includes two day old cultural supernatant of novel species Sinomonas mesophila MPKL 26 and silver nitrate solution, exposed to sunlight. The preliminary synthesis of silver nanoparticles was noted by the color change of the solution from colorless to brown; the synthesis was further confirmed using UV-visible spectroscopy which shows a peak between 400 and 450nm. Spherical shape silver nanoparticles of size range 4-50nm were synthesized, which were characterized using transmission electron microscopy. The Fourier transform infrared spectroscopy result indicates that, the metabolite produced by the novel species S. mesophila MPKL 26 was the probable reducing/capping agent involved in the synthesis of silver nanoparticles. The synthesized silver nanoparticles maintained consistent shape with respect to different time periods. The synthesized silver nanoparticles were evaluated for the antimicrobial activity against multi drug resistant Staphylococcus aureus which show good antimicrobial activity. The method developed for synthesis is easy, requires less time (20min) and produces spherical shape nanoparticles of size as small as 4nm, having good antimicrobial activity. Hence, our study enlarges the scope of actinobacteria for the rapid biosynthesis of silver nanoparticles and can be used in formulating remedies for multi drug resistant S. aureus.

  9. Antibacterial activities of polyethylene glycol, tween 80 and sodium dodecyl sulphate coated silver nanoparticles in normal and multi-drug resistant bacteria.

    PubMed

    Bhattacharya, Debalina; Samanta, Saheli; Mukherjee, Ananda; Santra, Chitta Ranjan; Ghosh, Amar N; Niyogi, Swapan Kumar; Karmakar, Parimal

    2012-03-01

    Antibacterial activity of silver nanoparticles coated with different functionalizing agents i.e., polyethylene glycol, tween 80 and sodium dodecyl sulphate were evaluated on both normal and multi-drug resistant strains of bacteria. Under the same reaction conditions, these functionalizing agents were added separately to coat silver nanoparticles. Among these, polyethylene glycol coated nanoparticles were most effective in killing all the bacterial strains which includes Escherichia coli DH5a, Bacillus subtilis, Micrococcus luteus, Staphylococcus aureus and multi-drug resistant clinical isolates of Shigella spp. (flexneri, boydii, sohnea) and Vibrio cholerae. The minimum inhibitory concentration of polyethylene glycol coated silver nanoparticles was also less compared to the other two sets of nanoparticles. Consistence with that polyethylene glycol coated nanoparticles produced more intracellular reactive oxygen species in bacteria. Moreover, when human cell lines MCF7 and Chang Liver were incubated in presence of these nanoparticles for 18 h with same concentrations as used for bacteria, no toxicity was observed. But significant increase in cell killing was observed with longer incubation time. Thus our present investigation implicates the potential therapeutic use of silver nanoparticles as antibacterial agent particularly the polyethylene glycol coated one.

  10. Survival of multi-drug resistant enteropathogenic Escherichia coli and Salmonella paratyphi in Vembanadu lake as a function of saltwater barrier along southwest coast of India.

    PubMed

    Chandran, Abhirosh; Suson, P S; Thomas, A P; Hatha, Mohamed; Mazumder, Asit

    2013-06-01

    The objective of the study was to evaluate the survival response of multi-drug resistant enteropathogenic Escherichia coli and Salmonella paratyphi to the salinity fluctuations induced by a saltwater barrier constructed in Vembanadu lake, which separates the lake into a freshwater dominated southern and brackish water dominated northern part. Therefore, microcosms containing freshwater, brackish water and microcosms with different saline concentrations (5, 10, 15, 20, 25 ppt) inoculated with E. coli/S. paratyphi were monitored up to 34 days at 20 and 30 °C. E. coli and S. paratyphi exhibited significantly higher (p < 0.05) survival at 20 °C compared to 30 °C in all microcosms. Despite fresh/brackish water, E. coli and S. paratyphi showed prolonged survival up to 34 days at both temperatures. They also demonstrated better survival potential at all tested saline concentrations except 25 ppt where a significantly higher (p < 0.0001) decay was observed. Therefore, enhanced survival exhibited by the multi-drug resistant enteropathogenic E. coli and S. paratyphi over a wide range of salinity levels suggest that they are able to remain viable for a very long time at higher densities in all seasons of the year in Vembanadu lake irrespective of saline concentrations, and may pose potential public health risks during recreational activities.

  11. Physical and biological characteristics of multi drug resistance (MDR): An integral approach considering pH and drug resistance in cancer.

    PubMed

    Omran, Ziad; Scaife, Paula; Stewart, Simon; Rauch, Cyril

    2017-04-01

    The role of the Warburg effect in cancer remains to be elucidated with a resurgence in research efforts over the past decade. Why a cancer cell would prefer to use energy inefficient glycolysis, leading to an alteration of pH both inside and outside of the cell, remains to be uncovered. The development of MDR represents a major challenge in the treatment of cancer and it is explained, so far, by the over expression of drug transporters such as the well-known and archetypal P-glycoprotein (Pgp). However, controversies exist regarding the function of Pgp in multi-drug resistance. We suggest here that Pgp-mediated MDR relies fundamentally on pH alterations mediated by the Warburg effect. Furthermore, we propose that the use of proton pump and/or transporters inhibitors (PPIs/PTIs) in cancer are key to controlling both MDR, i.e. sensitize tumors to antineoplastic agents, and drug-related adverse effects. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  12. Antibiotic resistance and putative virulence factors of Serratia marcescens with respect to O and K serotypes.

    PubMed

    Aucken, H M; Pitt, T L

    1998-12-01

    Serratia marcescens serotypes O6:K14, O8:K14 and O28:K28 are common in the natural environment, but rare in hospitals. Serotypes O14:K14 and O27:K14 predominate among clinical strains, but not in the environment, suggesting that the latter serotypes may be more suited for survival in the clinical setting. Consequently, 469 epidemiologically distinct strains of S. marcescens were tested for various putative virulence factors and analysed for associations with serotype. The factors positively associated with serotype O14:K14 were agglutination of five different species of red blood cells and expression of type 1 fimbriae. These were found in 63% and 53% of O14:K14 strains, respectively, compared with 7% and 12% of the three 'environmental serotypes'. Almost a quarter of the collection expressed the mannose-resistant haemagglutinin indicative of type 3 fimbriae, but this was not associated with any serotype. The production of DNAase, haemolysin, lipase, lecithinase, proteases and siderophores was almost universal and showed no serotype correlations. Almost half of the strains (46%) were resistant to serum and serotypes O27:K14 and O6:K14 were strongly associated with this characteristic. Serotype O27:K14 was also associated with higher proportions of antibiotic-resistant strains than other serotypes, but the same was not true of serotype O14:K14. All three 'environmental serotypes' were associated with low frequencies of antibiotic resistance; <12% were resistant to gentamicin, carbenicillin or piperacillin, or any combination of these three, compared with 20-25% of O14:K14 strains and >42-51% of O27:K14 strains. Pigment production was strongly associated with serotype. None of the O14:K14 or O27:K14 strains produced prodigiosin, but frequencies for the three 'environmental serotypes' ranged from 31% of O28:K28 strains to 85% of O6:K14 strains. The results of this study suggest that the adherence capability of S. marcescens strains may play a role in the colonisation

  13. Resident Cats in Small Animal Veterinary Hospitals Carry Multi-Drug Resistant Enterococci and are Likely Involved in Cross-Contamination of the Hospital Environment

    PubMed Central

    Ghosh, Anuradha; KuKanich, Kate; Brown, Caitlin E.; Zurek, Ludek

    2012-01-01

    In the USA, small animal veterinary hospitals (SAVHs) commonly keep resident cats living permanently as pets within their facilities. Previously, multi-drug resistant (MDR) enterococci were found as a contaminant of multiple surfaces within such veterinary hospitals, and nosocomial infections are a concern. The objectives of this study were to determine whether resident cats carry MDR enterococci and to compare the feline isolates genotypically to those obtained from SAVH surfaces in a previous study. Enterococcal strains (n = 180) were isolated from the feces of six healthy resident cats from different SAVHs. The concentration of enterococci ranged from 1.1 × 105 to 6.0 × 108 CFU g−1 of feces, and the population comprised Enterococcus hirae (38.3 ± 18.6%), E. faecium (35.0 ± 14.3%), E. faecalis (23.9 ± 11.0%), and E. avium (2.8 ± 2.2%). Testing of phenotypic resistance to 14 antimicrobial agents revealed multi-drug resistance (≥3 antimicrobials) in 48.9% of all enterococcal isolates with most frequent resistance to tetracycline (75.0%), erythromycin (50.0%), and rifampicin (36.1%). Vancomycin resistant E. faecalis (3.9%) with vanB not horizontally transferable in in vitro conjugation assays were detected from one cat. Genotyping with pulsed-field gel electrophoresis demonstrated a host-specific clonal population of MDR E. faecalis and E. faecium. Importantly, several feline isolates were genotypically identical or closely related to isolates from surfaces of cage door, thermometer, and stethoscope of the corresponding SAVHs. These data demonstrate that healthy resident cats at SAVHs carry MDR enterococci and likely contribute to contamination of the SAVH environment. Proper disposal and handling of fecal material and restricted movement of resident cats within the ward are recommended. PMID:22363334

  14. Predominance of multi-drug-resistant LAM and Beijing family strains among Mycobacterium tuberculosis isolates recovered from prison inmates in Tula Region, Russia.

    PubMed

    Ignatova, Anna; Dubiley, Svetlana; Stepanshina, Valentina; Shemyakin, Igor

    2006-10-01

    The genotypic characteristics and drug susceptibility profiles of clinical isolates of Mycobacterium tuberculosis recovered from prison hospital patients in the Tula region (central Russia) during 2001 and 2002 are reported. The emergence of multi-drug-resistant tuberculosis (TB) poses a major health risk to the population, with economic implications for TB control. Prisons serve as a continuous source of TB transmission. The results showed that members of the LAM and Beijing families are major contributors to the epidemiological picture of TB in the population studied. The two families of strains accounted for most of the drug-resistant TB in the population. The genotypic characteristics of the M. tuberculosis predominant LAM strain that was responsible for 31 % of TB cases in this setting are presented.

  15. Antibacterial and antibiotic-potentiation activities of the methanol extract of some cameroonian spices against Gram-negative multi-drug resistant phenotypes.

    PubMed

    Voukeng, Igor K; Kuete, Victor; Dzoyem, Jean P; Fankam, Aimé G; Noumedem, Jaures A K; Kuiate, Jules R; Pages, Jean-Marie

    2012-06-15

    The present work was designed to evaluate the antibacterial properties of the methanol extracts of eleven selected Cameroonian spices on multi-drug resistant bacteria (MDR), and their ability to potentiate the effect of some common antibiotics used in therapy. The extract of Cinnamomum zeylanicum against Escherichia coli ATCC 8739 and AG100 strains showed the best activities, with the lowest minimal inhibitory concentration (MIC) of 64 μg/ml. The extract of Dorstenia psilurus was the most active when tested in the presence of an efflux pump inhibitor, phenylalanine Arginine-β- Naphtylamide (PAβN), a synergistic effect being observed in 56.25 % of the tested bacteria when it was combined with erythromycin (ERY). The present work evidently provides information on the role of some Cameroonian spices in the fight against multi-resistant bacteria.

  16. Antibacterial and antibiotic-potentiation activities of the methanol extract of some cameroonian spices against Gram-negative multi-drug resistant phenotypes

    PubMed Central

    2012-01-01

    Background The present work was designed to evaluate the antibacterial properties of the methanol extracts of eleven selected Cameroonian spices on multi-drug resistant bacteria (MDR), and their ability to potentiate the effect of some common antibiotics used in therapy. Results The extract of Cinnamomum zeylanicum against Escherichia coli ATCC 8739 and AG100 strains showed the best activities, with the lowest minimal inhibitory concentration (MIC) of 64 μg/ml. The extract of Dorstenia psilurus was the most active when tested in the presence of an efflux pump inhibitor, phenylalanine Arginine-β- Naphtylamide (PAβN), a synergistic effect being observed in 56.25 % of the tested bacteria when it was combined with Erythromycin (ERY). Conclusion The present work evidently provides information on the role of some Cameroonian spices in the fight against multi-resistant bacteria. PMID:22709668

  17. Targeted Antibiotic Delivery: Selective Siderophore Conjugation with Daptomycin Confers Potent Activity Against Multi-Drug Resistant Acinetobacter baumannii Both in vitro and in vivo.

    PubMed

    Ghosh, Manuka; Miller, Patricia A; Möllmann, Ute; Claypool, William D; Schroeder, Valerie A; Wolter, William R; Suckow, Mark; Yu, Honglin; Li, Shuang; Huang, Weiqiang; Zajicek, Jaroslav; Miller, Marvin J

    2017-03-13

    In order to address the dire need for new antibiotics to treat specific strains of drug resistant Gram-negative bacterial infections, a mixed ligand analog of the natural Acinetobacter baumannii selective siderophore, fimsbactin, was coupled to daptomycin, a Gram-positive only antibiotic. The resulting conjugate, 11, has potent activity against multi-drug resistant strains of A. baumannii, both in vitro and in vivo. The study also indicates that conjugation of siderophores to "drugs" that are much larger than the siderophore (iron transport agent) itself facilitates active uptake that circumvents the normal permeability problems in Gram-negative bacteria. The results demonstrate the ability to extend activity of a normally Gram-positive only antibiotic to create a potent and targeted Gram-negative antibiotic using a bacterial iron transport based sideromycin Trojan Horse strategy.

  18. Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors

    PubMed Central

    Schneider, Anna; Corona, Angela; Spöring, Imke; Jordan, Mareike; Buchholz, Bernd; Maccioni, Elias; Di Santo, Roberto; Bodem, Jochen; Tramontano, Enzo; Wöhrl, Birgitta M.

    2016-01-01

    We analyzed a multi-drug resistant (MR) HIV-1 reverse transcriptase (RT), subcloned from a patient-derived subtype CRF02_AG, harboring 45 amino acid exchanges, amongst them four thymidine analog mutations (TAMs) relevant for high-level AZT (azidothymidine) resistance by AZTMP excision (M41L, D67N, T215Y, K219E) as well as four substitutions of the AZTTP discrimination pathway (A62V, V75I, F116Y and Q151M). In addition, K65R, known to antagonize AZTMP excision in HIV-1 subtype B was present. Although MR-RT harbored the most significant amino acid exchanges T215Y and Q151M of each pathway, it exclusively used AZTTP discrimination, indicating that the two mechanisms are mutually exclusive and that the Q151M pathway is obviously preferred since it confers resistance to most nucleoside inhibitors. A derivative was created, additionally harboring the TAM K70R and the reversions M151Q as well as R65K since K65R antagonizes excision. MR-R65K-K70R-M151Q was competent of AZTMP excision, whereas other combinations thereof with only one or two exchanges still promoted discrimination. To tackle the multi-drug resistance problem, we tested if the MR-RTs could still be inhibited by RNase H inhibitors. All MR-RTs exhibited similar sensitivity toward RNase H inhibitors belonging to different inhibitor classes, indicating the importance of developing RNase H inhibitors further as anti-HIV drugs. PMID:26850643

  19. Cost-Effectiveness of a Model Infection Control Program for Preventing Multi-Drug-Resistant Organism Infections in Critically Ill Surgical Patients.

    PubMed

    Jayaraman, Sudha P; Jiang, Yushan; Resch, Stephen; Askari, Reza; Klompas, Michael

    2016-10-01

    Interventions to contain two multi-drug-resistant Acinetobacter (MDRA) outbreaks reduced the incidence of multi-drug-resistant (MDR) organisms, specifically methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and Clostridium difficile in the general surgery intensive care unit (ICU) of our hospital. We therefore conducted a cost-effective analysis of a proactive model infection-control program to reduce transmission of MDR organisms based on the practices used to control the MDRA outbreak. We created a model of a proactive infection control program based on the 2011 MDRA outbreak response. We built a decision analysis model and performed univariable and probabilistic sensitivity analyses to evaluate the cost-effectiveness of the proposed program compared with standard infection control practices to reduce transmission of these MDR organisms. The cost of a proactive infection control program would be $68,509 per year. The incremental cost-effectiveness ratio (ICER) was calculated to be $3,804 per aversion of transmission of MDR organisms in a one-year period compared with standard infection control. On the basis of probabilistic sensitivity analysis, a willingness-to-pay (WTP) threshold of $14,000 per transmission averted would have a 42% probability of being cost-effective, rising to 100% at $22,000 per transmission averted. This analysis gives an estimated ICER for implementing a proactive program to prevent transmission of MDR organisms in the general surgery ICU. To better understand the causal relations between the critical steps in the program and the rate reductions, a randomized study of a package of interventions to prevent healthcare-associated infections should be considered.

  20. Prevalence, serotype and antimicrobial resistance of salmonellae isolated from commercially processed broiler carcasses

    USDA-ARS?s Scientific Manuscript database

    This study was undertaken to determine the prevalence, serotype and antimicrobial resistance profiles of Salmonella on broiler carcasses collected from commercial processing plants. Twenty US commercial processing plants representing eight integrators in thirteen states were included in the survey....

  1. Antimicrobial resistance and serotype prevalence of Salmonella isolated from dairy cattle in the southwestern United States.

    PubMed

    Edrington, T S; Schultz, C L; Bischoff, K M; Callaway, T R; Looper, M L; Genovese, K J; Jung, Y S; McReynolds, J L; Anderson, R C; Nisbet, D J

    2004-01-01

    Mature dairy cattle were sampled over a 2-year period (2001-2002) on six farms in New Mexico and Texas. Fecal samples (n = 1560) were collected via rectal palpation and cultured for Salmonella, and one isolate from each positive sample was serotyped. Three isolates of each serotype, with the exception of Salmonella Newport (n = 12), were examined for susceptibility to 17 antimicrobial agents. Twenty-two different serotypes were identified from a total of 393 Salmonella isolates. Montevideo was the predominant serotype (27%) followed by Mbandaka (15%), Senftenberg (11.4%), Newport (6.4%), Anatum (4.8%), and Give (4.8%). Salmonella Typhimurium and Dublin, two frequently reported serotypes, accounted for only 1% of the observed serotypes in this study. Sixty-four percent of the serotypes were susceptible to all 17 antimicrobials, 14% were resistant to a single agent, and 22% were multiresistant (2-11 types of resistance). All isolates tested were susceptible to amikacin, apramycin, imipenem, ceftriaxone, nalidixic acid, and ciprofloxacin. The most frequent types of resistance were to sulfamethoxazole, tetracycline, streptomycin, kanamycin, chloramphenicol, and ampicillin (ranging from 8.9 to 22.4%). Serotypes demonstrating multiple resistance included Dublin and Give (resistant to three or more antibiotics), Typhimurium (resistant to five antibiotics), and Newport (four and two isolates resistant to six and nine antibiotics, respectively). Class 1 integrons were present in only two Salmonella Dublin isolates and one Salmonella Newport isolate. The most prevalent resistance patterns observed in this study were toward antimicrobial agents commonly used in cattle, while all Salmonella isolates were susceptible to ceftriaxone and ciprofloxacin, antibiotics used in human medicine.

  2. Co-delivery of docetaxel and verapamil by reduction-sensitive PEG-PLGA-SS-DTX conjugate micelles to reverse the multi-drug resistance of breast cancer.

    PubMed

    Guo, Yuanyuan; He, Wenxiu; Yang, Shengfeng; Zhao, Dujuan; Li, Zhonghao; Luan, Yuxia

    2017-03-01

    The clinical usage of docetaxel (DTX) has been blocked in the clinic because of its poor solubility and tumour multi-drug resistance (MDR). The dominating mechanism of MDR is the over-expression of p-gp on tumour cells. Traditional nano-medicines, such as nanoparticles and micelles, have been used to physically entrap DTX to improve their solubility, while the drug loading content was very low and the tumour resistance was neglected. In this study, the synthesized reduction-sensitive mPEG-PLGA-SS-DTX conjugate was utilized to load the p-gp inhibitor veraparmil (VRP) to prepare DTX and VRP co-delivered mPEG-PLGA-SS-DTX/VRP (PP-SS-DTX/VRP) multi-functional micelles to reverse MDR and enhance the anti-tumour effect of DTX. The micelles had a high drug loading content and showed an obvious reduction-sensitive release property for both DTX and VRP. In addition, an in vitro anti-tumour assay revealed that the micelles markedly inhibited the efflux activity of p-gp and accelerated cell apoptosis, resulting in the improvement of anti-tumour activity and reversal of MDR. The PP-SS-DTX micelles markedly enhanced the in vivo circulation time and increased the drug accumulation in tumour tissues. Therefore, the PP-SS-DTX/VRP micelle is a desirable drug delivery system for multi-drug resistance therapy of DTX and is very promising for clinical usage. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Solanum nigrum Unripe fruit fraction attenuates Adriamycin resistance by down-regulating multi-drug resistance protein (Mdr)-1 through Jak-STAT pathway.

    PubMed

    Jagadeeshan, Sankar; David, Diana; Jisha, S; Manjula, S; Asha Nair, S

    2017-07-18

    Solanum nigrum, herbal plant that commonly grows in temperate climate zone, has been used as a traditional folk medicine whose ripen fruits were proven to exhibit anti-tumor properties. In traditional Chinese medicine, it has been used for centuries to cure inflammation, edema, mastitis and hepatic cancer and in the Ayurvedic system of traditional medicine in India, S. nigrum is applied against enteric diseases, ulcer, diarrhea and skin diseases. A methanolic glycosidic extract fraction of unripe fruit of S. nigrum (SNME) was investigated for its anticancer property and possible mechanism to surmount adriamycin resistance in NCI/ADR-RES cells. The NCI/ADR-RES cells were treated with 7.8125, 15.625, 31.25, 62.5, 125 and 250 μg/ml of methanolic extract of S. nigrum (SNME) for 12, 24 and 48 h, to check the cell viability and proliferation. The cells were also exposed to adriamycin alone or in combination with SNME and the effects on cell growth were determined by MTT. Cell cycle analysis, Ethidium bromide and Acridine orange staining, Annexin-binding efficiency, nuclear condensation and DNA fragmentation of the apoptotic NCI/ADR-RES cells were also determined. To elucidate the relationship between SNME and multi drug resistance, we analyzed the expression levels of Mdr-1, JAK1, STAT3, and pSTAT3 in NCI/ADR-RES cells after treatment with SNME. Results from the cytotoxicity assay showed a direct correlation between the concentration of methanolic glycosidic extract fraction of S. nigrum (SNME) and the surviving cell population. Combination with Adriamycin, SNME exhibits a synergistic action on NCI/ADR-RES cells, giving the first line of evidence to overcoming Adriamycin resistance. The SNME mediated cell growth suppression was proven to be apoptotic, based on results obtained from DNA fragmentation, annexin V apoptosis assaay and PARP cleavage analysis. Looking into the molecular insight SNME surpasses the chemoresistance of NCI/ADR-RES cells by inhibiting the JAK

  4. Non-Invasive Pneumococcal Pneumonia in Portugal—Serotype Distribution and Antimicrobial Resistance

    PubMed Central

    Horácio, Andreia N.; Lopes, Joana P.; Ramirez, Mário; Melo-Cristino, José

    2014-01-01

    There is limited information on the serotypes causing non-invasive pneumococcal pneumonia (NIPP). Our aim was to characterize pneumococci causing NIPP in adults to determine recent changes in serotype prevalence, the potential coverage of pneumococcal vaccines and changes in antimicrobial resistance. Serotypes and antimicrobial susceptibility profiles of a sample of 1300 isolates recovered from adult patients (≥18 yrs) between 1999 and 2011 (13 years) were determined. Serotype 3 was the most frequent cause of NIPP accounting for 18% of the isolates. The other most common serotypes were 11A (7%), 19F (7%), 19A (5%), 14 (4%), 22F (4%), 23F (4%) and 9N (4%). Between 1999 and 2011, there were significant changes in the proportion of isolates expressing vaccine serotypes, with a steady decline of the serotypes included in the 7-valent conjugate vaccine from 31% (1999–2003) to 11% (2011) (P<0.001). Taking together the most recent study years (2009–2011), the potential coverage of the 13-valent conjugate vaccine was 44% and of the 23-valent polysaccharide vaccine was 66%. While erythromycin resistance increased from 8% in 1999–2003 to 18% in 2011 (P<0.001), no significant trend was identified for penicillin non-susceptibility, which had an average value of 18.5%. The serotype distribution found in this study for NIPP was very different from the one previously described for IPD, with only two serotypes in common to the ones responsible for half of each presentation in 2009–2011 – serotypes 3 and 19A. In spite of these differences, the overall prevalence of resistant isolates was similar in NIPP and in IPD. PMID:25075961

  5. The Effects and Mechanisms of Periplaneta americana Extract Reversal of Multi-Drug Resistance in BEL-7402/5-FU Cells.

    PubMed

    Yuan, Falu; Liu, Junyong; Qiao, Tingting; Li, Ting; Shen, Qi; Peng, Fang

    2016-06-28

    The present study reports the reversing effects of extracts from P. americana on multidrug resistance of BEL-7402/5-FU cells, as well as a preliminary investigation on their mechanism of action. A methylthiazolyl tetrazolium (MTT) method was applied to determine the multidrug resistance of BEL-7402/5-FU, while an intracellular drug accumulation assay was used to evaluate the effects of a column chromatography extract (PACC) and defatted extract (PADF) from P. americana on reversing multi-drug resistance. BEL-7402/5-FU reflected high resistance to 5-FU; PACC and PADF could promote drug accumulation in BEL-7402/5-FU cells, among which PADF was more effective than PACC. Moreover, results from the immunocytochemical method showed that PACC and PADF could downregulate the expression of drug resistance-associated proteins (P-gp, MRP, LRP); PACC and PADF had no effects on the expression of multidrug resistance-associated enzymes (GST-π), but PACC could increase the expression of multidrug resistance-associated enzymes (PKC). Results of real-time fluorescence quantitative PCR revealed that PACC and PADF were able to markedly inhibit the expression of multidrug resistance-associated genes (MDR1, LRP and MRP1); PACC presented a significant impact on the gene expression of multidrug resistance-associated enzymes, which increased the gene expression of GST-π and PKC. However, PADF had little impact on the expression of multidrug resistance-associated enzymes. These results demonstrated that PACC and PADF extracted from P. americana could effectively reverse MDR in BEL-7402/5-FU cells, whose mechanism was to inhibit the expression of P-gp, MRP, and LRP, and that PADF was more effective in the reversal of MDR than did PACC. In addition, some of extracts from P. americana altered (sometimes increasing) the expression of multidrug resistance-associated enzymes.

  6. Capsular Serotype and Antibiotic Resistance of Streptococcus pneumoniae Isolates in Two Chilean Cities

    PubMed Central

    Inostroza, Jaime; Trucco, Olivia; Prado, Valeria; Vinet, Ana Maria; Retamal, Gloria; Ossa, Gonzalo; Facklam, Richard R.; Sorensen, Ricardo U.

    1998-01-01

    We compared the incidence of nasopharyngeal colonization by Streptococcus pneumoniae, the serotypes causing mucosal and invasive diseases, and the antibiotic resistance of these strains in patients admitted to three large hospitals and children attending day care centers in two Chilean cities (Santiago and Temuco). The populations in both cities were similar in ethnic background, socioeconomic status, family size, and access to medical care. Significant differences in nasopharyngeal colonization rates, in serotypes causing infections, and in antibiotic resistance were found between the two cities. In children 0 to 2 years of age, 42% were colonized with S. pneumoniae in Santiago compared to 14% in Temuco. A total of 41 serotypes were identified in both Chilean cities studied. Six serotypes were found only in Santiago; 14 serotypes were found only in Temuco. Antibiotic-resistant serotypes 6A, 6B, 14, 19F, and 23F were detected only in Santiago. We show that important differences in the incidence of nasopharyngeal carriage, infection, and S. pneumoniae serotypes can exist in similar populations in different areas of the same country. Our findings are relevant for prevention strategies, antibiotic usage, and vaccine design. PMID:9521139

  7. Treatment of a lower urinary tract infection in a cat caused by a multi-drug methicillin-resistant Staphylococcus pseudintermedius and Enterococcus faecalis.

    PubMed

    Pomba, Constança; Couto, Natasha; Moodley, Arshnee

    2010-10-01

    Staphylococci and enterococci are common causes of urinary tract infections in cats. However, both species are rarely implicated together as causes of lower urinary tract infections associated with urethral obstruction. This report describes the first case of a multi-drug methicillin-resistant Staphylococcus pseudintermedius belonging to spa type t06 and Enterococcus faecalis urinary infection in a cat with pre-existing and recurrent urethral obstruction. Both species were isolated at >10(5)CFU/ml from a cystocentesis urine specimen. Clinical and ultrasound features, results from urinalysis, urine culture, molecular typing and susceptibility testing by minimal inhibitory concentrations determination are described. Oral treatment with nitrofurantoin, the only antimicrobial agent that constituted a viable therapeutic option, had a positive outcome.

  8. Comparative investigations of Klebsiella species of clinical origin: plasmid patterns, biochemical reactions, antibiotic resistances and serotypes.

    PubMed

    Podschun, R; Heineken, P; Ullmann, U; Sonntag, H G

    1986-09-01

    A total of 124 K. pneumoniae and 52 K. oxytoca isolates obtained from clinical specimens was investigated for plasmid patterns, biochemical reactions, antibiotic resistances and serotypes regarding to the distribution and relationships of these characters. A great diversity of plasmid patterns, bio/serotypes and resistance patterns was revealed. About 90% of strains contained plasmid DNA and up to seven plasmid bands per isolate could be shown. For K. pneumoniae, serotype 7 and for K. oxytoca, type 55 were most common. In general, little difference between both species was found and characters were similarly distributed. With respect to the site of isolation, serotype 7 was predominating in K. pneumoniae strains from the respiratory tract. Highly multiple-resistant organism were found in the largest number in specimens from the urogenital tract, in the lowest in specimens from wounds. Extensive statistical analyses did not detect any relationship among the characters investigated.

  9. Complete genome sequence, lifestyle, and multi-drug resistance of the human pathogen Corynebacterium resistens DSM 45100 isolated from blood samples of a leukemia patient.

    PubMed

    Schröder, Jasmin; Maus, Irena; Meyer, Katja; Wördemann, Stephanie; Blom, Jochen; Jaenicke, Sebastian; Schneider, Jessica; Trost, Eva; Tauch, Andreas

    2012-04-23

    Corynebacterium resistens was initially recovered from human infections and recognized as a new coryneform species that is highly resistant to antimicrobial agents. Bacteremia associated with this organism in immunocompromised patients was rapidly fatal as standard minocycline therapies failed. C. resistens DSM 45100 was isolated from a blood culture of samples taken from a patient with acute myelocytic leukemia. The complete genome sequence of C. resistens DSM 45100 was determined by pyrosequencing to identify genes contributing to multi-drug resistance, virulence, and the lipophilic lifestyle of this newly described human pathogen. The genome of C. resistens DSM 45100 consists of a circular chromosome of 2,601,311 bp in size and the 28,312-bp plasmid pJA144188. Metabolic analysis showed that the genome of C. resistens DSM 45100 lacks genes for typical sugar uptake systems, anaplerotic functions, and a fatty acid synthase, explaining the strict lipophilic lifestyle of this species. The genome encodes a broad spectrum of enzymes ensuring the availability of exogenous fatty acids for growth, including predicted virulence factors that probably contribute to fatty acid metabolism by damaging host tissue. C. resistens DSM 45100 is able to use external L-histidine as a combined carbon and nitrogen source, presumably as a result of adaptation to the hitherto unknown habitat on the human skin. Plasmid pJA144188 harbors several genes contributing to antibiotic resistance of C. resistens DSM 45100, including a tetracycline resistance region of the Tet W type known from Lactobacillus reuteri and Streptococcus suis. The tet(W) gene of pJA144188 was cloned in Corynebacterium glutamicum and was shown to confer high levels of resistance to tetracycline, doxycycline, and minocycline in vitro. The detected gene repertoire of C. resistens DSM 45100 provides insights into the lipophilic lifestyle and virulence functions of this newly recognized pathogen. Plasmid pJA144188 revealed a

  10. Complete genome sequence, lifestyle, and multi-drug resistance of the human pathogen Corynebacterium resistens DSM 45100 isolated from blood samples of a leukemia patient

    PubMed Central

    2012-01-01

    Background Corynebacterium resistens was initially recovered from human infections and recognized as a new coryneform species that is highly resistant to antimicrobial agents. Bacteremia associated with this organism in immunocompromised patients was rapidly fatal as standard minocycline therapies failed. C. resistens DSM 45100 was isolated from a blood culture of samples taken from a patient with acute myelocytic leukemia. The complete genome sequence of C. resistens DSM 45100 was determined by pyrosequencing to identify genes contributing to multi-drug resistance, virulence, and the lipophilic lifestyle of this newly described human pathogen. Results The genome of C. resistens DSM 45100 consists of a circular chromosome of 2,601,311 bp in size and the 28,312-bp plasmid pJA144188. Metabolic analysis showed that the genome of C. resistens DSM 45100 lacks genes for typical sugar uptake systems, anaplerotic functions, and a fatty acid synthase, explaining the strict lipophilic lifestyle of this species. The genome encodes a broad spectrum of enzymes ensuring the availability of exogenous fatty acids for growth, including predicted virulence factors that probably contribute to fatty acid metabolism by damaging host tissue. C. resistens DSM 45100 is able to use external L-histidine as a combined carbon and nitrogen source, presumably as a result of adaptation to the hitherto unknown habitat on the human skin. Plasmid pJA144188 harbors several genes contributing to antibiotic resistance of C. resistens DSM 45100, including a tetracycline resistance region of the Tet W type known from Lactobacillus reuteri and Streptococcus suis. The tet(W) gene of pJA144188 was cloned in Corynebacterium glutamicum and was shown to confer high levels of resistance to tetracycline, doxycycline, and minocycline in vitro. Conclusions The detected gene repertoire of C. resistens DSM 45100 provides insights into the lipophilic lifestyle and virulence functions of this newly recognized

  11. Correlation of Serotypes and Genotypes of Macrolide-Resistant Streptococcus agalactiae

    PubMed Central

    Kim, Hyo Youl; Jang, In Ho; Hwang, Gyu Yel; Yoon, Kap Jun

    2005-01-01

    Despite the necessity for studies of group B streptococci (GBS), due to the increase in serious adult infections, the emergence of new serotypes, and the increased resistance to macrolide antibiotics, such studies have been limited in Korea. The primary purpose of the present study was to determine the frequency trends of GBS serotypes, including serotypes VI, VII, and VIII. The final objective was to elucidate the relationship between the genotypes and serotypes of macrolide-resistant GBS isolates from a Korean population. Among 446 isolates of Streptococcus agalactiae, isolated between January 1990 and December 2002 in Korea, the frequency of serotypes were III (36.5%), Ib (22.0%), V (21.1%), Ia (9.6%), VI (4.3%), II (1.8%), VIII (1.3%), IV (1.1%), and VII (0.9%). The resistance rates to erythromycin, by serotype, were 85% (V), 23% (III), 21% (VI), 3% (Ib), and 2% (Ia). Of 135 erythromycin-resistant S. agalactiae, ermB was detected in 105 isolates, mefA in 20 isolates, and ermTR in seven isolates; most type V isolates harbored the ermB gene, Ib type isolates had an equal distribution of resistance genes, type III isolates accounted for 70% of all isolates carrying mefA genes, and one fourth of type VI isolates had mefA genes. PMID:16127771

  12. Identification and characterization of multidrug-resistant Salmonella enterica serotype Albert isolates in the United States.

    PubMed

    Folster, Jason P; Campbell, Davina; Grass, Julian; Brown, Allison C; Bicknese, Amelia; Tolar, Beth; Joseph, Lavin A; Plumblee, Jodie R; Walker, Carrie; Fedorka-Cray, Paula J; Whichard, Jean M

    2015-05-01

    Salmonella enterica is one of the most common causes of bacterial foodborne illness in the United States. Although most Salmonella infections are self-limiting, antimicrobial treatment of invasive salmonellosis is critical. The primary antimicrobial treatment options include fluoroquinolones or extended-spectrum cephalosporins, and resistance to these antimicrobial drugs may complicate treatment. At present, S. enterica is composed of more than 2,600 unique serotypes, which vary greatly in geographic prevalence, ecological niche, and the ability to cause human disease, and it is important to understand and mitigate the source of human infection, particularly when antimicrobial resistance is found. In this study, we identified and characterized 19 S. enterica serotype Albert isolates collected from food animals, retail meat, and humans in the United States during 2005 to 2013. All five isolates from nonhuman sources were obtained from turkeys or ground turkey, and epidemiologic data suggest poultry consumption or live-poultry exposure as the probable source of infection. S. enterica serotype Albert also appears to be geographically localized to the midwestern United States. All 19 isolates displayed multidrug resistance, including decreased susceptibility to fluoroquinolones and resistance to extended-spectrum cephalosporins. Turkeys are a likely source of multidrug-resistant S. enterica serotype Albert, and circulation of resistance plasmids, as opposed to the expansion of a single resistant strain, is playing a role. More work is needed to understand why these resistance plasmids spread and how their presence and the serotype they reside in contribute to human disease.

  13. Identification and Characterization of Multidrug-Resistant Salmonella enterica Serotype Albert Isolates in the United States

    PubMed Central

    Campbell, Davina; Grass, Julian; Brown, Allison C.; Bicknese, Amelia; Tolar, Beth; Joseph, Lavin A.; Plumblee, Jodie R.; Walker, Carrie; Fedorka-Cray, Paula J.; Whichard, Jean M.

    2015-01-01

    Salmonella enterica is one of the most common causes of bacterial foodborne illness in the United States. Although most Salmonella infections are self-limiting, antimicrobial treatment of invasive salmonellosis is critical. The primary antimicrobial treatment options include fluoroquinolones or extended-spectrum cephalosporins, and resistance to these antimicrobial drugs may complicate treatment. At present, S. enterica is composed of more than 2,600 unique serotypes, which vary greatly in geographic prevalence, ecological niche, and the ability to cause human disease, and it is important to understand and mitigate the source of human infection, particularly when antimicrobial resistance is found. In this study, we identified and characterized 19 S. enterica serotype Albert isolates collected from food animals, retail meat, and humans in the United States during 2005 to 2013. All five isolates from nonhuman sources were obtained from turkeys or ground turkey, and epidemiologic data suggest poultry consumption or live-poultry exposure as the probable source of infection. S. enterica serotype Albert also appears to be geographically localized to the midwestern United States. All 19 isolates displayed multidrug resistance, including decreased susceptibility to fluoroquinolones and resistance to extended-spectrum cephalosporins. Turkeys are a likely source of multidrug-resistant S. enterica serotype Albert, and circulation of resistance plasmids, as opposed to the expansion of a single resistant strain, is playing a role. More work is needed to understand why these resistance plasmids spread and how their presence and the serotype they reside in contribute to human disease. PMID:25733501

  14. 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 mechanisms behind and the extent of multi-drug resistance among bacteria living under an extreme antibiotic selection pressure.

  15. 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 mechanisms behind and the extent of multi-drug resistance among bacteria living under an extreme antibiotic selection pressure. PMID:24204801

  16. Prevalence of ColE1-like plasmids and kanamycinr resistance genes in Salmonella enterica serotypes

    USDA-ARS?s Scientific Manuscript database

    Multi-antibiotic resistant Salmonella enterica serotypes are increasing in prevalence and concern in human and animal health. Many strains carry resistance determinants on plasmids; current practices focus heavily on large plasmids, and the role that small plasmids play in resistance gene transfer ...

  17. Epidemiology of Multi-Drug Resistant Organisms in a Teaching Hospital in Oman: A One-Year Hospital-Based Study

    PubMed Central

    Balkhair, Abdullah; Al-Farsi, Yahya M.; Al-Muharrmi, Zakariya; Al-Rashdi, Raiya; Al-Jabri, Mansoor; Neilson, Fatma; Al-Adawi, Sara S.; El-Beeli, Marah

    2014-01-01

    Background. Antimicrobial resistance is increasingly recognized as a global challenge. A few studies have emerged on epidemiology of multidrug resistant organisms in tertiary care settings in the Arabian Gulf. Aim. To describe the epidemiology of multi-drug resistant organisms (MDRO) at Sultan Qaboos University Hospital, a tertiary hospital in Oman. Methods. A retrospective review of MDRO records has been conducted throughout the period from January 2012 till December 2012. Organisms were identified and tested by an automated identification and susceptibility system, and the antibiotic susceptibility testing was confirmed by the disk diffusion method. Results. Out of the total of 29,245 admissions, there have been 315 patients registered as MDRO patients giving an overall prevalence rate of 10.8 (95% CI 9.3, 12.4) MDRO cases per 1000 admissions. In addition, the prevalence rate of MDRO isolates was 11.2 (95% CI 9.7, 12.9) per 1000 admissions. Overall, increasing trends in prevalence rates of MDRO patients and MDRO isolates were observed throughout the study period. Conclusion. Antimicrobial resistance is an emerging challenge in Oman. Continuous monitoring of antimicrobial susceptibility and strict adherence to infection prevention guidelines are essential to prevent proliferation of MDRO. Along such quest, stringent antibiotic prescription guidelines are needed in the country. PMID:24526881

  18. Molecular analysis of plasmid encoded multi-drug resistance (MDR) in Salmonella enterica animal isolates by PFGE, replicon typing, and DNA microarray screening followed by high-throughput DNA sequencing

    USDA-ARS?s Scientific Manuscript database

    Background: The development of Multi-Drug Resistant (MDR) Salmonella is of global concern. MDR Salmonella genes can be transmitted in a number of ways including transfer of plasmids. To understand how MDR plasmids develop and are transmitted, their genetics must be thoroughly described. To achieve t...

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

    PubMed

    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.

  20. 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

  1. Prevalence of Class 1 Integrons and Extended Spectrum Beta Lactamases among Multi-Drug Resistant Escherichia coli Isolates from North of Iran

    PubMed Central

    Mehdipour Moghaddam, Mohammad Javad; Mirbagheri, Adeleh Alsadat; Salehi, Zivar; Habibzade, Seyyed Mahmood

    2015-01-01

    Background: Extended spectrum beta lactamases (ESBLs) are an important cause of transferable multidrug resistance (MDR) in gram-negative bacteria. The most described ESBL genes are generally found within integron-like structures as mobile genetic elements. The aim of this study was to identify the accompanying of class 1 integrons and ESBLs in the MDR E. coli isolates. Methods: Susceptibility to antimicrobial agents was determined for 33 E. coli strains by the disk diffusion method. Double-disk synergy test was applied for screening ESBL. To identify the strains carrying integrons, the conserved regions of integron-encoded integrase gene intI1 were amplified. For detection of gene cassettes, 5′CS and 3′CS primers were used. Results: All E. coli isolates were identified as multi-drug resistant. More than 50% of the isolates were resistant to tetracycline, cephalothin, cefuroxime, amoxicillin-clavulanic acid, and third generation cephalosporines. Nearly all of the isolates displayed sensitivity to piperacillin. There was a significant correlation between production of ESBL and resistance to all antibiotics except for ciprofloxacin and piperacillin (P < 0.01). Thirty two MDR strains (97%) included class 1 integron, and some isolates that included integrons were similar in the size of gene cassettes. The isolates were different in the resistance profiles; however, some others had similar resistance profiles. Of eight ESBL positive isolates, seven (87.5%) carried class 1 integrons. Conclusion: Class 1 integrons were frequent in MDR and also ESBL-producing E. coli isolates. High prevalence of class 1 integrons confirms that integron-mediated antimicrobial gene cassettes are important in E. coli resistance profile. PMID:26220727

  2. Study of antagonistic effects of Lactobacillus strains as probiotics on multi drug resistant (MDR) bacteria isolated from urinary tract infections (UTIs)

    PubMed Central

    Naderi, Atiyeh; Kasra-Kermanshahi, Roha; Gharavi, Sara; Imani Fooladi, Abbas Ali; Abdollahpour Alitappeh, Meghdad; Saffarian, Parvaneh

    2014-01-01

    Objective(s): Urinary tract infection (UTI) caused by bacteria is one of the most frequent infections in human population. Inappropriate use of antibiotics, often leads to appearance of drug resistance in bacteria. However, use of probiotic bacteria has been suggested as a partial replacement. This study was aimed to assess the antagonistic effects of Lactobacillus standard strains against bacteria isolated from UTI infections. Materials and Methods: Among 600 samples; those with ≥10,000 cfu/ml were selected as UTI positive samples. Enterococcus sp., Klebsiella pneumoniae, Enterobacter sp., and Escherichia coli were found the most prevalent UTI causative agents. All isolates were screened for multi drug resistance and subjected to the antimicrobial effects of three Lactobacillus strains by using microplate technique and the MICs amounts were determined. In order to verify the origin of antibiotic resistance of isolates, plasmid curing using ethidium bromide and acridine orange was carried out. Results: No antagonistic activity in Lactobacilli suspension was detected against test on Enterococcus and Enterobacter strains and K. pneumoniae, which were resistant to most antibiotics. However, an inhibitory effect was observed for E. coli which were resistant to 8-9 antibiotics. In addition, L. casei was determined to be the most effective probiotic. Results from replica plating suggested one of the plasmids could be related to the gene responsible for ampicillin resistance. Conclusion: Treatment of E. coli with probiotic suspension was not effective on inhibition of the plasmid carrying hypothetical ampicillin resistant gene. Moreover, the plasmid profiles obtained from probiotic-treated isolates were identical to untreated isolates. PMID:24847423

  3. High load of multi-drug resistant nosocomial neonatal pathogens carried by cockroaches in a neonatal intensive care unit at Tikur Anbessa specialized hospital, Addis Ababa, Ethiopia

    PubMed Central

    2012-01-01

    Background Cockroaches have been described as potential vectors for various pathogens for decades; although studies from neonatal intensive care units are scarce. This study assessed the vector potential of cockroaches (identified as Blatella germanica) in a neonatal intensive care unit setup in Tikur Anbessa Hospital, Addis Ababa, Ethiopia. Methods A total of 400 Blatella germanica roaches were aseptically collected for five consecutive months. Standard laboratory procedures were used to process the samples. Results From the external and gut homogenates, Klebsiella oxytoca, Klebsiella pneumoniae, Citrobacter spp. Enterobacter cloacae, Citrobacter diversus, Pseudomonas aeruginosa, Providencia rettgeri, Klebsiella ozaenae, Enterobacter aeruginosa, Salmonella C1, Non Group A streptococcus, Staphylococcus aureus, Escherichia coli, Acinetobacter spp. and Shigella flexneri were isolated. Multi-drug resistance was seen in all organisms. Resistance to up to all the 12 antimicrobials tested was observed in different pathogens. Conclusion Cockroaches could play a vector role for nosocomial infections in a neonatal intensive care unit and environmental control measures of these vectors is required to reduce the risk of infection. A high level of drug resistance pattern of the isolated pathogens was demonstrated. PMID:22958880

  4. Yu Ping Feng San reverses cisplatin-induced multi-drug resistance in lung cancer cells via regulating drug transporters and p62/TRAF6 signalling

    PubMed Central

    Lou, Jian-Shu; Yan, Lu; Bi, Cathy W. C.; Chan, Gallant K. L.; Wu, Qi-Yun; Liu, Yun-Le; Huang, Yun; Yao, Ping; Du, Crystal Y. Q.; Dong, Tina T. X.; Tsim, Karl W. K.

    2016-01-01

    Yu Ping Feng San (YPFS), an ancient Chinese herbal decoction composed of Astragali Radix, Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix, has been used in the clinic for treating immune deficiency. In cancer therapy, YPFS is being combined with chemotherapy drugs to achieve improved efficacy; however, scientific evidence to illustrate this combination effect is lacking. The present study aims to demonstrate the anti-drug resistance of YPFS in cisplatin (DDP)-resistant non-small cell lung cancer cells (A549/DDP). The application of YPFS exhibited a synergistic enhancement of DDP-induced cytotoxicity as well as of the apoptotic signalling molecules. DDP-induced expression of the multi-drug-resistance efflux transporters was markedly reduced in the presence of YPFS, resulting in a higher intracellular concentration of DDP. In addition, the application of YPFS increased DDP-induced ROS accumulation and MMP depletion, decreased p62/TRAF6 signalling in DDP-treated A549/DDP cells. The co-treatment of DDP and YPFS in tumour-bearing mice reduced the tumour size robustly (by more than 80%), which was much better than the effect of DDP alone. These results indicate that YPFS can notably improve the DDP-suppressed cancer effect, which may be a consequence of the elevation of intracellular DDP via the drug transporters as well as the down regulation of p62/TRAF6 signalling. PMID:27558312

  5. Antimicrobial resistance of Shigella flexneri serotypes in Israel during a period of three years: 2000-2002.

    PubMed Central

    Vasilev, V.; Japheth, R.; Yishai, R.; Andorn, N.

    2004-01-01

    This is a surveillance study of the antimicrobial resistance of the S. flexneri group in the context of its serotype diversity. It includes 1422 isolates, which were sent to the National Shigella Reference Centre (NSRC) by hospitals and outpatient clinics in Israel during a 3-year period (2000-2002). The strains were identified and classified according to the prevalence and antigenic structure of their serotypes. All samples were checked for resistance to ampicillin (AMP), trimethoprim-sulphamethoxazole (TMP-SMX), ceftriaxone (CRO), tetracycline (TE), nalidixic acid (NAL), and chloramphenicol (C) by the disk diffusion method of Bauer et al. There were significant differences in their resistance to the individual antimicrobials with resistance to AMP, TE and C being lower among the strains of serotype 6 than among those of serotypes 2a and 1b. The resistant phenotypes were also serotype-specific. The similarities both in individual and in phenotype resistance between the rare and the prevalent serotypes (but not serotype 6) may be attributed to their antigenic relatedness. The serospecificity of the antimicrobial resistance was not affected by external factors such as seasonality and source (hospital or outpatient laboratory) of the isolates, and the age and sex of the patients. The serotype-specific approach can assist in properly assessing the problem of the antimicrobial resistance of the Shigella flexneri group and may prove useful for the empirical therapy of shigellosis. The observed interdependency between resistance and the antigenic specificity and relatedness of the S. flexneri serotypes requires additional investigation. PMID:15635961

  6. Relation between serotype distribution and antibiotic resistance profiles of Listeria monocytogenes isolated from ground turkey.

    PubMed

    Ayaz, Naim Deniz; Erol, Irfan

    2010-05-01

    The objectives of this study were to determine the serotype distribution of Listeria monocytogenes isolated from ground turkey using a multiplex PCR assay and to determine antimicrobial resistance profiles of the isolates using the disc diffusion method. Of 78 isolates, 35 (44.9%), 29 (37.2%), 7 (9.0%), and 7 (9.0%) were identified as serotypes 1/2a (or 3a), 4b (or 4d or 4e), 1/2b (or 3b), and 1/2c (or 3c), respectively. Overall, 63 isolates (80.8%) were resistant to penicillin G, and 53 (67.9%) were resistant to ampicillin. All 1/2c (or 3c) serotype isolates were resistant to penicillin G and ampicillin, and all 1/2b (or 3b) serotype isolates were resistant to penicillin G. In addition, 91.4% (32 of 35) of 1/2a (or 3a), 57.1% (4 of 7) of 1/2b (or 3b), and 37.9% (11 of 29) of 4b (or 4d or 4e) serotype isolates were resistant to ampicillin, and 85.7% (30 of 35) of 1/2a (or 3a) and 65.5% (19 of 29) of 4b (or 4d or 4e) serotype isolates were resistant to penicillin G. In conclusion, most of the L. monocytogenes isolates identified were serotype 1/2a (or 3a) and 4b (or 4d or 4e). Serotype 1/2c (or 3c) isolates were highly resistant to antibiotics compared with isolates of serotypes 1/2a (or 3a), 1/2b (or 3b), and 4b (or 4d or 4e). Increasing resistance of L. monocytogenes to ampicillin and penicillin is an especially serious concern for public health because of the common use of these antibiotics in treatment of human listeriosis cases.

  7. Update on: Shigella new serogroups/serotypes and their antimicrobial resistance.

    PubMed

    Muthuirulandi Sethuvel, D P; Devanga Ragupathi, N K; Anandan, S; Veeraraghavan, B

    2017-01-01

    Shigellosis represents a major burden of disease in developing countries. A low infectious dose allows the disease to be spread effectively. Although shigellosis is mostly a self-limiting disease, antibiotics are recommended to reduce deaths, disease symptoms and organism-shedding time. However, in India, antimicrobial resistance among the genus Shigella is more common than among any other enteric bacteria. Notably, new serotypes or subserotypes in Shigella are reported from various parts of the world. Identification of new subserotypes of Shigella spp. is becoming a major issue as these strains are nontypeable by conventional serotyping. The commercially available antisera may not cover all possible epitopes of the O lipopolysaccharide antigen of Shigella serotypes. Therefore, molecular methods which most closely approach the resolution of full serotyping are necessary to identify such strains. In addition, the knowledge of a prevalent serotype in various geographic regions may assist in formulating strategies such as the development of a vaccine to prevent infection especially when the immunity to disease is serotype specific, and to understand the disease burden caused by new Shigella serotypes. © 2016 The Society for Applied Microbiology.

  8. Characteristics of plasmids in multi-drug-resistant enterobacteriaceae isolated during prospective surveillance of a newly opened hospital in Iraq

    USDA-ARS?s Scientific Manuscript database

    Multidrug-resistant (MDR) bacteria such as Escherichia coli and Klebsiella spp. are increasingly common causes of infections in hospitals worldwide and also in the U.S. military treatment facilities. Plasmids are thought to play an important role in the dissemination of antibiotic resistance in thes...

  9. Green synthesis of Al2O3 nanoparticles and their bactericidal potential against clinical isolates of multi-drug resistant Pseudomonas aeruginosa.

    PubMed

    Ansari, Mohammad A; Khan, Haris M; Alzohairy, Mohammad A; Jalal, Mohammad; Ali, Syed G; Pal, Ruchita; Musarrat, Javed

    2015-01-01

    -β-lactamases strains of P. aeruginosa, regardless of their drug resistance patterns and mechanisms. The results elucidated the clinical significance of Al2O3-NPs in developing an effective antibacterial therapeutic regimen against the multi-drug resistant bacterial infections. The use of leaf extract of lemongrass for the synthesis of Al2O3-NPs appears to be cost effective, nontoxic, eco-friendly and its strong antibacterial activity against multi-drug resistant strains of P. aeruginosa offers compatibility for pharmaceutical and other biomedical applications.

  10. Multi-drug resistance profile of PR20 HIV-1 protease is attributed to distorted conformational and drug binding landscape: molecular dynamics insights.

    PubMed

    Chetty, Sarentha; Bhakat, Soumendranath; Martin, Alberto J M; Soliman, Mahmoud E S

    2016-01-01

    The PR20 HIV-1 protease, a variant with 20 mutations, exhibits high levels of multi-drug resistance; however, to date, there has been no report detailing the impact of these 20 mutations on the conformational and drug binding landscape at a molecular level. In this report, we demonstrate the first account of a comprehensive study designed to elaborate on the impact of these mutations on the dynamic features as well as drug binding and resistance profile, using extensive molecular dynamics analyses. Comparative MD simulations for the wild-type and PR20 HIV proteases, starting from bound and unbound conformations in each case, were performed. Results showed that the apo conformation of the PR20 variant of the HIV protease displayed a tendency to remain in the open conformation for a longer period of time when compared to the wild type. This led to a phenomena in which the inhibitor seated at the active site of PR20 tends to diffuse away from the binding site leading to a significant change in inhibitor-protein association. Calculating the per-residue fluctuation (RMSF) and radius of gyration, further validated these findings. MM/GBSA showed that the occurrence of 20 mutations led to a drop in the calculated binding free energies (ΔGbind) by ~25.17 kcal/mol and ~5 kcal/mol for p2-NC, a natural peptide substrate, and darunavir, respectively, when compared to wild type. Furthermore, the residue interaction network showed a diminished inter-residue hydrogen bond network and changes in inter-residue connections as a result of these mutations. The increased conformational flexibility in PR20 as a result of loss of intra- and inter-molecular hydrogen bond interactions and other prominent binding forces led to a loss of protease grip on ligand. It is interesting to note that the difference in conformational flexibility between PR20 and WT conformations was much higher in the case of substrate-bound conformation as compared to DRV. Thus, developing analogues of DRV by

  11. The antimicrobial effects of cinnamon leaf oil against multi-drug resistant Salmonella Newport on organic leafy greens.

    PubMed

    Todd, Jennifer; Friedman, Mendel; Patel, Jitendra; Jaroni, Divya; Ravishankar, Sadhana

    2013-08-16

    There is generally no kill-step when preparing salad vegetables, so there is a greater risk for foodborne illness from contaminated vegetables. Some essential oils have antimicrobial activities and could provide a natural way to reduce pathogens on fresh produce. The objective of this study was to investigate the antimicrobial activity of cinnamon oil wash against Salmonella enterica serotype Newport on organic leafy greens. Organic romaine and iceberg lettuce, and organic baby and mature spinach were inoculated with Salmonella Newport and then dip treated in a phosphate buffered saline (PBS) control and 3 different concentrations (0.1, 0.3, and 0.5% v/v) of cinnamon oil. The treatment time varied at either 1 or 2min, and storage temperature varied at either 4 or 8°C. Samples were collected at days 0, 1, and 3. For romaine and iceberg lettuce, S. Newport was not recovered on day 3 for 2min 0.3% and 0.5% cinnamon oil treatments. For mature spinach, S. Newport was not recovered by day 3 for the 2min 0.3% and 0.5% 4°C treatments. For baby spinach, there was no recovery of S. Newport by day 1 for all 0.5% treatments. Overall, the cinnamon oil treatments were concentration and time dependent with higher concentrations and longer treatment times providing the greatest reduction in S. Newport population on leafy greens. In addition, the treatments had a residual effect with the greatest reduction generally seen on the last day of sampling. Storage temperature did not have a significant effect on the reduction of S. Newport. Based on the results of this study, cinnamon oil has the potential to be used as a treatment option for washing organic baby and mature spinach, and iceberg and romaine lettuces.

  12. Challenges with gonorrhea in the era of multi-drug and extensively drug resistance - are we on the right track?

    PubMed

    Unemo, Magnus; Golparian, Daniel; Shafer, William M

    2014-06-01

    Neisseria gonorrhoeae has retained antimicrobial resistance to drugs previously recommended for first-line empiric treatment of gonorrhea, and resistance to ceftriaxone, the last option for monotherapy, is evolving. Crucial actions to combat this developing situation include implementing response plans; considering use of dual antimicrobial regimens; enhancing surveillance of gonorrhea, gonococcal antimicrobial resistance, treatment failures and antimicrobial use/misuse and improving prevention, early diagnosis, contact tracing and treatment. The ways forward also include an intensified research to identify novel antimicrobial resistance determinants and develop and evaluate appropriate use of molecular antimicrobial resistance testing, ideally point-of-care and with simultaneous detection of gonococci, to supplement culture-based methods and ideally guide tailored treatment. It is crucial with an enhanced understanding of the dynamics of the national and international emergence, transmission and evolution of antimicrobial-resistant gonococcal strains. Genome sequencing combined with epidemiological metadata will detail these issues and might also revolutionize the molecular antimicrobial resistance testing. Ultimately, novel antimicrobials are essential and some antimicrobials in development have shown potent in vitro activity against gonococci. Several of these antimicrobials deserve further attention for potential future treatment of gonorrhea.

  13. Serotype Distribution and Antimicrobial Resistance of Streptococcus pneumoniae Isolated in Algiers, Algeria

    PubMed Central

    Ramdani-Bouguessa, Nadjia; Rahal, Kheira

    2003-01-01

    There are few data on antibiotic resistance of Streptococcus pneumoniae in Algeria. Among 309 strains, 34.6% were penicillin G-nonsusceptible S. pneumoniae strains (25.2% were intermediate and 9.4% were resistant). Serotypes 1, 5, 14, and 6 were the most frequent in invasive child infections. A multicenter study to standardize the national guidelines is needed. PMID:12543703

  14. Ciprofloxacin-Resistant Salmonella enterica Serotype Typhi, United States, 1999–2008

    PubMed Central

    Sjölund-Karlsson, Maria; Shin, Sanghyuk; Harvey, Emily; Joyce, Kevin; Theobald, Lisa; Nygren, Benjamin L.; Pecic, Gary; Gay, Kathryn; Austin, Jana; Stuart, Andrew; Blanton, Elizabeth; Mintz, Eric D.; Whichard, Jean M.; Barzilay, Ezra J.

    2011-01-01

    We report 9 ciprofloxacin-resistant Salmonella enterica serotype Typhi isolates submitted to the US National Antimicrobial Resistance Monitoring System during 1999–2008. The first 2 had indistinguishable pulsed-field gel electrophoresis patterns and identical gyrA and parC mutations. Eight of the 9 patients had traveled to India within 30 days before illness onset. PMID:21749779

  15. Quinolone-resistant Salmonella enterica serotype Enteritidis infections associated with international travel.

    PubMed

    O'Donnell, Allison T; Vieira, Antonio R; Huang, Jennifer Y; Whichard, Jean; Cole, Dana; Karp, Beth E

    2014-11-01

    We found a strong association between nalidixic acid-resistant Salmonella enterica serotype Enteritidis infections in the United States and recent international travel by linking Salmonella Enteritidis data from the National Antimicrobial Resistance Monitoring System and the Foodborne Diseases Active Surveillance Network.

  16. An outbreak of multi-drug resistant Escherichia coli urinary tract infection in an elderly population: a case-control study of risk factors.

    PubMed

    Ikram, Rosemary; Psutka, Rebecca; Carter, Alison; Priest, Patricia

    2015-06-09

    Prevention of infection due to multi-drug resistant organisms is particularly challenging because of the spread of resistant bacteria beyond hospitals into the community, including nursing homes. This study aimed to identify risk factors for the acquisition of a multidrug resistant (MDR) Escherichia coli in a local outbreak. Study participants were all aged over 65 years. Cases had the MDR E. coli isolated from a routine urine sample, and controls had a urine sample submitted to the laboratory in the same time period but the MDR E. coli was not isolated. Information from clinical records was used to identify risk factors both in the hospital and the community setting for acquisition of the MDR E. coli. 76 cases and 156 controls were identified and included in the study. In a multivariate analysis, risk factors statistically significantly associated with acquisition of the MDR E. coli were female gender (adjusted OR 3.2; 95 % confidence interval 1.5-6.9), level of care (high dependency OR 7.5; 2.2-25.7) compared with living independently), and in hospital prescription of antimicrobials to which the MDR E. coli was resistant (OR 5.6; 2.5-12.9). The major risk factors for the acquisition of a MDR E. coli were found to be residence in a nursing home and in-hospital prescription of antimicrobials to which the MDR E. coli was resistant. This emphasises that prevention of transmission of MDROs within a community needs to involve both hospitals and also other healthcare organizations, in this case nursing homes.

  17. Computational simulations of structural role of the active-site W374C mutation of acetyl-coenzyme-A carboxylase: multi-drug resistance mechanism.

    PubMed

    Zhu, Xiao-Lei; Yang, Wen-Chao; Yu, Ning-Xi; Yang, Sheng-Gang; Yang, Guang-Fu

    2011-03-01

    Herbicides targeting grass plastidic acetyl-CoA carboxylase (ACCase, EC 6.4.1.2) are selectively effective against graminicides. The intensive worldwide use of this herbicide family has selected for resistance genes in a number of grass weed species. Recently, the active-site W374C mutation was found to confer multi-drug resistance toward haloxyfop (HF), fenoxaprop (FR), Diclofop (DF), and clodinafop (CF) in A. myosuroides. In order to uncover the resistance mechanism due to W374C mutation, the binding of above-mentioned four herbicides to both wild-type and the mutant-type ACCase was investigated in the current work by molecular docking and molecular dynamics (MD) simulations. The binding free energies were calculated by molecular mechanics-Poisson-Boltzmann surface area (MM/PBSA) method. The calculated binding free energy values for four herbicides were qualitatively consistent with the experimental order of IC(50) values. All the computational model and energetic results indicated that the W374C mutation has great effects on the conformational change of the binding pocket and the ligand-protein interactions. The most significant conformational change was found to be associated with the aromatic amino acid residues, such as Phe377, Tyr161' and Trp346. As a result, the π-π interaction between the ligand and the residue of Phe377 and Tyr161', which make important contributions to the binding affinity, was decreased after mutation and the binding affinity for the inhibitors to the mutant-type ACCase was less than that to the wild-type enzyme, which accounts for the molecular basis of herbicidal resistance. The structural role and mechanistic insights obtained from computational simulations will provide a new starting point for the rational design of novel inhibitors to overcome drug resistance associated with W374C mutation.

  18. Glutathione-mediated antioxidant response and aerobic metabolism: two crucial factors involved in determining the multi-drug resistance of high-risk neuroblastoma

    PubMed Central

    Colla, Renata; Izzotti, Alberto; De Ciucis, Chiara; Fenoglio, Daniela; Ravera, Silvia; Speciale, Andrea; Ricciarelli, Roberta; Furfaro, Anna Lisa; Pulliero, Alessandra; Passalacqua, Mario; Traverso, Nicola; Pronzato, Maria Adelaide; Domenicotti, Cinzia; Marengo, Barbara

    2016-01-01

    Neuroblastoma, a paediatric malignant tumor, is initially sensitive to etoposide, a drug to which many patients develop chemoresistance. In order to investigate the molecular mechanisms responsible for etoposide chemoresistance, HTLA-230, a human MYCN-amplified neuroblastoma cell line, was chronically treated with etoposide at a concentration that in vitro mimics the clinically-used dose. The selected cells (HTLA-Chr) acquire multi-drug resistance (MDR), becoming less sensitive than parental cells to high doses of etoposide or doxorubicin. MDR is due to several mechanisms that together contribute to maintaining non-toxic levels of H2O2. In fact, HTLA-Chr cells, while having an efficient aerobic metabolism, are also characterized by an up-regulation of catalase activity and higher levels of reduced glutathione (GSH), a thiol antioxidant compound. The combination of such mechanisms contributes to prevent membrane lipoperoxidation and cell death. Treatment of HTLA-Chr cells with L-Buthionine-sulfoximine, an inhibitor of GSH biosynthesis, markedly reduces their tumorigenic potential that is instead enhanced by the exposure to N-Acetylcysteine, able to promote GSH synthesis. Collectively, these results demonstrate that GSH and GSH-related responses play a crucial role in the acquisition of MDR and suggest that GSH level monitoring is an efficient strategy to early identify the onset of drug resistance and to control the patient's response to therapy. PMID:27683112

  19. Proteome mining for the identification and in-silico characterization of putative drug targets of multi-drug resistant Clostridium difficile strain 630.

    PubMed

    Lohani, Mohtashim; Dhasmana, Anupam; Haque, Shafiul; Wahid, Mohd; Jawed, Arshad; Dar, Sajad A; Mandal, Raju K; Areeshi, Mohammed Y; Khan, Saif

    2017-05-01

    Clostridium difficile is an enteric pathogen that causes approximately 20% to 30% of antibiotic-associated diarrhea. In recent years, there has been a substantial rise in the rate of C. difficile infections as well as the emergence of virulent and antibiotic resistant C. difficile strains. So, there is an urgent need for the identification of therapeutic potential targets and development of new drugs for the treatment and prevention of C. difficile infections. In the current study, we used a hybrid approach by combining sequence similarity-based approach and protein-protein interaction network topology-based approach to identify and characterize the potential drug targets of C. difficile. A total of 155 putative drug targets of C. difficile were identified and the metabolic pathway analysis of these putative drug targets using DAVID revealed that 46 of them are involved in 9 metabolic pathways. In-silico characterization of these proteins identified seven proteins involved in pathogen-specific peptidoglycan biosynthesis pathway. Three promising targets viz. homoserine dehydrogenase, aspartate-semialdehyde dehydrogenase and aspartokinase etc. were found to be involved in multiple enzymatic pathways of the pathogen. These 3 drug targets are of particular interest as they can be used for developing effective drugs against multi-drug resistant C. difficile strain 630 in the near future.

  20. Putative histidine kinase inhibitors with antibacterial effect against multi-drug resistant clinical isolates identified by in vitro and in silico screens

    NASA Astrophysics Data System (ADS)

    Velikova, Nadya; Fulle, Simone; Manso, Ana Sousa; Mechkarska, Milena; Finn, Paul; Conlon, J. Michael; Oggioni, Marco Rinaldo; Wells, Jerry M.; Marina, Alberto

    2016-05-01

    Novel antibacterials are urgently needed to address the growing problem of bacterial resistance to conventional antibiotics. Two-component systems (TCS) are widely used by bacteria to regulate gene expression in response to various environmental stimuli and physiological stress and have been previously proposed as promising antibacterial targets. TCS consist of a sensor histidine kinase (HK) and an effector response regulator. The HK component contains a highly conserved ATP-binding site that is considered to be a promising target for broad-spectrum antibacterial drugs. Here, we describe the identification of putative HK autophosphorylation inhibitors following two independent experimental approaches: in vitro fragment-based screen via differential scanning fluorimetry and in silico structure-based screening, each followed up by the exploration of analogue compounds as identified by ligand-based similarity searches. Nine of the tested compounds showed antibacterial effect against multi-drug resistant clinical isolates of bacterial pathogens and include three novel scaffolds, which have not been explored so far in other antibacterial compounds. Overall, putative HK autophosphorylation inhibitors were found that together provide a promising starting point for further optimization as antibacterials.

  1. Susceptibility of the multi-drug resistant strain of Enterobacter aerogenes EA289 to the terpene alcohols from Cistus ladaniferus essential oil.

    PubMed

    Guinoiseau, Elodie; Lorenzi, Vannina; Luciani, Anne; Tomi, Félix; Casanova, Joseph; Berti, Liliane

    2011-08-01

    The essential oil (EO) of Cistus ladaniferus was separated into non polar, moderately polar and polar fractions by column chromatography. The EO and its fractions were analysed by gas chromatography in combination with retention indices [GC-(RI)] and 13C nuclear magnetic resonance (13C NMR) spectroscopy. A minimum inhibitory concentration (MIC) assay was used to evaluate their antibacterial activity against Gram-positive and Gram-negative pathogens of clinical relevance, including a multi-drug resistant (MDR) strain. The most polar fraction, constituted by mono- and sesquiterpene alcohols, strongly inhibited the growth of all tested bacteria with MIC values ranging from 0.05 to 0.8 mg/mL. More importantly, this fraction displayed high activity against the MDR strain of Enterobacter aerogenes EA289. Transmission electron microscopy (TEM) observations of the MDR bacteria treated with the terpene alcohol-rich fraction revealed cell wall distortion with an outer cytoplasmic membrane detachment. The susceptibility of the MDR strain of E. aerogenes EA289 to the polar fraction of C. ladaniferus oil suggests the possible use of these natural products to treat infections caused by highly resistant bacteria.

  2. Putative histidine kinase inhibitors with antibacterial effect against multi-drug resistant clinical isolates identified by in vitro and in silico screens

    PubMed Central

    Velikova, Nadya; Fulle, Simone; Manso, Ana Sousa; Mechkarska, Milena; Finn, Paul; Conlon, J. Michael; Oggioni, Marco Rinaldo; Wells, Jerry M.; Marina, Alberto

    2016-01-01

    Novel antibacterials are urgently needed to address the growing problem of bacterial resistance to conventional antibiotics. Two-component systems (TCS) are widely used by bacteria to regulate gene expression in response to various environmental stimuli and physiological stress and have been previously proposed as promising antibacterial targets. TCS consist of a sensor histidine kinase (HK) and an effector response regulator. The HK component contains a highly conserved ATP-binding site that is considered to be a promising target for broad-spectrum antibacterial drugs. Here, we describe the identification of putative HK autophosphorylation inhibitors following two independent experimental approaches: in vitro fragment-based screen via differential scanning fluorimetry and in silico structure-based screening, each followed up by the exploration of analogue compounds as identified by ligand-based similarity searches. Nine of the tested compounds showed antibacterial effect against multi-drug resistant clinical isolates of bacterial pathogens and include three novel scaffolds, which have not been explored so far in other antibacterial compounds. Overall, putative HK autophosphorylation inhibitors were found that together provide a promising starting point for further optimization as antibacterials. PMID:27173778

  3. Cross-talk between EPAS-1/HIF-2α and PXR signaling pathway regulates multi-drug resistance of stomach cancer cell.

    PubMed

    Zhao, Jiuda; Bai, Zhenzhong; Feng, Fan; Song, Erlin; Du, Feng; Zhao, Junhui; Shen, Guoshuang; Ji, Faxiang; Li, Guoyuan; Ma, Xinfu; Hang, Xingyi; Xu, Binghe

    2016-03-01

    EPAS-1/HIF-2α (Endothelial PAS domain-containing protein 1/hypoxia-inducible transcription factors 2α) is a transcription factor expressed in a wide range of human cancers, including stomach cancer. Although EPAS-1 has been studied for years, its function in oncogenic transformation processes needs to be further investigated. In this study, we found that EPAS-1 would promote the growth of stomach cancer cell line BGC-823. Our results revealed that EPAS-1 interacts with Pregnane X Receptor (PXR), a nuclear receptor that regulates multiple genes' transcription involved in multi-drugs resistance (MDR) process. Protein-protein interaction between EPAS-1 and PXR was identified by co-immunoprecipitation and GST-pull down assays. By this interaction, EPAS-1 recruited PXR to its response elements in promoter/enhancer regions of CYP3A4, a PXR target gene. Over-expression of EPAS-1 increased the expression of PXR responsive genes, enhanced the proliferation of BGC-823 cells and boosted the resistance of BGC-823 cells against the cytotoxicity of chemotherapeutic drugs, e.g. Mitomycin C and Paclitaxel. Reduction of EPAS-1 level via its siRNA disrupted the proliferation, and enhanced the susceptibility of BGC-823 cells to those chemotherapeutic drugs. Our findings suggested that EPAS-1 and PXR may cooperatively participate in development and especially MDR process of stomach cancer. These findings may contribute to more effective targeted drugs discovery for the stomach cancer therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Anticancer and antibacterial secondary metabolites from the endophytic fungus Penicillium sp. CAM64 against multi-drug resistant Gram-negative bacteria.

    PubMed

    Jouda, Jean-Bosco; Tamokou, Jean-de-Dieu; Mbazoa, Céline Djama; Sarkar, Prodipta; Bag, Prasanta Kumar; Wandji, Jean

    2016-09-01

    The emergence of multiple-drug resistance bacteria has become a major threat and thus calls for an urgent need to search for new effective and safe anti-bacterial agents. This study aims to evaluate the anticancer and antibacterial activities of secondary metabolites from Penicillium sp., an endophytic fungus associated with leaves of Garcinia nobilis. The culture filtrate from the fermentation of Penicillium sp. was extracted and analyzed by liquid chromatography-mass spectrometry, and the major metabolites were isolated and identified by spectroscopic analyses and by comparison with published data. The antibacterial activity of the compounds was assessed by broth microdilution method while the anticancer activity was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The fractionation of the crude extract afforded penialidin A-C (1-3), citromycetin (4), p-hydroxyphenylglyoxalaldoxime (5) and brefelfin A (6). All of the compounds tested here showed antibacterial activity (MIC = 0.50 - 128 µg/mL) against Gramnegative multi-drug resistance bacteria, Vibrio cholerae (causative agent of dreadful disease cholera) and Shigella flexneri (causative agent of shigellosis), as well as the significant anticancer activity (LC50 = 0.88 - 9.21 µg/mL) against HeLa cells. The results obtained indicate that compounds 1-6 showed good antibacterial and anticancer activities with no toxicity to human red blood cells and normal Vero cells.

  5. The hydrophobicity and roughness of a nasoenteral tube surface influences the adhesion of a multi-drug resistant strain of Staphylococcus Aureus.

    PubMed

    Lima, J C; Andrade, N J; Soares, N F F; Ferreira, S O; Fernandes, P E; Carvalho, C C P; Lopes, J P; Martins, J F L

    2011-04-01

    IN THIS STUDY, WE EXAMINED THE PHYSIOCHEMICAL PROPERTIES OF NASOENTERAL FEEDING TUBES MADE FROM TWO DIFFERENT TYPES OF POLYMER: silicone materials and polyurethane. The internal surfaces of the nasoenteral feeding tubes were analyzed for their hydrophobicity, roughness, microtopography, rupture-tension and ability to stretch. We also studied the adhesion of an isolated, multi-drug resistant strain of S. aureus to these polymers. The polyurethane nasoenteral tube, which was classified as hydrophilic, was more resistant to rupture-tension and stretching tests than the silicone tube, which was classified as hydrophobic. Additionally, the polyurethane tube had a rougher surface than the silicone tube. Approximately 1.0 log CFU.cm(-2) of S. aureus cells adhered to the tubes and this number was not statistically different between the two types of surfaces (p > 0.05). In future studies, new polymers for nasoenteral feeding tubes should be tested for their ability to support bacterial growth. Bacterial adhesion to these polymers can easily be reduced through modification of the polymer's physicochemical surface characteristics.

  6. Socio-economic implication of multi-drug resistant malaria in the community; how prepared is Nigeria for this emerging problem?

    PubMed

    Chukwuani, C M

    1999-01-01

    The control of faciparum malaria is becoming increasingly challenging in many endemic areas of the world, including Nigeria, due to the development of resistance to chloroquine and other anti-malarial drugs. Current rising health care costs demands that any preventive medicine and/or disease control program be judged according to its economic viability. As has been previously noted, any successful control of malaria will depend on socio-economic factors that influence its prevalence and management in the community. Cost-benefit or cost-effectiveness analysis of proposed and current intervention strategic are thus justified. This paper presents a review of studies involving socio-economic evaluation of the morbidity and mortality consequences of malaria. Studies involving health facility utilization profile for malaria in Nigeria and elsewhere are also reviewed. The review finds no studies evaluating or determining an appropriate economic model/framework for malaria control in Nigeria and concludes that as enormous and challenging the problem of multi-drug resistant malaria is, it can still be contained if control and management strategies are adopted based on sound and practical socio-economic judgement.

  7. The hydrophobicity and roughness of a nasoenteral tube surface influences the adhesion of a multi-drug resistant strain of Staphylococcus Aureus

    PubMed Central

    Lima, J.C.; Andrade, N.J.; Soares, N.F.F.; Ferreira, S.O.; Fernandes, P.E.; Carvalho, C.C.P.; Lopes, J.P.; Martins, J.F.L.

    2011-01-01

    In this study, we examined the physiochemical properties of nasoenteral feeding tubes made from two different types of polymer: silicone materials and polyurethane. The internal surfaces of the nasoenteral feeding tubes were analyzed for their hydrophobicity, roughness, microtopography, rupture-tension and ability to stretch. We also studied the adhesion of an isolated, multi-drug resistant strain of S. aureus to these polymers. The polyurethane nasoenteral tube, which was classified as hydrophilic, was more resistant to rupture-tension and stretching tests than the silicone tube, which was classified as hydrophobic. Additionally, the polyurethane tube had a rougher surface than the silicone tube. Approximately 1.0 log CFU.cm-2 of S. aureus cells adhered to the tubes and this number was not statistically different between the two types of surfaces (p > 0.05). In future studies, new polymers for nasoenteral feeding tubes should be tested for their ability to support bacterial growth. Bacterial adhesion to these polymers can easily be reduced through modification of the polymer’s physicochemical surface characteristics. PMID:24031660

  8. A 20(S)-protopanoxadiol derivative overcomes multi-drug resistance by antagonizing ATP-binding cassette subfamily B member 1 transporter function

    PubMed Central

    Chen, Wantao; Xu, Qin; Xiao, Meng; Hu, Lihong; Mao, Li; Wang, Xu

    2016-01-01

    In cancer cells, failure of chemotherapy is often caused by the ATP-binding cassette subfamily B member 1 (ABCB1), and few drugs have been successfully developed to overcome ABCB1-mediated multi-drug resistance (MDR). To suppress ABCB1 activity, we previously designed and synthesized a new series of derivatives based on 20(S)-protopanoxadiol (PPD). In the present study, we investigated the role of PPD derivatives in the function of ABC transporters. Non-toxic concentrations of the PPD derivative PPD12 sensitized ABCB1-overexpressing cells to their anti-cancer substrates better than either the parental PPD or inactive PPD11. PPD12 increased intracellular accumulation of adriamycin and rhodamine123 in resistant cancer cells. Although PPD12 did not suppress the expression of ABCB1 mRNA or protein, it stimulated the activity of ABCB1 ATPase. Because PPD12 is a competitive inhibitor, it was predicted to bind to the large hydrophobic cavity of homology-modeled human ABCB1. PPD12 also enhanced the efficacy of adriamycin against ABCB1-overexpressing KB/VCR xenografts in nude mice. In conclusion, PPD12 enhances the efficacy of substrate drugs in ABCB1-overexpressing cancer cells. These findings suggest that a combination therapy consisting of PPD12 with conventional chemotherapeutic agents may be an effective treatment for ABCB1-mediated MDR cancer patients. PMID:26824187

  9. Characteristics of Plasmids in Multi-Drug-Resistant Enterobacteriaceae Isolated during Prospective Surveillance of a Newly Opened Hospital in Iraq

    PubMed Central

    Chahine, Mohamad A.; Glenn, LaShanda M.; Ake, Julie A.; Su, Wanwen; Nikolich, Mikeljon P.; Lesho, Emil P.

    2012-01-01

    Background Gram-negative multidrug-resistant (MDR) bacteria are major causes of nosocomial infections, and antibiotic resistance in these organisms is often plasmid mediated. Data are scarce pertaining to molecular mechanisms of antibiotic resistance in resource constrained areas such as Iraq. Methodology/Principal Findings In this study, all MDR Enterobacteriaceae (n = 38) and randomly selected non-MDR counterparts (n = 41) isolated from patients, healthcare workers and environmental surfaces in a newly opened hospital in Iraq were investigated to characterize plasmids found in these isolates and determine their contribution to antibiotic resistance. Our results demonstrated that MDR E. coli and K. pneumoniae isolates harbored significantly more (≥3) plasmids compared to their non-MDR counterparts, which carried ≤2 plasmids (p<0.01). Various large plasmids (∼52 to 100 kb) from representative isolates were confirmed to contain multiple resistance genes by DNA microarray analysis. Aminoglycoside (acc, aadA, aph, strA/B, and ksgA), β-lactam (blaTEM1, blaAMPC, blaCTX-M-15, blaOXA-1, blaVIM-2 and blaSHV), sulfamethoxazole/trimethoprim (sul/dfr), tetracycline (tet) and chloramphenicol (cat) resistance genes were detected on these plasmids. Additionally, multiple plasmids carrying multiple antibiotic resistance genes were found in the same host strain. Genetic transfer-associated genes were identified on the plasmids from both MDR and non-MDR isolates. Seven plasmid replicon types (FII, FIA, FIB, B/O, K, I1 and N) were detected in the isolates, while globally disseminated IncA/C and IncHI1 plasmids were not detected in these isolates. Conclusions/Significance This is the first report of the characteristics of the plasmids found in Enterobacteriaceae isolated following the opening of a new hospital in Iraq. The information provided here furthers our understanding of the mechanisms of drug resistance in this specific region and their evolutionary

  10. Genomic insights into the ESBL and MCR-1-producing ST648 Escherichiacoli with multi-drug resistance.

    PubMed

    Zhang, Huimin; Seward, Christopher H; Wu, Zuowei; Ye, Huiyan; Feng, Youjun

    Polymyxin acts as an ultimate line of refuge against the severe infections by multidrug-resistant Gram-negative pathogens. This conventional idea is challenged dramatically by the recent discovery of mobile colistin resistance gene (mcr-1) is prevalent in food animals and human beings worldwide. More importantly, the mcr-1 gene was found to be co-localized with other antibiotic resistance genes, raising the possibility that super-bugs with pan-drug resistance are emerging. However, little is reported on the genomes of the mcr-1-positive bacterial host reservoirs. Here we report genome sequencing of three human isolates of the mcr-1-positive Escherichia coli (E15004, E15015 and E15017) and define general features through analyses of bacterial comparative genomics. Further genomic mining together with sequence typing allowed us to elucidate that the MCR-1-carrying E. coli E15017 belongs to the sequence type ST648 and coproduces extended-spectrum β-lactamase (ESBL). Given the fact that ST648 has been known to associate with either New Delhi metallo-β-lactamase 1 or ESBL, our results highlighted the possibility of ST648 as an epidemic clone with multidrug resistances.

  11. Community acquired multi drug resistant Staphylococcus aureus in a rural setting of North Western Ethiopia: a tough challenge.

    PubMed

    Tibebu, Martha; Embiyale, Wondimagegn

    2014-07-01

    Commnunity acquired Methicillin Resistant Staphylococcus aureus species are common causes of skin and soft tissue infections. Foot ulcer of former leprosy patients can be invaded by a multi-microbial infection. Cervicitis is usually caused by certain sexually transmitted agents. Here we report a series of cases of methicillin-resistant Staphylococcus aureus, isolated from two patients presenting with foot ulcer and cervicitis respectively, both in an outpatient or community setting (community onset) in rural North Western Ethiopia. The strains were resistant to all commonly available drugs such as trimethoprim-sulfamethoxazole, ciprofloxacin, erythromycin, chloramphenicol and tetracycline but sensitive to clindamycin. This is the first report of CA-MRSA in the study area.

  12. Genome sequence comparisons of serial multi-drug-resistant Mycobacterium tuberculosis isolates over 21 years of infection in a single patient

    PubMed Central

    Meumann, Ella M.; Globan, Maria; Fyfe, Janet A. M.; Leslie, David; Porter, Jessica L.; Seemann, Torsten; Denholm, Justin

    2015-01-01

    We report a case of chronic pulmonary multi-drug-resistant tuberculosis. Despite 14 years of treatment, Mycobacterium tuberculosis was persistently isolated from sputum. Following treatment cessation the patient remained well, although M. tuberculosis was isolated from sputum for a further 8 years. Genome sequencing of eight serial M. tuberculosis isolates cultured between 1991 and 2011 revealed 17 mutations (0.8 mutations per genome year− 1). Eight of these were persisting mutations and only two mutations were detected in the 7 years following cessation of treatment in 2004. In four isolates there were mixed alleles, suggesting the likely presence of bacterial subpopulations. The initial 1991 isolate demonstrated genotypic resistance to isoniazid (katG W91R), rifampicin (rpoB S531L), ethambutol (embB M306V), streptomycin (gidB L16R), quinolones (gyrA S95T) and P-aminosalicylic acid (thyA T202A). Subsequent resistance mutations developed for pyrazinamide (pncA I31F) and ethionamide (ethA frameshift). Such information might have been instructive when developing a treatment regimen. In retrospect and with the benefit of high-resolution genomic hindsight we were able to determine that the patient received only one or two active anti-tuberculous agents for most of their treatment. Additionally, mutations in bacA and Rv2326c were detected, which may have contributed to the persistent but mild disease course. BacA is likely to be associated with maintenance of chronic infection and Rv2326c with a decreased bacterial metabolic state. These results expand our understanding of M. tuberculosis evolution during human infection and underline the link between antibiotic resistance and clinical persistence. PMID:28348821

  13. Evaluation of GenoType® MTBDRplus assay for rapid detection of drug susceptibility testing of multi-drug resistance tuberculosis in Northern India.

    PubMed

    Maurya, Anand Kumar; Umrao, Jyoti; Singh, Amresh Kumar; Kant, Surya; Kushwaha, Ram Awadh Singh; Dhole, Tapan N

    2013-01-01

    The problem of multi-drug resistance tuberculosis (MDR-TB) is growing in several hotspots throughout the world. Rapid and accurate diagnosis of MDR-TB is crucial to facilitate early treatment and to reduce its spread in the community. The aim of the present study was to evaluate the new, novel GenoType® MTBDRplus assay for rapid detection of drug susceptibility testing (DST) of MDR-TB cases in Northern India. A total of 550 specimens were collected from highly suspected drug resistant from pulmonary and extra-pulmonary TB cases. All the specimens were processed by Ziehl- Neelsen staining, culture, differentiation by the GenoType® CM assay, first line DST using BacT/ALERT 3D system and GenoType® MTBDRplus assay. The concordance of the GenoType® MTBDRplus assay was calculated in comparison with conventional DST results. Overall the sensitivity for detection of rifampicin, isoniazid and MDR-TB resistance by GenoType® MTBDRplus assay was 98.0%, 98.4% and 98.2% respectively. Out of 55 MDR-TB strains, 45 (81.8%), 52 (94.5%) and 17 (30.9%) strains showed mutation in rpoB, katG and inhA genes respectively (P < 0.05). The most prominent mutations in rpoB, katG and inhA genes were; 37 (67.3%) in S531L, 52 (94.5%) in S315T1 and 11 (20%) in C15T regions respectively (P < 0.05). Our study demonstrated a high concordance between the GenoType® MTBDRplus assay resistance patterns and those were observed by conventional DST with good sensitivity, specificity with short turnaround times and to control new cases of MDR-TB in countries with a high prevalence of MDR-TB.

  14. Cytotoxic and antibacterial substances against multi-drug resistant pathogens from marine sponge symbiont: Citrinin, a secondary metabolite of Penicillium sp.

    PubMed Central

    Subramani, Ramesh; Kumar, Rohitesh; Prasad, Pritesh; Aalbersberg, William

    2013-01-01

    Objective To Isolate, purify, characterize, and evaluate the bioactive compounds from the sponge-derived fungus Penicillium sp. FF001 and to elucidate its structure. Methods The fungal strain FF001 with an interesting bioactivity profile was isolated from a marine Fijian sponge Melophlus sp. Based on conidiophores aggregation, conidia development and mycelia morphological characteristics, the isolate FF001 was classically identified as a Penicillium sp. The bioactive compound was identified using various spectral analysis of UV, high resolution electrospray ionization mass spectra, 1H and 13C NMR spectral data. Further minimum inhibitory concentrations (MICs) assay and brine shrimp cytotoxicity assay were also carried out to evaluate the biological properties of the purified compound. Results Bioassay guided fractionation of the EtOAc extract of a static culture of this Penicillium sp. by different chromatographic methods led the isolation of an antibacterial, anticryptococcal and cytotoxic active compound, which was identified as citrinin (1). Further, citrinin (1) is reported for its potent antibacterial activity against methicillin-resistant Staphylococcus aureus (S. aureus), rifampicin-resistant S. aureus, wild type S. aureus and vancomycin-resistant Enterococcus faecium showed MICs of 3.90, 0.97, 1.95 and 7.81 µg/mL, respectively. Further citrinin (1) displayed significant activity against the pathogenic yeast Cryptococcus neoformans (MIC 3.90 µg/mL), and exhibited cytotoxicity against brine shrimp larvae LD50 of 96 µg/mL. Conclusions Citrinin (1) is reported from sponge associated Penicillium sp. from this study and for its strong antibacterial activity against multi-drug resistant human pathogens including cytotoxicity against brine shrimp larvae, which indicated that sponge associated Penicillium spp. are promising sources of natural bioactive metabolites. PMID:23620853

  15. Combining essential oils and olive extract for control of multi-drug resistant Salmonella enterica on organic leafy greens

    USDA-ARS?s Scientific Manuscript database

    We investigated the combined antimicrobial effects of plant essential oils and olive extract against antibiotic resistant Salmonella enterica serovar Newport on organic leafy greens. Organic baby spinach, mature spinach, romaine lettuce, and iceberg lettuce were inoculated with S. Newport and dip-t...

  16. [Thin layer agar represents a cost-effective alternative for the rapid diagnosis of multi-drug resistant tuberculosis].

    PubMed

    Hernández-Sarmiento, José M; Martínez-Negrete, Milton A; Castrillón-Velilla, Diana M; Mejía-Espinosa, Sergio A; Mejía-Mesa, Gloria I; Zapata-Fernández, Elsa M; Rojas-Jiménez, Sara; Marín-Castro, Andrés E; Robledo-Restrepo, Jaime A

    2014-01-01

    Using cost-benefit analysis for comparing the thin-layer agar culture method to the standard multiple proportion method used in diagnosing multidrug-resistant tuberculosis (MDR TB). A cost-benefit evaluation of two diagnostic tests was made at the Corporación para Investigaciones Biológicas (CIB) in Medellín, Colombia. 100 patients were evaluated; 10.8% rifampicin resistance and 14.3% isoniazid resistance were found. A computer-based decision tree model was used for cost-effectiveness analysis (Treeage Pro); the thin-layer agar culture method was most cost-effective, having 100% sensitivity, specificity and predictive values for detecting rifampicin and isoniazid resistance. The multiple proportion method value was calculated as being US$ 71 having an average 49 day report time compared to US$ 18 and 14 days for the thin-layer agar culture method. New technologies have been developed for diagnosing tuberculosis which are apparently faster and more effective; their operating characteristics must be evaluated as must their effectiveness in terms of cost-benefit. The present study established that using thin-layer agar culture was cheaper, equally effective and could provide results more quickly than the traditional method. This implies that a patient could receive MDR TB treatment more quickly.

  17. Multi-drug resistant oral Candida species isolated from HIV-positive patients in South Africa and Cameroon.

    PubMed

    Dos Santos Abrantes, Pedro Miguel; McArthur, Carole P; Africa, Charlene Wilma Joyce

    2014-06-01

    Candida species are a common cause of infection in immune-compromised HIV-positive individuals, who are usually treated with the antifungal drug, fluconazole, in public hospitals in Africa. However, information about the prevalence of drug resistance to fluconazole and other antifungal agents on Candida species is very limited. This study examined 128 Candida isolates from South Africa and 126 Cameroonian Candida isolates for determination of species prevalence and antifungal drug susceptibility. The isolates were characterized by growth on chromogenic and selective media and by their susceptibility to 9 antifungal drugs tested using the TREK™ YeastOne9 drug panel (Thermo Scientific, USA). Eighty-three percent (82.8%) of South African isolates were Candida albicans (106 isolates), 9.4% were Candida glabrata (12 isolates), and 7.8% were Candida dubliniensis (10 isolates). Of the Cameroonian isolates, 73.02% were C. albicans (92 isolates); 19.05% C. glabrata (24 isolates); 3.2% Candida tropicalis (4 isolates); 2.4% Candida krusei (3 isolates); 1.59% either Candida kefyr, Candida parapsilopsis, or Candida lusitaneae (2 isolates); and 0.79% C. dubliniensis (1 isolate). Widespread C. albicans resistance to azoles was detected phenotypically in both populations. Differences in drug resistance were seen within C. glabrata found in both populations. Echinocandin drugs were more effective on isolates obtained from the Cameroon than in South Africa. A multiple-drug resistant C. dubliniensis strain isolated from the South African samples was inhibited only by 5-flucytosine in vitro on the YO9 panel. Drug resistance among oral Candida species is common among African HIV patients in these 2 countries. Regional surveillance of Candida species drug susceptibility should be undertaken to ensure effective treatment for HIV-positive patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Spread of Streptococcus pneumoniae Serotype 8-ST63 Multidrug-Resistant Recombinant Clone, Spain

    PubMed Central

    de la Campa, Adela G.; García, Ernesto; Fenoll, Asunción; Calatayud, Laura; Cercenado, Emilia; Pérez-Trallero, Emilio; Bouza, Emilio; Liñares, Josefina

    2014-01-01

    Since 2004, a total of 131 isolates of Streptococcus pneumoniae multidrug-resistant invasive serotype 8 have been detected in Spain. These isolates showed resistance to erythromycin, clindamycin, tetracycline, and ciprofloxacin. All isolates were obtained from adult patients and shared a common genotype (sequence type [ST]63; penicillin-binding protein 1a [pbp1a], pbp2b, and pbp2x gene profiles; ermB and tetM genes; and a ParC-S79F change). Sixty-eight isolates that required a ciprofloxacin MIC ≥16 μg/mL had additional gyrA gene changes. Serotype 8-ST63 pbp2x sequences were identical with those of antimicrobial drug–susceptible serotype 8-ST53 isolates. Serotype 8-ST63 pbp2b sequences were identical with those of the multidrug-resistant Sweden 15A-ST63 clone. Recombination between the capsular locus and flanking regions of an ST53 isolate (donor) and an ST63 pneumococcus (recipient) generated the novel 15A-ST63 clone. One recombination point was upstream of pbp2x and another was within pbp1a. A serotype 8-ST63 clone was identified as a cause of invasive disease in Spain. PMID:25340616

  19. Multifunctional Cu2-xTe Nanocubes Mediated Combination Therapy for Multi-Drug Resistant MDA MB 453

    NASA Astrophysics Data System (ADS)

    Poulose, Aby Cheruvathoor; Veeranarayanan, Srivani; Mohamed, M. Sheikh; Aburto, Rebeca Romero; Mitcham, Trevor; Bouchard, Richard R.; Ajayan, Pulickel M.; Sakamoto, Yasushi; Maekawa, Toru; Kumar, D. Sakthi

    2016-10-01

    Hypermethylated cancer populations are hard to treat due to their enhanced chemo-resistance, characterized by aberrant methylated DNA subunits. Herein, we report on invoking response from such a cancer lineage to chemotherapy utilizing multifunctional copper telluride (Cu2-XTe) nanocubes (NCs) as photothermal and photodynamic agents, leading to significant anticancer activity. The NCs additionally possessed photoacoustic and X-ray contrast imaging abilities that could serve in image-guided therapeutic studies.

  20. Bactericidal Activity of Methanol Extracts of Crabapple Mangrove Tree (Sonneratia caseolaris Linn.) Against Multi-Drug Resistant Pathogens.

    PubMed

    Yompakdee, C; Thunyaharn, S; Phaechamud, T

    2012-05-01

    The crabapple mangrove tree, Sonneratia caseolaris Linn. (Family: Sonneratiaceae), is one of the foreshore plants found in estuarine and tidal creek areas and mangrove forests. Bark and fruit extracts from this plant have previously been shown to have an anti-oxidative or cytotoxic effect, whereas flower extracts of this plant exhibited an antimicrobial activity against some bacteria. According to the traditional folklore, it is medicinally used as an astringent and antiseptic. Hence, this investigation was carried out on the extract of the leaves, pneumatophore and different parts of the flower or fruit (stamen, calyx, meat of fruit, persistent calyx of fruit and seeds) for antibacterial activity using the broth microdilution method. The antibacterial activity was evaluated against five antibiotic-sensitive species (three Gram-positive and two Gram-negative bacteria) and six drug-resistant species (Gram-positive i.e. Methicillin-resistant Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium and Gram-negative i.e. Extended-spectrum beta-lactamase-Escherichia coli, multidrug-resistant-Pseudomonas aeruginosa and Acenetobacter baumannii). The methanol extracts from all tested parts of the crabapple mangrove tree exhibited antibacterial activity against both Gram-positive and Gram-negative bacteria, but was mainly a bactericidal against the Gram-negative bacteria, including the multidrug-resistant strains, when compared with only bacteriostatic on the Gram-positive bacteria. Using Soxhlet apparatus, the extracts obtained by sequential extraction with hexane, dichloromethane and ethyl acetate revealed no discernable antibacterial activity and only slightly, if at all, reduced the antibacterial activity of the subsequently obtained methanol extract. Therefore, the active antibacterial compounds of the crabapple mangrove tree should have a rather polar structure.

  1. Profile of Virulence Factors in the Multi-Drug Resistant Pseudomonas aeruginosa Strains of Human Urinary Tract Infections (UTI)

    PubMed Central

    Habibi, Asghar; Honarmand, Ramin

    2015-01-01

    Background: Putative virulence factors are responsible for the pathogenicity of UTIs caused by Pseudomonas aeruginosa (P. aeruginosa). Resistance of P. aeruginosa to commonly used antibiotics is caused by the extreme overprescription of those antibiotics. Objectives: The goal of the present study was to investigate the prevalence of virulence factors and the antibiotic resistance patterns of P. aeruginosa isolates in UTI cases in Iran. Patients and Methods: Two hundred and fifty urine samples were collected from patients who suffered from UTIs. Samples were cultured immediately, and those that were P. aeruginosa-positive were analyzed for the presence of virulence genes using polymerase chain reaction (PCR) testing. Antimicrobial susceptibility testing (AST) was performed using the disk diffusion method. Results: Of the 250 urine samples analyzed, 8 samples (3.2%) were positive for P. aeruginosa. The prevalence of P. aeruginosa in male and female patients was 2.7% and 3.5%, respectively, (P = 0.035). In patients less than 10 years old, it was 4.2%, and in patients more than 55 years old, it was 4.2%. These were the most commonly infected groups. The highest levels of resistance were seen against ampicillin (87.5%), norfloxacin (62.5%), gentamycin (62.5%), amikacin (62.5%), and aztreonam (62.5%), while the lowest were seen for meropenem (0%), imipenem (12.5%), and polymyxin B (12.5%). LasB (87.5%), pclH (75%), pilB (75%), and exoS (75%) were the most commonly detected virulence factors in the P. aeruginosa isolates. Conclusions: It is logical to first prescribe meropenem, imipenem, and polymyxin B in cases of UTIs caused by P. aeruginosa. Medical practitioners should be aware of the presence of levels of antibiotic resistance in hospitalized UTI patients in Iran. PMID:26756017

  2. Multifunctional Cu2−xTe Nanocubes Mediated Combination Therapy for Multi-Drug Resistant MDA MB 453

    PubMed Central

    Poulose, Aby Cheruvathoor; Veeranarayanan, Srivani; Mohamed, M. Sheikh; Aburto, Rebeca Romero; Mitcham, Trevor; Bouchard, Richard R.; Ajayan, Pulickel M.; Sakamoto, Yasushi; Maekawa, Toru; Kumar, D. Sakthi

    2016-01-01

    Hypermethylated cancer populations are hard to treat due to their enhanced chemo-resistance, characterized by aberrant methylated DNA subunits. Herein, we report on invoking response from such a cancer lineage to chemotherapy utilizing multifunctional copper telluride (Cu2−XTe) nanocubes (NCs) as photothermal and photodynamic agents, leading to significant anticancer activity. The NCs additionally possessed photoacoustic and X-ray contrast imaging abilities that could serve in image-guided therapeutic studies. PMID:27775048

  3. Molecular Epidemiology of ESBL Genes and Multi-Drug Resistance in Diarrheagenic Escherichia Coli Strains Isolated from Adults in Iran

    PubMed Central

    Ghorbani-Dalini, Sadegh; Kargar, Mohammad; Doosti, Abbas; Abbasi, Pejman; Sarshar, Meysam

    2015-01-01

    Resistance to oxyimino cephalosporins antibiotics in Enterobacteriaceae is primarily done by the extended spectrum β-lactamases (ESBLs). Clear identification of risk factors for ESBLs-producing infections is necessary. Therefore, efficient strategies can be developed to decrease outbreak of these infections. The aim of this study was to determine the antibacterial susceptibility and ESBLs pattern of diarrhogenic Escherichia coli (E. coli) strains isolated from adult patients. In the present study, diarrheogenic E. coli strains were isolated from 54 patients from the University of Medical Sciences hospitals in Shiraz. Antimicrobial susceptibility testing was done by disk diffusion method by CLSI criteria. The presence of blaTEM, blaSHV and blaCTX-M genes was investigated by PCR using designated primers. The prevalence of ESBLs-producer E. coli strains was 12.96%. Antimicrobial resistance testing showed a high resistance to cefexime, trimethoprim-sulfamethoxazole, ampicillin and penicillin. Overall, β-lactamase genes were identified in 52 (96.30%) isolates which were identified as 45 (83.33%) blaTEM, 17 (31.48%) blaSHV and 11 (20.37%) blaCTX-M. ESBLs-producer E. coli is very prevalent in Diarrheogenic strains isolated from adult patients. Also, this study clearly showed that the blaTEM gene for ESBLs-producer E. coli was widespread in Iran. PMID:26664394

  4. National Department of Defense Surveillance for Invasive Streptococcus Pneumoniae: Antibiotic Resistance, Serotype Distribution, and Arbitrarily Primed Polymerase Chain Reaction Analyses

    DTIC Science & Technology

    2008-02-15

    penicillin -susceptible and peni- cillin-resistant Streptococcnspneuttmoniae serotypes in Canada. J Infect Dis Streptococcus pneumoniae Surveillance Group...Gray for the Streptococcus pneumonia Surveillance Group Report No. 00-44 Approved for public release; distribution unlimited. NAVAL HEALTH RESEARCH...Defense Surveillance for Invasive Streptococcus pneumoniae : Antibiotic Resistance, Serotype Distribution, and Arbitrarily Primed Polymerase Chain

  5. The TolC Protein of Legionella pneumophila Plays a Major Role in Multi-Drug Resistance and the Early Steps of Host Invasion

    PubMed Central

    Ferhat, Mourad; Atlan, Danièle; Vianney, Anne; Lazzaroni, Jean-Claude; Doublet, Patricia; Gilbert, Christophe

    2009-01-01

    Pneumonia associated with Iegionnaires's disease is initiated in humans after inhalation of contaminated aerosols. In the environment, Legionella pneumophila is thought to survive and multiply as an intracellular parasite within free-living amoeba. In the genome of L. pneumophila Lens, we identified a unique gene, tolC, encoding a protein that is highly homologous to the outer membrane protein TolC of Escherichia coli. Deletion of tolC by allelic exchange in L. pneumophila caused increased sensitivity to various drugs. The complementation of the tolC mutation in trans restored drug resistance, indicating that TolC is involved in multi-drug efflux machinery. In addition, deletion of tolC caused a significant attenuation of virulence towards both amoebae and macrophages. Thus, the TolC protein appears to play a crucial role in virulence which could be mediated by its involvement in efflux pump mechanisms. These findings will be helpful in unraveling the pathogenic mechanisms of L. pneumophila as well as in developing new therapeutic agents affecting the efflux of toxic compounds. PMID:19888467

  6. Green synthesis of silver nanoparticles from leaf extract of Mimusops elengi, Linn. for enhanced antibacterial activity against multi drug resistant clinical isolates.

    PubMed

    Prakash, P; Gnanaprakasam, P; Emmanuel, R; Arokiyaraj, S; Saravanan, M

    2013-08-01

    Green synthesis of metallic silver nanoparticles has attracted nowadays and alternative to physical and chemical approaches. In the present study, silver nanoparticles (AgNPs) were synthesized from leaf extract of Mimusops elengi, L. at room temperature. Formation of stable AgNPs at 1mM concentrations of silver nitrate (AgNO3) typically gave spherical shape particles with diameter range from 55 to 83nm. The kinetic properties of particle formation were proportional to the effect of concentration of AgNO3 solution. In order to identify the compounds responsible for the bioreduction of Ag(+) ion and the stabilization of AgNPs produced, the functional group present in Mimusops elengi, L. leaf extract was investigated using FTIR. The formation of nanoparticle was confirmed using the surface plasmon resonance band shown in UV-vis spectrophotometer. The topography and morphology of the particles were determined using scanning electron microscopy. The crystalline nature of nanoparticles was confirmed from the XRD pattern. Furthermore these green synthesized AgNPs were found to show higher antimicrobial efficacy against multi drug resistant clinical isolates.

  7. [Inhibitory Effect of Serum Containing Fuzheng Jiedu Decoction on the Leukemia K562/A02 Multi-drug Resistance Cells and Its Mechanism].

    PubMed

    Cao, Yi-Xiong; Luo, Ze-Yu; Li, Jun-Jun; Wen, Feng; Huang, Li-Fang

    2016-08-01

    To study the inhibitory effect of serum containing Fuzheng Jiedu decoction on leukemia multi-drug-resistance K562/A02 cells and its possible mechanism. The MTT method was used to detect the inhibitory rate of K562/AO2 cells treated with serum containing Fuzheng Jiedu decoction; the flow cytometry was used to detect the inhibitory effect of serum containing medicin on growth of K562/AO2 cells and P-gp expression; the Q-PCR was used to assay the BCL-2 mRNA expression; the Western blot was used to detect the BCL-2 protein expression. MTT cytotoxic test showed serum containing Fuzheng Jiedu decoction could inhibit K562/A02 cell growth, and the inhibitory rate increased with the increase of drug concentration; the flow cytometry showed that the serum containing Fuzheng Jiedu decoction could promote K562/A02 cell apoptosis in a concentration-dependent manner. qPCR and Western blot showed that serum containing Fuzheng Jiedu decoction could down-regulate the protein expression of BCL-2. Fuzheng Jiedu decoction could reduce the protein expression of P-gp on the K562/A02 cell membrane. serum containing Fuzheng Jiedu decoction can promote K562/A02 cell apoptosis, its mechanism of inducing apoptosis may be related with the inhibition of BCL-2 and P-gp protein expression.

  8. Biodistribution and Pharmacokinetic Analysis of Combination Lonidamine and Paclitaxel Delivery in an Orthotopic Animal Model of Multi-drug Resistant Breast Cancer Using EGFR-Targeted Polymeric Nanoparticles

    PubMed Central

    Milane, Lara; Duan, Zhen-feng; Amiji, Mansoor

    2011-01-01

    The aim of this study was to assess the biodistribution and pharmacokinetics of epidermal growth factor receptor (EGFR)-targeted polymer blend nanoparticles loaded with the anticancer drugs lonidamine and paclitaxel. Plasma, tumor, and tissue distribution profiles were quantified in an orthotopic animal model of multi-drug resistant (MDR) breast cancer and were compared to treatment with non-targeted nanoparticles and to treatment with drug solution. Poly(D,L-lactide-co-glycolide)/poly(ethylene glycol)/EGFR targeting peptide (PLGA/PEG/EFGR peptide) construct was synthesized for incorporation in poly(ε-caprolactone) (PCL) particles to achieve active EGFR targeting. An isocratic HPLC method was developed to quantify lonidamine and paclitaxel in mice plasma, tumors, and vital organs. The targeted nanoparticles demonstrated superior pharmacokinetic profile relative to drug solution and non-targeted nanoparticles, particularly for lonidamine delivery. The first target site of accumulation is the liver, followed by the kidneys, and then the tumor mass; maximal tumor accumulation occurs at 3 hours post-administration. Lonidamine/paclitaxel combination therapy administered via EGFR-targeted polymer blend nanocarriers may become a viable platform for the future treatment of MDR cancer. PMID:21220050

  9. Molecular identification of marine symbiont bacteria of gastropods from the waters of the Krakal coast Yogyakarta and its potential as a Multi-Drug Resistant (MDR) antibacterial agent

    NASA Astrophysics Data System (ADS)

    Bahry, Muhammad Syaifudien; Pringgenies, Delianis; Trianto, Agus

    2017-01-01

    The resistance of pathogenic bacteria may occur to many types of antibiotics, especially in cases of non-compliance use of antibiotics, which likely to allow the evolution of Multi-Drug Resistant (MDR) bacteria. Gastropods seas are marine invertebrates informed capable of production of secondary metabolites as antibacterial MDR. The purpose of the study was the isolation and identification of gastropod symbiont bacteria found in the waters of Krakal, Gunung Kidul, Yogyakarta, which has the ability to produce antibacterial compounds against MDR(Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, MRSA (methicillin-Resistant Staphylococcus aureus), Staphylococcus aureus, and Staphylococcus homunis) molecular. Stages of this research began with the isolation of bacteria, bacteria screening for anti-MDR compound, mass culture, and extraction, antibacterial activity test, DNA extraction, amplification by PCR 16S rDNA and sequencing. The results of the study showed that 19 isolates of bacteria were isolated from three species of gastropods namely Littorina scabra, Cypraea moneta and Conus ebraeus. Among them, 4 isolates showed activity against MDR test bacteria (E. coli, E. cloacae, K. pneumoniae, S. aureus and S. homunis). The highest activity was displayed by code LS.G1.8 isolate with the largest inhibition zone 15.47±0.45mm on S. humonis at 250 µg/disk concentration. Isolate CM.G2.1 showed largest inhibition zone, with 21.5±0.07mm on MRSA at 1000 µg/disk concentration and isolate the largest inhibition zone CM.G2.5 14.37±0.81mm on MRSA 14.37±0.81mm at concentrations 1000 µg/disk. The molecular identification of isolates LS.G1.8 has 99% homology with Bacillus subtilis and isolates CM.G2.1 has 99% homology with Bacillus pumillus.

  10. Analysis and characterization of dimerization inhibition of a multi-drug-resistant Human Immunodeficiency Virus Type 1 protease using a novel size-exclusion chromatographic approach

    PubMed Central

    DAVIS, David A.; TEBBS, Irene R.; DANIELS, Sarah I.; STAHL, Stephen J.; KAUFMAN, Joshua D.; WINGFIELD, Paul; BOWMAN, Michael J.; CHMIELEWSKI, Jean; YARCHOAN, Robert

    2009-01-01

    Active-site inhibitors of HIV-1 PR (protease) block viral replication by preventing viral maturation. However, HIV-1 often develops resistance to active-site inhibitors through multiple mutations in PR and therefore recent efforts have focused on inhibiting PR dimerization as an alternative approach. Dimerization inhibitors have been identified using kinetic analysis, but additional characterization of the effect of these inhibitors on PR by physical methods has been difficult. In the present study, we identified a PRMDR (multi-drug-resistant HIV-1 PR) that was highly resistant to autoproteolysis. Using this PR and a novel size-exclusion chromatographic approach that incorporated fluorescence and MS detection, we were able to demonstrate inhibition of dimerization using P27 (peptide 27), a peptide dimerization inhibitor of PR previously identified on the basis of kinetic analysis. Incubation of PRMDR with P27, or other dimerization inhibitors, led to a dose- and time-dependent formation of PR monomers based on the change in elution time by size exclusion and its similar elution time to engineered forms of monomeric PR, namely PRT26A and glutathionylated PR. In contrast, incubation of PRMDR with a potent active-site inhibitor did not change the elution time for the PRMDR dimer. The monomeric PR induced by P27 had fluorescent characteristics which were consistent with unfolded PR. Structure–activity studies identified the active regions of P27 and experiments were performed to examine the effect of other dimerization inhibitors on PR. The present study is the first characterization of dimerization inhibition of PRMDR, a prime target for these inhibitors, using a novel size-exclusion chromatographic approach. PMID:19149765

  11. Multi-drug resistant gram negative infections and use of intravenous polymyxin B in critically ill children of developing country: retrospective cohort study.

    PubMed

    Siddiqui, Naveed-ur-Rehman; Qamar, Farah Naz; Jurair, Humaira; Haque, Anwarul

    2014-11-28

    Patients in pediatric intensive care Units (PICU) are susceptible to infections with antibiotic resistant organisms which increase the morbidity, mortality and cost of care. To describe the clinical characteristics and mortality in patients with Multi-Drug Resistant (MDR) gram negative organisms. We also report safety of Polymyxin B use in these patients. Files of patients admitted in PICU of Aga Khan University Hospital, from January 2010 to December 2011, one month to 15 years of age were reviewed. Demographic and clinical features of patients with MDR gram negative infections, antibiotic susceptibility pattern of isolates, discharge disposition and adverse effects of Polymyxin B were recorded. A total of 44.8/1000(36/803) admitted patients developed MDR gram negative infections, of which 47.2%(17/36) were male, with mean age of 3.4 yrs(+/-4.16). Acinetobacter Species (25.5%) was the most frequently isolated MDR organisms followed by Klebsiella Pneumoniae (17%). Sensitivity of isolates was 100% to Polymyxin B, followed by Imipenem (50%), and piperacillin/tazobactem (45%). The crude mortality rate of patients with MDR gram negative infections was 44.4% (16/36). Fourteen of 36 patients received Polymyxin B and 57.1%; (8/14) of them were cured. Nephrotoxicity was observed in 21.4% (3/14) cases, none of the patients showed signs of neuropathy. Our study highlights high rates of Carbapenem resistant gram negative isolates, leading to increasing use of Polymyxin B as the only drug to combat against these critically ill children. Therefore, we emphasizeon Stewardship of Antibiotics and continuous surveillance system as strategies in overall management of these critically ill children.

  12. Emergence of Multidrug-Resistant Pneumococcal Serotype 35B among Children in the United States.

    PubMed

    Olarte, Liset; Kaplan, Sheldon L; Barson, William J; Romero, José R; Lin, Philana Ling; Tan, Tina Q; Hoffman, Jill A; Bradley, John S; Givner, Laurence B; Mason, Edward O; Hultén, Kristina G

    2017-03-01

    Streptococcus pneumoniae serotype 35B is a nonvaccine serotype associated with high rates of penicillin nonsusceptibility. An increase in the proportion of multidrug-resistant (MDR) 35B isolates has recently been reported. The genetic events contributing to the emergence of MDR serotype 35B are unknown. The sequence type (ST) composition of 78 serotype 35B isolates obtained from pediatric patients with invasive pneumococcal disease from 1994 to 2014 and 48 isolates from pediatric patients with otitis media (noninvasive) from 2011 to 2014 was characterized by multilocus sequence typing (MLST). The most common STs were ST558 (69.2%), ST156 (10.3%), and ST452 (3.8%). Two major clonal complexes (CC), CC558 and CC156, were identified by eBURST analysis. Overall, 91% (71/78) of isolates were penicillin nonsusceptible and 16.7% (13/78) were MDR. Among all invasive serotype 35B isolates, MDR isolates increased significantly, from 2.9% (1/35) to 27.9% (12/43) (P = 0.004), after the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced. All CC156 isolates were identified after the introduction of PCV13 (0/35 [0%] before versus 9/43 [20.9%] after; P = 0.003) and were MDR. All CC156 isolates had similar antimicrobial susceptibility patterns; in contrast, high variability in antimicrobial susceptibility was observed among CC558 isolates. The distributions of CC558 and CC156 among invasive and noninvasive isolates were not different. The increased prevalence of MDR serotype 35B after the introduction of PCV13 was directly associated with the emergence of ST156. Genotyping suggests that capsular switching has occurred between MDR vaccine serotypes belonging to ST156 (e.g., 9V, 14, and 19A) and serotype 35B.

  13. Emergence of Neoteric Serotypes Among Multidrug Resistant Strains of Streptococcus pneumoniae Prevalent in Egypt

    PubMed Central

    Bahy, Rehab H; Hamouda, Hayam M; Shahat, Amal S; Yassin, Aymen S; Amin, Magdy A

    2016-01-01

    Background Streptococcus pneumoniae is still one of the major causes of morbidity and mortality worldwide. The prevalent serotype distribution had shown variation along different studies conducted at different time intervals. In order to efficiently assess the epidemiology of the diseases for effective preventive and treatment strategies, serotype prevalence need to be periodically reassessed. Objectives Conducting a reassessment of the prevalent S. pneumoniae serotypes in Egypt as an essential step in the search for a regional vaccine. In addition, monitoring the antibiotic susceptibility patterns of pneumococcal strains currently causing infections as an evaluation of therapeutic strategies applied. Materials and Methods A total of 100 specimens of different sources were collected in Cairo, Egypt, from 2011 to 2013, representing almost all different types of diseases caused by S. pneumoniae such as meningitis, pneumonia, otitis media and sinusitis. Conventional and molecular identification methods were performed, the antimicrobial susceptibility patterns were assessed and serotyping was done using PCR assays to identify the most prevalent types. In addition, detection of certain virulence genes for the most prevalent serotypes was carried out. Results Our results revealed that in Egypt, currently, the most prevalent serotypes were serogroup 6 and serotype 19F as they represented 58% of all isolates. High rates of resistance were found to different antibiotic classes. The lytA and psaA genes were found to be more sensitive for S. pneumoniae identification than ply. Conclusions Our study illustrates the importance of constantly monitoring the prevalent serotypes in any region in order to aid in the development of more effective vaccines. PMID:27303614

  14. Bactericidal Activity of Methanol Extracts of Crabapple Mangrove Tree (Sonneratia caseolaris Linn.) Against Multi-Drug Resistant Pathogens

    PubMed Central

    Yompakdee, C.; Thunyaharn, S.; Phaechamud, T.

    2012-01-01

    The crabapple mangrove tree, Sonneratia caseolaris Linn. (Family: Sonneratiaceae), is one of the foreshore plants found in estuarine and tidal creek areas and mangrove forests. Bark and fruit extracts from this plant have previously been shown to have an anti-oxidative or cytotoxic effect, whereas flower extracts of this plant exhibited an antimicrobial activity against some bacteria. According to the traditional folklore, it is medicinally used as an astringent and antiseptic. Hence, this investigation was carried out on the extract of the leaves, pneumatophore and different parts of the flower or fruit (stamen, calyx, meat of fruit, persistent calyx of fruit and seeds) for antibacterial activity using the broth microdilution method. The antibacterial activity was evaluated against five antibiotic-sensitive species (three Gram-positive and two Gram-negative bacteria) and six drug-resistant species (Gram-positive i.e. Methicillin-resistant Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium and Gram-negative i.e. Extended-spectrum beta-lactamase-Escherichia coli, multidrug-resistant–Pseudomonas aeruginosa and Acenetobacter baumannii). The methanol extracts from all tested parts of the crabapple mangrove tree exhibited antibacterial activity against both Gram-positive and Gram-negative bacteria, but was mainly a bactericidal against the Gram-negative bacteria, including the multidrug-resistant strains, when compared with only bacteriostatic on the Gram-positive bacteria. Using Soxhlet apparatus, the extracts obtained by sequential extraction with hexane, dichloromethane and ethyl acetate revealed no discernable antibacterial activity and only slightly, if at all, reduced the antibacterial activity of the subsequently obtained methanol extract. Therefore, the active antibacterial compounds of the crabapple mangrove tree should have a rather polar structure. PMID:23441048

  15. Prevalence and characterization of multi-drug resistant Salmonella Enterica serovar Gallinarum biovar Pullorum and Gallinarum from chicken

    PubMed Central

    Parvej, Md. Shafiullah; Nazir, K. H. M. Nazmul Hussain; Rahman, M. Bahanur; Jahan, Mueena; Khan, Mohammad Ferdousur Rahman; Rahman, Marzia

    2016-01-01

    Aim: Salmonella is an important zoonotic pathogen responsible for animal and human diseases. The aim of the present study was to determine the prevalence and stereotyping of Salmonella isolates isolated from apparently healthy poultry. Furthermore, the clonal relatedness among the isolated Salmonella serovars was assessed. Materials and Methods: A total of 150 cloacal swab samples from apparently healthy chickens were collected, and were subjected for the isolation and identification of associated Salmonella organisms. The isolated colonies were identified and characterized on the basis of morphology, cultural characters, biochemical tests, slide agglutination test, polymerase chain reaction, and pulsed-field gel electrophoresis (PFGE). Antibiotic sensitivity patterns were also investigated using commonly used antibiotics. Results: Of the 150 samples, 11 (7.33%) produced characteristics pink colony with black center on XLD agar medium, and all were culturally and biochemically confirmed to be Salmonella. All possessed serovar-specific gene SpeF and reacted uniformly with group D antisera, suggesting that all of the isolates were Salmonella Enterica serovar Gallinarum, biovar Pullorum and/or Gallinarum. Antimicrobial susceptibility testing revealed that 54.54% of the isolated Salmonella Enterica serovars were highly sensitive to ciprofloxacin, whereas the 81.81% isolates were resistant to amoxycillin, doxycycline, kanamycin, gentamycin, and tetracycline. Pulsed-field gel electrophoresis of the XbaI-digested genomic DNA exhibited identical banding patterns, suggesting that the multidrug resistant Salmonella Enterica serovars occurring in commercial layers are highly clonal in Bangladesh. Conclusion: The present study was conducted to find out the prevalence of poultry Salmonella in layer chicken and to find out the clonal relationship among them. The data in this study suggest the prevalence of Salmonella Enterica, which is multidrug resistant and highly clonal for

  16. Antibacterial activity of novel cationic peptides against clinical isolates of multi-drug resistant Staphylococcus pseudintermedius from infected dogs.

    PubMed

    Mohamed, Mohamed F; Hammac, G Kenitra; Guptill, Lynn; Seleem, Mohamed N

    2014-01-01

    Staphylococcus pseudintermedius is a major cause of skin and soft tissue infections in companion animals and has zoonotic potential. Additionally, methicillin-resistant S. pseudintermedius (MRSP) has emerged with resistance to virtually all classes of antimicrobials. Thus, novel treatment options with new modes of action are required. Here, we investigated the antimicrobial activity of six synthetic short peptides against clinical isolates of methicillin-susceptible and MRSP isolated from infected dogs. All six peptides demonstrated potent anti-staphylococcal activity regardless of existing resistance phenotype. The most effective peptides were RRIKA (with modified C terminus to increase amphipathicity and hydrophobicity) and WR-12 (α-helical peptide consisting exclusively of arginine and tryptophan) with minimum inhibitory concentration50 (MIC50) of 1 µM and MIC90 of 2 µM. RR (short anti-inflammatory peptide) and IK8 "D isoform" demonstrated good antimicrobial activity with MIC50 of 4 µM and MIC90 of 8 µM. Penetratin and (KFF)3K (two cell penetrating peptides) were the least effective with MIC50 of 8 µM and MIC90 of 16 µM. Killing kinetics revealed a major advantage of peptides over conventional antibiotics, demonstrating potent bactericidal activity within minutes. Studies with propidium iodide and transmission electron microscopy revealed that peptides damaged the bacterial membrane leading to leakage of cytoplasmic contents and consequently, cell death. A potent synergistic increase in the antibacterial effect of the cell penetrating peptide (KFF)3K was noticed when combined with other peptides and with antibiotics. In addition, all peptides displayed synergistic interactions when combined together. Furthermore, peptides demonstrated good therapeutic indices with minimal toxicity toward mammalian cells. Resistance to peptides did not evolve after 10 passages of S. pseudintermedius at sub-inhibitory concentration. However, the MICs of amikacin and

  17. Risk factors for Candida colonization and Co-colonization with multi-drug resistant organisms at admission.

    PubMed

    Schulte, Danielle M; Sethi, Ajay; Gangnon, Ronald; Duster, Megan; Maki, Dennis G; Safdar, Nasia

    2015-01-01

    Candida species are major causes of healthcare-associated infections with colonization preceding infection. Understanding risk factors for colonization by Candida species is important in prevention. However, data on risk factors for colonization by Candida species alone or with other healthcare-associated pathogens is limited. From 2002 to 2006, 498 patients were enrolled into a prospective cohort study at our institution. Surveillance perirectal, nasal and skin swab samples were obtained upon enrollment. Samples were cultured for the presence of Candida species, Methicillin Resistant Staphylococcus aureus, Vancomycin Resistant Enterococcus, and Resistant Gram Negative organisms. Data on demographics, comorbidities, device use, and antibiotic use were also collected for each subject and analyzed using univariate and multivariate logistic regression. Factors associated with Candida colonization at admission in univariate analysis included ambulatory status, a history of Candida colonization and the use of antibiotics prior to enrollment. In multivariate analysis, ambulatory status (odds ratio; OR = 0.45, 95 % CI: 0.27-0.73) and fluroquinolone use (OR = 3.01, 95 % CI: 1.80-5.01) were associated with Candida colonization at admission. Factors predicting Candida co-colonization with one or more MDROs at admission in univariate analysis included, older age, malnutrition, days spent in an ICU in the 2 years prior to enrollment, a history of MRSA colonization, and using antibiotics prior to enrollment. In multivariate analysis malnutrition (OR = 3.97, 95 % CI: 1.80-8.78) a history of MRSA (OR = 5.51, 95 % CI: 1.89-16.04) and the use of macrolides (OR = 3.75, 95 % CI: 1.18-11.93) and other antibiotics (OR = 4.94, 95 % CI: 1.52-16.03) were associated with Candida co-colonization at admission. Antibiotic use was associated with an increased risk of colonization by Candida species alone and in conjunction with other multidrug-resistant organisms

  18. Antibacterial Activity of Novel Cationic Peptides against Clinical Isolates of Multi-Drug Resistant Staphylococcus pseudintermedius from Infected Dogs

    PubMed Central

    Mohamed, Mohamed F.; Hammac, G. Kenitra; Guptill, Lynn; Seleem, Mohamed N.

    2014-01-01

    Staphylococcus pseudintermedius is a major cause of skin and soft tissue infections in companion animals and has zoonotic potential. Additionally, methicillin-resistant S. pseudintermedius (MRSP) has emerged with resistance to virtually all classes of antimicrobials. Thus, novel treatment options with new modes of action are required. Here, we investigated the antimicrobial activity of six synthetic short peptides against clinical isolates of methicillin-susceptible and MRSP isolated from infected dogs. All six peptides demonstrated potent anti-staphylococcal activity regardless of existing resistance phenotype. The most effective peptides were RRIKA (with modified C terminus to increase amphipathicity and hydrophobicity) and WR-12 (α-helical peptide consisting exclusively of arginine and tryptophan) with minimum inhibitory concentration50 (MIC50) of 1 µM and MIC90 of 2 µM. RR (short anti-inflammatory peptide) and IK8 “D isoform” demonstrated good antimicrobial activity with MIC50 of 4 µM and MIC90 of 8 µM. Penetratin and (KFF)3K (two cell penetrating peptides) were the least effective with MIC50 of 8 µM and MIC90 of 16 µM. Killing kinetics revealed a major advantage of peptides over conventional antibiotics, demonstrating potent bactericidal activity within minutes. Studies with propidium iodide and transmission electron microscopy revealed that peptides damaged the bacterial membrane leading to leakage of cytoplasmic contents and consequently, cell death. A potent synergistic increase in the antibacterial effect of the cell penetrating peptide (KFF)3K was noticed when combined with other peptides and with antibiotics. In addition, all peptides displayed synergistic interactions when combined together. Furthermore, peptides demonstrated good therapeutic indices with minimal toxicity toward mammalian cells. Resistance to peptides did not evolve after 10 passages of S. pseudintermedius at sub-inhibitory concentration. However, the MICs of amikacin and

  19. Frequency and factors associated with carriage of multi-drug resistant commensal Escherichia coli among women attending antenatal clinics in Central India

    PubMed Central

    2013-01-01

    Background Commensal Escherichia coli are a prominent reservoir of genes coding for antibiotic resistance and also responsible for endogenous infections in pregnant women. We studied the factors in pregnant women associated with carriage of multi-drug resistant (MDR) E. coli and genetic determinants of antibiotic resistance in them. Methods Women attending to Obstetric and Gynaecology department outpatient clinics for routine antenatal check-up were administered a questionnaire. Peri-anal swabs were collected for culture isolation and identification of E.coil. Antibiotic sensitivity was done using the Kirby-Bauer disc diffusion method as recommended by the CLSI guidelines. MICs for quinolones and third generation cephalosporins were done using the agar dilution method. Genes coding for production of beta lactamses and for the quinolone resistance determinant were screened by polymerase chain reaction. Rep-PCR was done on MDR isolates for detecting possible genetic similarity. Multiple logistic regression models were used to determine the independent factors associated with carriage of MDR isolates. Results A total of 710 isolates of E. coli from 710 women (mean age 26 years) were included in the study. Resistance to at least one antibiotic tested was detected in 94% of the E. coli isolates. A total of 109 isolates were ESBL producing and 35 isolates were MDR. In the MDR isolates MIC50 and MIC90 for quinolones and third generation cephalosporins were high for those isolates that carried blaTEM gene (26 isolates) and blaCTX-M gene (24 isolates). Both blaTEM and blaCTX-M genes were detected in 19 isolates. The commonest Plasmid Mediated Quinolone Resistance (PMQR) gene identified was aac(6′)-Ib-cr (n = 23/25). All isolates carrying the PMQR genes were also positive for blaCTX-M and blaTEM gene. Mutations in gyr A and par C genes were present in all 35 MDR isolates. The statistically significant risk factors for carriage of MDR E. coli were graduate or post

  20. Molecular Epidemiology and Distribution of Serotypes, Surface Proteins, and Antibiotic Resistance among Group B Streptococci in Italy▿

    PubMed Central

    Gherardi, Giovanni; Imperi, Monica; Baldassarri, Lucilla; Pataracchia, Marco; Alfarone, Giovanna; Recchia, Simona; Orefici, Graziella; Dicuonzo, Giordano; Creti, Roberta

    2007-01-01

    Group B streptococci (GBS) comprising three different sets of isolates (31 invasive, 36 noninvasive, and 24 colonizing isolates) were collected in Italy during the years 2002 to 2005. Clonal groups were established by pulsed-field gel electrophoresis (PFGE), and selected isolates were studied by multilocus sequence typing (MLST). GBS isolates were also characterized by classical and molecular techniques for serotyping and protein gene and antibiotic resistance profiling. Some serotypes were significantly associated with a particular isolate population: serotype Ia more frequently corresponded to invasive strains than other strains, serotype V was more frequently encountered among noninvasive strains, and nontypeable strains were more common among isolates from carriers. Four major clonal groups accounted for 52.7% of all isolates: PFGE type 1/clonal complex 1 (CC1) comprised mainly serotype V isolates carrying the alp3 gene, PFGE type 2/CC23 encompassed serotype Ia isolates with the alp1 or alpha gene, PFGE type 3/CC17 comprised serotype III isolates carrying the rib gene, and PFGE type 4/CC19 consisted mainly of serotype II isolates possessing the rib gene. The same serotypes were shared by isolates of different clonal groups, and conversely, isolates belonging to the same clonal groups were found to be of different serotypes, presumably due to capsular switching by the horizontal transfer of capsular genes. Erythromycin resistance (prevalence, 16.5%; 15 resistant isolates of 91) was restricted to strains isolated from patients with noninvasive infections and carriers, while tetracycline resistance was evenly distributed (prevalence, 68.1%; 62 resistant isolates of 91). Most erythromycin-resistant GBS strains were of serotype V, were erm(B) positive, and belonged to the PFGE type 1/CC1 group, suggesting that macrolide resistance may have arisen both by clonal dissemination and by the horizontal transfer of resistance genes. PMID:17634303

  1. Multiple Clones within Multidrug-Resistant Salmonella enterica Serotype Typhimurium Phage Type DT104

    PubMed Central

    Markogiannakis, Antonis; Tassios, Panayotis T.; Lambiri, Maria; Ward, Linda R.; Kourea-Kremastinou, Jenny; Legakis, Nicholas J.; Vatopoulos, Alkiviadis C.

    2000-01-01

    Six distinct clones were present among Greek multidrug-resistant Salmonella enterica serotype Typhimurium phage type DT104, since isolates belonging to resistance phenotypes including the ACSSuT (ampicillin, chloramphenicol, streptomycin, sulfonamides, and tetracycline) core could be distinguished with respect to their pulsed-field gel electrophoresis patterns, int1 integron structures, and presence or absence of antibiotic resistance genes ant(3")-Ia, pse-1, and tem-1. PMID:10699039

  2. Mekong malaria. II. Update of malaria, multi-drug resistance and economic development in the Mekong region of Southeast Asia.

    PubMed

    Socheat, Doung; Denis, Mey Bouth; Fandeur, Thierry; Zhang, Zaixing; Yang, Henglin; Xu, Jianwei; Zhou, Xingwu; Phompida, Samlane; Phetsouvanh, Rattanaxay; Lwin, Saw; Lin, Khin; Win, Than; Than, Soe Win; Htut, Ye; Prajakwong, Somsak; Rojanawatsirivet, Chaiporn; Tipmontree, Rungrawee; Vijaykadga, Saowanit; Konchom, Supawadee; Cong, Le Dinh; Thien, Nong Thi; Thuan, Le Khanh; Ringwald, Pascal; Schapira, Allan; Christophel, Eva; Palmer, Kevin; Arbani, P R; Prasittisuk, Chusak; Rastogi, R; Monti, Feliciano; Urbani, Carlo; Tsuyuoka, Reiko; Hoyer, Stefan; Otega, Leonard; Thimasarn, Krongthong; Songcharoen, Sakda; Meert, Jean-Pierre; Gay, Frederick; Crissman, Lawrence; Cho-Min-Naing; Chansuda, Wongsrichanalai; Darasri, Dowreang; Indaratna, Kaemthong; Singhasivanon, Pratap; Chuprapawan, Sirichai; Looareesuwan, Sornchai; Supavej, Suvanee; Kidson, Chev; Baimai, Visut; Yimsamran, Surapon; Buchachart, Kasinee

    2003-01-01

    In an expansion of the first Mekong Malaria monograph published in 1999, this second monograph updates the malaria database in the countries comprising the Mekong region of Southeast Asia. The update adds another 3 years' information to cover cumulative data from the 6 Mekong countries (Cambodia, China/Yunnan, Lao PDR, Myanmar, Thailand, Viet Nam) for the six-year period 1999-2001. The objective is to generate a more comprehensive regional perspective in what is a global epicenter of drug resistant falciparum malaria, in order to improve malaria control on a regional basis in the context of social and economic change. The further application of geographical information systems (GIS) to the analysis has underscored the overall asymmetry of disease patterns in the region, with increased emphasis on population mobility in disease spread. Of great importance is the continuing expansion of resistance of P. falciparum to antimalarial drugs in common use and the increasing employment of differing drug combinations as a result. The variation in drug policy among the 6 countries still represents a major obstacle to the institution of region-wide restrictions on drug misuse. An important step forward has been the establishment of 36 sentinel sites throughout the 6 countries, with the objective of standardizing the drug monitoring process; while not all sentinel sites are fully operational yet, the initial implementation has already given encouraging results in relation to disease monitoring. Some decreases in malaria mortality have been recorded. The disease patterns delineated by GIS are particularly instructive when focused on inter-country distribution, which is where more local collaborative effort can be made to rationalize resource utilization and policy development. Placing disease data in the context of socio-economic trends within and between countries serves to further identify the needs and the potential for placing emphasis on resource rationalization on a

  3. HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia

    PubMed Central

    Jiamsakul, Awachana; Sungkanuparph, Somnuek; Law, Matthew; Kantor, Rami; Praparattanapan, Jutarat; Li, Patrick CK; Phanuphak, Praphan; Merati, Tuti; Ratanasuwan, Winai; Lee, Christopher KC; Ditangco, Rossana; Mustafa, Mahiran; Singtoroj, Thida; Kiertiburanakul, Sasisopin

    2014-01-01

    Introduction First-line antiretroviral therapy (ART) failure often results from the development of resistance-associated mutations (RAMs). Three patterns, including thymidine analogue mutations (TAMs), 69 Insertion (69Ins) and the Q151M complex, are associated with resistance to multiple-nucleoside reverse transcriptase inhibitors (NRTIs) and may compromise treatment options for second-line ART. Methods We investigated patterns and factors associated with multi-NRTI RAMs at first-line failure in patients from The TREAT Asia Studies to Evaluate Resistance – Monitoring study (TASER-M), and evaluated their impact on virological responses at 12 months after switching to second-line ART. RAMs were compared with the IAS-USA 2013 mutations list. We defined multi-NRTI RAMs as the presence of either Q151M; 69Ins; ≥2 TAMs; or M184V+≥1 TAM. Virological suppression was defined as viral load (VL) <400 copies/ml at 12 months from switch to second-line. Logistic regression was used to analyze (1) factors associated with multi-NRTI RAMs at first-line failure and (2) factors associated with virological suppression after 12 months on second-line. Results A total of 105 patients from 10 sites in Thailand, Hong Kong, Indonesia, Malaysia and Philippines were included. There were 97/105 (92%) patients harbouring ≥1 RAMs at first-line failure, 39/105 with multi-NRTI RAMs: six with Q151M; 24 with ≥2 TAMs; and 32 with M184V+≥1 TAM. Factors associated with multi-NRTI RAMs were CD4 ≤200 cells/µL at genotyping (OR=4.43, 95% CI [1.59–12.37], p=0.004) and ART duration >2 years (OR=6.25, 95% CI [2.39–16.36], p<0.001). Among 87/105 patients with available VL at 12 months after switch to second-line ART, virological suppression was achieved in 85%. The median genotypic susceptibility score (GSS) for the second-line regimen was 2.00. Patients with ART adherence ≥95% were more likely to be virologically suppressed (OR=9.33, 95% CI (2.43–35.81), p=0.001). Measures of patient

  4. Selection of multi-drug resistant influenza A and B viruses under zanamivir pressure and their replication fitness in ferrets.

    PubMed

    Oh, Ding Yuan; Panozzo, Jacqueline; Vitesnik, Sophie; Farrukee, Rubaiyea; Piedrafita, David; Mosse, Jennifer; Hurt, Aeron C

    2017-02-14

    Intravenous zanamivir has been used to treat patients with severe influenza. Because the majority of cases (including immunocompromised patients) require the drug for an extended period of treatment, there is a higher risk that the virus will develop resistance. Therefore, knowing the possible amino acid substitutions that may arise in recently circulating influenza strains under prolonged zanamivir exposure and their impact on antiviral susceptibility is important. Influenza A(H1N1)pdm09, A(H3N2) and B virus were serially passaged under increasing zanamivir pressure in vitro. Neuraminidase (NA) mutations that arose were introduced into recombinant viruses and the susceptibility to oseltamivir, zanamivir, peramivir and laninamivir was determined. The replication fitness of the recombinant variants was assessed in the ferret. NA mutations E119D (N1 numbering) and E117D (B numbering) were detected in A(H1N1)pdm09 and B (Victoria-lineage) viruses respectively and were associated with reduced susceptibility to all four NA inhibitors. No NA mutations were detected in the A(H3N2) or B (Yamagata-lineage) viruses. In ferrets, the A(H1N1)pdm09 E119D variant caused a lower degree of morbidity and the mutation was found to be unstable with E119 reverted virus detected 4 days post-infection of ferrets with the variant E119D virus. In contrast, the influenza B E117D variant was genetically stable in ferrets, caused a noticeable level of morbidity but had a significant reduction in replication fitness compared to wild-type virus. The NA mutations E119D in influenza A(H1N1)pdm09 and E117D in influenza B viruses that arose under zanamivir pressure conferred resistance to multiple NAIs but had compromised viral replication in ferrets compared to wild-type virus without antiviral drug pressure.

  5. Changing Trends in the Prevalence of Shigella Species: Emergence of Multi-Drug Resistant Shigella sonnei Biotype g in Bangladesh

    PubMed Central

    Ud-Din, Abu I. M. S.; Wahid, Syeda U. H.; Latif, Hasan A.; Shahnaij, Mohammad; Akter, Mahmuda; Azmi, Ishrat J.; Hasan, Trisheeta N.; Ahmed, Dilruba; Hossain, Mohammad A.; Faruque, Abu S. G.; Faruque, Shah M.; Talukder, Kaisar A.

    2013-01-01

    Shigellosis, caused by Shigella species, is a major public health problem in Bangladesh. To determine the prevalence and distribution of different Shigella species, we analyzed 10,827 Shigella isolates from patients between 2001 and 2011. S. flexneri was the predominant species isolated throughout the period. However, the prevalence of S. flexneri decreased from 65.7% in 2001 to 47% in 2011, whereas the prevalence of S. sonnei increased from 7.2% in 2001 to 25% in 2011. S. boydii and S. dysenteriae accounted for 17.3% and 7.7% of the isolates respectively throughout the period. Of 200 randomly selected S. sonnei isolates for extensive characterization, biotype g strains were predominant (95%) followed by biotype a (5%). Resistance to commonly used antibiotics including trimethoprim-sulfamethoxazole, nalidixic acid, ciprofloxacin, mecillinam and ampicillin was 89.5%, 86.5%, 17%, 10.5%, and 9.5%, respectively. All isolates were susceptible to ceftriaxone, cefotaxime, ceftazidime and imipenem. Ninety-eight percent of the strains had integrons belonging to class 1, 2 or both. The class 1 integron contained only dfrA5 gene, whereas among class 2 integron, 16% contained dhfrAI-sat1-aadA1-orfX gene cassettes and 84% harbored dhfrA1-sat2 gene cassettes. Plasmids of ∼5, ∼1.8 and ∼1.4 MDa in size were found in 92% of the strains, whereas only 33% of the strains carried the 120 MDa plasmid. PFGE analysis showed that strains having different integron patterns belonged to different clusters. These results show a changing trend in the prevalence of Shigella species with the emergence of multidrug resistant S. sonnei. Although S. flexneri continues to be the predominant species albeit with reduced prevalence, S. sonnei has emerged as the second most prevalent species replacing the earlier dominance by S. boydii and S. dysenteriae in Bangladesh. PMID:24367527

  6. New mouse xenograft model modulated by tumor-associated fibroblasts for human multi-drug resistance in cancer

    PubMed Central

    MA, YAN; LIN, ZHIQIANG; FALLON, JOHN K.; ZHAO, QIANG; LIU, DAN; WANG, YONGJUN; LIU, FENG

    2015-01-01

    We developed an MDR tumor model that is modulated by tumor-associated fibroblasts. Studies on proliferation of tumor cell lines including paclitaxel-sensitive and resistant cell lines were performed. The expressions of P-gp and α-smooth muscle actin (α-SMA) antigen were evaluated by immunohistochemistry and western blot analysis. Quantitative P-gp analyses of different cell lines were accomplished by nanoUPLC-MS/MS. Tumor cell colony formation assay and established xenograft model was used to investigate the relationship between P-gp expression, fibroblast levels and tumorigenesis. The mouse xenograft model was developed after co-inoculation with MDR tumor cells and NIH/3T3 fibroblast cells. There was no correlation between tumorigenesis in vivo and the growth rate of cells in vitro. The proliferation among different cell lines had no significant differences, but the P-gp expression and tumor growth in the xenograft model were fairly different. P-gp determination and α-SMA immunofluorescence staining clarified the relationship between P-gp expression, fibroblast levels and tumorigenesis. It was more difficult for tumor cells with higher P-gp levels to recruit fibroblasts in vivo, resulting in lower tumorigenesis due to the lack of structural and chemical support during tumor progression. In the established paclitaxel-resistant mouse xenograft model, no obvious antitumor effect was observed after Taxol treatment, but a significant decrease in tumor size for the group treated with gemcitabine sensitive to the model. The results show that the added fibroblasts do not disturb the applicability of the model in MDR. Therefore, this mouse xenograft MDR model could serve as an effective tool for MDR research. PMID:26352907

  7. Variation in Salmonella resistance to poultry chemical decontaminants, based on serotype, phage type, and antibiotic resistance patterns.

    PubMed

    Capita, Rosa

    2007-08-01

    Chemical decontaminants are currently under review for final approval by the European Union authorities with the aim of reducing the number and/or prevalence of pathogenic microorganisms on poultry. The purpose of the research being reported here was to determine the association, if any, of decontaminant resistance with the serotype, phage type, and antibiotic resistance of Salmonella strains. Sixty poultry isolates of Salmonella enterica (serotypes Enteritidis: phage types 1, 4, 4b, 6a, 14b, and 35; Typhimurium; Newport; Infantis; Poona; Virchow; Agona; Derby; and Paratyphi B) showing resistance to none (sensitive), one (resistant), two, three, four, five, six, seven, or nine (multiresistant) antibiotics were screened for resistance to 1,000 ppm acidified sodium chlorite, 1.2% trisodium phosphate, or 25% citric acid. D-values (seconds required for 1-log reduction in the number of bacteria) in peptone water, using a linear regression, of Salmonella in the presence of acidified sodium chlorite varied widely with serotype (the highest resistance levels were shown by serotypes Typhimurium, Newport, and Derby) and antibiotic resistance pattern (average values of 8.37 +/- 1.69 s for multiresistant strains as compared with 5.96 +/- 0.54 s for sensitive, P < 0.05). A positive relationship (0.775, P < 0.001) was found between acidified sodium chlorite D-values and the number of antibiotics to which strains were resistant. Both serotype and antibiotic resistance had only a slight influence over Salmonella resistance to trisodium phosphate, with average D-values from 12.44 +/- 0.91 s (sensitive strains) to 13.28 +/- 0.77 s (multiresistant) (P < 0.05). Neither serotype nor antibiotic profile was associated with Salmonella resistance to citric acid (average D-value of 12.20 +/- 0.81 s). Minimal differences in resistance to decontaminants were found among Salmonella Enteritidis phage types. Results in the present study highlight the importance of selecting an adequate strain

  8. Streptococcus pneumoniae nasopharyngeal carriage prevalence, serotype distribution, and resistance patterns among children on Lombok Island, Indonesia.

    PubMed

    Soewignjo, S; Gessner, B D; Sutanto, A; Steinhoff, M; Prijanto, M; Nelson, C; Widjaya, A; Arjoso, S

    2001-04-01

    Few data exist on childhood pneumococcal carriage prevalence, serotype distribution, and resistance patterns for Indonesia, the world's fourth most populous country. During August 1997, nasopharyngeal samples were collected from a population-based, island-wide sample of 484 healthy children (age, 0-25 months) from Lombok Island, Indonesia. Two hundred twenty-one pneumococcal isolates were identified, for a carriage prevalence of 48%; 66% of isolates were of serogroup or serotype 6, 23, 15, 33, or 12. All isolates were susceptible to penicillin and cefotaxime. Twelve percent of the isolates were nonsusceptible to sulfamethoxazole or chloramphenicol and 4% were nonsusceptible to both of these drugs. Nonsusceptible organisms were most frequently serogroup or serotype 6, 12, and 33. Lombok has a moderate pneumococcal carriage prevalence and a relatively low proportion of resistant isolates. At least 3 of the 5 most common serogroups and serotypes and 2 of the 3 most common nonsusceptible serogroups and serotypes are not included in the current 7-valent pneumococcal conjugate vaccine.

  9. Multi-drug resistant toxigenic Vibrio cholerae O1 is persistent in water sources in New Bell-Douala, Cameroon

    PubMed Central

    2013-01-01

    Background Cholera has been endemic in Douala, since 1971 when it was first recorded in Cameroon. Outbreaks have often started in slum areas of the city including New Bell. Despite the devastating nature of outbreaks, always resulting in high mortality and morbidity, a paucity of information exists on the reservoirs of the causative agent, V. cholerae, and factors maintaining its persistence. This has complicated disease prevention, resulting in frequent outbreaks of cholera. We investigated water sources in New Bell for contamination with V. cholerae O1 with pathogenic potential, to highlight their role in disease transmission. Antibiotic susceptibility pattern of isolates and the environmental factors maintaining its persistence were investigated. Method Water samples from various sources (taps, dug wells, streams) were analyzed for contamination with V. cholerae O1 using standard methods. Antibiotic susceptibility was determined by disc diffusion method. Pathogenic potential of isolates was determined by analyzing for genes for cholera toxin (ctx), toxin co-regulated pilus (tcpA), and zonula occludens toxin (zot) by PCR. Physico-chemical characteristics of water (pH, temperature and salinity) were investigated using standard methods. The Spearman’s Rank correlation was used to analyze the relationship between physico-chemical factors and the occurrence of V. cholerae O1. Differences were considered significant at P≤0.05. Results Twenty-five V. cholerae O1 strains were isolated from stream and well samples in both dry and rainy seasons. Twenty-three (92%) isolates were multidrug resistant. All isolates had genes for at least one virulence factor. Cholera toxin gene was detected in 7 isolates. Of the 15 isolates positive for tcpA gene, two had Classical type tcpA while 13 had tcpA El Tor. All tcpA Classical positive isolates were positive for ctx gene. Isolates were grouped into nine genotypes based on the genes analyzed. pH and salinity significantly

  10. Multi-drug resistant toxigenic Vibrio cholerae O1 is persistent in water sources in New Bell-Douala, Cameroon.

    PubMed

    Akoachere, Jane-Francis Tatah Kihla; Masalla, Thomas Njinuwoh; Njom, Henry Akum

    2013-08-07

    Cholera has been endemic in Douala, since 1971 when it was first recorded in Cameroon. Outbreaks have often started in slum areas of the city including New Bell. Despite the devastating nature of outbreaks, always resulting in high mortality and morbidity, a paucity of information exists on the reservoirs of the causative agent, V. cholerae, and factors maintaining its persistence. This has complicated disease prevention, resulting in frequent outbreaks of cholera. We investigated water sources in New Bell for contamination with V. cholerae O1 with pathogenic potential, to highlight their role in disease transmission. Antibiotic susceptibility pattern of isolates and the environmental factors maintaining its persistence were investigated. Water samples from various sources (taps, dug wells, streams) were analyzed for contamination with V. cholerae O1 using standard methods. Antibiotic susceptibility was determined by disc diffusion method. Pathogenic potential of isolates was determined by analyzing for genes for cholera toxin (ctx), toxin co-regulated pilus (tcpA), and zonula occludens toxin (zot) by PCR. Physico-chemical characteristics of water (pH, temperature and salinity) were investigated using standard methods. The Spearman's Rank correlation was used to analyze the relationship between physico-chemical factors and the occurrence of V. cholerae O1. Differences were considered significant at P≤0.05. Twenty-five V. cholerae O1 strains were isolated from stream and well samples in both dry and rainy seasons. Twenty-three (92%) isolates were multidrug resistant. All isolates had genes for at least one virulence factor. Cholera toxin gene was detected in 7 isolates. Of the 15 isolates positive for tcpA gene, two had Classical type tcpA while 13 had tcpA El Tor. All tcpA Classical positive isolates were positive for ctx gene. Isolates were grouped into nine genotypes based on the genes analyzed. pH and salinity significantly correlated with isolation of V

  11. Characterization of the genetic environment of blaESBL genes, integrons and toxin-antitoxin systems identified on large transferrable plasmids in multi-drug resistant Escherichia coli

    PubMed Central

    Wang, Juan; Stephan, Roger; Zurfluh, Katrin; Hächler, Herbert; Fanning, Séamus

    2015-01-01

    Objectives: Previously 14 conjugative plasmids from multi-drug resistant (MDR) Escherichia coli from healthy humans and food-producing animals in Switzerland were sequenced. The aim of this study was to extend the genetic characterization of these plasmids with a focus on blaESBL genes including blaCTX-M-1 and blaTEM, class 1 integrons and toxin-antitoxin (TA) systems contained therein. Methods: The nucleotide sequences and subsequent annotation therein of 14 conjugative plasmids were previously determined from their corresponding transconjugants. The TA loci were confirmed by RASTA-Bacteria. Results: Eight of the conjugative plasmids identified were found to encode genes expressing ESBLs. Structural heterogeneity was noted in the regions flanking both the blaCTX-M-1 and blaTEM genes. The blaCTX-M-1 genes were associated with the common insertion sequences ISEcp1 and IS26, and uniquely with an IS5 element in one case; while blaTEM genes were found to be associated with IS26 and Tn2. A new blaTEM-210 gene was identified. Seven class 1 integrons were also identified and assigned into 3 groups, denoted as In54, In369 and In501. Sixteen TA loci belonging to 4 of the TA gene families (relBE, vapBC, ccd and mazEF) were identified on 11 of these plasmids. Conclusions: Comparative sequence analysis of these plasmids provided data on the structures likely to contribute to sequence diversity associated with these accessory genes, including IS26, ISEcp1 and Tn2. All of them contribute to the dissemination of the corresponding resistance genes located on the different plasmids. There appears to be no association between β-lactam encoding genes and TA systems. PMID:25610429

  12. Prevalence and antimicrobial resistance of Salmonella serotypes isolated from retail chicken meat and giblets in Iran.

    PubMed

    Sodagari, Hamid Reza; Mashak, Zohreh; Ghadimianazar, Amir

    2015-05-18

    Salmonella is one of the major foodborne pathogens responsible for outbreaks of foodborne illness in humans worldwide. A total of 560 samples of chicken meat and giblets were collected from retail markets for Salmonella identification, serotyping, and antimicrobial resistance testing. Salmonella was detected in 19.8% of samples. Among the five serotypes identified, S. Thompson was the predominant type (48.7%). High antimicrobial resistance rates were observed to nalidixic acid (92.8%), tetracycline (81%), trimethoprim (68.4%), sulfamethoxazole / trimethoprim (61.2%), streptomycin (56.7%), and kanamycin (36.9%). Although resistance to chloramphenicol (3.6%), amoxicillin-clavulanic acid (5.4%), and ampicillin (11.7%) was detected, none of the isolates were resistant to ceftazidime, ceftriaxone, cefotaxime, ciprofloxacin, colistin, gentamicin, nor imipenem. Restrictions on the irrational use of antibiotics in humans and animals are suggested for the reduction of resistant strains.

  13. Recent Advances in Multi-Drug Resistance (MDR) Efflux Pump Inhibitors of Gram-Positive Bacteria S. aureus

    PubMed Central

    Handzlik, Jadwiga; Matys, Anna; Kieć-Kononowicz, Katarzyna

    2013-01-01

    The paper focuses on recent achievements in the search for new chemical compounds able to inhibit multidrug resistance (MDR) mechanisms in Gram-positive pathogens. An analysis of the results of the search for new efflux pump inhibitors (EPIs) for Gram-positive bacteria, which have been performed over the last decade, indicates that almost all efforts are focused on the NorA (MFS) efflux pump in S. aureus. Considering the chemical structures of the NorA EPIs that have been identified, it can be observed that the most active agents belong to the families of compounds possessing conjugated double bonds, e.g., chalcones, piperine-like compounds, N-cinnamoylphenalkylamides or citral amide derivatives. Indole-, dihydronaphthyl-, 2-chloro-5-bromo-phenyl- or piperidine moieties seem to be profitable for the EPI properties, as well. These results, together with an increasing knowledge about a variety of efflux pumps that are involved in MDR of Gram-positive pathogens underline that further search for new EPIs should pay more attention to develop MDR efflux protein targets, including SMR, MATE, ABC or other members of the MFS family. PMID:27029290

  14. Phospholipid-modified PEI-based nanocarriers for in vivo siRNA therapeutics against multi-drug resistant tumors

    PubMed Central

    Sabhachandani, Pooja; Chordia, Aabha; Trivedi, Malav; Movassaghian, Sara; Torchilin, Vladimir P.

    2014-01-01

    Multidrug resistance (MDR) mediated by P-glycoprotein overexpression in solid tumors is a major factor in the failure of many forms of chemotherapy. Here, we evaluated phospholipid-modified, low molecular weight polyethylenimine (DOPE-PEI) nanocarriers for intravenous delivery of anti-P-pg siRNA to tumors with the final goal of modulating MDR in breast cancer. First, we studied the biodistribution of DOPE-PEI nanocarriers and the effect of PEG coating in a s.c. breast tumor model. Four hours post-injection, PEGylated carriers showed an 8% injected dose (ID) accumulation in solid tumor via the enhanced permeability and retention effect and 22% ID in serum due to a prolonged, PEG-mediated circulation. Second, we established the therapeutic efficacy and safety of DOPE-PEI/siRNA-mediated P-gp down-regulation in combination with Doxorubicin (Dox) chemotherapy in MCF-7/MDR xenografts. Weekly injection of siRNA nanopreparations and Dox for up to 5 weeks sensitized the tumors to otherwise non-effective doses of Dox and decreased the tumor volume by 3-fold versus controls. This therapeutic improvement in response to Dox was attributed to the significant, sequence-specific P-gp down-regulation in excised tumors mediated by the DOPE-PEI formulations. PMID:25354685

  15. A data-driven mathematical model of multi-drug resistant Acinetobacter baumannii transmission in an intensive care unit.

    PubMed

    Wang, Xia; Chen, Yong; Zhao, Wei; Wang, Yan; Song, Qing; Liu, Hui; Zhao, Jingya; Han, Xuelin; Hu, Xiaohua; Grundmann, Hajo; Xiao, Yanni; Han, Li

    2015-03-25

    Major challenges remain when attempting to quantify and evaluate the impacts of contaminated environments and heterogeneity in the cohorting of health care workers (HCWs) on hospital infections. Data on the detection rate of multidrug-resistant Acinetobacter baumannii (MRAB) in a Chinese intensive care unit (ICU) were obtained to accurately evaluate the level of environmental contamination and also to simplify existing models. Data-driven mathematical models, including mean-field and pair approximation models, were proposed to examine the comprehensive effect of integrated measures including cohorting, increasing nurse-patient ratios and improvement of environmental sanitation on MRAB infection. Our results indicate that for clean environments and with strict cohorting, increasing the nurse-patient ratio results in an initial increase and then a decline in MRAB colonization. In contrast, in contaminated environments, increasing the nurse-patient ratio may lead to either a consistent increase or an initial increase followed by a decline of MRAB colonization, depending on the level of environmental contamination and the cohorting rate. For developing more effective control strategies, the findings suggest that increasing the cohorting rate and nurse-patient ratio are effective interventions for relatively clean environments, while cleaning the environment more frequently and increasing hand washing rate are suitable measures in contaminated environments.

  16. MTB-DR-RIF 9G test: Detection and discrimination of tuberculosis and multi-drug resistant tuberculosis strains.

    PubMed

    Song, Keum-Soo; Nimse, Satish Balasaheb; Cho, Nam Hoon; Sung, Nackmoon; Kim, Hee-Jin; Yang, Jeongseong; Kim, Taisun

    2015-12-01

    This report describes the evaluation of the novel MTB-DR-RIF 9G test for the accurate detection and discrimination of Mycobacterium tuberculosis (MTB) and rifampicin-resistant M. tuberculosis (MTB-DR-RIF) in the clinical samples. The procedure included the amplification of a nucleotide fragment of the rpoB gene of the MTB and MTB-DR-RIF strains and their hybridization with the immobilized probes. The MTB-DR-RIF 9G test was evaluated for its ability to detect and discriminate MTB and MTB-DR-RIF strains in 113 known clinical samples. The accuracy of the MTB-DR-RIF 9G test was determined by comparing its results with sequencing analysis and drug susceptibility testing. The sensitivity and specificity of the MTB-DR-RIF 9G test at 95% confidence interval were found to be 95.4% (89.5-98.5) and 100% (69.2-100), respectively. The positive predictive value and negative predictive value of the MTB-DR-RIF 9G test at 95% confidence interval were found to be 100% (85.0-95.9) and 66.7% (38.4-88.18), respectively. Sequencing analysis of all samples indicated that the mutations present in the regions identified with the MTB-DR-RIF 9G assay can be detected accurately. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Current and developing therapies for the treatment of multi drug resistant tuberculosis (MDR-TB) in India.

    PubMed

    Muniyandi, Malaisamy; Ramachandran, Rajeswari

    2017-09-01

    India accounts for 25% of the global burden of MDR-TB. In 2016, the India's Revised National TB Control Programme reported a success rate of 46% among 19,298 MDR-TB patients treated under the programme. This suboptimal treatment outcome warrants an urgent need for newer drugs and newer regimens in the treatment of MDR-TB. India requires new shorter, cheap, safe and effective anti-TB regimen to treat MDR-TB. Areas covered: We used different search strategies to obtain relevant literature from PubMed, on Indian experiences of developing therapies for the treatment of MDR-TB. Further information from the Central TB Division Government of India on programmatic management of resistant TB was collected. Expert opinion: In 2016 WHO recommended a shorter MDR-TB regimen of 9-12 months (4-6 Km-Mfx-Pto-Cfz-Z-Hhigh-dose-E /5 Mfx-Cfz-Z-E) may be used instead of longer regimens. Currently, conducting trials involving newer drugs such as bedaquiline, have been proposed. The regimen will be of a shorter duration containing isoniazid, prothionamide, bedaquiline, levofloxacin, ciprofloxacin, ethambutol and pyrazinamide (STREAM regimen). To successfully treat MDR-TB one requires new classes of antibiotic and newer diagnostic tests. This represents an enormous financial and technical challenge to the programme managers and policy makers.

  18. Recent Advances in Multi-Drug Resistance (MDR) Efflux Pump Inhibitors of Gram-Positive Bacteria S. aureus.

    PubMed

    Handzlik, Jadwiga; Matys, Anna; Kieć-Kononowicz, Katarzyna

    2013-02-05

    The paper focuses on recent achievements in the search for new chemical compounds able to inhibit multidrug resistance (MDR) mechanisms in Gram-positive pathogens. An analysis of the results of the search for new efflux pump inhibitors (EPIs) for Gram-positive bacteria, which have been performed over the last decade, indicates that almost all efforts are focused on the NorA (MFS) efflux pump in S. aureus. Considering the chemical structures of the NorA EPIs that have been identified, it can be observed that the most active agents belong to the families of compounds possessing conjugated double bonds, e.g., chalcones, piperine-like compounds, N-cinnamoylphenalkylamides or citral amide derivatives. Indole-, dihydronaphthyl-, 2-chloro-5-bromo-phenyl- or piperidine moieties seem to be profitable for the EPI properties, as well. These results, together with an increasing knowledge about a variety of efflux pumps that are involved in MDR of Gram-positive pathogens underline that further search for new EPIs should pay more attention to develop MDR efflux protein targets, including SMR, MATE, ABC or other members of the MFS family.

  19. Aloe vera extract functionalized zinc oxide nanoparticles as nanoantibiotics against multi-drug resistant clinical bacterial isolates.

    PubMed

    Ali, Khursheed; Dwivedi, Sourabh; Azam, Ameer; Saquib, Quaiser; Al-Said, Mansour S; Alkhedhairy, Abdulaziz A; Musarrat, Javed

    2016-06-15

    ZnO nanoparticles (ZnONPs) were synthesised through a simple and efficient biogenic synthesis approach, exploiting the reducing and capping potential of Aloe barbadensis Miller (A. vera) leaf extract (ALE). ALE-capped ZnO nanoparticles (ALE-ZnONPs) were characterized using UV-Vis spectroscopy, X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and transmission electron microscopy (TEM) analyses. XRD analysis provided the average size of ZnONPs as 15 nm. FTIR spectral analysis suggested the role of phenolic compounds, terpenoids and proteins present in ALE, in nucleation and stability of ZnONPs. Flow cytometry and atomic absorption spectrophotometry (AAS) data analyses revealed the surface binding and internalization of ZnONPs in Gram +ve (Staphylococcus aureus) and Gram -ve (Escherichia coli) cells, respectively. Significant antibacterial activity of ALE-ZnONPs was observed against extended spectrum beta lactamases (ESBL) positive E. coli, Pseudomonas aeruginosa, and methicillin resistant S. aureus (MRSA) clinical isolates exhibiting the MIC and MBC values of 2200, 2400 μg/ml and 2300, 2700 μg/ml, respectively. Substantial inhibitory effects of ALE-ZnONPs on bacterial growth kinetics, exopolysaccharides and biofilm formation, unequivocally suggested the antibiotic and anti-biofilm potential. Overall, the results elucidated a rapid, environmentally benign, cost-effective, and convenient method for ALE-ZnONPs synthesis, for possible applications as nanoantibiotics or drug carriers. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Aggregatibacter actinomycetemcomitans serotype prevalence and antibiotic resistance in a UK population with periodontitis.

    PubMed

    Akrivopoulou, Chaido; Green, Ingrid M; Donos, Nikolaos; Nair, Sean P; Ready, Derren

    2017-09-01

    Aggregatibacter actinomycetemcomitans is a recognised pathogen involved in aggressive periodontitis. Seven serotypes of A. actinomycetemcomitans exist with a range of virulence and distribution dependent on ethnicity and geography. The ability of A. actinomycetemcomitans to invade soft tissue can necessitate the use of systemic antibiotics for treatment, however variations in its antibiotic susceptibility exist dependent on geographical location. Serotypes of A. actinomycetemcomitans isolates from a UK cohort of 50 patients with aggressive periodontitis were determined by PCR. Resistance of the isolates to eight antibiotics [penicillin (1U), amoxicillin (2μg), amoxicillin/clavulanic acid (30μg), metronidazole (5μg), clindamycin (2μg), tetracycline (10μg), ciprofloxacin (5μg) and ceftazidime (30μg)] were determined by disk diffusion according to BSAC guidelines. Prevalences of serotypes a, c, b, e and mixed serotypes were 48%, 22%, 2%, 2% and 12%, respectively. The serotype of isolates from seven patients (14%) could not be deduced by PCR. Of the 56 isolates tested, 100% were resistant to penicillin and metronidazole, 87.5% to clindamycin, 83.9% to amoxicillin and 76.8% to ceftazidime. Low rates of resistance to tetracycline (8.9% resistant) and amoxicillin/clavulanic acid (14.3% resistant) were observed, whereas no isolates were resistant to ciprofloxacin. As in a number of publications the suggested treatment of aggressive periodontitis includes the combined use of amoxicillin with metronidazole, these results highlight the need for culture and antimicrobial susceptibility investigations in patients with aggressive periodontitis prior to systemic use of antibiotics concomitantly to periodontal therapy. Copyright © 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

  1. Chemical conjugation of 2-hexadecynoic acid to C5-curcumin enhances its antibacterial activity against multi-drug resistant bacteria.

    PubMed

    Sanabria-Ríos, David J; Rivera-Torres, Yaritza; Rosario, Joshua; Gutierrez, Ricardo; Torres-García, Yeireliz; Montano, Nashbly; Ortíz-Soto, Gabriela; Ríos-Olivares, Eddy; Rodríguez, José W; Carballeira, Néstor M

    2015-11-15

    The first total synthesis of a C5-curcumin-2-hexadecynoic acid (C5-Curc-2-HDA, 6) conjugate was successfully performed. Through a three-step synthetic route, conjugate 6 was obtained in 13% overall yield and tested for antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) strains. Our results revealed that 6 was active against eight MRSA strains at MICs that range between 31.3 and 62.5 μg/mL. It was found that the presence of 2-hexadecynoic acid (2-HDA, 4) in conjugate 6 increased 4-8-fold its antibacterial activity against MRSA strains supporting our hypothesis that the chemical connection of 4 to C5-curcumin (2) increases the antibacterial activity of 2 against Gram-positive bacteria. Combinational index (CIn) values that range between 1.6 and 2.3 were obtained when eight MRSA strains were treated with an equimolar mixture of 2 and 4. These results demonstrated that an antagonistic effect is taking place. Finally, it was investigated whether conjugate 6 can affect the replication process of S. aureus, since this compound inhibited the supercoiling activity of the S. aureus DNA gyrase at minimum inhibitory concentrations (MIC) of 250 μg/mL (IC50=100.2±13.9 μg/mL). Moreover, it was observed that the presence of 4 in conjugate 6 improves the anti-topoisomerase activity of 2 towards S. aureus DNA gyrase, which is in agreement with results obtained from antibacterial susceptibility tests involving MRSA strains.

  2. Results of antiretroviral treatment interruption and intensification in advanced multi-drug resistant HIV infection from the OPTIMA trial.

    PubMed

    Holodniy, Mark; Brown, Sheldon T; Cameron, D William; Kyriakides, Tassos C; Angus, Brian; Babiker, Abdel; Singer, Joel; Owens, Douglas K; Anis, Aslam; Goodall, Ruth; Hudson, Fleur; Piaseczny, Mirek; Russo, John; Schechter, Martin; Deyton, Lawrence; Darbyshire, Janet

    2011-03-31

    Guidance is needed on best medical management for advanced HIV disease with multidrug resistance (MDR) and limited retreatment options. We assessed two novel antiretroviral (ARV) treatment approaches in this setting. We conducted a 2×2 factorial randomized open label controlled trial in patients with a CD4 count≤300 cells/µl who had ARV treatment (ART) failure requiring retreatment, to two options (a) re-treatment with either standard (≤4 ARVs) or intensive (≥5 ARVs) ART and b) either treatment starting immediately or after a 12-week monitored ART interruption. Primary outcome was time to developing a first AIDS-defining event (ADE) or death from any cause. Analysis was by intention to treat. From 2001 to 2006, 368 patients were randomized. At baseline, mean age was 48 years, 2% were women, median CD4 count was 106/µl, mean viral load was 4.74 log(10) copies/ml, and 59% had a prior AIDS diagnosis. Median follow-up was 4.0 years in 1249 person-years of observation. There were no statistically significant differences in the primary composite outcome of ADE or death between re-treatment options of standard versus intensive ART (hazard ratio 1.17; CI 0.86-1.59), or between immediate retreatment initiation versus interruption before re-treatment (hazard ratio 0.93; CI 0.68-1.30), or in the rate of non-HIV associated serious adverse events between re-treatment options. We did not observe clinical benefit or harm assessed by the primary outcome in this largest and longest trial exploring both ART interruption and intensification in advanced MDR HIV infection with poor retreatment options. Clinicaltrials.gov NCT00050089.

  3. Chemical conjugation of 2-hexadecynoic acid to C5-Curcumin enhances its antibacterial activity against multi-drug resistant bacteria

    PubMed Central

    Sanabria-Ríos, David J.; Rivera-Torres, Yaritza; Rosario, Joshua; Gutierrez, Ricardo; Torres-García, Yeireliz; Montano, Nashbly; Ortíz-Soto, Gabriela; Ríos-Olivares, Eddy; Rodríguez, José W.; Carballeira, Néstor M.

    2015-01-01

    The first total synthesis of a C5-Curcumin-2-Hexadecynoic Acid (C5-Curc-2-HDA, 6) conjugate was successfully performed. Through a three-step synthetic route, conjugate 6 was obtained in 13 % overall yield and tested for antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) strains. Our results revealed that 6 was active against eight MRSA strains at MICs that range between 31.3 and 62.5 μg/mL. It was found that the presence of 2-hexadecynoic acid (2-HDA, 4) in conjugate 6 increased 4-8-fold its antibacterial activity against MRSA strains supporting our hypothesis that the chemical connection of 4 to C5-Curcumin (2) increases the antibacterial activity of 2 against Gram-positive bacteria. Combinational index (CIn) values that range between 1.6 and 2.3 were obtained when eight MRSA strains were treated with an equimolar mixture of 2 and 4. These results demonstrated that an antagonistic effect is taking place. Finally, it was investigated whether conjugate 6 can affect the replication process of S. aureus, since this compound inhibited the supercoiling activity of the S. aureus DNA gyrase at minimum inhibitory concentrations (MIC) of 250 μg/mL (IC50 = 100.2 ± 13.9 μg/mL). Moreover, it was observed that the presence of 4 in conjugate 6 improves the anti-topoisomerase activity of 2 towards S. aureus DNA gyrase, which is in agreement with results obtained from antibacterial susceptibility tests involving MRSA strains. PMID:26483137

  4. Results of Antiretroviral Treatment Interruption and Intensification in Advanced Multi-Drug Resistant HIV Infection from the OPTIMA Trial

    PubMed Central

    Holodniy, Mark; Brown, Sheldon T.; Cameron, D. William; Kyriakides, Tassos C.; Angus, Brian; Babiker, Abdel; Singer, Joel; Owens, Douglas K.; Anis, Aslam; Goodall, Ruth; Hudson, Fleur; Piaseczny, Mirek; Russo, John; Schechter, Martin; Deyton, Lawrence; Darbyshire, Janet

    2011-01-01

    Background Guidance is needed on best medical management for advanced HIV disease with multidrug resistance (MDR) and limited retreatment options. We assessed two novel antiretroviral (ARV) treatment approaches in this setting. Methods and Findings We conducted a 2×2 factorial randomized open label controlled trial in patients with a CD4 count ≤300 cells/µl who had ARV treatment (ART) failure requiring retreatment, to two options (a) re-treatment with either standard (≤4 ARVs) or intensive (≥5 ARVs) ART and b) either treatment starting immediately or after a 12-week monitored ART interruption. Primary outcome was time to developing a first AIDS-defining event (ADE) or death from any cause. Analysis was by intention to treat. From 2001 to 2006, 368 patients were randomized. At baseline, mean age was 48 years, 2% were women, median CD4 count was 106/µl, mean viral load was 4.74 log10 copies/ml, and 59% had a prior AIDS diagnosis. Median follow-up was 4.0 years in 1249 person-years of observation. There were no statistically significant differences in the primary composite outcome of ADE or death between re-treatment options of standard versus intensive ART (hazard ratio 1.17; CI 0.86–1.59), or between immediate retreatment initiation versus interruption before re-treatment (hazard ratio 0.93; CI 0.68–1.30), or in the rate of non-HIV associated serious adverse events between re-treatment options. Conclusions We did not observe clinical benefit or harm assessed by the primary outcome in this largest and longest trial exploring both ART interruption and intensification in advanced MDR HIV infection with poor retreatment options. Trial Registration Clinicaltrials.gov NCT00050089 PMID:21483491

  5. Targeting autophagy augments the activity of DHA-E3 to overcome p-gp mediated multi-drug resistance.

    PubMed

    Xi, Guangmin; Wang, Ming; Sun, Bing; Shaikh, Abdul Sami; Liu, Yongqing; Wang, Wei; Lou, Hongxiang; Yuan, Huiqing

    2016-12-01

    Multidrug resistance (MDR) is a major obstacle for successful chemotherapy treatment. Searching for effective MDR modulators and combining them with anticancer drug therapies has been a promising strategy against clinical MDR. In our previous study, we have found that DHA-E3, a synthetic derivative of DHA, has the ability to modulate the function of P-glycoprotein (P-gp) and reverse MDR in cancer cells. In this study, we further evaluated the reversal effect of DHA-E3 on MDR and explored its mechanism of action in vitro. Our findings showed that DHA-E3 significantly potentiated the cytotoxicity of vincristine(VCR) and adriamycin(ADR) in the P-gp over-expressing KB/VCR and A02 cells. The mechanistic study found that DHA-E3 increased the intracellular accumulation of ADR and rhodamine-123 by directly inhibiting the drug-transport activity of P-gp. In the present study, we found that DHA-E3 not only reversed MDR, but also induced autophagy in MDR cancer cells. To determine whether DHA-E3-induced autophagy is an adaptive survival response or contributes to cell death, we manipulated autophagic activity using autophagy inhibitor 3-MA or siRNA targeting Beclin1. We found that the reversal activity of DHA-E3 was significantly exacerbated in the presence of 3-MA or blocking the expression of Beclin1. These results suggest that DHA-E3 is capable of reversing MDR, induction of autophagy represents a defense mechanism and inhibiting this process may be an effective strategy to augment the reversal activity of reversal agents. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  6. Genetic diversity and natural selection of Plasmodium vivax multi-drug resistant gene (pvmdr1) in Mesoamerica.

    PubMed

    González-Cerón, Lilia; Montoya, Alberto; Corzo-Gómez, Josselin C; Cerritos, Rene; Santillán, Frida; Sandoval, Marco A

    2017-07-01

    The Plasmodium vivax multidrug resistant 1 gene (pvmdr1) codes for a transmembrane protein of the parasite's digestive vacuole. It is likely that the pvmdr1 gene mutations occur at different sites by convergent evolution. In here, the genetic variation of pvmdr1 at three sites of the Mesoamerican region was studied. Since 1950s, malarious patients of those areas have been treated only with chloroquine and primaquine. Blood samples from patients infected with P. vivax were obtained in southern Mexico (SMX), in the Northwest (NIC-NW) and in the northeast (NIC-NE) of Nicaragua. Genomic DNA was obtained and fragments of pvmdr1 were amplified and sequenced. The nucleotide and amino acid changes as well as the haplotype frequency in pvmdr1 were determined per strain and per geographic site. The sequences of pvmdr1 obtained from the studied regions were compared with homologous sequences from the GenBank database to explore the P. vivax genetic structure. In 141 parasites, eight nucleotide changes (two changes were synonymous and other six were nonsynonymous) were detected in 1536 bp. The PvMDR1 amino acid changes Y976F, F1076FL were predominant in endemic parasites from NIC-NE and outbreak parasites in NIC-NW but absent in SMX. Thirteen haplotypes were resolved, and found to be closely related, but their frequency at each geographic site was different (P = 0.0001). The pvmdr1 codons 925-1083 gene fragment showed higher genetic and haplotype diversity in parasites from NIC-NE than the other areas outside Latin America. The haplotype networks suggested local diversification of pvmdr1 and no significant departure from neutrality. The F ST values were low to moderate regionally, but high between NIC-NE or NIC-NW and other regions inside and outside Latin America. The pvmdr1 gene might have diversified recently at regional level. In the absence of significant natural, genetic drift might have caused differential pvmdr1 haplotype frequencies at different geographic sites

  7. Clonal expansion of the macrolide resistant ST386 within pneumococcal serotype 6C in France.

    PubMed

    Janoir, Claire; Cohen, Robert; Levy, Corinne; Bingen, Edouard; Lepoutre, Agnès; Gutmann, Laurent; Varon, Emmanuelle

    2014-01-01

    In France, the use of the 7-valent pneumococcal conjugate vaccine (PCV7) lead to an overall significant decrease in PCV7 invasive pneumococcal disease (IPD) incidence. However, the decrease in vaccine serotype prevalence was partially counterbalanced by the serotype replacement phenomenon. In this study, we analyzed the role of the newly described serotype 6C as one of the replacement serotypes. This work was conducted on a large time scale from the early PCV7 era (2002-2003) to the PCV13 era (2010-2011), both on IPD strains recovered from the whole population and nasopharyngeal colonizing strains isolated in infant less than two years, who are known to be the main reservoir for pneumococci. Serotype 6C took advantage over 6A and 6B serotypes, which both decreased over time. A continuous and significant increase in 6C IPD was observed in adults along the study period; in contrast, in children less than two years, only an increase in 6C nasopharyngeal carriage was found, the prevalence of serotype 6C in IPD remaining very low over time. Among 101 6C invasive and colonizing strains studied by MLST, 24 STs were found to be related to three major clonal complexes, CC395, CC176, and CC315. STs related to CC176 tend to disappear after 2009 and were essentially replaced by ST386 (CC315), which dramatically increased over time. This clonal expansion may be explained by the erythromycin and tetracycline resistances associated with this clone. Finally, the decrease observed in nasopharyngeal 6C carriage since 2010, likely related to the PCV13 introduction in the French immunization schedule, is expected to lead to a decrease in 6C IPD in adults thereafter.

  8. Clonal Expansion of the Macrolide Resistant ST386 within Pneumococcal Serotype 6C in France

    PubMed Central

    Janoir, Claire; Cohen, Robert; Levy, Corinne; Bingen, Edouard; Lepoutre, Agnès; Gutmann, Laurent; Varon, Emmanuelle

    2014-01-01

    In France, the use of the 7-valent pneumococcal conjugate vaccine (PCV7) lead to an overall significant decrease in PCV7 invasive pneumococcal disease (IPD) incidence. However, the decrease in vaccine serotype prevalence was partially counterbalanced by the serotype replacement phenomenon. In this study, we analyzed the role of the newly described serotype 6C as one of the replacement serotypes. This work was conducted on a large time scale from the early PCV7 era (2002–2003) to the PCV13 era (2010–2011), both on IPD strains recovered from the whole population and nasopharyngeal colonizing strains isolated in infant less than two years, who are known to be the main reservoir for pneumococci. Serotype 6C took advantage over 6A and 6B serotypes, which both decreased over time. A continuous and significant increase in 6C IPD was observed in adults along the study period; in contrast, in children less than two years, only an increase in 6C nasopharyngeal carriage was found, the prevalence of serotype 6C in IPD remaining very low over time. Among 101 6C invasive and colonizing strains studied by MLST, 24 STs were found to be related to three major clonal complexes, CC395, CC176, and CC315. STs related to CC176 tend to disappear after 2009 and were essentially replaced by ST386 (CC315), which dramatically increased over time. This clonal expansion may be explained by the erythromycin and tetracycline resistances associated with this clone. Finally, the decrease observed in nasopharyngeal 6C carriage since 2010, likely related to the PCV13 introduction in the French immunization schedule, is expected to lead to a decrease in 6C IPD in adults thereafter. PMID:24603763

  9. Antimicrobial activity of the bioactive components of essential oils from Pakistani spices against Salmonella and other multi-drug resistant bacteria

    PubMed Central

    2013-01-01

    activities against selected multi drug resistant clinical and soil bacterial strains. Cinnamaldehyde was identified as the most active antimicrobial component present in the cinnamon essential oil which acted as a strong inhibitory agent in MIC assay against the tested bacteria. The results indicate that essential oils from Pakistani spices can be pursued against multidrug resistant bacteria. PMID:24119438

  10. Antimicrobial activity of the bioactive components of essential oils from Pakistani spices against Salmonella and other multi-drug resistant bacteria.

    PubMed

    Naveed, Rasheeha; Hussain, Iftikhar; Tawab, Abdul; Tariq, Muhammad; Rahman, Moazur; Hameed, Sohail; Mahmood, M Shahid; Siddique, Abu Baker; Iqbal, Mazhar

    2013-10-14

    The main objective of this study was the phytochemical characterization of four indigenous essential oils obtained from spices and their antibacterial activities against the multidrug resistant clinical and soil isolates prevalent in Pakistan, and ATCC reference strains. Chemical composition of essential oils from four Pakistani spices cumin (Cuminum cyminum), cinnamon (Cinnamomum verum), cardamom (Amomum subulatum) and clove (Syzygium aromaticum) were analyzed on GC/MS. Their antibacterial activities were investigated by minimum inhibitory concentration (MIC) and Thin-Layer Chromatography-Bioautographic (TLC-Bioautographic) assays against pathogenic strains Salmonella typhi (D1 Vi-positive), Salmonella typhi (G7 Vi-negative), Salmonella paratyphi A, Escherichia coli (SS1), Staphylococcus aureus, Pseudomonas fluorescens and Bacillus licheniformis (ATCC 14580). The data were statistically analyzed by using Analysis of Variance (ANOVA) and Least Significant Difference (LSD) method to find out significant relationship of essential oils biological activities at p <0.05. Among all the tested essential oils, oil from the bark of C. verum showed best antibacterial activities against all selected bacterial strains in the MIC assay, especially with 2.9 mg/ml concentration against S. typhi G7 Vi-negative and P. fluorescens strains. TLC-bioautography confirmed the presence of biologically active anti-microbial components in all tested essential oils. P. fluorescens was found susceptible to C. verum essential oil while E. coli SS1 and S. aureus were resistant to C. verum and A. subulatum essential oils, respectively, as determined in bioautography assay. The GC/MS analysis revealed that essential oils of C. cyminum, C. verum, A. subulatum, and S. aromaticum contain 17.2% cuminaldehyde, 4.3% t-cinnamaldehyde, 5.2% eucalyptol and 0.73% eugenol, respectively. Most of the essential oils included in this study possessed good antibacterial activities against selected multi drug

  11. In vitro susceptibility of multi-drug resistant Pseudomonas aeruginosa and extended-spectrum β-lactamase-producing Klebsiella pneumoniae isolated from clinical specimens at Bugando Medical Centre, Tanzania to Piperacillin-Tazobactam.

    PubMed

    Petro, Daudi; Mushi, Martha F; Moremi, Nyambura; Iddi, Shabani; Mirambo, Mariam; Seni, Jeremiah; Mshana, Stephen E

    2014-01-01

    Pseudomonas spp. and Klebsiella pneumoniae are common causes of serious health care associated infections (HCAIs) worldwide. The treatment options for infections caused by multi-drug resistant (MDR) organisms are limited to tigecycline and carbapenems. A total of 172 isolates of multi-drug resistant Pseudomonas. spp and extended-spectrum β- (ESBL) producing Klebsiella pneumoniae isolated from clinical specimens at the Bugando Medical Centre were tested for their in vitro susceptibility to piperacillin-tazobactam 100/10μg using disc diffusion test as recommended by Clinical Laboratory Standard Institute (CLSI). Out of 59 multi-drug resistant Pseudomonas spp, 54 (92.0%) were susceptible to piperacillin-tazobactam while of 113 ESBL producing Klebsiella pneumoniae, 55 (48.7%) were susceptible to piperacillin-tazobactam 100/10μg. Also, 20 (34.0%) of the Pseudomonas spp were both ESBL producers and susceptible to piperacillin-tazobactam 100/10μg. A significant proportion of Pseudomonas spp isolates from clinical specimens in our setting are susceptible to piperacillin/tazobactam. This study shows that piperacillin-tazobactam offer a better option to clinicians for the treatment of health care associated infections due to Pseudomonas spp. and ESBL producing Klebsiella pneumoniae in our setting and other health facilities where these organisms are of significance.

  12. Serotype distribution and antimicrobial resistance of invasive and noninvasive pneumococcal isolates in Tunisia.

    PubMed

    Marzouk, Manel; Ferjani, Asma; Bouafia, Nabiha; Harb, Hanen; Ben Salem, Youssef; Boukadida, Jalel

    2015-02-01

    Pneumococcal conjugate vaccines have not yet been introduced into the national program for childhood vaccination in Tunisia. The aim of this 7-year study was to obtain local data about serotype distribution and antimicrobial resistance of Streptococcus pneumoniae. A total of 203 isolates of culture confirmed that S. pneumoniae was evaluated. Invasive (n=108) and noninvasive (n=95) pneumococcal isolates were obtained from patients aged from 1 month to 85 years old. Considering all age groups, vaccine coverage was 40%, 62%, and 68% for PCV7, PCV10, and PCV13 serotypes, respectively. Overall, 31% of these isolates were penicillin G nonsusceptible. The most prevalent serotypes identified were those found in currently available pneumococcal conjugate vaccines, emphasizing the importance of implementing the vaccine in the routine immunization schedule at the national level.

  13. Population Structure and Antimicrobial Resistance Profiles of Streptococcus suis Serotype 2 Sequence Type 25 Strains

    PubMed Central

    Athey, Taryn B. T.; Teatero, Sarah; Takamatsu, Daisuke; Wasserscheid, Jessica; Dewar, Ken; Gottschalk, Marcelo; Fittipaldi, Nahuel

    2016-01-01

    Strains of serotype 2 Streptococcus suis are responsible for swine and human infections. Different serotype 2 genetic backgrounds have been defined using multilocus sequence typing (MLST). However, little is known about the genetic diversity within each MLST sequence type (ST). Here, we used whole-genome sequencing to test the hypothesis that S. suis serotype 2 strains of the ST25 lineage are genetically heterogeneous. We evaluated 51 serotype 2 ST25 S. suis strains isolated from diseased pigs and humans in Canada, the United States of America, and Thailand. Whole-genome sequencing revealed numerous large-scale rearrangements in the ST25 genome, compared to the genomes of ST1 and ST28 S. suis strains, which result, among other changes, in disruption of a pilus island locus. We report that recombination and lateral gene transfer contribute to ST25 genetic diversity. Phylogenetic analysis identified two main and distinct Thai and North American clades grouping most strains investigated. These clades also possessed distinct patterns of antimicrobial resistance genes, which correlated with acquisition of different integrative and conjugative elements (ICEs). Some of these ICEs were found to be integrated at a recombination hot spot, previously identified as the site of integration of the 89K pathogenicity island in serotype 2 ST7 S. suis strains. Our results highlight the limitations of MLST for phylogenetic analysis of S. suis, and the importance of lateral gene transfer and recombination as drivers of diversity in this swine pathogen and zoonotic agent. PMID:26954687

  14. Development of EGFR-Targeted Polymer Blend Nanocarriers for Combination Paclitaxel/Lonidamine Delivery to Treat Multi-Drug Resistance in Human Breast and Ovarian Tumor Cells

    PubMed Central

    Milane, Lara; Duan, Zhenfeng; Amiji, Mansoor

    2013-01-01

    Multi-drug resistant (MDR) cancer is a significant clinical obstacle and is often implicated in cases of recurrent, non-responsive disease. Targeted nanoparticles were made by synthesizing a poly(D,L-lactide-co-glycolide)/poly(ethylene glycol)/epidermal growth factor receptor targeting peptide (PLGA/PEG/EGFR-peptide) construct for incorporation in poly(epsilon-caprolactone) (PCL) nanoparticles. MDR was induced in a panel of nine human breast and ovarian cancer cell lines using hypoxia. EGFR-targeted polymer blend nanoparticles were shown to actively target EGFR over-expressing cell lines, especially upon induction of hypoxia. The nanoparticles were capable of sustained drug release. Combination therapy with lonidamine and paclitaxel significantly improved the therapeutic index of both drugs. Treatment with a nanoparticle dose of 1 μM paclitaxel/10 μM lonidamine resulted in less than 10% cell viability for all hypoxic/MDR cell lines and less than 5% cell viability for all normoxic cell lines. Comparatively, treatment with 1 μM paclitaxel alone was the approximate IC50 value of the MDR cells while treatment with lonidamine alone had very little effect. PLGA/PEG/EGFR-peptide delivery system actively targets a MDR cell by exploiting the expression of EGFR. This system treats MDR by inhibiting the Warburg effect and promoting mitochondrial binding of pro-apoptotic Bcl-2 proteins (lonidamine), while hyperstabilizing microtubules (paclitaxel). This nanocarrier system actively targets a MDR associated phenotype (EGFR receptor over-expression), further enhancing the therapeutic index of both drugs and potentiating the use of lonidamine/paclitaxel combination therapy in the treatment of MDR cancer. PMID:20942457

  15. Adenovirus vector infection of non-small-cell lung cancer cells is a trigger for multi-drug resistance mediated by P-glycoprotein

    SciTech Connect

    Tomono, Takumi; Kajita, Masahiro; Yano, Kentaro; Ogihara, Takuo

    2016-08-05

    P-glycoprotein (P-gp) is an ATP-binding cassette protein involved in cancer multi-drug resistance (MDR). It has been reported that infection with some bacteria and viruses induces changes in the activities of various drug-metabolizing enzymes and transporters, including P-gp. Although human adenoviruses (Ad) cause the common cold, the effect of Ad infection on MDR in cancer has not been established. In this study, we investigated whether Ad infection is a cause of MDR in A549, H441 and HCC827 non-small-cell lung cancer (NSCLC) cell lines, using an Ad vector system. We found that Ad vector infection of NSCLC cell lines induced P-gp mRNA expression, and the extent of induction was dependent on the number of Ad vector virus particles and the infection time. Heat-treated Ad vector, which is not infectious, did not alter P-gp mRNA expression. Uptake experiments with doxorubicin (DOX), a P-gp substrate, revealed that DOX accumulation was significantly decreased in Ad vector-infected A549 cells. The decrease of DOX uptake was blocked by verapamil, a P-gp inhibitor. Our results indicated that Ad vector infection of NSCLC cells caused MDR mediated by P-gp overexpression. The Ad vector genome sequence is similar to that of human Ad, and therefore human Ad infection of lung cancer patients may lead to chemoresistance in the clinical environment. -- Highlights: •Adenovirus vector infection induced P-gp mRNA expression in three NSCLC cell lines. •Adenovirus vector infection enhanced P-gp-mediated doxorubicin efflux from the cells. •The increase of P-gp was not mediated by nuclear receptors (PXR, CAR) or COX-2.

  16. Therapeutic Efficacy and Safety of Paclitaxel/Lonidamine Loaded EGFR-Targeted Nanoparticles for the Treatment of Multi-Drug Resistant Cancer

    PubMed Central

    Milane, Lara; Duan, Zhenfeng; Amiji, Mansoor

    2011-01-01

    The treatment of multi-drug resistant (MDR) cancer is a clinical challenge. Many MDR cells over-express epidermal growth factor receptor (EGFR). We exploit this expression through the development of EGFR-targeted, polymer blend nanocarriers for the treatment of MDR cancer using paclitaxel (a common chemotherapeutic agent) and lonidamine (an experimental drug; mitochondrial hexokinase 2 inhibitor). An orthotopic model of MDR human breast cancer was developed in nude mice and used to evaluate the safety and efficacy of nanoparticle treatment. The efficacy parameters included tumor volume measurements from day 0 through 28 days post-treatment, terminal tumor weight measurements, tumor density and morphology assessment through hematoxylin and eosin staining of excised tumors, and immunohistochemistry of tumor sections for MDR protein markers (P-glycoprotein, Hypoxia Inducible Factor, EGFR, Hexokinase 2, and Stem Cell Factor). Toxicity was assessed by tracking changes in animal body weight from day 0 through 28 days post-treatment, by measuring plasma levels of the liver enzymes ALT (Alanine Aminotransferase) and LDH (lactate dehydrogenase), and by white blood cell and platelet counts. In these studies, this nanocarrier system demonstrated superior efficacy relative to combination (paclitaxel/lonidamine) drug solution and single agent treatments in nanoparticle and solution form. The combination nanoparticles were the only treatment group that decreased tumor volume, sustaining this decrease until the 28 day time point. In addition, treatment with the EGFR-targeted lonidamine/paclitaxel nanoparticles decreased tumor density and altered the MDR phenotype of the tumor xenografts. These EGFR-targeted combination nanoparticles were considerably less toxic than solution treatments. Due to the flexible design and simple conjugation chemistry, this nanocarrier system could be used as a platform for the development of other MDR cancer therapies; the use of this system for EGFR

  17. Development of a Patient-Centred, Psychosocial Support Intervention for Multi-Drug-Resistant Tuberculosis (MDR-TB) Care in Nepal.

    PubMed

    Khanal, Sudeepa; Elsey, Helen; King, Rebecca; Baral, Sushil C; Bhatta, Bharat Raj; Newell, James N

    2017-01-01

    Multi-drug-resistant tuberculosis (MDR-TB) poses a major threat to public health worldwide, particularly in low-income countries. The current long (20 month) and arduous treatment regime uses powerful drugs with side-effects that include mental ill-health. It has a high loss-to-follow-up (25%) and higher case fatality and lower cure-rates than those with drug sensitive tuberculosis (TB). While some national TB programmes provide small financial allowances to patients, other aspects of psychosocial ill-health, including iatrogenic ones, are not routinely assessed or addressed. We aimed to develop an intervention to improve psycho-social well-being for MDR-TB patients in Nepal. To do this we conducted qualitative work with MDR-TB patients, health professionals and the National TB programme (NTP) in Nepal. We conducted semi-structured interviews (SSIs) with 15 patients (10 men and 5 women, aged 21 to 68), four family members and three frontline health workers. In addition, three focus groups were held with MDR-TB patients and three with their family members. We conducted a series of meetings and workshops with key stakeholders to design the intervention, working closely with the NTP to enable government ownership. Our findings highlight the negative impacts of MDR-TB treatment on mental health, with greater impacts felt among those with limited social and financial support, predominantly married women. Michie et al's (2011) framework for behaviour change proved helpful in identifying corresponding practice- and policy-level changes. The findings from this study emphasise the need for tailored psycho-social support. Recent work on simple psychological support packages for the general population can usefully be adapted for use with people with MDR-TB.

  18. The VACS Index Accurately Predicts Mortality and Treatment Response among Multi-Drug Resistant HIV Infected Patients Participating in the Options in Management with Antiretrovirals (OPTIMA) Study

    PubMed Central

    Brown, Sheldon T.; Tate, Janet P.; Kyriakides, Tassos C.; Kirkwood, Katherine A.; Holodniy, Mark; Goulet, Joseph L.; Angus, Brian J.; Cameron, D. William; Justice, Amy C.

    2014-01-01

    Objectives The VACS Index is highly predictive of all-cause mortality among HIV infected individuals within the first few years of combination antiretroviral therapy (cART). However, its accuracy among highly treatment experienced individuals and its responsiveness to treatment interventions have yet to be evaluated. We compared the accuracy and responsiveness of the VACS Index with a Restricted Index of age and traditional HIV biomarkers among patients enrolled in the OPTIMA study. Methods Using data from 324/339 (96%) patients in OPTIMA, we evaluated associations between indices and mortality using Kaplan-Meier estimates, proportional hazards models, Harrel’s C-statistic and net reclassification improvement (NRI). We also determined the association between study interventions and risk scores over time, and change in score and mortality. Results Both the Restricted Index (c = 0.70) and VACS Index (c = 0.74) predicted mortality from baseline, but discrimination was improved with the VACS Index (NRI = 23%). Change in score from baseline to 48 weeks was more strongly associated with survival for the VACS Index than the Restricted Index with respective hazard ratios of 0.26 (95% CI 0.14–0.49) and 0.39(95% CI 0.22–0.70) among the 25% most improved scores, and 2.08 (95% CI 1.27–3.38) and 1.51 (95%CI 0.90–2.53) for the 25% least improved scores. Conclusions The VACS Index predicts all-cause mortality more accurately among multi-drug resistant, treatment experienced individuals and is more responsive to changes in risk associated with treatment intervention than an index restricted to age and HIV biomarkers. The VACS Index holds promise as an intermediate outcome for intervention research. PMID:24667813

  19. Development of a Patient-Centred, Psychosocial Support Intervention for Multi-Drug-Resistant Tuberculosis (MDR-TB) Care in Nepal

    PubMed Central

    Khanal, Sudeepa; Elsey, Helen; Baral, Sushil C.; Bhatta, Bharat Raj; Newell, James N.

    2017-01-01

    Multi-drug-resistant tuberculosis (MDR-TB) poses a major threat to public health worldwide, particularly in low-income countries. The current long (20 month) and arduous treatment regime uses powerful drugs with side-effects that include mental ill-health. It has a high loss-to-follow-up (25%) and higher case fatality and lower cure-rates than those with drug sensitive tuberculosis (TB). While some national TB programmes provide small financial allowances to patients, other aspects of psychosocial ill-health, including iatrogenic ones, are not routinely assessed or addressed. We aimed to develop an intervention to improve psycho-social well-being for MDR-TB patients in Nepal. To do this we conducted qualitative work with MDR-TB patients, health professionals and the National TB programme (NTP) in Nepal. We conducted semi-structured interviews (SSIs) with 15 patients (10 men and 5 women, aged 21 to 68), four family members and three frontline health workers. In addition, three focus groups were held with MDR-TB patients and three with their family members. We conducted a series of meetings and workshops with key stakeholders to design the intervention, working closely with the NTP to enable government ownership. Our findings highlight the negative impacts of MDR-TB treatment on mental health, with greater impacts felt among those with limited social and financial support, predominantly married women. Michie et al’s (2011) framework for behaviour change proved helpful in identifying corresponding practice- and policy-level changes. The findings from this study emphasise the need for tailored psycho-social support. Recent work on simple psychological support packages for the general population can usefully be adapted for use with people with MDR-TB. PMID:28099475

  20. The Evaluation of the virulence factors of clinical Candida isolates and the anti-biofilm activity of Elettaria cardamomum against multi-drug resistant Candida albicans

    PubMed Central

    Vijayalakshmi, P; Thenmozhi, S; Rajeswari, P

    2016-01-01

    Background and Purpose: Today, treatment of life-threatening fungal infections, caused by Candida species, has become a major problem. In the present study, we aimed to evaluate the antifungal susceptibility patterns of different clinical Candida isolates, determine the virulence factors in multi-drug resistant (MDR) Candida species, and assess the anti-biofilm activity of Elettaria cardamomum against MDR Candida species. Materials and Methods: A total of 202 isolates from different Candida species were obtained from three governmental hospitals in Senthamangalam, Tiruchengode, and Namakkal, Tamil Nadu, India. The isolates were identified, using conventional methods. Candida species were tested for virulence factors such as biofilm, protease, and phospholipase activity. The minimum inhibitory concentration (MIC) of Elettaria cardamomum against MDR biofilm-forming C. albicans was determined, using plate and tube methods. Results: The identified Candida isolates (n=202) were C. albicans (74/202), C. glabrata (53/202), C. parapsilosis (44/202), C. tropicalis (15/202), and C. dubliniensis (16/202). The isolates were subjected to antifungal susceptibility testing and the virulence factors were determined. In terms of biofilm production, non-C. albicans species such as C. dubliniensis showed 75% activity. Also, regarding protease activity, C. parapsilosis (75%) showed the highest percentage of protease production. In addition, Candida species showed strong positivity for phospholipase activity (62.87%). In the MIC method, the acetonic extract completely inhibited biofilm production at a concentration of 125 µl (56.25 µg). In comparison with the ethanolic extract, the acetonic extract showed major activity against biofilm production. Conclusion: Based on the findings, pathogenic C. albicans species were inhibited by the ethanolic and acetonic extracts of E. cardamomum. In recent years, MDR and biofilm-forming pathogenic Candida species have been increasingly detected in

  1. The Evaluation of the virulence factors of clinical Candida isolates and the anti-biofilm activity of Elettaria cardamomum against multi-drug resistant Candida albicans.

    PubMed

    Vijayalakshmi, P; Thenmozhi, S; Rajeswari, P

    2016-06-01

    Today, treatment of life-threatening fungal infections, caused by Candida species, has become a major problem. In the present study, we aimed to evaluate the antifungal susceptibility patterns of different clinical Candida isolates, determine the virulence factors in multi-drug resistant (MDR) Candida species, and assess the anti-biofilm activity of Elettaria cardamomum against MDR Candida species. A total of 202 isolates from different Candida species were obtained from three governmental hospitals in Senthamangalam, Tiruchengode, and Namakkal, Tamil Nadu, India. The isolates were identified, using conventional methods. Candida species were tested for virulence factors such as biofilm, protease, and phospholipase activity. The minimum inhibitory concentration (MIC) of Elettaria cardamomum against MDR biofilm-forming C. albicans was determined, using plate and tube methods. The identified Candida isolates (n=202) were C. albicans (74/202), C. glabrata (53/202), C. parapsilosis (44/202), C. tropicalis (15/202), and C. dubliniensis (16/202). The isolates were subjected to antifungal susceptibility testing and the virulence factors were determined. In terms of biofilm production, non-C. albicans species such as C. dubliniensis showed 75% activity. Also, regarding protease activity, C. parapsilosis (75%) showed the highest percentage of protease production. In addition, Candida species showed strong positivity for phospholipase activity (62.87%). In the MIC method, the acetonic extract completely inhibited biofilm production at a concentration of 125 µl (56.25 µg). In comparison with the ethanolic extract, the acetonic extract showed major activity against biofilm production. Based on the findings, pathogenic C. albicans species were inhibited by the ethanolic and acetonic extracts of E. cardamomum. In recent years, MDR and biofilm-forming pathogenic Candida species have been increasingly detected in clinical settings. Therefore, herbal derivatives might contribute

  2. The VACS index accurately predicts mortality and treatment response among multi-drug resistant HIV infected patients participating in the options in management with antiretrovirals (OPTIMA) study.

    PubMed

    Brown, Sheldon T; Tate, Janet P; Kyriakides, Tassos C; Kirkwood, Katherine A; Holodniy, Mark; Goulet, Joseph L; Angus, Brian J; Cameron, D William; Justice, Amy C

    2014-01-01

    The VACS Index is highly predictive of all-cause mortality among HIV infected individuals within the first few years of combination antiretroviral therapy (cART). However, its accuracy among highly treatment experienced individuals and its responsiveness to treatment interventions have yet to be evaluated. We compared the accuracy and responsiveness of the VACS Index with a Restricted Index of age and traditional HIV biomarkers among patients enrolled in the OPTIMA study. Using data from 324/339 (96%) patients in OPTIMA, we evaluated associations between indices and mortality using Kaplan-Meier estimates, proportional hazards models, Harrel's C-statistic and net reclassification improvement (NRI). We also determined the association between study interventions and risk scores over time, and change in score and mortality. Both the Restricted Index (c = 0.70) and VACS Index (c = 0.74) predicted mortality from baseline, but discrimination was improved with the VACS Index (NRI = 23%). Change in score from baseline to 48 weeks was more strongly associated with survival for the VACS Index than the Restricted Index with respective hazard ratios of 0.26 (95% CI 0.14-0.49) and 0.39(95% CI 0.22-0.70) among the 25% most improved scores, and 2.08 (95% CI 1.27-3.38) and 1.51 (95%CI 0.90-2.53) for the 25% least improved scores. The VACS Index predicts all-cause mortality more accurately among multi-drug resistant, treatment experienced individuals and is more responsive to changes in risk associated with treatment intervention than an index restricted to age and HIV biomarkers. The VACS Index holds promise as an intermediate outcome for intervention research.

  3. Genotyping and serotyping of macrolide and multidrug resistant Streptococcus pneumoniae isolated from carrier children.

    PubMed

    Swedan, S F; Hayajneh, W A; Bshara, G N

    2016-01-01

    Streptococcus pneumoniae, an opportunistic pathogen commonly carried asymptomatically in the nasopharynx of children, is associated with increasing rates of treatment failures due to a worldwide increase in drug resistance. We investigated the carriage of S. pneumoniae in children 5 years or younger, the identity of prevalent serotypes, the rates of resistance to macrolides and other antimicrobial agents and the genotypes responsible for macrolide resistance. Nasopharyngeal swabs were collected from 157 children under 5 years for cultural isolation of S. pneumoniae. Antibiogram of isolates  was determined using the disk diffusion test, and the minimal inhibitory concentration to macrolides was determined using the E-test. Isolate serotypes and macrolide resistance genes, erm(B) and mef(E), were identified using multiplex polymerase chain reactions. S. pneumoniae was recovered from 33.8% of children; 41.9% among males and 21.9% among females (P = 0.009). The highest carriage rate occurred among age groups 7-12 months and 49-60 months. Most frequent serotypes were 19F, 6A/B, 11A, 19A, 14 and 15B/C.  Resistance to macrolides was 60.4%. Resistance to oxacillin, trimethoprim/sulfamethoxazole and clindamycin was present among 90.6%, 54.7% and 32.1% of isolates, respectively. All isolates were susceptible to chloramphenicol, levofloxacin and vancomycin. Isolates resistant to one or more macrolide drugs were more likely to be multidrug resistant. Resistance to clindamycin or oxacillin coexisted with macrolide resistance. Among the erythromycin-resistant isolates, erm(B), mef(E) and erm(B) and mef(E) genes were present at rates of 43.8%, 37.5% and 6.3%, respectively. Erm(B) and mef(E) were associated with very high level and moderate-to-high level resistance to macrolides, respectively. A significant proportion of children harboured macrolide and multidrug-resistant S. pneumoniae.

  4. Rise of multidrug-resistant non-vaccine serotype 15A Streptococcus pneumoniae in the United Kingdom, 2001 to 2014

    PubMed Central

    Sheppard, Carmen; Fry, Norman K.; Mushtaq, Shazad; Woodford, Neil; Reynolds, Rosy; Janes, Regina; Pike, Rachel; Hill, Robert; Kimuli, Maimuna; Staves, Peter; Doumith, Michel; Harrison, Timothy; Livermore, David M

    2016-01-01

    Conjugate vaccines have reduced pneumococcal disease in vaccinated children and unvaccinated adults, but non-vaccine serotypes are of concern, particularly if antibiotic resistant. We reviewed Streptococcus pneumoniae collected via: (i) the British Society for Antimicrobial Chemotherapy (BSAC) surveillances from 2001–2014; (ii) Public Health England’s (PHE) invasive isolate surveillance from 2005–2014 and (iii) referral to PHE for resistance investigation from 2005–2014. Serotype 15A increased in all series, with many representatives showing triple resistance to macrolides, tetracyclines and penicillin. 15A was consistently among the 10 most prevalent serotypes from 2011 in PHE and BSAC invasive isolate/bacteraemia surveillance but never previously; 26–33% of these invasive 15A isolates had triple resistance. BSAC respiratory isolates were only serotyped in 2013/14 and 2014/15 (October to September); 15A was most prevalent serotype in both periods, comprising 9–11% of isolates, 38–48% of them with triple resistance. Serotype 15A represented 0–4% of S. pneumoniae referred to PHE for reference investigation annually until 2008 but rose to 29% (2013) and 32% (2014). Almost all multidrug-resistant 15A isolates were sequence type (ST) 63 variants, whereas susceptible 15A isolates were clonally diverse. The rise of serotype 15A suggests that pneumococcal conjugate vaccines will need ongoing adaptation. PMID:28006650

  5. Shigella serotypes among hospitalized patients in urban Bangladesh and their antimicrobial resistance.

    PubMed Central

    Khan, A. I.; Huq, S.; Malek, M. A.; Hossain, M. I.; Talukder, K. A.; Faruque, A. S. G.; Salam, M. A.; Sack, D. A.

    2004-01-01

    We studied the isolation of Shigella spp., and their antimicrobial resistance. S. flexneri (54 %) was most frequently isolated, followed by S. dysenteriae (20 %), S. boydii (16 %) and S. sonnei (10 %). Among S. flexneri (n = 122), 29 (24 %) were 2a, and 23 (19 %) were 2b. None of the Shigella strains were resistant to mecillinam or ciprofloxacin. Resistance to nalidixic acid was most frequent among S. dysenteriae type 1 (100%) followed by S. flexneri 2a (69%), and S. flexneri 2b (52 %). Systematic monitoring is needed to identify most prevalent serotypes, and to detect changes in the prevalence and antimicrobial resistance pattern. PMID:15310182

  6. Antimicrobial Resistance of Shigella flexneri Serotype 1b Isolates in China.

    PubMed

    Cui, Xianyan; Yang, Chaojie; Wang, Jian; Liang, Beibei; Yi, Shengjie; Li, Hao; Liu, Hongbo; Li, Peng; Wu, Zhihao; Xie, Jing; Jia, Leili; Hao, Rongzhang; Wang, Ligui; Hua, Yuejin; Qiu, Shaofu; Song, Hongbin

    2015-01-01

    Shigella flexneri serotype 1b is among the most prominent serotypes in developing countries, followed by serotype 2a. However, only limited data is available on the global phenotypic and genotypic characteristics of S. flexneri 1b. In the present study, 40 S. flexneri 1b isolates from different regions of China were confirmed by serotyping and biochemical characterization. Antimicrobial susceptibility testing showed that 85% of these isolates were multidrug-resistant strains and antibiotic susceptibility profiles varied between geographical locations. Strains from Yunnan were far more resistant than those from Xinjiang, while only one strain from Shanghai was resistant to ceftazidime and aztreonam. Fifteen cephalosporin resistant isolates were identified in this study. ESBL genes (blaSHV, blaTEM, blaOXA, and blaCTX-M) and ampC genes (blaMOX, blaFOX, blaMIR(ACT-1), blaDHA, blaCIT and blaACC) were subsequently detected among the 15 isolates. The results showed that these strains were positive only for blaTEM, blaOXA, blaCTX-M, intI1, and intI2. Furthermore, pulsed-field gel electrophoresis (PFGE) analysis showed that the 40 isolates formed different profiles, and the PFGE patterns of Xinjiang isolates were distinct from Yunnan and Shanghai isolates by one obvious, large, missing band. In summary, similarities in resistance patterns were observed in strains with the same PFGE pattern. Overall, the results supported the need for more prudent selection and use of antibiotics in China. We suggest that antibiotic susceptibility testing should be performed at the start of an outbreak, and antibiotic use should be restricted to severe Shigella cases, based on resistance pattern variations observed in different regions. The data obtained in the current study might help to develop a strategy for the treatment of infections caused by S. flexneri 1b in China.

  7. Antimicrobial activity of Eucalyptus camaldulensis essential oils and their interactions with conventional antimicrobial agents against multi-drug resistant Acinetobacter baumannii.

    PubMed

    Knezevic, Petar; Aleksic, Verica; Simin, Natasa; Svircev, Emilija; Petrovic, Aleksandra; Mimica-Dukic, Neda

    2016-02-03

    Traditional herbal medicine has become an important issue on the global scale during the past decade. Among drugs of natural origin, special place belongs to essential oils, known as strong antimicrobial agents that can be used to combat antibiotic-resistant bacteria. Eucalyptus camaldulensis leaves are traditional herbal remedy used for various purposes, including treatment of infections. The aim of this study was to determine antimicrobial potential of two E. camaldulensis essential oils against multi-drug resistant (MDR) Acinetobacter baumannii wound isolates and to examine possible interactions of essential oils with conventional antimicrobial agents. Chemical composition of essential oils was determined by gas chromatography-mass spectrometry analysis (GC-MS). MIC values of essential oils against A. baumannii strains were estimated by modified broth microdilution method. The components responsible for antimicrobial activity were detected by bioautographic analysis. The potential synergy between the essential oils and antibiotics (ciprofloxacin, gentamicin and polymyxin B) was examined by checkerboard method and time kill curve. The dominant components of both essential oils were spatulenol, cryptone, p-cimene, 1,8-cineole, terpinen-4-ol and β-pinene. The detected MICs for the E. camaldulensis essential oils were in range from 0.5 to 2 μl mL(-1). The bioautographic assay confirmed antibacterial activity of polar terpene compounds. In combination with conventional antibiotics (ciprofloxacin, gentamicin and polymyxin B), the examined essential oils showed synergistic antibacterial effect in most of the cases, while in some even re-sensitized MDR A. baumannii strains. The synergistic interaction was confirmed by time-kill curves for E. camaldulensis essential oil and polymyxin B combination which reduced bacterial count under detection limit very fast, i.e. after 6h of incubation. The detected anti-A. baumannii activity of E. camaldulensis essential oils

  8. Clonal dissemination of the multi-drug resistant Salmonella enterica serovar Braenderup, but not the serovar Bareilly, of prevalent serogroup C1 Salmonella from Taiwan

    PubMed Central

    2009-01-01

    Background Nontyphoidal Salmonella is the main cause of human salmonellosis. In order to study the prevalent serogroups and serovars of clinical isolates in Taiwan, 8931 Salmonellae isolates were collected from 19 medical centers and district hospitals throughout the country from 2004 to 2007. The pulsed-field eletrophoresis types (PFGE) and antibiotic resistance profiles of Salmonella enterica serovars Bareilly (S. Bareilly) and Braenderup (S. Braenderup) were compared, and multi-drug resistance (MDR) plasmids were characterized. Results Over 95% of human salmonellosis in Taiwan was caused by five Salmonella serogroups: B, C1, C2-C3, D1, and E1. S. Typhymurium, S. Enteritidis, S. Stanley and S. Newport were the four most prevalent serovars, accounting for about 64% of isolates. While only one or two major serovars from four of the most prevalent serogroups were represented, four predominant serovars were found in serogroup C1 Salmonellae. The prevalence was decreasing for S. Choleraeuis and S. Braenderup, and S. Virchow and increasing for S. Bareilly. S. Braenderup mainly caused gastroenteritis in children; in contrast, S. Bareiley infected children and elderly people. Both serovars differed by XbaI-PFGE patterns. Almost all S. Bareilly isolates were susceptible to antibiotics of interest, while all lacked plasmids and belonged to one clone. Two distinct major clones in S. Braenderup were cluster A, mainly including MDR isolates with large MDR plasmid from North Taiwan, and cluster B, mainly containing susceptible isolates without R plasmid from South Taiwan. In cluster A, there were two types of conjugative R plasmids with sizes ranging from 75 to 130 kb. Type 1 plasmids consisted of replicons F1A/F1B, blaTEM, IS26, and a class 1 integron with the genes dfrA12-orfF-aadA2-qacEΔ1-sulI. Type 2 plasmids belonged to incompatibility group IncI, contained tnpA-blaCMY-2-blc-sugE genetic structures and lacked both IS26 and class 1 integrons. Although type 2 plasmids

  9. Inoculation with enterococci does not affect colon inflammation in the multi-drug resistance 1a-deficient mouse model of IBD.

    PubMed

    Barnett, Matthew P G; Dommels, Yvonne E M; Butts, Christine A; Zhu, Shuotun; McNabb, Warren C; Roy, Nicole C

    2016-03-03

    Intestinal bacteria are thought to play a role in the pathogenesis of human inflammatory bowel disease (IBD). We investigated whether oral inoculation with specific intestinal bacteria increased colon inflammation in the multi-drug resistance 1a-deficient (Mdr1a (-/-) ) mouse model of IBD. Five-week-old Mdr1a (-/-) mice (FVB background) and FVB mice were randomly assigned to one of two treatment groups (Control or Inoculation, n = 12 per group). All mice were fed AIN-76A rodent diet, and mice in the Inoculation groups also received a single oral bacterial inoculation consisting of twelve cultured Enterococcus species combined with conventional intestinal flora obtained from the gastrointestinal tract of healthy mice (EF.CIF). Body weight, food intake, and disease activity index (DAI) were assessed throughout the study, and at 21 or 24 weeks of age, inflammation was assessed post-mortem by determining colon length and histological injury score (HIS), and plasma serum amyloid A (SAA). Mdr1a (-/-) mice consumed more food than FVB mice at 13 weeks of age (P < 0.05). There was also a significant effect of genotype on body weight, with Mdr1a (-/-) mice weighing less than FVB mice throughout the study (P < 0.05) regardless of treatment, but there was no effect of inoculation on body weight (P > 0.25). Colon HIS of Mdr1a (-/-) mice was significantly higher than that of FVB mice in the Control (9.3 ± 4.7 (mean ± SD) vs. 0.58 ± 0.51; P < 0.001) and Inoculation (6.7 ± 5.1 vs. 0.92 ± 0.39; P < 0.001) groups. There was no difference in colon HIS of Mdr1a (-/-) mice in the Control group compared with Mdr1a (-/-) mice in the Inoculation group (P = 0.25), nor was there any difference in within-group variation of colon HIS in these two Mdr1a (-/-) groups. DAI was higher in Mdr1a (-/-) mice than in FVB mice, but there was no effect of treatment in either strain, nor were there any differences in colon length or plasma SAA. Inoculation of Mdr1a (-/-) mice with the EF

  10. The importance of providing counselling and financial support to patients receiving treatment for multi-drug resistant TB: mixed method qualitative and pilot intervention studies

    PubMed Central

    2014-01-01

    Background People with multi-drug resistant tuberculosis (MDR-TB) in low-income countries face many problems during treatment, and cure rates are low. The purpose of the study was (a) to identify and document the problems experienced by people receiving care for MDR-TB, and how they cope when support is not provided, to inform development of strategies; (b) to estimate the effectiveness of two resultant strategies, counselling alone, and joint counselling and financial support, of increasing DOTS-plus treatment success under routine programme conditions. Methods A mixed-method study comprising a formative qualitative study, pilot intervention study and explanatory qualitative study to better understand barriers to completion of treatment for MDR-TB. Participants were all people starting MDR-TB treatment in seven DOTS-plus centres in the Kathmandu Valley, Nepal during January to December 2008. The primary outcome measure was cure, as internationally defined. Results MDR-TB treatment caused extreme social, financial and employment hardship. Most patients had to move house and leave their job, and reported major stigmatisation. They were concerned about the long-term effects of their disease, and feared infecting others. In the resultant pilot intervention study, the two strategies appeared to improve treatment outcomes: cure rates for those receiving counselling, combined support and no support were 85%, 76% and 67% respectively. Compared with no support, the (adjusted) risk ratios of cure for those receiving counselling and receiving combined support were 1.2 (95% CI 1.0 to 1.6) and 1.2 (95% CI 0.9 to 1.6) respectively. The explanatory study demonstrated that patients valued both forms of support. Conclusions MDR-TB patients are extremely vulnerable to stigma and extreme financial hardship. Provision of counselling and financial support may not only reduce their vulnerability, but also increase cure rates. National Tuberculosis Programmes should consider

  11. Towards understanding the drivers of policy change: a case study of infection control policies for multi-drug resistant tuberculosis in South Africa.

    PubMed

    Saidi, Trust; Salie, Faatiema; Douglas, Tania S

    2017-05-30

    Explaining policy change is one of the central tasks of contemporary policy analysis. In this article, we examine the changes in infection control policies for multi-drug resistant tuberculosis (MDR-TB) in South Africa from the time the country made the transition to democracy in 1994, until 2015. We focus on MDR-TB infection control and refer to decentralised management as a form of infection control. Using Kingdon's theoretical framework of policy streams, we explore the temporal ordering of policy framework changes. We also consider the role of research in motivating policy changes. Policy documents addressing MDR-TB in South Africa over the period 1994 to 2014 were extracted. Literature on MDR-TB infection control in South Africa was extracted from PubMed using key search terms. The documents were analysed to identify the changes that occurred and the factors driving them. During the period under study, five different policy frameworks were implemented. The policies were meant to address the overwhelming challenge of MDR-TB in South Africa, contextualised by high prevalence of HIV infection, that threatened to undermine public health programmes and the success of antiretroviral therapy rollouts. Policy changes in MDR-TB infection control were supported by research evidence and driven by the high incidence and complexity of the disease, increasing levels of dissatisfaction among patients, challenges of physical, human and financial resources in public hospitals, and the ideologies of the political leadership. Activists and people living with HIV played an important role in highlighting the importance of MDR-TB as well as exerting pressure on policymakers, while the mass media drew public attention to infection control as both a cause of and a solution to MDR-TB. The critical factors for policy change for infection control of MDR-TB in South Africa were rooted in the socioeconomic and political environment, were supported by extensive research, and can be framed

  12. Molecular fingerprinting of multidrug-resistant Salmonella enterica serotype Typhi.

    PubMed Central

    Hampton, M. D.; Ward, L. R.; Rowe, B.; Threlfall, E. J.

    1998-01-01

    For epidemiologic investigations, the primary subdivision of Salmonella Typhi is vi-phage typing; 106 Vi-phage types are defined. For multidrug-resistant strains the most common types have been M1 (Pakistan) and E1 (India, Pakistan, Bangladesh, and the Arabian Gulf); a strain untypable with the Vi phages has been responsible for a major epidemic in Tajikistan. Most often, isolates from the Indian subcontinent have been resistant to ampicillin, chloramphenicol, streptomycin, sulfonamides, tetracyclines, and trimethoprim; but in the 1997 Tajikistan outbreak, the epidemic strain was also resistant to ciprofloxacin. For multidrug-resistant strains, subdivision within phage type can be achieved by plasmid profile typing and pulsed-field gel electrophoresis. PMID:9621206

  13. Multidrug-Resistant Salmonella enterica Serotype Typhi, Gulf of Guinea Region, Africa

    PubMed Central

    Baltazar, Murielle; Ngandjio, Antoinette; Holt, Kathryn Elizabeth; Lepillet, Elodie; Pardos de la Gandara, Maria; Collard, Jean-Marc; Bercion, Raymond; Nzouankeu, Ariane; Le Hello, Simon; Dougan, Gordon; Fonkoua, Marie-Christine

    2015-01-01

    We identified 3 lineages among multidrug-resistant (MDR) Salmonella enterica serotype Typhi isolates in the Gulf of Guinea region in Africa during the 2000s. However, the MDR H58 haplotype, which predominates in southern Asia and Kenya, was not identified. MDR quinolone-susceptible isolates contained a 190-kb incHI1 pST2 plasmid or a 50-kb incN pST3 plasmid. PMID:25811307

  14. Mechanisms of first-line antimicrobial resistance in multi-drug and extensively drug resistant strains of Mycobacterium tuberculosis in KwaZulu-Natal, South Africa.

    PubMed

    Dookie, Navisha; Sturm, A Willem; Moodley, Prashini

    2016-10-26

    In South Africa, drug resistant tuberculosis is a major public health crisis in the face of the colossal HIV pandemic. In an attempt to understand the distribution of drug resistance in our setting, we analysed the rpoB, katG, inhA, pncA and embB genes associated with resistance to key drugs used in the treatment of tuberculosis in clinical isolates of Mycobacterium tuberculosis in the KwaZulu-Natal province. Classical mutations were detected in the katG, inhA and embB genes associated with resistance to isoniazid and ethambutol. Diverse mutations were recorded in the multidrug resistant (MDR) and extensively drug resistant (XDR) isolates for the rpoB and pncA gene associated with resistance to rifampicin and pyrazinamide. M.tuberculosis strains circulating in our setting display a combination of previously observed mutations, each mediating resistance to a different drug. The MDR and XDR TB isolates analysed in this study displayed classical mutations linked to INH and EMB resistance, whilst diverse mutations were linked to RIF and PZA resistance. The similarity of the XDR strains confirms reports of the clonality of the XDR epidemic. The successful dissemination of the drug resistant strains in the province underscores the need for rapid diagnostics to effectively diagnose drug resistance and guide treatment.

  15. Drug resistance profile and serotype of streptococcus of pneumoniae infected pediatric patients.

    PubMed

    Wang, Jiefei; Huang, Nannan; Wang, Guangzhou; Yu, Fengqin

    2016-07-01

    To investigate the surveillance of drug resistance and serotype monitoring of steptococcus pneumoniae in hospitalized children. the pathogenic bacteria isolation and identification methods were employed to do the bacteria isolation identification and drug sensitive test on the specimens from Women & Infants Hospital of Zhengzhou. From the specimens, there were 134 detected strains of Streptococcus pneumoniae, and the drug resistance to erythromycin and clindamycin were respectively 97.7% and 89.9%, and the drug resistance to tetracycline, azithromycin and paediatric compound sulfamethoxazole were respectively 86. 3%, 58. 3%, 51. 2%. The vancomycin resistant Streptococcus pneumoniae were often not found. the Streptococcus pneumoniae in children were generally with drug resistant in Zhengzhou area. It shall strengthen drug resistance surveillance, and reasonably choose antibacterial agents.

  16. Homeopathic treatment in addition to standard care in multi drug resistant pulmonary tuberculosis: a randomized, double blind, placebo controlled clinical trial.

    PubMed

    Chand, Kusum S; Manchanda, Raj K; Mittal, Renu; Batra, Sudhir; Banavaliker, Jayant N; De, Indra

    2014-04-01

    Multi drug resistant-tuberculosis (MDR-TB) [resistant to Isoniazid and Rifampicin] is a major global public health problem. In India the incidence is rising in spite of implementation of Revised National Tuberculosis Control Program. Standard MDR-TB drugs are second generation antibiotics taken for 24-27 months. The present study was undertaken to evaluate the efficacy of add on homeopathic intervention to the standard MDR-TB regimen (SR). A randomized, double blind, placebo controlled study was conducted from 2003 to 2008. 120 diagnosed MDR-TB patients (both culture positive and negative) were enrolled and randomized to receive Standard Regimen + individualized homeopathic medicine (SR + H) or Standard Regimen + identical placebo (SR + P). The medicines have been used in infrequent doses. The outcome measures were sputum conversion, changes in chest X-ray (CXR), hemoglobin, erythrocyte sedimentation rate (ESR), weight gain, and clinical improvement. There was an improvement in all the outcome measures as per intention to treat (ITT) and per protocol (PP) analyses. ITT analyses revealed sputum culture conversion from positive to negative in 23 (38.3%) in SR + H; 23 (38.3%) patients in SR + P group; (p = 0.269) and 27 (55.1); 21 (42.8%), p = 0.225 as PP analyses. The mean weight gain in SR + H group was 2.4 ± 4.9 and in SR + P was 0.8 ± 4.4; [p = 0.071], reduction in ESR in SR + H was -8.7 ± 13.2; SR + P was 3.9 ± 15.4 [p = 0.068]. The mean increase in hemoglobin was by 0.6 ± 1.7 in SR + H & 0.3 ± 2.3 [p = 0.440] in SR + P group at 95% confidence interval. Statistically significant improvement was seen in CXR in 37 (61.7%) in SR + H and 20 (33.3%) patients in SR + P group (p = 0.002). Subgroup analyses of culture positive patients showed statistically significant improvement in CXR (p = 0.0005), weight gain (p = 0.026), increase in hemoglobin (p = 0.017) and reduction in ESR (p = 0.025) with add on

  17. Typing and characterization of ColE1-like plasmids conferring kanamycin resistance in Salmonella enterica serotypes

    USDA-ARS?s Scientific Manuscript database

    Background: Multi-antibiotic resistant Salmonella enterica serotypes are increasing in prevalence and concern in human and animal health. Many strains carry resistance determinants on plasmids; current practices focus heavily on large plasmids and the role small plasmids play in resistance gene tra...

  18. Genetic determinants for cadmium and arsenic resistance among Listeria monocytogenes serotype 4b isolates from sporadic human listeriosis patients

    USDA-ARS?s Scientific Manuscript database

    In Listeria monocytogenes serotype 4b from sporadic listeriosis, heavy metal resistance was primarily encountered in certain clonal groups (ECI, ECII, ECIa). All arsenic-resistant isolates harbored the arsenic resistance cassette previously identified in pLI100; ECIa harbored additional arsenic resi...

  19. Nontyphoidal salmonella infection in children with acute gastroenteritis: prevalence, serotypes, and antimicrobial resistance in Shanghai, China.

    PubMed

    Li, Yuefang; Xie, Xinbao; Xu, Xuebing; Wang, Xiangshi; Chang, Hailing; Wang, Chuanqing; Wang, Aiming; He, Yanlei; Yu, Hui; Wang, Xiaohong; Zeng, Mei

    2014-03-01

    Information about nontyphoidal Salmonella (NTS) infection in children is limited in mainland China. The objective of this study was to investigate the prevalence, serotypes, and antibiotic resistance patterns of NTS infection in children in Shanghai. All cases with probable bacterial diarrhea were enrolled from the enteric clinic of a tertiary pediatric hospital between July 2010 and December 2011. Salmonella isolation, serotyping, and antimicrobial susceptibility testing were conducted by the microbiological laboratory. NTS were recovered from 316 (17.2%) of 1833 cases with isolation rate exceeding Campylobacter (7.1%) and Shigella (5.7%). NTS infection was prevalent year-round with a seasonal peak during summer and autumn. The median age of children with NTS gastroenteritis was 18 months. Fever and blood-in-stool were reported in 52.5% and 42.7% of cases, respectively. Salmonella Enteritidis (38.9%) and Salmonella Typhimurium (29.7%) were the most common serovars. Antimicrobial susceptibility showed 60.5% of isolates resistant to ≥1 clinically important antibiotics. Resistance to ciprofloxacin and the third-generation cephalosporins was detected in 5.5% and 7.1%-11.7% of isolates, respectively. NTS is a major enteropathogen responsible for bacterial gastroenteritis in children in Shanghai. Resistance to the current first-line antibiotics is of concern. Ongoing surveillance for NTS infection and antibiotic resistance is needed to control this pathogen in Shanghai.

  20. Salmonella serotypes, resistance patterns, and food vehicles of salmonellosis in southern Brazil between 2007 and 2012.

    PubMed

    Capalonga, Roberta; Ramos, Rosane Campanher; Both, Jane Mari Correa; Soeiro, Mara Lúcia Tiba; Longaray, Solange Mendes; Haas, Simone; Tondo, Eduardo Cesar

    2014-07-14

    Previous studies have identified Salmonella as the main causative agent of foodborne diseases in the state of Rio Grande do Sul (RS), southern Brazil, between 1997 and 2006. This study aimed to describe the Salmonella serotypes, antimicrobial patterns, and food vehicles of salmonellosis that occurred in RS between 2007 and 2012. Information about Salmonella isolates and salmonellosis outbreaks registered in the official records of the Central Laboratory of RS (FEEPS/IPB-LACEN/RS) was analyzed. Among the 163 isolates investigated, 138 (84.7%) were identified as S. Enteritidis. The second and third most frequent serovars identified were S. Schwarzengrund (5.5%) and S. Typhimurium (3.7%). Homemade mayonnaise was the food vehicle most frequently identified (17.39%), followed by pastry products (15.94%) and beef (12.32%). Antimicrobial resistance was analyzed; 12 drugs were tested. Higher percentages of resistance were observed to nitrofurantoin (94.2%) and nalidixic acid (89.1%). The resistance to these two drugs was verified in 80.43% of the isolates. Multi-resistance to three and five drugs was verified in four and two isolates, respectively. Comparing the results of the present study with results of previous reports, it was possible to conclude that S. Enteritidis and homemade mayonnaise are still the main serotype and food vehicle of salmonellosis in RS and that antimicrobial resistance has been increasing among S. Enteritidis responsible for foodborne outbreaks in southern Brazil.

  1. Fluoroquinolone-Resistant Pneumococci: Dynamics of Serotypes and Clones in Spain in 2012 Compared with Those from 2002 and 2006

    PubMed Central

    Domenech, Arnau; Tirado-Vélez, Jose M.; Fenoll, Asunción; Ardanuy, Carmen; Yuste, Jose; Liñares, Josefina

    2014-01-01

    In Spain, rates of ciprofloxacin resistance in pneumococci were low during the last decade (2.6% in 2002 and 2.3% in 2006). In 2012, the rate remained at 2.3%, equivalent to 83 of 3,621 isolates. Of the 83 resistant isolates, 15 showed a low level (MIC of 4 to 8 μg/ml) and 68 a high level (MIC of 16 to 128 μg/ml) of ciprofloxacin resistance. Thirteen low-level-resistant isolates had single changes in ParC, one had a single ParE change, and one did not present any mutations. High-level-resistant isolates had GyrA changes plus additional ParC and/or ParE changes: 51, 15, and 2 isolates had 2, 3, or 4 mutations, respectively. Although 24 different serotypes were observed, 6 serotypes accounted for 51.8% of ciprofloxacin-resistant isolates: 8 (14.5%), 19A (10.8%), 11A (7.2%), 23A (7.2%), 15A (6.0%), and 6B (6.0%). A decrease in pneumococcal 7-valent conjugate vaccine (PCV7) serotypes was observed from 2006 (35.7%) to 2012 (16.9%), especially of serotype 14 (from 16.3% to 2.4%; P < 0.001). In comparison with findings in 2006, multidrug resistance was greater in 2012 (P = 0.296), mainly due to the increased presence and/or emergence of clonal complexes associated with non-PCV7 serotypes: CC63 expressing serotypes 8, 15A, and 19A; CC320 (with serotype 19A); and CC42 (with serotype 23A). Although rates of ciprofloxacin resistance remained low and stable throughout the last decade, changes in serotype and genotype distributions were observed in 2012, notably the expansion of a preexisting multidrug-resistant clone, CC63, and the emergence of the CC156 clone expressing serotype 11A. PMID:24514095

  2. Membrane disruption and anti-quorum sensing effects of synergistic interaction between Lavandula angustifolia (lavender oil) in combination with antibiotic against plasmid-conferred multi-drug-resistant Escherichia coli.

    PubMed

    Yap, P S X; Krishnan, T; Yiap, B C; Hu, C P; Chan, K-G; Lim, S H E

    2014-05-01

    The aim of this study was to investigate the mode of action of the lavender essential oil (LV) on antimicrobial activity against multi-drug-resistant Escherichia coli J53 R1 when used singly and in combination with piperacillin. In the time-kill analysis, a complete killing of bacteria was observed based on colony counts within 4 h when LV was combined with piperacillin during exposure at determined FIC concentrations. Analysis of the membrane permeabilizing effects of LV on treated cultures through their stability against sodium dodecyl sulphate revealed that the LV played a role in disrupting the bacterial cell membrane. The finding is further supported by scanning electron microscopy analysis and zeta potential measurement. In addition, reduction in light production expression of E. coli [pSB1075] by the LV showed the presence of potential quorum sensing (QS) inhibitors. These results indicated that the LV has the potential to reverse bacterial resistance to piperacillin in E. coli J53 R1. It may operate via two mechanisms: alteration of outer membrane permeability and inhibition of bacterial QS. These findings offer a novel approach to develop a new option of phytopharmaceuticals against multi-drug-resistant E. coli. © 2014 The Society for Applied Microbiology.

  3. Contribution of efflux pumps in fluroquinolone resistance in multi-drug resistant nosocomial isolates of Pseudomanas aeruginosa from a tertiary referral hospital in north east India.

    PubMed

    Choudhury, D; Talukdar, A Das; Maurya, A P; Choudhury, M Dutta; Dhar Chanda, D; Chakravarty, A; Bhattacharjee, A

    2015-01-01

    Pseudomonas aeruginosa is one of the leading opportunistic pathogen and its ability to acquire resistance against series of antimicrobial agents confine treatment option for nosocomial infections. Increasing resistance to fluroquinolone (FQ) agents has further worsened the scenario. The major mechanism of resistance to FQs includes mutation in FQs target genes in bacteria (DNA gyrase and/or topoisomerases) and overexpression of antibiotic efflux pumps. We have investigated the role of efflux pump mediated FQ resistance in nosocomial isolates of P. aeruginosa from a tertiary referral hospital in north eastern part of India. A total of 234 non-duplicate, consecutive clinical isolates of P. aeruginosa were obtained from a tertiary referral hospital of north-east India. An efflux pump inhibitor (EPI), carbonyl cyanide m-chlorophenylhydrazone (CCCP) based method was used for determination of efflux pump activity and multiplex polymerase chain reaction (PCR) was performed for molecular characterisation of efflux pump. Minimum inhibitory concentration (MIC) reduction assay was also performed for all the isolates. A total number of 56 (23%) have shown efflux mediated FQ resistance. MexAB-OprM efflux system was predominant type. This is the first report of efflux pump mediated FQ resistance from this part of the world and the continued emergence of these mutants with such high MIC range from this part of the world demands serious awareness, diagnostic intervention, and proper therapeutic option.

  4. Defining Catastrophic Costs and Comparing Their Importance for Adverse Tuberculosis Outcome with Multi-Drug Resistance: A Prospective Cohort Study, Peru

    PubMed Central

    Wingfield, Tom; Boccia, Delia; Tovar, Marco; Gavino, Arquímedes; Zevallos, Karine; Montoya, Rosario; Lönnroth, Knut; Evans, Carlton A.

    2014-01-01

    Background Even when tuberculosis (TB) treatment is free, hidden costs incurred by patients and their households (TB-affected households) may worsen poverty and health. Extreme TB-associated costs have been termed “catastrophic” but are poorly defined. We studied TB-affected households' hidden costs and their association with adverse TB outcome to create a clinically relevant definition of catastrophic costs. Methods and Findings From 26 October 2002 to 30 November 2009, TB patients (n = 876, 11% with multi-drug-resistant [MDR] TB) and healthy controls (n = 487) were recruited to a prospective cohort study in shantytowns in Lima, Peru. Patients were interviewed prior to and every 2–4 wk throughout treatment, recording direct (household expenses) and indirect (lost income) TB-related costs. Costs were expressed as a proportion of the household's annual income. In poorer households, costs were lower but constituted a higher proportion of the household's annual income: 27% (95% CI = 20%–43%) in the least-poor houses versus 48% (95% CI = 36%–50%) in the poorest. Adverse TB outcome was defined as death, treatment abandonment or treatment failure during therapy, or recurrence within 2 y. 23% (166/725) of patients with a defined treatment outcome had an adverse outcome. Total costs ≥20% of household annual income was defined as catastrophic because this threshold was most strongly associated with adverse TB outcome. Catastrophic costs were incurred by 345 households (39%). Having MDR TB was associated with a higher likelihood of incurring catastrophic costs (54% [95% CI = 43%–61%] versus 38% [95% CI = 34%–41%], p<0.003). Adverse outcome was independently associated with MDR TB (odds ratio [OR] = 8.4 [95% CI = 4.7–15], p<0.001), previous TB (OR = 2.1 [95% CI = 1.3–3.5], p = 0.005), days too unwell to work pre-treatment (OR = 1.01 [95% CI = 1.00–1.01], p = 0.02), and catastrophic costs (OR = 1

  5. [The relationship between multi-drug resistance and proportion of leukemia stem cells and expression of drug transporters in drug-resistant leukemia K562/ADM cells].

    PubMed

    Yi, Juan; Chen, Jing; Sun, Jing; Wei, Hu-Lai

    2009-07-07

    To investigate the drug resistance, proportion of leukemia stem cells (LSC) and expression of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) in drug-sensitive and multidrug-resistant leukemia cell population. The multidrug-resistant leukemia K562/ADM cell and its parental K562 cell were used as the model cells. The drug sensitivity was tested with a MTT assay. Flow cytometry was employed to detect the immunophenotype of stem cells and the expression of P-gp and BCRP. The self-renewal and proliferating potential were examined with methylcellulose colony-forming unit assay. K562/ADM cells were highly resistant to adriamycin, daunorubicin and etoposide. The amount of CD34+, CD123+ and CD34+ CD38- cells in K562/ADM cells was much higher than that in K562 cells, and the proportion of CD34+ CD38- CD123+ cells (LSC) in K562/ADM cells was (5.23 +/- 0.21)% versus (1.27 + 0.17)% in K562 cells, which was 4.12-fold higher than that in K562 cells. Both P-gp and BCRP were overexpressed in K562/ADM cells relative to K562 cells, and the K562/ADM cells coexpressing P-gp and BCRP were 11.25-fold higher over K562 cells. The proportion of CD34+ CD38- CD123+ BCRP+ and CD34+ CD38- P-gp+ BCRP+ cells in K562/ADM cells were (4.13 +/- 0.40)% and (5.80 +/- 1.19)% respectively, which were 3.66- and 11.37-fold higher than the same cells in K562 cells [(1.13 +/- 0.15)% and (0.51 +/- 0.01)%]. Furthermore, drug-resistant K562/ADM cells displayed 4.17-time greater colony-forming ability over the parent K562 cells, corresponding to the proportion of LSCs in K562/ADM cells. The ABC transporters-overexpressing LSC population exists in drug-resistant leukemic K562/ADM cells relative to drug-sensitive K562 cells, and the drug-resistant LSCs may be the source of chemotherapeutic resistance of leukemia.

  6. Serotypes and antibiotic resistance in Group B streptococcus isolated from patients at the Maternity Hospital, Kuwait.

    PubMed

    Boswihi, Samar S; Udo, Edet E; Al-Sweih, Noura

    2012-01-01

    A total of 143 group B streptococcus (GBS) isolates collected from mothers at the Maternity Hospital in Kuwait were investigated for their serotypes and antibiotic resistance, and screened by PCR for the carriage of genes for resistance to tetracycline (tetk, tetM, tetL, tetO), erythromycin (ermA, ermB, ermC, ermTR, ermM, mefA, mefE, msrA) and aminoglycosides (aph3, ant4, ant6). All isolates were serotyped using a latex agglutination test. Most of the isolates belonged to serotypes V (38.5 %), III (20.9 %), Ia (7.7 %) and II (11.2 %). Sixteen isolates (11.2 %) were nontypable. All isolates were susceptible to penicillin, ampicillin and cefotaxime (MICs 0.016-0.094 µg ml(-1)) but were resistant to trimethoprim (92.3 %), tetracycline (89.5 %), minocycline (89.5 %), high-level kanamycin (76.9 %), chloramphenicol (30.0 %), erythromycin (12.6 %), clindamycin (7.0 %), high-level streptomycin (3.5 %) and ciprofloxacin (0.7 %). The tetracycline-resistant isolates contained tetM (94.5 %), tetO (3.9 %), tetL (1.6 %) and tetK (0.8 %). The erythromycin-resistant isolates contained ermB (61.1 %), ermTR (38.9 %), ermA (5.5 %), mefA (5.5 %) and mefE (11 %). All high-level kanamycin-resistant isolates contained aph3. One of the high-level streptomycin-resistant isolates contained ant6. Partial DNA sequencing of aph3 revealed sequences with 99 % similarity to aph3 found in Enterococcus faecium, Enterococcus faecalis, Staphylococcus aureus and Staphylococcus epidermidis, suggesting that the GBS isolates could have acquired aph3 from other Gram-positive cocci. The high proportion of isolates with resistance to tetracycline, high-level kanamycin and trimethoprim, and the increase in the prevalence of erythromycin resistance, represents an emerging public health concern that needs further surveillance.

  7. Nasal carriage of multi-drug resistant Panton-Valentine leucocidin-positive methicillin-resistant Staphylococcus aureus in children in Tripoli-Libya.

    PubMed

    Al-haddad, Omaima H; Zorgani, Abdulaziz; Ghenghesh, Khalifa Sifaw

    2014-04-01

    Methicillin-resistant Staphylococcus aureus (MRSA) colonized children are at an increased risk of developing infections than methicillin-sensitive S. aureus colonized children. Nasal specimens from inpatient children, mothers of inpatient children, healthcare workers, and outpatient children at Tripoli Children Hospital (TCH) were examined for MRSA by chromogenic MRSA ID medium. Susceptibility of MRSA isolates to antibiotics was determined by the disc diffusion method. The nasal carriage rate of MRSA among inpatient children (8.3%, 24 of 289), their mothers (11%, 22 of 200), and healthcare workers (12.4%, 22 of 178) was significantly higher than among outpatient children (2.2%, 2 of 91) (P < 0.05, P < 0.02, and P < 0.006, respectively). Of the examined MRSA isolates (N = 35) 10 (28.6%) were positive for Panton-Valentine leucocidin genes by polymerase chain reaction. Multidrug resistance was found in 24.3% (17 of 70) of MRSA isolates. Nasal carriage of multidrug-resistant Panton-Valentine leucocidin-positive MRSA is not uncommon among inpatient children and their mothers in Tripoli.

  8. Multidrug Resistance in Non-PCV13 Serotypes of Streptococcus pneumoniae in Northern Japan, 2014.

    PubMed

    Kawaguchiya, Mitsuyo; Urushibara, Noriko; Kobayashi, Nobumichi

    2017-03-01

    Since the implementation of routine PCV13 immunization in Japan, nonvaccine serotypes (NVTs) have been increasing among clinical isolates of Streptococcus pneumoniae. In this study, susceptibility to 18 antibiotics was tested for all the 231 isolates with NVTs, which were collected from children <16 years of age in northern Japan in 2014 (July-November). High resistance rates were observed for macrolides (>90.9%), tetracycline (91.3%), and clindamycin (75.3%), while penicillin (PEN) nonsusceptibility (PNSP; MIC ≥0.12 μg/ml) was detected in 42.9% of the pneumococci [39.4%; PEN-intermediate S. pneumoniae (PISP), 3.5%; PEN-resistant S. pneumoniae (PRSP)]. All serotype 15A isolates were PRSP (MIC, ≥2 μg/ml) or PISP, and PNSP was prevalent in also serotypes 23A (96.9%), 6C (41%), and 35B (33.3%). Overall, 42.0% of the isolates showed multidrug resistance (MDR). Sequence types (STs) determined for 20 PNSP isolates with NVTs were ST63 (15A), STs 242 or 5832 (6C), STs 338 or 5242 (23A), and ST558 (35B). All the PNSP isolates possessed tet(M), and erm(B) or mefA(A/E), and 70% of them were gPRSP having three altered genes pbp1a, pbp2x, and pbp2b. Among alterations in transpeptidase-coding region of penicillin-binding proteins (PBPs), two substitutions of T371S in the STMK motif and TSQF574-577NTGY in PBP1a were common to all PRSP isolates. The present study showed the spread of PNSP in NVTs 15A, 23A, 6C, and 35B, and the emergence of the MDR international clone Sweden(15A)-ST63 in northern Japan.

  9. Prevalence, serotype distribution, and antimicrobial resistance of Salmonella isolated from food products in Morocco.

    PubMed

    Amajoud, Nadia; Bouchrif, Brahim; El Maadoudi, Mohammed; Skalli Senhaji, Nadia; Karraouan, Bouchra; El Harsal, Abdeltif; El Abrini, Jamal

    2017-02-28

    Salmonellosis is one of the most common foodborne diseases worldwide. The irrational use of antibiotics in medicine and in animal feed has greatly promoted the emergence and spread of resistant strains of non-typhoidal Salmonella. A total of 464 food products were collected in Tetouan from January 2010 to December 2012. The isolation and identification of Salmonella were performed according to Moroccan standard 08.0.116. All isolates were serotyped and were then tested for antibiotic resistance using the disk diffusion method. The microbiological analysis showed that 10.3% of food samples were contaminated with Salmonella. Eleven serotypes were identified: Kentucky 22.9% (11/48), Agona 16.7% (8/48), Reading 12.5% (6/48), Corvallis 8.3% (4/48), Saintpaul 8.3% (4/48), Typhimurium 6.2% (3/48), Montevideo 6.2% (3/48), Enteritidis 4.2% (2/48), and 2% (1/48) for each of Israel, Hadar, and Branderup. Drug susceptibility testing showed that 39.6% of Salmonella were resistant to at least one antibiotic and 60.4% were susceptible to all tested antibiotics. The highest percentage of resistance was found to the following antimicrobial agents: nalidixic acid (27.1%), sulfonamides (25%), amoxicillin (12.5%), amoxicillin/clavulanic acid 12.5%, trimethoprim (10.4%), cephalothin (4.2%), and chloramphenicol (2.1%). This study revealed a relatively high prevalence of Salmonella in food products in Tetouan and a large percentage of drug-resistant strains. Hygienic measures should be rigorously implemented, and monitoring resistance of Salmonella is required to reduce the risks related to the emergence of multi-resistant bacteria.

  10. Telithromycin Susceptibility and Genomic Diversity of Macrolide-Resistant Serotype III Group B Streptococci Isolated in Perinatal Infections

    PubMed Central

    Bingen, Edouard; Doit, Catherine; Bidet, Philippe; Brahimi, Naima; Deforche, Dominique

    2004-01-01

    We studied the telithromycin, erythromycin, azithromycin, and clindamycin susceptibilities of serotype III macrolide-resistant group B streptococci, together with genetic mechanisms of resistance and genomic diversity. ermB, ermA, and mefA were found in, respectively, 57, 32, and 9% of isolates. The telithromycin MIC at which 90% of isolates were inhibited was 0.5 μg/ml. Macrolide resistance was associated with dissemination of resistance determinants among isolates of different genetic backgrounds. PMID:14742237

  11. Highly drug-resistant Salmonella enterica serotype Kentucky ST198-X1: a microbiological study.

    PubMed

    Le Hello, Simon; Harrois, Dorothée; Bouchrif, Brahim; Sontag, Lucile; Elhani, Dalèle; Guibert, Véronique; Zerouali, Khalid; Weill, François-Xavier

    2013-08-01

    Salmonella enterica is a major global food-borne pathogen, causing life-threatening infections. Ciprofloxacin and extended-spectrum cephalosporins (ESCs) are the drugs of choice for severe infections. We previously reported a ciprofloxacin-resistant S. enterica serotype Kentucky (S Kentucky) ST198-X1 strain that emerged in Egypt and spread throughout Africa and the Middle East from 2002 to 2008. We aimed to monitor recent trends in the location of transmission and antimicrobial resistance of this strain. We analysed isolates of S Kentucky collected by the French national surveillance system for salmonellosis in France from Jan 1, 2000, to Dec 31, 2011, and at two sites in Casablanca, Morocco, between Jan 1, 2003, and Dec 31, 2011. We analysed patterns of travel of patients infected with a ciprofloxacin-resistant strain of S Kentucky. We identified isolates showing resistance to ESCs or decreased susceptibility to carbapenems, characterised isolates by XbaI-pulsed field gel electrophoresis and multilocus sequence typing, and assessed mechanisms of bacterial resistance to antimicrobial drugs. 954 (1%) of 128,836 serotyped Salmonella spp isolates in France were identified as S Kentucky, as were 30 (13%) of 226 Salmonella spp isolates from Morocco. During 2000-08, 200 (40%) of 497 subculturable isolates of S Kentucky obtained in France were resistant to ciprofloxacin, compared with 376 (83%) of 455 isolates in 2009-11, suggesting a recent increase in ciprofloxacin resistance in France. Travel histories suggested S Kentucky infections originated predominantly in east Africa, north Africa, west Africa, and the Middle East, but also arose in India. We report several occurrences of acquisition of extended-spectrum β-lactamase (CTX-M-1, CTX-M-15), plasmid-encoded cephalosporinase (CMY-2), or carbapenemase (OXA-48, VIM-2) genes by ciprofloxacin-resistant isolates of S Kentucky ST198-X1 from the Mediterranean area since 2009. Many of these highly drug-resistant isolates were

  12. Evaluation of resistance mechanisms and serotype and genotype distributions of macrolide-resistant strains in clinical isolates of Streptococcus pneumoniae [corrected] in Aydın, Turkey.

    PubMed

    Telli, Murat; Eyigör, Mete; Gültekin, Berna; Aydın, Neriman

    2011-10-01

    Macrolide resistance mechanisms in 89 Streptococcus pneumoniae strains isolated from several clinical samples between February 2007 and May 2009 were investigated. Erythromycin resistance was noted in 35 (40%) S. pneumoniae strains. In these strains, the most frequent resistance phenotype was cMLS(B) (74%), and the most frequent resistance genotype was ermB (82%). Both ermB and mefA genes were positive in 20% of macrolide-resistant strains. While no resistance to vancomycin, linezolid and telithromycin was noted in 89 S. pneumoniae strains, 12 (13%) strains were penicillin resistant, 26 (30%) strains were clindamycin resistant, 35 (40%) were azithromycin resistant, 32 (36%) strains were tetracycline resistant, and 1 (1%) strain was levofloxacin resistant. The serotype distribution of 35 macrolide-resistant S. pneumoniae strains revealed that the most frequent serotype was serogroup 19 (45%). Multidrug resistance was present in 19 (86%) of 22 strains carrying only the ermB resistance gene. No clonal dissemination was noted in the macrolide-resistant pneumococcal strains. These findings suggest that macrolide resistance rates, resistance phenotype and genotype, as well as resistant serotypes of S. pneumoniae strains should be continuously monitored in our country.

  13. International spread of an epidemic population of Salmonella enterica serotype Kentucky ST198 resistant to ciprofloxacin.

    PubMed

    Le Hello, Simon; Hendriksen, Rene S; Doublet, Benoît; Fisher, Ian; Nielsen, Eva Møller; Whichard, Jean M; Bouchrif, Brahim; Fashae, Kayode; Granier, Sophie A; Jourdan-Da Silva, Nathalie; Cloeckaert, Axel; Threlfall, E John; Angulo, Frederick J; Aarestrup, Frank M; Wain, John; Weill, François-Xavier

    2011-09-01

    National Salmonella surveillance systems from France, England and Wales, Denmark, and the United States identified the recent emergence of multidrug-resistant isolates of Salmonella enterica serotype Kentucky displaying high-level resistance to ciprofloxacin. A total of 489 human cases were identified during the period from 2002 (3 cases) to 2008 (174 cases). These isolates belonged to a single clone defined by the multilocus sequence type ST198, the XbaI-pulsed-field gel electrophoresis cluster X1, and the presence of the Salmonella genomic island 1 variant SGI1-K. This clone was probably selected in 3 steps in Egypt during the 1990s and the early 2000s and has now spread to several countries in Africa and, more recently, in the Middle East. Poultry has been identified as a potential major vehicle for infection by this clone. Continued surveillance and appropriate control measures should be implemented by national and international authorities to limit the spread of this strain.

  14. Pathogenic multiple antimicrobial resistant Escherichia coli serotypes in recreational waters of Mumbai, India: a potential public health risk.

    PubMed

    Maloo, Aayushi; Fulke, Abhay B; Mulani, Najmuddin; Sukumaran, Soniya; Ram, Anirudh

    2017-03-18

    Globally, coastal waters have emerged into a pool of antibiotic resistance genes and multiple antibiotic resistant microorganisms, and pathogenicity of these resistant microorganisms in terms of serotypes and virulence genes has made the environment vulnerable. The current study underscores the presence of multiple antibiotic resistant pathogenic serotypes and pathotypes of Escherichia coli, the predominant faecal indicator bacteria (FIB), in surface water and sediment samples of famous recreational beaches (Juhu, Versova, Mahim, Dadar, and Girgaon) of Mumbai. Out of 65 faecal coliforms (FC) randomly selected, 38 isolates were biochemically characterized, serotyped (for 'O' antigen), antibiogram-phenotyped (for 22 antimicrobial agents), and genotyped by polymerase chain reaction (for virulence factors). These isolates belonged to 16 different serotypes (UT, O141, O2, O119, O120, O9, O35, O126, O91, O128, O87, O86, R, O101, O118, and O15) out of which UT (18.4%), O141 (15.7%), and O2 (13.1%) were predominant, indicating its remarkable diversity. Furthermore, the generated antibiogram profile revealed that 95% of these isolates were multiple antibiotic resistant. More than 60% of aminoglycoside-sensitive E. coli isolates exhibited resistance to penicillin, extended penicillin, quinolone, and cephalosporin classes of antibiotic while resistance to other antibiotics was comparatively less. Antibiotic resistance (AR) indexing indicated that these isolates may have rooted from a high-risk source of contamination. Preliminary findings revealed the presence of enterotoxin-encoding genes (stx1 and stx2 specific for enterohaemorrhagic E. coli and Shiga toxin-producing E. coli, heat-stable toxin enterotoxin specific for enterotoxigenic E. coli) in pathogenic serotypes. Thus, government authorities and environmental planners should create public awareness and adopt effective measures for coastal management to prevent serious health risks associated with these contaminated

  15. [Isolation of a carbapenem-resistant K1 serotype Klebsiella pneumonia strain and the study of resistance mechanism].

    PubMed

    Zhang, Rong; Wang, Xuan; Lü, Jianxin

    2014-12-16

    To study the virulence and mechanism of carbapenem resistance of a clinical isolate of carbapenem-resistant K1 serotype Klebsiella pneumonia strain. Identification of isolate was carried out with VITEK-2 compact system. Antimicrobial susceptibility was determined by E-test; Metallo β-lactamases and carbapenemases screening were conducted by imipenem-EDTA double disc synergy test and modified Hodge test, respectively.Specific polymerehse chain reaction (PCR) and DNA sequencing were preformed to detect the virulence genes including K1, K2, K5, K20, K54, K57, magA, rmpA, wcaG and a series of β-lactamase resistence genes. Conjunction experiment was also performed. The plasmids of transconjugants were submitted to PCR-based replicon typing (PBRT) method. Molecular typing was performed by multilocus sequence typing (MLST). Antimicrobial susceptibility testing revealed that the Klebsiella pneumonia strain was resistant to most of the antibiotics used in clinic. Phynotype confirmary rest revealed the production of carbapanemases, while Metallo β-lactamases were negative; PCR and DNA sequencing confirmed the isolate was positive for blaKPC-2, blaCTX-M-15, blaTEM-1, blaSHV-1 and virulence genes K1, magA, rmpA, wcaG simultaneously; blaKPC-2 was transferred from donor to Escherichia EC600 by conjunction experiment, while no virulence genes were found in the transconjugants. PBRT revealed that Frep plasmid was found in transconjugants. MLST analysis revealed that this strain belonged to ST23. K1 serotype Klebsiella pneumonia strain carries virulence genes and carbapenem resistance gene blaKPC-2, noteworthily the carbapenem resistance genes can be transferred through horizontal transmission on plasmids.

  16. A comparison of cecal colonization of Salmonella enterica serotype Typhimurium in white leghorn chicks and Salmonella-resistant mice

    PubMed Central

    Sivula, Christine P; Bogomolnaya, Lydia M; Andrews-Polymenis, Helene L

    2008-01-01

    Background Salmonellosis is one of the most important bacterial food borne illnesses worldwide. A major source of infection for humans is consumption of chicken or egg products that have been contaminated with Salmonella enterica serotype Typhimurium, however our knowledge regarding colonization and persistence factors in the chicken is small. Results We compared intestinal and systemic colonization of 1-week-old White Leghorn chicks and Salmonella-resistant CBA/J mice during infection with Salmonella enterica serotype Typhimurium ATCC14028, one of the most commonly studied isolates. We also studied the distribution of wild type serotype Typhimurium ATCC14028 and an isogenic invA mutant during competitive infection in the cecum of 1-week-old White Leghorn chicks and 8-week-old CBA/J mice. We found that although the systemic levels of serotype Typhimurium in both infected animal models are low, infected mice have significant splenomegaly beginning at 15 days post infection. In the intestinal tract itself, the cecal contents are the major site for recovery of serotype Typhimurium in the cecum of 1-week-old chicks and Salmonella-resistant mice. Additionally we show that only a small minority of Salmonellae are intracellular in the cecal epithelium of both infected animal models, and while SPI-1 is important for successful infection in the murine model, it is important for association with the cecal epithelium of 1-week-old chicks. Finally, we show that in chicks infected with serotype Typhimurium at 1 week of age, the level of fecal shedding of this organism does not reflect the level of cecal colonization as it does in murine models. Conclusion In our study, we highlight important differences in systemic and intestinal colonization levels between chick and murine serotype Typhimurium infections, and provide evidence that suggests that the role of SPI-1 may not be the same during colonization of both animal models. PMID:18922185

  17. DNA Sequence Analysis of Plasmids from Multidrug Resistant Salmonella enterica Serotype Heidelberg Isolates

    PubMed Central

    David, Donna E.; Tang, Hailin; Xu, Joshua; Nayak, Rajesh; Kaldhone, Pravin; Logue, Catherine M.; Foley, Steven L.

    2012-01-01

    Salmonella enterica serovar Heidelberg is among the most detected serovars in swine and poultry, ranks among the top five serotypes associated with human salmonellosis and is disproportionately associated with invasive infections and mortality in humans. Salmonella are known to carry plasmids associated with antimicrobial resistance and virulence. To identify plasmid-associated genes in multidrug resistant S. enterica serovar Heidelberg, antimicrobial resistance plasmids from five isolates were sequenced using the 454 LifeSciences pyrosequencing technology. Four of the isolates contained incompatibility group (Inc) A/C multidrug resistance plasmids harboring at least eight antimicrobial resistance genes. Each of these strains also carried a second resistance plasmid including two IncFIB, an IncHI2 and a plasmid lacking an identified Inc group. The fifth isolate contained an IncI1 plasmid, encoding resistance to gentamicin, streptomycin and sulfonamides. Some of the IncA/C plasmids lacked the full concert of transfer genes and yet were able to be conjugally transferred, likely due to the transfer genes carried on the companion plasmids in the strains. Several non-IncA/C resistance plasmids also carried putative virulence genes. When the sequences were compared to previously sequenced plasmids, it was found that while all plasmids demonstrated some similarity to other plasmids, they were unique, often due to differences in mobile genetic elements in the plasmids. Our study suggests that Salmonella Heidelberg isolates harbor plasmids that co-select for antimicrobial resistance and virulence, along with genes that can mediate the transfer of plasmids within and among other bacterial isolates. Prevalence of such plasmids can complicate efforts to control the spread of S. enterica serovar Heidelberg in food animal and human populations. PMID:23251446

  18. Prevalence, Serotype, and Antimicrobial Resistance of Salmonella on Broiler Carcasses Postpick and Postchill in 20 U. S. Processing Plants

    USDA-ARS?s Scientific Manuscript database

    The objective of this study was to measure the effect of broiler processing on the prevalence, serotype and antimicrobial resistance profiles of salmonellae. Twenty US commercial processing plants representing eight integrators in thirteen states were included in the survey. In each of four replic...

  19. Mobilization properties of small ColE1-like plasmids carrying kanamycin resistance gene isolated from Salmonella enterica serotypes

    USDA-ARS?s Scientific Manuscript database

    Background: Previously we isolated and characterized various groups of small kanamycin resistance (KanR) ColE1-like plasmids from different serotypes of Salmonella enterica isolates. These plasmids all carried the aph(3)-I gene encoding the aminoglycoside phosphotransferase responsible for the kanam...

  20. Development of ceftriaxone resistance in Salmonella enterica serotype Oranienburg during therapy for bacteremia.

    PubMed

    Yang, Wei-Chiun; Chan, Oi-Wa; Wu, Tsu-Lan; Chen, Chyi-Liang; Su, Lin-Hui; Chiu, Cheng-Hsun

    2016-02-01

    The majority of nontyphoid Salmonella infection is identified in children. When an invasive or severe Salmonella infection is encountered, ceftriaxone is recommended for such patients. A 2-year-old girl was hospitalized for the treatment of Salmonella bacteremia and discharged with standard ceftriaxone treatment. She was readmitted to the hospital after 2 days due to the recurrence of the Salmonella bacteremia. The study aimed to unveil the mechanism for the relapse. Six isolates (4 blood and 2 stool) were recovered from the patient, with the last two blood isolates being ceftriaxone-resistant. Pulsed-field gel electrophoresis was used for genotyping. Ceftriaxone resistance genes and transferability of the resistance plasmid were examined by molecular methods. All isolates were identified as Salmonella enterica serotype Oranienburg. Five isolates demonstrated almost identical electrophoresis patterns, except that in the two ceftriaxone-resistant isolates an extra band (>100 kb) was noted. A blaCMY-2 gene, carried by a 120-kb conjugative IncI1 plasmid of the sequence type 53, was identified in the two ceftriaxone-resistant isolates. Transfer of the resistance plasmid from one blood isolate to Escherichia coli J53 resulted in the increase of ceftriaxone minimum inhibitory concentration from 0.125 μg/mL to 32 μg/mL in the recipient. Ceftriaxone is the standard therapeutic choice for invasive or serious Salmonella infections in children. Pediatricians should be aware of the possibility of resistance development during therapy, especially in areas with a widespread of ceftriaxone resistance genes that are carried by a self-transferrable plasmid, such as the blaCMY-2-carrying IncI1 plasmid identified herein. Copyright © 2014. Published by Elsevier B.V.

  1. Patterns of multi-drug resistant bacteria at first culture from patients admitted to a third level University hospital in Calabria from 2011 to 2014: implications for empirical therapy and infection control.

    PubMed

    Reale, Mariaconcetta; Strazzulla, Alessio; Quirino, Angela; Rizzo, Claudia; Marano, Vito; Postorino, Maria Concetta; Mazzitelli, Maria; Greco, Giuseppe; Pisani, Vincenzo; Costa, Chiara; Cesana, Bruno Mario; Liberto, Maria Carla; Torti, Carlo; Focà, Alfredo

    2017-06-01

    Surveillance of antimicrobial drug resistance is fundamental to guide empirical treatment. However, the European Antimicrobial Resistance Surveillance Network provides a general picture, which might not be applicable to clinical settings that are excluded from this survey. We evaluated resistance patterns of ESKAPE isolates over a four-year period in a third level University hospital in the province of Catanzaro (Southern Italy). In this retrospective study, we evaluated the frequency of ESKAPE isolates with different resistance patterns (group 1=low-resistant bacteria; group 2=multi-drug and extremely drug-resistant bacteria; group 3=pan-resistant bacteria), stratified by year (2011, 2012, 2013 and 2014), hospital units (intensive care units, medical and surgical units) and by sample type (urine, blood, wound swabs, respiratory samples, other samples). Chi square test was applied to find differences between isolates with different resistance patterns by hospital unit and by organs and systems. Cochran-Armitage trend test was applied to assess the trend in resistance patterns during the four years analyzed. Amongst 2385 isolates, Escherichia coli (38%) was the most frequent, followed by Pseudomonas aeruginosa (15%), Klebsiella pneumoniae (14%), Staphylococcus aureus (13%), Acinetobacter baumannii (9%), Enterococcus faecalis (8%) and Enterococcus faecium (3%). From 2011 to 2014, frequency of isolates in group 2 plus 3 decreased from 23% to 14% (chi square=55.093; p<0.0001), particularly for E. coli and K. pneumoniae, but the trend increased for S. aureus (from 5% in 2011 to 10% in 2014), and remained stable for the other species. Frequency of isolates in group 2 plus 3 was higher in intensive care units for K. pneumoniae (chi square =32.292; p<0.0001), A. baumannii (chi square =6.947; p<0.0001) and S. aureus (chi square =22.079; p<0.0001). It was also higher from blood than from different sources for most species.

  2. Changing Trends in Antimicrobial Resistance and Serotypes of Streptococcus pneumoniae Isolates in Asian Countries: an Asian Network for Surveillance of Resistant Pathogens (ANSORP) Study

    PubMed Central

    Kim, So Hyun; Chung, Doo Ryeon; Thamlikitkul, Visanu; Yang, Yonghong; Wang, Hui; Lu, Min; So, Thomas Man-kit; Hsueh, Po-Ren; Yasin, Rohani M.; Carlos, Celia C.; Pham, Hung Van; Lalitha, M. K.; Shimono, Nobuyuki; Perera, Jennifer; Shibl, Atef M.; Baek, Jin Yang; Kang, Cheol-In; Ko, Kwan Soo; Peck, Kyong Ran

    2012-01-01

    Antimicrobial resistance in Streptococcus pneumoniae remains a serious concern worldwide, particularly in Asian countries, despite the introduction of heptavalent pneumococcal conjugate vaccine (PCV7). The Asian Network for Surveillance of Resistant Pathogens (ANSORP) performed a prospective surveillance study of 2,184 S. pneumoniae isolates collected from patients with pneumococcal infections from 60 hospitals in 11 Asian countries from 2008 to 2009. Among nonmeningeal isolates, the prevalence rate of penicillin-nonsusceptible pneumococci (MIC, ≥4 μg/ml) was 4.6% and penicillin resistance (MIC, ≥8 μg/ml) was extremely rare (0.7%). Resistance to erythromycin was very prevalent in the region (72.7%); the highest rates were in China (96.4%), Taiwan (84.9%), and Vietnam (80.7%). Multidrug resistance (MDR) was observed in 59.3% of isolates from Asian countries. Major serotypes were 19F (23.5%), 23F (10.0%), 19A (8.2%), 14 (7.3%), and 6B (7.3%). Overall, 52.5% of isolates showed PCV7 serotypes, ranging from 16.1% in Philippines to 75.1% in Vietnam. Serotypes 19A (8.2%), 3 (6.2%), and 6A (4.2%) were the most prominent non-PCV7 serotypes in the Asian region. Among isolates with serotype 19A, 86.0% and 79.8% showed erythromycin resistance and MDR, respectively. The most remarkable findings about the epidemiology of S. pneumoniae in Asian countries after the introduction of PCV7 were the high prevalence of macrolide resistance and MDR and distinctive increases in serotype 19A. PMID:22232285

  3. MULTI-DRUG RESISTANCE PATTERNS OF ENTERIC BACTERIA IN TWO POPULATIONS OF FREE-RANGING EASTERN BOX TURTLES (TERRAPENE CAROLINA CAROLINA).

    PubMed

    Rasmussen, Cari; Allender, Matthew C; Phillips, Christopher A; Byrd, John; Lloyd, Terrell; Maddox, Carol

    2017-09-01

    Gram-negative isolates (n = 84) from 71% of free-ranging Eastern box turtles (Terrapene carolina carolina) in Illinois and Tennessee, United States, demonstrated resistance to at least one antibiotic while 30% of isolates demonstrated resistance to two or more antibiotics. Resistance was observed against cefoxitin, amoxicillin-clavulanic acid, cefazolin, ampicillin, ticarcillin, cefovecin, and ceftiofur. Gram-positive bacteria were isolated from 49 turtles, and all were observed to be resistant to two or more antibiotics. Gram-positive isolate resistance was observed to penicillin, cefoxitin, oxacillin, clindamycin, amikacin, enrofloxacin, cefovecin, ceftiofur, cefazolin, marbofloxacin, gentamicin, erythromycin, trimethoprim-sulfamethoxazole, and chloramphenicol. Health parameters including packed cell volume, total white blood cell count (WBC), total solids (TS), and weight were not significantly different based on antibiotic resistance patterns; however, decreasing WBC and TS were observed when the number of antibiotic-resistant detections in Gram-positive bacteria increased.

  4. The global establishment of a highly-fluoroquinolone resistant Salmonella enterica serotype Kentucky ST198 strain

    PubMed Central

    Le Hello, Simon; Bekhit, Amany; Granier, Sophie A.; Barua, Himel; Beutlich, Janine; Zając, Magdalena; Münch, Sebastian; Sintchenko, Vitali; Bouchrif, Brahim; Fashae, Kayode; Pinsard, Jean-Louis; Sontag, Lucile; Fabre, Laetitia; Garnier, Martine; Guibert, Véronique; Howard, Peter; Hendriksen, Rene S.; Christensen, Jens P.; Biswas, Paritosh K.; Cloeckaert, Axel; Rabsch, Wolfgang; Wasyl, Dariusz; Doublet, Benoit; Weill, François-Xavier

    2013-01-01

    While the spread of Salmonella enterica serotype Kentucky resistant to ciprofloxacin across Africa and the Middle-East has been described recently, the presence of this strain in humans, food, various animal species (livestock, pets, and wildlife) and in environment is suspected in other countries of different continents. Here, we report results of an in-depth molecular epidemiological study on a global human and non-human collection of S. Kentucky (n = 70). We performed XbaI-pulsed field gel electrophoresis and multilocus sequence typing, assessed mutations in the quinolone resistance-determining regions, detected β-lactam resistance mechanisms, and screened the presence of the Salmonella genomic island 1 (SGI1). In this study, we highlight the rapid and extensive worldwide dissemination of the ciprofloxacin-resistant S. Kentucky ST198-X1-SGI1 strain since the mid-2000s in an increasingly large number of contaminated sources, including the environment. This strain has accumulated an increasing number of chromosomal and plasmid resistance determinants and has been identified in the Indian subcontinent, Southeast Asia and Europe since 2010. The second substitution at position 87 in GyrA (replacing the amino acid Asp) appeared helpful for epidemiological studies to track the origin of contamination. This global study provides evidence leading to the conclusion that high-level resistance to ciprofloxacin in S. Kentucky is a simple microbiological trait that facilitates the identification of the epidemic clone of interest, ST198-X1-SGI1. Taking this into account is essential in order to detect and monitor it easily and to take rapid measures in livestock to ensure control of this infection. PMID:24385975

  5. The global establishment of a highly-fluoroquinolone resistant Salmonella enterica serotype Kentucky ST198 strain.

    PubMed

    Le Hello, Simon; Bekhit, Amany; Granier, Sophie A; Barua, Himel; Beutlich, Janine; Zając, Magdalena; Münch, Sebastian; Sintchenko, Vitali; Bouchrif, Brahim; Fashae, Kayode; Pinsard, Jean-Louis; Sontag, Lucile; Fabre, Laetitia; Garnier, Martine; Guibert, Véronique; Howard, Peter; Hendriksen, Rene S; Christensen, Jens P; Biswas, Paritosh K; Cloeckaert, Axel; Rabsch, Wolfgang; Wasyl, Dariusz; Doublet, Benoit; Weill, François-Xavier

    2013-01-01

    While the spread of Salmonella enterica serotype Kentucky resistant to ciprofloxacin across Africa and the Middle-East has been described recently, the presence of this strain in humans, food, various animal species (livestock, pets, and wildlife) and in environment is suspected in other countries of different continents. Here, we report results of an in-depth molecular epidemiological study on a global human and non-human collection of S. Kentucky (n = 70). We performed XbaI-pulsed field gel electrophoresis and multilocus sequence typing, assessed mutations in the quinolone resistance-determining regions, detected β-lactam resistance mechanisms, and screened the presence of the Salmonella genomic island 1 (SGI1). In this study, we highlight the rapid and extensive worldwide dissemination of the ciprofloxacin-resistant S. Kentucky ST198-X1-SGI1 strain since the mid-2000s in an increasingly large number of contaminated sources, including the environment. This strain has accumulated an increasing number of chromosomal and plasmid resistance determinants and has been identified in the Indian subcontinent, Southeast Asia and Europe since 2010. The second substitution at position 87 in GyrA (replacing the amino acid Asp) appeared helpful for epidemiological studies to track the origin of contamination. This global study provides evidence leading to the conclusion that high-level resistance to ciprofloxacin in S. Kentucky is a simple microbiological trait that facilitates the identification of the epidemic clone of interest, ST198-X1-SGI1. Taking this into account is essential in order to detect and monitor it easily and to take rapid measures in livestock to ensure control of this infection.

  6. Serotypes, antimicrobial resistance and genotypes of Streptococcus pneumoniae associated with infections in cancer patients in Brazil.

    PubMed

    Cardoso, Nayara Torres; Santos, Bárbara Araújo; Barbosa, André Victor; Superti, Silvana Vargas; Teixeira, Lúcia Martins; Neves, Felipe Piedade Gonçalves

    2017-03-01

    We sought to characterize pneumococcal isolates associated with bacteremia, pneumonia and meningitis in cancer patients and to estimate the coverage of the available pneumococcal vaccines. Fifty isolates recovered from 49 patients attending a cancer reference center over a 1-year period were analyzed. The prevalent serotypes were: 23F (12%), 6A (8%), 3, 4, 20, and 23A (6% each). All isolates were susceptible to chloramphenicol, levofloxacin, rifampicin, and vancomycin. Resistance or reduced susceptibility to penicillin made up 14%, and one isolate was also intermediately resistant to ceftriaxone. The three (6%) erythromycin-resistant isolates presented the M or cMLSB phenotypes and harbored the mef(A/E) gene exclusively or along with the erm(B) gene. Twenty-two (44%) isolates were closely related to 11 international clones, being strongly associated with penicillin non-susceptibility. Combined immunization with the 13-valent conjugate and the 23-valent polysaccharide vaccines might contribute to reduce (76%) the burden of the pneumococcal infections in the population investigated.

  7. Serotypes and antibiotic resistance of Streptococcus pneumoniae from adenoids in preschool children with recurrent upper respiratory tract infections.

    PubMed

    Korona-Glowniak, Izabela; Niedzielski, Artur; Malm, Anna; Niedzielska, Grazyna

    2013-01-01

    We investigated children aged 2-5, who had gone adenoidectomy for recurrent and/or persistent symptoms of upper respiratory tract infections for prevalence of pneumococci in adenoid tissue. Serotypes and antibiotic resistance patterns of the isolated pneumococci were determined and also risk factors of pneumococcal colonization were defined. S. pneumoniae colonization in adenoids was found in 62 (60.2%) children. Serotypes belonged to 10-valent and 13-valent pneumococcal conjugated vaccines (PCVs) constituted 56.1% and 68.2% of the isolates, respectively. Decreased susceptibility to penicillin was found in 45.5% of isolates; pneumococci were resistant to cotrimoxazole (62.1%), tetracycline (43.9%), erythromycin (54.5%), clindamycin (54.5%) and chloramphenicol (31.8%). Multidrug resistant S. pneumoniae comprised 57.6% of the isolates. Antibiotic resistant pneumococci were mostly distributed among serotypes belonged to 10-valent and 13-valent PCVs. Good vaccine coverage among the isolated pneumococci confirmed that the introduction of PCVs in the national immunization programme may reduce the pool of resistant and multidrug resistant pneumococci in a community.

  8. 5'-Triphosphate siRNA targeting MDR1 reverses multi-drug resistance and activates RIG-I-induced immune-stimulatory and apoptotic effects against human myeloid leukaemia cells.

    PubMed

    Li, Dengzhe; Gale, Robert Peter; Liu, Yanfeng; Lei, Baoxia; Wang, Yuan; Diao, Dongmei; Zhang, Mei

    2017-07-01

    Multi-drug resistance (MDR), immune suppression and decreased apoptosis are important causes of therapy-failure in leukaemia. Short interfering RNAs (siRNAs) down-regulate gene transcription, have sequence-independent immune-stimulatory effects and synergize with other anti-cancer therapies in some experimental models. We designed a siRNA targeting MDR1 with 5'-triphosphate ends (3p-siRNA-MDR1). Treatment of leukaemia cells with 3p-siRNA-MDR1 down-regulated MDR1 expression, reduced-drug resistance and induced immune and pro-apoptotic effects in drug-resistant HL-60/Adr and K562/Adr human leukaemia cell lines. We show mechanisms-of-action of these effects involve alterations in the anti-viral cytosolic retinoic acid-inducible protein-I (RIG-I; encoded by RIG-I or DDX58) mediated type-I interferon signal induction, interferon-gamma-inducible protein 10 (IP-10; encoded by IP10 or CXCL10) secretion, major histocompatibility complex-I expression (MHC-I) and caspase-mediated cell apoptosis. 3p-siRNA-MDR1 transfection also enhanced the anti-leukaemia efficacy of doxorubicin. These data suggest a possible synergistic role for 3p-siRNA-MDR1 in anti-leukaemia therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Genetic characterization of two fully sequenced multi-drug resistant plasmids pP10164-2 and pP10164-3 from Leclercia adecarboxylata

    PubMed Central

    Sun, Fengjun; Zhou, Dongsheng; Sun, Qiang; Luo, Wenbo; Tong, Yigang; Zhang, Defu; Wang, Qian; Feng, Wei; Chen, Weijun; Fan, Yahan; Xia, Peiyuan

    2016-01-01

    We previously reported the complete sequence of the resistance plasmid pP10164-NDM, harboring blaNDM (conferring carbapenem resistance) and bleMBL (conferring bleomycin resistance), which is recovered from a clinical Leclercia adecarboxylata isolate P10164 from China. This follow-up work disclosed that there were still two multidrug-resistant (MDR) plasmids pP10164-2 and pP10164-3 coexisting in this strain. pP10164-2 and pP10164-3 were completely sequenced and shown to carry a wealth of resistance genes, which encoded the resistance to at least 10 classes of antibiotics (β-lactams. macrolides, quinolones, aminoglycosides, tetracyclines, amphenicols, quaternary ammonium compounds, sulphonamides, trimethoprim, and rifampicin) and 7 kinds of heavy mental (mercury, silver, copper, nickel, chromate, arsenic, and tellurium). All of these antibiotic resistance genes are associated with mobile elements such as transposons, integrons, and insertion sequence-based transposable units, constituting a total of three novel MDR regions, two in pP10164-2 and the other one in pP10164-3. Coexistence of three resistance plasmids pP10164-NDM, pP10164-2 and pP10164-3 makes L. adecarboxylata P10164 tend to become extensively drug-resistant. PMID:27658354

  10. The spread of multi drug resistant infections is leading to an increase in the empirical antibiotic treatment failure in cirrhosis: a prospective survey.

    PubMed

    Merli, Manuela; Lucidi, Cristina; Di Gregorio, Vincenza; Falcone, Marco; Giannelli, Valerio; Lattanzi, Barbara; Giusto, Michela; Ceccarelli, Giancarlo; Farcomeni, Alessio; Riggio, Oliviero; Venditti, Mario

    2015-01-01

    The spread of multi-resistant infections represents a continuously growing problem in cirrhosis, particularly in patients in contact with the healthcare environment. Our prospective study aimed to analyze epidemiology, prevalence and risk factors of multi-resistant infections, as well as the rate of failure of empirical antibiotic therapy in cirrhotic patients. All consecutive cirrhotic patients hospitalized between 2008 and 2013 with a microbiologically-documented infection (MDI) were enrolled. Infections were classified as Community-Acquired (CA), Hospital-Acquired (HA) and Healthcare-Associated (HCA). Bacteria were classified as Multidrug-Resistant (MDR) if resistant to at least three antimicrobial classes, Extensively-Drug-Resistant (XDR) if only sensitive to one/two classes and Pandrug-Resistant (PDR) if resistant to all classes. One-hundred-twenty-four infections (15% CA, 52% HA, 33% HCA) were observed in 111 patients. Urinary tract infections, pneumonia and spontaneous bacterial peritonitis were the more frequent. Forty-seven percent of infections were caused by Gram-negative bacteria. Fifty-one percent of the isolates were multi-resistant to antibiotic therapy (76% MDR, 21% XDR, 3% PDR): the use of antibiotic prophylaxis (OR = 8.4; 95%CI = 1.03-76; P = 0,05) and current/recent contact with the healthcare-system (OR = 3.7; 95%CI = 1.05-13; P = 0.04) were selected as independent predictors. The failure of the empirical antibiotic therapy was progressively more frequent according to the degree of resistance. The therapy was inappropriate in the majority of HA and HCA infections. Multi-resistant infections are increasing in hospitalized cirrhotic patients. A better knowledge of the epidemiological characteristics is important to improve the efficacy of empirical antibiotic therapy. The use of preventive measures aimed at reducing the spread of multi-resistant bacteria is also essential.

  11. Serotype Emergence and Genotype Distribution among Macrolide-Resistant Invasive Streptococcus Pneumoniae Isolates in the Postconjugate Vaccine (PCV-7) Era

    PubMed Central

    Liu, Zhenying; Nachamkin, Irving; Edelstein, Paul H.; Lautenbach, Ebbing

    2012-01-01

    We conducted population-based surveillance for pneumococcal bacteremia within a 5-county region surrounding Philadelphia from October 2001 through September 2008, the period following introduction of the seven-valent pneumococcal conjugate vaccine. Erythromycin resistance increased from 14.7% in 2001-2002 to 20.3% in 2007-2008, while the resistance rate to penicillin (MIC, ≥2 μg/ml) decreased from 7.2% to 4.2% during the same period. The most predominant serotypes associated with erythromycin resistance in 2007-2008 included 19A (29.7%), 15A (29.2%), 6C (10.1%), 3 (5.6%), and 6A (4.5%). The molecular mechanisms for the increasing erythromycin resistance were mainly due to the growing presence of mef(A) negative erm(B)+ and mef(A)+ erm(B)+ genotypes, which increased from 20.0% to 46.1% and from 1.8% to 19.1%, respectively, from 2001-2002 to 2007-2008. However, mef(A)-mediated erythromycin resistance decreased from 72.7% in 2001-2002 to 34.8% in 2007-2008. Serotypes related to the erm(B) gene were 15A (45.6%), 19A (20.9%), 3 (10.1%), and 6B (6.3%); serotypes related to the mef(A) gene were 6A (18.6%), 19A (15.0%), 6C (9.3%), and 14(8.4%); serotypes associated with the presence of both erm(B) and mef(A) were 19A (81.5%), 15A (7.7%), and 19F (6.2%). Pulsed-field gel electrophoresis analysis demonstrated that erythromycin-resistant isolates within the 19A serotype were genetically diverse and related to several circulating international clones. In contrast, erythromycin-resistant isolates within the 15A serotype consisted of clonally identical or closely related isolates. PMID:22123697

  12. SEROTYPES AND ANTIMICROBIAL RESISTANCE OF SALMONELLA ENTERICA ISOLATED FROM PORK, CHICKEN MEAT AND LETTUCE, BANGKOK AND CENTRAL THAILAND.

    PubMed

    Niyomdecha, Nattamon; Mungkornkaew, Narissara; Samosornsuk, Worada

    2016-01-01

    Food of animal origins, particularly pork and chicken meat, has long been recognized as major sources of human salmonellosis. There have been recent reports of human salmonellosis outbreaks due to consumption of leafy green vegetables such as lettuce. In this study, 120 (40 pork, 40 chicken meat and 40 lettuce) samples were randomly collected from retail markets in Bangkok and central Thailand during June to August 2015 for Salmonella serotype identification and antimicrobial susceptibility testing. Salmonella was found in 82%, 62% and 20% of pork, chicken meat and lettuce samples, respectively. The top 5 most common Salmonella serotypes were Panama (15%), Schwarzengrund (12%), Rissen, Anatum, and Stanley (11% each), Albany (9%), and Indiana (8%). A high percentage of Salmonella isolated from food of animal origin were resistant to multiple antimicrobial drugs, including ampicillin, chloramphenicol, nalidixic acid, sulfamethoxazole-trimethoprim, and tetracycline. From antibiogram pattern analysis, the most common serotypes constituted isolates that were multidrug resistant. The study indicates that Salmonella was still present in various kinds of food and that certain serotypes have become predominant, a phenomenon not previously reported in Thailand.

  13. β-lactam Resistance, Serotype Distribution, and Genotypes of Meningitis-causing Streptococcus pneumoniae, Rio de Janeiro, Brazil

    PubMed Central

    Barroso, David E.; Godoy, Daniel; Castiñeiras, Terezinha M. P. P.; Tulenko, Mary M.; Rebelo, Maria C.; Harrison, Lee H.

    2016-01-01

    Background Here, we report a laboratory-based study of Streptococcus pneumoniae recovered from patients with meningitis in Rio de Janeiro State, Brazil. Methods The aim of this study was to determine the evolution of β-lactam resistance, antimicrobial susceptibility pattern, serotypes, and genetic diversity of S. pneumoniae, isolated from meningitis patients between 2000 and 2008. Results A total of 264 S. pneumoniae recovered from patients between 2000 and 2008 were included. Susceptibility testing (E-test) of S. pneumoniae showed resistance to penicillin, ceftriaxone, oxacillin, cotrimoxazole, tetracycline, ofloxacin, erythromycin, chloramphenicol, and rifampicin. Penicillin resistance (PEN-R, minimal inhibitory concentration [MIC] ≥0.12 μg/mL) increased from 8% of isolates in 2000–2002, to 12% in 2003–2005, and to 20% in 2006–2008. Ceftriaxone resistance (MIC ≥1.0 μg/mL) was detected among some PEN-R isolates (13%) from 2004 onward. Within the PEN-R isolates, serotypes that are included in 10-valent pneumococcal conjugate vaccine predominated (90%), and resistance was detected mostly in isolates of serotypes 14 (61%), 23F (16%), 6B (10%), and 19F (3%). Multilocus sequence typing showed that 52% of the PEN-R isolates, and 89% of those with MICs ≥0.5 μg/mL, were sequence type (ST)-156 or single-locus variants of this ST (ST-557 or ST-4388); all of these isolates were serotype 14 and were assigned to the Spain9V-3 clone. Conclusions β-lactam resistance increased recently among cerebrospinal fluid isolates and was mainly due to the surge of the ST-4388, a previously undescribed gki single-locus variants of ST-156. Regional surveillance is shown to be essential to provide optimal antimicrobial therapy, monitor highly successful clones, and formulate adequate vaccination strategy. PMID:21860337

  14. Challenges with gonorrhea in the era of multi-drug and extensively drug resistance – are we on the right track?

    PubMed Central

    Unemo, Magnus; Golparian, Daniel; Shafer, William M

    2015-01-01

    Neisseria gonorrhoeae has retained antimicrobial resistance to drugs previously recommended for first-line empiric treatment of gonorrhea, and resistance to ceftriaxone, the last option for monotherapy, is evolving. Crucial actions to combat this developing situation include implementing response plans; considering use of dual antimicrobial regimens; enhancing surveillance of gonorrhea, gonococcal antimicrobial resistance, treatment failures and antimicrobial use/misuse and improving prevention, early diagnosis, contact tracing and treatment. The ways forward also include an intensified research to identify novel antimicrobial resistance determinants and develop and evaluate appropriate use of molecular antimicrobial resistance testing, ideally point-of-care and with simultaneous detection of gonococci, to supplement culture-based methods and ideally guide tailored treatment. It is crucial with an enhanced understanding of the dynamics of the national and international emergence, transmission and evolution of antimicrobial-resistant gonococcal strains. Genome sequencing combined with epidemiological metadata will detail these issues and might also revolutionize the molecular antimicrobial resistance testing. Ultimately, novel antimicrobials are essential and some antimicrobials in development have shown potent in vitro activity against gonococci. Several of these antimicrobials deserve further attention for potential future treatment of gonorrhea. PMID:24702589

  15. Presence of multi-drug resistant pathogenic Escherichia coli in the San Pedro River located in the State of Aguascalientes, Mexico

    PubMed Central

    Ramírez Castillo, Flor Y.; Avelar González, Francisco J.; Garneau, Philippe; Márquez Díaz, Francisco; Guerrero Barrera, Alma L.; Harel, Josée

    2013-01-01

    Contamination of surface waters in developing countries is a great concern. Treated and untreated wastewaters have been discharged into rivers and streams, leading to possible waterborne infection outbreaks and may represent a significant dissemination mechanism of antibiotic resistance genes. In this study, the water quality of San Pedro River, the main river and pluvial collector of the Aguascalientes State, Mexico was assessed. Thirty sample locations were tested throughout the River. The main physicochemical parameters of water were evaluated. Results showed high levels of fecal pollution as well as inorganic and organic matter abundant enough to support the heterotrophic growth of microorganisms. These results indicate poor water quality in samples from different locations. One hundred and fifty Escherichia coli were collected and screened by PCR for several virulence genes. Isolates were classified as either pathogenic (n = 91) or commensal (n = 59). The disc diffusion method was used to determine antimicrobial susceptibility to 13 antibiotics. Fifty-two percent of the isolates were resistant to at least one antimicrobial agent and 30.6% were multi-resistant. Eighteen E. coli strains were quinolone resistant of which 16 were multi-resistant. Plasmid-mediated quinolone resistance (PMQR) genes were detected in 12 isolates. Mutations at the Ser-83→Leu and/or Asp-87→Asn in the gyrA gene were detected as well as mutations at the Ser-80→Ile in parC. An E. coli microarray (Maxivirulence V 3.1) was used to characterize the virulence and antimicrobial resistance genes profiles of the fluoroquinolone-resistant isolates. Antimicrobial resistance genes such as blaTEM, sulI, sulII, dhfrIX, aph3 (strA), and tet (B) as well as integrons were found in fluoroquinolone (FQ) resistance E. coli strains. The presence of potential pathogenic E. coli and antibiotic resistance in San Pedro River such as FQ resistant E. coli could pose a potential threat to human and animal

  16. SEROTYPING AND ANTIMICROBIAL DRUG RESISTANCE OF SALMONELLA ISOLATED FROM LETTUCE AND HUMAN DIARRHEA SAMPLES IN BURKINA FASO.

    PubMed

    Siourimè, Somda Namwin; Isidore, Bonkoungou Ouindgueta Juste; Oumar, Traoré; Nestor, Bassolé Ismael Henri; Yves, Traoré; Nicolas, Barro; Aly, Savadogo

    2017-01-01

    In Burkina Faso dirty water in particular those of the stoppings and the gutter ones are used for vegetables irrigation in the gardens. The aim of this study was to determine the prevalence and antibiotic susceptibility of Salmonella serotypes from humans and lettuce samples inBurkina Faso. Materials and Methods:Salmonella strains isolated from patients in 2009 to 2015 and lettuce samples in 2014 in Burkina Faso were serotyped using specific antisera. All strains were subjected to a set of 14 antibiotics to study their antibiogram by using Baeur-Kirby disk diffusion method. Out of 154 Salmonella isolated, 60 were from human and 94 from lettuce samples. Serotyping revealed four different serotypes and 39% (60) untypeable strains from human and lettuce (14 and 46 strains). Salmonella serotypes from human and lettuce samples were: Paratyphi A (10% and 22%), Paratyphi B (34% and 8%), Paratyphi C (14% and 18%) and Typhi (21% and 1%). A high resistance of Salmonella Paratyphi B and Salmonella spp to tetracycline were 70% from human and 35 % from lettuce samples. Multiresistance was observed to tetracycline, chloramphenicol and amoxicillin/clavulanic-acid or ampicillin with Salmonella ParatyphiB 35% and Salmonella Typhi 33% from human samples and Salmonella spp 4% from lettuce samples. This study showed the diversity of Salmonella serotypes from both clinical and environmental samples and emergence of multiresistant Salmonella to antibiotics in Burkina Faso. A lettuce is a potential source of transmission of Salmonella causing diarrhea among human in Burkina Faso. List of non-standard Abbreviations : HDB: Hôpital du District de Bogodogo, LNSP: Laboratoire National de Santé Publique, DSG : District Sanitaire de Gourcy, DSB : District Sanitaire de Boromo.

  17. SEROTYPING AND ANTIMICROBIAL DRUG RESISTANCE OF SALMONELLA ISOLATED FROM LETTUCE AND HUMAN DIARRHEA SAMPLES IN BURKINA FASO.

    PubMed Central

    Siourimè, Somda Namwin; Isidore, Bonkoungou Ouindgueta Juste; Oumar, Traoré; Nestor, Bassolé Ismael Henri; Yves, Traoré; Nicolas, Barro; Aly, Savadogo

    2017-01-01

    Background: In Burkina Faso dirty water in particular those of the stoppings and the gutter ones are used for vegetables irrigation in the gardens. The aim of this study was to determine the prevalence and antibiotic susceptibility of Salmonella serotypes from humans and lettuce samples inBurkina Faso. Materials and Methods:Salmonella strains isolated from patients in 2009 to 2015 and lettuce samples in 2014 in Burkina Faso were serotyped using specific antisera. All strains were subjected to a set of 14 antibiotics to study their antibiogram by using Baeur–Kirby disk diffusion method. Results: Out of 154 Salmonella isolated, 60 were from human and 94 from lettuce samples. Serotyping revealed four different serotypes and 39% (60) untypeable strains from human and lettuce (14 and 46 strains). Salmonella serotypes from human and lettuce samples were: Paratyphi A (10% and 22%), Paratyphi B (34% and 8%), Paratyphi C (14% and 18%) and Typhi (21% and 1%). A high resistance of Salmonella Paratyphi B and Salmonella spp to tetracycline were 70% from human and 35 % from lettuce samples. Multiresistance was observed to tetracycline, chloramphenicol and amoxicillin/clavulanic-acid or ampicillin with Salmonella ParatyphiB 35% and Salmonella Typhi 33% from human samples and Salmonella spp 4% from lettuce samples. Conclusion: This study showed the diversity of Salmonella serotypes from both clinical and environmental samples and emergence of multiresistant Salmonella to antibiotics in Burkina Faso. A lettuce is a potential source of transmission of Salmonella causing diarrhea among human in Burkina Faso. List of non-standard Abbreviations : HDB: Hôpital du District de Bogodogo, LNSP: Laboratoire National de Santé Publique, DSG : District Sanitaire de Gourcy, DSB : District Sanitaire de Boromo PMID:28670637

  18. Synergistic effect of folate-mediated targeting and verapamil-mediated P-gp inhibition with paclitaxel -polymer micelles to overcome multi-drug resistance.

    PubMed

    Wang, Feihu; Zhang, Dianrui; Zhang, Qiang; Chen, Yuxuan; Zheng, Dandan; Hao, Leilei; Duan, Cunxian; Jia, Lejiao; Liu, Guangpu; Liu, Yue

    2011-12-01

    Multidrug resistance (MDR) in tumor cells is a significant obstacle for successful cancer chemotherapy. Overexpression of drug efflux transporters such as P-glycoprotein (P-gp) is a key factor contributing to the development of tumor drug resistance. Verapamil (VRP), a P-gp inhibitor, has been reported to be able to reverse completely the resistance caused by P-gp. For optimal synergy, the drug and inhibitor combination may need to be temporally colocalized in the tumor cells. Herein, we investigated the effectiveness of simultaneous and targeted delivery of anticancer drug, paclitaxel (PTX), along with VRP, using DOMC-FA micelles to overcome tumor drug resistance. The floate-functionalized dual agent loaded micelles resulted in the similar cytotoxicity to PTX-loaded micelles/free VRP combination and co-administration of two single-agent loaded micelles, which was higher than that of PTX-loaded micelles. Enhanced therapeutic efficacy of dual agent micelles could be ascribe to increased accumulation of PTX in drug-resistant tumor cells. We suggest that the synergistic effect of folate receptor-mediated internalization and VRP-mediated overcoming MDR could be beneficial in treatment of MDR solid tumors by targeting delivery of micellar PTX into tumor cells. As a result, the difunctional micelle systems is a very promising approach to overcome tumor drug resistance. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

  19. Altered Antibiotic Transport in OmpC Mutants Isolated from a Series of Clinical Strains of Multi-Drug Resistant E. coli

    PubMed Central

    Ceccarelli, Matteo; Mach, Tivadar; Beis, Konstantinos; Low, Alison S.; Bamford, Victoria A.; Booth, Ian R.; Bayley, Hagan; Naismith, James H.

    2011-01-01

    Antibiotic-resistant bacteria, particularly Gram negative species, present significant health care challenges. The permeation of antibiotics through the outer membrane is largely effected by the porin superfamily, changes in which contribute to antibiotic resistance. A series of antibiotic resistant E. coli isolates were obtained from a patient during serial treatment with various antibiotics. The sequence of OmpC changed at three positions during treatment giving rise to a total of four OmpC variants (denoted OmpC20, OmpC26, OmpC28 and OmpC33, in which OmpC20 was derived from the first clinical isolate). We demonstrate that expression of the OmpC K12 porin in the clinical isolates lowers the MIC, consistent with modified porin function contributing to drug resistance. By a range of assays we have established that the three mutations that occur between OmpC20 and OmpC33 modify transport of both small molecules and antibiotics across the outer membrane. This results in the modulation of resistance to antibiotics, particularly cefotaxime. Small ion unitary conductance measurements of the isolated porins do not show significant differences between isolates. Thus, resistance does not appear to arise from major changes in pore size. Crystal structures of all four OmpC clinical mutants and molecular dynamics simulations also show that the pore size is essentially unchanged. Molecular dynamics simulations suggest that perturbation of the transverse electrostatic field at the constriction zone reduces cefotaxime passage through the pore, consistent with laboratory and clinical data. This subtle modification of the transverse electric field is a very different source of resistance than occlusion of the pore or wholesale destruction of the transverse field and points to a new mechanism by which porins may modulate antibiotic passage through the outer membrane. PMID:22053181

  20. Prevalence, serotyping and antimicrobials resistance mechanism of Salmonella enterica isolated from clinical and environmental samples in Saudi Arabia.

    PubMed

    El-Tayeb, Mohamed A; Ibrahim, Abdelnasser S S; Al-Salamah, Ali A; Almaary, Khalid S; Elbadawi, Yahya B

    2017-02-14

    Salmonella is recognized as a common foodborne pathogen, causing major health problems in Saudi Arabia. Herein, we report epidemiology, antimicrobial susceptibility and the genetic basis of resistance among S. enterica strains isolated in Saudi Arabia. Isolation of Salmonella spp. from clinical and environmental samples resulted in isolation of 33 strains identified as S. enterica based on their biochemical characteristics and 16S-rDNA sequences. S. enterica serovar Enteritidis showed highest prevalence (39.4%), followed by S. Paratyphi (21.2%), S. Typhimurium (15.2%), S. Typhi and S. Arizona (12.1%), respectively. Most isolates were resistant to 1st and 2nd generation cephalosporin; and aminoglycosides. Moreover, several S. enterica isolates exhibited resistance to the first-line antibiotics used for Salmonellosis treatment including ampicillin, trimethoprim-sulfamethoxazole and chloramphenicol. In addition, the results revealed the emergence of two S. enterica isolates showing resistance to third-generation cephalosporin. Analysis of resistance determinants in S. enterica strains (n=33) revealed that the resistance to β-lactam antibiotics, trimethoprim-sulfamethoxazole, chloramphenicol, and tetracycline, was attributed to the presence of carb-like, dfrA1, floR, tetA gene, respectively. On the other hand, fluoroquinolone resistance was related to the presence of mutations in gyrA and parC genes. These findings improve the information about foodborne Salmonella in Saudi Arabia, alarming the emergence of multi-drug resistant S. enterica strains, and provide useful data about the resistance mechanisms.

  1. Chlorine Dioxide is a Better Disinfectant than Sodium Hypochlorite against Multi-Drug Resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii.

    PubMed

    Hinenoya, Atsushi; Awasthi, Sharda Prasad; Yasuda, Noritomo; Shima, Ayaka; Morino, Hirofumi; Koizumi, Tomoko; Fukuda, Toshiaki; Miura, Takanori; Shibata, Takashi; Yamasaki, Shinji

    2015-01-01

    In this study, we evaluated and compared the antibacterial activity of chlorine dioxide (ClO2) and sodium hypochlorite (NaClO) on various multidrug-resistant strains in the presence of bovine serum albumin and sheep erythrocytes to mimic the blood contamination that frequently occurs in the clinical setting. The 3 most important species that cause nosocomial infections, i.e., methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Pseudomonas aeruginosa (MDRP), and multidrug-resistant Acinetobacter baumannii (MDRA), were evaluated, with three representative strains of each. At a 10-ppm concentration, ClO2 drastically reduced the number of bacteria of all MDRP and MDRA strains, and 2 out of 3 MRSA strains. However, 10 ppm of NaClO did not significantly kill any of the 9 strains tested in 60 seconds (s). In addition, 100 ppm of ClO2 completely killed all MRSA strains, whereas 100 ppm of NaClO failed to significantly lower the number of 2 MRSA strains and 1 MDRA strain. A time-course experiment demonstrated that, within 15 s, 100 ppm of ClO2, but not 100 ppm of NaClO, completely killed all tested strains. Taken together, these data suggest that ClO2 is more effective than NaClO against MRSA, MDRP, and MDRA, and 100 ppm is an effective concentration against these multidrug-resistant strains, which cause fatal nosocomial infections.

  2. Establishment and multi drug resistance evolution of ST235 Pseudomonas aeruginosa strains in the intensive care unit of a Colombian hospital.

    PubMed

    Martinez, Elena; Pérez, Javier Escobar; Buelvas, Francisco; Tovar, Catalina; Vanegas, Natasha; Stokes, H W

    2014-12-01

    Drug resistant Pseudomonas aeruginosa represents a therapeutic challenge. To assess the diversity of P. aeruginosa antibiotic resistant variants, isolates were recovered from hospital patients in Colombia. Thirty of 60 isolates contained class 1 integrons and five were of Sequence Type ST235 having appeared in a single intensive care unit. All five possessed an unusual integron but showed differences in gene cassette content and the presence/absence of insertion sequence IS26. This showed that differences can arise rapidly, even within a single ICU. Also, the emergence of IS26 in P. aeruginosa is contributing to the evolution of resistance in this bacterium. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  3. Intrathecal/intraventricular colistin in external ventricular device-related infections by multi-drug resistant Gram negative bacteria: case reports and review.

    PubMed

    Bargiacchi, O; Rossati, A; Car, P; Brustia, D; Brondolo, R; Rosa, F; Garavelli, P L; De Rosa, F G

    2014-10-01

    We report three cases of external ventricular derivation infections caused by multidrug-resistant Gram-negative rods and treated successfully with intraventricular colistin. The intrathecal or intraventricular use of colistin have been reported in more than 100 cases without any consensus on dosage, duration and type (monotherapy or combination therapy) of treatment. Based on our comprehensive review of the relevant literature relating to both clinical and pharmacokinetic data, we conclude that the intrathecal/intraventricular administration of colistin is a safe and effective option to treat central nervous system infections caused by multidrug-resistant Gram-negative bacteria.

  4. Tenofovir Alafenamide as Part of a Salvage Regimen in A Patient with Multi-Drug Resistant HIV and Tenofovir DF-Associated Renal Tubulopathy

    PubMed Central

    Mikula, James M.; Manion, Maura M.; Maldarelli, Frank; Suarez, Lucila M.; Norman-Wheeler, Jaha F.; Ober, Alex G.; Dewar, Robin L.; Kopp, Jeffrey B.; Lane, H. Clifford; Pau, Alice K.

    2016-01-01

    Brief Summary We describe a patient with two recent episodes of tenofovir disoproxil fumarate (TDF)-associated acute kidney injury and six-class drug-resistant HIV infection who achieved and maintained viral suppression without worsening kidney function on a regimen including tenofovir alafenamide (TAF) through 48 weeks of therapy. The safety and efficacy of TAF in patients with TDF-associated renal tubulopathy and multiple drug resistance HIV has not yet been described. TAF may represent a useful option to maximally suppress HIV in patients with these complications. PMID:26954372

  5. Antibacterial activities of multi drug resistant Myroides odoratimimus bacteria isolated from adult flesh flies (Diptera: sarcophagidae) are independent of metallo beta-lactamase gene

    PubMed Central

    Dharne, M.S.; Gupta, A.K.; Rangrez, A.Y.; Ghate, H.V.; Patole, M.S.; Shouche, Y.S.

    2008-01-01

    Flesh flies (Diptera: Sarcophagidae) are well known cause of myiasis and their gut bacteria have never been studied for antimicrobial activity against bacteria. Antimicrobial studies of Myroides spp. are restricted to nosocomial strains. A Gram-negative bacterium, Myroides sp., was isolated from the gut of adult flesh flies (Sarcophaga sp.) and submitted to evaluation of nutritional parameters using Biolog GN, 16S rRNA gene sequencing, susceptibility to various antimicrobials by disc diffusion method and detection of metallo β-lactamase genes (TUS/MUS). The antagonistic effects were tested on Gram-negative and Gram-positive bacteria isolated from human clinical specimens, environmental samples and insect mid gut. Bacterial species included were Aeromonas hydrophila, A. culicicola, Morganella morganii subsp. sibonii, Ochrobactrum anthropi, Weissella confusa, Escherichia coli, Ochrobactrum sp., Serratia sp., Kestersia sp., Ignatzschineria sp., Bacillus sp. The Myroides sp. strain was resistant to penicillin-G, erythromycin, streptomycin, amikacin, kanamycin, gentamycin, ampicillin, trimethoprim and tobramycin. These strain showed antibacterial action against all bacterial strains except W. confusa, Ignatzschineria sp., A. hydrophila and M. morganii subsp. sibonii. The multidrug resistance of the strain was similar to the resistance of clinical isolates, inhibiting growth of bacteria from clinical, environmental and insect gut samples. The metallo β-lactamase (TUS/MUS) genes were absent, and resistance due to these genes was ruled out, indicating involvement of other secretion machinery. PMID:24031236

  6. Multi-drug resistance and reduced susceptibility to ciprofloxacin among Salmonella enterica serovar Typhi isolates from the Middle East and Central Asia

    PubMed Central

    Rahman, B A; Wasfy, M O; Maksoud, M A; Hanna, N; Dueger, E; House, B

    2014-01-01

    Typhoid fever is common in developing countries, with an estimated 120 million infections and 700 000 annual deaths, worldwide. Fluoroquinolones have been the treatment of choice for infection with multidrug-resistant (MDR) Salmonella enterica serovar Typhi (S. Typhi). However, alarming reports of fluoroquinolone-resistance and failure of typhoid fever treatment have recently been published. To determine the proportion of S. Typhi isolates with reduced susceptibility to ciprofloxacin (RSC) from six countries in the Middle East and Central Asia, 968 S. Typhi isolates collected between 2002 and 2007 from Egypt, Uzbekistan, Pakistan, Qatar, Jordan and Iraq were tested for antibiotic susceptibility to five antibiotics using the disc-diffusion method. MDR was defined as resistance to amicillin, chloramphenicol and trimethoprim-sulfamethoxazole. The E-test was employed to determine the MIC of ciprofloxacin only. Nalidixic acid resistance was evaluated as a marker for RSC. Interpretations were made according to CLSI guidelines. MDR strains were considerably more prevalent in Iraq (83%) and Pakistan (52%) compared with the other countries studied (13–52%). Nearly all isolates were susceptible (99.7%) to ceftriaxone. RSC was detected in a total of 218 isolates (22%), mostly from Iraq (54/59, 92%), Uzbekistan (98/123, 80%), Qatar (23/43, 54%) and Pakistan (31/65, 47%). Many of these (21%) were also MDR. Use of nalidixic acid resistance as an indicator for RSC was 99% sensitive and 98% specific. This study reinforces the need for routine antimicrobial susceptibility surveillance of enteric fever isolates and close review of current therapeutic policies in the region. PMID:25356352

  7. Serotype distribution and antibiotic resistance of Salmonella in food-producing animals in Shandong province of China, 2009 and 2012.

    PubMed

    Lai, Jing; Wu, Congming; Wu, Chenbin; Qi, Jing; Wang, Yang; Wang, Hongyu; Liu, Yuqing; Shen, Jianzhong

    2014-06-16

    The aims of this study were to investigate the serotype distribution, genetic relationships and antibiotic resistance of Salmonella from food-producing animals in Shandong province of China in 2009 and 2012. A total of 362 out of 1825 samples from chickens, 53 out of 445 samples from ducks, and 50 out of 692 samples from pigs were positive for Salmonella. Isolates were subjected to serotyping, antibiotic susceptibility testing (15 antibiotics) and pulsed-field gel electrophoresis (PFGE). The most common serotypes recovered in the chicken samples were Enteritidis (n=294, 81.2%) and Indiana (n=45, 12.4%). For ducks, Cremieu (n=25, 47.2%), Indiana (n=13, 24.5%) and Typhimurium (n=9, 17%) were frequently isolated. In the pig samples, Derby (n=29, 58%), Typhimurium (n=9, 18%), and Enteritidis (n=6, 12%) were the most common serovars. PFGE results indicated that clonal dissemination of each serovar was prevalent, and that the Salmonella found on the poultry carcasses was caused by cross-contamination in the abattoirs. More than 99% of the Salmonella isolates collected were resistant to at least one antibiotic. The Salmonella resistance rates for 15 antibiotics in 2012 were significantly higher than those in 2009. In 2012, the highest resistance was to nalidixic acid (95.9%), followed by sulphafurazole (78.2%) and ampicillin (72.3%); the lowest levels of resistance were to kanamycin (40.1%) and amikacin (38.7%). Additionally, 41.5% and 42.2% of the Salmonella were resistant to ciprofloxacin and ceftiofur, respectively. Noticeably, 25% of the serovar Enteritidis and all of the serovar Indiana were resistant to at least 10 antibiotics in 2012. The increasing trend of antibiotic resistance in Shandong province indicates the need for more careful use of antibiotics.

  8. Complete Sequences of Six IncA/C Plasmids of Multidrug-Resistant Salmonella enterica subsp. enterica Serotype Newport.

    PubMed

    Cao, Guojie; Allard, Marc W; Hoffmann, Maria; Monday, Steven R; Muruvanda, Tim; Luo, Yan; Payne, Justin; Rump, Lydia; Meng, Kevin; Zhao, Shaohua; McDermott, Patrick F; Brown, Eric W; Meng, Jianghong

    2015-02-26

    Multidrug-resistant (MDR) Salmonella enterica subsp. enterica serotype Newport has been a long-standing public health concern in the United States. We present the complete sequences of six IncA/C plasmids from animal-derived MDR S. Newport ranging from 80.1 to 158.5 kb. They shared a genetic backbone with S. Newport IncA/C plasmids pSN254 and pAM04528.

  9. Synergistic interactions in two-drug and three-drug combinations (thymol, EDTA and vancomycin) against multi drug resistant bacteria including E. coli.

    PubMed

    Hamoud, Razan; Zimmermann, Stefan; Reichling, Jürgen; Wink, Michael

    2014-03-15

    Combinations of two or more drugs, which affect different targets, have frequently been used as a new approach against resistant bacteria. In our work we studied the antimicrobial activity (MIC, MBC) of individual drugs (the phenolic monoterpene thymol, EDTA and vancomycin), of two-drug interactions between thymol and EDTA in comparison with three-drug interactions with vancomycin against sensitive and resistant bacteria. Thymol demonstrated moderate bactericidal activity (MBC between 60 and 4000μg/ml) while EDTA only exhibited bacteriostatic activity over a range of 60-4000μg/ml. MICs of vancomycin were between 0.125 and 16μg/ml against Gram-positive and between 32 and 128μg/ml against Gram-negative bacteria. Checkerboard dilution and time-kill curve assays were performed to evaluate the mode of interaction of several combinations against Methicillin-resistant Staphylococcus aureus (MRSA NCTC 10442) and Escherichia coli (ATCC 25922). Checkerboard data indicate indifferent interaction against Gram-positive (FICI=1-1.3) and synergy against Gram-negative bacteria (FICI≈0.4), while time kill analyses suggest synergistic effect in different combinations against both types of bacteria. It is remarkable that the combinations could enhance the sensitivity of E. coli to vancomycin 16-fold to which it is normally insensitive. We have provided proof for the concept, that combinations of known antibiotics with modern phytotherapeutics can expand the spectrum of useful therapeutics.

  10. [Implementation of a telediagnostic system for tuberculosis and determination of multi-drug resistance based in the MODS method in Trujillo, Peru].

    PubMed