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Sample records for acquired antimicrobial resistance

  1. Identification of acquired antimicrobial resistance genes

    PubMed Central

    Zankari, Ea; Hasman, Henrik; Cosentino, Salvatore; Vestergaard, Martin; Rasmussen, Simon; Lund, Ole; Aarestrup, Frank M.; Larsen, Mette Voldby

    2012-01-01

    Objectives Identification of antimicrobial resistance genes is important for understanding the underlying mechanisms and the epidemiology of antimicrobial resistance. As the costs of whole-genome sequencing (WGS) continue to decline, it becomes increasingly available in routine diagnostic laboratories and is anticipated to substitute traditional methods for resistance gene identification. Thus, the current challenge is to extract the relevant information from the large amount of generated data. Methods We developed a web-based method, ResFinder that uses BLAST for identification of acquired antimicrobial resistance genes in whole-genome data. As input, the method can use both pre-assembled, complete or partial genomes, and short sequence reads from four different sequencing platforms. The method was evaluated on 1862 GenBank files containing 1411 different resistance genes, as well as on 23 de-novo-sequenced isolates. Results When testing the 1862 GenBank files, the method identified the resistance genes with an ID = 100% (100% identity) to the genes in ResFinder. Agreement between in silico predictions and phenotypic testing was found when the method was further tested on 23 isolates of five different bacterial species, with available phenotypes. Furthermore, ResFinder was evaluated on WGS chromosomes and plasmids of 30 isolates. Seven of these isolates were annotated to have antimicrobial resistance, and in all cases, annotations were compatible with the ResFinder results. Conclusions A web server providing a convenient way of identifying acquired antimicrobial resistance genes in completely sequenced isolates was created. ResFinder can be accessed at www.genomicepidemiology.org. ResFinder will continuously be updated as new resistance genes are identified. PMID:22782487

  2. Acquired inducible antimicrobial resistance in Gram-positive bacteria

    PubMed Central

    Chancey, Scott T; Zähner, Dorothea; Stephens, David S

    2012-01-01

    A major contributor to the emergence of antibiotic resistance in Gram-positive bacterial pathogens is the expansion of acquired, inducible genetic elements. Although acquired, inducible antibiotic resistance is not new, the interest in its molecular basis has been accelerated by the widening distribution and often ‘silent’ spread of the elements responsible, the diagnostic challenges of such resistance and the mounting limitations of available agents to treat Gram-positive infections. Acquired, inducible antibiotic resistance elements belong to the accessory genome of a species and are horizontally acquired by transformation/recombination or through the transfer of mobile DNA elements. The two key, but mechanistically very different, induction mechanisms are: ribosome-sensed induction, characteristic of the macrolide–lincosamide–streptogramin B antibiotics and tetracycline resistance, leading to ribosomal modifications or efflux pump activation; and resistance by cell surface-associated sensing of β-lactams (e.g., oxacillin), glycopeptides (e.g., vancomycin) and the polypeptide bacitracin, leading to drug inactivation or resistance due to cell wall alterations. PMID:22913355

  3. Acquired antimicrobial resistance in the intestinal microbiota of diverse cat populations.

    PubMed

    Moyaert, H; De Graef, E M; Haesebrouck, F; Decostere, A

    2006-08-01

    The aim of this study was to investigate the prevalence of acquired antimicrobial resistance in the resident intestinal microbiota of cats and to identify significant differences between various cat populations. Escherichia coli, Enterococcus faecalis, E. faecium and Streptococcus canis were isolated as faecal indicator bacteria from rectal swabs of 47 individually owned cats, 47 cattery cats and 18 hospitalised cats, and submitted through antimicrobial sensitivity tests. The results revealed that bacteria isolated from hospitalised and/or cattery cats were more frequently resistant than those from individually owned cats. E. coli isolates from hospitalised cats were particularly resistant to ampicillin, tetracycline and sulfonamide. Both enterococci and streptococci showed high resistance to tetracycline and in somewhat lesser extent to erythromycin and tylosin. Most E. faecium isolates were resistant to lincomycin and penicillin. One E. faecalis as well as one E. faecium isolate from hospitalised cats showed 'high-level resistance' (MIC > 500 microg/ml) against gentamicin, a commonly used antimicrobial agent in case of human enterococcal infections. The results of this research demonstrate that the extent of acquired antimicrobial resistance in the intestinal microbiota of cats depends on the social environment of the investigated population. It is obvious that the flora of healthy cats may act as a reservoir of resistance genes. PMID:16330058

  4. Multidrug efflux pumps as main players in intrinsic and acquired resistance to antimicrobials.

    PubMed

    Hernando-Amado, Sara; Blanco, Paula; Alcalde-Rico, Manuel; Corona, Fernando; Reales-Calderón, Jose A; Sánchez, María B; Martínez, José L

    2016-09-01

    Multidrug efflux pumps constitute a group of transporters that are ubiquitously found in any organism. In addition to other functions with relevance for the cell physiology, efflux pumps contribute to the resistance to compounds used for treating different diseases, including resistance to anticancer drugs, antibiotics or antifungal compounds. In the case of antimicrobials, efflux pumps are major players in both intrinsic and acquired resistance to drugs currently in use for the treatment of infectious diseases. One important aspect not fully explored of efflux pumps consists on the identification of effectors able to induce their expression. Indeed, whereas the analysis of clinical isolates have shown that mutants overexpressing these resistance elements are frequently found, less is known on the conditions that may trigger expression of efflux pumps, hence leading to transient induction of resistance in vivo, a situation that is barely detectable using classical susceptibility tests. In the current article we review the structure and mechanisms of regulation of the expression of bacterial and fungal efflux pumps, with a particular focus in those for which a role in clinically relevant resistance has been reported. PMID:27620952

  5. The Viriato study: update on antimicrobial resistance of microbial pathogens responsible for community-acquired respiratory tract infections in Portugal.

    PubMed

    Melo-Cristino, José; Santos, Letícia; Silva-Costa, Catarina; Friães, Ana; Pinho, Marcos D; Ramirez, Mário

    2010-06-29

    The Viriato study is a prospective, multicentre laboratory-based surveillance study of antimicrobial susceptibility in which 30 microbiology laboratories throughout Portugal are asked to isolate, identify and submit to a central laboratory for testing Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis responsible for community-acquired lower respiratory tract infections and Streptococcus pyogenes from tonsillitis. To monitor changes in antimicrobial resistance patterns of these frequent respiratory pathogens. Susceptibility was determined by disk diffusion (Kirby-Bauer) or using Etest strips following the Clinical and Laboratory Standards Institute guidelines. From 1999 to 2007 over 13 900 isolates were analysed. Among S. pneumoniae penicillin non-susceptibility decreased from 25% in 1999 to 18% in 2007 (p = 0.002) but resistance to macrolides showed a steady increase, reaching 20% in the last 6 years. Resistance to amoxicillin and the quinolones remained stable and very low (1-2%) throughout the study period. Antimicrobial resistance among H. influenzae and M. catarrhalis remained stable. The most significant resistance was to ampicillin, of 10-12% and greater than 80%, respectively, as a result of the production of beta-lactamases. Macrolide resistance among S. pyogenes was stable during 1999-2003 (20-23%) but after 2003 there was a steady decline in resistance, which in 2007 reached 10%. The Viriato surveillance study showed that penicillin remains the most active antimicrobial agent against S. pyogenes causing tonsillitis, and amoxicillin-clavulanate and the quinolones are the most active in vitro simultaneously against S. pneumoniae, H. influenzae and M. catarrhalis responsible for community-acquired lower respiratory tract infections in Portugal. PMID:20590169

  6. Antimicrobial Resistance

    MedlinePlus

    ... antibiotic are known as methicillin-resistant S. aureus or MRSA. Antibiotics and other antimicrobial drugs first became widely ... factors for infection are known as community-associated MRSA (CA-MRSA). Recently, several cases overseas and in ...

  7. Antimicrobial (Drug) Resistance

    MedlinePlus

    ... Antimicrobial (Drug) Resistance Antibiotic-Resistant Mycobacterium tuberculosis (TB) Methicillin-Resistant Staphylococcus aureus (MRSA) Vancomycin-Resistant Enterococci (VRE) Multidrug-Resistant Neisseria ...

  8. Animation of Antimicrobial Resistance

    MedlinePlus

    ... major obstacles to understanding the issue of antimicrobial resistance is that the subject material appears abstract and is complex. This video was designed to make the concept of antimicrobial resistance more real and understandable to veterinarians, livestock producers, ...

  9. Trends towards lower antimicrobial susceptibility and characterization of acquired resistance among clinical isolates of Brachyspira hyodysenteriae in Spain.

    PubMed

    Hidalgo, Álvaro; Carvajal, Ana; Vester, Birte; Pringle, Märit; Naharro, Germán; Rubio, Pedro

    2011-07-01

    The antimicrobial susceptibility of clinical isolates of Brachyspira hyodysenteriae in Spain was monitored, and the underlying molecular mechanisms of resistance were investigated. MICs of tylosin, tiamulin, valnemulin, lincomycin, and tylvalosin were determined for 87 B. hyodysenteriae isolates recovered from 2008 to 2009 by broth dilution. Domain V of the 23S rRNA gene and the ribosomal protein L3 gene were sequenced in 20 isolates for which the tiamulin MIC was ≥ 4 μg/ml, presenting decreased susceptibility, and in 18 tiamulin-susceptible isolates (MIC ≤ 0.125 μg/ml), and all isolates were typed by multiple-locus variable-number tandem repeats analysis. A comparison with antimicrobial susceptibility data from 2000 to 2007 showed an increase in pleuromutilin resistance over time, doubling the number of isolates with decreased susceptibility to tiamulin. No alteration in susceptibility was detected for lincomycin, and the MIC of tylosin remained high (MIC(50) > 128 μg/ml). The decreased susceptibility to tylosin and lincomycin can be explained by mutations at position A2058 of the 23S rRNA gene (Escherichia coli numbering). A2058T was the predominant mutation, but A2058G also was found together with a change of the neighboring base pair at positions 2057 to 2611. The role of additional point mutations in the vicinity of the peptidyl transferase center and mutations in the L3 at amino acids 148 and 149 and their possible involvement in antimicrobial susceptibility are considered. An association between G2032A and high levels of tiamulin and lincomycin MICs was found, suggesting an increasing importance of this mutation in antimicrobial resistance of clinical isolates of B. hyodysenteriae. PMID:21555771

  10. Antimicrobial Resistance

    MedlinePlus

    ... and health professionals can play their part; rewarding innovation and development of new treatment options and other ... and industry can help tackle resistance by: fostering innovation and research and development of new vaccines, diagnostics, ...

  11. Intrinsic and acquired resistance mechanisms in enterococcus

    PubMed Central

    Hollenbeck, Brian L.; Rice, Louis B.

    2012-01-01

    Enterococci have the potential for resistance to virtually all clinically useful antibiotics. Their emergence as important nosocomial pathogens has coincided with increased expression of antimicrobial resistance by members of the genus. The mechanisms underlying antibiotic resistance in enterococci may be intrinsic to the species or acquired through mutation of intrinsic genes or horizontal exchange of genetic material encoding resistance determinants. This paper reviews the antibiotic resistance mechanisms in Enterococcus faecium and Enterococcus faecalis and discusses treatment options. PMID:23076243

  12. Antimicrobial activity of tigecycline against community-acquired methicillin-resistant Staphylococcus aureus isolates recovered from North American medical centers.

    PubMed

    Mendes, Rodrigo E; Sader, Helio S; Deshpande, Lalitagauri; Jones, Ronald N

    2008-04-01

    A total of 1989 community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) were susceptibility tested by broth microdilution. Pulsed-field gel electrophoresis, SCCmec type, and polymerase chain reaction for Panton-Valentine leukocidin (PVL) genes were also performed. The overall tigecycline susceptibility rate was 98.2%. Glycopeptides, quinupristin/dalfopristin, linezolid, and chloramphenicol were also active against this collection (< or =0.7% resistant). The vast majority (70.8%) of the CA-MRSA was SCCmec type IV, from which 88.4% belonged to the USA300-0114 clone and 94.7% were PVL positive. Tigecycline showed in vitro activity comparable with other highly active parenteral agents and represents an option for treating complicated infections caused by CA-MRSA. PMID:18068326

  13. USDA Data on Antimicrobial Resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antimicrobial susceptibility testing remains an important tool as investigators devise ways to arrest the development of antimicrobial resistance, particularly in food borne bacteria. In 1996, the Food and Drug Administration (FDA) initiated the National Antimicrobial Resistance Monitoring System -...

  14. Increasing antimicrobial resistance in Escherichia coli isolates from community-acquired urinary tract infections during 1998-2003 in Manisa, Turkey.

    PubMed

    Kurutepe, Semra; Surucuoglu, Suheyla; Sezgin, Cenk; Gazi, Horu; Gulay, Mehmet; Ozbakkaloglu, Beril

    2005-06-01

    Urinary tract infections are among the most common infections with an increasing resistance to antimicrobials. The aim of this study was to determine the change in antimicrobial susceptibility of Escherichia coli isolates from patients with community-acquired urinary tract infection (UTI) for the years 1998 through 2003 and to suggest that the current empirical antibiotic therapy used for these patients is inappropriate. During the study period, 7,335 community urine samples of which 1,203 (16.4%) grew bacterial isolates were analyzed. Among the total of 1,203 isolates, 880 (73.2%) were E. coli. The range of resistance of E. coli to ampicillin was 47.8 to 64.6% and that to trimethoprim-sulfamethoxazole was 37.1 to 44.6% during the study period. The susceptibility pattern of E. coli to nitrofurantoin and cefuroxime did not vary significantly over the 6-year period. There was a significant increase in the susceptibility of E. coli to ciprofloxacin (11.3 - 26.7%), amoxicillin-clavulanate (18.4 - 29.2%) and gentamicin (7.0 - 25.6%) (P < 0.05). Empirical initial treatment with ampicillin and trimethoprim-sulfamethoxazole was thus inadequate in approximately half of UTI cases in our region. PMID:15973007

  15. Acquired Antibiotic Resistance Genes: An Overview

    PubMed Central

    van Hoek, Angela H. A. M.; Mevius, Dik; Guerra, Beatriz; Mullany, Peter; Roberts, Adam Paul; Aarts, Henk J. M.

    2011-01-01

    In this review an overview is given on antibiotic resistance (AR) mechanisms with special attentions to the AR genes described so far preceded by a short introduction on the discovery and mode of action of the different classes of antibiotics. As this review is only dealing with acquired resistance, attention is also paid to mobile genetic elements such as plasmids, transposons, and integrons, which are associated with AR genes, and involved in the dispersal of antimicrobial determinants between different bacteria. PMID:22046172

  16. Antimicrobial Drugs in Fighting against Antimicrobial Resistance

    PubMed Central

    Cheng, Guyue; Dai, Menghong; Ahmed, Saeed; Hao, Haihong; Wang, Xu; Yuan, Zonghui

    2016-01-01

    The outbreak of antimicrobial resistance, together with the lack of newly developed antimicrobial drugs, represents an alarming signal for both human and animal healthcare worldwide. Selection of rational dosage regimens for traditional antimicrobial drugs based on pharmacokinetic/pharmacodynamic principles as well as development of novel antimicrobials targeting new bacterial targets or resistance mechanisms are key approaches in tackling AMR. In addition to the cellular level resistance (i.e., mutation and horizontal gene transfer of resistance determinants), the community level resistance (i.e., bilofilms and persisters) is also an issue causing antimicrobial therapy difficulties. Therefore, anti-resistance and antibiofilm strategies have currently become research hotspot to combat antimicrobial resistance. Although metallic nanoparticles can both kill bacteria and inhibit biofilm formation, the toxicity is still a big challenge for their clinical applications. In conclusion, rational use of the existing antimicrobials and combinational use of new strategies fighting against antimicrobial resistance are powerful warranties to preserve potent antimicrobial drugs for both humans and animals. PMID:27092125

  17. Superior in vitro activity of carbapenems over anti-methicillin-resistant Staphylococcus aureus (MRSA) and some related antimicrobial agents for community-acquired MRSA but not for hospital-acquired MRSA.

    PubMed

    Takano, Tomomi; Higuchi, Wataru; Yamamoto, Tatsuo

    2009-02-01

    Eighty-eight strains of Panton-Valentine leukocidin (PVL)-positive and -negative community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) and 152 strains of hospital-acquired MRSA (HA-MRSA) were examined for susceptibility to carbapenems, oxacillin, and other antimicrobial agents. CA-MRSA strains were more susceptible to carbapenems (MIC(90), 1-4 microg/ml) than HA-MRSA strains (MIC(90), 32-64 microg/ml). Among the carbapenems examined, CA-MRSA strains were most susceptible to imipenem (MIC(50), 0.12 microg/ml; MIC(90), 1 microg/ml). A similar tendency was observed with oxacillin, but less markedly (MIC(90): 32 microg/ml for CA-MRSA and > or =256 microg/ml for HA-MRSA). This difference was also observed between CA-MRSA and HA-MRSA in susceptibility levels to cephems, erythromycin, clindamycin, and levofloxacin, but not to ampicillin, vancomycin, teicoplanin, linezolid, and arbekacin. The data indicate that, in terms of MIC(50) or MIC(90) values, CA-MRSA is 64-256 times more susceptible to imipenem than HA-MRSA, and for CA-MRSA, some carbapenems, e.g., imipenem, show better in vitro activity than anti-MRSA or some related agents. PMID:19280303

  18. Antimicrobial Resistance in Agriculture

    PubMed Central

    Thanner, Sophie; Drissner, David

    2016-01-01

    ABSTRACT In this article, the current knowledge and knowledge gaps in the emergence and spread of antimicrobial resistance (AMR) in livestock and plants and importance in terms of animal and human health are discussed. Some recommendations are provided for generation of the data required in order to develop risk assessments for AMR within agriculture and for risks through the food chain to animals and humans. PMID:27094336

  19. Health and economic impacts of antimicrobial resistance.

    PubMed

    Holmberg, S D; Solomon, S L; Blake, P A

    1987-01-01

    For comparison of the impacts of infections due to antimicrobial-resistant bacteria with those of infections due to antimicrobial-susceptible strains of the same bacteria, data were evaluated from 175 published and unpublished reports of investigations of nosocomial and community-acquired infections with selected bacteria. The evaluation of outcomes of hospital-acquired infections with resistant organisms was often confounded by risk factors also associated with poor outcomes. Nevertheless, for both nosocomial and community-acquired infections, the mortality, the likelihood of hospitalization, and the length of hospital stay were usually at least twice as great for patients infected with drug-resistant strains as for those infected with drug-susceptible strains of the same bacteria. Poor outcomes could be attributed both to the expected effects of ineffective antimicrobial therapy and to the unexpected occurrence of drug-resistant infections complicated by prior antimicrobial therapy for other medical problems. Although the adverse economic and health effects of drug-resistant bacterial infections can only be roughly quantified, it is concluded that antimicrobial resistance is an important health problem and an economic burden to society. PMID:3321356

  20. PROGRAMS FOR MONITORING ANTIMICROBIAL RESISTANCE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Use of antimicrobials has increased in both human and veterinary medicine and the emergence of resistance to antimicrobials has become a global problem. This is due, in part, to the widespread availability of antimicrobials and the efficacy they impart in control of certain infectious diseases. An...

  1. Clinical, Paraclinical, and Antimicrobial Resistance Features of Community-Acquired Acute Bacterial Meningitis at a Large Infectious Diseases Ward in Tehran, Iran.

    PubMed

    Heydari, Behrooz; Khalili, Hossein; Karimzadeh, Iman; Emadi-Kochak, Hamid

    2016-01-01

    In this study demographic, clinical, paraclinical, microbiological, and therapeutic features of patients with community-acquired acute bacterial meningitis admitted to a referral center for infectious diseases in Iran, have been evaluated. Medical records of adult (> 18 years) individuals with confirmed diagnosis of community-acquired bacterial meningitis during a 4-year period were retrospectively reviewed. All required data were obtained from patients' medical charts. Available findings about antimicrobial susceptibility of isolated bacteria from CSF and/or blood were also collected. Kirby-Bauer disc diffusion method was used to determine their antimicrobial susceptibility profile. Details of medical management including antibiotic regimen, duration, patients' outcome, and possible sequelae of meningitis were recorded. The most commonly isolated microorganism from CSF or blood of patients was Streptococcus pneumonia (33.33%) followed by Neisseria meningitidis (27.78%) and Haemophilus influenza (16.67%). The most common antimicrobial regimen was ceftriaxone plus vancomycin (69.44%) followed by ceftriaxone plus vancomycin plus ampicillin (11.11%). Neurological sequelae of meningitis including cranial nerve palsy, deafness, and hemiparesis were identified in 4 (11.11%), 2 (5.56%), and 1 (2.78%) subjects, respectively. Regarding mortality, only 3 (8.33%) patients died from bacterial meningitis and the remaining 33 individuals discharged from the hospital. In conclusion, findings of the current study demonstrated that the mean incidence of acute bacterial meningitis in a referral infectious diseases ward in Iran was 9 episodes per year. The majority cases of community-acquired acute bacterial meningitis admitted to our center had negative CSF culture and classic triad of meningitis was absent in them. PMID:27610176

  2. Clinical, Paraclinical, and Antimicrobial Resistance Features of Community-Acquired Acute Bacterial Meningitis at a Large Infectious Diseases Ward in Tehran, Iran

    PubMed Central

    Heydari, Behrooz; Khalili, Hossein; Karimzadeh, Iman; Emadi-Kochak, Hamid

    2016-01-01

    In this study demographic, clinical, paraclinical, microbiological, and therapeutic features of patients with community-acquired acute bacterial meningitis admitted to a referral center for infectious diseases in Iran, have been evaluated. Medical records of adult (> 18 years) individuals with confirmed diagnosis of community-acquired bacterial meningitis during a 4-year period were retrospectively reviewed. All required data were obtained from patients’ medical charts. Available findings about antimicrobial susceptibility of isolated bacteria from CSF and/or blood were also collected. Kirby-Bauer disc diffusion method was used to determine their antimicrobial susceptibility profile. Details of medical management including antibiotic regimen, duration, patients’ outcome, and possible sequelae of meningitis were recorded. The most commonly isolated microorganism from CSF or blood of patients was Streptococcus pneumonia (33.33%) followed by Neisseria meningitidis (27.78%) and Haemophilus influenza (16.67%). The most common antimicrobial regimen was ceftriaxone plus vancomycin (69.44%) followed by ceftriaxone plus vancomycin plus ampicillin (11.11%). Neurological sequelae of meningitis including cranial nerve palsy, deafness, and hemiparesis were identified in 4 (11.11%), 2 (5.56%), and 1 (2.78%) subjects, respectively. Regarding mortality, only 3 (8.33%) patients died from bacterial meningitis and the remaining 33 individuals discharged from the hospital. In conclusion, findings of the current study demonstrated that the mean incidence of acute bacterial meningitis in a referral infectious diseases ward in Iran was 9 episodes per year. The majority cases of community-acquired acute bacterial meningitis admitted to our center had negative CSF culture and classic triad of meningitis was absent in them. PMID:27610176

  3. The battle against multi-resistant strains: Renaissance of antimicrobial essential oils as a promising force to fight hospital-acquired infections.

    PubMed

    Warnke, Patrick H; Becker, Stephan T; Podschun, Rainer; Sivananthan, Sureshan; Springer, Ingo N; Russo, Paul A J; Wiltfang, Joerg; Fickenscher, Helmut; Sherry, Eugene

    2009-10-01

    Hospital-acquired infections and antibiotic-resistant bacteria continue to be major health concerns worldwide. Particularly problematic is methicillin-resistant Staphylococcus aureus (MRSA) and its ability to cause severe soft tissue, bone or implant infections. First used by the Australian Aborigines, Tea tree oil and Eucalyptus oil (and several other essential oils) have each demonstrated promising efficacy against several bacteria and have been used clinically against multi-resistant strains. Several common and hospital-acquired bacterial and yeast isolates (6 Staphylococcus strains including MRSA, 4 Streptococcus strains and 3 Candida strains including Candida krusei) were tested for their susceptibility for Eucalyptus, Tea tree, Thyme white, Lavender, Lemon, Lemongrass, Cinnamon, Grapefruit, Clove Bud, Sandalwood, Peppermint, Kunzea and Sage oil with the agar diffusion test. Olive oil, Paraffin oil, Ethanol (70%), Povidone iodine, Chlorhexidine and hydrogen peroxide (H(2)O(2)) served as controls. Large prevailing effective zones of inhibition were observed for Thyme white, Lemon, Lemongrass and Cinnamon oil. The other oils also showed considerable efficacy. Remarkably, almost all tested oils demonstrated efficacy against hospital-acquired isolates and reference strains, whereas Olive and Paraffin oil from the control group produced no inhibition. As proven in vitro, essential oils represent a cheap and effective antiseptic topical treatment option even for antibiotic-resistant strains as MRSA and antimycotic-resistant Candida species. PMID:19473851

  4. Engineering Antimicrobials Refractory to Resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Multi-drug resistant superbugs are a persistent problem in modern health care, demonstrating the need for a new class of antimicrobials that can address this concern. Triple-acting peptidoglycan hydrolase fusions are a novel class of antimicrobials which have qualities well suited to avoiding resis...

  5. Antimicrobial use and antimicrobial resistance in nosocomial pathogens at a tertiary care hospital in Pune

    PubMed Central

    Nair, Velu; Sharma, Dinesh; Sahni, A.K.; Grover, Naveen; Shankar, S.; Jaiswal, S.S.; Dalal, S.S.; Basannar, D.R.; Phutane, Vivek S.; Kotwal, Atul; Gopal Rao, G.; Batura, Deepak; Venkatesh, M.D.; Sinha, Tapan; Kumar, Sushil; Joshi, D.P.

    2015-01-01

    Background Resistance to antimicrobial agents is emerging in wide variety of nosocomial and community acquired pathogens. Widespread and often inappropriate use of broad spectrum antimicrobial agents is recognized as a significant contributing factor to the development and spread of bacterial resistance. This study was conducted to gain insight into the prevalent antimicrobial prescribing practices, and antimicrobial resistance pattern in nosocomial pathogens at a tertiary care hospital in Pune, India. Methods Series of one day cross sectional point prevalence surveys were carried out on four days between March and August 2014. All eligible in patients were included in the study. A structured data entry form was used to collect the data for each patient. Relevant samples were collected for microbiological examination from all the clinically identified hospital acquired infection cases. Results 41.73% of the eligible patients (95% CI: 39.52–43.97) had been prescribed at least one antimicrobial during their stay in the hospital. Beta-lactams (38%) were the most prescribed antimicrobials, followed by Protein synthesis inhibitors (24%). Majority of the organisms isolated from Hospital acquired infection (HAI cases) were found to be resistant to the commonly used antimicrobials viz: Cefotaxime, Ceftriaxone, Amikacin, Gentamicin and Monobactams. Conclusion There is need to have regular antimicrobial susceptibility surveillance and dissemination of this information to the clinicians. In addition, emphasis on the rational use of antimicrobials, antimicrobial rotation and strict adherence to the standard treatment guidelines is very essential. PMID:25859071

  6. National and Regional Assessment of Antimicrobial Resistance among Community-Acquired Respiratory Tract Pathogens Identified in a 2005-2006 U.S. Faropenem Surveillance Study▿

    PubMed Central

    Critchley, Ian A.; Brown, Steven D.; Traczewski, Maria M.; Tillotson, Glenn S.; Janjic, Nebojsa

    2007-01-01

    Surveillance studies conducted in the United States over the last decade have revealed increasing resistance among community-acquired respiratory pathogens, especially Streptococcus pneumoniae, that may limit future options for empirical therapy. The objective of this study was to assess the scope and magnitude of the problem at the national and regional levels during the 2005-2006 respiratory season (the season when community-acquired respiratory pathogens are prevalent) in the United States. Also, since faropenem is an oral penem being developed for the treatment of community-acquired respiratory tract infections, another study objective was to provide baseline data to benchmark changes in the susceptibility of U.S. respiratory pathogens to the drug in the future. The in vitro activities of faropenem and other agents were determined against 1,543 S. pneumoniae isolates, 978 Haemophilus influenzae isolates, and 489 Moraxella catarrhalis isolates collected from 104 U.S. laboratories across six geographic regions during the 2005-2006 respiratory season. Among S. pneumoniae isolates, the rates of resistance to penicillin, amoxicillin-clavulanate, and cefdinir were 16, 6.4, and 19.2%, respectively. The least effective agents were trimethoprim-sulfamethoxazole (SXT) and azithromycin, with resistance rates of 23.5 and 34%, respectively. Penicillin resistance rates for S. pneumoniae varied by region (from 8.7 to 22.5%), as did multidrug resistance rates for S. pneumoniae (from 8.8 to 24.9%). Resistance to β-lactams, azithromycin, and SXT was higher among S. pneumoniae isolates from children than those from adults. β-Lactamase production rates among H. influenzae and M. catarrhalis isolates were 27.4 and 91.6%, respectively. Faropenem MICs at which 90% of isolates are inhibited were 0.5 μg/ml for S. pneumoniae, 1 μg/ml for H. influenzae, and 0.5 μg/ml for M. catarrhalis, suggesting that faropenem shows promise as a treatment option for respiratory infections caused

  7. National and regional assessment of antimicrobial resistance among community-acquired respiratory tract pathogens identified in a 2005-2006 U.S. Faropenem surveillance study.

    PubMed

    Critchley, Ian A; Brown, Steven D; Traczewski, Maria M; Tillotson, Glenn S; Janjic, Nebojsa

    2007-12-01

    Surveillance studies conducted in the United States over the last decade have revealed increasing resistance among community-acquired respiratory pathogens, especially Streptococcus pneumoniae, that may limit future options for empirical therapy. The objective of this study was to assess the scope and magnitude of the problem at the national and regional levels during the 2005-2006 respiratory season (the season when community-acquired respiratory pathogens are prevalent) in the United States. Also, since faropenem is an oral penem being developed for the treatment of community-acquired respiratory tract infections, another study objective was to provide baseline data to benchmark changes in the susceptibility of U.S. respiratory pathogens to the drug in the future. The in vitro activities of faropenem and other agents were determined against 1,543 S. pneumoniae isolates, 978 Haemophilus influenzae isolates, and 489 Moraxella catarrhalis isolates collected from 104 U.S. laboratories across six geographic regions during the 2005-2006 respiratory season. Among S. pneumoniae isolates, the rates of resistance to penicillin, amoxicillin-clavulanate, and cefdinir were 16, 6.4, and 19.2%, respectively. The least effective agents were trimethoprim-sulfamethoxazole (SXT) and azithromycin, with resistance rates of 23.5 and 34%, respectively. Penicillin resistance rates for S. pneumoniae varied by region (from 8.7 to 22.5%), as did multidrug resistance rates for S. pneumoniae (from 8.8 to 24.9%). Resistance to beta-lactams, azithromycin, and SXT was higher among S. pneumoniae isolates from children than those from adults. beta-Lactamase production rates among H. influenzae and M. catarrhalis isolates were 27.4 and 91.6%, respectively. Faropenem MICs at which 90% of isolates are inhibited were 0.5 mug/ml for S. pneumoniae, 1 mug/ml for H. influenzae, and 0.5 mug/ml for M. catarrhalis, suggesting that faropenem shows promise as a treatment option for respiratory infections

  8. Molecular Detection of Antimicrobial Resistance

    PubMed Central

    Fluit, Ad C.; Visser, Maarten R.; Schmitz, Franz-Josef

    2001-01-01

    The determination of antimicrobial susceptibility of a clinical isolate, especially with increasing resistance, is often crucial for the optimal antimicrobial therapy of infected patients. Nucleic acid-based assays for the detection of resistance may offer advantages over phenotypic assays. Examples are the detection of the methicillin resistance-encoding mecA gene in staphylococci, rifampin resistance in Mycobacterium tuberculosis, and the spread of resistance determinants across the globe. However, molecular assays for the detection of resistance have a number of limitations. New resistance mechanisms may be missed, and in some cases the number of different genes makes generating an assay too costly to compete with phenotypic assays. In addition, proper quality control for molecular assays poses a problem for many laboratories, and this results in questionable results at best. The development of new molecular techniques, e.g., PCR using molecular beacons and DNA chips, expands the possibilities for monitoring resistance. Although molecular techniques for the detection of antimicrobial resistance clearly are winning a place in routine diagnostics, phenotypic assays are still the method of choice for most resistance determinations. In this review, we describe the applications of molecular techniques for the detection of antimicrobial resistance and the current state of the art. PMID:11585788

  9. Antimicrobial resistance in Libya: 1970–2011

    PubMed Central

    Ghenghesh, Khalifa Sifaw; Rahouma, Amal; Tawil, Khaled; Zorgani, Abdulaziz; Franka, Ezzedin

    2013-01-01

    Resistance to antimicrobial agents is a major health problem that affects the whole world. Providing information on the past state of antimicrobial resistance in Libya may assist the health authorities in addressing the problem more effectively in the future. Information was obtained mainly from Highwire Press (including PubMed) search for the period 1970–2011 using the terms ‘antibiotic resistance in Libya’, ‘antimicrobial resistance in Libya’, ‘tuberculosis in Libya’, and ‘primary and acquired resistance in Libya’ in title and abstract. From 1970 to 2011 little data was available on antimicrobial resistance in Libya due to lack of surveillance and few published studies. Available data shows high resistance rates for Salmonella species in the late 1970s and has remained high to the present day. High prevalence rates (54–68%) of methicillin-resistant Staphylococcus aureus (MRSA) were reported in the last decade among S. aureus from patients with burns and surgical wound infections. No reports were found of vancomycin-resistant S. aureus (VRSA) or vancomycin-intermediate-resistant S. aureus (VISA) using standard methods from Libya up to the end of 2011. Reported rates of primary (i.e. new cases) and acquired (i.e. retreatment cases) multidrug-resistant tuberculosis (MDR-TB) from the eastern region of Libya in 1971 were 16.6 and 33.3% and in 1976 were 8.6 and 14.7%, in western regions in 1984–1986 were 11 and 21.5% and in the whole country in 2011 were estimated at 3.4 and 29%, respectively. The problem of antibiotic resistance is very serious in Libya. The health authorities in particular and society in general should address this problem urgently. Establishing monitoring systems based on the routine testing of antimicrobial sensitivity and education of healthcare workers, pharmacists, and the community on the health risks associated with the problem and benefits of prudent use of antimicrobials are some steps that can be taken to tackle the

  10. Antimicrobial susceptibility patterns of community- and hospital-acquired methicillin-resistant Staphylococcus aureus from United States Hospitals: results from the AWARE Ceftaroline Surveillance Program (2012-2014).

    PubMed

    Sader, Helio S; Mendes, Rodrigo E; Jones, Ronald N; Flamm, Robert K

    2016-09-01

    Among 8437 methicillin-resistant Staphylococcus aureus (MRSA) isolates collected from 143 medical centers in the United States (2012-2014), 7116 and 1321 were reported as community-acquired (CA) and hospital-acquired (HA) MRSA, respectively. CA-/HA-MRSA were most often isolated from patients with skin and skin structure infections (SSSI; 68.4/26.9%), pneumonia (13.7/49.0%) and bacteremia (10.0/17.7%). Overall, susceptibility rates were generally lower among HA-MRSA compared to CA-MRSA strains, especially for clindamycin (44.6 vs. 66.1%) and levofloxacin (21.4 vs. 35.5%). Also, susceptibility rates were lower for these two compounds among isolates from pneumonia compared to SSSI and bacteremia. Ceftaroline was broadly active against 98.0% of CA-MRSA and 94.3% of HA-MRSA (MIC50/90, 1μg/mL for both; no resistant isolate) overall, with little variation among infection type subsets. PMID:27394637

  11. Antimicrobial Resistance Mechanisms among Campylobacter

    PubMed Central

    2013-01-01

    Campylobacter jejuni and Campylobacter coli are recognized as the most common causative agents of bacterial gastroenteritis in the world. Humans most often become infected by ingesting contaminated food, especially undercooked chicken, but also other sources of bacteria have been described. Campylobacteriosis is normally a self-limiting disease. Antimicrobial treatment is needed only in patients with more severe disease and in those who are immunologically compromised. The most common antimicrobial agents used in the treatment of Campylobacter infections are macrolides, such as erythromycin, and fluoroquinolones, such as ciprofloxacin. Tetracyclines have been suggested as an alternative choice in the treatment of clinical campylobacteriosis but in practice are not often used. However, during the past few decades an increasing number of resistant Campylobacter isolates have developed resistance to fluoroquinolones and other antimicrobials such as macrolides, aminoglycosides, and beta-lactams. Trends in antimicrobial resistance have shown a clear correlation between use of antibiotics in the veterinary medicine and animal production and resistant isolates of Campylobacter in humans. In this review, the patterns of emerging resistance to the antimicrobial agents useful in treatment of the disease are presented and the mechanisms of resistance to these drugs in Campylobacter are discussed. PMID:23865047

  12. ANTIMICROBIAL RESISTANCE TRENDS IN SALMONELLA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Since the early 1990’s there has been increasing awareness and concern regarding the development of antimicrobial resistance among bacteria of public health significance. Reports targeting zoonotic bacteria, and in particular Salmonella species, suggest that resistance is trending upwar...

  13. Antimicrobial resistance: a global response.

    PubMed Central

    Smith, Richard D.; Coast, Joanna

    2002-01-01

    Resistance to antimicrobial therapies reduces the effectiveness of these drugs, leading to increased morbidity, mortality, and health care expenditure. Because globalization increases the vulnerability of any country to diseases occurring in other countries, resistance presents a major threat to global public health, and no country acting on its own can adequately protect the health of its population against it. International collective action is therefore essential. Nevertheless, responsibility for health remains predominantly national. Consequently, there is a potentially significant disparity between the problems and solutions related to antimicrobial resistance and the institutions and mechanisms that are available to deal with them. This paper considers the capacity of national and international institutions and mechanisms to generate a collective response to antimicrobial resistance. Strategies for containing resistance are outlined, with particular reference to globally coordinated activities of countries. The adequacy of national and international responses to resistance is assessed, and the actions that international bodies could take to solve difficulties associated with present responses are highlighted. Approaches are suggested for securing international collective action for the containment of antimicrobial resistance. PMID:11953791

  14. Ecology of antimicrobial resistance: humans, animals, food and environment.

    PubMed

    González-Zorn, Bruno; Escudero, José A

    2012-09-01

    Antimicrobial resistance is a major health problem. After decades of research, numerous difficulties in tackling resistance have emerged, from the paucity of new antimicrobials to the inefficient contingency plans to reduce the use of antimicrobials; consequently, resistance to these drugs is out of control. Today we know that bacteria from the environment are often at the very origin of the acquired resistance determinants found in hospitals worldwide. Here we define the genetic components that flow from the environment to pathogenic bacteria and thereby confer a quantum increase in resistance levels, as resistance units (RU). Environmental bacteria as well as microbiomes from humans, animals, and food represent an infinite reservoir of RU, which are based on genes that have had, or not, a resistance function in their original bacterial hosts. This brief review presents our current knowledge of antimicrobial resistance and its consequences, with special focus on the importance of an ecologic perspective of antimicrobial resistance. This discipline encompasses the study of the relationships of entities and events in the framework of curing and preventing disease, a definition that takes into account both microbial ecology and antimicrobial resistance. Understanding the flux of RU throughout the diverse ecosystems is crucial to assess, prevent and eventually predict emerging scaffolds before they colonize health institutions. Collaborative horizontal research scenarios should be envisaged and involve all actors working with humans, animals, food and the environment. PMID:23847814

  15. [Biofilms, tolerance and antimicrobial resistance].

    PubMed

    Bahar, Gül

    2002-01-01

    Virtually every surface examined in natural, industrial and pathogenic ecosystems are colonized by biofilms consisting of adherent populations of microorganisms surrounded with a glycocalyx matrix. The development of biofilms has important economic and medical consequences. The development and use of a broad range of medical devices made us recognize a variety of infections caused by microorganisms that were regarded previously as harmless. Infections caused by biofilms are difficult to eradicate with antimicrobial treatment, and in-vitro susceptibility tests show significant resistance of biofilm cells to be killed. Advances in our understanding of biofilm formation can assist in the development of novel strategies for the prevention and treatment of infections caused by biofilms. In this review article, structures, general properties and antimicrobial resistance mechanisms of biofilms were discussed under the light of recent literature. PMID:12838670

  16. Antimicrobial (Drug) Resistance Prevention

    MedlinePlus

    ... Action Plan for Combating Antibiotic-Resistant Bacteria (PDF) ​​​​​​ Javascript Error Your browser JavaScript is turned off causing certain features of the ... incorrectly. Please visit your browser settings and turn JavaScript on. Read more information on enabling JavaScript. Skip ...

  17. Antimicrobial Resistance in the Environment.

    PubMed

    Williams, Maggie R; Stedtfeld, Robert D; Guo, Xueping; Hashsham, Syed A

    2016-10-01

    This review summarizes important publications from 2015 pertaining to the occurrence of antimicrobial resistance (AMR) in the environment. Emphasis is placed on sources of antibiotic resistance in the aquatic environment including wastewater treatment plants, hospitals, and agriculture, treatment and mitigation techniques, and surveillance and analysis methodologies for characterizing abundance data. As such, this review is organized into the following sections: i) occurrence of AMR in the environment, including surface waters, aquaculture, and wastewater ii) treatment technologies, and iii) technologies for rapid surveillance of AMR, iv) transmission between matrices, v) databases and analysis methods, and vi) gaps in AMR understanding. PMID:27620115

  18. Stress responses as determinants of antimicrobial resistance in Pseudomonas aeruginosa: multidrug efflux and more.

    PubMed

    Poole, Keith

    2014-12-01

    Pseudomonas aeruginosa is a notoriously antimicrobial-resistant organism that is increasingly refractory to antimicrobial chemotherapy. While the usual array of acquired resistance mechanisms contribute to resistance development in this organism a multitude of endogenous genes also play a role. These include a variety of multidrug efflux loci that contribute to both intrinsic and acquired antimicrobial resistance. Despite their roles in resistance, however, it is clear that these efflux systems function in more than just antimicrobial efflux. Indeed, recent data indicate that they are recruited in response to environmental stress and, therefore, function as components of the organism's stress responses. In fact, a number of endogenous resistance-promoting genes are linked to environmental stress, functioning as part of known stress responses or recruited in response to a variety of environmental stress stimuli. Stress responses are, thus, important determinants of antimicrobial resistance in P. aeruginosa. As such, they represent possible therapeutic targets in countering antimicrobial resistance in this organism. PMID:25388098

  19. The Relationship between Antimicrobial Use and Antimicrobial Resistance in Europe

    PubMed Central

    Cars, Otto; Buchholz, Udo; Mölstad, Sigvard; Goettsch, Wim; Veldhuijzen, Irene K.; Kool, Jacob L.; Sprenger, Marc J.W.; Degener, John E.

    2002-01-01

    In Europe, antimicrobial resistance has been monitored since 1998 by the European Antimicrobial Resistance Surveillance System (EARSS). We examined the relationship between penicillin nonsusceptibility of invasive isolates of Streptococcus pneumoniae (an indicator organism) and antibiotic sales. Information was collected on 1998-99 resistance data for invasive isolates of S. pneumoniae to penicillin, based on surveillance data from EARSS and on outpatient sales during 1997 for beta-lactam antibiotics and macrolides. Our results show that in Europe antimicrobial resistance is correlated with use of beta-lactam antibiotics and macrolides. PMID:11927025

  20. Can We Prevent Antimicrobial Resistance by Using Antimicrobials Better?

    PubMed Central

    Soothill, Germander; Hu, Yanmin; Coates, Anthony

    2013-01-01

    Since their development over 60 years ago, antimicrobials have become an integral part of healthcare practice worldwide. Recently, this has been put in jeopardy by the emergence of widespread antimicrobial resistance, which is one of the major problems facing modern medicine. In the past, the development of new antimicrobials kept us one step ahead of the problem of resistance, but only three new classes of antimicrobials have reached the market in the last thirty years. A time is therefore approaching when we may not have effective treatment against bacterial infections, particularly for those that are caused by Gram-negative organisms. An important strategy to reduce the development of antimicrobial resistance is to use antimicrobials more appropriately, in ways that will prevent resistance. This involves a consideration of the pharmacokinetic and pharmacodynamics properties of antimicrobials, the possible use of combinations, and more appropriate choice of antimicrobials, which may include rapid diagnostic testing and antimicrobial cycling. Examples given in this review include Mycobacterium tuberculosis, Gram-negative and Gram-positive organisms. We shall summarise the current evidence for these strategies and outline areas for future development. PMID:25437042

  1. Antimicrobial Resistance: Is the World UNprepared?

    PubMed

    2016-09-01

    Long Blurb: On September 21st 2016 the United Nations General Assembly convenes in New York, United States to tackle a looming and seemingly inevitable global challenge with the potential to threaten the health and wellbeing of all people: antimicrobial resistance. In an Editorial, the PLOS Medicine Editors reflect on the challenge of coordinating the response to antimicrobial resistance in order to ensure the viability of current antimicrobials and the development of new therapies against resistant pathogens. Short Blurb: In this month's Editorial, the PLOS Medicine Editors reflect on the upcoming United Nations General Assembly meeting which convenes to discuss the global challenge of antimicrobial resistance. PMID:27618631

  2. Correlations between Income Inequality and Antimicrobial Resistance

    PubMed Central

    Kirby, Andrew; Herbert, Annie

    2013-01-01

    Objectives The aim of this study is to investigate if correlations exist between income inequality and antimicrobial resistance. This study’s hypothesis is that income inequality at the national level is positively correlated with antimicrobial resistance within developed countries. Data collection and analysis Income inequality data were obtained from the Standardized World Income Inequality Database. Antimicrobial resistance data were obtained from the European antimicrobial Resistance Surveillance Network and outpatient antimicrobial consumption data, measured by Defined daily Doses per 1000 inhabitants per day, from the European Surveillance of antimicrobial Consumption group. Spearman’s correlation coefficient (r) defined strengths of correlations of: > 0.8 as strong, > 0.5 as moderate and > 0.2 as weak. Confidence intervals and p values were defined for all r values. Correlations were calculated for the time period 2003-10, for 15 European countries. Results Income inequality and antimicrobial resistance correlations which were moderate or strong, with 95% confidence intervals > 0, included the following. Enterococcus faecalis resistance to aminopenicillins, vancomycin and high level gentamicin was moderately associated with income inequality (r= ≥0.54 for all three antimicrobials). Escherichia coli resistance to aminoglycosides, aminopenicillins, third generation cephalosporins and fluoroquinolones was moderately-strongly associated with income inequality (r= ≥0.7 for all four antimicrobials). Klebsiella pneumoniae resistance to third generation cephalosporins, aminoglycosides and fluoroquinolones was moderately associated with income inequality (r= ≥0.5 for all three antimicrobials). Staphylococcus aureus methicillin resistance and income inequality were strongly associated (r=0.87). Conclusion As income inequality increases in European countries so do the rates of antimicrobial resistance for bacteria including E. faecalis, E. coli, K. pneumoniae

  3. Burden of Hospital Acquired Infections and Antimicrobial Use in Vietnamese Adult Intensive Care Units

    PubMed Central

    Larsson, Mattias; Nadjm, Behzad; Dinh, Quynh-Dao; Nilsson, Lennart E.; Rydell, Ulf; Le, Tuyet Thi Diem; Trinh, Son Hong; Pham, Hung Minh; Tran, Cang Thanh; Doan, Hanh Thi Hong; Tran, Nguyen Thua; Le, Nhan Duc; Huynh, Nhuan Van; Tran, Thao Phuong; Tran, Bao Duc; Nguyen, Son Truong; Pham, Thao Thi Ngoc; Dang, Tam Quang; Nguyen, Chau Van Vinh; Lam, Yen Minh; Thwaites, Guy; Van Nguyen, Kinh; Hanberger, Hakan

    2016-01-01

    Background Vietnam is a lower middle-income country with no national surveillance system for hospital-acquired infections (HAIs). We assessed the prevalence of hospital-acquired infections and antimicrobial use in adult intensive care units (ICUs) across Vietnam. Methods Monthly repeated point prevalence surveys were systematically conducted to assess HAI prevalence and antimicrobial use in 15 adult ICUs across Vietnam. Adults admitted to participating ICUs before 08:00 a.m. on the survey day were included. Results Among 3287 patients enrolled, the HAI prevalence was 29.5% (965/3266 patients, 21 missing). Pneumonia accounted for 79.4% (804/1012) of HAIs Most HAIs (84.5% [855/1012]) were acquired in the survey hospital with 42.5% (363/855) acquired prior to ICU admission and 57.5% (492/855) developed during ICU admission. In multivariate analysis, the strongest risk factors for HAI acquired in ICU were: intubation (OR 2.76), urinary catheter (OR 2.12), no involvement of a family member in patient care (OR 1.94), and surgery after admission (OR 1.66). 726 bacterial isolates were cultured from 622/1012 HAIs, most frequently Acinetobacter baumannii (177/726 [24.4%]), Pseudomonas aeruginosa (100/726 [13.8%]), and Klebsiella pneumoniae (84/726 [11.6%]), with carbapenem resistance rates of 89.2%, 55.7%, and 14.9% respectively. Antimicrobials were prescribed for 84.8% (2787/3287) patients, with 73.7% of patients receiving two or more. The most common antimicrobial groups were third generation cephalosporins, fluoroquinolones, and carbapenems (20.1%, 19.4%, and 14.1% of total antimicrobials, respectively). Conclusion A high prevalence of HAIs was observed, mainly caused by Gram-negative bacteria with high carbapenem resistance rates. This in combination with a high rate of antimicrobial use illustrates the urgent need to improve rational antimicrobial use and infection control efforts. PMID:26824228

  4. Antimicrobial (Drug) Resistance: Vancomycin-Resistant Enterococci (VRE) Frequently Asked Questions

    MedlinePlus

    ... Understanding Antimicrobial (Drug) Resistance Examples of Antimicrobial Resistance Methicillin-Resistant Staphylococcus aureus (MRSA) Vancomycin-Resistant Enterococci (VRE) Overview Transmission Diagnosis ...

  5. Antimicrobial resistance issues in beef production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antimicrobial resistance threats to human health as identified have been recognized as a critical global public health concern. Linkage of some threats to beef production is discussed. The relevance to beef production of recent government actions will be examined. Prominent antimicrobial resistance ...

  6. An Ecological Perspective on Antimicrobial Resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacteria are ubiquitous, covering every ecological niche known to man. Within these ecological niches bacterial populations adapt to ensure their survival and the development of antimicrobial resistance is an example of a bacterium's ability to adapt and survive. Resistance to antimicrobials often ...

  7. Mycoplasma bovis: Mechanisms of Resistance and Trends in Antimicrobial Susceptibility.

    PubMed

    Lysnyansky, Inna; Ayling, Roger D

    2016-01-01

    Mycoplasma bovis is a cell-wall-less bacterium and belongs to the class Mollicutes. It is the most important etiological agent of bovine mycoplasmoses in North America and Europe, causing respiratory disease, mastitis, otitis media, arthritis, and reproductive disease. Clinical disease associated with M. bovis is often chronic, debilitating, and poorly responsive to antimicrobial therapy, resulting in significant economic loss, the full extent of which is difficult to estimate. Until M. bovis vaccines are universally available, sanitary control measures and antimicrobial treatment are the only approaches that can be used in attempts to control M. bovis infections. However, in vitro studies show that many of the current M. bovis isolates circulating in Europe have high minimum inhibitory concentrations (MIC) for many of the commercially available antimicrobials. In this review we summarize the current MIC trends indicating the development of antimicrobial resistance in M. bovis as well as the known molecular mechanisms by which resistance is acquired. PMID:27199926

  8. Mycoplasma bovis: Mechanisms of Resistance and Trends in Antimicrobial Susceptibility

    PubMed Central

    Lysnyansky, Inna; Ayling, Roger D.

    2016-01-01

    Mycoplasma bovis is a cell-wall-less bacterium and belongs to the class Mollicutes. It is the most important etiological agent of bovine mycoplasmoses in North America and Europe, causing respiratory disease, mastitis, otitis media, arthritis, and reproductive disease. Clinical disease associated with M. bovis is often chronic, debilitating, and poorly responsive to antimicrobial therapy, resulting in significant economic loss, the full extent of which is difficult to estimate. Until M. bovis vaccines are universally available, sanitary control measures and antimicrobial treatment are the only approaches that can be used in attempts to control M. bovis infections. However, in vitro studies show that many of the current M. bovis isolates circulating in Europe have high minimum inhibitory concentrations (MIC) for many of the commercially available antimicrobials. In this review we summarize the current MIC trends indicating the development of antimicrobial resistance in M. bovis as well as the known molecular mechanisms by which resistance is acquired. PMID:27199926

  9. Socioeconomic and behavioral factors leading to acquired bacterial resistance to antibiotics in developing countries.

    PubMed Central

    Okeke, I. N.; Lamikanra, A.; Edelman, R.

    1999-01-01

    In developing countries, acquired bacterial resistance to antimicrobial agents is common in isolates from healthy persons and from persons with community-acquired infections. Complex socioeconomic and behavioral factors associated with antibiotic resistance, particularly regarding diarrheal and respiratory pathogens, in developing tropical countries, include misuse of antibiotics by health professionals, unskilled practitioners, and laypersons; poor drug quality; unhygienic conditions accounting for spread of resistant bacteria; and inadequate surveillance. PMID:10081668

  10. Acquired resistance to immunotherapy and future challenges.

    PubMed

    Restifo, Nicholas P; Smyth, Mark J; Snyder, Alexandra

    2016-02-01

    Advances in immunotherapy have resulted in remarkable clinical responses in some patients. However, one of the biggest challenges in cancer therapeutics is the development of resistant disease and disease progression on or after therapy. Given that many patients have now received various types of immunotherapy, we asked three scientists to give their views on the current evidence for whether acquired resistance to immunotherapy exists in patients and the future challenges posed by immunotherapy. PMID:26822578

  11. Antimicrobial Resistance in Haemophilus influenzae

    PubMed Central

    Tristram, Stephen; Jacobs, Michael R.; Appelbaum, Peter C.

    2007-01-01

    Haemophilus influenzae is a major community-acquired pathogen causing significant morbidity and mortality worldwide. Meningitis and bacteremia due to type b strains occur in areas where the protein-conjugated type b vaccine is not in use, whereas nontypeable strains are major causes of otitis media, sinusitis, acute exacerbations of chronic bronchitis, and pneumonia. Antibiotic resistance in this organism is more diverse and widespread than is commonly appreciated. Intrinsic efflux resistance mechanisms limit the activity of the macrolides, azalides, and ketolides. β-Lactamase production is highly prevalent worldwide and is associated with resistance to ampicillin and amoxicillin. Strains with alterations in penicillin binding proteins, particularly PBP3 (β-lactamase negative ampicillin resistant and β-lactamase positive amoxicillin-clavulanate resistant), are increasing in prevalence, particularly in Japan, with increasing resistance to ampicillin, amoxicillin, amoxicillin-clavulanate, and many cephalosporins, limiting the efficacy of expanded-spectrum cephalosporins against meningitis and of many oral cephalosporins against other diseases. Most strains remain susceptible to the carbapenems, which are not affected by penicillin binding protein changes, and the quinolones. The activity of many oral agents is limited by pharmacokinetics achieved with administration by this route, and the susceptibility of isolates based on pharmacokinetic and pharmacodynamic parameters is reviewed. PMID:17428889

  12. National Antimicrobial Resistance Monitoring System (NARMS) Program

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The National Antimicrobial Resistance Monitoring System (NARMS) – Enteric Bacteria is a national public health surveillance system in the United States that tracks changes in the susceptibility of certain enteric bacteria to antimicrobial agents of human and veterinary medical importance. The NARMS ...

  13. Analysis of antimicrobial resistance genes and plasmids from commensal Escherichia coli

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Escherichia coli are commonly associated with various animal and environmental sources. They often acquire antimicrobial resistance (AR) to classes of drugs that are used to treat Gram-negative infections such as aminoglycosides, cephalosporins, fluoroquinolones and sulfonamides. Plasmi...

  14. Natural and acquired macrolide resistance in mycobacteria.

    PubMed

    Doucet-Populaire, F; Buriánková, K; Weiser, J; Pernodet, J-L

    2002-12-01

    The genus Mycobacterium contains two of the most important human pathogens, Mycobacterium tuberculosis and Mycobacterium leprae, the etiologic agents of tuberculosis and leprosy, respectively. Other mycobacteria are mostly saprophytic organisms, living in soil and water, but some of them can cause opportunistic infections. The increasing incidence of tuberculosis as well as infections with non-tuberculous mycobacteria (NTM) in AIDS patients has renewed interest in molecular mechanisms of drug resistance in these pathogens. Mycobacteria show a high degree of intrinsic resistance to most common antibiotics. For instance, species from the M. tuberculosis complex (MTC) are intrinsically resistant to macrolides. Nevertheless, some semi-synthetic macrolides as the erythromycin derivatives clarithromycin, azithromycin and most recently the ketolides, are active against NTM, particularly Mycobacterium avium, and some of them are widely used for infection treatment. However, shortly after the introduction of these new drugs, resistant strains appeared due to mutations in the macrolide target, the ribosome. The mycobacterial cell wall with its specific composition and structure is considered to be a major factor in promoting the natural resistance of mycobacteria to various antibiotics. However, to explain the difference in macrolide sensitivity between the MTC and NTM, the synergistic contribution of a specific resistance mechanism might be required, in addition to possible differences in cell wall permeability. This mini-review summarizes the current knowledge on the natural and acquired macrolide resistance in mycobacteria, gives an overview of potential mechanisms implicated in the intrinsic resistance and brings recent data concerning a macrolide resistance determinant in the MTC. PMID:12570741

  15. Tetracycline resistance genes acquired at birth.

    PubMed

    Alicea-Serrano, Angela M; Contreras, Mónica; Magris, Magda; Hidalgo, Glida; Dominguez-Bello, Maria G

    2013-06-01

    Newborns acquire their first microbiota at birth. Maternal vaginal or skin bacteria colonize newborns delivered vaginally or by C-section, respectively (Dominguez-Bello et al. 2010 #884). We aimed to determine differences in the presence of four tetracycline (tet) resistance genes, in the microbes of ten newborns and in the mouth and vagina of their mothers, at the time of birth. DNA was amplified by PCR with primers specific for [tet(M), tet(O), tet(Q), and tet(W)]. Maternal vaginas harbored all four tet resistance genes, but most commonly tet(M) and tet(O) (63 and 38 %, respectively). Genes coding for tet resistance differed by birth mode, with 50 % of vaginally delivered babies had tet(M) and tet(O) and 16 and 13 % of infants born by C-section had tet(O) and tet(W), respectively. Newborns acquire antibiotic resistance genes at birth, and the resistance gene profile varies by mode of delivery. PMID:23483141

  16. Antimicrobial resistance of enterococci from animals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There is increasing concern over antimicrobial resistance in bacteria of animal and human origin including the possibility of transfer of resistance genes between animal to human bacteria, particularly, those that may be pathogenic. The reported increases in resistance are thought to result from ant...

  17. Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens

    PubMed Central

    Santajit, Sirijan; Indrawattana, Nitaya

    2016-01-01

    The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are the leading cause of nosocomial infections throughout the world. Most of them are multidrug resistant isolates, which is one of the greatest challenges in clinical practice. Multidrug resistance is amongst the top three threats to global public health and is usually caused by excessive drug usage or prescription, inappropriate use of antimicrobials, and substandard pharmaceuticals. Understanding the resistance mechanisms of these bacteria is crucial for the development of novel antimicrobial agents or other alternative tools to combat these public health challenges. Greater mechanistic understanding would also aid in the prediction of underlying or even unknown mechanisms of resistance, which could be applied to other emerging multidrug resistant pathogens. In this review, we summarize the known antimicrobial resistance mechanisms of ESKAPE pathogens. PMID:27274985

  18. Search Engine for Antimicrobial Resistance: A Cloud Compatible Pipeline and Web Interface for Rapidly Detecting Antimicrobial Resistance Genes Directly from Sequence Data

    PubMed Central

    Rowe, Will; Baker, Kate S.; Verner-Jeffreys, David; Baker-Austin, Craig; Ryan, Jim J.; Maskell, Duncan; Pearce, Gareth

    2015-01-01

    Background Antimicrobial resistance remains a growing and significant concern in human and veterinary medicine. Current laboratory methods for the detection and surveillance of antimicrobial resistant bacteria are limited in their effectiveness and scope. With the rapidly developing field of whole genome sequencing beginning to be utilised in clinical practice, the ability to interrogate sequencing data quickly and easily for the presence of antimicrobial resistance genes will become increasingly important and useful for informing clinical decisions. Additionally, use of such tools will provide insight into the dynamics of antimicrobial resistance genes in metagenomic samples such as those used in environmental monitoring. Results Here we present the Search Engine for Antimicrobial Resistance (SEAR), a pipeline and web interface for detection of horizontally acquired antimicrobial resistance genes in raw sequencing data. The pipeline provides gene information, abundance estimation and the reconstructed sequence of antimicrobial resistance genes; it also provides web links to additional information on each gene. The pipeline utilises clustering and read mapping to annotate full-length genes relative to a user-defined database. It also uses local alignment of annotated genes to a range of online databases to provide additional information. We demonstrate SEAR’s application in the detection and abundance estimation of antimicrobial resistance genes in two novel environmental metagenomes, 32 human faecal microbiome datasets and 126 clinical isolates of Shigella sonnei. Conclusions We have developed a pipeline that contributes to the improved capacity for antimicrobial resistance detection afforded by next generation sequencing technologies, allowing for rapid detection of antimicrobial resistance genes directly from sequencing data. SEAR uses raw sequencing data via an intuitive interface so can be run rapidly without requiring advanced bioinformatic skills or

  19. Use of a bacterial antimicrobial resistance gene microarray for the identification of resistant Staphylococcus aureus.

    PubMed

    Garneau, P; Labrecque, O; Maynard, C; Messier, S; Masson, L; Archambault, M; Harel, J

    2010-11-01

    As diagnostic and surveillance activities are vital to determine measures needed to control antimicrobial resistance (AMR), new and rapid laboratory methods are necessary to facilitate this important effort. DNA microarray technology allows the detection of a large number of genes in a single reaction. This technology is simple, specific and high-throughput. We have developed a bacterial antimicrobial resistance gene DNA microarray that will allow rapid antimicrobial resistance gene screening for all Gram-positive and Gram-negative bacteria. A prototype microarray was designed using a 70-mer based oligonucleotide set targeting AMR genes of Gram-negative and Gram-positive bacteria. In the present version, the microarray consists of 182 oligonucleotides corresponding to 166 different acquired AMR gene targets, covering most of the resistance genes found in both Gram-negative and -positive bacteria. A test study was performed on a collection of Staphylococcus aureus isolates from milk samples from dairy farms in Québec, Canada. The reproducibility of the hybridizations was determined, and the microarray results were compared with those obtained by phenotypic resistance tests (either MIC or Kirby-Bauer). The microarray genotyping demonstrated a correlation between penicillin, tetracycline and erythromycin resistance phenotypes with the corresponding acquired resistance genes. The hybridizations showed that the 38 antimicrobial resistant S. aureus isolates possessed at least one AMR gene. PMID:21083822

  20. Inappropriate use of antibiotics in hospitals: the complex relationship between antibiotic use and antimicrobial resistance.

    PubMed

    Cantón, Rafael; Horcajada, Juan Pablo; Oliver, Antonio; Garbajosa, Patricia Ruiz; Vila, Jordi

    2013-09-01

    Hospitals are considered an excellent compartment for the selection of resistant and multi-drug resistant (MDR) bacteria. The overuse and misuse of antimicrobial agents are considered key points fuelling this situation. Antimicrobial stewardship programs have been designed for better use of these compounds to prevent the emergence of resistant microorganisms and to diminish the upward trend in resistance. Nevertheless, the relationship between antibiotic use and antimicrobial resistance is complex, and the desired objectives are difficult to reach. Various factors affecting this relationship have been advocated including, among others, antibiotic exposure and mutant selection windows, antimicrobial pharmacodynamics, the nature of the resistance (natural or acquired, including mutational and that associated with horizontal gene transfer) and the definition of resistance. Moreover, antimicrobial policies to promote better use of these drugs should be implemented not only in the hospital setting coupled with infection control programs, but also in the community, which should also include animal and environmental compartments. Within hospitals, the restriction of antimicrobials, cycling and mixing strategies and the use of combination therapies have been used to avoid resistance. Nevertheless, the results have not always been favorable and resistant bacteria have persisted despite the theoretical benefits of these strategies. Mathematical models as well as microbiological knowledge can explain this failure, which is mainly related to the current scenario involving MDR bacteria and overcoming the fitness associated with resistance. New antimicrobials, rapid diagnostic and antimicrobial susceptibility testing and biomarkers will be useful for future antimicrobial stewardship interventions. PMID:24129283

  1. Danish Integrated Antimicrobial Resistance Monitoring and Research Program

    PubMed Central

    Heuer, Ole E.; Emborg, Hanne-Dorthe; Bagger-Skjøt, Line; Jensen, Vibeke F.; Rogues, Anne-Marie; Skov, Robert L.; Agersø, Yvonne; Brandt, Christian T.; Seyfarth, Anne Mette; Muller, Arno; Hovgaard, Karin; Ajufo, Justin; Bager, Flemming; Aarestrup, Frank M.; Frimodt-Møller, Niels; Wegener, Henrik C.; Monnet, Dominique L.

    2007-01-01

    Resistance to antimicrobial agents is an emerging problem worldwide. Awareness of the undesirable consequences of its widespread occurrence has led to the initiation of antimicrobial agent resistance monitoring programs in several countries. In 1995, Denmark was the first country to establish a systematic and continuous monitoring program of antimicrobial drug consumption and antimicrobial agent resistance in animals, food, and humans, the Danish Integrated Antimicrobial Resistance Monitoring and Research Program (DANMAP). Monitoring of antimicrobial drug resistance and a range of research activities related to DANMAP have contributed to restrictions or bans of use of several antimicrobial agents in food animals in Denmark and other European Union countries. PMID:18217544

  2. Signal regulators of systemic acquired resistance

    PubMed Central

    Gao, Qing-Ming; Zhu, Shifeng; Kachroo, Pradeep; Kachroo, Aardra

    2015-01-01

    Salicylic acid (SA) is an important phytohormone that plays a vital role in a number of physiological responses, including plant defense. The last two decades have witnessed a number of breakthroughs related to biosynthesis, transport, perception and signaling mediated by SA. These findings demonstrate that SA plays a crictical role in both local and systemic defense responses. Systemic acquired resistance (SAR) is one such SA-dependent response. SAR is a long distance signaling mechanism that provides broad spectrum and long-lasting resistance to secondary infections throughout the plant. This unique feature makes SAR a highly desirable trait in crop production. This review summarizes the recent advances in the role of SA in SAR and discusses its relationship to other SAR inducers. PMID:25918514

  3. Mechanisms of biofilm resistance to antimicrobial agents.

    PubMed

    Mah, T F; O'Toole, G A

    2001-01-01

    Biofilms are communities of microorganisms attached to a surface. It has become clear that biofilm-grown cells express properties distinct from planktonic cells, one of which is an increased resistance to antimicrobial agents. Recent work has indicated that slow growth and/or induction of an rpoS-mediated stress response could contribute to biocide resistance. The physical and/or chemical structure of exopolysaccharides or other aspects of biofilm architecture could also confer resistance by exclusion of biocides from the bacterial community. Finally, biofilm-grown bacteria might develop a biofilm-specific biocide-resistant phenotype. Owing to the heterogeneous nature of the biofilm, it is likely that there are multiple resistance mechanisms at work within a single community. Recent research has begun to shed light on how and why surface-attached microbial communities develop resistance to antimicrobial agents. PMID:11166241

  4. Antimicrobial susceptibility and serotype distribution of Streptococcus pneumoniae isolated from patients with community-acquired pneumonia and molecular analysis of multidrug-resistant serotype 19F and 23F strains in Japan.

    PubMed

    Qin, L; Watanabe, H; Yoshimine, H; Guio, H; Watanabe, K; Kawakami, K; Iwagaki, A; Nagai, H; Goto, H; Kuriyama, T; Fukuchi, Y; Matsushima, T; Kudoh, S; Shimada, K; Matsumoto, K; Nagatake, T; Mizota, T; Oishi, K

    2006-12-01

    A nationwide study was undertaken to determine the susceptibility to penicillin and serotypes of Streptococcus pneumoniae in Japan. S. pneumoniae was isolated from 114 adult patients with community-acquired pneumonia over 22 months at 20 hospitals and medical centres in different regions in Japan. All but five isolates were from sputum. Forty-eight isolates (42.1%) were susceptible, 40 (35.1%) showed intermediate resistance (MIC, 0.12-1.0 microg/ml) and 26 (22.8%) were resistant (MIC, >or=2.0 microg/ml) to penicillin G. All isolates were susceptible to ceftriaxone (breakpoint 1 microg/ml), imipenem (4 microg/ml) and vancomycin (4 microg/ml). Most were resistant to erythromycin, clarithromycin and azithromycin; only two were resistant to levofloxacin. Differences were found in the distribution of serotypes among isolates showing susceptibility to penicillin (predominant types 3, 6B, and 19F), intermediate resistance (6B, 14, 19F, and 23F) and full resistance (19F and 23F). PFGE typing showed that 14 of the 25 strains of serotype 19F had a single DNA profile, pattern A, a pattern closely similar to that of the Taiwan multidrug-resistant 19F clone. Twelve pattern A strains were not susceptible to penicillin but carried the macrolide resistance gene mef(A). The DNA profiles of the 15 strains of 23F were also heterogeneous but six were highly similar (pattern b) yet distinct from the Spanish multidrug-resistant 23F clone although possibly related to the Taiwan multidrug-resistant 23F clone. The pattern b strains were not susceptible to penicillin and also harboured either mef(A) or erm(B). Our results indicate that multidrug-resistant pneumococci are spreading rapidly in Japan. Efforts to prevent the spread of the pandemic multidrug-resistant serotypes should be intensified. PMID:16650327

  5. Bacterial strategies of resistance to antimicrobial peptides.

    PubMed

    Joo, Hwang-Soo; Fu, Chih-Iung; Otto, Michael

    2016-05-26

    Antimicrobial peptides (AMPs) are a key component of the host's innate immune system, targeting invasive and colonizing bacteria. For successful survival and colonization of the host, bacteria have a series of mechanisms to interfere with AMP activity, and AMP resistance is intimately connected with the virulence potential of bacterial pathogens. In particular, because AMPs are considered as potential novel antimicrobial drugs, it is vital to understand bacterial AMP resistance mechanisms. This review gives a comparative overview of Gram-positive and Gram-negative bacterial strategies of resistance to various AMPs, such as repulsion or sequestration by bacterial surface structures, alteration of membrane charge or fluidity, degradation and removal by efflux pumps.This article is part of the themed issue 'Evolutionary ecology of arthropod antimicrobial peptides'. PMID:27160595

  6. Understanding the mechanisms and drivers of antimicrobial resistance.

    PubMed

    Holmes, Alison H; Moore, Luke S P; Sundsfjord, Arnfinn; Steinbakk, Martin; Regmi, Sadie; Karkey, Abhilasha; Guerin, Philippe J; Piddock, Laura J V

    2016-01-01

    To combat the threat to human health and biosecurity from antimicrobial resistance, an understanding of its mechanisms and drivers is needed. Emergence of antimicrobial resistance in microorganisms is a natural phenomenon, yet antimicrobial resistance selection has been driven by antimicrobial exposure in health care, agriculture, and the environment. Onward transmission is affected by standards of infection control, sanitation, access to clean water, access to assured quality antimicrobials and diagnostics, travel, and migration. Strategies to reduce antimicrobial resistance by removing antimicrobial selective pressure alone rely upon resistance imparting a fitness cost, an effect not always apparent. Minimising resistance should therefore be considered comprehensively, by resistance mechanism, microorganism, antimicrobial drug, host, and context; parallel to new drug discovery, broad ranging, multidisciplinary research is needed across these five levels, interlinked across the health-care, agriculture, and environment sectors. Intelligent, integrated approaches, mindful of potential unintended results, are needed to ensure sustained, worldwide access to effective antimicrobials. PMID:26603922

  7. Antimicrobial resistance in internal medicine wards.

    PubMed

    Menichetti, Francesco; Tagliaferri, Enrico

    2012-10-01

    Antimicrobial resistance is a global medical problem, affecting most bacterial pathogens. The major challenges are currently posed by methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), Enterobacteriaceae producing extended-spectrum-beta-lactamases (ESBL) and carbapenemases, and multi-resistant strains of Pseudomonas aeruginosa and Acinetobacter baumannii. Therapeutic options are very limited and, in some cases, virtually unavailable. This article provides an overview of the recent epidemiological trends exhibited by the most important multi-resistant pathogens, and of the treatment options that are currently available for these infections. PMID:23073868

  8. NATIONAL ANTIMICROBIAL RESISTANCE MONITORING SYSTEM (NARMS)

    EPA Science Inventory

    The main activity of NARMS is to monitor antimicrobial resistance of human enteric bacteria, including Campylobacter, Salmonella, Escherichia coli O157, and Shigella. NARMS is an active surveillance system that collects every 10th non-typhi Salmonella and Shigella isolate, every ...

  9. Potency and antimicrobial spectrum update for piperacillin/tazobactam (2000): emphasis on its activity against resistant organism populations and generally untested species causing community-acquired respiratory tract infections.

    PubMed

    Johnson, David M; Biedenbach, Douglas J; Jones, Ronald N

    2002-05-01

    ceftazidime inhibited 100.0% of the isolates at < or = 0.25 microg/ml. These in vitro surveillance results from the year 2000 on three continents, demonstrated a sustained potent activity of piperacillin/tazobactam against selected problematic nosocomial and community-acquired pathogens. The potential importance of these findings is that this beta-lactamase inhibitor combination can be used an empiric treatment of serious infections in hospital environments where resistance has emerged, as well as covering nearly all isolates of fastidious respiratory tract pathogens acquired in the community setting. PMID:12052629

  10. Clinical implications of antimicrobial resistance: how big is the problem?

    PubMed

    Duckworth, Georgia

    2002-03-01

    This presentation addresses the question of the size of the antimicrobial resistance problem by examining the monitoring of antimicrobial use and resistance. It focuses on the main sources of information, possible pitfalls of the data and the susceptibility of the main pathogens responsible for bacteraemias in England and Wales. It addresses some of the difficulties in establishing the link between antimicrobial resistance and antimicrobial prescribing and concludes with some thoughts on necessary developments. PMID:12044283

  11. The changing landscape of antimicrobial resistance in New Zealand.

    PubMed

    Williamson, Deborah A; Heffernan, Helen

    2014-09-26

    Antimicrobial resistance is one of the biggest health threats of the modern age, threatening the routine treatment of many common infectious diseases. Resistance to many common antimicrobials is now endemic in New Zealand, in both community and healthcare settings. Over the past two decades, the landscape of antimicrobial resistance has changed considerably in New Zealand, with the emergence and spread of pathogens such as community-associated methicillin-resistant Staphylococcus aureus, extended-spectrum β-lactamase-producing Enterobacteriaceae and multi- resistant Neisseria gonorrhoeae. Factors contributing to the emergence and spread of antimicrobial-resistant pathogens in New Zealand include the use and overuse of antimicrobials, transmission of resistant organisms in community and healthcare settings, and importation of resistant pathogens from areas where multi-resistant pathogens are endemic. In this review, we provide a summary of major antimicrobial-resistant bacteria in New Zealand, with a specific focus on those pathogens that pose major threats to human health. PMID:25290498

  12. Mechanisms of antimicrobial resistance in Gram-negative bacilli.

    PubMed

    Ruppé, Étienne; Woerther, Paul-Louis; Barbier, François

    2015-12-01

    The burden of multidrug resistance in Gram-negative bacilli (GNB) now represents a daily issue for the management of antimicrobial therapy in intensive care unit (ICU) patients. In Enterobacteriaceae, the dramatic increase in the rates of resistance to third-generation cephalosporins mainly results from the spread of plasmid-borne extended-spectrum beta-lactamase (ESBL), especially those belonging to the CTX-M family. The efficacy of beta-lactam/beta-lactamase inhibitor associations for severe infections due to ESBL-producing Enterobacteriaceae has not been adequately evaluated in critically ill patients, and carbapenems still stands as the first-line choice in this situation. However, carbapenemase-producing strains have emerged worldwide over the past decade. VIM- and NDM-type metallo-beta-lactamases, OXA-48 and KPC appear as the most successful enzymes and may threaten the efficacy of carbapenems in the near future. ESBL- and carbapenemase-encoding plasmids frequently bear resistance determinants for other antimicrobial classes, including aminoglycosides (aminoglycoside-modifying enzymes or 16S rRNA methylases) and fluoroquinolones (Qnr, AAC(6')-Ib-cr or efflux pumps), a key feature that fosters the spread of multidrug resistance in Enterobacteriaceae. In non-fermenting GNB such as Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia, multidrug resistance may emerge following the sole occurrence of sequential chromosomal mutations, which may lead to the overproduction of intrinsic beta-lactamases, hyper-expression of efflux pumps, target modifications and permeability alterations. P. aeruginosa and A. baumannii also have the ability to acquire mobile genetic elements encoding resistance determinants, including carbapenemases. Available options for the treatment of ICU-acquired infections due to carbapenem-resistant GNB are currently scarce, and recent reports emphasizing the spread of colistin resistance in environments with high

  13. Antimicrobial Susceptibility/Resistance of Streptococcus Pneumoniae

    PubMed Central

    Karcic, Emina; Aljicevic, Mufida; Bektas, Sabaheta; Karcic, Bekir

    2015-01-01

    Introduction: Pneumococcal infections are a major cause of morbidity and mortality worldwide, whose treatment is threatened with an increase in the number of strains resistant to antibiotic therapy. Goal: The main goal of this research was to investigate the presence of antimicrobial susceptibility/resistance of S. pneumoniae. Material and methods: Taken are swabs of the nose and nasopharynx, eye and ear. In vitro tests that were made in order to study the antimicrobial resistance of pneumococci are: disk diffusion method and E-test. Results: The resistance to inhibitors of cell wall synthesis was recorded at 39.17%, protein synthesis inhibitors 19.67%, folate antagonists 47.78% and quinolone in 1.11%. S. pneumoniae has shown drug resistance to erythromycin in 45%, clindamycin in 45%, chloramphenicol–0.56%, rifampicin–6.11%, tetracycline–4.67%, penicillin-G in 4.44%, oxacillin in 73.89%, ciprofloxacin in 1.11% and trimethoprim-sulfamethoxazole in 5.34% of cases. Conclusion: The highest resistance pneumococcus showed to erythromycin, clindamycin and trimethoprim-sulfamethoxazole and these should be avoided in the treatment. The least resistance pneumococcus showed to tetracycline, rifampicin, chloramphenicol, penicillin-G and ciprofloxacin. PMID:26236165

  14. 'No action today means no cure tomorrow': the threat of antimicrobial resistance.

    PubMed

    While, Alison

    2016-07-01

    Antimicrobial resistance is a major concern for UK healthcare professionals, following growing evidence of multi-resistant pathogens. Poor prescribing practices, partly driven by patient demand, and poor patient adherence to prescribed regimens are two of the causes of growing antimicrobial resisitance. Improved infection prevention and control practices will not only reduce healthcare-acquired infections, but also reduce the necessity for antimicrobials. Community nurses can also support their clients to promote their own health and wellbeing, increasing resilience to infections through a healthy lifestyle which includes a well-balanced diet, good personal hygiene and the take up of offered vaccinations. PMID:27401198

  15. Antimicrobial Resistance in the Food Chain: A Review

    PubMed Central

    Verraes, Claire; Van Boxstael, Sigrid; Van Meervenne, Eva; Van Coillie, Els; Butaye, Patrick; Catry, Boudewijn; de Schaetzen, Marie-Athénaïs; Van Huffel, Xavier; Imberechts, Hein; Dierick, Katelijne; Daube, George; Saegerman, Claude; De Block, Jan; Dewulf, Jeroen; Herman, Lieve

    2013-01-01

    Antimicrobial resistant zoonotic pathogens present on food constitute a direct risk to public health. Antimicrobial resistance genes in commensal or pathogenic strains form an indirect risk to public health, as they increase the gene pool from which pathogenic bacteria can pick up resistance traits. Food can be contaminated with antimicrobial resistant bacteria and/or antimicrobial resistance genes in several ways. A first way is the presence of antibiotic resistant bacteria on food selected by the use of antibiotics during agricultural production. A second route is the possible presence of resistance genes in bacteria that are intentionally added during the processing of food (starter cultures, probiotics, bioconserving microorganisms and bacteriophages). A last way is through cross-contamination with antimicrobial resistant bacteria during food processing. Raw food products can be consumed without having undergone prior processing or preservation and therefore hold a substantial risk for transfer of antimicrobial resistance to humans, as the eventually present resistant bacteria are not killed. As a consequence, transfer of antimicrobial resistance genes between bacteria after ingestion by humans may occur. Under minimal processing or preservation treatment conditions, sublethally damaged or stressed cells can be maintained in the food, inducing antimicrobial resistance build-up and enhancing the risk of resistance transfer. Food processes that kill bacteria in food products, decrease the risk of transmission of antimicrobial resistance. PMID:23812024

  16. Klebsiella pneumoniae Antimicrobial Drug Resistance, United States, 1998–2010

    PubMed Central

    Sanchez, Guillermo V.; Master, Ronald N.; Clark, Richard B.; Fyyaz, Madiha; Duvvuri, Padmaraj; Ekta, Gupta

    2013-01-01

    We studied antimicrobial-resistant Klebsiella pneumoniae for 1998–2010 by using data from The Surveillance Network. Susceptibility results (n = 3,132,354) demonstrated significant increases in resistance to all antimicrobial drugs studied, except tetracycline. Cross-resistance among carbapenem-resistant K. pneumoniae was lower for tetracycline and amikacin. PMID:23260464

  17. Changes in antimicrobial resistance of Salmonella isolated from humans in the United States.

    PubMed

    MacDonald, K L; Cohen, M L; Hargrett-Bean, N T; Wells, J G; Puhr, N D; Collin, S F; Blake, P A

    1987-09-18

    Changes were examined that occurred in the antimicrobial susceptibility between 1979-1980 and 1984-1985 of Salmonella organisms isolated from humans who resided in a random sample of counties in the United States. Resistance to one or more antimicrobials rose significantly from 16% (82 of 511 isolates) in 1979-1980 to 24% (117 of 485 isolates) in 1984-1985. In addition, statistically significant increases occurred in the proportion of organisms resistant to only one antimicrobial (from 4% to 9%), the rate of resistance of Salmonella typhimurium (from 14% to 26%), and the rate of resistance to tetracycline. For one commonly occurring serotype, Salmonella heidelberg, the proportion of resistant strains fell significantly from 67% in 1979-1980 to 35% in 1984-1985. When epidemiologic characteristics of patients were examined, previous use of antimicrobials for treatment of other illnesses was a significant risk factor for acquiring clinically important infections with antimicrobial-resistant Salmonella. Changes detected in the antimicrobial resistance of Salmonella during this time will ultimately affect the efficacy of antimicrobial therapy in treating human disease. PMID:3625949

  18. Antimicrobial Resistance in Salmonella Isolates Recovered from Cattle at Slaughter

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Since 1997, the animal arm of the National Antimicrobial Resistance Monitoring System (NARMS) has monitored changes in antimicrobial susceptibilities of Salmonella isolates from animal origin. Additionally, since 2000, susceptibility of bovine Salmonella isolates collected in the US has ...

  19. Antimicrobial susceptibility of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolated from community-acquired respiratory tract infections in China: Results from the CARTIPS Antimicrobial Surveillance Program.

    PubMed

    Zhang, Yawei; Zhang, Feifei; Wang, Hui; Zhao, Chunjiang; Wang, Zhanwei; Cao, Bin; Du, Yan; Feng, Xianju; Hu, Yunjian; Hu, Bijie; Ji, Ping; Liu, Zhiyong; Liu, Yong; Liao, Wanzhen; Lu, Juan; Sun, Hongli; Wang, Zhongxin; Xu, Xiuli; Xu, Xuesong; Yang, Qing; Yu, Yunsong; Zhang, Rong; Zhuo, Chao

    2016-06-01

    This study investigated the antimicrobial susceptibilities of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolates causing adult community-acquired respiratory tract infections (CARTIs) in China. A multicentre resistance surveillance study (CARTIPS) investigating 1046 clinical isolates from 19 hospitals in China was conducted from 2013 to 2014. Based on the minimum inhibitory concentration (MIC) breakpoints of oral penicillin, the percentages of penicillin-resistant, penicillin-intermediate and penicillin-susceptible S. pneumoniae were 44.1%, 13.7%, and 42.2%, respectively. The rates of penicillin-non-susceptible S. pneumoniae ranged from 27.9% to 72.2% in different cities, with the highest rate in Nanchang. Macrolides, including azithromycin, clarithromycin and erythromycin, showed the lowest activities against S. pneumoniae isolates, with resistance rates of 90.5%, 92.2% and 93.0%, respectively. However, 98% of these strains were susceptible to levofloxacin and moxifloxacin. For H. influenzae isolates, most of the antimicrobials agents exhibited good activities. However, ampicillin and trimethoprim/sulfamethoxazole showed relatively lower activity against H. influenzae, with resistance rates of 35.0% and 54.4%, respectively. β-lactamase production rates amongst H. influenzae and M. catarrhalis were 31.0% and 87.1%, respectively. In addition, a total of 15 β-lactamase-negative ampicillin-resistant (BLNAR) strains identified in this study were resistant to ampicillin, amoxicillin/clavulanic acid, cefaclor and cefuroxime. Most of the antimicrobial agents showed excellent activity against M. catarrhalis, with susceptibility rates of >90%. The results from the current study confirmed the regional variations in antimicrobial susceptibility of major CARTI pathogens and provided some choices for the treatment of these organisms. Continuous national surveillance of the epidemiology of CARTIs is strongly warranted in China. PMID:27436464

  20. Resistance to Antimicrobial Peptides in Vibrios

    PubMed Central

    Destoumieux-Garzón, Delphine; Duperthuy, Marylise; Vanhove, Audrey Sophie; Schmitt, Paulina; Wai, Sun Nyunt

    2014-01-01

    Vibrios are associated with a broad diversity of hosts that produce antimicrobial peptides (AMPs) as part of their defense against microbial infections. In particular, vibrios colonize epithelia, which function as protective barriers and express AMPs as a first line of chemical defense against pathogens. Recent studies have shown they can also colonize phagocytes, key components of the animal immune system. Phagocytes infiltrate infected tissues and use AMPs to kill the phagocytosed microorganisms intracellularly, or deliver their antimicrobial content extracellularly to circumvent tissue infection. We review here the mechanisms by which vibrios have evolved the capacity to evade or resist the potent antimicrobial defenses of the immune cells or tissues they colonize. Among their strategies to resist killing by AMPs, primarily vibrios use membrane remodeling mechanisms. In particular, some highly resistant strains substitute hexaacylated Lipid A with a diglycine residue to reduce their negative surface charge, thereby lowering their electrostatic interactions with cationic AMPs. As a response to envelope stress, which can be induced by membrane-active agents including AMPs, vibrios also release outer membrane vesicles to create a protective membranous shield that traps extracellular AMPs and prevents interaction of the peptides with their own membranes. Finally, once AMPs have breached the bacterial membrane barriers, vibrios use RND efflux pumps, similar to those of other species, to transport AMPs out of their cytoplasmic space. PMID:27025756

  1. Bacterial resistance to antimicrobials in urinary isolates.

    PubMed

    Muratani, Tetsuro; Matsumoto, Tetsuro

    2004-09-01

    Escherichia coli accounted for about 80% of organisms in uncomplicated urinary tract infections (UTIs), followed by Staphylococcus spp. especially Staphylococcus saprophyticus, and Proteus mirabilis. Against E. coli isolates from patients with uncomplicated UTI, faropenem was the most effective. Up to 1999, fluoroquinolone-resistant isolates were not observed in patients with uncomplicated UTI, but in 2001 fluoroquinolone-resistant E. coli isolates emerged and accounted for about 8%. Various types of organisms were isolated in patients with complicated UTI. Enterococcus faecalis, E. coli, and Pseudomonas aeruginosa were the three most frequent organisms isolated. These three organisms accounted for 44.6%. Amongst oral agents, faropenem showed the lowest rate of resistance against E. coli followed by cephems. The rates of highly fluoroquinolone-resistant and cefpodoxime-resistant E. coli isolates increased rapidly from 1998 to 2001. Fluoroquinolone-resistant P. aeruginosa isolates accounted for about 40% in 2001. Against this species, amikacin was the most effective antimicrobials among all agents tested. About 17% of Pseudomonas were resistant to carbapenem. Eight milligram per litre of ampicillin inhibited all E. faecalis isolates; about 60% of Enterococcus faecium were resistant to ampicillin. The rates of levofloxacin-resistant isolates of E. faecalis and E. faecium were 38 and 97% respectively. UTIs caused by vancomycin resistant enterococci (VRE) are rare in Japan. PMID:15364302

  2. Antimicrobial resistance in bacteria from Swiss veal calves at slaughter.

    PubMed

    Di Labio, E; Regula, G; Steiner, A; Miserez, R; Thomann, A; Ledergerber, U

    2007-01-01

    Bacteria with antimicrobial resistance can be transferred from animals to humans and may compromise antimicrobial treatment in case of infection. To determine the antimicrobial resistance situation in bacteria from Swiss veal calves, faecal samples from 500 randomly selected calves originating from 129 farms were collected at four big slaughterhouses. Samples were cultured for Escherichia coli, Enterococcus sp. and Campylobacter sp. and isolated strains were tested for antimicrobial susceptibility to selected antimicrobial agents by the minimal inhibitory concentration technique using the broth microdilution method. From 100 farms, data on farm management, animal husbandry and antimicrobial treatments of the calves were collected by questionnaire. Risk factors associated with antimicrobial resistance were identified by logistic regression. In total, 467 E. coli, 413 Enterococcus sp. and 202 Campylobacter sp. were isolated. Of those, 68.7%, 98.7% and 67.8%, respectively, were resistant to at least one of the tested antimicrobial agents. Resistance was mainly observed to antimicrobials frequently used in farm animals. Prevalence of resistance to antimicrobials important for human treatment was generally low. However, a rather high number of quinupristin/dalfopristin-resistant Enterococcus faecium and ciprofloxacin-resistant Campylobacter sp. were detected. External calf purchase, large finishing groups, feeding of milk by-products and administration of antimicrobials through feed upon arrival of the animals on the farm significantly increased the risk of antimicrobial resistance at farm level. Participation in a quality assurance programme and injection of a macrolide upon arrival of the animals on the farm had a protective effect. The present study showed that veal calves may serve as a reservoir for resistant bacteria. To ensure food safety, veal calves should be included in the national monitoring programme for antimicrobial resistance in farm animals. By

  3. Salt-resistant short antimicrobial peptides.

    PubMed

    Mohanram, Harini; Bhattacharjya, Surajit

    2016-05-01

    Antimicrobial peptides (AMPs) are promising leads for the development of antibiotics against drug resistant bacterial pathogens. However, in vivo applications of AMPs remain obscure due to salt and serum mediated inactivation. The high cost of chemical synthesis of AMPs also impedes potential clinical application. Consequently, short AMPs resistant toward salt and serum inactivation are desirable for the development of peptide antibiotics. In this work, we designed a 12-residue amphipathic helical peptide RR12 (R-R-L-I-R-L-I-L-R-L-L-R-amide) and two Trp containing analogs of RR12 namely RR12Wpolar (R-R-L-I-W-L-I-L-R-L-L-R-amide), and RR12Whydro (R-R-L-I-R-L-W-L-R-L-L-R-amide). Designed peptides demonstrated potent antibacterial activity; MIC ranging from 2 to 8 μM, in the presence of sodium chloride (150 mM and 300 mM). Antibacterial activity of these peptides was also detected in the presence of human serum. Designed peptides, in particular RR12 and RR12Whydro, were only poorly hemolytic. As a mode of action; these peptides demonstrated efficient permeabilization of bacterial cell membrane and lysis of cell structure. We further investigated interactions of the designed peptides with lipopolysaccharide (LPS), the major component of the outer membrane permeability barrier of Gram-negative bacteria. Designed peptides adopted helical conformations in complex with LPS. Binding of peptides with LPS has yielded dissociation the aggregated structures of LPS. Collectively, these designed peptides hold ability to be developed for salt-resistant antimicrobial compounds. Most importantly, current work provides insights for designing salt-resistant antimicrobial peptides. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 345-356, 2016. PMID:26849911

  4. Shigella Antimicrobial Drug Resistance Mechanisms, 2004-2014.

    PubMed

    Nüesch-Inderbinen, Magdalena; Heini, Nicole; Zurfluh, Katrin; Althaus, Denise; Hächler, Herbert; Stephan, Roger

    2016-06-01

    To determine antimicrobial drug resistance mechanisms of Shigella spp., we analyzed 344 isolates collected in Switzerland during 2004-2014. Overall, 78.5% of isolates were multidrug resistant; 10.5% were ciprofloxacin resistant; and 2% harbored mph(A), a plasmid-mediated gene that confers reduced susceptibility to azithromycin, a last-resort antimicrobial agent for shigellosis. PMID:27191035

  5. Shigella Antimicrobial Drug Resistance Mechanisms, 2004–2014

    PubMed Central

    Nüesch-Inderbinen, Magdalena; Heini, Nicole; Zurfluh, Katrin; Althaus, Denise; Hächler, Herbert

    2016-01-01

    To determine antimicrobial drug resistance mechanisms of Shigella spp., we analyzed 344 isolates collected in Switzerland during 2004–2014. Overall, 78.5% of isolates were multidrug resistant; 10.5% were ciprofloxacin resistant; and 2% harbored mph(A), a plasmid-mediated gene that confers reduced susceptibility to azithromycin, a last-resort antimicrobial agent for shigellosis. PMID:27191035

  6. Antimicrobial susceptibility in gram-negative bacteremia: are nosocomial isolates really more resistant?

    PubMed Central

    McGowan, J E; Hall, E C; Parrott, P L

    1989-01-01

    Bloodstream isolates of gram-negative aerobic bacilli from nosocomial infections are more likely to be resistant to antimicrobial agents than isolates from community-acquired cases are. It is not clear, however, how much this is due to the markedly different distribution of organisms in the two groups. We compared the susceptibilities of organisms of a given species which caused community-acquired bacteremia with the susceptibilities of isolates from nosocomial cases. Nine antimicrobial agents were tested against 1,077 isolates which were obtained during a 4-year nonepidemic period. Marked differences in crude rates of resistance were noted for all isolates from nosocomial cases versus all isolates from cases acquired in the community. When results were adjusted for the different organism distributions in the two groups, statistically significant differences were found for only six drug-organism pairs; in each of these, resistance rates were higher in nosocomial isolates. However, when results were further adjusted for the effect of multiple analyses, no significant differences were seen. The major factor leading to the greater prevalence of antimicrobial resistance in our hospital organisms was the markedly different distribution of organisms in the nosocomial and community-acquired groups. For individual organisms, greater resistance in nosocomial strains was confined to certain drugs. Factors that influence differences in organism distribution may not be solely the result of antimicrobial use. PMID:2610495

  7. Surveillance for Travel and Domestically Acquired Multidrug-Resistant Human Shigella Infections-Pennsylvania, 2006-2014.

    PubMed

    Li, Yu Lung; Tewari, Deepanker; Yealy, Courtney C; Fardig, David; M'ikanatha, Nkuchia M

    2016-01-01

    Shigellosis is a leading cause of enteric infections in the United States. We compared antimicrobial resistance in Shigella infections related to overseas travel (travel-associated) and in those acquired domestically by analyzing antimicrobial resistance patterns, geographic distributions, and pulsed-field gel electrophoresis (PFGE) patterns. We tested samples (n = 204) from a collection of isolates recovered from patients in Pennsylvania between 2006 and 2014. Isolates were grouped into travel- and non-travel-associated categories. Eighty-one (79.4%) of the Shigella isolates acquired during international travel were resistant to multiple antibiotics compared to 53 (52.1%) of the infections transmitted in domestic settings. A majority (79.4%) of isolates associated with international travel demonstrated resistance to aminoglycosides and tetracyclines, whereas 47 (46.1%) of the infections acquired domestically were resistant to tetracycline. Almost all isolates (92.2%) transmitted in domestic settings were resistant to aminoglycosides, and 5 isolates from adult male patients were resistant to azithromycin, a drug often used for empiric treatment of severe shigellosis. Twenty (19.6%) isolates associated with illnesses acquired during overseas travel in 4 countries were resistant to quinolones. One S. sonnei PFGE pattern was traced to a multidrug-resistant isolate acquired overseas that had caused a multistate outbreak of shigellosis, suggesting global dissemination of a drug-resistant species. Resistance to certain drugs-for example, tetracycline-increased in both overseas- and domestic-acquired infections during the study period. The prevalence of resistance to macrolides (azithromycin) and third-generation cephalosporins (ceftriaxone) was less than 1%; however, efforts to better monitor changes in drug resistance over time combined with increased antimicrobial stewardship are essential at the local, national, and global levels. PMID:27314654

  8. Antimicrobial use in swine production and its effect on the swine gut microbiota and antimicrobial resistance.

    PubMed

    Holman, Devin B; Chénier, Martin R

    2015-11-01

    Antimicrobials have been used in swine production at subtherapeutic levels since the early 1950s to increase feed efficiency and promote growth. In North America, a number of antimicrobials are available for use in swine. However, the continuous administration of subtherapeutic, low concentrations of antimicrobials to pigs also provides selective pressure for antimicrobial-resistant bacteria and resistance determinants. For this reason, subtherapeutic antimicrobial use in livestock remains a source of controversy and concern. The swine gut microbiota demonstrates a number of changes in response to antimicrobial administration depending on the dosage, duration of treatment, age of the pigs, and gut location that is sampled. Both culture-independent and -dependent studies have also shown that the swine gut microbiota contains a large number of antimicrobial resistance determinants even in the absence of antimicrobial exposure. Heavy metals, such as zinc and copper, which are often added at relatively high doses to swine feed, may also play a role in maintaining antimicrobial resistance and in the stability of the swine gut microbiota. This review focuses on the use of antimicrobials in swine production, with an emphasis on the North American regulatory context, and their effect on the swine gut microbiota and on antimicrobial resistance determinants in the gut microbiota. PMID:26414105

  9. Evolution of acquired resistance to anti-cancer therapy

    PubMed Central

    Foo, Jasmine; Michor, Franziska

    2014-01-01

    Acquired drug resistance is a major limitation for the successful treatment of cancer. Resistance can emerge due to a variety of reasons including host environmental factors as well as genetic or epigenetic alterations in the cancer cells. Evolutionary theory has contributed to the understanding of the dynamics of resistance mutations in a cancer cell population, the risk of resistance pre-existing before the initiation of therapy, the composition of drug cocktails necessary to prevent the emergence of resistance, and optimum drug administration schedules for patient populations at risk of evolving acquired resistance. Here we review recent advances towards elucidating the evolutionary dynamics of acquired drug resistance and outline how evolutionary thinking can contribute to outstanding questions in the field. PMID:24681298

  10. CIPROFLOXACIN RESISTANCE PATTERN AMONG BACTERIA ISOLATED FROM PATIENTS WITH COMMUNITY-ACQUIRED URINARY TRACT INFECTION

    PubMed Central

    REIS, Ana Carolina Costa; SANTOS, Susana Regia da Silva; de SOUZA, Siane Campos; SALDANHA, Milena Góes; PITANGA, Thassila Nogueira; OLIVEIRA, Ricardo Riccio

    2016-01-01

    SUMMARY Objective: To identify the main bacterial species associated with community-acquired urinary tract infection (UTI) and to assess the pattern of ciprofloxacin susceptibility among bacteria isolated from urine cultures. Methods: We conducted a retrospective study in all the patients with community-acquired UTI seen in Santa Helena Laboratory, Camaçari, Bahia, Brazil during five years (2010-2014). All individuals who had a positive urine culture result were included in this study. Results: A total of 1,641 individuals met the inclusion criteria. Despite the fact that participants were female, we observed a higher rate of resistance to ciprofloxacin in males. The most frequent pathogens identified in urine samples were Escherichia coli, Klebsiella pneumoniae and Staphylococcus saprophyticus. Antimicrobial resistance has been observed mainly for ampicillin, sulfamethoxazole + trimethoprim and ciprofloxacin. Moreover, E. coli has shown the highest rate of ciprofloxacin resistance, reaching 36% of ciprofloxacin resistant strains in 2014. Conclusion: The rate of bacterial resistance to ciprofloxacin observed in the studied population is much higher than expected, prompting the need for rational use of this antibiotic, especially in infections caused by E. coli. Prevention of bacterial resistance can be performed through control measures to limit the spread of resistant microorganisms and a rational use of antimicrobial policy. PMID:27410913

  11. Is Antimicrobial Resistance a Slowly Emerging Disaster?

    PubMed Central

    Viens, A. M.

    2015-01-01

    The problem of antimicrobial resistance is so dire that people are predicting that the era of antibiotics may be coming to an end, ushering in a ‘post-antibiotic’ era. A comprehensive policy response is therefore urgently needed. A part of this response will require framing the problem in such a way that adequately reflects its nature as well as encompassing an approach that has the best prospect of success. This paper considers framing the problem as a slowly emerging disaster, including its potential benefits and difficulties, from a conceptual and policy perspective. PMID:26566396

  12. Antimicrobial Resistance Prediction in PATRIC and RAST

    PubMed Central

    Davis, James J.; Boisvert, Sébastien; Brettin, Thomas; Kenyon, Ronald W.; Mao, Chunhong; Olson, Robert; Overbeek, Ross; Santerre, John; Shukla, Maulik; Wattam, Alice R.; Will, Rebecca; Xia, Fangfang; Stevens, Rick

    2016-01-01

    The emergence and spread of antimicrobial resistance (AMR) mechanisms in bacterial pathogens, coupled with the dwindling number of effective antibiotics, has created a global health crisis. Being able to identify the genetic mechanisms of AMR and predict the resistance phenotypes of bacterial pathogens prior to culturing could inform clinical decision-making and improve reaction time. At PATRIC (http://patricbrc.org/), we have been collecting bacterial genomes with AMR metadata for several years. In order to advance phenotype prediction and the identification of genomic regions relating to AMR, we have updated the PATRIC FTP server to enable access to genomes that are binned by their AMR phenotypes, as well as metadata including minimum inhibitory concentrations. Using this infrastructure, we custom built AdaBoost (adaptive boosting) machine learning classifiers for identifying carbapenem resistance in Acinetobacter baumannii, methicillin resistance in Staphylococcus aureus, and beta-lactam and co-trimoxazole resistance in Streptococcus pneumoniae with accuracies ranging from 88–99%. We also did this for isoniazid, kanamycin, ofloxacin, rifampicin, and streptomycin resistance in Mycobacterium tuberculosis, achieving accuracies ranging from 71–88%. This set of classifiers has been used to provide an initial framework for species-specific AMR phenotype and genomic feature prediction in the RAST and PATRIC annotation services. PMID:27297683

  13. Antimicrobial Resistance Prediction in PATRIC and RAST.

    PubMed

    Davis, James J; Boisvert, Sébastien; Brettin, Thomas; Kenyon, Ronald W; Mao, Chunhong; Olson, Robert; Overbeek, Ross; Santerre, John; Shukla, Maulik; Wattam, Alice R; Will, Rebecca; Xia, Fangfang; Stevens, Rick

    2016-01-01

    The emergence and spread of antimicrobial resistance (AMR) mechanisms in bacterial pathogens, coupled with the dwindling number of effective antibiotics, has created a global health crisis. Being able to identify the genetic mechanisms of AMR and predict the resistance phenotypes of bacterial pathogens prior to culturing could inform clinical decision-making and improve reaction time. At PATRIC (http://patricbrc.org/), we have been collecting bacterial genomes with AMR metadata for several years. In order to advance phenotype prediction and the identification of genomic regions relating to AMR, we have updated the PATRIC FTP server to enable access to genomes that are binned by their AMR phenotypes, as well as metadata including minimum inhibitory concentrations. Using this infrastructure, we custom built AdaBoost (adaptive boosting) machine learning classifiers for identifying carbapenem resistance in Acinetobacter baumannii, methicillin resistance in Staphylococcus aureus, and beta-lactam and co-trimoxazole resistance in Streptococcus pneumoniae with accuracies ranging from 88-99%. We also did this for isoniazid, kanamycin, ofloxacin, rifampicin, and streptomycin resistance in Mycobacterium tuberculosis, achieving accuracies ranging from 71-88%. This set of classifiers has been used to provide an initial framework for species-specific AMR phenotype and genomic feature prediction in the RAST and PATRIC annotation services. PMID:27297683

  14. Antimicrobial resistance prediction in PATRIC and RAST

    DOE PAGESBeta

    Davis, James J.; Boisvert, Sebastien; Brettin, Thomas; Kenyon, Ronald W.; Mao, Chunhong; Olson, Robert; Overbeek, Ross; Santerre, John; Shukla, Maulik; Wattam, Alice R.; et al

    2016-06-14

    The emergence and spread of antimicrobial resistance (AMR) mechanisms in bacterial pathogens, coupled with the dwindling number of effective antibiotics, has created a global health crisis. Being able to identify the genetic mechanisms of AMR and predict the resistance phenotypes of bacterial pathogens prior to culturing could inform clinical decision-making and improve reaction time. At PATRIC (http://patricbrc.org/), we have been collecting bacterial genomes with AMR metadata for several years. In order to advance phenotype prediction and the identification of genomic regions relating to AMR, we have updated the PATRIC FTP server to enable access to genomes that are binned bymore » their AMR phenotypes, as well as metadata including minimum inhibitory concentrations. Using this infrastructure, we custom built AdaBoost (adaptive boosting) machine learning classifiers for identifying carbapenem resistance in Acinetobacter baumannii, methicillin resistance in Staphylococcus aureus, and beta-lactam and co-trimoxazole resistance in Streptococcus pneumoniae with accuracies ranging from 88–99%. We also did this for isoniazid, kanamycin, ofloxacin, rifampicin, and streptomycin resistance in Mycobacterium tuberculosis, achieving accuracies ranging from 71–88%. Lastly, this set of classifiers has been used to provide an initial framework for species-specific AMR phenotype and genomic feature prediction in the RAST and PATRIC annotation services.« less

  15. Curbing the menace of antimicrobial resistance in developing countries

    PubMed Central

    2009-01-01

    Several reports suggest that antimicrobial resistance is an increasing global problem; but like most pandemics, the greatest toll is in the less developed countries. The dismally low rate of discovery of antimicrobials compared to the rate of development of antimicrobial resistance places humanity on a very dangerous precipice. Since antimicrobial resistance is part of an organism's natural survival instinct, total eradication might be unachievable; however, it can be reduced to a level that it no longer poses a threat to humanity. While inappropriate antimicrobial consumption contributes to the development of antimicrobial resistance, other complex political, social, economic and biomedical factors are equally important. Tackling the menace therefore should go beyond the conventional sensitization of members of the public and occasional press releases to include a multi-sectoral intervention involving the formation of various alliances and partnerships. Involving civil society organisations like the media could greatly enhance the success of the interventions PMID:19922676

  16. The Ethical Significance of Antimicrobial Resistance

    PubMed Central

    Littmann, Jasper

    2015-01-01

    In this paper, we provide a state-of-the-art overview of the ethical challenges that arise in the context of antimicrobial resistance (AMR), which includes an introduction to the contributions to the symposium in this issue. We begin by discussing why AMR is a distinct ethical issue, and should not be viewed purely as a technical or medical problem. In the second section, we expand on some of these arguments and argue that AMR presents us with a broad range of ethical problems that must be addressed as part of a successful policy response to emerging drug resistance. In the third section, we discuss how some of these ethical challenges should be addressed, and we argue that this requires contributions from citizens, ethicists, policy makers, practitioners and industry. We conclude with an overview of steps that should be taken in moving forward and addressing the ethical problems of AMR. PMID:26566395

  17. National Antimicrobial Resistance Monitoring System (NARMS) 2010 Report

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In an effort to prospectively monitor the emergence of antimicrobial resistance in zoonotic pathogens, the National Antimicrobial Resistance Monitoring System (NARMS) was established in 1996 by the Food and Drug Administration’s Center for Veterinary Medicine in collaboration with the Centers for Di...

  18. Food Production and Antimicrobial Resistance – The Next 100 Years

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Production of food is complex and ensuring the safety of food for human consumption provides serious challenges. Since 1996 the U.S. has conducted surveillance on food borne and commensal antimicrobial resistance bacteria through the National Antimicrobial Resistance Monitoring System - Enteric Bac...

  19. Antimicrobial resistance of foodborne pathogens in the United States

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antimicrobial resistance has become a global concern since antibiotics were first introduced for clinical treatment of human and animal infections. Surveillance systems that monitor for antimicrobial resistance are often quite valuable. In 1996, three U.S. federal agencies: the U.S. Food and Drug A...

  20. Engineering Antimicrobials that are Refractory to Resistance Development.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Multi-drug resistant pathogens are a serious problem in modern health care and there is a need for novel antimicrobials that are refractory to resistance development. Several US government agencies (FDA, CDC and NIH) recommend avoiding the use of broad range antimicrobials, a practice that is known...

  1. Acquired Drug Resistance in Mycobacterium tuberculosis and Poor Outcomes among Patients with Multidrug-Resistant Tuberculosis

    PubMed Central

    Kipiani, Maia; Mirtskhulava, Veriko; Tukvadze, Nestani; Magee, Matthew J.; Blumberg, Henry M.

    2015-01-01

    Rates and risk factors for acquired drug resistance and association with outcomes among patients with multidrug-resistant tuberculosis (MDR TB) are not well defined. In an MDR TB cohort from the country of Georgia, drug susceptibility testing for second-line drugs (SLDs) was performed at baseline and every third month. Acquired resistance was defined as any SLD whose status changed from susceptible at baseline to resistant at follow-up. Among 141 patients, acquired resistance in Mycobacterium tuberculosis was observed in 19 (14%); prevalence was 9.1% for ofloxacin and 9.8% for capreomycin or kanamycin. Baseline cavitary disease and resistance to >6 drugs were associated with acquired resistance. Patients with M. tuberculosis that had acquired resistance were at significantly increased risk for poor treatment outcome compared with patients without these isolates (89% vs. 36%; p<0.01). Acquired resistance occurs commonly among patients with MDR TB and impedes successful treatment outcomes. PMID:25993036

  2. [Susceptibility and resistence of Pseudomonas aeruginosa to antimicrobial agents].

    PubMed

    Gamero Delgado, M C; García-Mayorgas, A D; Rodríguez, F; Ibarra, A; Casal, M

    2007-06-01

    Pseudomonas aeruginosa is an opportunistic microorganism that is frequently the cause of nosocomial infections. Multiple mechanisms are involved in its natural and acquired resistance to many of the antimicrobial agents commonly used in clinical practice. The objective of this study was to assess the susceptibility and resistance patterns of P. aeruginosa strains isolated in Hospital Reina Sofia between 2000 and 2005, as well as to analyze the differences between intrahospital and extrahospital isolates in 2005 and to compare the results with those obtained in other studies. A total of 3,019 strains of P. aeruginosa from different hospitals and nonhospital settings were evaluated, taking into consideration their degree of sensitivity to different antibiotics. The MICs were determined by means of the Wider I automated system (Soria Melguizo), taking into consideration the criteria of susceptibility and resistance recommended by MENSURA. Results of the analysis showed that P. aeruginosa maintained similar levels of antimicrobial susceptibility during the period 2000-2005, with increased susceptibility to amikacin, gentamicin and tobramycin. There were also important differences in the degree of susceptibility between intrahospital and extrahospital strains, except for imipenem and fosfomycin. The intrahospital difference in susceptibility was also evaluated, emphasizing the importance of periodically studying susceptibility and resistance patterns of P. aeruginosa in each setting in order to evaluate different therapeutic guidelines, as it is not always advisable to extrapolate data from different regions. These differences can be explained by the different use of antibiotics in each center and the geographic variations of the resistance mechanisms of P. aeruginosa. PMID:17893761

  3. A Research-Inspired Laboratory Sequence Investigating Acquired Drug Resistance

    ERIC Educational Resources Information Center

    Taylor, Elizabeth Vogel; Fortune, Jennifer A.; Drennan, Catherine L.

    2010-01-01

    Here, we present a six-session laboratory exercise designed to introduce students to standard biochemical techniques in the context of investigating a high impact research topic, acquired resistance to the cancer drug Gleevec. Students express a Gleevec-resistant mutant of the Abelson tyrosine kinase domain, the active domain of an oncogenic…

  4. Antimicrobial-resistant bacterial populations and antimicrobial resistance genes obtained from environments impacted by livestock and municipal waste

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study compared the populations of antimicrobial-resistant bacteria and the repertoire of antimicrobial resistance genes in four environments: effluent of three municipal waste water treatment facilities, three cattle feedlot runoff catchment ponds, three swine waste lagoons, and two "low impact...

  5. Salmon Aquaculture and Antimicrobial Resistance in the Marine Environment

    PubMed Central

    Buschmann, Alejandro H.; Tomova, Alexandra; López, Alejandra; Maldonado, Miguel A.; Henríquez, Luis A.; Ivanova, Larisa; Moy, Fred; Godfrey, Henry P.; Cabello, Felipe C.

    2012-01-01

    Antimicrobials used in salmon aquaculture pass into the marine environment. This could have negative impacts on marine environmental biodiversity, and on terrestrial animal and human health as a result of selection for bacteria containing antimicrobial resistance genes. We therefore measured the numbers of culturable bacteria and antimicrobial-resistant bacteria in marine sediments in the Calbuco Archipelago, Chile, over 12-month period at a salmon aquaculture site approximately 20 m from a salmon farm and at a control site 8 km distant without observable aquaculture activities. Three antimicrobials extensively used in Chilean salmon aquaculture (oxytetracycline, oxolinic acid, and florfenicol) were studied. Although none of these antimicrobials was detected in sediments from either site, traces of flumequine, a fluoroquinolone antimicrobial also widely used in Chile, were present in sediments from both sites during this period. There were significant increases in bacterial numbers and antimicrobial-resistant fractions to oxytetracycline, oxolinic acid, and florfenicol in sediments from the aquaculture site compared to those from the control site. Interestingly, there were similar numbers of presumably plasmid-mediated resistance genes for oxytetracycline, oxolinic acid and florfenicol in unselected marine bacteria isolated from both aquaculture and control sites. These preliminary findings in one location may suggest that the current use of large amounts of antimicrobials in Chilean aquaculture has the potential to select for antimicrobial-resistant bacteria in marine sediments. PMID:22905164

  6. Antimicrobial resistance in Escherichia coli O157 and non-O157 recovered from feces of domestic farm animals in Northwestern Mexico

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antimicrobial resistance in Shiga toxin-producing Escherichia coli (STEC) O157 and non-O157 is a matter of increasing concern. Inappropriate antimicrobial use in human and animal therapy has been associated with an acquired resistance in enteric microorganisms. The aim of the present study was to de...

  7. An economic perspective on policy to reduce antimicrobial resistance.

    PubMed

    Coast, J; Smith, R D; Millar, M R

    1998-01-01

    Resistance to antimicrobial drugs is increasing worldwide. This resistance is, at least in part, associated with high antimicrobial usage. Despite increasing awareness, economists (and policy analysts more generally) have paid little attention to the problem. In this paper antimicrobial resistance is conceptualised as a negative externality associated with the consumption of antimicrobials and is set within the broader context of the costs and benefits associated with antimicrobial usage. It is difficult to determine the overall impact of attempting to reduce resistance, given the extremely limited ability to model the epidemiology of resistant and sensitive micro-organisms. It is assumed for the purposes of the paper, however, that dealing with resistance by reducting antimicrobial usage would lead to a positive societal benefit. Three policy options traditionally associated with environmental economics (regulation, permits and charges) are examined in relation to their potential ability to impact upon the problem of resistance. The primary care sector of the U.K.'s National Health Service provides the context for this examination. Simple application of these policies to health care is likely to be problematic, with difficulties resulting particularly from the potential reduction in clinical freedom to prescribe when appropriate, and from the desire for equity in health care provision. The paper tentatively concludes that permits could offer the best policy response to antimicrobial resistance, with the caveat that empirical research is needed to develop the most practical and efficient system. This research must be conducted alongside the required epidemiological research. PMID:9464666

  8. Analysis of Antimicrobial Resistance Genes Detected in MDR Salmonella enterica Serovar Typhimurium animal isolates from the National Antimicrobial Resistance Monitoring System

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: The presence of Multi-Drug Resistant (MDR) Salmonella in food animals is concerning. To understand how antimicrobial resistance (AR) develops, the genetic elements responsible for MDR phenotypes in Salmonella animal isolates were investigated. National Antimicrobial Resistance Monitoring...

  9. Multiple antimicrobial resistance in Enterobacteriaceae isolates from pristine freshwater.

    PubMed

    Lima-Bittencourt, C I; Cursino, L; Gonçalves-Dornelas, H; Pontes, D S; Nardi, R M D; Callisto, M; Chartone-Souza, E; Nascimento, A M A

    2007-01-01

    A freshwater enterobacterial population (N = 111) was studied for antimicrobial and mercury resistance patterns, and for its possible association with biotic and abiotic factors in that environment. Conventional biochemical tests identified Klebsiella sp, Morganella sp, Serratia sp, Escherichia sp, Enterobacter sp, Edwarsiella sp, Proteus sp, Citrobacter sp, Providencia sp, and Kluyvera sp. There was no correlation between antimicrobial resistance patterns of isolates and bacterial genera, but resistance patterns varied among water samples and between seasons. Resistance to multiple antimicrobials was common (61%). The percentage of bacteria resistant to at least one antimicrobial differed between the rainy (100%) and dry seasons (89%). Resistance to beta-lactams and chloramphenicol was the most frequent and resistance to amikacin, gentamicin and kanamycin was less frequent. The main water variables examined (abiotic factors pH and temperature; biotic factor chlorophyll a concentration) did not influence antimicrobial resistance. Significant impact on freshwater enterobacteria, as evidenced by antimicrobial-multiple resistance and by the presence of bla(TEM) gene, may point to the fact that it has an important role in horizontal spread of resistance. PMID:17985304

  10. Integrating Hospital-Acquired Lessons into Community Health Practice: Optimizing Antimicrobial Use in Bangalore

    ERIC Educational Resources Information Center

    Biswas, Rakesh; Dineshan, Vineeth; Narasimhamurthy, N. S.; Kasthuri, A. S.

    2007-01-01

    Introduction: Even as antimicrobial resistance is a serious public health concern worldwide, the uncertainties of diagnosis and treatment of fever strongly influence community practitioners toward prescribing antibiotics. To help community practitioners resolve their diagnostic questions and reduce the unnecessary use of antibiotics for viral…

  11. Update: The National Antimicrobial Resistance Monitoring System Enteric Bacteria (NARMS): Animal Arm

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antimicrobial susceptibility testing remains an important tool as investigators devise ways to arrest the development of antimicrobial resistance, particularly in food borne bacteria. In 1996, the Food and Drug Administration (FDA) initiated the National Antimicrobial Resistance Monitoring System -...

  12. Overview Of Antimicrobial Resistance In Food Borne Pathogens In The United States

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antimicrobial susceptibility testing remains an important tool as investigators devise ways to arrest the development of antimicrobial resistance, particularly in food borne bacteria. In 1996, the Food and Drug Administration (FDA) initiated the National Antimicrobial Resistance Monitoring System -...

  13. Characterization and Tracking of Antimicrobial Resistant Pathogens at Various Points along the Poultry Production Chain

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antimicrobial susceptibility testing remains an important tool as investigators devise ways to arrest the development of antimicrobial resistance, particularly in food borne bacteria. In 1996, the Food and Drug Administration (FDA) initiated the National Antimicrobial Resistance Monitoring System -...

  14. Antimicrobial resistance of three species of Bacillus to thirty various antimicrobial agents.

    PubMed

    Moldenhauer, J E; Bass, S; Rubio, S L

    1996-01-01

    Three frequently used strains of Bacillus were tested using antimicrobial susceptibility test discs to determine their resistance to various antimicrobial drug agents. The organisms selected were B. subtilis ATCC 6633 (used for USP B and F tests), B. stearothermophilus ATCC 12980 (used as a biological indicator for steam sterilization) and B. coagulans ATCC 51232 (used as a biological indicator for steam sterilization). The results indicated that for the thirty antimicrobial drug agents tested, the only organisms which exhibited any resistance to these agents was B. subtilis, and it only showed resistance to two drugs (Aztreonam and Bacitracin). PMID:8973119

  15. Association between antimicrobial consumption and resistance in Escherichia coli.

    PubMed

    Bergman, Miika; Nyberg, Solja T; Huovinen, Pentti; Paakkari, Pirkko; Hakanen, Antti J

    2009-03-01

    During a 9-year study period from 1997 through 2005, the association between antimicrobial resistance rates in Escherichia coli and outpatient antimicrobial consumption was investigated in 20 hospital districts in Finland. A total of 754,293 E. coli isolates, mainly from urine samples, were tested for antimicrobial resistance in 26 clinical microbiology laboratories. The following antimicrobials were studied: ampicillin, amoxicillin-clavulanate, cephalosporins, fluoroquinolones, trimethoprim, trimethoprim-sulfamethoxazole, pivmecillinam, and nitrofurantoin. We applied a protocol used in earlier studies in which the level of antimicrobial consumption over 1 year was compared with the level of resistance in the next year. Statistically significant associations were found for nitrofurantoin use versus nitrofurantoin resistance (P < 0.0001), cephalosporin use versus nitrofurantoin resistance (P = 0.0293), amoxicillin use versus fluoroquinolone resistance (P = 0.0031), and fluoroquinolone use versus ampicillin resistance (P = 0.0046). Interestingly, we found only a few associations between resistance and antimicrobial consumption. The majority of the associations studied were not significant, including the association between fluoroquinolone use and fluoroquinolone resistance. PMID:19104012

  16. Shigellosis in Subjects with Traveler's Diarrhea Versus Domestically Acquired Diarrhea: Implications for Antimicrobial Therapy and Human Immunodeficiency Virus Surveillance.

    PubMed

    Toro, Carlos; Arroyo, Ana; Sarria, Ana; Iglesias, Nuria; Enríquez, Ana; Baquero, Margarita; de Guevara, Concepción Ladrón

    2015-09-01

    An increase of sexually transmitted shigellosis is currently being reported in developed countries. In addition, travel-related shigellosis can introduce resistant strains that could be disseminated within this new scenario. Epidemiological features and antimicrobial susceptibility of shigellosis depending on where infection was acquired were investigated. From 2008 to 2013, subjects with shigellosis were studied. Patients were classified according to acquisition of Shigella as traveler's diarrhea (TD) or domestically acquired diarrhea (DAD). Ninety cases of shigellosis were identified: 76 corresponding to the TD group and 14 to the DAD group. In the DAD group, most of patients were human immunodeficiency virus (HIV)-positive men who have sex with men (MSM), being shigellosis associated to male sex (P = 0.007) and HIV infection (P < 0.0001). S. sonnei (47.8%) and S. flexneri (42.2%) were the predominant species. The highest resistance was detected for trimethoprim/sulfamethoxazole (SXT) (81.8%), followed by ampicillin (AMP) (37.8%) and ciprofloxacin (CIP) (23.3%). Resistant Shigella strains were more frequent in subjects with TD than those with DAD, although only for CIP the difference was significant (P = 0.034). Continuous monitoring of patients with shigellosis is necessary to control the spread of resistant Shigella strains and for effective therapy. Men with shigellosis who have not traveled to an endemic area should be screened for HIV infection. PMID:26195465

  17. Shigellosis in Subjects with Traveler's Diarrhea versus Domestically Acquired Diarrhea: Implications for Antimicrobial Therapy and Human Immunodeficiency Virus Surveillance

    PubMed Central

    Toro, Carlos; Sarria, Ana Arroyo, Ana; Iglesias, Nuria; Enríquez, Ana; Baquero, Margarita; de Guevara, Concepción Ladrón

    2015-01-01

    An increase of sexually transmitted shigellosis is currently being reported in developed countries. In addition, travel-related shigellosis can introduce resistant strains that could be disseminated within this new scenario. Epidemiological features and antimicrobial susceptibility of shigellosis depending on where infection was acquired were investigated. From 2008 to 2013, subjects with shigellosis were studied. Patients were classified according to acquisition of Shigella as traveler's diarrhea (TD) or domestically acquired diarrhea (DAD). Ninety cases of shigellosis were identified: 76 corresponding to the TD group and 14 to the DAD group. In the DAD group, most of patients were human immunodeficiency virus (HIV)-positive men who have sex with men (MSM), being shigellosis associated to male sex (P = 0.007) and HIV infection (P < 0.0001). S. sonnei (47.8%) and S. flexneri (42.2%) were the predominant species. The highest resistance was detected for trimethoprim/sulfamethoxazole (SXT) (81.8%), followed by ampicillin (AMP) (37.8%) and ciprofloxacin (CIP) (23.3%). Resistant Shigella strains were more frequent in subjects with TD than those with DAD, although only for CIP the difference was significant (P = 0.034). Continuous monitoring of patients with shigellosis is necessary to control the spread of resistant Shigella strains and for effective therapy. Men with shigellosis who have not traveled to an endemic area should be screened for HIV infection. PMID:26195465

  18. Antimicrobial resistance-a threat to the world's sustainable development.

    PubMed

    Jasovský, Dušan; Littmann, Jasper; Zorzet, Anna; Cars, Otto

    2016-08-01

    This commentary examines how specific sustainable development goals (SDGs) are affected by antimicrobial resistance and suggests how the issue can be better integrated into international policy processes. Moving beyond the importance of effective antibiotics for the treatment of acute infections and health care generally, we discuss how antimicrobial resistance also impacts on environmental, social, and economic targets in the SDG framework. The paper stresses the need for greater international collaboration and accountability distribution, and suggests steps towards a broader engagement of countries and United Nations agencies to foster global intersectoral action on antimicrobial resistance. PMID:27416324

  19. The complex interplay of iron, biofilm formation, and mucoidy affecting antimicrobial resistance of Pseudomonas aeruginosa.

    PubMed

    Oglesby-Sherrouse, Amanda G; Djapgne, Louise; Nguyen, Angela T; Vasil, Adriana I; Vasil, Michael L

    2014-04-01

    Pseudomonas aeruginosa is a Gram-negative opportunistic bacterial pathogen that is refractory to a variety of current antimicrobial therapeutic regimens. Complicating treatment for such infections is the ability of P. aeruginosa to form biofilms, as well as several innate and acquired resistance mechanisms. Previous studies suggest iron plays a role in resistance to antimicrobial therapy, including the efficacy of an FDA-approved iron chelator, deferasirox (DSX), or Gallium, an iron analog, in potentiating antibiotic-dependent killing of P. aeruginosa biofilms. Here, we show that iron-replete conditions enhance resistance of P. aeruginosa nonbiofilm growth against tobramycin and tigecycline. Interestingly, the mechanism of iron-enhanced resistance to each of these antibiotics is distinct. Whereas pyoverdine-mediated iron uptake is important for optimal resistance to tigecycline, it does not enhance tobramycin resistance. In contrast, heme supplementation results in increased tobramycin resistance, while having no significant effect on tigecycline resistance. Thus, nonsiderophore bound iron plays an important role in resistance to tobramycin, while pyoverdine increases the ability of P. aeruginosa to resist tigecycline treatment. Lastly, we show that iron increases the minimal concentration of tobramycin, but not tigecycline, required to eradicate P. aeruginosa biofilms. Moreover, iron depletion blocks the previous observed induction of biofilm formation by subinhibitory concentrations of tobramycin, suggesting iron and tobramycin signal through overlapping regulatory pathways to affect biofilm formation. These data further support the role of iron in P. aeruginosa antibiotic resistance, providing yet another compelling case for targeting iron acquisition for future antimicrobial drug development. PMID:24436170

  20. Antimicrobial-resistant enterococci in animals and meat: a human health hazard?

    PubMed

    Hammerum, Anette M; Lester, Camilla H; Heuer, Ole E

    2010-10-01

    Enterococcus faecium and Enterococcus faecalis belong to the gastrointestinal flora of humans and animals. Although normally regarded harmless commensals, enterococci may cause a range of different infections in humans, including urinary tract infections, sepsis, and endocarditis. The use of avoparcin, gentamicin, and virginiamycin for growth promotion and therapy in food animals has lead to the emergence of vancomycin- and gentamicin-resistant enterococci and quinupristin/dalfopristin-resistant E. faecium in animals and meat. This implies a potential risk for transfer of resistance genes or resistant bacteria from food animals to humans. The genes encoding resistance to vancomycin, gentamicin, and quinupristin/dalfopristin have been found in E. faecium of human and animal origin; meanwhile, certain clones of E. faecium are found more frequently in samples from human patients, while other clones predominate in certain animal species. This may suggest that antimicrobial-resistant E. faecium from animals could be regarded less hazardous to humans; however, due to their excellent ability to acquire and transfer resistance genes, E. faecium of animal origin may act as donors of antimicrobial resistance genes for other more virulent enterococci. For E. faecalis, the situation appears different, as similar clones of, for example, vancomycin- and gentamicin-resistant E. faecalis have been obtained from animals and from human patients. Continuous surveillance of antimicrobial resistance in enterococci from humans and animals is essential to follow trends and detect emerging resistance. PMID:20578915

  1. ANTIMICROBIAL RESISTANCE PATTERNS OF SALMONELLA FROM RETAIL CHICKEN

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Salmonella is frequently reported as a cause of food-borne illness. The emergence of antimicrobial resistant Salmonella associated with meat products has heightened concerns regarding antimicrobial use in food animal production. Eighty Salmonella isolates recovered from fresh whole chicken carcass...

  2. Targets for Combating the Evolution of Acquired Antibiotic Resistance.

    PubMed

    Culyba, Matthew J; Mo, Charlie Y; Kohli, Rahul M

    2015-06-16

    Bacteria possess a remarkable ability to rapidly adapt and evolve in response to antibiotics. Acquired antibiotic resistance can arise by multiple mechanisms but commonly involves altering the target site of the drug, enzymatically inactivating the drug, or preventing the drug from accessing its target. These mechanisms involve new genetic changes in the pathogen leading to heritable resistance. This recognition underscores the importance of understanding how such genetic changes can arise. Here, we review recent advances in our understanding of the processes that contribute to the evolution of antibiotic resistance, with a particular focus on hypermutation mediated by the SOS pathway and horizontal gene transfer. We explore the molecular mechanisms involved in acquired resistance and discuss their viability as potential targets. We propose that additional studies into these adaptive mechanisms not only can provide insights into evolution but also can offer a strategy for potentiating our current antibiotic arsenal. PMID:26016604

  3. Targets for Combating the Evolution of Acquired Antibiotic Resistance

    PubMed Central

    2015-01-01

    Bacteria possess a remarkable ability to rapidly adapt and evolve in response to antibiotics. Acquired antibiotic resistance can arise by multiple mechanisms but commonly involves altering the target site of the drug, enzymatically inactivating the drug, or preventing the drug from accessing its target. These mechanisms involve new genetic changes in the pathogen leading to heritable resistance. This recognition underscores the importance of understanding how such genetic changes can arise. Here, we review recent advances in our understanding of the processes that contribute to the evolution of antibiotic resistance, with a particular focus on hypermutation mediated by the SOS pathway and horizontal gene transfer. We explore the molecular mechanisms involved in acquired resistance and discuss their viability as potential targets. We propose that additional studies into these adaptive mechanisms not only can provide insights into evolution but also can offer a strategy for potentiating our current antibiotic arsenal. PMID:26016604

  4. Antimicrobial-Resistant Bacterial Populations and Antimicrobial Resistance Genes Obtained from Environments Impacted by Livestock and Municipal Waste.

    PubMed

    Agga, Getahun E; Arthur, Terrance M; Durso, Lisa M; Harhay, Dayna M; Schmidt, John W

    2015-01-01

    This study compared the populations of antimicrobial-resistant bacteria and the repertoire of antimicrobial resistance genes in four environments: effluent of three municipal wastewater treatment facilities, three cattle feedlot runoff catchment ponds, three swine waste lagoons, and two "low impact" environments (an urban lake and a relict prairie). Multiple liquid and solid samples were collected from each environment. The prevalences and concentrations of antimicrobial-resistant (AMR) Gram-negative (Escherichia coli and Salmonella enterica) and Gram-positive (enterococci) bacteria were determined from individual samples (n = 174). The prevalences of 84 antimicrobial resistance genes in metagenomic DNA isolated from samples pooled (n = 44) by collection date, location, and sample type were determined. The prevalences and concentrations of AMR E. coli and Salmonella were similar among the livestock and municipal sample sources. The levels of erythromycin-resistant enterococci were significantly higher in liquid samples from cattle catchment ponds and swine waste lagoons than in liquid samples from municipal wastewater treatment facilities, but solid samples from these environments did not differ significantly. Similarly, trimethoprim/sulfamethoxazole-resistant E. coli concentrations were significantly higher in swine liquid than in municipal liquid samples, but there was no difference in solid samples. Multivariate analysis of the distribution of antimicrobial resistance genes using principal coordinate analysis showed distinct clustering of samples with livestock (cattle and swine), low impact environment and municipal samples forming three separate clusters. The numbers of class A beta-lactamase, class C beta-lactamase, and fluoroquinolone resistance genes detected were significantly higher (P < 0.05) in municipal samples than in cattle runoff or swine lagoon samples. In conclusion, we report that AMR is a very widespread phenomenon and that similar prevalences

  5. Antimicrobial-Resistant Bacterial Populations and Antimicrobial Resistance Genes Obtained from Environments Impacted by Livestock and Municipal Waste

    PubMed Central

    Durso, Lisa M.; Harhay, Dayna M.; Schmidt, John W.

    2015-01-01

    This study compared the populations of antimicrobial-resistant bacteria and the repertoire of antimicrobial resistance genes in four environments: effluent of three municipal wastewater treatment facilities, three cattle feedlot runoff catchment ponds, three swine waste lagoons, and two “low impact” environments (an urban lake and a relict prairie). Multiple liquid and solid samples were collected from each environment. The prevalences and concentrations of antimicrobial-resistant (AMR) Gram-negative (Escherichia coli and Salmonella enterica) and Gram-positive (enterococci) bacteria were determined from individual samples (n = 174). The prevalences of 84 antimicrobial resistance genes in metagenomic DNA isolated from samples pooled (n = 44) by collection date, location, and sample type were determined. The prevalences and concentrations of AMR E. coli and Salmonella were similar among the livestock and municipal sample sources. The levels of erythromycin-resistant enterococci were significantly higher in liquid samples from cattle catchment ponds and swine waste lagoons than in liquid samples from municipal wastewater treatment facilities, but solid samples from these environments did not differ significantly. Similarly, trimethoprim/sulfamethoxazole-resistant E. coli concentrations were significantly higher in swine liquid than in municipal liquid samples, but there was no difference in solid samples. Multivariate analysis of the distribution of antimicrobial resistance genes using principal coordinate analysis showed distinct clustering of samples with livestock (cattle and swine), low impact environment and municipal samples forming three separate clusters. The numbers of class A beta-lactamase, class C beta-lactamase, and fluoroquinolone resistance genes detected were significantly higher (P < 0.05) in municipal samples than in cattle runoff or swine lagoon samples. In conclusion, we report that AMR is a very widespread phenomenon and that similar

  6. Antimicrobial susceptibilities of Escherichia coli isolates as agents of community-acquired urinary tract infection (2008–2014)

    PubMed Central

    Yılmaz, Nisel; Ağuş, Neval; Bayram, Arzu; Şamlıoğlu, Pınar; Şirin, M. Cem; Derici, Yeşer Karaca; Hancı, Sevgi Yılmaz

    2016-01-01

    Objective Urinary tract infections (UTIs) are among the most frequently seen community-acquired infections worldwide. E. coli causes 90% of urinary system infections. To guide the empirical therapy, the resistance pattern of E. coli responsible for community-acquired UTI was evaluated throughout a seven-year period in this study. Material and methods The urine cultures of patients with urinary tract infections admitted to outpatient clinics between 1st January 2008 and 31st December 2014 were analyzed. Presence of ≥105 colony-forming units/mL in urine culture media was considered as significant for UTI. Isolated bacteria were identified by standard laboratory techniques or automated system VITEK2 (BioMerieux, France) and BD PhoenixTM 100 (BD, USA), as required. Antibiotic susceptibility testing was performed by Kirby-Bauer disk diffusion method using Clinical Laboratory Standard Institute (CLSI) criteria. Results A total of 13281 uropathogens were isolated. Overall E. coli accounted for 8975 (67%) of all isolates. Resistance rates of E. coli to antimicrobial agents was demonstrated to be as follows: ampicillin 66.9%, cefazolin 30.9%, cefuroxime 30.9%, ceftazidime 14.9%, cefotaxime 28%, cefepime 12%, amoxicillin-clavulanic acid 36.9%, trimethoprim-sulfamethoxazole (TMP-SXT) 20%, ciprofloxacin 49.9%, amikacin 0.3%, gentamycin 24%, nitrofurantoin 0.9%, and fosfomycin 4.3%. There was no resistance to imipenem nor meropenem. The frequency of ESBL-producing E. coli strains was 24%. Conclusion It is concluded that fosfomycin and nitrofurantoin are appropriate empirical therapy for community-acquired UTI empirical therapy, but the fluoroquinolones and the TMP-SXT shall not be used in the emprical treatment of UTI at this stage. In conclusion, as resistance rates show regional differences, it is necessary to regularly examine regional resistance rates to determine the appropriate empiric antibiotic treatment and national antibiotic usage policies must be reorganized

  7. Bacterial resistance to antimicrobial peptides: an evolving phenomenon.

    PubMed

    Fleitas, Osmel; Agbale, Caleb M; Franco, Octavio L

    2016-01-01

    Bacterial resistance to conventional antibiotics is currently a real problem all over the world, making novel antimicrobial compounds a real research priority. Some of the most promising compounds found to date are antimicrobial peptides (AMPs). The benefits of these drugs include their broad spectrum of activity that affects several microbial processes, making the emergence of resistance less likely. However, bacterial resistance to AMPs is an evolving phenomenon that compromises the therapeutic potential of these compounds. Therefore, it is mandatory to understand bacterial mechanisms of resistance to AMPs in depth, in order to develop more powerful AMPs that overcome the bacterial resistance response. PMID:27100488

  8. Antimicrobial resistance profiles in pathogens isolated from chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antimicrobial resistance profiles are frequently studied from the perspective of epidemiology and not so often from the perspective of population genetics. The population geneticist assumes that gene flow, vertically (generation to generation), horizontally (individual to individual) or migratory (...

  9. Surveillance for Antimicrobial Drug Resistance in Under-Resourced Countries

    PubMed Central

    Mary, Catherine; Altmann, Dany M.; Doumbo, Ogobara; Morpeth, Susan; Bhutta, Zulfiqar A.; Klugman, Keith P.

    2014-01-01

    Antimicrobial drug resistance is usually not monitored in under-resourced countries because they lack surveillance networks, laboratory capacity, and appropriate diagnostics. This accelerating problem accounts for substantial number of excess deaths, especially among infants. Infections particularly affected by antimicrobial drug resistance include tuberculosis, malaria, severe acute respiratory infections, and sepsis caused by gram-negative bacteria. Nonetheless, mapping antimicrobial drug resistance is feasible in under-resourced countries, and lessons can be learned from previous successful efforts. Specimen shipping conditions, data standardization, absence of contamination, and adequate diagnostics must be ensured. As a first step toward solving this problem, we propose that a road map be created at the international level to strengthen antimicrobial resistance surveillance in under-resourced countries. This effort should include a research agenda; a map of existing networks and recommendations to unite them; and a communication plan for national, regional, and international organizations and funding agencies. PMID:24564906

  10. Staphylococci in community-acquired infections: Increased resistance to penicillin.

    PubMed

    Hughes, G B; Chidi, C C; Macon, W L

    1976-04-01

    One hundred patients with community-acquired staphylococcal infections of the skin and soft tissues were treated in the Emergency Ward of Cleveland Metropolitan General Hospital from June to October of 1974. Each staphylococcal infection was considered community-acquired if, within two weeks prior to being treated for the first time, the patient had not received antibiotics, had not been hospitalized, and had not been in contact with other recently hospitalized persons. Of 100 community-acquired staphylococcal infections, 85 were resistant to penicillin. Almost no resistance to other tested antibiotics was observed. Unless indicated otherwise by bacteriologic testing, penicillin is a poor drug of choice in those skin and soft tissue infections suspected of harboring staphylococci. PMID:1267491

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

    PubMed

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

    2016-02-01

    Enterococci and staphylococci are frequent contaminants on poultry meat. Enterococcus faecalis, Enterococcus faecium and Staphylococcus aureus are also well-known aetiological agents of a wide variety of infections resulting in major healthcare costs. This review provides an overview of the human health risks associated with the occurrence of these opportunistic human pathogens on poultry meat with particular focus on the risk of food-borne transmission of antimicrobial resistance. In the absence of conclusive evidence of transmission, this risk was inferred using data from scientific articles and national reports on prevalence, bacterial load, antimicrobial resistance and clonal distribution of these three species on poultry meat. The risks associated with ingestion of antimicrobial-resistant enterococci of poultry origin comprise horizontal transfer of resistance genes and transmission of multidrug-resistant E. faecalis lineages such as sequence type ST16. Enterococcus faecium lineages occurring in poultry meat products are distantly related to those causing hospital-acquired infections but may act as donors of quinupristin/dalfopristin resistance and other resistance determinants of clinical interest to the human gut microbiota. Ingestion of poultry meat contaminated with S. aureus may lead to food poisoning. However, antimicrobial resistance in the toxin-producing strains does not have clinical implications because food poisoning is not managed by antimicrobial therapy. Recently methicillin-resistant S. aureus of livestock origin has been reported on poultry meat. In theory handling or ingestion of contaminated meat is a potential risk factor for colonization by methicillin-resistant S. aureus. However, this risk is presently regarded as negligible by public health authorities. PMID:26706616

  12. Antimicrobial Use and Resistance in Swine Waste Treatment Systems▿

    PubMed Central

    Jindal, Archana; Kocherginskaya, Svetlana; Mehboob, Asma; Robert, Matthew; Mackie, Roderick I.; Raskin, Lutgarde; Zilles, Julie L.

    2006-01-01

    Chlortetracycline and the macrolide tylosin were identified as commonly used antimicrobials for growth promotion and prophylaxis in swine production. Resistance to these antimicrobials was measured throughout the waste treatment processes at five swine farms by culture-based and molecular methods. Conventional farm samples had the highest levels of resistance with both culture-based and molecular methods and had similar levels of resistance despite differences in antimicrobial usage. The levels of resistance in organic farm samples, where no antimicrobials were used, were very low by a culture-based method targeting fecal streptococci. However, when the same samples were analyzed with a molecular method detecting methylation of a specific nucleotide in the 23S rRNA that results in resistance to macrolides, lincosamides, and streptogramin B (MLSB), an unexpectedly high level of resistant rRNA (approximately 50%) was observed, suggesting that the fecal streptococci were not an appropriate target group to evaluate resistance in the overall microbial community and that background levels of MLSB resistance may be substantial. All of the feed samples tested, including those from the organic farm, contained tetracycline resistance genes. Generally, the same tetracycline resistance genes and frequency of detection were found in the manure and lagoon samples for each commercial farm. The levels of tetracycline and MLSB resistance remained high throughout the waste treatment systems, suggesting that the potential impact of land application of treated wastes and waste treatment by-products on environmental levels of resistance should be investigated further. PMID:17041160

  13. DETECTION OF ANTIMICROBIAL RESISTANCE GENES BY DNA MICROARRAY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To study the spread of antimicrobial resistance in bacteria it is necessary to identify the genes responsible for resistance. Currently, each gene must be screened individually in order to identify the gene(s) responsible for the observed resistance expressed by a bacterium. The inability to rapidly...

  14. Detection of antimicrobial resistance genes by DNA microarray

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To study the spread of antimicrobial resistance in bacteria it is necessary to detect and characterize the genes responsible for resistance. Currently, each gene must be screened individually in order to identify the gene(s) responsible for the observed resistance expressed by a bacterium. The inabi...

  15. Detection of antimicrobial resistance genes by DNA microarray

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To study the spread of antimicrobial resistance in bacteria it is necessary to identify the genes responsible for resistance. Currently, each gene must be screened individually in order to identify the gene(s) responsible for the observed resistance expressed by a bacterium. The inability to rapidly...

  16. Antimicrobial use and resistance in swine waste treatment systems.

    PubMed

    Jindal, Archana; Kocherginskaya, Svetlana; Mehboob, Asma; Robert, Matthew; Mackie, Roderick I; Raskin, Lutgarde; Zilles, Julie L

    2006-12-01

    Chlortetracycline and the macrolide tylosin were identified as commonly used antimicrobials for growth promotion and prophylaxis in swine production. Resistance to these antimicrobials was measured throughout the waste treatment processes at five swine farms by culture-based and molecular methods. Conventional farm samples had the highest levels of resistance with both culture-based and molecular methods and had similar levels of resistance despite differences in antimicrobial usage. The levels of resistance in organic farm samples, where no antimicrobials were used, were very low by a culture-based method targeting fecal streptococci. However, when the same samples were analyzed with a molecular method detecting methylation of a specific nucleotide in the 23S rRNA that results in resistance to macrolides, lincosamides, and streptogramin B (MLSB), an unexpectedly high level of resistant rRNA (approximately 50%) was observed, suggesting that the fecal streptococci were not an appropriate target group to evaluate resistance in the overall microbial community and that background levels of MLSB resistance may be substantial. All of the feed samples tested, including those from the organic farm, contained tetracycline resistance genes. Generally, the same tetracycline resistance genes and frequency of detection were found in the manure and lagoon samples for each commercial farm. The levels of tetracycline and MLSB resistance remained high throughout the waste treatment systems, suggesting that the potential impact of land application of treated wastes and waste treatment by-products on environmental levels of resistance should be investigated further. PMID:17041160

  17. An antimicrobial TiO2 coating for reducing hospital-acquired infection.

    PubMed

    Chung, Chi-Jen; Lin, Hsin-I; Tsou, Hsi-Kai; Shi, Zhi-Yuan; He, Ju-Liang

    2008-04-01

    Titanium dioxide (TiO2) has been developed and applied extensively in the form of coatings, in particular for its unique properties such as non-toxicity, high photocatalytic activity, and strong self-cleaning ability. These coatings, which can be prepared via various processes, have not yet been proved to be antimicrobial. This research involves an arc ion plating method to produce TiO2 film on medical grade AISI 304 stainless steel. Antimicrobial efficacy of the deposits is expected due to the photocatalysis action of the anatase phase presented in the deposit. The performance of the coating is evaluated by a JIS Z2801:2000 industrial standard. Experimental results show that TiO2 film mainly consisting of anatase structure can be prepared with a high growth rate of 5 microm/h. Antimicrobial activity (R) of the deposited TiO2 film against Staphylococcus aureus and Escherichia coli was 3.0 and 2.5, respectively, far beyond the value designated in JIS standard. This provides an effective antimicrobial surface coating method for medical implements thereby reducing the risk of hospital-acquired infections. PMID:17854067

  18. The global threat of antimicrobial resistance: science for intervention

    PubMed Central

    Roca, I.; Akova, M.; Baquero, F.; Carlet, J.; Cavaleri, M.; Coenen, S.; Cohen, J.; Findlay, D.; Gyssens, I.; Heure, O.E.; Kahlmeter, G.; Kruse, H.; Laxminarayan, R.; Liébana, E.; López-Cerero, L.; MacGowan, A.; Martins, M.; Rodríguez-Baño, J.; Rolain, J.-M.; Segovia, C.; Sigauque, B.; Taconelli, E.; Wellington, E.; Vila, J.

    2015-01-01

    In the last decade we have witnessed a dramatic increase in the proportion and absolute number of bacterial pathogens resistant to multiple antibacterial agents. Multidrug-resistant bacteria are currently considered as an emergent global disease and a major public health problem. The B-Debate meeting brought together renowned experts representing the main stakeholders (i.e. policy makers, public health authorities, regulatory agencies, pharmaceutical companies and the scientific community at large) to review the global threat of antibiotic resistance and come up with a coordinated set of strategies to fight antimicrobial resistance in a multifaceted approach. We summarize the views of the B-Debate participants regarding the current situation of antimicrobial resistance in animals and the food chain, within the community and the healthcare setting as well as the role of the environment and the development of novel diagnostic and therapeutic strategies, providing expert recommendations to tackle the global threat of antimicrobial resistance. PMID:26029375

  19. The global threat of antimicrobial resistance: science for intervention.

    PubMed

    Roca, I; Akova, M; Baquero, F; Carlet, J; Cavaleri, M; Coenen, S; Cohen, J; Findlay, D; Gyssens, I; Heuer, O E; Kahlmeter, G; Kruse, H; Laxminarayan, R; Liébana, E; López-Cerero, L; MacGowan, A; Martins, M; Rodríguez-Baño, J; Rolain, J-M; Segovia, C; Sigauque, B; Tacconelli, E; Wellington, E; Vila, J

    2015-07-01

    In the last decade we have witnessed a dramatic increase in the proportion and absolute number of bacterial pathogens resistant to multiple antibacterial agents. Multidrug-resistant bacteria are currently considered as an emergent global disease and a major public health problem. The B-Debate meeting brought together renowned experts representing the main stakeholders (i.e. policy makers, public health authorities, regulatory agencies, pharmaceutical companies and the scientific community at large) to review the global threat of antibiotic resistance and come up with a coordinated set of strategies to fight antimicrobial resistance in a multifaceted approach. We summarize the views of the B-Debate participants regarding the current situation of antimicrobial resistance in animals and the food chain, within the community and the healthcare setting as well as the role of the environment and the development of novel diagnostic and therapeutic strategies, providing expert recommendations to tackle the global threat of antimicrobial resistance. PMID:26029375

  20. Antimicrobial resistance of Actinobacillus pleuropneumoniae isolated from swine.

    PubMed

    Vanni, Michele; Merenda, Marianna; Barigazzi, Giuseppe; Garbarino, Chiara; Luppi, Andrea; Tognetti, Rosalba; Intorre, Luigi

    2012-04-23

    The aim of this retrospective study was to evaluate the antimicrobial resistance rates and the trend in resistance of Actinobacillus pleuropneumoniae isolated from pigs in Italy from 1994 to 2009. A total of 992 A. pleuropneumoniae isolates were tested for their susceptibility to a panel of antimicrobial agents in a disk diffusion method. Resistance to 7 drugs (amoxicillin, amoxicillin/clavulanic acid, ampicillin, cefquinome, cotrimoxazole, penicillin G and tilmicosin) showed a significant increasing trend over the time, while for 2 drugs (gentamycin and marbofloxacin) a significant decrease was observed. Resistance to the remaining 14 antimicrobial agents tested did not change significantly over the study period. Most of the isolates retained high susceptibility to antimicrobials usually effective against A. pleuropneumoniae such as amphenicols, fluoroquinolones and ceftiofur. However, high rates of resistance were observed for potentiated sulfa drugs, tetracyclines and penicillins which are currently recommended antimicrobials for pig pleuropneumonia therapy. Our results suggest the importance of continued monitoring of A. pleuropneumoniae clinical isolates in order to choose the most appropriate treatment of infections and to control the increase of resistance to currently used antimicrobials. PMID:22104584

  1. Development and spread of bacterial resistance to antimicrobial agents: an overview.

    PubMed

    Tenover, F C

    2001-09-15

    Resistance to antimicrobial agents is emerging in a wide variety of nosocomial and community-acquired pathogens. The emergence and spread of multiply resistant organisms represent the convergence of a variety of factors that include mutations in common resistance genes that extend their spectrum of activity, the exchange of genetic information among microorganisms, the evolution of selective pressures in hospitals and communities that facilitate the development and spread of resistant organisms, the proliferation and spread of multiply resistant clones of bacteria, and the inability of some laboratory testing methods to detect emerging resistance phenotypes. Twenty years ago, bacteria that were resistant to antimicrobial agents were easy to detect in the laboratory because the concentration of drug required to inhibit their growth was usually quite high and distinctly different from that of susceptible strains. Newer mechanisms of resistance, however, often result in much more subtle shifts in bacterial population distributions. Perhaps the most difficult phenotypes to detect, as shown in several proficiency testing surveys, are decreased susceptibility to beta-lactams in pneumococci and decreased susceptibility to vancomycin in staphylococci. In summary, emerging resistance has required adaptations and modifications of laboratory diagnostic techniques, empiric anti-infective therapy for such diseases as bacterial meningitis, and infection control measures in health care facilities of all kinds. Judicious use is imperative if we are to preserve our arsenal of antimicrobial agents into the next decade. PMID:11524705

  2. Extensive Drug Resistance Acquired During Treatment of Multidrug-Resistant Tuberculosis

    PubMed Central

    Cegielski, J. Peter; Dalton, Tracy; Yagui, Martin; Wattanaamornkiet, Wanpen; Volchenkov, Grigory V.; Via, Laura E.; Van Der Walt, Martie; Tupasi, Thelma; Smith, Sarah E.; Odendaal, Ronel; Leimane, Vaira; Kvasnovsky, Charlotte; Kuznetsova, Tatiana; Kurbatova, Ekaterina; Kummik, Tiina; Kuksa, Liga; Kliiman, Kai; Kiryanova, Elena V.; Kim, HeeJin; Kim, Chang-ki; Kazennyy, Boris Y.; Jou, Ruwen; Huang, Wei-Lun; Ershova, Julia; Erokhin, Vladislav V.; Diem, Lois; Contreras, Carmen; Cho, Sang Nae; Chernousova, Larisa N.; Chen, Michael P.; Caoili, Janice Campos; Bayona, Jaime; Akksilp, Somsak; Calahuanca, Gloria Yale; Wolfgang, Melanie; Viiklepp, Piret; Vasilieva, Irina A.; Taylor, Allison; Tan, Kathrine; Suarez, Carmen; Sture, Ingrida; Somova, Tatiana; Smirnova, Tatyana G.; Sigman, Erika; Skenders, Girts; Sitti, Wanlaya; Shamputa, Isdore C.; Riekstina, Vija; Pua, Kristine Rose; Therese, M.; Perez, C.; Park, Seungkyu; Norvaisha, Inga; Nemtsova, Evgenia S.; Min, Seonyeong; Metchock, Beverly; Levina, Klavdia; Lei, Yung-Chao; Lee, Jongseok; Larionova, Elena E.; Lancaster, Joey; Jeon, Doosoo; Jave, Oswaldo; Khorosheva, Tatiana; Hwang, Soo Hee; Huang, Angela Song-En; Gler, M. Tarcela; Dravniece, Gunta; Eum, Seokyong; Demikhova, Olga V.; Degtyareva, Irina; Danilovits, Manfred; Cirula, Anda; Cho, Eunjin; Cai, Ying; Brand, Jeanette; Bonilla, Cesar; Barry, Clifton E.; Asencios, Luis; Andreevskaya, Sofia N.; Akksilp, Rattanawadee

    2014-01-01

    Background. Increasing access to drugs for the treatment of multidrug-resistant (MDR) tuberculosis is crucial but could lead to increasing resistance to these same drugs. In 2000, the international Green Light Committee (GLC) initiative began to increase access while attempting to prevent acquired resistance. Methods. To assess the GLC's impact, we followed adults with pulmonary MDR tuberculosis from the start to the end of treatment with monthly sputum cultures, drug susceptibility testing, and genotyping. We compared the frequency and predictors of acquired resistance to second-line drugs (SLDs) in 9 countries that volunteered to participate, 5 countries that met GLC criteria, and 4 countries that did not apply to the GLC. Results. In total, 832 subjects were enrolled. Of those without baseline resistance to specific SLDs, 68 (8.9%) acquired extensively drug-resistant (XDR) tuberculosis, 79 (11.2%) acquired fluoroquinolone (FQ) resistance, and 56 (7.8%) acquired resistance to second-line injectable drugs (SLIs). The relative risk (95% confidence interval [CI]) of acquired resistance was lower at GLC-approved sites: 0.27 (.16–.47) for XDR tuberculosis, 0.28 (.17–.45) for FQ, and 0.15 (.06–.39) to 0.60 (.34–1.05) for 3 different SLIs. The risk increased as the number of potentially effective drugs decreased. Controlling for baseline drug resistance and differences between sites, the odds ratios (95% CIs) were 0.21 (.07–.62) for acquired XDR tuberculosis and 0.23 (.09–.59) for acquired FQ resistance. Conclusions. Treatment of MDR tuberculosis involves substantial risk of acquired resistance to SLDs, increasing as baseline drug resistance increases. The risk was significantly lower in programs documented by the GLC to meet specific standards. PMID:25057101

  3. Antimicrobial Resistance of Faecal Escherichia coli Isolates from Pig Farms with Different Durations of In-feed Antimicrobial Use.

    PubMed

    Gibbons, J F; Boland, F; Egan, J; Fanning, S; Markey, B K; Leonard, F C

    2016-05-01

    Antimicrobial use and resistance in animal and food production are of concern to public health. The primary aims of this study were to determine the frequency of resistance to 12 antimicrobials in Escherichia coli isolates from 39 pig farms and to identify patterns of antimicrobial use on these farms. Further aims were to determine whether a categorization of farms based on the duration of in-feed antimicrobial use (long-term versus short-term) could predict the occurrence of resistance on these farms and to identify the usage of specific antimicrobial drugs associated with the occurrence of resistance. Escherichia coli were isolated from all production stages on these farms; susceptibility testing was carried out against a panel of antimicrobials. Antimicrobial prescribing data were collected, and farms were categorized as long term or short term based on these. Resistance frequencies and antimicrobial use were tabulated. Logistic regression models of resistance to each antimicrobial were constructed with stage of production, duration of antimicrobial use and the use of 5 antimicrobial classes included as explanatory variables in each model. The greatest frequencies of resistance were observed to tetracycline, trimethoprim/sulphamethoxazole and streptomycin with the highest levels of resistance observed in isolates from first-stage weaned pigs. Differences in the types of antimicrobial drugs used were noted between long-term and short-term use farms. Categorization of farms as long- or short-term use was sufficient to predict the likely occurrence of resistance to 3 antimicrobial classes and could provide an aid in the control of resistance in the food chain. Stage of production was a significant predictor variable in all models of resistance constructed and did not solely reflect antimicrobial use at each stage. Cross-selection and co-selection for resistance was evident in the models constructed, and the use of trimethoprim/sulphonamide drugs in particular was

  4. A new strategy to fight antimicrobial resistance: the revival of old antibiotics

    PubMed Central

    Cassir, Nadim; Rolain, Jean-Marc; Brouqui, Philippe

    2014-01-01

    The increasing prevalence of hospital and community-acquired infections caused by multidrug-resistant (MDR) bacterial pathogens is limiting the options for effective antibiotic therapy. Moreover, this alarming spread of antimicrobial resistance has not been paralleled by the development of novel antimicrobials. Resistance to the scarce new antibiotics is also emerging. In this context, the rational use of older antibiotics could represent an alternative to the treatment of MDR bacterial pathogens. It would help to optimize the armamentarium of antibiotics in the way to preserve new antibiotics and avoid the prescription of molecules known to favor the spread of resistance (i.e., quinolones). Furthermore, in a global economical perspective, this could represent a useful public health orientation knowing that several of these cheapest “forgotten” antibiotics are not available in many countries. We will review here the successful treatment of MDR bacterial infections with the use of old antibiotics and discuss their place in current practice. PMID:25368610

  5. Surveillance of Antibiotic Resistance among Hospital- and Community-Acquired Toxigenic Clostridium difficile Isolates over 5-Year Period in Kuwait

    PubMed Central

    Jamal, Wafaa Y.; Rotimi, Vincent O.

    2016-01-01

    Clostridium difficile infection (CDI) is a leading and an important cause of diarrhea in a healthcare setting especially in industrialized countries. Community-associated CDI appears to add to the burden on healthcare setting problems. The aim of the study was to investigate the antimicrobial resistance of healthcare-associated and community-acquired C. difficile infection over 5 years (2008–2012) in Kuwait. A total of 111 hospital-acquired (HA-CD) and 35 community-acquired Clostridium difficile (CA-CD) clinical isolates from stool of patients with diarrhoea were studied. Antimicrobial susceptibility testing of 15 antimicrobial agents against these pathogens was performed using E test method. There was no evidence of resistance to amoxicillin-clavulanic acid, daptomycin, linezolid, piperacillin-tazobactam, teicoplanin and vancomycin by both HA-CD and CA-CD isolates. Metronidazole had excellent activity against CA-CD but there was a 2.9% resistance rate against HA-CD isolates. Ampicillin, clindamycin, levofloxacin and imipenem resistance rates among the HC-CD vs. CA-CD isolates were 100 vs. 47.4%; 43 vs. 47.4%; 100 vs. 100% and 100 vs. 89%, respectively. An unexpected high rifampicin resistance rate of 15.7% emerged amongst the HA-CD isolates. In conclusion, vancomycin resistance amongst the HA-CD and CA-CD isolates was not encountered in this series but few metronidazole resistant hospital isolates were isolated. High resistance rates of ampicillin, clindamycin, levofloxacin, and imipenem resistance were evident among both CA-CD and HA-CD isolates. Rifampicin resistance is emerging among the HA-CD isolates. PMID:27536994

  6. Associations between host characteristics and antimicrobial resistance of Salmonella typhimurium.

    PubMed

    Ruddat, I; Tietze, E; Ziehm, D; Kreienbrock, L

    2014-10-01

    A collection of Salmonella Typhimurium isolates obtained from sporadic salmonellosis cases in humans from Lower Saxony, Germany between June 2008 and May 2010 was used to perform an exploratory risk-factor analysis on antimicrobial resistance (AMR) using comprehensive host information on sociodemographic attributes, medical history, food habits and animal contact. Multivariate resistance profiles of minimum inhibitory concentrations for 13 antimicrobial agents were analysed using a non-parametric approach with multifactorial models adjusted for phage types. Statistically significant associations were observed for consumption of antimicrobial agents, region type and three factors on egg-purchasing behaviour, indicating that besides antimicrobial use the proximity to other community members, health consciousness and other lifestyle-related attributes may play a role in the dissemination of resistances. Furthermore, a statistically significant increase in AMR from the first study year to the second year was observed. PMID:24300336

  7. The World Health Assembly resolution on antimicrobial resistance.

    PubMed

    Shallcross, Laura J; Davies, Sally C

    2014-11-01

    Antimicrobial resistance is a global problem that can only be tackled successfully through strengthened international partnerships. A concerted political, scientific and media campaign has garnered support for the recent World Health Assembly resolution on antimicrobial resistance, mandating the WHO to develop a global action plan. This resolution has the 'One Health' approach at its core, emphasizing collaboration across human and animal health sectors at the international, national and regional levels, coupled with strong leadership and the political will to act. Key themes are communication, prevention of infection, using knowledge to guide action, sustainability and optimizing the use of antimicrobial medicines and diagnostic devices. Implementation of the global action plan will require member states to make a commitment to developing national action plans and strengthening capacity, building on collaborations between the WHO, the World Organisation for Animal Health, the World Bank, Codex Alimentarius and the Transatlantic Task Force on Antimicrobial Resistance. PMID:25204342

  8. Analysis of antimicrobial resistance mechanisms in MDR bacteria by microarray and high-throughput sequencing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antimicrobial resistance in pathogenic bacteria is a major concern in human and animal health. The National Antimicrobial Resistance Monitoring System (NARMS) was designed by the CDC, FDA, and USDA to monitor antimicrobial resistance in the U.S. The Bacterial Epidemiology and Antimicrobial Resistanc...

  9. Mechanobiology of Antimicrobial Resistant Escherichia coli and Listeria innocua

    PubMed Central

    Tajkarimi, Mehrdad; Harrison, Scott H.; Hung, Albert M.; Graves, Joseph L.

    2016-01-01

    A majority of antibiotic-resistant bacterial infections in the United States are associated with biofilms. Nanoscale biophysical measures are increasingly revealing that adhesive and viscoelastic properties of bacteria play essential roles across multiple stages of biofilm development. Atomic Force Microscopy (AFM) applied to strains with variation in antimicrobial resistance enables new opportunities for investigating the function of adhesive forces (stickiness) in biofilm formation. AFM force spectroscopy analysis of a field strain of Listeria innocua and the strain Escherichia coli K-12 MG1655 revealed differing adhesive forces between antimicrobial resistant and nonresistant strains. Significant increases in stickiness were found at the nanonewton level for strains of Listeria innocua and Escherichia coli in association with benzalkonium chloride and silver nanoparticle resistance respectively. This advancement in the usage of AFM provides for a fast and reliable avenue for analyzing antimicrobial resistant cells and the molecular dynamics of biofilm formation as a protective mechanism. PMID:26914334

  10. Antimicrobial resistance of Pseudomonas spp. isolated from wastewater and wastewater-impacted marine coastal zone.

    PubMed

    Luczkiewicz, Aneta; Kotlarska, Ewa; Artichowicz, Wojciech; Tarasewicz, Katarzyna; Fudala-Ksiazek, Sylwia

    2015-12-01

    In this study, species distribution and antimicrobial susceptibility of cultivated Pseudomonas spp. were studied in influent (INF), effluent (EFF), and marine outfall (MOut) of wastewater treatment plant (WWTP). The susceptibility was tested against 8 antimicrobial classes, active against Pseudomonas spp.: aminoglycosides, carbapenems, broad-spectrum cephalosporins from the 3rd and 4th generation, extended-spectrum penicillins, as well as their combination with the β-lactamase inhibitors, monobactams, fluoroquinolones, and polymyxins. Among identified species, resistance to all antimicrobials but colistin was shown by Pseudomonas putida, the predominant species in all sampling points. In other species, resistance was observed mainly against ceftazidime, ticarcillin, ticarcillin-clavulanate, and aztreonam, although some isolates of Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas pseudoalcaligenes, and Pseudomonas protegens showed multidrug-resistance (MDR) phenotype. Among P. putida, resistance to β-lactams and to fluoroquinolones as well as multidrug resistance become more prevalent after wastewater treatment, but the resistance rate decreased in marine water samples. Obtained data, however, suggests that Pseudomonas spp. are equipped or are able to acquire a wide range of antibiotic resistance mechanisms, and thus should be monitored as possible source of resistance genes. PMID:26286796

  11. Survival proteomes: the emerging proteotype of antimicrobial resistance.

    PubMed

    Park, Amber J; Krieger, Jonathan R; Khursigara, Cezar M

    2016-05-01

    Antimicrobial resistance is one of the greatest challenges in modern medicine. Infectious diseases that have historically been eliminated with routine antibiotic therapy are now re-emerging as life threatening illnesses. A better understanding of the specific mechanisms that contribute to resistance are required to optimize the treatment of infectious microorganisms and limit the survival of recalcitrant populations. This challenging area of research is made more problematic by the observation that multiple, overlapping, and/or compensatory resistance mechanism are often present within a single bacterial species. High-resolution proteomics has emerged as an effective tool to study antimicrobial resistance as it allows for the quantitative investigation of multiple systems concurrently. Furthermore, the ability to examine extracellular mechanisms of resistance and important post-translational modifications make this research tool well suited for the challenge. This review discusses how proteomics has contributed to the understanding of antimicrobial resistance and focuses on advances afforded by the more recent development of technologies that produce quantitative high-resolution proteomic information. We discuss current strategies for studying resistance, including comparative analysis of resistant and susceptible strains and protein-based responses to antimicrobial challenge. Lastly, we suggest specific experimental approaches aimed at advancing our understanding of protein-based resistance mechanisms and maximizing therapeutic outcomes in the future. PMID:26790948

  12. Transcriptional plasticity promotes primary and acquired resistance to BET inhibition.

    PubMed

    Rathert, Philipp; Roth, Mareike; Neumann, Tobias; Muerdter, Felix; Roe, Jae-Seok; Muhar, Matthias; Deswal, Sumit; Cerny-Reiterer, Sabine; Peter, Barbara; Jude, Julian; Hoffmann, Thomas; Boryń, Łukasz M; Axelsson, Elin; Schweifer, Norbert; Tontsch-Grunt, Ulrike; Dow, Lukas E; Gianni, Davide; Pearson, Mark; Valent, Peter; Stark, Alexander; Kraut, Norbert; Vakoc, Christopher R; Zuber, Johannes

    2015-09-24

    Following the discovery of BRD4 as a non-oncogene addiction target in acute myeloid leukaemia (AML), bromodomain and extra terminal protein (BET) inhibitors are being explored as a promising therapeutic avenue in numerous cancers. While clinical trials have reported single-agent activity in advanced haematological malignancies, mechanisms determining the response to BET inhibition remain poorly understood. To identify factors involved in primary and acquired BET resistance in leukaemia, here we perform a chromatin-focused RNAi screen in a sensitive MLL-AF9;Nras(G12D)-driven AML mouse model, and investigate dynamic transcriptional profiles in sensitive and resistant mouse and human leukaemias. Our screen shows that suppression of the PRC2 complex, contrary to effects in other contexts, promotes BET inhibitor resistance in AML. PRC2 suppression does not directly affect the regulation of Brd4-dependent transcripts, but facilitates the remodelling of regulatory pathways that restore the transcription of key targets such as Myc. Similarly, while BET inhibition triggers acute MYC repression in human leukaemias regardless of their sensitivity, resistant leukaemias are uniformly characterized by their ability to rapidly restore MYC transcription. This process involves the activation and recruitment of WNT signalling components, which compensate for the loss of BRD4 and drive resistance in various cancer models. Dynamic chromatin immunoprecipitation sequencing and self-transcribing active regulatory region sequencing of enhancer profiles reveal that BET-resistant states are characterized by remodelled regulatory landscapes, involving the activation of a focal MYC enhancer that recruits WNT machinery in response to BET inhibition. Together, our results identify and validate WNT signalling as a driver and candidate biomarker of primary and acquired BET resistance in leukaemia, and implicate the rewiring of transcriptional programs as an important mechanism promoting

  13. Transcriptional plasticity promotes primary and acquired resistance to BET inhibition

    PubMed Central

    Neumann, Tobias; Muerdter, Felix; Roe, Jae-Seok; Muhar, Matthias; Deswal, Sumit; Cerny-Reiterer, Sabine; Peter, Barbara; Jude, Julian; Hoffmann, Thomas; Boryń, Łukasz M.; Axelsson, Elin; Schweifer, Norbert; Tontsch-Grunt, Ulrike; Dow, Lukas E.; Gianni, Davide; Pearson, Mark; Valent, Peter; Stark, Alexander; Kraut, Norbert; Vakoc, Christopher R.; Zuber, Johannes

    2016-01-01

    Summary Following the discovery of BRD4 as a non-oncogene addiction target in acute myeloid leukemia (AML)1,2, BET inhibitors are being explored as promising therapeutic avenue in numerous cancers3–5. While clinical trials have reported single-agent activity in advanced hematologic malignancies6, mechanisms determining the response to BET inhibition remain poorly understood. To identify factors involved in primary and acquired BET resistance in leukemia, we performed a chromatin-focused RNAi screen in a sensitive MLL/AF9; NrasG12D -driven AML model, and investigated dynamic transcriptional profiles in sensitive and resistant murine and human leukemias. Our screen reveals that suppression of the PRC2 complex, contrary to effects in other contexts, promotes BET inhibitor resistance in AML. PRC2 suppression does not directly affect the regulation of Brd4-dependent transcripts, but facilitates the remodeling of regulatory pathways that restore the transcription of key targets such as Myc. Similarly, while BET inhibition triggers acute MYC repression in human leukemias regardless of their sensitivity, resistant leukemias are uniformly characterized by their ability to rapidly restore MYC transcription. This process involves the activation and recruitment of WNT signaling components, which compensate for the loss of BRD4 and drive resistance in various cancer models. Dynamic ChIP- and STARR-seq enhancer profiles reveal that BET-resistant states are characterized by remodeled regulatory landscapes, involving the activation of a focal MYC enhancer that recruits WNT machinery in response to BET inhibition. Together, our results identify and validate WNT signaling as a driver and candidate biomarker of primary and acquired BET resistance in leukemia, and implicate the rewiring of transcriptional programs as an important mechanism promoting resistance to BET inhibitors and, potentially, other chromatin-targeted therapies. PMID:26367798

  14. Inducible and Acquired Clarithromycin Resistance in the Mycobacterium abscessus Complex

    PubMed Central

    Rubio, Marc; March, Francesca; Garrigó, Montserrat; Moreno, Carmen; Español, Montserrat; Coll, Pere

    2015-01-01

    Purpose Clarithromycin was considered the cornerstone for the treatment of Mycobacterium abscessus complex infections. Genetic resistance mechanisms have been described and many experts propose amikacin as an alternative. Nevertheless, clarithromycin has several advantages; therefore, it is necessary to identify the non-functional erm(41) allele to determine the most suitable treatment. The aims of this study were to characterize the molecular mechanisms of clarithromycin resistance in a collection of Mycobacterium abscessus complex isolates and to verify the relationship between these mechanisms and the antibiogram. Materials and Methods Clinical isolates of M. abscessus complex (n = 22) from 16 patients were identified using four housekeeping genes (rpoB, secA1, sodA and hsp65), and their genetic resistance was characterized by studying erm(41) and rrl genes. Nine strains were recovered from the clinical isolates and subjected to E-test and microdilution clarithromycin susceptibility tests, with readings at 3, 7 and 14 days. Results We classified 11/16 (68.8%) M. abscessus subsp. abscessus, 4/16 (25.0%) M. abscessus subsp. bolletii, and 1/16 (6.3%) M. abscessus subsp. massiliense. T28 erm(41) allele was observed in 8 Mycobacterium abscessus subps. abscessus and 3 Mycobacterium abscessus subsp. bolletii. One strain of M. abscessus subsp. bolletii had an erm(41) gene truncated and was susceptible to clarithromycin. No mutations were observed in rrl gene first isolates. In three patients, follow-up of initial rrl wild-type strains showed acquired resistance. Conclusions Most clinical isolates of M. abscessus complex had inducible resistance to clarithromycin and total absence of constitutive resistance. Our findings showed that the acquisition of resistance mutations in rrl gene was associated with functional and non-functional erm(41) gene. Caution is needed when using erm(41) sequencing alone to identify M. abscessus subspecies. This study reports an acquired

  15. Oral administration of antimicrobials increase antimicrobial resistance in E. coli from chicken--a systematic review.

    PubMed

    Simoneit, C; Burow, E; Tenhagen, B-A; Käsbohrer, A

    2015-01-01

    Antimicrobials play an important role in animal and human health care. It was the aim of this systematic review to assess the effects of oral administration of antimicrobials on the development of antimicrobial resistance (AMR) in Escherichia coli (E. coli) from chickens. Moreover, the effects of the administration of more than one antimicrobial and of different dosages were studied. Literature was searched in November 2012 from the electronic databases ISI Web of Science, PubMed, Scopus and a national literature database (DIMDI) as well as the database ProQuest LLC. The search was updated in March 2014. Original studies describing a treatment (A) and a control group of either non-treatment (C) or initial value (0) and determining AMR in E. coli at different sample points (SP) were included. The literature search resulted in 35 full text articles on the topic, seven (20%) of which contained sufficient information on the administered antimicrobial and the impact of treatment on AMR. Most papers described the use of more than one antimicrobial, several dosages, controls (non-treatment or pre-treatment) and measured AMR at different SPs leading to a total of 227 SPs on the impact of the use of antimicrobials on AMR in chickens. 74% of the SPs (168/227) described a higher AMR-rate in E. coli from treated animals than from controls. After the administration of a single antimicrobial, AMR increased at 72% of the SPs. Administration of more than one antimicrobial increased AMR at 82% of the SPs. Higher dosages were associated with similar or higher AMR rates. The limited number of studies for each antimicrobial agent and the high variability in the resistance effect call for more well designed studies on the impact of oral administration on AMR development and spread. PMID:25433717

  16. Narrow grass hedges reduce tylosin and associated antimicrobial resistance genes in agricultural runoff

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Agricultural runoff from areas receiving livestock manure can potentially contaminate surface water with antimicrobials and antimicrobial resistance genes (ARGs). The objective of this study was to investigate the effectiveness of narrow grass hedges (NGHs) on reducing the transport of antimicrobial...

  17. Perception, Attitude, and Knowledge Regarding Antimicrobial Resistance, Appropriate Antimicrobial Use, and Infection Control Among Future Medical Practitioners: A Multicenter Study.

    PubMed

    Chuenchom, Nuttagarn; Thamlikitkul, Visanu; Chaiwarith, Romanee; Deoisares, Rawisut; Rattanaumpawan, Pinyo

    2016-05-01

    A questionnaire-based study was conducted among final-year Thai medical students. The problem of antimicrobial resistance is well recognized, but their knowledge of antimicrobial resistance, appropriate antimicrobial use, and infection control was substantially limited. Only half of these students recognized existence of an antimicrobial stewardship program or infection control unit in their hospitals. Infect Control Hosp Epidemiol 2016;37:603-605. PMID:26809753

  18. Value of rapid aetiological diagnosis in optimization of antimicrobial treatment in bacterial community acquired pneumonia.

    PubMed

    Mareković, Ivana; Plecko, Vanda; Boras, Zagorka; Pavlović, Ladislav; Budimir, Ana; Bosnjak, Zrinka; Puretić, Hrvoje; Zele-Starcević, Lidija; Kalenić, Smilja

    2012-06-01

    In 80 adult patients with community acquired pneumonia (CAP) conventional microbiological methods, polymerase chain reaction (PCR) and serum C-reactive protein (CRP) levels were performed and the appropriateness of the empirical antimicrobial treatment was evaluated according to bacterial pathogen detected. The aetiology was determined in 42 (52.5%) patients, with Streptococcus pneumoniae as the most common pathogen. PCR applied to bronchoalveolar lavage (BAL) provided 2 and PCR on sputum samples 1 additional aetiological diagnosis of CAP The mean CRP values in the S. pneumoniae group were not significantly higher than in the group with other aetiological diagnoses (166.89 mg/L vs. 160.11 mg/L, p = 0.457). In 23.8% (10/42) of patients with determined aetiology, the empirical antimicrobial treatment was inappropriate. PCR tests need further investigation, particularly those for the atypical pathogens, as they are predominant in inappropriately treated patients. Our results do not support the use of CRP as a rapid test to guide the antimicrobial treatment in patients with CAP. PMID:22856222

  19. Bacteremia and Antimicrobial Drug Resistance over Time, Ghana

    PubMed Central

    Amuzu, Sylvarius K.; de Ciman, Ring; Kassimova, Iparkhan; Groß, Lisa; Rabsch, Wolfgang; Rosenberg, Ulrike; Schulze, Marco; Stich, August; Zimmermann, Ortrud

    2011-01-01

    Bacterial distribution and antimicrobial drug resistance were monitored in patients with bacterial bloodstream infections in rural hospitals in Ghana. In 2001–2002 and in 2009, Salmonella enterica serovar Typhi was the most prevalent pathogen. Although most S. enterica serovar Typhi isolates were chloramphenicol resistant, all isolates tested were susceptible to ciprofloxacin. PMID:22000360

  20. Antimicrobial Resistance in Salmonella Isolates Recovered from Slaughter Cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    *Background*: Antimicrobial resistance is of global concern and first emerged in bacteria shortly after the introduction of penicillin. It is common to see resistance develop after new compounds (regardless of class) are released. However many factors influence the persistence and transmission of r...

  1. Hospitalization and Antimicrobial Resistance in Salmonella Outbreaks, 1984–2002

    PubMed Central

    Greene, Katherine D.; Ovitt, Jessa; Barrett, Timothy J.; Medalla, Felicita; Angulo, Frederick J.

    2005-01-01

    Few studies have evaluated the health consequences of antimicrobial-resistant Salmonella strains associated with outbreaks. Among 32 outbreaks occurring in the United States from 1984 to 2002, 22% of 13,286 persons in 10 Salmonella-resistant outbreaks were hospitalized, compared with 8% of 2,194 persons in 22 outbreaks caused by pansusceptible Salmonella strains (p<0.01). PMID:15963293

  2. Multiple Antimicrobial Resistance in Plague: An Emerging Public Health Risk

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antimicrobial resistance in Yersinia pestis is rare, yet constitutes a significant international public health and biodefense threat. In 1995, the first multidrug resistant (MDR) isolate of Y. pestis (strain IP275) was identified, and shown to contain a self-transmissible plasmid (pIP1202) that con...

  3. Antimicrobial resistance in aviary and enriched housing environments

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antimicrobial resistance continues to be a global problem. The purpose of this study was to elucidate the emergence of resistance in populations of bacteria over time in layers in different housing systems. Houses were newly constructed and tested for pathogens prior to placement of hens. Hens we...

  4. ANTIMICROBIAL RESISTANCE IN SALMONELLA ISOLATES RECOVERED FROM EGGS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Antimicrobial resistance is of global concern and first emerged in bacteria shortly after the introduction of penicillin. It is common to see resistance develop after new compounds (regardless of class) are released. However many factors influence the persistence and transmission of r...

  5. Australian Group on Antimicrobial Resistance Australian Staphylococcus aureus Sepsis Outcome Programme annual report, 2014.

    PubMed

    Coombs, Geoffrey W; Daley, Denise A; Thin Lee, Yung; Pearson, Julie C; Robinson, J Owen; Nimmo, Graeme R; Collignon, Peter; Howden, Benjamin P; Bell, Jan M; Turnidge, John D

    2016-01-01

    From 1 January to 31 December 2014, 27 institutions around Australia participated in the Australian Staphylococcal Sepsis Outcome Programme (ASSOP). The aim of ASSOP 2014 was to determine the proportion of Staphylococcus aureus bacteraemia (SAB) isolates in Australia that are antimicrobial resistant, with particular emphasis on susceptibility to methicillin and to characterise the molecular epidemiology of the isolates. Overall, 18.8% of the 2,206 SAB episodes were methicillin resistant, which was significantly higher than that reported in most European countries. The 30-day all-cause mortality associated with methicillin-resistant SAB was 23.4%, which was significantly higher than the 14.4% mortality associated with methicillin-sensitive SAB (P <0.0001). With the exception of the beta-lactams and erythromycin, antimicrobial resistance in methicillin-sensitive S. aureus remains rare. However in addition to the beta-lactams, approximately 50‰ of methicillin-resistant S. aureus (MRSA) were resistant to erythromycin and ciprofloxacin and approximately 15% were resistant to co-trimoxazole, tetracycline and gentamicin. When applying the European Committee on Antimicrobial Susceptibility Testing breakpoints, teicoplanin resistance was detected in 2 S. aureus isolates. Resistance was not detected for vancomycin or linezolid. Resistance to non-beta-lactam antimicrobials was largely attributable to 2 healthcare-associated MRSA clones; ST22-IV [2B] (EMRSA-15) and ST239-III [3A] (Aus-2/3 EMRSA). ST22-IV [2B] (EMRSA-15) has become the predominant healthcare associated clone in Australia. Sixty per cent of methicillin-resistant SAB were due to community-associated (CA) clones. Although polyclonal, almost 44% of community-associated clones were characterised as ST93-IV [2B] (Queensland CA-MRSA) and ST1-IV [2B] (WA1). CA-MRSA, in particular the ST45-V [5C2&5] (WA84) clone, has acquired multiple antimicrobial resistance determinants including ciprofloxacin, erythromycin

  6. Pseudomonas aeruginosa: arsenal of resistance mechanisms, decades of changing resistance profiles, and future antimicrobial therapies.

    PubMed

    El Zowalaty, Mohamed E; Al Thani, Asmaa A; Webster, Thomas J; El Zowalaty, Ahmed E; Schweizer, Herbert P; Nasrallah, Gheyath K; Marei, Hany E; Ashour, Hossam M

    2015-01-01

    Antimicrobial resistance is one of the most serious public health issues facing humans since the discovery of antimicrobial agents. The frequent, prolonged, and uncontrolled use of antimicrobial agents are major factors in the emergence of antimicrobial-resistant bacterial strains, including multidrug-resistant variants. Pseudomonas aeruginosa is a leading cause of nosocomial infections. The abundant data on the increased resistance to antipseudomonal agents support the need for global action. There is a paucity of new classes of antibiotics active against P. aeruginosa. Here, we discuss recent antibacterial resistance profiles and mechanisms of resistance by P. aeruginosa. We also review future potential methods for controlling antibiotic-resistant bacteria, such as phage therapy, nanotechnology and antipseudomonal vaccines. PMID:26439366

  7. Race Against Antimicrobial Resistance Requires Coordinated Action – An Overview

    PubMed Central

    Premanandh, J.; Samara, B. S.; Mazen, A. N.

    2016-01-01

    Resistance developed by microbes is challenging success stories of treatment of infectious diseases with anti-microbials. Developing new antimicrobials against these resistant organisms does not progress at the same speed. In an effort to address this key issue, this work overviews the role of different stakeholders and discusses preventative and control measures for effective management of available resources. Roles and concerns of physicians, pharmacists and the public are also discussed. More than anything, this situation requires immediate action to establish antimicrobial stewardship program, control over the counter sale and promote public awareness. The paper also confronts the idea of curbing the use of antimicrobials using mass media, while detailing the consequences of non-therapeutic use. The role of policy makers in taking global action is essential to establishing authority or agency for formulating national guidelines and regulations for prudently using antimicrobials. To do this, this paper recommend the establishment of a global fund. In conclusion, the race against resistance is a collective responsibility requiring coordinated action at local, national, regional and international levels to ensure sustained utilization of antimicrobials. PMID:26869998

  8. Race Against Antimicrobial Resistance Requires Coordinated Action - An Overview.

    PubMed

    Premanandh, J; Samara, B S; Mazen, A N

    2015-01-01

    Resistance developed by microbes is challenging success stories of treatment of infectious diseases with anti-microbials. Developing new antimicrobials against these resistant organisms does not progress at the same speed. In an effort to address this key issue, this work overviews the role of different stakeholders and discusses preventative and control measures for effective management of available resources. Roles and concerns of physicians, pharmacists and the public are also discussed. More than anything, this situation requires immediate action to establish antimicrobial stewardship program, control over the counter sale and promote public awareness. The paper also confronts the idea of curbing the use of antimicrobials using mass media, while detailing the consequences of non-therapeutic use. The role of policy makers in taking global action is essential to establishing authority or agency for formulating national guidelines and regulations for prudently using antimicrobials. To do this, this paper recommend the establishment of a global fund. In conclusion, the race against resistance is a collective responsibility requiring coordinated action at local, national, regional and international levels to ensure sustained utilization of antimicrobials. PMID:26869998

  9. Antibiotic Resistance Pattern of Community Acquired Uropathogens at a Tertiary Care Hospital in Jaipur, Rajasthan

    PubMed Central

    Sood, Smita; Gupta, Ravi

    2012-01-01

    Background: Urinary tract infections (UTIs) are amongst the most common infections described in outpatients setting. Objectives: A study was conducted to evaluate the uropathogenic bacterial flora and its antimicrobial susceptibility profile among patients presenting to the out-patient clinics of a tertiary care hospital at Jaipur, Rajasthan. Materials and Methods: 2012 consecutive urine specimens from symptomatic UTI cases attending to the outpatient clinics were processed in the Microbiology lab. Bacterial isolates obtained were identified using biochemical reactions. Antimicrobial susceptibility testing was performed by the Kirby-Bauer disc diffusion method. Extended spectrum beta lactamase (ESBL) production was determined by the double disk approximation test and the Clinical and Laboratory Standards Institute (formerly NCCLS) confirmatory method. Results: Pathogens were isolated from 346 (17.16%) of the 2012 patients who submitted a urine sample. Escherichia coli was the most frequently isolated community acquired uropathogen accounting for 61.84% of the total isolates. ESBL production was observed in 23.83% of E. coli strains and 8.69% of Klebsiella strains. With the exception of Nitrofurantoin, resistance to agents commonly used as empiric oral treatments for UTI was quite high. Conclusion: The study revealed E. coli as the predominant bacterial pathogen for the community acquired UTIs in Jaipur, Rajasthan. An increasing trend in the production ESBLs among UTI pathogens in the community was noted. Nitrofurantoin should be used as empirical therapy for primary, uncomplicated UTIs. PMID:22529539

  10. Antimicrobial resistance surveillance in the AFHSC-GEIS network.

    PubMed

    Meyer, William G; Pavlin, Julie A; Hospenthal, Duane; Murray, Clinton K; Jerke, Kurt; Hawksworth, Anthony; Metzgar, David; Myers, Todd; Walsh, Douglas; Wu, Max; Ergas, Rosa; Chukwuma, Uzo; Tobias, Steven; Klena, John; Nakhla, Isabelle; Talaat, Maha; Maves, Ryan; Ellis, Michael; Wortmann, Glenn; Blazes, David L; Lindler, Luther

    2011-01-01

    International infectious disease surveillance has been conducted by the United States (U.S.) Department of Defense (DoD) for many years and has been consolidated within the Armed Forces Health Surveillance Center, Division of Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) since 1998. This includes activities that monitor the presence of antimicrobial resistance among pathogens. AFHSC-GEIS partners work within DoD military treatment facilities and collaborate with host-nation civilian and military clinics, hospitals and university systems. The goals of these activities are to foster military force health protection and medical diplomacy. Surveillance activities include both community-acquired and health care-associated infections and have promoted the development of surveillance networks, centers of excellence and referral laboratories. Information technology applications have been utilized increasingly to aid in DoD-wide global surveillance for diseases significant to force health protection and global public health. This section documents the accomplishments and activities of the network through AFHSC-GEIS partners in 2009. PMID:21388568

  11. Strategic measures for the control of surging antimicrobial resistance in Hong Kong and mainland of China.

    PubMed

    Cheng, Vincent C C; Wong, Sally C Y; Ho, Pak-Leung; Yuen, Kwok-Yung

    2015-02-01

    Antimicrobial-resistant bacteria are either highly prevalent or increasing rapidly in Hong Kong and China. Treatment options for these bacteria are generally limited, less effective and more expensive. The emergence and dynamics of antimicrobial resistance genes in bacteria circulating between animals, the environment and humans are not entirely known. Nonetheless, selective pressure by antibiotics on the microbiomes of animal and human, and their associated environments (especially farms and healthcare institutions), sewage systems and soil are likely to confer survival advantages upon bacteria with antimicrobial-resistance genes, which may be further disseminated through plasmids or transposons with integrons. Therefore, antibiotic use must be tightly regulated to eliminate such selective pressure, including the illegalization of antibiotics as growth promoters in animal feed and regulation of antibiotic use in veterinary practice and human medicine. Heightened awareness of infection control measures to reduce the risk of acquiring resistant bacteria is essential, especially during antimicrobial use or institutionalization in healthcare facilities. The transmission cycle must be interrupted by proper hand hygiene, environmental cleaning, avoidance of undercooked or raw food and compliance with infection control measures by healthcare workers, visitors and patients, especially during treatment with antibiotics. In addition to these routine measures, proactive microbiological screening of hospitalized patients with risk factors for carrying resistant bacteria, including history of travel to endemic countries, transfer from other hospitals, and prolonged hospitalization; directly observed hand hygiene before oral intake of drugs, food and drinks; and targeted disinfection of high-touch or mutual-touch items, such as bed rails and bed curtains, are important. Transparency of surveillance data from each institute for public scrutiny provides an incentive for

  12. Strategic measures for the control of surging antimicrobial resistance in Hong Kong and mainland of China

    PubMed Central

    Cheng, Vincent CC; Wong, Sally CY; Ho, Pak-Leung; Yuen, Kwok-Yung

    2015-01-01

    Antimicrobial-resistant bacteria are either highly prevalent or increasing rapidly in Hong Kong and China. Treatment options for these bacteria are generally limited, less effective and more expensive. The emergence and dynamics of antimicrobial resistance genes in bacteria circulating between animals, the environment and humans are not entirely known. Nonetheless, selective pressure by antibiotics on the microbiomes of animal and human, and their associated environments (especially farms and healthcare institutions), sewage systems and soil are likely to confer survival advantages upon bacteria with antimicrobial-resistance genes, which may be further disseminated through plasmids or transposons with integrons. Therefore, antibiotic use must be tightly regulated to eliminate such selective pressure, including the illegalization of antibiotics as growth promoters in animal feed and regulation of antibiotic use in veterinary practice and human medicine. Heightened awareness of infection control measures to reduce the risk of acquiring resistant bacteria is essential, especially during antimicrobial use or institutionalization in healthcare facilities. The transmission cycle must be interrupted by proper hand hygiene, environmental cleaning, avoidance of undercooked or raw food and compliance with infection control measures by healthcare workers, visitors and patients, especially during treatment with antibiotics. In addition to these routine measures, proactive microbiological screening of hospitalized patients with risk factors for carrying resistant bacteria, including history of travel to endemic countries, transfer from other hospitals, and prolonged hospitalization; directly observed hand hygiene before oral intake of drugs, food and drinks; and targeted disinfection of high-touch or mutual-touch items, such as bed rails and bed curtains, are important. Transparency of surveillance data from each institute for public scrutiny provides an incentive for

  13. Antimicrobial resistance: moving from professional engagement to public action.

    PubMed

    Ashiru-Oredope, D; Hopkins, S

    2015-11-01

    Antimicrobial-resistant infections claim ≥700 000 lives each year globally. It is therefore important that both healthcare professionals and the public know the threat antimicrobial resistance poses and the individual actions they can take to combat antimicrobial resistance. Antibiotic awareness campaigns in England using posters or leaflets have had little or no impact on knowledge, behaviour or prescription rates. Centrally coordinated, multimodal campaigns in two European countries (ongoing for several years and including print and mass media, web site and guidelines, as well as academic detailing and individual feedback to prescribers) have led to reductions in antibiotic use. To change behaviour and reduce antibiotic use in England, a coordinated and comprehensive interdisciplinary and multifaceted (multimodal) approach using behavioural science and targeted at specific groups (both professional and public) is required. Such campaigns should have an integrated evaluation plan using a combination of formative, process and summative measures from the outset to completion of a campaign. PMID:26377862

  14. A versatile plasmonic thermogel for disinfection of antimicrobial resistant bacteria.

    PubMed

    Abdou Mohamed, Mohamed A; Raeesi, Vahid; Turner, Patricia V; Rebbapragada, Anu; Banks, Kate; Chan, Warren C W

    2016-08-01

    The increasing occurrence of antimicrobial resistance among bacteria is a global problem that requires the development of alternative techniques to eradicate these superbugs. Herein, we used a combination of thermosensitive biocompatible polymer and gold nanorods to specifically deliver, preserve and confine heat to the area of interest. Our data demonstrates that this technique can be used to kill both Gram positive and Gram negative antimicrobial resistant bacteria in vitro. Our approach significantly reduces the antimicrobial resistant bacteria load in experimentally infected wounds by 98% without harming the surrounding tissues. More importantly, this polymer-nanocomposite can be prepared easily and applied to the wounds, can generate heat using a hand-held laser device, is safe for the operator, and does not have any adverse effects on the wound tissue and healing process. PMID:27174687

  15. Relationship of Antimicrobial Control Policies and Hospital and Infection Control Characteristics to Antimicrobial Resistance Rates

    PubMed Central

    Larson, Elaine L.; Quiros, Dave; Giblin, Tara; Lin, Susan

    2007-01-01

    Background Antibiotic misuse and noncompliance with infection control precautions have contributed to increasing levels of antimicrobial resistance in hospitals. Objectives To assess the extent to which resistance is monitored in infection control programs and to correlate resistance rates with characteristics of antimicrobial control policies, provider attitudes and practices, and systems-level indicators of implementation of the hand hygiene guideline of the Centers for Disease Control and Prevention. Methods An on-site survey of intensive care unit staff and infection control directors of 33 hospitals in the United States was conducted. The following data were collected: antimicrobial control policies; rates during the previous 12 months of methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and ceftazidime-resistant Klebsiella pneumoniae; an implementation score of systems-level efforts to implement the guideline; staff attitudes toward practice guidelines; and observations of staff hand hygiene. Variables associated with resistance rates were examined for independent effects by using logistic regression. Results Resistance rates for S aureus, enterococci, and K pneumoniae were 52.5%, 18.2%, and 16.0%, respectively. Ten (30.3%) hospitals had an antibiotic control policy. No statistically significant correlation was observed between staff attitudes toward practice guidelines, observed hand hygiene behavior, or having an antibiotic use policy and resistance rates. In logistic regression analysis, higher scores on measures of systems-level efforts to implement the guideline were associated with lower rates of resistant S aureus and enterococci (P=.046). Conclusions Organizational-level factors independent of the practices of individual clinicians may be associated with rates of antimicrobial resistance. PMID:17322010

  16. Bacteraemia and antibiotic-resistant pathogens in community acquired pneumonia: risk and prognosis.

    PubMed

    Torres, Antoni; Cillóniz, Catia; Ferrer, Miquel; Gabarrús, Albert; Polverino, Eva; Villegas, Santiago; Marco, Francesc; Mensa, Josep; Menéndez, Rosario; Niederman, Michael

    2015-05-01

    The sensitivity of blood cultures in the diagnosis of bacteraemia for community-acquired pneumonia is low. Recommendations, by guidelines, to perform blood cultures are discordant. We aimed to determine the incidence, microbial aetiology, risk factors and outcomes of bacteraemic patients with community-acquired pneumonia, including cases with antibiotic-resistant pathogens (ARP). A prospective, observational study was undertaken on consecutive adult patients admitted to the Hospital Clinic of Barcelona (Barcelona, Spain) with community-acquired pneumonia and blood cultures were obtained. Of the 2892 patients included, bacteraemia was present in 297 (10%) patients; 30 (10%) of whom had ARP (multidrug-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and an extended spectrum of beta-lactamase producing Enterobacteriaceae). In multivariate analyses, pleuritic pain, C-reactive protein ≥21.6 mg·dL(-1) and intensive care unit admissions were independently associated with bacteraemia, while prior antibiotic treatment and pneumococcal vaccine were protective factors. The risk factors for ARP bacteraemia were previous antibiotics and C-reactive protein <22.2 mg·dL(-1), while pleuritic pain was the only protective factor in the multivariate analysis. Bacteraemia (excluding ARP), appropriate empiric treatment, neurological disease, arterial oxygen tension/inspiratory oxygen fraction <250, pneumonia severity index risk classes IV and V, and intensive care unit admission were independently associated with a 30-day hospital mortality in the multivariate analysis. Inappropriate therapy was more frequent in ARP bacteraemia, compared with other bacteraemias (27% versus 3%, respectively, p<0.001). Antibiotic therapy protected against bacteraemia, but increased specifically the risk of bacteraemia from ARP due to the inappropriate coverage of these pathogens. Identifying patients at risk of ARP bacteraemia would help in

  17. Antimicrobial Resistance in Mycobacterium tuberculosis: The Odd One Out.

    PubMed

    Eldholm, Vegard; Balloux, François

    2016-08-01

    Antimicrobial resistance (AMR) threats are typically represented by bacteria capable of extensive horizontal gene transfer (HGT). One clear exception is Mycobacterium tuberculosis (Mtb). It is an obligate human pathogen with limited genetic diversity and a low mutation rate which lacks any evidence for HGT. Such features should, in principle, reduce its ability to rapidly evolve AMR. We identify key features in its biology and epidemiology that allow it to overcome its low adaptive potential. We focus in particular on its innate resistance to drugs, its unusual life cycle, including an often extensive latent phase, and its ability to shelter from exposure to antimicrobial drugs within cavities it induces in the lungs. PMID:27068531

  18. Fate and transport of antimicrobials and antimicrobial resistance genes in soil and runoff following land application of swine slurry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Due to the use of antimicrobials in livestock production, residual antimicrobials and antimicrobial resistance genes (ARGs) could enter the environment following the land application of animal wastes and could further contaminate surface and groundwater. The objective of this study was to determine ...

  19. Diversity of plasmids and antimicrobial resistance genes in multidrug-resistant Escherichia coli isolated from healthy companion animals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The presence and transfer of antimicrobial resistance genes from commensal bacteria in companion animals to more pathogenic bacteria may contribute to dissemination of antimicrobial resistance. The purpose of this study was to determine antimicrobial resistance gene content and the presence of gene...

  20. Strategies for achieving global collective action on antimicrobial resistance

    PubMed Central

    Caleo, Grazia M; Daulaire, Nils; Elbe, Stefan; Matsoso, Precious; Mossialos, Elias; Rizvi, Zain; Røttingen, John-Arne

    2015-01-01

    Abstract Global governance and market failures mean that it is not possible to ensure access to antimicrobial medicines of sustainable effectiveness. Many people work to overcome these failures, but their institutions and initiatives are insufficiently coordinated, led and financed. Options for promoting global collective action on antimicrobial access and effectiveness include building institutions, crafting incentives and mobilizing interests. No single option is sufficient to tackle all the challenges associated with antimicrobial resistance. Promising institutional options include monitored milestones and an inter-agency task force. A global pooled fund could be used to craft incentives and a special representative nominated as an interest mobilizer. There are three policy components to the problem of antimicrobials – ensuring access, conservation and innovation. To address all three components, the right mix of options needs to be matched with an effective forum and may need to be supported by an international legal framework. PMID:26668439

  1. Strategies for achieving global collective action on antimicrobial resistance.

    PubMed

    Hoffman, Steven J; Caleo, Grazia M; Daulaire, Nils; Elbe, Stefan; Matsoso, Precious; Mossialos, Elias; Rizvi, Zain; Røttingen, John-Arne

    2015-12-01

    Global governance and market failures mean that it is not possible to ensure access to antimicrobial medicines of sustainable effectiveness. Many people work to overcome these failures, but their institutions and initiatives are insufficiently coordinated, led and financed. Options for promoting global collective action on antimicrobial access and effectiveness include building institutions, crafting incentives and mobilizing interests. No single option is sufficient to tackle all the challenges associated with antimicrobial resistance. Promising institutional options include monitored milestones and an inter-agency task force. A global pooled fund could be used to craft incentives and a special representative nominated as an interest mobilizer. There are three policy components to the problem of antimicrobials--ensuring access, conservation and innovation. To address all three components, the right mix of options needs to be matched with an effective forum and may need to be supported by an international legal framework. PMID:26668439

  2. The complex interplay of iron, biofilm formation, and mucoidy affecting antimicrobial resistance of Pseudomonas aeruginosa

    PubMed Central

    Oglesby-Sherrouse, Amanda G.; Djapgne, Louise; Nguyen, Angela T.; Vasil, Adriana I.; Vasil, Michael L.

    2014-01-01

    Pseudomonas aeruginosa is a Gram-negative opportunistic bacterial pathogen that is refractory to a variety of current antimicrobial therapeutic regimens. Complicating treatment of such infections is the ability of P. aeruginosa to form biofilms, as well as several innate and acquired resistance mechanisms. Previous studies suggest iron plays a role in resistance to antimicrobial therapy, including the efficacy of an FDA-approved iron chelator, deferasirox (DSX), or Gallium, an iron analog, in potentiating antibiotic-dependent killing of P. aeruginosa biofilms. Here we show that iron-replete conditions enhance resistance of P. aeruginosa nonbiofilm growth against tobramycin and tigecycline. Interestingly, the mechanism of iron-enhanced resistance to each of these antibiotics is distinct. Whereas pyoverdine-mediated iron uptake is important for optimal resistance to tigecycline, it does not enhance tobramycin resistance. In contrast, heme supplementation results in increased tobramycin resistance, while having no significant effect on tigecycline resistance. Thus, non-siderophore bound iron plays an important role in resistance to tobramycin, while pyoverdine increases the ability of P. aeruginosa to resist tigecycline treatment. Lastly, we show that iron increases the minimal concentration of tobramycin, but not tigecycline, required to eradicate P. aeruginosa biofilms. Moreover, iron depletion blocks the previous observed induction of biofilm formation by sub-inhibitory concentrations of tobramycin, suggesting iron and tobramycin signal through overlapping regulatory pathways to affect biofilm formation. These data further support the role of iron in P. aeruginosa antibiotic resistance, providing yet another compelling case for targeting iron acquisition for future antimicrobial drug development. PMID:24436170

  3. The Evolving Role of Antimicrobial Stewardship in Management of Multidrug Resistant Infections.

    PubMed

    Goff, Debra A; File, Thomas M

    2016-06-01

    This article summarizes the current literature describing how antimicrobial stewardship interventions impact antimicrobial resistance. Discussion includes why we need stewardship, how to collaborate with team members, and the evidence of stewardship's impact on resistance. PMID:27208772

  4. Prevalence and antimicrobial resistance in Escherichia coli from food and animals in Lagos, Nigeria

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background Foodborne bacteria are often associated with human infections; these infections can become more complicated to treat if the bacteria are also resistant to antimicrobials. In this study, prevalence, antimicrobial resistance, and genetic relatedness of Escherichia coli among food producing ...

  5. Resistance to Antimicrobial Peptides and Stress Response in Mycoplasma pulmonis

    PubMed Central

    Fehri, Lina Fassi; Sirand-Pugnet, Pascal; Gourgues, Géraldine; Jan, Gwenaël; Wróblewski, Henri; Blanchard, Alain

    2005-01-01

    Antimicrobial peptides are widely distributed in nature, and in vertebrates, they play a key function in the innate immune defense system. It is generally agreed that these molecules may provide new antibiotics with therapeutic value. However, there are still many unsolved questions regarding the mechanisms underlying their antimicrobial activity as well as the mechanisms of resistance evolved by microorganisms against these molecules. The second point was addressed in this study. After determining the activity of 10 antimicrobial peptides against Mycoplasma pulmonis, a murine respiratory pathogen, the development of resistance was investigated. Following in vitro selection using subinhibitory concentrations of peptides, clones of this bacterium showing increased resistance to melittin or gramicidin D were obtained. For some of the clones, a cross-resistance was observed between these two peptides, in spite of their deep structural differences, and also with tetracycline. A proteomic analysis suggested that the stress response in these clones was constitutively activated, and this was confirmed by finding mutations in the hrcA gene; in mycoplasmas, bacteria which lack alternative sigma factors, the HrcA protein is supposed to play a key role as a negative regulator of heat shock proteins. By complementation of the hrcA mutants with the wild-type gene, the initial MICs of melittin and gramicidin D decreased to values close to the initial ones. This indicates that the resistance of M. pulmonis to these two antimicrobial peptides could result from a stress response involving HrcA-regulated genes. PMID:16189093

  6. The Antimicrobial Resistance Crisis: Causes, Consequences, and Management

    PubMed Central

    Michael, Carolyn Anne; Dominey-Howes, Dale; Labbate, Maurizio

    2014-01-01

    The antimicrobial resistance (AMR) crisis is the increasing global incidence of infectious diseases affecting the human population, which are untreatable with any known antimicrobial agent. This crisis will have a devastating cost on human society as both debilitating and lethal diseases increase in frequency and scope. Three major factors determine this crisis: (1) the increasing frequency of AMR phenotypes among microbes is an evolutionary response to the widespread use of antimicrobials; (2) the large and globally connected human population allows pathogens in any environment access to all of humanity; and (3) the extensive and often unnecessary use of antimicrobials by humanity provides the strong selective pressure that is driving the evolutionary response in the microbial world. Of these factors, the size of the human population is least amenable to rapid change. In contrast, the remaining two factors may be affected, so offering a means of managing the crisis: the rate at which AMR, as well as virulence factors evolve in microbial world may be slowed by reducing the applied selective pressure. This may be accomplished by radically reducing the global use of current and prospective antimicrobials. Current management measures to legislate the use of antimicrobials and to educate the healthcare world in the issues, while useful, have not comprehensively addressed the problem of achieving an overall reduction in the human use of antimicrobials. We propose that in addition to current measures and increased research into new antimicrobials and diagnostics, a comprehensive education program will be required to change the public paradigm of antimicrobial usage from that of a first line treatment to that of a last resort when all other therapeutic options have failed. PMID:25279369

  7. Antimicrobial resistance in beef and dairy cattle production.

    PubMed

    Call, Douglas R; Davis, Margaret A; Sawant, Ashish A

    2008-12-01

    Observational studies of cattle production systems usually find that cattle from conventional dairies harbor a higher prevalence of antimicrobial resistant (AMR) enteric bacteria compared to organic dairies or beef-cow operations; given that dairies usually use more antimicrobials, this result is not unexpected. Experimental studies have usually verified that application of antimicrobials leads to at least a transient expansion of AMR bacterial populations in treated cattle. Nevertheless, on dairy farms the majority of antibiotics are used to treat mastitis and yet AMR remains relatively low in mastitis pathogens. Other studies have shown no correlation between antimicrobial use and prevalence of AMR bacteria including documented cases where the prevalence of AMR bacteria is non-responsive to antimicrobial applications or remains relatively high in the absence of antimicrobial use or any other obvious selective pressures. Thus, there are multi-factorial events and pressures that influence AMR bacterial populations in cattle production systems. We introduce a heuristic model that illustrates how repeated antimicrobial selection pressure can increase the probability of genetic linkage between AMR genes and niche- or growth-specific fitness traits. This linkage allows persistence of AMR bacteria at the herd level because subpopulations of AMR bacteria are able to reside long-term within the host animals even in the absence of antimicrobial selection pressure. This model highlights the need for multiple approaches to manage herd health so that the total amount of antimicrobials is limited in a manner that meets animal welfare and public health needs while reducing costs for producers and consumers over the long-term. PMID:18983724

  8. Oral antimicrobials increase antimicrobial resistance in porcine E. coli--a systematic review.

    PubMed

    Burow, E; Simoneit, C; Tenhagen, B-A; Käsbohrer, A

    2014-03-01

    Administration of antimicrobials to livestock increases the risk of antimicrobial resistance (AMR) in commensal bacteria. Antimicrobials in pig production are usually administered per pen via feed which implies treatment of sick alongside with healthy animals. The objective of this systematic literature review was to investigate the effect of orally administered antimicrobials on AMR in Escherichia coli of swine. Studies published in peer reviewed journals were retrieved from the international online databases ISI Web of Knowledge, PubMed, Scopus and the national electronic literature data base of Deutsches Institut für Medizinische Dokumentation und Information. The studies were assessed using the eligibility criteria English or German language, access to full paper version, defined treatment and control group (initial value or non-treatment) as well as administration and resistance testing of the same antimicrobial class. In the qualitative synthesis, only studies were included presenting the summary measures odds ratio or prevalence of resistance, the category of the applied antimicrobial and the dosage. An effect of the antimicrobial on AMR in E. coli was evaluated as an "increase", "no effect" or "decrease" if the odds or alternatively the prevalence ratio were >1.0, 1.0 or <1.0, respectively. Eleven studies, describing 36 different trials, fulfilled the eligibility criteria and were finally assessed. An increase of AMR in E. coli was found in 10 out of 11 trials comparing AMR after with AMR prior to oral treatment and in 22 of the 25 trials comparing orally treated with untreated groups. Effects expressed as odds or prevalence ratios were highest for the use of aminoglycosides, quinolones and tetracycline. There was no clear association between the reported dosage and AMR towards tetracycline. Information on antimicrobial substance and dosage was missing in 4 and 5 of the 11 finally selected studies. The 36 identified trials were inhomogenous in usage and

  9. Nuclear EGFR Contributes to Acquired Resistance to Cetuximab

    PubMed Central

    Li, Chunrong; Iida, Mari; Dunn, Emily F.; Ghia, Amol J.; Wheeler, Deric L.

    2010-01-01

    Epidermal growth factor receptor (EGFR) is a ubiquitously expressed receptor tyrosine kinase involved in the etiology of several human cancers. Cetuximab is an EGFR blocking-antibody that has been approved for the treatment of patients with cancers of the head and neck (HNSCC) and metastatic colorectal cancer (mCRC). Previous reports have shown that EGFR translocation to the nucleus is associated with cell proliferation. Here we investigated mechanisms of acquired resistance to cetuximab using a model derived from the non-small cell lung cancer line H226. We demonstrated that cetuximab-resistant cells overexpress HER family ligands including epidermal growth factor (EGF), amphiregulin (AR), heparin-binding EGF (HB-EGF) and β-cellulin. Overexpression of these ligands is associated with the nuclear translocation of the EGFR and this process was mediated by the Src family kinases (SFK). Treatment of cetuximab-resistant cells with the SFK inhibitor, dasatinib, resulted in loss of nuclear EGFR, increased membrane expression of the EGFR and re-sensitization to cetuximab. In addition, expression of a nuclear localization sequence tagged EGFR in cetuximab-sensitive cells increased resistance to cetuximab both in vitro and in mouse xenografts. Collectively, these data suggest that nuclear expression of EGFR may be an important molecular determinant of resistance to cetuximab therapy and provides a rationale for investigating nuclear EGFR as a biomarker for cetuximab response. Further, these data suggest a rationale for the design of clinical trials that examine the value of treating patients with cetuximab-resistant tumors with inhibitors of SFKs in combination with cetuximab. PMID:19684613

  10. Nuclear EGFR contributes to acquired resistance to cetuximab.

    PubMed

    Li, C; Iida, M; Dunn, E F; Ghia, A J; Wheeler, D L

    2009-10-29

    Epidermal growth factor receptor (EGFR) is a ubiquitously expressed receptor tyrosine kinase involved in the etiology of several human cancers. Cetuximab is an EGFR-blocking antibody that has been approved for the treatment of patients with head and neck squamous cell carcinoma and metastatic colorectal cancer. Previous reports have shown that EGFR translocation to the nucleus is associated with cell proliferation. Here we investigated mechanisms of acquired resistance to cetuximab using a model derived from the non-small cell lung cancer line H226. We demonstrated that cetuximab-resistant cells overexpress HER family ligands including epidermal growth factor (EGF), amphiregulin, heparin-binding EGF and beta-cellulin. Overexpression of these ligands is associated with the nuclear translocation of the EGFR and this process was mediated by the Src family kinases (SFK). Treatment of cetuximab-resistant cells with the SFK inhibitor, dasatinib, resulted in loss of nuclear EGFR, increased membrane expression of the EGFR and resensitization to cetuximab. In addition, expression of a nuclear localization sequence-tagged EGFR in cetuximab-sensitive cells increased resistance to cetuximab both in vitro and in mouse xenografts. Collectively, these data suggest that nuclear expression of EGFR may be an important molecular determinant of resistance to cetuximab therapy and provides a rationale for investigating nuclear EGFR as a biomarker for cetuximab response. Further, these data suggest a rationale for the design of clinical trials that examine the value of treating patients with cetuximab-resistant tumors with inhibitors of SFKs in combination with cetuximab. PMID:19684613

  11. ASSOCIATION OF ANTIMICROBIAL RESISTANCE PATTERNS AND REPORTED USAGE OF ANTIMICROBIALS IN COMMERCIAL GROWING PIGS PRODUCTION

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The relationship between microbial use and the development of resistance to antimicrobials has been demonstrated through both external models and has been observed clinically. However, the strength of this relationship in practical production systems has not been clearly quantified. We designed th...

  12. Acinetobacter baumannii: evolution of antimicrobial resistance-treatment options.

    PubMed

    Doi, Yohei; Murray, Gerald L; Peleg, Anton Y

    2015-02-01

    The first decade of the 20th century witnessed a surge in the incidence of infections due to several highly antimicrobial-resistant bacteria in hospitals worldwide. Acinetobacter baumannii is one such organism that turned from an occasional respiratory pathogen into a major nosocomial pathogen. An increasing number of A. baumannii genome sequences have broadened our understanding of the genetic makeup of these bacteria and highlighted the extent of horizontal transfer of DNA. Animal models of disease combined with bacterial mutagenesis have provided some valuable insights into mechanisms of A. baumannii pathogenesis. Bacterial factors known to be important for disease include outer membrane porins, surface structures including capsule and lipopolysaccharide, enzymes such as phospholipase D, iron acquisition systems, and regulatory proteins. A. baumannii has a propensity to accumulate resistance to various groups of antimicrobial agents. In particular, carbapenem resistance has become commonplace, accounting for the majority of A. baumannii strains in many hospitals today. Carbapenem-resistant strains are often resistant to all other routinely tested agents. Treatment of carbapenem-resistant A. baumannii infection therefore involves the use of combinations of last resort agents such as colistin and tigecycline, but the efficacy and safety of these approaches are yet to be defined. Antimicrobial-resistant A. baumannii has high potential to spread among ill patients in intensive care units. Early recognition and timely implementation of appropriate infection control measures is crucial in preventing outbreaks. PMID:25643273

  13. Geographical Patterns in Antimicrobial Resistance of Acinetobacter in Clinical Isolates

    PubMed Central

    Sehgal, Sonal; Prakash, S. Krishna

    2014-01-01

    Objectives: Acinetobacter spp. has emerged as a threat to the healthcare workers throughout the globe, owing to its property of multidrug resistance. The aim of the present study was to evaluate the antimicrobial resistance patterns of Acinetobacter spp. among indoor and out patients in our hospital and compare the resistance patterns in India and abroad. Materials and Methods: In this retrospective study, which was carried out between Over a period of one year, a total of 5593 clinical specimens of pus and purulent fluids were examined and antimicrobial resistance pattern for Acinetobacter spp. using Modified Stoke’s were evaluated. Also a comparison was done with the other similar studies. Statistical Analysis: Using the proportions of sensitive and resistant, the statistical analysis was done. The total, mean and percentage were calculated by using SPSS. Results: A high level of antimicrobial multidrug-resistance was found in almost all the clinical isolate. Our study was also found to be concordant with the results of other studies. Conclusion: There is an emerging need for identification of the genes and mechanisms for multidrug resistance among Acinetobacter spp. PMID:24959441

  14. Antimicrobial Resistance in Campylobacter Isolates Recovered from Chicken Carcass Rinsates in 2007

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: Since the 1990’s there has been increasing concern regarding the development of antimicrobial resistance among food borne bacteria. To monitor resistance trends in food borne bacteria, the U.S. National Antimicrobial Resistance Monitoring System (NARMS) tracks antimicrobial susceptib...

  15. Strategies and molecular tools to fight antimicrobial resistance: resistome, transcriptome, and antimicrobial peptides

    PubMed Central

    Tavares, Letícia S.; Silva, Carolina S. F.; de Souza, Vinicius C.; da Silva, Vânia L.; Diniz, Cláudio G.; Santos, Marcelo O.

    2013-01-01

    The increasing number of antibiotic resistant bacteria motivates prospective research toward discovery of new antimicrobial active substances. There are, however, controversies concerning the cost-effectiveness of such research with regards to the description of new substances with novel cellular interactions, or description of new uses of existing substances to overcome resistance. Although examination of bacteria isolated from remote locations with limited exposure to humans has revealed an absence of antibiotic resistance genes, it is accepted that these genes were both abundant and diverse in ancient living organisms, as detected in DNA recovered from Pleistocene deposits (30,000 years ago). Indeed, even before the first clinical use of antibiotics more than 60 years ago, resistant organisms had been isolated. Bacteria can exhibit different strategies for resistance against antibiotics. New genetic information may lead to the modification of protein structure affecting the antibiotic carriage into the cell, enzymatic inactivation of drugs, or even modification of cellular structure interfering in the drug-bacteria interaction. There are still plenty of new genes out there in the environment that can be appropriated by putative pathogenic bacteria to resist antimicrobial agents. On the other hand, there are several natural compounds with antibiotic activity that may be used to oppose them. Antimicrobial peptides (AMPs) are molecules which are wide-spread in all forms of life, from multi-cellular organisms to bacterial cells used to interfere with microbial growth. Several AMPs have been shown to be effective against multi-drug resistant bacteria and have low propensity to resistance development, probably due to their unique mode of action, different from well-known antimicrobial drugs. These substances may interact in different ways with bacterial cell membrane, protein synthesis, protein modulation, and protein folding. The analysis of bacterial transcriptome

  16. Molecular Characterization of Multidrug Resistant Hospital Isolates Using the Antimicrobial Resistance Determinant Microarray

    PubMed Central

    Leski, Tomasz A.; Vora, Gary J.; Barrows, Brian R.; Pimentel, Guillermo; House, Brent L.; Nicklasson, Matilda; Wasfy, Momtaz; Abdel-Maksoud, Mohamed; Taitt, Chris Rowe

    2013-01-01

    Molecular methods that enable the detection of antimicrobial resistance determinants are critical surveillance tools that are necessary to aid in curbing the spread of antibiotic resistance. In this study, we describe the use of the Antimicrobial Resistance Determinant Microarray (ARDM) that targets 239 unique genes that confer resistance to 12 classes of antimicrobial compounds, quaternary amines and streptothricin for the determination of multidrug resistance (MDR) gene profiles. Fourteen reference MDR strains, which either were genome, sequenced or possessed well characterized drug resistance profiles were used to optimize detection algorithms and threshold criteria to ensure the microarray's effectiveness for unbiased characterization of antimicrobial resistance determinants in MDR strains. The subsequent testing of Acinetobacter baumannii, Escherichia coli and Klebsiella pneumoniae hospital isolates revealed the presence of several antibiotic resistance genes [e.g. belonging to TEM, SHV, OXA and CTX-M classes (and OXA and CTX-M subfamilies) of β-lactamases] and their assemblages which were confirmed by PCR and DNA sequence analysis. When combined with results from the reference strains, ∼25% of the ARDM content was confirmed as effective for representing allelic content from both Gram-positive and –negative species. Taken together, the ARDM identified MDR assemblages containing six to 18 unique resistance genes in each strain tested, demonstrating its utility as a powerful tool for molecular epidemiological investigations of antimicrobial resistance in clinically relevant bacterial pathogens. PMID:23936031

  17. Antimicrobial Photodynamic Therapy for Methicillin-Resistant Staphylococcus aureus Infection

    PubMed Central

    Fu, Xiu-jun; Fang, Yong; Yao, Min

    2013-01-01

    Nowadays methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common multidrug resistant bacteria both in hospitals and in the community. In the last two decades, there has been growing concern about the increasing resistance to MRSA of the most potent antibiotic glycopeptides. MRSA infection poses a serious problem for physicians and their patients. Photosensitizer-mediated antimicrobial photodynamic therapy (PDT) appears to be a promising and innovative approach for treating multidrug resistant infection. In spite of encouraging reports of the use of antimicrobial PDT to inactivate MRSA in large in vitro studies, there are only few in vivo studies. Therefore, applying PDT in the clinic for MRSA infection is still a long way off. PMID:23555074

  18. ANTIMICROBIAL RESISTANCE RATES IN CAMPYLOBACTER ISOLATES DERIVED FROM SWINE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Campylobacter, a microaerophilic gram-negative rod, is a major foodborne pathogen and commonly present in swine intestinal tract without causing any clinical disease. In this project, we investigated the antimicrobial resistance profiles of fecal Campylobacter isolates (n= 194) obtained from a swin...

  19. Evaluation of antimicrobial resistance of bovine bacteria to antibiotics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antimicrobial resistance (AMR) is one of the most formidable threats to human medicine today. Therefore, the research objective is to evaluate the susceptibility of Staphylococcus species isolated from beef cows to 12 antibiotics commonly used in treating human and animal infections. This research w...

  20. Microbial Ecology of and Antimicrobial Resistance in Stored Swine Manure

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antimicrobial compounds such as tylosin have been commonly used as feed additives for domestic animals to reduce infection and promote growth. Recent reports have suggested such feeding practices may result in increased microbial resistance to antibiotics, which can have an impact on human health. ...

  1. Relationship between super antigenicity, antimicrobial resistance and origin of Staphylococcus aureus isolated

    PubMed Central

    Corredor Arias, Luisa Fernanda; Luligo Espinal, Jenna Samara; Santacruz Ibarra, Jorge Javier; Álvarez Aldana, Adalucy

    2016-01-01

    Introduction: Staphylococcus aureus is a pathogen that causes food poisoning as well as hospital and community acquired infections. Objective: Establish the profile of superantigen genes among hospital isolates in relation to clinical specimen type, susceptibility to antibiotics and hospital or community acquisition. Methods: Eighty one isolates obtained from patients at Colombian hospital, were classified by antimicrobial susceptibility, specimen type and hospital or community acquired . The PCR uniplex and multiplex was used for detection of 22 superantigen genes (18 enterotoxins, tsst-1 and three exfoliative toxins). Results: Ninety five point one percent of isolates harbored one or more of the genes with an average of 5.6 genes. Prevalence of individual genes was variable and the most prevalent was seg (51.9%). Thirty nine genotypes were obtained, and the genotype gimnou (complete egc cluster) was the most prevalent alone (16.0%) and in association with other genes (13.6%). The correlation between presence of superantigens and clinical specimen or antimicrobial susceptibility showed no significant difference. But there was significant difference between presence of superantigens and the origin of the isolates, hospital or community acquired (p= 0.049). Conclusions: The results show the variability of the superantigen genes profile in hospital isolates and shows no conclusive relationship with the clinical sample type and antimicrobial susceptibility, but there was correlation with community and hospital isolates. The analysis of the interplay between virulence, epidemic and antibiotic resistance of bacterial populations is needed to predict the future of infectious diseases. PMID:27226659

  2. Prevalence and antimicrobial resistance of Salmonella recovered from processed poultry.

    PubMed

    Parveen, Salina; Taabodi, Maryam; Schwarz, Jurgen G; Oscar, Thomas P; Harter-Dennis, Jeanine; White, David G

    2007-11-01

    This study was conducted to determine the prevalence and antimicrobial resistance of Salmonella isolates recovered from processed poultry. Four hundred eighty pre- and postchill whole broiler chicken carcasses were collected from a poultry processing plant between July 2004 and June 2005. Water samples also were collected at the entrance and exit of the chiller. After preenrichment, carcass and water samples were analyzed for the presence of Salmonella using the automated BAX system followed by traditional culture methods. The proportions of pre- and postchill carcasses that were positive for Salmonella were 88.4 and 84.1%, respectively. Ninety-two percent of water samples collected at the entrance of the chiller were positive for Salmonella, but all exit samples were negative. There was no significant difference in the prevalence of Salmonella between pre- and postchill carcasses (P > 0.05). Salmonella isolates recovered were serotyped and tested for susceptibility to antimicrobials. Thirteen serotypes were identified; the most common were Salmonella Kentucky (59.5%) and Salmonella Typhimurium (17.8%). Three hundred thirty-nine (79.8%) of the isolates were resistant to at least one antimicrobial, and 53.4% were resistant to three or more antimicrobials. Resistance was most often observed to tetracycline (73.4% of isolates), ampicillin (52.9%), amoxicillin-clavulanic acid (52%), ceftiofur (51.7%), streptomycin (35.2%), and sulfisoxazole (21.8%). These results indicate the high prevalence of Salmonella contamination in whole broiler carcasses, and a large number of these Salmonella isolates were resistant to commonly used antimicrobials. PMID:18044422

  3. Antimicrobial resistance and management of invasive Salmonella disease

    PubMed Central

    Kariuki, Samuel; Gordon, Melita A.; Feasey, Nicholas; Parry, Christopher M

    2015-01-01

    Invasive Salmonella infections (typhoidal and non-typhoidal) cause a huge burden of illness estimated at nearly 3.4 million cases and over 600,000 deaths annually especially in resource-limited settings. Invasive non-typhoidal Salmonella (iNTS) infections are particularly important in immunosuppressed populations especially in sub-Saharan Africa, causing a mortality of 20–30% in vulnerable children below 5 years of age. In these settings, where routine surveillance for antimicrobial resistance is rare or non-existent, reports of 50–75% multidrug resistance (MDR) in NTS are common, including strains of NTS also resistant to flouroquinolones and 3rd generation cephalosporins. Typhoid (enteric) fever caused by Salmonella Typhi and Salmonella Paratyphi A remains a major public health problem in many parts of Asia and Africa. Currently over a third of isolates in many endemic areas are MDR, and diminished susceptibility or resistance to fluoroquinolones, the drugs of choice for MDR cases over the last decade is an increasing problem. The situation is particularly worrying in resource-limited settings where the few remaining effective antimicrobials are either unavailable or altogether too expensive to be afforded by either the general public or by public health services. Although the prudent use of effective antimicrobials, improved hygiene and sanitation and the discovery of new antimicrobial agents may offer hope for the management of invasive salmonella infections, it is essential to consider other interventions including the wider use of WHO recommended typhoid vaccines and the acceleration of trials for novel iNTS vaccines. The main objective of this review is to describe existing data on the prevalence and epidemiology of antimicrobial resistant invasive Salmonella infections and how this affects the management of these infections, especially in endemic developing countries. PMID:25912288

  4. Antimicrobial resistance and management of invasive Salmonella disease.

    PubMed

    Kariuki, Samuel; Gordon, Melita A; Feasey, Nicholas; Parry, Christopher M

    2015-06-19

    Invasive Salmonella infections (typhoidal and non-typhoidal) cause a huge burden of illness estimated at nearly 3.4 million cases and over 600,000 deaths annually especially in resource-limited settings. Invasive non-typhoidal Salmonella (iNTS) infections are particularly important in immunosuppressed populations especially in sub-Saharan Africa, causing a mortality of 20-30% in vulnerable children below 5 years of age. In these settings, where routine surveillance for antimicrobial resistance is rare or non-existent, reports of 50-75% multidrug resistance (MDR) in NTS are common, including strains of NTS also resistant to flouroquinolones and 3rd generation cephalosporins. Typhoid (enteric) fever caused by Salmonella Typhi and Salmonella Paratyphi A remains a major public health problem in many parts of Asia and Africa. Currently over a third of isolates in many endemic areas are MDR, and diminished susceptibility or resistance to fluoroquinolones, the drugs of choice for MDR cases over the last decade is an increasing problem. The situation is particularly worrying in resource-limited settings where the few remaining effective antimicrobials are either unavailable or altogether too expensive to be afforded by either the general public or by public health services. Although the prudent use of effective antimicrobials, improved hygiene and sanitation and the discovery of new antimicrobial agents may offer hope for the management of invasive salmonella infections, it is essential to consider other interventions including the wider use of WHO recommended typhoid vaccines and the acceleration of trials for novel iNTS vaccines. The main objective of this review is to describe existing data on the prevalence and epidemiology of antimicrobial resistant invasive Salmonella infections and how this affects the management of these infections, especially in endemic developing countries. PMID:25912288

  5. Antimicrobial resistance and genetic characterization of fluoroquinolone resistance of Pseudomonas aeruginosa isolated from canine infections.

    PubMed

    Rubin, J; Walker, R D; Blickenstaff, K; Bodeis-Jones, S; Zhao, S

    2008-09-18

    Infections with antimicrobial-resistant bacteria are a great challenge in both human and veterinary medicine. The purpose of this study was to determine antimicrobial susceptibility of 106 strains of Pseudomonas aeruginosa isolated from dogs with otitis and pyoderma from 2003 to 2006 in the United States. Three antimicrobial panels, including 6 classes and 32 antimicrobial agents, were used. A wide range of susceptibility patterns were noted with some isolates being resistant to between 8 and 28 (mean 16) of the antimicrobials tested. Among the beta-lactams, all isolates were resistant to ampicillin, cefoxitin, cefpodoxime, cephalothin and cefazolin followed by amoxicillin/clavulanic acid (99%), ceftiofur (97%), ceftriaxone (39%), cefotaxime (26%), and cefotaxime/clavulanic acid (20%), whereas less than 7% of isolates were resistant to ceftazidime/clavulanic acid, ceftazidime, piperacillin/tazobactam or cefepime. Two isolates were resistant to the carbapenems. Among the quinolones and fluoroquinolones, the most isolates were resistant to naladixic acid (96%), followed by orbifloxacin (52%), difloxacin (43%), enrofloxacin (31%), marbofloxacin (27%), gatifloxacin (23%), levofloxacin (21%), and ciprofloxacin (16%). Among the aminoglycosides, the most resistance was seen to kanamycin (90%), followed by streptomycin (69%), gentamicin (7%), and amikacin (3%). Of the remaining antimicrobials 100% of the isolates were resistant to chloramphenicol followed by tetracycline (98%), trimethoprim/sulfamethoxazole (57%), and sulfisoxazole (51%). Point mutations were present in gyrA, gyrB, parC, and/or parE genes among 34 of the 102 naladixic acid-resistant isolates. Two isolates contained class 1 integrons carrying aadA gene conferring streptomycin and spectinomycin resistance. The findings suggest that many antimicrobial agents commonly used in companion animals may not constitute appropriate therapy for canine pseudomonas infections. PMID:18395369

  6. Community-Acquired Methicillin-Resistant Pyogenic Liver Abscess

    PubMed Central

    Cherian, Joel; Singh, Rahul; Varma, Muralidhar; Vidyasagar, Sudha; Mukhopadhyay, Chiranjay

    2016-01-01

    Pyogenic liver abscesses are rare with an incidence of 0.5% to 0.8% and are mostly due to hepatobiliary causes (40% to 60%). Most are polymicrobial with less than 10% being caused by Staphylococcus aureus. Of these, few are caused by methicillin-resistant Staphylococcus aureus (MRSA) and fewer still by a community-acquired strain. Here we present a case study of a patient with a community-acquired MRSA liver abscess. The patient presented with fever since 1 month and tender hepatomegaly. Blood tests revealed elevated levels of alkaline phosphatase, C-reactive protein, erythrocyte sedimentation rate, and neutrophilic leukocytosis. Blood cultures were sterile. Ultrasound of the abdomen showed multiple abscesses, from which pus was drained and MRSA isolated. Computed tomography of the abdomen did not show any source of infection, and an amebic serology was negative. The patient was started on vancomycin for 2 weeks, following which he became afebrile and was discharged on oral linezolid for 4 more weeks. Normally a liver abscess is treated empirically with ceftriaxone for pyogenic liver abscess and metronidazole for amebic liver abscess. However, if the patient has risk factors for a Staphylococcal infection, it is imperative that antibiotics covering gram-positive organisms be added while waiting for culture reports. PMID:27540556

  7. Emergent and evolving antimicrobial resistance cassettes in community-associated fusidic acid and meticillin-resistant Staphylococcus aureus.

    PubMed

    Ellington, Matthew J; Reuter, Sandra; Harris, Simon R; Holden, Matthew T G; Cartwright, Edward J; Greaves, Daniel; Gerver, Sarah M; Hope, Russell; Brown, Nicholas M; Török, M Estee; Parkhill, Julian; Köser, Claudio U; Peacock, Sharon J

    2015-05-01

    Fusidic acid is a topical and systemic antimicrobial used for the treatment of staphylococcal infections in hospitals and the community. Sales of fusidic acid and resistance rates among meticillin-resistant Staphylococcus aureus (MRSA) doubled between 1990 and 2001. For the following decade, fusidic acid resistance rates among isolates from Addenbrooke's Hospital (Cambridge, UK) were compared with national resistance rates from MRSA bacteraemia surveillance data and with antimicrobial sales data. Sales of fusidic acid remained relatively constant between 2002 and 2012, whilst fusidic acid resistance increased two- and four-fold in MRSA bacteraemias nationally and in MRSA isolates from Cambridge, respectively. A subgroup of MRSA resistant only to fusidic acid increased after 2006 by 5-fold amongst bacteraemias nationally and 17-fold (to 7.7% in 2012) amongst Cambridge MRSA isolates. All of the available local isolates from 2011 to 2012 (n=23) were acquired in the community, were not related epidemiologically and belonged to multilocus sequence typing (MLST) groups ST1, 5, 8, 45 or 149 as revealed from analysis of whole-genome sequence data. All harboured the fusC gene on one of six distinct staphylococcal cassette chromosome (SCC) elements, four of which were dual-resistance chimeras that encoded β-lactam and fusidic acid resistance. In summary, fusidic acid-resistant MRSA increased in prevalence during the 2000s with notable rises after 2006. The development of chimeric cassettes that confer dual resistance to β-lactams and fusidic acid demonstrates that the genetics underpinning resistance in community-associated MRSA are evolving. PMID:25769787

  8. Emergent and evolving antimicrobial resistance cassettes in community-associated fusidic acid and meticillin-resistant Staphylococcus aureus

    PubMed Central

    Ellington, Matthew J.; Reuter, Sandra; Harris, Simon R.; Holden, Matthew T.G.; Cartwright, Edward J.; Greaves, Daniel; Gerver, Sarah M.; Hope, Russell; Brown, Nicholas M.; Török, M. Estee; Parkhill, Julian; Köser, Claudio U.; Peacock, Sharon J.

    2015-01-01

    Fusidic acid is a topical and systemic antimicrobial used for the treatment of staphylococcal infections in hospitals and the community. Sales of fusidic acid and resistance rates among meticillin-resistant Staphylococcus aureus (MRSA) doubled between 1990 and 2001. For the following decade, fusidic acid resistance rates among isolates from Addenbrooke's Hospital (Cambridge, UK) were compared with national resistance rates from MRSA bacteraemia surveillance data and with antimicrobial sales data. Sales of fusidic acid remained relatively constant between 2002 and 2012, whilst fusidic acid resistance increased two- and four-fold in MRSA bacteraemias nationally and in MRSA isolates from Cambridge, respectively. A subgroup of MRSA resistant only to fusidic acid increased after 2006 by 5-fold amongst bacteraemias nationally and 17-fold (to 7.7% in 2012) amongst Cambridge MRSA isolates. All of the available local isolates from 2011 to 2012 (n = 23) were acquired in the community, were not related epidemiologically and belonged to multilocus sequence typing (MLST) groups ST1, 5, 8, 45 or 149 as revealed from analysis of whole-genome sequence data. All harboured the fusC gene on one of six distinct staphylococcal cassette chromosome (SCC) elements, four of which were dual-resistance chimeras that encoded β-lactam and fusidic acid resistance. In summary, fusidic acid-resistant MRSA increased in prevalence during the 2000s with notable rises after 2006. The development of chimeric cassettes that confer dual resistance to β-lactams and fusidic acid demonstrates that the genetics underpinning resistance in community-associated MRSA are evolving. PMID:25769787

  9. Susceptibility and resistance of ruminal bacteria to antimicrobial feed additives.

    PubMed Central

    Nagaraja, T G; Taylor, M B

    1987-01-01

    Susceptibility and resistance of ruminal bacterial species to avoparcin, narasin, salinomycin, thiopeptin, tylosin, virginiamycin, and two new ionophore antibiotics, RO22-6924/004 and RO21-6447/009, were determined. Generally, antimicrobial compounds were inhibitory to gram-positive bacteria and those bacteria that have gram-positive-like cell wall structure. MICs ranged from 0.09 to 24.0 micrograms/ml. Gram-negative bacteria were resistant at the highest concentration tested (48.0 micrograms/ml). On the basis of their fermentation products, ruminal bacteria that produce lactic acid, butyric acid, formic acid, or hydrogen were susceptible and bacteria that produce succinic acid or ferment lactic acid were resistant to the antimicrobial compounds. Selenomonas ruminantium was the only major lactic acid-producing bacteria resistant to all the antimicrobial compounds tested. Avoparcin and tylosin appeared to be less inhibitory (MIC greater than 6.0 micrograms/ml) than the other compounds to the two major lactic acid-producing bacteria, Streptococcus bovis and Lactobacillus sp. Ionophore compounds seemed to be more inhibitory (MIC, 0.09 to 1.50 micrograms/ml) than nonionophore compounds (MIC, 0.75 to 12.0 micrograms/ml) to the major butyric acid-producing bacteria. Treponema bryantii, an anaerobic rumen spirochete, was less sensitive to virginiamycin than to the other antimicrobial compounds. Ionophore compounds were generally bacteriostatic, and nonionophore compounds were bactericidal. The specific growth rate of Bacteroides ruminicola was reduced by all the antimicrobial compounds except avoparcin. The antibacterial spectra of the feed additives were remarkably similar, and it appears that MICs may not be good indicators of the potency of the compounds in altering ruminal fermentation characteristics. PMID:3116929

  10. Evaluation of Camellia sinensis catechins as a swine antimicrobial feed additive that does not cause antibiotic resistance.

    PubMed

    Ohno, Akira; Kataoka, Shinichiro; Ishii, Yoshikazu; Terasaki, Toshiaki; Kiso, Masaaki; Okubo, Mitsuyuki; Yamaguchi, Keizo; Tateda, Kazuhiro

    2013-01-01

    Antimicrobial growth promoters (AGPs) have been banned and phased out because their use has been linked to the emergence and spread of antibiotic-resistant pathogens; however, the ban has had a marked impact on livestock production, and feed additive alternatives to AGPs are required. We focused on green tea leaves as potential alternatives to AGPs because they contain significant amounts of polyphenol catechins, which have antivirus and antimicrobial effects. We examined cross-resistance between epigallocatechin gallate (EGCG), which is the most abundant catechin of green tea leaves, and commercially available antimicrobials in clinically problematic antimicrobial-resistant bacteria, and whether bacteria have the ability to acquire resistance by consecutive passage in sub-inhibitory concentrations of EGCG. EGCG did not display any cross-resistance with reference antimicrobials and the bacteria did not acquire EGCG resistance. Further, we examined the growth-promoting effects of dried green tea leaves on the breeding of a new Japanese breed, Tokyo-X pigs. While the mortality rates of the green tea leaf (GTL) and AGP groups were both 11.1% (one in nine piglets), the mortality rate was 50% for the control group with an additive-free diet (four in eight piglets). The rate of body weight increase in both the GTL and AGP groups was approximately the same. The growth-promoting effects of green tea leaves and AGPs were similar, and there was no possibility that the antimicrobial properties of catechins caused the same problem as AGPs. Thus, it can be concluded that green tea leaves are a safe feed additive alternative to AGPs. PMID:23138151

  11. Pheno- and genotypic analysis of antimicrobial resistance properties of Yersinia ruckeri from fish.

    PubMed

    Huang, Yidan; Michael, Geovana Brenner; Becker, Roswitha; Kaspar, Heike; Mankertz, Joachim; Schwarz, Stefan; Runge, Martin; Steinhagen, Dieter

    2014-07-16

    Enteric red-mouth disease, caused by Yersinia ruckeri, is an important disease in rainbow trout aquaculture. Antimicrobial agents are frequently used in aquaculture, thereby causing a selective pressure on bacteria from aquatic organisms under which they may develop resistance to antimicrobial agents. In this study, the distribution of minimal inhibitory concentrations (MICs) of antimicrobial agents for 83 clinical and non-clinical epidemiologically unrelated Y. ruckeri isolates from north west Germany was determined. Antimicrobial susceptibility was conducted by broth microdilution at 22 ± 2°C for 24, 28 and 48 h. Incubation for 24h at 22 ± 2°C appeared to be suitable for susceptibility testing of Y. ruckeri. In contrast to other antimicrobial agents tested, enrofloxacin and nalidixic acid showed a bimodal distribution of MICs, with one subpopulation showing lower MICs for enrofloxacin (0.008-0.015 μg/mL) and nalidixic acid (0.25-0.5 μg/mL) and another subpopulation exhibiting elevated MICs of 0.06-0.25 and 8-64 μg/mL, respectively. Isolates showing elevated MICs revealed single amino acid substitutions in the quinolone resistance-determining region (QRDR) of the GyrA protein at positions 83 (Ser83-Arg or -Ile) or 87 (Asn87-Tyr), which raised the MIC values 8- to 32-fold for enrofloxacin or 32- to 128-fold for nalidixic acid. An isolate showing elevated MICs for sulfonamides and trimethoprim harbored a ∼ 8.9 kb plasmid, which carried the genes sul2, strB and a dfrA14 gene cassette integrated into the strA gene. These observations showed that Y. ruckeri isolates were able to develop mutations that reduce their susceptibility to (fluoro)quinolones and to acquire plasmid-borne resistance genes. PMID:24331744

  12. Insect Antimicrobial Peptide Complexes Prevent Resistance Development in Bacteria

    PubMed Central

    Chernysh, Sergey; Gordya, Natalia; Suborova, Tatyana

    2015-01-01

    In recent decades much attention has been paid to antimicrobial peptides (AMPs) as natural antibiotics, which are presumably protected from resistance development in bacteria. However, experimental evolution studies have revealed prompt resistance increase in bacteria to any individual AMP tested. Here we demonstrate that naturally occurring compounds containing insect AMP complexes have clear advantage over individual peptide and small molecule antibiotics in respect of drug resistance development. As a model we have used the compounds isolated from bacteria challenged maggots of Calliphoridae flies. The compound isolated from blow fly Calliphora vicina was found to contain three distinct families of cell membrane disrupting/permeabilizing peptides (defensins, cecropins and diptericins), one family of proline rich peptides and several unknown antimicrobial substances. Resistance changes under long term selective pressure of the compound and reference antibiotics cefotaxime, meropenem and polymyxin B were tested using Escherichia coli, Klebsiella pneumonia and Acinetobacter baumannii clinical strains. All the strains readily developed resistance to the reference antibiotics, while no signs of resistance growth to the compound were registered. Similar results were obtained with the compounds isolated from 3 other fly species. The experiments revealed that natural compounds containing insect AMP complexes, in contrast to individual AMP and small molecule antibiotics, are well protected from resistance development in bacteria. Further progress in the research of natural AMP complexes may provide novel solutions to the drug resistance problem. PMID:26177023

  13. Coping with antibiotic resistance: combining nanoparticles with antibiotics and other antimicrobial agents.

    PubMed

    Allahverdiyev, Adil M; Kon, Kateryna Volodymyrivna; Abamor, Emrah Sefik; Bagirova, Malahat; Rafailovich, Miriam

    2011-11-01

    The worldwide escalation of bacterial resistance to conventional medical antibiotics is a serious concern for modern medicine. High prevalence of multidrug-resistant bacteria among bacteria-based infections decreases effectiveness of current treatments and causes thousands of deaths. New improvements in present methods and novel strategies are urgently needed to cope with this problem. Owing to their antibacterial activities, metallic nanoparticles represent an effective solution for overcoming bacterial resistance. However, metallic nanoparticles are toxic, which causes restrictions in their use. Recent studies have shown that combining nanoparticles with antibiotics not only reduces the toxicity of both agents towards human cells by decreasing the requirement for high dosages but also enhances their bactericidal properties. Combining antibiotics with nanoparticles also restores their ability to destroy bacteria that have acquired resistance to them. Furthermore, nanoparticles tagged with antibiotics have been shown to increase the concentration of antibiotics at the site of bacterium-antibiotic interaction, and to facilitate binding of antibiotics to bacteria. Likewise, combining nanoparticles with antimicrobial peptides and essential oils generates genuine synergy against bacterial resistance. In this article, we aim to summarize recent studies on interactions between nanoparticles and antibiotics, as well as other antibacterial agents to formulate new prospects for future studies. Based on the promising data that demonstrated the synergistic effects of antimicrobial agents with nanoparticles, we believe that this combination is a potential candidate for more research into treatments for antibiotic-resistant bacteria. PMID:22029522

  14. Molecular approaches to enhance surveillance of gonococcal antimicrobial resistance.

    PubMed

    Goire, Namraj; Lahra, Monica M; Chen, Marcus; Donovan, Basil; Fairley, Christopher K; Guy, Rebecca; Kaldor, John; Regan, David; Ward, James; Nissen, Michael D; Sloots, Theo P; Whiley, David M

    2014-03-01

    The best available data indicate that the world is heading towards a pandemic of extensively drug-resistant Neisseria gonorrhoeae. At the same time, clinical microbiology laboratories have moved away from using culture-based methods to diagnose gonorrhoea, thus undermining our ability to detect antimicrobial resistance (AMR) using current technologies. In this Opinion article, we discuss the problem of N. gonorrhoeae AMR, particularly emerging resistance to the cephalosporin ceftriaxone, outline current concerns about the surveillance of N. gonorrhoeae AMR and propose the use of molecular methods on a large scale to systematically enhance surveillance. PMID:24509781

  15. Antimicrobial Resistance in Escherichia coli Recovered from Feedlot Cattle and Associations with Antimicrobial Use

    PubMed Central

    Benedict, Katharine M.; Gow, Sheryl P.; McAllister, Tim A.; Booker, Calvin W.; Hannon, Sherry J.; Checkley, Sylvia L.; Noyes, Noelle R.; Morley, Paul S.

    2015-01-01

    The objectives of this study were to estimate the prevalence of antimicrobial resistance (AMR) and to investigate the associations between exposures to antimicrobial drugs (AMDs) and AMR in fecal non-type specific Escherichia coli (NTSEC) recovered from a large population of feedlot cattle. Two-stage random sampling was used to select individually identified cattle for enrollment, which were sampled at arrival and then a second time later in the feeding period. Advanced regression techniques were used to estimate resistance prevalences, and to investigate associations between AMD exposures in enrolled cattle and penmates and AMR identified in NTSEC recovered from the second sample set. Resistance was most commonly detected to tetracycline, streptomycin, and sulfisoxazole, and was rarely identified for critically important AMDs. All cattle were exposed to AMDs in feed, and 45% were treated parenterally. While resistance prevalence generally increased during the feeding period, most AMD exposures were not significantly associated with AMR outcomes. Exposures of enrolled cattle to tetracycline were associated with increased resistance to tetracycline and trimethoprim sulfa, while beta-lactam exposures were associated with decreased likelihood of detecting streptomycin resistance. Pen-level AMD exposure measures were not associated with resistance outcomes. These findings suggest that tetracycline treatment of feedlot cattle can be associated with modest increases in risk for recovery of resistant NTSEC, but the numerous treatments with an advanced macrolide (tulathromycin) were not associated with detectable increases in resistance in NTSEC. All cattle were exposed to in-feed treatments of tetracycline and this could limit the ability to identify the full impact of these exposures, but these exposures varied for enrolled cattle varied, providing an opportunity to evaluate a dose response. While AMD exposures were not associated with detectably increased risks for

  16. Antimicrobial Resistance in Escherichia coli Recovered from Feedlot Cattle and Associations with Antimicrobial Use.

    PubMed

    Benedict, Katharine M; Gow, Sheryl P; McAllister, Tim A; Booker, Calvin W; Hannon, Sherry J; Checkley, Sylvia L; Noyes, Noelle R; Morley, Paul S

    2015-01-01

    The objectives of this study were to estimate the prevalence of antimicrobial resistance (AMR) and to investigate the associations between exposures to antimicrobial drugs (AMDs) and AMR in fecal non-type specific Escherichia coli (NTSEC) recovered from a large population of feedlot cattle. Two-stage random sampling was used to select individually identified cattle for enrollment, which were sampled at arrival and then a second time later in the feeding period. Advanced regression techniques were used to estimate resistance prevalences, and to investigate associations between AMD exposures in enrolled cattle and penmates and AMR identified in NTSEC recovered from the second sample set. Resistance was most commonly detected to tetracycline, streptomycin, and sulfisoxazole, and was rarely identified for critically important AMDs. All cattle were exposed to AMDs in feed, and 45% were treated parenterally. While resistance prevalence generally increased during the feeding period, most AMD exposures were not significantly associated with AMR outcomes. Exposures of enrolled cattle to tetracycline were associated with increased resistance to tetracycline and trimethoprim sulfa, while beta-lactam exposures were associated with decreased likelihood of detecting streptomycin resistance. Pen-level AMD exposure measures were not associated with resistance outcomes. These findings suggest that tetracycline treatment of feedlot cattle can be associated with modest increases in risk for recovery of resistant NTSEC, but the numerous treatments with an advanced macrolide (tulathromycin) were not associated with detectable increases in resistance in NTSEC. All cattle were exposed to in-feed treatments of tetracycline and this could limit the ability to identify the full impact of these exposures, but these exposures varied for enrolled cattle varied, providing an opportunity to evaluate a dose response. While AMD exposures were not associated with detectably increased risks for

  17. Efficacy of triclosan as an antimicrobial hand soap and its potential impact on antimicrobial resistance: a focused review.

    PubMed

    Giuliano, Christopher A; Rybak, Michael J

    2015-03-01

    Triclosan is a synthetic biocide found in many household products, including antimicrobial hand soap. Levels of triclosan have been found throughout the environment and in human urine, blood, and even breast milk. Increasing levels of exposure to triclosan have led to concerns over the development of resistance to triclosan and cross-resistance to other antimicrobials. We performed a literature search to assess whether the widespread use of triclosan displays a favorable benefit: risk ratio, defined by evaluation of triclosan's efficacy as an antimicrobial hand soap and its potential effect on the development of antimicrobial resistance. Data from laboratory-based studies regarding the efficacy of triclosan are conflicting, although well-designed studies suggest no significant difference in efficacy over nonantimicrobial soap. In addition, when triclosan was introduced in a community setting, no beneficial effects were observed on the reduction of infections over nonantimicrobial soap. Resistance to triclosan and cross-resistance to antimicrobials have been consistently demonstrated in laboratory settings, although overall resistance rates and cross-resistance rates in the community setting are low. Based on the available evidence, the risk of potential antimicrobial resistance outweighs the benefit of widespread triclosan use in antimicrobial soaps. PMID:25809180

  18. Enhancing US-Japan Cooperation to Combat Antimicrobial Resistance

    PubMed Central

    2014-01-01

    The Global Health Security Agenda (GHSA) is aimed at preventing, detecting, and responding to infectious disease threats. To move toward these goals, the United States has committed to partner with at least 30 countries around the world. One of the objectives of the GHSA includes “[p]reventing the emergence and spread of antimicrobial drug resistant organisms.” Antimicrobial resistance (AMR) has become a growing global health security problem, with inappropriate use of antimicrobial medications in humans and animals and a lack of new antimicrobial medications contributing to this problem. While AMR is a growing global concern, working on it regionally can make this multifaceted problem more manageable. The United States and Japan, both world leaders in the life sciences, are close allies that have established cooperative programs in medical research and global health that can be used to work on combating AMR and advance the GHSA. Although the United States and Japan have cooperated on health issues in the past, their cooperation on the growing problem of AMR has been limited. Their existing networks, cooperative programs, and close relationships can and should be used to work on combating this expanding problem. PMID:25470465

  19. Enhancing US-Japan cooperation to combat antimicrobial resistance.

    PubMed

    Gerbin, C Sachi

    2014-01-01

    The Global Health Security Agenda (GHSA) is aimed at preventing, detecting, and responding to infectious disease threats. To move toward these goals, the United States has committed to partner with at least 30 countries around the world. One of the objectives of the GHSA includes "[p]reventing the emergence and spread of antimicrobial drug resistant organisms." Antimicrobial resistance (AMR) has become a growing global health security problem, with inappropriate use of antimicrobial medications in humans and animals and a lack of new antimicrobial medications contributing to this problem. While AMR is a growing global concern, working on it regionally can make this multifaceted problem more manageable. The United States and Japan, both world leaders in the life sciences, are close allies that have established cooperative programs in medical research and global health that can be used to work on combating AMR and advance the GHSA. Although the United States and Japan have cooperated on health issues in the past, their cooperation on the growing problem of AMR has been limited. Their existing networks, cooperative programs, and close relationships can and should be used to work on combating this expanding problem. PMID:25470465

  20. Antimicrobial Resistance in Wildlife: Implications for Public Health.

    PubMed

    Carroll, D; Wang, J; Fanning, S; McMahon, B J

    2015-11-01

    The emergence and spread of antimicrobial-resistant (AMR) bacteria in natural environments is a major concern with serious implications for human and animal health. The aim of this study was to determine the prevalence of AMR Escherichia coli (E. coli) in wild birds and mammalian species. Thirty faecal samples were collected from each of the following wildlife species: herring gulls (Larus argentatus), black-headed gulls (Larus ridibundus), lesser black-back gulls (Larus fuscus), hybrid deer species (Cervus elaphus x Cervus nippon) and twenty-six from starlings (Sturnus vulgaris). A total of 115 E. coli isolates were isolated from 81 of 146 samples. Confirmed E. coli isolates were tested for their susceptibility to seven antimicrobial agents by disc diffusion. In total, 5.4% (8/146) of samples exhibited multidrug-resistant phenotypes. The phylogenetic group and AMR-encoding genes of all multidrug resistance isolates were determined by PCR. Tetracycline-, ampicillin- and streptomycin-resistant isolates were the most common resistant phenotypes. The following genes were identified in E. coli: bla(TEM), strA, tet(A) and tet(B). Plasmids were identified in all samples that exhibited multidrug-resistant phenotypes. This study indicates that wild birds and mammals may function as important host reservoirs and potential vectors for the spread of resistant bacteria and genetic determinants of AMR. PMID:25639901

  1. Antimicrobial resistance profiles and mechanisms of resistance in Campylobacter jejuni isolates from pets.

    PubMed

    Acke, Els; McGill, Kevina; Quinn, Teresa; Jones, Boyd R; Fanning, Seamus; Whyte, Paul

    2009-01-01

    The presence of antimicrobial resistance in 51 Campylobacter jejuni isolates obtained from cats and dogs was determined by E-testing. Resistance to nalidixic acid (37.3% of isolates), ciprofloxacin (19.6%), tetracycline (13.7%), ampicillin (13.7%), erythromycin (11.8%), and chloramphenicol (5.9%) was detected. Resistance to two antimicrobials or more was present in 31.4% of isolates, and one isolate was resistant to all six antimicrobials. Of the isolates with ciprofloxacin and/or nalidixic acid resistance, 54.5% had the gyrA substitution Thr-86-Ile on sequencing. The tet o gene was detected in 75.0% isolates with high-level resistance to tetracycline. With the observed antimicrobial resistance in C. jejuni isolates from pets in this study, and the detection of identical mechanisms for quinolone and tetracycline resistance in pets and humans, pets should be considered a potential source of (multi)resistant C. jejuni infections in humans. PMID:19580444

  2. Genetic characterization of antimicrobial resistance in coagulase-negative staphylococci from bovine mastitis milk.

    PubMed

    Frey, Yvonne; Rodriguez, Joan Peña; Thomann, Andreas; Schwendener, Sybille; Perreten, Vincent

    2013-04-01

    Coagulase-negative staphylococci (CNS; n=417) were isolated from bovine milk and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Nineteen different species were identified, and Staphylococcus xylosus, Staphylococcus chromogenes, Staphylococcus haemolyticus, and Staphylococcus sciuri were the most prevalent species. Resistance to oxacillin (47.0% of the isolates), fusidic acid (33.8%), tiamulin (31.9%), penicillin (23.3%), tetracycline (15.8%), streptomycin (9.6%), erythromycin (7.0%), sulfonamides (5%), trimethoprim (4.3%), clindamycin (3.4%), kanamycin (2.4%), and gentamicin (2.4%) was detected. Resistance to oxacillin was attributed to the mecA gene in 9.7% of the oxacillin-resistant isolates. The remaining oxacillin-resistant CNS did not contain the mecC gene or mecA1 promoter mutations. The mecA gene was detected in Staphylococcus fleurettii, Staphylococcus epidermidis, Staph. haemolyticus, and Staph. xylosus. Resistance to tetracycline was attributed to the presence of tet(K) and tet(L), penicillin resistance to blaZ, streptomycin resistance to str and ant(6)-Ia, and erythromycin resistance to erm(C), erm(B), and msr. Resistance to tiamulin and fusidic acid could not be attributed to an acquired resistance gene. In total, 15.1% of the CNS isolates were multidrug resistant (i.e., resistant to 2 or more antimicrobials). The remaining CNS isolates were susceptible to antimicrobials commonly used in mastitis treatment. Methicillin-resistant CNS isolates were diverse, as determined by mecA gene sequence analysis, staphylococcal cassette chromosome mec typing, and pulsed-field gel electrophoresis. Arginine catabolic mobile element types 1 and 3 were detected in both methicillin-resistant and methicillin-susceptible Staph. epidermidis and were associated with sequence types ST59 and ST111. Because this study revealed the presence of multidrug-resistant CNS in a heterogeneous CNS population, we recommend antibiogram analysis

  3. Aquaculture as yet another environmental gateway to the development and globalisation of antimicrobial resistance.

    PubMed

    Cabello, Felipe C; Godfrey, Henry P; Buschmann, Alejandro H; Dölz, Humberto J

    2016-07-01

    Aquaculture uses hundreds of tonnes of antimicrobials annually to prevent and treat bacterial infection. The passage of these antimicrobials into the aquatic environment selects for resistant bacteria and resistance genes and stimulates bacterial mutation, recombination, and horizontal gene transfer. The potential bridging of aquatic and human pathogen resistomes leads to emergence of new antimicrobial-resistant bacteria and global dissemination of them and their antimicrobial resistance genes into animal and human populations. Efforts to prevent antimicrobial overuse in aquaculture must include education of all stakeholders about its detrimental effects on the health of fish, human beings, and the aquatic ecosystem (the notion of One Health), and encouragement of environmentally friendly measures of disease prevention, including vaccines, probiotics, and bacteriophages. Adoption of these measures is a crucial supplement to efforts dealing with antimicrobial resistance by developing new therapeutic agents, if headway is to be made against the increasing problem of antimicrobial resistance in human and veterinary medicine. PMID:27083976

  4. Antimicrobial resistance in commensal Escherichia coli in veal calves is associated with antimicrobial drug use.

    PubMed

    Bosman, A B; Wagenaar, J A; Stegeman, J A; Vernooij, J C M; Mevius, D J

    2014-09-01

    The aim of this study was to determine the association between farm management factors, including antimicrobial drug usage, and resistance in commensal Escherichia coli isolates from the faeces of white veal calves. Ninety E. coli isolates from one pooled sample per farm (n = 48) were tested for their phenotypical resistance against amoxicillin, tetracycline, cefotaxime, ciprofloxacin and trimethoprim/sulfamethoxazole (TMP/SMX). Logistic regression analysis revealed the following risk factors (P < 0·05); farmer wearing the same work clothes for several days [ciprofloxacin, odds ratio (OR) 2·6; tetracycline, OR 2·4], administration of trimethoprim-sulfonamide combinations (TMP/SMX, OR 3·0; amoxicillin, OR 3·1; tetracycline, OR 2·6), ⩾0·3 animal daily dosage per production cycle (ADD/pc), quinolones (ciprofloxacin, OR 2·8), ⩾1·3 ADD/pc, penicillins (ciprofloxacin, OR 3·3; tetracycline, OR 3·4), 20-40 ADD/pc, tetracyclines (tetracycline, OR 3·2) and >40 ADD/pc, tetracyclines (tetracycline, OR 13·1; amoxicillin, OR 6·5). In this study antimicrobial resistance in commensal E. coli was mainly associated with antimicrobial drug use. PMID:24152540

  5. Epidemiology, ecology, and molecular genetics of antimicrobial resistance in pathogenic and commensal bacteria from food animals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The National Antimicrobial Resistance Monitoring System (NARMS) is a collaborative program between the Food and Drug Administration (FDA), the Centers for Disease Control (CDC), and the United States Department of Agriculture to prospectively monitor changes in antimicrobial susceptibilities of zoon...

  6. Antimicrobial resistance in humans, livestock and the wider environment.

    PubMed

    Woolhouse, Mark; Ward, Melissa; van Bunnik, Bram; Farrar, Jeremy

    2015-06-01

    Antimicrobial resistance (AMR) in humans is inter-linked with AMR in other populations, especially farm animals, and in the wider environment. The relatively few bacterial species that cause disease in humans, and are the targets of antibiotic treatment, constitute a tiny subset of the overall diversity of bacteria that includes the gut microbiota and vast numbers in the soil. However, resistance can pass between these different populations; and homologous resistance genes have been found in pathogens, normal flora and soil bacteria. Farm animals are an important component of this complex system: they are exposed to enormous quantities of antibiotics (despite attempts at reduction) and act as another reservoir of resistance genes. Whole genome sequencing is revealing and beginning to quantify the two-way traffic of AMR bacteria between the farm and the clinic. Surveillance of bacterial disease, drug usage and resistance in livestock is still relatively poor, though improving, but achieving better antimicrobial stewardship on the farm is challenging: antibiotics are an integral part of industrial agriculture and there are very few alternatives. Human production and use of antibiotics either on the farm or in the clinic is but a recent addition to the natural and ancient process of antibiotic production and resistance evolution that occurs on a global scale in the soil. Viewed in this way, AMR is somewhat analogous to climate change, and that suggests that an intergovernmental panel, akin to the Intergovernmental Panel on Climate Change, could be an appropriate vehicle to actively address the problem. PMID:25918441

  7. Antimicrobial resistance in humans, livestock and the wider environment

    PubMed Central

    Woolhouse, Mark; Ward, Melissa; van Bunnik, Bram; Farrar, Jeremy

    2015-01-01

    Antimicrobial resistance (AMR) in humans is inter-linked with AMR in other populations, especially farm animals, and in the wider environment. The relatively few bacterial species that cause disease in humans, and are the targets of antibiotic treatment, constitute a tiny subset of the overall diversity of bacteria that includes the gut microbiota and vast numbers in the soil. However, resistance can pass between these different populations; and homologous resistance genes have been found in pathogens, normal flora and soil bacteria. Farm animals are an important component of this complex system: they are exposed to enormous quantities of antibiotics (despite attempts at reduction) and act as another reservoir of resistance genes. Whole genome sequencing is revealing and beginning to quantify the two-way traffic of AMR bacteria between the farm and the clinic. Surveillance of bacterial disease, drug usage and resistance in livestock is still relatively poor, though improving, but achieving better antimicrobial stewardship on the farm is challenging: antibiotics are an integral part of industrial agriculture and there are very few alternatives. Human production and use of antibiotics either on the farm or in the clinic is but a recent addition to the natural and ancient process of antibiotic production and resistance evolution that occurs on a global scale in the soil. Viewed in this way, AMR is somewhat analogous to climate change, and that suggests that an intergovernmental panel, akin to the Intergovernmental Panel on Climate Change, could be an appropriate vehicle to actively address the problem. PMID:25918441

  8. Correlation between antimicrobial resistance and virulence in Klebsiella pneumoniae.

    PubMed

    Hennequin, C; Robin, F

    2016-03-01

    Klebsiella pneumoniae is responsible for a wide range of infections, including urinary tract infections, pneumonia, bacteremia, and liver abscesses. In addition to susceptible clinical isolates involved in nosocomial infections, multidrug-resistant (MDR) and hypervirulent (hvKP) strains have evolved separately in distinct clonal groups. The rapid geographic spread of these isolates is of particular concern. However, we still know little about the virulence of K. pneumoniae except for hvKP, whose secrets are beginning to be revealed. The treatment of K. pneumoniae infections is threatened by the emergence of antimicrobial resistance. The dissemination of resistance is associated with genetic mobile elements, such as plasmids that may also carry virulence determinants. A proficient pathogen should be virulent, resistant to antibiotics, and epidemic. However, the interplay between resistance and virulence is poorly understood. Here, we review current knowledge on the topic. PMID:26718943

  9. DNA microarray detection of antimicrobial resistance genes in Detection and Characterization of Antibiotic Resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Detection of antimicrobial resistance genes is essential for research and an important tool for clinical diagnostics. Most techniques used to identify resistance genes can only detect one or a few genes per assay, whereas DNA microarray technology can detect thousands of genes in a single assay. Sev...

  10. SSTAR, a Stand-Alone Easy-To-Use Antimicrobial Resistance Gene Predictor.

    PubMed

    de Man, Tom J B; Limbago, Brandi M

    2016-01-01

    We present the easy-to-use Sequence Search Tool for Antimicrobial Resistance, SSTAR. It combines a locally executed BLASTN search against a customizable database with an intuitive graphical user interface for identifying antimicrobial resistance (AR) genes from genomic data. Although the database is initially populated from a public repository of acquired resistance determinants (i.e., ARG-ANNOT), it can be customized for particular pathogen groups and resistance mechanisms. For instance, outer membrane porin sequences associated with carbapenem resistance phenotypes can be added, and known intrinsic mechanisms can be included. Unique about this tool is the ability to easily detect putative new alleles and truncated versions of existing AR genes. Variants and potential new alleles are brought to the attention of the user for further investigation. For instance, SSTAR is able to identify modified or truncated versions of porins, which may be of great importance in carbapenemase-negative carbapenem-resistant Enterobacteriaceae. SSTAR is written in Java and is therefore platform independent and compatible with both Windows and Unix operating systems. SSTAR and its manual, which includes a simple installation guide, are freely available from https://github.com/tomdeman-bio/Sequence-Search-Tool-for-Antimicrobial-Resistance-SSTAR-. IMPORTANCE Whole-genome sequencing (WGS) is quickly becoming a routine method for identifying genes associated with antimicrobial resistance (AR). However, for many microbiologists, the use and analysis of WGS data present a substantial challenge. We developed SSTAR, software with a graphical user interface that enables the identification of known AR genes from WGS and has the unique capacity to easily detect new variants of known AR genes, including truncated protein variants. Current software solutions do not notify the user when genes are truncated and, therefore, likely nonfunctional, which makes phenotype predictions less accurate. SSTAR

  11. SSTAR, a Stand-Alone Easy-To-Use Antimicrobial Resistance Gene Predictor

    PubMed Central

    Limbago, Brandi M.

    2016-01-01

    ABSTRACT We present the easy-to-use Sequence Search Tool for Antimicrobial Resistance, SSTAR. It combines a locally executed BLASTN search against a customizable database with an intuitive graphical user interface for identifying antimicrobial resistance (AR) genes from genomic data. Although the database is initially populated from a public repository of acquired resistance determinants (i.e., ARG-ANNOT), it can be customized for particular pathogen groups and resistance mechanisms. For instance, outer membrane porin sequences associated with carbapenem resistance phenotypes can be added, and known intrinsic mechanisms can be included. Unique about this tool is the ability to easily detect putative new alleles and truncated versions of existing AR genes. Variants and potential new alleles are brought to the attention of the user for further investigation. For instance, SSTAR is able to identify modified or truncated versions of porins, which may be of great importance in carbapenemase-negative carbapenem-resistant Enterobacteriaceae. SSTAR is written in Java and is therefore platform independent and compatible with both Windows and Unix operating systems. SSTAR and its manual, which includes a simple installation guide, are freely available from https://github.com/tomdeman-bio/Sequence-Search-Tool-for-Antimicrobial-Resistance-SSTAR-. IMPORTANCE Whole-genome sequencing (WGS) is quickly becoming a routine method for identifying genes associated with antimicrobial resistance (AR). However, for many microbiologists, the use and analysis of WGS data present a substantial challenge. We developed SSTAR, software with a graphical user interface that enables the identification of known AR genes from WGS and has the unique capacity to easily detect new variants of known AR genes, including truncated protein variants. Current software solutions do not notify the user when genes are truncated and, therefore, likely nonfunctional, which makes phenotype predictions less

  12. Signaling by small metabolites in systemic acquired resistance.

    PubMed

    Shah, Jyoti; Chaturvedi, Ratnesh; Chowdhury, Zulkarnain; Venables, Barney; Petros, Robby A

    2014-08-01

    Plants can retain the memory of a prior encounter with a pest. This memory confers upon a plant the ability to subsequently activate defenses more robustly when challenged by a pest. In plants that have retained the memory of a prior, localized, foliar infection by a pathogen, the pathogen-free distal organs develop immunity against subsequent infections by a broad-spectrum of pathogens. The long-term immunity conferred by this mechanism, which is termed systemic acquired resistance (SAR), is inheritable over a few generations. Signaling mediated by the phenolic metabolite salicylic acid (SA) is critical for the manifestation of SAR. Recent studies have described the involvement of additional small metabolites in SAR signaling, including methyl salicylate, the abietane diterpenoid dehydroabietinal, the lysine catabolite pipecolic acid, a glycerol-3-phosphate-dependent factor and the dicarboxylic acid azelaic acid. Many of these metabolites can be systemically transported through the plant and probably facilitate communication by the primary infected tissue with the distal tissues, which is essential for the activation of SAR. Some of these metabolites have been implicated in the SAR-associated rapid activation of defenses in response to subsequent exposure to the pathogen, a mechanism termed priming. Here, we summarize the role of these signaling metabolites in SAR, and the relationship between them and SA signaling in SAR. PMID:24506415

  13. Prolongation of acquired cellular resistance to Listeria monocytogenes

    PubMed Central

    Willers, J. M. N.; Hofhuis, F. M. A.; Meer, C. Vander

    1982-01-01

    Intracutaneous immunization of mice with 105 or 106 viable listeria resulted in acquired cellular resistance (ACR) of short duration (7 days) and in delayed-type hypersensitivity (DH) lasting at least 27 days. The ACR was partially non-specific, as 50% of the mice were also protected against a lethal challenge with Salmonella enteritidis. The specific element of the ACR could be transferred by non-adherent spleen cells from immune mice to normal recipient mice. Such transfer was not possible with adherent spleen cells from immune mice or with spleen cells from normal mice. Two systems of multiple immunizations to extend the period during which mice were protected against a challenge with 50 LD50 listeria were used. In the first system, mice were immunized with 106 viable listeria and subsequently challenged with 50 LD50 (= 107) viable listeria. Mice surviving the challenge were actually boosted at the challenge injection for ACR. In the second system mice were immunized and boosted with 108 killed listeria mixed with the adjuvant dimethyl dioctadecyl ammonium bromide (DDA). In the former system after each booster injection with viable listeria the interval during which the mice were protected doubled and reached a maximum of 31 days. In the latter system all intervals between two booster injections were equally long and never exceeded 28 days. In both systems the existence of immunological memory was suggested. The difference in results obtained after immunization with viable listeria and killed listeria mixed with DDA are discussed. PMID:6809603

  14. The generation of wear-resistant antimicrobial stainless steel surfaces by active screen plasma alloying with N and nanocrystalline Ag.

    PubMed

    Dong, Yangchun; Li, Xiaoying; Sammons, Rachel; Dong, Hanshan

    2010-04-01

    Hospital-acquired infections (HAIs), a large proportion of which are derived from contact transmission, represent a massive global challenge. In this study a novel active screen plasma (ASP) alloying technology has been developed to generate highly durable antimicrobial surfaces by combining a wear-resistant S-phase with nanocrystalline silver for medical grade stainless steel. The phase constituent, microstructure, composition and surface roughness of the alloyed surfaces were fully characterized, and the surface hardness, wear resistance and antimicrobial efficiency of the treated surfaces were evaluated. Experimental results showed that the surface hardness and sliding wear resistance of medical grade 316LVM stainless steel can be effectively improved by the ASP alloying treatment; furthermore, the Ag alloyed S-phase can achieve 93% reduction in Escherichia coli (E. coli) after 6 h contact time. Therefore, the novel ASP alloying treatment can not only improve wear resistance but also confer antibacterial activity to stainless steel surfaces. PMID:20119942

  15. How Can Vaccines Contribute to Solving the Antimicrobial Resistance Problem?

    PubMed Central

    Siber, George R.

    2016-01-01

    ABSTRACT There is a growing appreciation for the role of vaccines in confronting the problem of antimicrobial resistance (AMR). Vaccines can reduce the prevalence of resistance by reducing the need for antimicrobial use and can reduce its impact by reducing the total number of cases. By reducing the number of pathogens that may be responsible for a particular clinical syndrome, vaccines can permit the use of narrower-spectrum antibiotics for empirical therapy. These effects may be amplified by herd immunity, extending protection to unvaccinated persons in the population. Because much selection for resistance is due to selection on bystander members of the normal flora, vaccination can reduce pressure for resistance even in pathogens not included in the vaccine. Some vaccines have had disproportionate effects on drug-resistant lineages within the target species, a benefit that could be more deliberately exploited in vaccine design. We describe the effects of current vaccines in controlling AMR, survey some vaccines in development with the potential to do so further, and discuss strategies to amplify these benefits. We conclude with a discussion of research and policy priorities to more fully enlist vaccines in the battle against AMR. PMID:27273824

  16. Role of Antimicrobial Selective Pressure and Secondary Factors on Antimicrobial Resistance Prevalence in Escherichia coli from Food-Producing Animals in Japan

    PubMed Central

    Harada, Kazuki; Asai, Tetsuo

    2010-01-01

    The use of antimicrobial agents in the veterinary field affects the emergence, prevalence, and dissemination of antimicrobial resistance in bacteria isolated from food-producing animals. To control the emergence, prevalence, and dissemination of antimicrobial resistance, it is necessary to implement appropriate actions based on scientific evidence. In Japan, the Japanese Veterinary Antimicrobial Resistance Monitoring System (JVARM) was established in 1999 to monitor the antimicrobial susceptibility of foodborne and commensal bacteria from food-producing animals. The JVARM showed that the emergence and prevalence of resistant Escherichia coli were likely linked to the therapeutic antimicrobial use in food-producing animals through not only direct selection of the corresponding resistance but also indirect selections via cross-resistance and coresistance. In addition, relevant factors such as host animals and bacterial properties might affect the occurrence and prevalence of antimicrobial-resistant E. coli under the selective pressure from antimicrobial usage. This paper reviews the trends in antimicrobial resistance in E. coli and consumption of antimicrobials agents in Japan and introduces the relationship between antimicrobial usage and prevalence of antimicrobial-resistant bacteria, from food-producing animals under the JVARM program. In this paper, we will provide the underlying information about the significant factors that can help control antimicrobial resistance in bacteria in veterinary medicine. PMID:20589071

  17. [Antimicrobial resistance forever? Judicious and appropriate use of antibiotics].

    PubMed

    Cagliano, Stefano

    2015-06-01

    This article takes its cue from the original work of sir Alexander Fleming on penicillin, published in the first issue of Recenti Progressi in Medicina in 1946 and reproduced here on the occasion of the approaching 70-year anniversary of the journal. In 1928, at the time when penicillin was discovered, it could not be imagined that bacterial resistance to antibiotics would develop so rapidly: the introduction of every new class of antibiotics has been shortly followed by the emergence of new strains of bacteria resistant to that class. Bacterial resistance to antibiotic treatment is a huge concern. In this respect, an action plan against antimicrobial resistance has been devised in the United States that is targeted for a 50% reduction over the next five years. PMID:26076416

  18. Adaptive and Acquired Resistance to EGFR Inhibitors Converge on the MAPK Pathway

    PubMed Central

    Ma, Pengfei; Fu, Yujie; Chen, Minjiang; Jing, Ying; Wu, Jie; Li, Ke; Shen, Ying; Gao, Jian-Xin; Wang, Mengzhao; Zhao, Xiaojing; Zhuang, Guanglei

    2016-01-01

    Both adaptive and acquired resistance significantly limits the efficacy of the epidermal growth factor receptor (EGFR) kinase inhibitors. However, the distinct or common mechanisms of adaptive and acquired resistance have not been fully characterized. Here, through systematic modeling of erlotinib resistance in lung cancer, we found that feedback reactivation of MAPK signaling following erlotinib treatment, which was dependent on the MET receptor, contributed to the adaptive resistance of EGFR inhibitors. Interestingly, acquired resistance to erlotinib was also associated with the MAPK pathway activation as a result of CRAF or NRAS amplification. Consequently, combined inhibition of EGFR and MAPK impeded the development of both adaptive and acquired resistance. These observations demonstrate that adaptive and acquired resistance to EGFR inhibitors can converge on the same pathway and credential cotargeting EGFR and MAPK as a promising therapeutic approach in EGFR mutant tumors. PMID:27279914

  19. Transcriptome Profiling of Antimicrobial Resistance in Pseudomonas aeruginosa.

    PubMed

    Khaledi, Ariane; Schniederjans, Monika; Pohl, Sarah; Rainer, Roman; Bodenhofer, Ulrich; Xia, Boyang; Klawonn, Frank; Bruchmann, Sebastian; Preusse, Matthias; Eckweiler, Denitsa; Dötsch, Andreas; Häussler, Susanne

    2016-08-01

    Emerging resistance to antimicrobials and the lack of new antibiotic drug candidates underscore the need for optimization of current diagnostics and therapies to diminish the evolution and spread of multidrug resistance. As the antibiotic resistance status of a bacterial pathogen is defined by its genome, resistance profiling by applying next-generation sequencing (NGS) technologies may in the future accomplish pathogen identification, prompt initiation of targeted individualized treatment, and the implementation of optimized infection control measures. In this study, qualitative RNA sequencing was used to identify key genetic determinants of antibiotic resistance in 135 clinical Pseudomonas aeruginosa isolates from diverse geographic and infection site origins. By applying transcriptome-wide association studies, adaptive variations associated with resistance to the antibiotic classes fluoroquinolones, aminoglycosides, and β-lactams were identified. Besides potential novel biomarkers with a direct correlation to resistance, global patterns of phenotype-associated gene expression and sequence variations were identified by predictive machine learning approaches. Our research serves to establish genotype-based molecular diagnostic tools for the identification of the current resistance profiles of bacterial pathogens and paves the way for faster diagnostics for more efficient, targeted treatment strategies to also mitigate the future potential for resistance evolution. PMID:27216077

  20. Potential Sources and Transmission of Salmonella and Antimicrobial Resistance in Kampala, Uganda

    PubMed Central

    Afema, Josephine A.; Byarugaba, Denis K.; Shah, Devendra H.; Atukwase, Esther; Nambi, Maria; Sischo, William M.

    2016-01-01

    In sub‒Saharan Africa, non‒typhoidal Salmonellae (NTS) cause invasive disease particularly in children and HIV infected adults, but the disease epidemiology is poorly understood. Between 2012 and 2013, we investigated NTS sources and transmission in Kampala. We detected Salmonella in 60% of the influent and 60% of the effluent samples from a wastewater treatment plant and 53.3% of the influent and 10% of the effluent samples from waste stabilization ponds that serve the human population; 40.9% of flush‒water samples from ruminant slaughterhouses, 6.6% of the poultry fecal samples from live bird markets and 4% of the fecal samples from swine at slaughter; and in 54.2% of the water samples from a channel that drains storm–water and effluents from the city. We obtained 775 Salmonella isolates, identified 32 serovars, and determined resistance to 15 antimicrobials. We genotyped common serovars using multiple‒locus variable number tandem repeats analysis or pulsed‒field gel electrophoresis. In addition, we analyzed 49 archived NTS isolates from asymptomatic livestock and human clinical cases. Salmonella from ruminant and swine sources were mostly pan‒susceptible (95%) while poultry isolates were generally more resistant. Salmonella Kentucky isolated from poultry exhibited extensive drug resistance characterized by resistance to 10 antimicrobials. Interestingly, similar genotypes of S. Kentucky but with less antimicrobial resistance (AMR) were found in poultry, human and environmental sources. The observed AMR patterns could be attributed to host or management factors associated with production. Alternatively, S. Kentucky may be prone to acquiring AMR. The factors driving AMR remain poorly understood and should be elucidated. Overall, shared genotypes and AMR phenotypes were found in NTS from human, livestock and environmental sources, suggesting zoonotic and environmental transmissions most likely occur. Information from this study could be used to control

  1. Potential Sources and Transmission of Salmonella and Antimicrobial Resistance in Kampala, Uganda.

    PubMed

    Afema, Josephine A; Byarugaba, Denis K; Shah, Devendra H; Atukwase, Esther; Nambi, Maria; Sischo, William M

    2016-01-01

    In sub‒Saharan Africa, non‒typhoidal Salmonellae (NTS) cause invasive disease particularly in children and HIV infected adults, but the disease epidemiology is poorly understood. Between 2012 and 2013, we investigated NTS sources and transmission in Kampala. We detected Salmonella in 60% of the influent and 60% of the effluent samples from a wastewater treatment plant and 53.3% of the influent and 10% of the effluent samples from waste stabilization ponds that serve the human population; 40.9% of flush‒water samples from ruminant slaughterhouses, 6.6% of the poultry fecal samples from live bird markets and 4% of the fecal samples from swine at slaughter; and in 54.2% of the water samples from a channel that drains storm-water and effluents from the city. We obtained 775 Salmonella isolates, identified 32 serovars, and determined resistance to 15 antimicrobials. We genotyped common serovars using multiple‒locus variable number tandem repeats analysis or pulsed‒field gel electrophoresis. In addition, we analyzed 49 archived NTS isolates from asymptomatic livestock and human clinical cases. Salmonella from ruminant and swine sources were mostly pan‒susceptible (95%) while poultry isolates were generally more resistant. Salmonella Kentucky isolated from poultry exhibited extensive drug resistance characterized by resistance to 10 antimicrobials. Interestingly, similar genotypes of S. Kentucky but with less antimicrobial resistance (AMR) were found in poultry, human and environmental sources. The observed AMR patterns could be attributed to host or management factors associated with production. Alternatively, S. Kentucky may be prone to acquiring AMR. The factors driving AMR remain poorly understood and should be elucidated. Overall, shared genotypes and AMR phenotypes were found in NTS from human, livestock and environmental sources, suggesting zoonotic and environmental transmissions most likely occur. Information from this study could be used to control

  2. In vitro antimicrobial susceptibility of Helcococcus kunzii and molecular analysis of macrolide and tetracycline resistance.

    PubMed

    Vergne, A; Guérin, F; Lienhard, R; Le Coustumier, A; Daurel, C; Isnard, C; Marty, N; Poyart, C; Cattoir, V

    2015-10-01

    Thanks to the recent advent of matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) technology, Helcococcus kunzii is now easily identifiable and considered as an opportunistic pathogen. However, data about antimicrobial susceptibilities remain very limited. The aim of the study was, then, to assess its in vitro susceptibility to 18 antimicrobial agents and to investigate the genetic basis of macrolide and tetracycline resistance. Thirty-nine human clinical isolates of H. kunzii collected from 2008 to 2013 were studied, as well as the type strain ATCC 51366(T). Minimum inhibitory concentrations (MICs) of penicillin G, amoxicillin, cefotaxime, imipenem, gentamicin, erythromycin, clindamycin, quinupristin-dalfopristin, ciprofloxacin, levofloxacin, tetracycline, tigecycline, vancomycin, teicoplanin, linezolid, daptomycin, cotrimoxazole and rifampin were determined by the microdilution method. Screening for macrolide [erm(A) including erm(TR), erm(B), erm(C), erm(F), erm(T), erm(X), msr(A) and mef(A)] and tetracycline [tet(L), tet(M) and tet(O)] resistance genes was performed, as well as the detection of mutations in 23S rRNA. Except for one strain resistant to cefotaxime, all strains were categorised as susceptible to β-lactams, glycopeptides, linezolid, daptomycin and tigecycline. Whereas ciprofloxacin and gentamicin exhibited limited activity, 95% of strains were categorised as susceptible to levofloxacin. Concerning erythromycin, a bimodal distribution was observed, with 29 'wild-type' strains (MICs from 0.25 to 2 mg/L) and 11 'resistant' strains (MICs ≥ 256 mg/L), including ten harbouring erm(TR). Two isolates exhibited acquired tetracycline resistance (MICs of 16 mg/L) by the production of tet(M). This large study on the in vitro antimicrobial susceptibility of H. kunzii suggests that β-lactams (especially penicillins) should be preferred for the treatment. PMID:26194694

  3. Fate of antimicrobials and antimicrobial resistance genes in simulated swine manure storage.

    PubMed

    Joy, Stacey R; Li, Xu; Snow, Daniel D; Gilley, John E; Woodbury, Bryan; Bartelt-Hunt, Shannon L

    2014-05-15

    The behavior of three antibiotics (bacitracin, chlortetracycline, and tylosin) and two classes of antibiotic resistance genes (ARGs), tet and erm, were monitored in swine manure slurry under anaerobic conditions. First-order decay rates were determined for each antibiotic with half-lives ranging from 1 day (chlortetracycline) to 10 days (tylosin). ARGs were monitored in the swine manure slurry, and losses of approximately 1 to 3 orders of magnitude in relative abundance were observed during the 40 day storage period. First-order degradation profiles were observed for chlortetracycline and its corresponding resistance genes, tet(X) and tet(Q). Tylosin was degraded to approximately 10% of the starting concentration by day 40; however, the relative abundance of erm(B) remained at 50-60% of the initial relative abundance while the relative abundance of erm(F) decreased by 80-90%, consistent with tylosin. These results indicate that tet resistance genes respond primarily to chlortetracycline antimicrobials, and may be lost when the parent tetracycline compound is degraded. In contrast, erm(B) resistance gene may respond to a range of antimicrobials in animal manure, and may persist despite losses of tylosin. PMID:24583946

  4. Staphylococcus aureus – antimicrobial resistance and the immunocompromised child

    PubMed Central

    McNeil, J Chase

    2014-01-01

    Children with immunocompromising conditions represent a unique group for the acquisition of antimicrobial resistant infections due to their frequent encounters with the health care system, need for empiric antimicrobials, and immune dysfunction. These infections are further complicated in that there is a relative paucity of literature on the clinical features and management of Staphylococcus aureus infections in immunocompromised children. The available literature on the clinical features, antimicrobial susceptibility, and management of S. aureus infections in immunocompromised children is reviewed. S. aureus infections in children with human immunodeficiency virus (HIV) are associated with higher HIV viral loads and a greater degree of CD4 T-cell suppression. In addition, staphylococcal infections in children with HIV often exhibit a multidrug resistant phenotype. Children with cancer have a high rate of S. aureus bacteremia and associated complications. Increased tolerance to antiseptics among staphylococcal isolates from pediatric oncology patients is an emerging area of research. The incidence of S. aureus infections among pediatric solid organ transplant recipients varies considerably by the organ transplanted; in general however, staphylococci figure prominently among infections in the early posttransplant period. Staphylococcal infections are also prominent pathogens among children with a number of immunodeficiencies, notably chronic granulomatous disease. Significant gaps in knowledge exist regarding the epidemiology and management of S. aureus infection in these vulnerable children. PMID:24855381

  5. Effect of Tulathromycin on Colonization Resistance, Antimicrobial Resistance, and Virulence of Human Gut Microbiota in Chemostats

    PubMed Central

    Hao, Haihong; Zhou, Shengxi; Cheng, Guyue; Dai, Menghong; Wang, Xu; Liu, Zhenli; Wang, Yulian; Yuan, Zonghui

    2016-01-01

    To evaluate microbiological safety of tulathromycin on human intestinal bacteria, tulathromycin (0, 0.1, 1, 10, and 100 μg/mL) was added into Chemostats. Before and after drug exposure, we monitored (1) population, SCFA products, antimicrobial resistance, and colonization resistance of gut microbiota, and (2) the antimicrobial resistance genes, transferability, virulent genes, pathogenicity of Enterococus faecalis. Results showed that low level of tulathromycin did not exhibit microbiological hazard on resistance selection and colonization resistance. However, high level of tulathromycin (10 and 100 μg/mL) may disturb colonization resistance of human gut microbiota and select antimicrobial resistant E. faecalis. Most of the selected resistant E. faecalis carried resistant gene of ermB, transferable element of Tn1545 and three virulence genes (esp, cylA, and ace). One of them (E. faecalis 143) was confirmed to have higher horizontal transfer risk and higher pathogenicity. The calculated no observable adverse effect concentration (NOAEC) and microbiological acceptable daily intake (mADI) in our study was 1 μg/mL and 14.66 μg/kg.bw/day, respectively. PMID:27092131

  6. Antimicrobial resistance in Acinetobacter baumannii: From bench to bedside

    PubMed Central

    Lin, Ming-Feng; Lan, Chung-Yu

    2014-01-01

    Acinetobacter baumannii (A. baumannii) is undoubtedly one of the most successful pathogens in the modern healthcare system. With invasive procedures, antibiotic use and immunocompromised hosts increasing in recent years, A. baumannii has become endemic in hospitals due to its versatile genetic machinery, which allows it to quickly evolve resistance factors, and to its remarkable ability to tolerate harsh environments. Infections and outbreaks caused by multidrug-resistant A. baumannii (MDRAB) are prevalent and have been reported worldwide over the past twenty or more years. To address this problem effectively, knowledge of species identification, typing methods, clinical manifestations, risk factors, and virulence factors is essential. The global epidemiology of MDRAB is monitored by persistent surveillance programs. Because few effective antibiotics are available, clinicians often face serious challenges when treating patients with MDRAB. Therefore, a deep understanding of the resistance mechanisms used by MDRAB can shed light on two possible strategies to combat the dissemination of antimicrobial resistance: stringent infection control and antibiotic treatments, of which colistin-based combination therapy is the mainstream strategy. However, due to the current unsatisfying therapeutic outcomes, there is a great need to develop and evaluate the efficacy of new antibiotics and to understand the role of other potential alternatives, such as antimicrobial peptides, in the treatment of MDRAB infections. PMID:25516853

  7. Anatomical Distribution and Genetic Relatedness of Antimicrobial Resistant E. coli from Healthy Companion Animals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aims: Escherichia coli have been targeted for studying antimicrobial resistance in companion animals due to opportunistic infections and as a surrogate for resistance patterns in zoonotic organisms. The aim of our study examined antimicrobial resistance in E. coli isolated from various anatomical ...

  8. ANTIMICROBIAL RESISTANCE IN SALMONELLA FROM 1997-2003 NARMS SWINE SAMPLES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A total of 3246 swine slaughter and 3147 swine diagnostic Salmonella isolates from the National Antimicrobial Resistance Monitoring System (NARMS) for the years 1997-2003 were tested for antimicrobial resistance. No resistance was detected in any Salmonella isolates for ciprofloxacin or amikacin. Fo...

  9. Characterization of antimicrobial resistance of foodborne Listeria monocytogenes.

    PubMed

    Conter, Mauro; Paludi, Domenico; Zanardi, Emanuela; Ghidini, Sergio; Vergara, Alberto; Ianieri, Adriana

    2009-01-15

    The objective of this study was to evaluate the susceptibility of 120 Listeria monocytogenes strains isolated from food and food-processing environments to 19 antibiotics currently used in veterinary and human therapy. Susceptibility tests were performed by using the automated VITEK2 system. Apart from penicillin, ampicillin and trimethoprim-sulfamethoxazole, for which clinical breakpoints for Listeria susceptibility testing are defined according to the Clinical and Laboratory Standard Institute (CLSI), in the present study the CLSI criteria for staphylococci were applied. Among the 120 tested strains, 14 (11.7%) displayed resistance to at least one antibiotic. In particular, resistance to one antibiotic was more common than multiple resistance, i.e., 10 (8.3%) isolates were resistant to one antibiotic, 3 (2.5%) to two antibiotics and one (0.8%) to five antibiotics. Resistance to clindamycin was the most common, followed by linezolid, ciprofloxacin, ampicillin and rifampicin, trimethoprim/sulphamethoxazole and, finally, vancomycin and tetracycline. This study shows that L. monocytogenes strains from food and food-processing environments are susceptible to the antibiotics commonly used in veterinary and human listeriosis treatment. Considering that L. monocytogenes is slowly becoming antibiotic resistant, a continued surveillance of emerging antimicrobial resistance of this pathogen is important to ensure effective treatment of human listeriosis. These data are useful in improving background data on antibiotic resistance of strains isolated from food and food environment. PMID:19012982

  10. Antimicrobial resistance of major foodborne pathogens from major meat products.

    PubMed

    Gousia, Panagiota; Economou, Vagelis; Sakkas, Hercules; Leveidiotou, Stamatina; Papadopoulou, Chrissanthy

    2011-01-01

    The bacterial contamination of raw and processed meat products with resistant pathogens was studied. The raw samples included sheep (40), goat (40), pork (120), beef (80), and chicken (19) meat, and the processed samples included turkey filets (33), salami (8), readymade mincemeat (16), stuffing (22), and roast-beef (50). The samples were collected from retail shops in Northwestern Greece over a period of 3 years. The isolated pathogens were evaluated for susceptibilities to 19 antimicrobial agents used in humans. Out of 428 samples, 157 strains of Escherichia coli, 25 of Yersinia enterocolitica, 57 of Staphylococcus aureus, 57 of Enterococcus spp., 4 of Salmonella spp., and 3 of Campylobacter jejuni were isolated. Among the isolates 14.6% of the E. coli, 10.5% of S. aureus, 4% of Y. enterocolitica, 25% of Salmonella spp., and 42.1% of Enterococcus spp. were susceptible to antibiotics. E. coli from chicken exhibited high rates of resistance to ciprofloxacin (62.5%) followed by lamb/goat (10.9%), pork (15.7%), and beef (27.9%) meat. Resistance to nitrofurantoin dominated in the lamb/goat isolates (60%). Resistance to tetracycline predominated in pork (68.2%) and chicken (62.5%), and resistance to aminoglycosides dominated in lamb/goat meat isolates. S. aureus resistance to clindamycin predominated in lamb/goat isolates (50%), whereas resistance to ciprofloxacin predominated in the pork strains, but no resistance to methicillin was observed. Of the enterococci isolates 21.1% were resistant to vancomycin. High resistance to ampicillin (96%) was observed in Y. enterocolitica and all of the C. jejuni isolates were resistant to ampicillin, cephalothin, and cefuroxime. These results indicate that meat can be a source of resistant bacteria, which could potentially be spread to the community through the food chain. PMID:21039131

  11. Antimicrobial (Drug) Resistance: Methicillin-Resistant Staphylococcus aureus (MRSA)

    MedlinePlus

    ... NIAID invests in basic research to understand the biology of microbes, their behavior, and how drug resistance ... Nucleotide Polymorphism Phylogenetics & Ontology Proteomics & Protein Analysis Systems Biology Data Portals Software Applications BCBB Mobyle Interface Designer ( ...

  12. An update on antimicrobial resistance research activities in the ARS-BEAR Unit

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the 1990’s, Because of the public health concerns associated with the use of antimicrobials in livestock were increasing, and the potential utility of antimicrobial susceptibility testing for monitoring trends in antimicrobial resistance development was recognized. To meet this challenge, an ant...

  13. Prevalence of antimicrobial resistance and resistance genes in faecal Escherichia coli isolates recovered from healthy pets.

    PubMed

    Costa, Daniela; Poeta, Patricia; Sáenz, Yolanda; Coelho, Ana Cláudia; Matos, Manuela; Vinué, Laura; Rodrigues, Jorge; Torres, Carmen

    2008-02-01

    Faecal samples of healthy dogs (n=39) and cats (n=36) obtained in Northern Portugal were seeded on Levine agar plates, and two Escherichia coli isolates per sample were recovered (78 of dogs and 66 of cats). The susceptibility to 16 antimicrobial agents was tested in this series of 144 E. coli isolates. Almost 20% of them showed tetracycline resistance and 12 and 15% presented ampicillin or streptomycin resistance, respectively. The percentage of resistance to the other antimicrobial agents was in all cases below 4%, and no resistant isolates were detected for ceftazidime, imipenem, cefoxitin or amikacin. Two isolates (from one dog) showed cefotaxime-resistance and harboured both the CTX-M-1 and OXA-30 beta-lactamases. A bla(TEM) gene was detected in 12 of 17 ampicillin-resistant isolates, the aac(3)-II gene in the three gentamicin-resistant isolates, aadA in 7 of 22 streptomycin-resistant isolates, and tet(A) and/or tet(B) gene in all 28 tetracycline-resistant isolates. The gene encoding class 1 integrase was detected in six E. coli isolates, including the four trimethoprim-sulfamethoxazole-resistant isolates and those two harbouring CTX-M-1 and OXA-30 beta-lactamases; different gene cassette arrangements were identified: dfrA1+aadA1 (two isolates), dfrA12+orfF+aadA2 (two isolates) and bla(OXA30)+aadA1 (two isolates). One amino acid change in GyrA protein (Ser83Leu or Asp87Tyr) was detected in four nalidixic acid-resistant and ciprofloxacin-susceptible isolates and two amino acid changes in GyrA (Ser83Leu+Asp87Asn) and one in ParC (Ser80Ile) were identified in one nalidixic acid- and ciprofloxacin-resistant isolate. Faecal E. coli isolates of healthy pets could be a reservoir of antimicrobial resistance genes. PMID:17870255

  14. CRISPR provides acquired resistance against viruses in prokaryotes.

    PubMed

    Barrangou, Rodolphe; Fremaux, Christophe; Deveau, Hélène; Richards, Melissa; Boyaval, Patrick; Moineau, Sylvain; Romero, Dennis A; Horvath, Philippe

    2007-03-23

    Clustered regularly interspaced short palindromic repeats (CRISPR) are a distinctive feature of the genomes of most Bacteria and Archaea and are thought to be involved in resistance to bacteriophages. We found that, after viral challenge, bacteria integrated new spacers derived from phage genomic sequences. Removal or addition of particular spacers modified the phage-resistance phenotype of the cell. Thus, CRISPR, together with associated cas genes, provided resistance against phages, and resistance specificity is determined by spacer-phage sequence similarity. PMID:17379808

  15. Prevalence and Antimicrobial Resistance of Microbes Causing Bloodstream Infections in Unguja, Zanzibar

    PubMed Central

    Onken, Annette; Said, Abdulrahman K.; Jørstad, Melissa; Jenum, Pål A.; Blomberg, Bjørn

    2015-01-01

    Background Bloodstream infections (BSI) are frequent and cause high case-fatality rates. Urgent antibiotic treatment can save patients’ lives, but antibiotic resistance can render antibiotic therapy futile. This study is the first to collect epidemiological data on BSI from Unguja, Zanzibar. Methods Clinical data and blood for culturing and susceptibility testing of isolated microbes were obtained from 469 consecutively enrolled neonates, children and adults presenting with signs of systemic infections at Mnazi Mmoja Hospital (MMH), Zanzibar. Results Pathogenic bacteria were recovered from the blood of 14% of the patients (66/469). The most frequently isolated microbes were Klebsiella pneumoniae, Escherichia coli, Acinetobacter spp. and Staphylococcus aureus. Infections were community-acquired in 56 patients (85%) and hospital-acquired in 8 (12%) (data missing for 2 patients). BSI caused by extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae (E. coli, K. pneumoniae) was found in 5 cases, of which 3 were community-acquired and 2 hospital-acquired. Three of these patients died. Six of 7 Salmonella Typhi isolates were multidrug resistant. Streptococcus pneumoniae was found in one patient only. Conclusions This is the first report of ESBL-producing bacteria causing BSI from the Zanzibar archipelago. Our finding of community-acquired BSI caused by ESBL-producing bacteria is alarming, as it implies that these difficult-to-treat bacteria have already spread in the society. In the local setting these infections are virtually impossible to cure. The findings call for increased awareness of rational antibiotic use, infection control and surveillance to counteract the problem of emerging antimicrobial resistance. PMID:26700032

  16. Coping with the rising tide of resistance to antimicrobial agents.

    PubMed

    Hunter, P A

    2001-06-01

    The 11th European Congress of Clinical Microbiology and Infectious Diseases was held in Istanbul, Turkey, from April 2nd to April 4th, 2001. The meeting was attended by approximately 4,500 people. Sessions were well attended and included a number of workshops, keynote lectures, symposia, free papers and posters. As at many chemotherapy meetings in recent years, a major topic was the continuing growth of resistance among all microbes to antimicrobial agents, and this is the topic highlighted in this report. PMID:12813593

  17. Phenothiazinium antimicrobial photosensitizers are substrates of bacterial multidrug resistance pumps.

    PubMed

    Tegos, George P; Hamblin, Michael R

    2006-01-01

    Antimicrobial photodynamic therapy (PDT) combines a nontoxic photoactivatable dye, or photosensitizer (PS), with harmless visible light to generate singlet oxygen and free radicals that kill microbial cells. Although the light can be focused on the diseased area, the best selectivity is achieved by choosing a PS that binds and penetrates microbial cells. Cationic phenothiazinium dyes, such as methylene blue and toluidine blue O, have been studied for many years and are the only PSs used clinically for antimicrobial PDT. Multidrug resistance pumps (MDRs) are membrane-localized proteins that pump drugs out of cells and have been identified for a wide range of organisms. We asked whether phenothiazinium salts with structures that are amphipathic cations could potentially be substrates of MDRs. We used MDR-deficient mutants of Staphylococcus aureus (NorA), Escherichia coli (TolC), and Pseudomonas aeruginosa (MexAB) and found 2 to 4 logs more killing than seen with wild-type strains by use of three different phenothiazinium PSs and red light. Mutants that overexpress MDRs were protected from killing compared to the wild type. Effective antimicrobial PSs of different chemical structures showed no difference in light-mediated killing depending on MDR phenotype. Differences in uptake of phenothiazinium PS by the cells depending on level of MDR expression were found. We propose that specific MDR inhibitors could be used in combination with phenothiazinium salts to enhance their photodestructive efficiency. PMID:16377686

  18. Strategies to potentiate antimicrobial photoinactivation by overcoming resistant phenotypes†

    PubMed Central

    Vera, D. Mariano A.; Haynes, Mark H; Ball, Anthony R.; Dai, D. Tianhong; Astrakas, Christos; Kelso, Michael J; Hamblin, Michael R; Tegos, George P.

    2012-01-01

    Conventional antimicrobial strategies have become increasingly ineffective due to the emergence of multidrug resistance among pathogenic microorganisms. The need to overcome these deficiencies has triggered the exploration of alternative treatments and unconventional approaches towards controlling microbial infections. Photodynamic therapy was originally established as an anti-cancer modality and is currently used in the treatment of age related macular degeneration. The concept of photodynamic inactivation requires cell exposure to light energy, typically wavelengths in the visible region that causes the excitation of photosensitizer molecules either exogenous or endogenous, which results in the production of reactive oxygen species. ROS produce cell inactivation and death through modification of intracellular components. The versatile characteristics of PDT prompted its investigation as an anti-infective discovery platform. Advances in understanding of microbial physiology have shed light on a series of pathways, and phenotypes that serve as putative targets for antimicrobial drug discovery. Investigations of these phenotypic elements in concert with PDT have been reported focused on multidrug efflux systems, biofilms, virulence and pathogenesis determinants. In many instances the results are promising but only preliminary and require further investigation. This review discusses the different antimicrobial PDT strategies and highlights the need for highly informative and comprehensive discovery approaches. PMID:22242675

  19. Antimicrobial susceptibility and genetic characteristics of Haemophilus influenzae isolated from community-acquired respiratory tract infection patients in Shanghai City, China.

    PubMed

    Qin, Liang; Zhou, Zhaoyan; Hu, Bijie; Yamamoto, Taro; Watanabe, Hiroshi

    2012-08-01

    Haemophilus influenzae is an important causative pathogen of community-acquired respiratory infection in China. In this study we investigated 37 H. influenzae strains isolated from patients with community-acquired respiratory tract infections (CARTI) in Shanghai city between Dec 2008 and Apr 2009. H. influenzae clinical isolates were identified, and b-lactamase production tests were conducted and minimal inhibitory concentrations(MIC) were measured. Pulsed-field gel electrophoresis(PFGE) was introduced as an effective finger printing method. Two isolates (5.4%) were verified as serotype b strains, and 30 strains (81.1%) were nontypeable H. influenzae. Furthermore, 10 (27.0%) were b-lactamase-producing ampicillin-resistance (BLPAR) (TEM-1 type)strains, 11 (29.8%) were low-b-lactamase-nonproducing ampicillin-resistant H. influenzae (Low-BLNAR) strains,and the rest were b-lactamase-negative ampicillin-susceptible(BLNAS) strains. Minimum inhibitory concentrations(MIC90; lg/ml) were 2 for ampicillin/sulbactam, 0.05 force fotaxime, 16 for cefaclor, 2 for azithromycin, 0.12 for levofloxacin, and 4 for imipenem. Fingerprint typing by PFGE revealed 23 independent patterns for the isolates. Pattern A (defined in this study) was predominant in BLPAR strains, and a variety of other patterns were detected in Low-BLNAR and BLNAS strains. Although the incidence of ampicillin resistant H. influenzae is increasing in CARTI patients in China, current antimicrobial chemotherapy seems to be effective. PMID:22302696

  20. Epidemiology, Clinical Presentation, Laboratory Diagnosis, Antimicrobial Resistance, and Antimicrobial Management of Invasive Salmonella Infections.

    PubMed

    Crump, John A; Sjölund-Karlsson, Maria; Gordon, Melita A; Parry, Christopher M

    2015-10-01

    Salmonella enterica infections are common causes of bloodstream infection in low-resource areas, where they may be difficult to distinguish from other febrile illnesses and may be associated with a high case fatality ratio. Microbiologic culture of blood or bone marrow remains the mainstay of laboratory diagnosis. Antimicrobial resistance has emerged in Salmonella enterica, initially to the traditional first-line drugs chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole. Decreased fluoroquinolone susceptibility and then fluoroquinolone resistance have developed in association with chromosomal mutations in the quinolone resistance-determining region of genes encoding DNA gyrase and topoisomerase IV and also by plasmid-mediated resistance mechanisms. Resistance to extended-spectrum cephalosporins has occurred more often in nontyphoidal than in typhoidal Salmonella strains. Azithromycin is effective for the management of uncomplicated typhoid fever and may serve as an alternative oral drug in areas where fluoroquinolone resistance is common. In 2013, CLSI lowered the ciprofloxacin susceptibility breakpoints to account for accumulating clinical, microbiologic, and pharmacokinetic-pharmacodynamic data suggesting that revision was needed for contemporary invasive Salmonella infections. Newly established CLSI guidelines for azithromycin and Salmonella enterica serovar Typhi were published in CLSI document M100 in 2015. PMID:26180063

  1. Response and Acquired Resistance to Everolimus in Anaplastic Thyroid Cancer

    PubMed Central

    Wagle, Nikhil; Grabiner, Brian C.; Van Allen, Eliezer M.; Amin-Mansour, Ali; Taylor-Weiner, Amaro; Rosenberg, Mara; Gray, Nathanael; Barletta, Justine A.; Guo, Yanan; Swanson, Scott J.; Ruan, Daniel T.; Hanna, Glenn J.; Haddad, Robert I.; Getz, Gad; Kwiatkowski, David J.; Carter, Scott L.; Sabatini, David M.; Jänne, Pasi A.; Garraway, Levi A.; Lorch, Jochen H.

    2015-01-01

    SUMMARY Everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), is effective in treating tumors harboring alterations in the mTOR pathway. Mechanisms of resistance to everolimus remain undefined. Resistance developed in a patient with metastatic anaplastic thyroid carcinoma after an extraordinary 18-month response. Whole-exome sequencing of pretreatment and drug-resistant tumors revealed a nonsense mutation in TSC2, a negative regulator of mTOR, suggesting a mechanism for exquisite sensitivity to everolimus. The resistant tumor also harbored a mutation in MTOR that confers resistance to allosteric mTOR inhibition. The mutation remains sensitive to mTOR kinase inhibitors. PMID:25295501

  2. Distribution and antimicrobial susceptibility of bacteria from adults with community-acquired pneumonia or complicated skin and soft tissue infections in France: the nationwide French PREMIUM study.

    PubMed

    Leprince, C; Desroches, M; Emirian, A; Coutureau, C; Anais, L; Fihman, V; Soussy, C J; Decousser, J W

    2015-10-01

    The empirical therapy of community-acquired pneumonia (CAP) and complicated skin and soft tissue infections (cSSTIs) must be based on updated bacterial distribution and susceptibility data. A nationwide study consecutively collected 1288 isolates from CAP (n=467) and cSSTIs (n=821) from 18 French hospitals between 2012 and 2013. The MIC values of commonly used antimicrobial agents, including ceftaroline, were determined. Bacterial distribution featured Pneumococcus, Haemophilus influenzae, and Staphylococcus aureus for CAPs and S. aureus, β-hemolytic streptococci and Enterobacteriaceae for cSSTIs. Antimicrobial susceptibility testing indicated i) the sustained third-generation cephalosporins and levofloxacin activity against pneumococci and H. influenzae, ii) no methicillin-resistant Staphylococcus aureus emergence among respiratory pathogens, iii) the high in vitro activity of ceftaroline against staphylococci from cSSTIs (98.7% susceptibility), and iv) the worrisome decreasing fluoroquinolone and third-generation cephalosporin susceptibilities among Enterobacteriaceae. This laboratory-based survey depicts a contrasting situation and supports the scoring of patients for the resistant pathogen risk before empirical therapy. PMID:26166208

  3. Characterization of multidrug-resistant Escherichia coli by antimicrobial resistance profiles, plasmid replicon typing, and pulsed-field gel electrophoresis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aim: Plasmid characterization has particular clinical importance because genes encoding significant traits including antimicrobial resistance are frequently carried on plasmids. The objective of this study was to examine the distribution of multidrug resistance (MDR) in Escherichia coli in relation ...

  4. Mutational and acquired carbapenem resistance mechanisms in multidrug resistant Pseudomonas aeruginosa clinical isolates from Recife, Brazil

    PubMed Central

    Cavalcanti, Felipe Lira de Sá; Mirones, Cristina Rodríguez; Paucar, Elena Román; Montes, Laura Álvarez; Leal-Balbino, Tereza Cristina; de Morais, Marcia Maria Camargo; Martínez-Martínez, Luis; Ocampo-Sosa, Alain Antonio

    2015-01-01

    An investigation was carried out into the genetic mechanisms responsible for multidrug resistance in nine carbapenem-resistant Pseudomonas aeruginosaisolates from different hospitals in Recife, Brazil. Susceptibility to antimicrobial agents was determined by broth microdilution. Polymerase chain reaction (PCR) was employed to detect the presence of genes encoding β-lactamases, aminoglycoside-modifying enzymes (AMEs), 16S rRNA methylases, integron-related genes and OprD. Expression of genes coding for efflux pumps and AmpC cephalosporinase were assessed by quantitative PCR. The outer membrane proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The blaSPM-1, blaKPC-2 and blaGES-1 genes were detected in P. aeruginosaisolates in addition to different AME genes. The loss of OprD in nine isolates was mainly due to frameshift mutations, premature stop codons and point mutations. An association of loss of OprD with the overexpression of MexAB-OprM and MexXY-OprM was observed in most isolates. Hyper-production of AmpC was also observed in three isolates. Clonal relationship of the isolates was determined by repetitive element palindromic-PCR and multilocus sequence typing. Our results show that the loss of OprD along with overexpression of efflux pumps and β-lactamase production were responsible for the multidrug resistance in the isolates analysed. PMID:26676375

  5. Antimicrobial resistance and molecular epidemiology of streptococci from bovine mastitis.

    PubMed

    Rato, Márcia G; Bexiga, Ricardo; Florindo, Carlos; Cavaco, Lina M; Vilela, Cristina L; Santos-Sanches, Ilda

    2013-01-25

    Streptococcus agalactiae (Group B Streptococcus, GBS), Streptococcus dysgalactiae subsp. dysgalactiae (Group C Streptococcus, GCS) and Streptococcus uberis are relevant mastitis pathogens, a highly prevalent and costly disease in dairy industry due to antibiotherapy and loss in milk production. The aims of this study were the evaluation of antimicrobial drug resistance patterns, particularly important for streptococcal mastitis control and the identification of strain molecular features. Antimicrobial resistance was assessed by disk diffusion against amoxicillin-clavulanic acid, cefazolin, cefoperazone, pirlimycin-PRL, rifaximin, streptomycin, chloramphenicol, erythromycin-ERY, gentamicin, tetracycline-TET and vancomycin. Genotypic relationships were identified using pulsed-field gel electrophoresis (PFGE), macrolide and/or tetracycline resistance gene profiling, GBS capsular typing, GBS virulence gene profiling and GBS and S. uberis multi locus sequence typing (MLST). The majority of the isolates were susceptible to all drugs except to aminoglycoside, macrolide, lincosamide and tetracycline. Close to half of the TET resistant isolates have tetO and tetK and almost all ERY-PRL resistant isolates have ermB. A high degree of intra-species polymorphism was found for GCS. The GBS belonged to ST-2, -554, -61, -23 lineages and five new molecular serotypes and human GBS insertion sequences in the cpsE gene were found. Also, GBS of serotype V with scpB and lmb seem to be related with GBS isolates of human origin (same ST-2 and similar PFGE). Overall our results suggested that different therapeutic programs may have been implemented in the different farms and that in most cases clones were herd-specific. PMID:22964008

  6. Antimicrobial resistance in food and clinical Aeromonas isolates.

    PubMed

    Palú, Angela Peres; Gomes, Luciana Martins; Miguel, Marco Antônio Lemos; Balassiano, Ilana Teruzkin; Queiroz, Mara Lucia Penna; Freitas-Almeida, Angela Corrêa; de Oliveira, Selma Soares

    2006-08-01

    This study highlights the incidence of resistance and the presence of plasmids in human and food isolates of Aeromonas in Brazil. A total of 83 Aeromonas spp. strains (28 isolated from human and 55 from fresh lettuce) were studied. Thirty-five were identified as A. hydrophila complex and 48 as A. caviae complex. All strains were shown to be susceptible to imipenem, amikacin, gentamicin, tobramycin and ciprofloxacin by the disk diffusion method. Resistance to antimicrobial agents was observed in strains of both food and clinical origin. The food strains were resistant to ampicillin/sulbactam, cefoxitin and tetracycline, while the clinical strains presented resistance to ampicillin/sulbactam, cefotaxime, ceftazidime, cefoxitin, sulfamethoxazole/trimethoprim, chloramphenicol and tetracycline. The minimal inhibitory concentrations of chloramphenicol, tetracycline and sulfamethoxazole/trimethoprim were tested by agar dilution. Thirteen strains isolated from vegetables were resistant to tetracycline (MIC 16 microg ml-1). Two A. hydrophila strains and one A. caviae strain presented extracromosomal DNA (3 and 15 kb plasmids, respectively). The tetracycline resistance phenotype determinant was related to the 15 kb plasmid according to cure and transformation experiments. PMID:16943044

  7. Antimicrobial resistance of Salmonella isolated from finishing swine and the environment of 60 Alberta swine farms.

    PubMed

    Rajić, Andrijana; McFall, Margaret E; Deckert, Anne E; Reid-Smith, Richard; Manninen, Ken; Poppe, Cornelius; Dewey, Catherine E; McEwen, Scott A

    2004-12-01

    The study objective was to describe and evaluate antimicrobial resistance profiles in Salmonella isolated from Alberta swine finishing farms. Salmonella isolates (n = 322) were obtained from 192 fecal and 84 environmental samples of the 60 Salmonella-positive swine finishing farms. Isolates were classified susceptible, intermediate or resistant based on NCCLS guidelines. More than half of the isolates (53.4%) were susceptible to all of the 18 antimicrobials in the testing panel. No resistance was observed to amikacin, amoxicillin/clavulanic acid, cefoxitin, ceftiofur, ceftriaxone, cephalothin, ciprofloxacin, imipenem or nalidixic acid. Less than 1% of isolates were resistant to apramycin, gentamicin and trimethoprim/sulfamethoxazole. Higher frequencies of resistance were observed for chloramphenicol (4.7%), ampicillin (7.8%), kanamycin (11.8%), sulfamethoxazole (21.1%), streptomycin (25.5%) and tetracycline (38.8%). Eleven Salmonella serovars had isolates with resistance to > or =3 antimicrobials. The most frequently resistant serovar was Salmonella Derby, with 27 (38.0%) isolates resistant to > or =3 antimicrobials, including resistance to five and six antimicrobials. An absence of resistance to cephalosporins and fluoroquniolones and a low proportion of isolates resistant to amikacin, amoxicillin/clavulanic acid, apramycin, gentamicin and trimethoprim/sulfamethoxazole are encouraging findings from public health and animal health perspectives. Frequent resistance observed for ampicillin, kanamycin, sulfamethoxazole, streptomycin and tetracycline, antimicrobials commonly used in veterinary medicine for decades, indicates an urgent need to utilize these antimicrobials more prudently if their benefits are to be preserved. PMID:15564027

  8. 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.

  9. Recent Exposure to Antimicrobials and Carbapenem-Resistant Enterobacteriaceae: The Role of Antimicrobial Stewardship

    PubMed Central

    Marchaim, Dror; Chopra, Teena; Bhargava, Ashish; Bogan, Christopher; Dhar, Sorabh; Hayakawa, Kayoko; Pogue, Jason M.; Bheemreddy, Suchitha; Blunden, Christopher; Shango, Maryann; Swan, Jessie; Lephart, Paul R.; Perez, Federico; Bonomo, Robert A.; Kaye, Keith S.

    2014-01-01

    BACKGROUND Carbapenem-resistant Enterobacteriaceae (CRE) are rapidly emerging worldwide. Control group selection is critically important when analyzing predictors of antimicrobial resistance. Focusing on modifiable risk factors can optimize prevention and resource expenditures. To identify specific predictors of CRE, patients with CRE were compared with 3 control groups: (1) patients with extended-spectrum β-lactamase (ESBL)–producing Enterobacteriaceae, (2) patients with non-ESBL-containing Enterobacteriaceae, and (3) uninfected controls. DESIGN Matched multivariable analyses. PATIENTS AND SETTING Patients possessing CRE that were isolated at Detroit Medical Center from September 1, 2008, to August 31, 2009. METHODS Patients were matched (1 : 1 ratio) to the 3 sets of controls. Matching parameters included (1) bacteria type, (2) hospital/facility, (3) unit/clinic, (4) calendar year, and (5) time at risk (ie, from admission to culture). Matched multivariable analyses were conducted between uninfected controls and patients with CRE, ESBL, and non-ESBL Enterobacteriaceae. Models were also designed comparing patients with CRE to patients with ESBL, patients with non-ESBL Enterobacteriaceae, and all 3 non-CRE groups combined. RESULTS Ninety-one unique patients with CRE were identified, and 6 matched models were constructed. Recent (less than 3 months) exposure to antibiotics was the only parameter that was consistently associated with CRE, regardless of the group to which CRE was compared, and was not independently associated with isolation of ESBL or non-ESBL Enterobacteriaceae. CONCLUSIONS Exposure to antibiotics within 3 months was an independent predictor that characterized patients with CRE isolation. As a result, antimicrobial stewardship efforts need to become a major focus of preventive interventions. Regulatory focus regarding appropriate antimicrobial use might decrease the detrimental effects of antibiotic misuse and spread of CRE. PMID:22759550

  10. Antimicrobial drug prescribing patterns for community-acquired pneumonia in hospitalized patients: A retrospective pilot study from New Delhi, India

    PubMed Central

    Kotwani, Anita; Kumar, Santosh; Swain, Prafulla Kumar; Suri, J. C.; Gaur, S. N.

    2015-01-01

    Objective: The objective of this study was to determine patterns and frequency of antimicrobial drug use among hospitalized patients with community-acquired pneumonia (CAP). Methodology: A retrospective 5 years (April 2007–March 2012) detailed medical record review of patients diagnosed with CAP and discharged to home from Non-Intensive Care Unit respiratory medicine wards of two public hospitals in Delhi. Results: A total of 261 medical records were analyzed. Over the 5 years, 82.0% (2007–08), 78.6% (2008–09), 59.5% (2009–10), 64.7% (2010–11), and 67.8% (2011–12) patients were prescribed two antimicrobials. In the last two study years, the proportion of patients receiving three antimicrobials increased (from 2.0% to 26.5% and 28.8%), while the proportion receiving monotherapy decreased (from 16.0% to 8.8% and 3.4%). In accordance with guidelines, beta-lactams and macrolides were the two most frequently prescribed antimicrobials (34.1%). However, newer generation beta-lactams were prescribed. A total of 37 patients were prescribed beta-lactam-tazobactam combination preparations. Overall, beta-lactams constituted more than 40% of prescriptions while macrolides were the second most prescribed class. Cephalosporin prescriptions significantly increased (P < 0.01) and penicillin prescriptions significantly decreased over study periods. The prescription of fluoroquinolones also decreased (21.5–6.0%, P < 0.01) and aminoglycoside prescription ranged from 9.7% to 16.4%, over 5 years. Reasons for prescribing three antimicrobials, use of aminoglycosides, or higher-end/reserve antibiotics were not mentioned in the medical records. There were no hospital-specific guidelines for doctors to follow in the treatment of CAP. Conclusions: These findings suggest the need for implementing antimicrobial treatment guidelines. Adequate documentation and monitoring of antibiotic use for feedback are also lacking. An antimicrobial stewardship program may offer the most

  11. Antimicrobial Resistance of Escherichia fergusonii Isolated from Broiler Chickens.

    PubMed

    Simmons, Karen; Islam, M Rashedul; Rempel, Heidi; Block, Glenn; Topp, Edward; Diarra, Moussa S

    2016-06-01

    The objective of this study was to investigate the antibiotic resistance of Escherichia fergusonii isolated from commercial broiler chicken farms. A total of 245 isolates from cloacal and cecal samples of 28- to 36-day-old chickens were collected from 32 farms. Isolates were identified using PCR, and their susceptibility to 16 antibiotics was determined by disk diffusion assay. All isolates were susceptible to meropenem, amikacin, and ciprofloxacin. The most common resistances were against ampicillin (75.1%), streptomycin (62.9%), and tetracycline (57.1%). Of the 184 ampicillin-resistant isolates, 127 were investigated using a DNA microarray carrying 75 probes for antibiotic resistance genetic determinants. Of these 127 isolates, the β-lactamase blaCMY2, blaTEM, blaACT, blaSHV, and blaCTX-M-15 genes were detected in 120 (94.5%), 31 (24.4%), 8 (6.3%), 6 (4.7%), and 4 (3.2%) isolates, respectively. Other detected genes included those conferring resistance to aminoglycosides (aadA1, strA, strB), trimethoprims (dfrV, dfrA1), tetracyclines (tetA, tetB, tetC, tetE), and sulfonamides (sul1, sul2). Class 1 integron was found in 35 (27.6%) of the ampicillin-resistant isolates. However, our data showed that the tested E. fergusonii did not carry any carbapenemase blaOXA genes. Pulsed-field gel electrophoresis revealed that the selected ampicillin-resistant E. fergusonii isolates were genetically diverse. The present study indicates that the monitoring of antimicrobial-resistant bacteria should include enteric bacteria such as E. fergusonii, which could be a reservoir of antibiotic resistance genes. The detection of isolates harboring extended-spectrum β-lactamase genes, particularly blaCTX-M-15, in this work suggests that further investigations on the occurrence of such genes in broilers are warranted. PMID:27296596

  12. Mechanisms and consequences of bacterial resistance to antimicrobial peptides.

    PubMed

    Andersson, D I; Hughes, D; Kubicek-Sutherland, J Z

    2016-05-01

    Cationic antimicrobial peptides (AMPs) are an intrinsic part of the human innate immune system. Over 100 different human AMPs are known to exhibit broad-spectrum antibacterial activity. Because of the increased frequency of resistance to conventional antibiotics there is an interest in developing AMPs as an alternative antibacterial therapy. Several cationic peptides that are derivatives of AMPs from the human innate immune system are currently in clinical development. There are also ongoing clinical studies aimed at modulating the expression of AMPs to boost the human innate immune response. In this review we discuss the potential problems associated with these therapeutic approaches. There is considerable experimental data describing mechanisms by which bacteria can develop resistance to AMPs. As for any type of drug resistance, the rate by which AMP resistance would emerge and spread in a population of bacteria in a natural setting will be determined by a complex interplay of several different factors, including the mutation supply rate, the fitness of the resistant mutant at different AMP concentrations, and the strength of the selective pressure. Several studies have already shown that AMP-resistant bacterial mutants display broad cross-resistance to a variety of AMPs with different structures and modes of action. Therefore, routine clinical administration of AMPs to treat bacterial infections may select for resistant bacterial pathogens capable of better evading the innate immune system. The ramifications of therapeutic levels of exposure on the development of AMP resistance and bacterial pathogenesis are not yet understood. This is something that needs to be carefully studied and monitored if AMPs are used in clinical settings. PMID:27180309

  13. Navigating the World Wide Web in search of resources on antimicrobial resistance.

    PubMed

    Harbarth, Stephan; Emonet, Stephane

    2006-07-01

    This overview gives information on navigating for English-language Web sites on antimicrobial resistance. Web sites were gathered on the basis of personal files, articles, and an exhaustive Web search of cross-links from other Web pages. The Web sites were categorized according to users' needs into 5 broad categories, as follows: comprehensive Web sites, with information on all aspects of antimicrobial resistance-related issues; Web sites with patient information about antimicrobial resistance and about methicillin-resistant Staphylococcus aureus, in particular; Web sites covering current multinational surveillance programs; Web sites on prevention of antimicrobial resistance in health care facilities; and Web sites on control of antimicrobial resistance in the community. We compiled a selection of Web sites that seemed to be useful as starting points for physicians, epidemiologists, researchers, or patients interested in this topic. PMID:16758421

  14. A new class of nifuroxazide analogues: synthesis of 5-nitrothiophene derivatives with antimicrobial activity against multidrug-resistant Staphylococcus aureus.

    PubMed

    Masunari, Andrea; Tavares, Leoberto Costa

    2007-06-15

    Hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) has been an increasing problem worldwide since the initial reports over 40 years ago. To examine new drug leads with potential antibacterial activities, 14 p-substituted benzoic acid [(5-nitro-thiophen-2-yl)-methylene]-hydrazides were designed, synthesized, and tested against standard and multidrug-resistant S. aureus strains by serial dilution tests. All compounds exhibited significant bacteriostatic activity and some of them also showed bactericidal activity. The results confirmed the potential of this class of compounds as an alternative for the development of selective antimicrobial agents. PMID:17419064

  15. Laboratory-based nationwide surveillance of antimicrobial resistance in Ghana

    PubMed Central

    Opintan, Japheth A; Newman, Mercy J; Arhin, Reuben E; Donkor, Eric S; Gyansa-Lutterodt, Martha; Mills-Pappoe, William

    2015-01-01

    Global efforts are underway to combat antimicrobial resistance (AMR). A key target in this intervention is surveillance for local and national action. Data on AMR in Ghana are limited, and monitoring of AMR is nonexistent. We sought to generate baseline data on AMR, and to assess the readiness of Ghana in laboratory-based surveillance. Biomedical scientists in laboratories across Ghana with capacity to perform bacteriological culture were selected and trained. In-house standard operating protocols were used to perform microbiological investigations on clinical specimens. Additional microbiological tests and data analyses were performed at a centralized laboratory. Surveillance data were stored and analyzed using WHONET program files. A total of 24 laboratories participated in the training, and 1,598 data sets were included in the final analysis. A majority of the bacterial species were isolated from outpatients (963 isolates; 60.3%). Urine (617 isolates; 38.6%) was the most common clinical specimen cultured, compared to blood (100 isolates; 6.3%). Ten of 18 laboratories performed blood culture. Bacteria isolated included Escherichia coli (27.5%), Pseudomonas spp. (14.0%), Staphylococcus aureus (11.5%), Streptococcus spp. (2.3%), and Salmonella enterica serovar Typhi (0.6%). Most of the isolates were multidrug-resistant, and over 80% of them were extended-spectrum beta-lactamases-producing. Minimum inhibitory concentration levels at 50% and at 90% for ciprofloxacin, ceftriaxone, and amikacin on selected multidrug-resistant bacteria species ranged between 2 µg/mL and >256 µg/mL. A range of clinical bacterial isolates were resistant to important commonly used antimicrobials in the country, necessitating an effective surveillance to continuously monitor AMR in Ghana. With local and international support, Ghana can participate in global AMR surveillance. PMID:26604806

  16. Antimicrobial resistance of Salmonella and E. coli from Pennsylvania dairy herds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antimicrobial resistance in bacterial pathogens is an increasing public health concern. The objective of this study was to examine antimicrobial resistance in Salmonella and E. coli isolates from Pennsylvania dairy herds. Manure composite samples were collected from 76 farms: on each farm one sample...

  17. Prevalence and antimicrobial resistance in Escherichia coli from food animals in Lagos, Nigeria

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foodborne bacteria are often associated with human infections; these infections can become more complicated to treat if the bacteria are also resistant to antimicrobials. In this study, prevalence, antimicrobial resistance, and genetic relatedness of Escherichia coli among food producing animals fr...

  18. Antimicrobial resistance: a global view from the 2013 World Healthcare-Associated Infections Forum

    PubMed Central

    2013-01-01

    Antimicrobial resistance (AMR) is now a global threat. Its emergence rests on antimicrobial overuse in humans and food-producing animals; globalization and suboptimal infection control facilitate its spread. While aggressive measures in some countries have led to the containment of some resistant gram-positive organisms, extensively resistant gram-negative organisms such as carbapenem-resistant enterobacteriaceae and pan-resistant Acinetobacter spp. continue their rapid spread. Antimicrobial conservation/stewardship programs have seen some measure of success in reducing antimicrobial overuse in humans, but their reach is limited to acute-care settings in high-income countries. Outside the European Union, there is scant or no oversight of antimicrobial administration to food-producing animals, while evidence mounts that this administration leads directly to resistant human infections. Both horizontal and vertical infection control measures can interrupt transmission among humans, but many of these are costly and essentially limited to high-income countries as well. Novel antimicrobials are urgently needed; in recent decades pharmaceutical companies have largely abandoned antimicrobial discovery and development given their high costs and low yield. Against this backdrop, international and cross-disciplinary collaboration appears to be taking root in earnest, although specific strategies still need defining. Educational programs targeting both antimicrobial prescribers and consumers must be further developed and supported. The general public must continue to be made aware of the current scale of AMR’s threat, and must perceive antimicrobials as they are: a non-renewable and endangered resource. PMID:24237856

  19. Association between Mycobacterium tuberculosis Complex Phylogenetic Lineage and Acquired Drug Resistance

    PubMed Central

    Yuen, Courtney M.; Kurbatova, Ekaterina V.; Click, Eleanor S.; Cavanaugh, J. Sean; Cegielski, J. Peter

    2013-01-01

    Background Development of resistance to antituberculosis drugs during treatment (i.e., acquired resistance) can lead to emergence of resistant strains and consequent poor clinical outcomes. However, it is unknown whether Mycobacterium tuberculosis complex species and lineage affects the likelihood of acquired resistance. Methods We analyzed data from the U.S. National Tuberculosis Surveillance System and National Tuberculosis Genotyping Service for tuberculosis cases during 2004–2011 with assigned species and lineage and both initial and final drug susceptibility test results. We determined univariate associations between species and lineage of Mycobacterium tuberculosis complex bacteria and acquired resistance to isoniazid, rifamycins, fluoroquinolones, and second-line injectables. We used Poisson regression with backward elimination to generate multivariable models for acquired resistance to isoniazid and rifamycins. Results M. bovis was independently associated with acquired resistance to isoniazid (adjusted prevalence ratio = 8.46, 95% CI 2.96–24.14) adjusting for HIV status, and with acquired resistance to rifamycins (adjusted prevalence ratio = 4.53, 95% CI 1.29–15.90) adjusting for homelessness, HIV status, initial resistance to isoniazid, site of disease, and administration of therapy. East Asian lineage was associated with acquired resistance to fluoroquinolones (prevalence ratio = 6.10, 95% CI 1.56–23.83). Conclusions We found an association between mycobacterial species and lineage and acquired drug resistance using U.S. surveillance data. Prospective clinical studies are needed to determine the clinical significance of these findings, including whether rapid genotyping of isolates at the outset of treatment may benefit patient management. PMID:24376623

  20. Isolation and Characterization of Antimicrobial-Resistant Nontyphoidal Salmonella enterica Serovars from Imported Food Products.

    PubMed

    Bae, Dongryeoul; Kweon, Ohgew; Khan, Ashraf A

    2016-08-01

    The objective of this study was to determine antimicrobial resistance and elucidate the resistance mechanism in nontyphoidal Salmonella enterica serovars isolated from food products imported into the United States from 2011 to 2013. Food products contaminated with antimicrobial-resistant nontyphoidal S. enterica were mainly imported from Taiwan, Indonesia, Vietnam, and China. PCR, DNA sequencing, and plasmid analyses were used to characterize antimicrobial resistance determinants. Twentythree of 110 S. enterica isolates were resistant to various antimicrobial classes, including β-lactam, aminoglycoside, phenicol, glycopeptide, sulfonamide, trimethoprim, and/or fluoroquinolone antimicrobial agents. Twelve of the isolates were multidrug resistant strains. Antimicrobial resistance determinants blaTEM-1, blaCTX-M-9, blaOXA-1, tetA, tetB, tetD, dfrA1, dfrV, dhfrI, dhfrXII, drf17, aadA1, aadA2, aadA5, orfC, qnrS, and mutations of gyrA and parC were detected in one or more antimicrobial-resistant nontyphoidal S. enterica strains. Plasmid profiles revealed that 12 of the 23 antimicrobial-resistant strains harbored plasmids with incompatibility groups IncFIB, IncHI1, IncI1, IncN, IncW, and IncX. Epidemiologic and antimicrobial resistance monitoring data combined with molecular characterization of antimicrobial resistance determinants in Salmonella strains isolated from imported food products may provide information that can be used to establish or implement food safety programs to improve public health. PMID:27497122

  1. Bacteriophages Isolated from Chicken Meat and the Horizontal Transfer of Antimicrobial Resistance Genes.

    PubMed

    Shousha, Amira; Awaiwanont, Nattakarn; Sofka, Dmitrij; Smulders, Frans J M; Paulsen, Peter; Szostak, Michael P; Humphrey, Tom; Hilbert, Friederike

    2015-07-01

    Antimicrobial resistance in microbes poses a global and increasing threat to public health. The horizontal transfer of antimicrobial resistance genes was thought to be due largely to conjugative plasmids or transposons, with only a minor part being played by transduction through bacteriophages. However, whole-genome sequencing has recently shown that the latter mechanism could be highly important in the exchange of antimicrobial resistance genes between microorganisms and environments. The transfer of antimicrobial resistance genes by phages could underlie the origin of resistant bacteria found in food. We show that chicken meat carries a number of phages capable of transferring antimicrobial resistance. Of 243 phages randomly isolated from chicken meat, about a quarter (24.7%) were able to transduce resistance to one or more of the five antimicrobials tested into Escherichia coli ATCC 13706 (DSM 12242). Resistance to kanamycin was transduced the most often, followed by that to chloramphenicol, with four phages transducing tetracycline resistance and three transducing ampicillin resistance. Phages able to transduce antimicrobial resistance were isolated from 44% of the samples of chicken meat that we tested. The statistically significant (P = 0.01) relationship between the presence of phages transducing kanamycin resistance and E. coli isolates resistant to this antibiotic suggests that transduction may be an important mechanism for transferring kanamycin resistance to E. coli. It appears that the transduction of resistance to certain antimicrobials, e.g., kanamycin, not only is widely distributed in E. coli isolates found on meat but also could represent a major mechanism for resistance transfer. The result is of high importance for animal and human health. PMID:25934615

  2. Bacteriophages Isolated from Chicken Meat and the Horizontal Transfer of Antimicrobial Resistance Genes

    PubMed Central

    Shousha, Amira; Awaiwanont, Nattakarn; Sofka, Dmitrij; Smulders, Frans J. M.; Paulsen, Peter; Szostak, Michael P.; Humphrey, Tom

    2015-01-01

    Antimicrobial resistance in microbes poses a global and increasing threat to public health. The horizontal transfer of antimicrobial resistance genes was thought to be due largely to conjugative plasmids or transposons, with only a minor part being played by transduction through bacteriophages. However, whole-genome sequencing has recently shown that the latter mechanism could be highly important in the exchange of antimicrobial resistance genes between microorganisms and environments. The transfer of antimicrobial resistance genes by phages could underlie the origin of resistant bacteria found in food. We show that chicken meat carries a number of phages capable of transferring antimicrobial resistance. Of 243 phages randomly isolated from chicken meat, about a quarter (24.7%) were able to transduce resistance to one or more of the five antimicrobials tested into Escherichia coli ATCC 13706 (DSM 12242). Resistance to kanamycin was transduced the most often, followed by that to chloramphenicol, with four phages transducing tetracycline resistance and three transducing ampicillin resistance. Phages able to transduce antimicrobial resistance were isolated from 44% of the samples of chicken meat that we tested. The statistically significant (P = 0.01) relationship between the presence of phages transducing kanamycin resistance and E. coli isolates resistant to this antibiotic suggests that transduction may be an important mechanism for transferring kanamycin resistance to E. coli. It appears that the transduction of resistance to certain antimicrobials, e.g., kanamycin, not only is widely distributed in E. coli isolates found on meat but also could represent a major mechanism for resistance transfer. The result is of high importance for animal and human health. PMID:25934615

  3. Effect of antimicrobial peptides on colistin-susceptible and colistin-resistant strains of Klebsiella pneumoniae and Enterobacter asburiae.

    PubMed

    Kádár, Béla; Kocsis, Béla; Kristof, Katalin; Tóth, Ákos; Szabó, Dóra

    2015-12-01

    In this study susceptibility to different antimicrobial peptides was investigated on colistin-susceptible and colistin-resistant identical pulsotype strains of KPC-2 producing Klebsiella pneumoniae ST258 as well as colistin-susceptible and colistin-resistant Enterobacter asburiae strains isolated from clinical samples. In our test, bacteria were exposed to 50 mg/ml lactoferrin, lysozyme and protamine - cationic antimicrobial peptides belonging to innate immune system and having structural similarity to polymyxins - in separate reactions. After 18 hours incubation of colonies were counted. 40% of colistin-resistant K. pneumoniae strains and 97% of colistin-susceptible counterpart strains were lysed by protamine whereas 87% and 100% colony forming unit decrease by lysozyme was seen, respectively. In the case of colistin-resistant E. asburiae strains 1 log10 cell count increase were observed after treatment with lysozyme and 1.56 log10 after lactoferrin exposure compared to the initial number whereas the colistin-susceptible showed no relevant cell count increase. Our findings suggest that acquired colistin-resistance in Enterobacteriaceae is associated with tolerance against antimicrobial peptides. PMID:26689883

  4. 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

  5. Acquired Multidrug Antifungal Resistance in Candida lusitaniae during Therapy

    PubMed Central

    Asner, Sandra A.; Giulieri, Stefano; Diezi, Manuel; Marchetti, Oscar

    2015-01-01

    Candida lusitaniae is usually susceptible to echinocandins. Beta-1,3-glucan synthase encoded by FKS genes is the target of echinocandins. A few missense mutations in the C. lusitaniae FKS1 hot spot 1 (HS1) have been reported. We report here the rapid emergence of antifungal resistance in C. lusitaniae isolated during therapy with amphotericin B (AMB), caspofungin (CAS), and azoles for treatment of persistent candidemia in an immunocompromised child with severe enterocolitis and visceral adenoviral disease. As documented from restriction fragment length polymorphism (RFLP) and random amplified polymorphic DNA (RAPD) analysis, the five C. lusitaniae isolates examined were related to each other. From antifungal susceptibility and molecular analyses, 5 different profiles (P) were obtained. These profiles included the following: profile 1 (P1) (CAS MIC [μg/ml], 0.5; fluconazole [FLC] MIC, 0.25), determined while the patient was being treated with liposomal AMB for 3 months; P2 (FLC MIC [μg/ml], 0.25; CAS MIC, 4), while the patient was being treated with CAS for 2 weeks; P3 (CAS MIC [μg/ml], 0.5; FLC MIC, 32), while the patient was being treated with azoles and CAS initially followed by azoles alone for a week; P4 (CAS MIC [μg/ml], 8; FLC MIC, 8), while the patient was being treated with both drugs for 3 weeks; and P5 (AMB MIC [μg/ml], 0.125; CAS MIC, 8), while the patient was being treated with AMB and FLC for 2 weeks. CAS resistance was associated with resistance not only to micafungin and anidulafungin but also to AMB. Analysis of CAS resistance revealed 3 novel FKS1 mutations in CAS-resistant isolates (S638Y in P2; S631Y in P4; S638P in P5). While S638Y and -P are within HS1, S631Y is in close proximity to this domain but was confirmed to confer candin resistance using a site-directed mutagenesis approach. FLC resistance could be linked with overexpression of major facilitator gene 7 (MFS7) in C. lusitaniae P2 and P4 and was associated with resistance to 5

  6. Incidence and Diversity of Antimicrobial Multidrug Resistance Profiles of Uropathogenic Bacteria

    PubMed Central

    Linhares, Inês; Raposo, Teresa; Rodrigues, António

    2015-01-01

    The aim of this study was to assess the most frequent multidrug resistant (MDR) profiles of the main bacteria implicated in community-acquired urinary tract infections (UTI). Only the MDR profiles observed in, at least, 5% of the MDR isolates were considered. A quarter of the bacteria were MDR and the most common MDR profile, including resistance to penicillins, quinolones, and sulfonamides (antibiotics with different mechanisms of action, all mainly recommended by the European Association of Urology for empirical therapy of uncomplicated UTI), was observed, alone or in association with resistance to other antimicrobial classes, in the main bacteria implicated in UTI. The penicillin class was included in all the frequent MDR profiles observed in the ten main bacteria and was the antibiotic with the highest prescription during the study period. The sulfonamides class, included in five of the six more frequent MDR profiles, was avoided between 2000 and 2009. The results suggest that the high MDR percentage and the high diversity of MDR profiles result from a high prescription of antibiotics but also from antibiotic-resistant genes transmitted with other resistance determinants on mobile genetic elements and that the UTI standard treatment guidelines must be adjusted for the community of Aveiro District. PMID:25834814

  7. Incidence and diversity of antimicrobial multidrug resistance profiles of uropathogenic bacteria.

    PubMed

    Linhares, Inês; Raposo, Teresa; Rodrigues, António; Almeida, Adelaide

    2015-01-01

    The aim of this study was to assess the most frequent multidrug resistant (MDR) profiles of the main bacteria implicated in community-acquired urinary tract infections (UTI). Only the MDR profiles observed in, at least, 5% of the MDR isolates were considered. A quarter of the bacteria were MDR and the most common MDR profile, including resistance to penicillins, quinolones, and sulfonamides (antibiotics with different mechanisms of action, all mainly recommended by the European Association of Urology for empirical therapy of uncomplicated UTI), was observed, alone or in association with resistance to other antimicrobial classes, in the main bacteria implicated in UTI. The penicillin class was included in all the frequent MDR profiles observed in the ten main bacteria and was the antibiotic with the highest prescription during the study period. The sulfonamides class, included in five of the six more frequent MDR profiles, was avoided between 2000 and 2009. The results suggest that the high MDR percentage and the high diversity of MDR profiles result from a high prescription of antibiotics but also from antibiotic-resistant genes transmitted with other resistance determinants on mobile genetic elements and that the UTI standard treatment guidelines must be adjusted for the community of Aveiro District. PMID:25834814

  8. Multidrug resistance genes in staphylococci from animals that confer resistance to critically and highly important antimicrobial agents in human medicine.

    PubMed

    Wendlandt, Sarah; Shen, Jianzhong; Kadlec, Kristina; Wang, Yang; Li, Beibei; Zhang, Wan-Jiang; Feßler, Andrea T; Wu, Congming; Schwarz, Stefan

    2015-01-01

    Most antimicrobial resistance genes known so far to occur in staphylococci of animal origin confer resistance to a specific class of antimicrobial agents or to selected members within such a class. However, there are also a few examples of multidrug resistance (MDR) genes that confer resistance to antimicrobial agents of different classes by either target site methylation or active efflux via ATP-binding cassette (ABC) transporters. The present review provides an overview of these MDR genes with particular reference to those genes involved in resistance to critically or highly important antimicrobial agents used in human and veterinary medicine. Moreover, their location on mobile genetic elements and colocated resistance genes, which may play a role in coselection and persistence of the MDR genes, are addressed. PMID:25455417

  9. Widespread acquisition of antimicrobial resistance among Campylobacter isolates from UK retail poultry and evidence for clonal expansion of resistant lineages

    PubMed Central

    2013-01-01

    Background Antimicrobial resistance is increasing among clinical Campylobacter cases and is common among isolates from other sources, specifically retail poultry - a major source of human infection. In this study the antimicrobial susceptibility of isolates from a UK-wide survey of Campylobacter in retail poultry in 2001 and 2004–5 was investigated. The occurrence of phenotypes resistant to tetracycline, quinolones (ciprofloxacin and naladixic acid), erythromycin, chloramphenicol and aminoglycosides was quantified. This was compared with a phylogeny for these isolates based upon Multi Locus Sequence Typing (MLST) to investigate the pattern of antimicrobial resistance acquisition. Results Antimicrobial resistance was present in all lineage clusters, but statistical testing showed a non-random distribution. Erythromycin resistance was associated with Campylobacter coli. For all antimicrobials tested, resistant isolates were distributed among relatively distant lineages indicative of widespread acquisition. There was also evidence of clustering of resistance phenotypes within lineages; indicative of local expansion of resistant strains. Conclusions These results are consistent with the widespread acquisition of antimicrobial resistance among chicken associated Campylobacter isolates, either through mutation or horizontal gene transfer, and the expansion of these lineages as a proportion of the population. As Campylobacter are not known to multiply outside of the host and long-term carriage in humans is extremely infrequent in industrialized countries, the most likely location for the proliferation of resistant lineages is in farmed chickens. PMID:23855904

  10. Eight-year Surveillance of Antimicrobial Resistance among Enterococcus Spp. Isolated in the First Bethune Hospital

    NASA Astrophysics Data System (ADS)

    Xu, Jiancheng; Wang, Liqiang; Wang, Kai; Zhou, Qi

    This study was to investigate the antimicrobial resistance of Enterococcus spp. isolated in 8 consecutive years in the First Bethune Hospital. Disk diffusion test was used to study the antimicrobial resistance. The data were analyzed by WHONET 5 software according to Clinical and Laboratory Standards Institute (CLSI). Most of 1446 strains of Enterococcus spp. were collected from urine 640 (44.3%), sputum 315 (21.8%), secretions and pus 265 (18.3%) during the past 8 years. The rates of high-level aminoglycoside resistance in Enterococcus faecalis and Enterococcus faecium were 57.4%∼75.9% and 69.0%∼93.8% during the past 8 years, respectively. No Enterococcus spp. was resistant to vancomycin. The antimicrobial resistance of Enterococcus spp. had increased in recent 8 years. The change of the antimicrobial resistance should be investigated in order to direct rational drug usage in the clinic and prevent bacterial strain of drug resistance from being transmitted.

  11. Acquired antifungal drug resistance in Aspergillus fumigatus: epidemiology and detection.

    PubMed

    Howard, Susan Julie; Arendrup, Maiken Cavling

    2011-04-01

    Voriconazole is the recommended agent for invasive aspergillosis, with lipid amphotericin B or caspofungin as second line treatment choices. Being the only agents available in oral formulation, azoles are used in chronic infections and often over longer time periods. In addition to being used in clinical medicine, azoles are employed extensively in agriculture. Azole-resistant Aspergillus has been isolated in azole naïve patients, in azole exposed patients and in the environment. The primary underlying mechanism of resistance is as a result of alterations in the cyp51A target gene, with a variety of mutations found in clinical isolates but just one identified in a environmental strain (a point mutation at codon 98 accompanied by a tandem repeat in the promoter region). Much less is currently known about echinocandin resistance in Aspergillus, in part because susceptibility testing is not routinely performed and because the methods suffer from technical difficulties and suboptimal reproducibility. Clinical breakthrough cases have been reported however, and resistance has been confirmed in vivo. In this paper we review the current knowledge on epidemiology, susceptibility testing and underlying mechanisms involved in azole and echinocandin resistance in Aspergillus. PMID:20795765

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

    PubMed Central

    Yazdankhah, Siamak; Rudi, Knut; Bernhoft, Aksel

    2014-01-01

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

  13. Antimicrobial hydrogels: a new weapon in the arsenal against multidrug-resistant infections.

    PubMed

    Ng, Victor W L; Chan, Julian M W; Sardon, Haritz; Ono, Robert J; García, Jeannette M; Yang, Yi Yan; Hedrick, James L

    2014-11-30

    The rapid emergence of antibiotic resistance in pathogenic microbes is becoming an imminent global public health problem. Treatment with conventional antibiotics often leads to resistance development as the majority of these antibiotics act on intracellular targets, leaving the bacterial morphology intact. Thus, they are highly prone to develop resistance through mutation. Much effort has been made to develop macromolecular antimicrobial agents that are less susceptible to resistance as they function by microbial membrane disruption. Antimicrobial hydrogels constitute an important class of macromolecular antimicrobial agents, which have been shown to be effective in preventing and treating multidrug-resistant infections. Advances in synthetic chemistry have made it possible to tailor molecular structure and functionality to impart broad-spectrum antimicrobial activity as well as predictable mechanical and rheological properties. This has significantly broadened the scope of potential applications that range from medical device and implant coating, sterilization, wound dressing, to antimicrobial creams for the prevention and treatment of multidrug-resistant infections. In this review, advances in both chemically and physically cross-linked natural and synthetic hydrogels possessing intrinsic antimicrobial properties or loaded with antibiotics, antimicrobial polymers/peptides and metal nanoparticles are highlighted. Relationships between physicochemical properties and antimicrobial activity/selectivity, and possible antimicrobial mechanisms of the hydrogels are discussed. Approaches to mitigating toxicity of metal nanoparticles that are encapsulated in hydrogels are reviewed. In addition, challenges and future perspectives in the development of safe and effective antimicrobial hydrogel systems especially involving co-delivery of antimicrobial polymers/peptides and conventional antimicrobial agents for eventual clinical applications are presented. PMID:25450263

  14. Toxigenic genes, spoilage potential, and antimicrobial resistance of Bacillus cereus group strains from ice cream.

    PubMed

    Arslan, Seza; Eyi, Ayla; Küçüksarı, Rümeysa

    2014-02-01

    Bacillus spp. can be recovered from almost every environment. It is also found readily in foods, where it may cause food spoilage and/or food poisoning due to its toxigenic and pathogenic nature, and extracellular enzymes. In this study, 29 Bacillus cereus group strains from ice cream were examined for the presence of following virulence genes hblC, nheA, cytK and ces genes, and tested for a range of the extracellular enzymes, and antimicrobial susceptibility. The strains were found to produce extracellular enzymes: proteolytic and lipolytic activity, gelatin hydrolysis and lecithinase production (100%), DNase production (93.1%) and amylase activity (93.1%). Of 29 strains examined, 24 (82.8%) showed hemolytic activity on blood agar. Beta-lactamase enzyme was only produced by 20.7% of B. cereus group. Among 29 B. cereus group from ice cream, nheA was the most common virulence gene detected in 44.8% of the strains, followed by hblC gene with 17.2%. Four (13.8%) of the 29 strains were positive for both hblC gene and nheA gene. Contrarily, cytK and ces genes were not detected in any of the strains. Antimicrobial susceptibility of ice cream isolates was tested to 14 different antimicrobial agents using the disc diffusion method. We detected resistance to penicillin and ampicillin with the same rate of 89.7%. Thirty-one percent of the strains were multiresistant to three or more antibiotics. This study emphasizes that the presence of natural isolates of Bacillus spp. harboring one or more enterotoxin genes, producing extracellular enzymes which may cause spoilage and acquiring antibiotic resistance might hold crucial importance in the food safety and quality. PMID:24309214

  15. Evaluation of Antimicrobial Resistance in Staphylococcus aureus Isolates by Years

    PubMed Central

    Rağbetli, Cennet; Parlak, Mehmet; Bayram, Yasemin; Guducuoglu, Huseyin; Ceylan, Nesrin

    2016-01-01

    Objective. Recently, community and hospital-acquired infections with Staphylococcus aureus have increased and raised antibiotic resistant isolates. In this study, we aimed to evaluate the antibiotic resistance profile of S. aureus isolates over several years in various clinical specimens from our hospital. Materials and Methods. S. aureus strains from 2009 to 2014 were isolated from various clinical samples at Yuzuncu Yil University, Dursun Odabas Medical Center, Microbiology Laboratory, and their antibiotic susceptibility test results were retrospectively investigated. The isolates were identified by conventional methods, and antibiotic susceptibility tests were performed by the Phoenix (Becton Dickinson, USA) automated system method according to Clinical and Laboratory Standards Institute (CLSI) standards. Results. A total of 1,116 S. aureus isolates were produced and methicillin-resistant S. aureus (MRSA) to 21% of all S. aureus isolates between 2009 and 2014. According to the results of susceptibility tests of all isolates of S. aureus, they have been identified as sensitive to vancomycin, daptomycin, linezolid, and levofloxacin. While the resistance rates to nitrofurantoin, quinupristin-dalfopristin, and trimethoprim-sulfamethoxazole were determined as 0.3%, 2.4%, and 6%, respectively, resistance rates to penicillin, erythromycin, rifampicin, gentamicin, and clindamycin were determined as 100%, 18%, 14%, 14%, and 11%, respectively. The highest percentage of methicillin resistance was determined as 30% in 2009, and the resistance was determined to have decreased in subsequent years (20%, 16%, 13%, 19%, and 21%) (p < 0.001). Conclusion. Currently, retrospective evaluations of causes of nosocomial infection should be done periodically. We think that any alteration of resistance over the years has to be identified, and all centers must determine their own resistance profiles, in order to guide empirical therapies. Reducing the rate of antibiotic resistance will

  16. Mathematical modelling of antimicrobial resistance in agricultural waste highlights importance of gene transfer rate.

    PubMed

    Baker, Michelle; Hobman, Jon L; Dodd, Christine E R; Ramsden, Stephen J; Stekel, Dov J

    2016-04-01

    Antimicrobial resistance is of global concern. Most antimicrobial use is in agriculture; manures and slurry are especially important because they contain a mix of bacteria, including potential pathogens, antimicrobial resistance genes and antimicrobials. In many countries, manures and slurry are stored, especially over winter, before spreading onto fields as organic fertilizer. Thus, these are a potential location for gene exchange and selection for resistance. We develop and analyse a mathematical model to quantify the spread of antimicrobial resistance in stored agricultural waste. We use parameters from a slurry tank on a UK dairy farm as an exemplar. We show that the spread of resistance depends in a subtle way on the rates of gene transfer and antibiotic inflow. If the gene transfer rate is high, then its reduction controls resistance, while cutting antibiotic inflow has little impact. If the gene transfer rate is low, then reducing antibiotic inflow controls resistance. Reducing length of storage can also control spread of resistance. Bacterial growth rate, fitness costs of carrying antimicrobial resistance and proportion of resistant bacteria in animal faeces have little impact on spread of resistance. Therefore, effective treatment strategies depend critically on knowledge of gene transfer rates. PMID:26906100

  17. Antimicrobial resistance and biological governance: explanations for policy failure.

    PubMed

    Wallinga, D; Rayner, G; Lang, T

    2015-10-01

    The paper reviews the state of policy on antimicrobial use and the growth of antimicrobial resistance (AMR). AMR was anticipated at the time of the first use of antibiotics by their originators. For decades, reports and scientific papers have expressed concern about AMR at global and national policy levels, yet the problem, first exposed a half-century ago, worsened. The paper considers the explanations for this policy failure and the state of arguments about ways forward. These include: a deficit of economic incentivisation; complex interventions in behavioural dynamics; joint and separate shifts in medical and animal health regimes; consumerism; belief in technology; and a narrative that in a 'war on bugs' nature can be beaten by human ingenuity. The paper suggests that these narratives underplay the biological realities of the human-animal-biosphere being in constant flux, an understanding which requires an ecological public health analysis of AMR policy development and failure. The paper suggests that effective policy change requires simultaneous actions across policy levels. No single solution is possible, since AMR is the result of long-term human intervention which has accelerated certain trends in the evolution of a microbial ecosystem shared by humans, animals and other biological organisms inhabiting that ecosystem. Viewing the AMR crisis today through an ecological public health lens has the advantage of reuniting the social-ecological and bio-ecological perspectives which have been separated within public health. PMID:26454427

  18. Antimicrobial Organometallic Dendrimers with Tunable Activity against Multidrug-Resistant Bacteria.

    PubMed

    Abd-El-Aziz, Alaa S; Agatemor, Christian; Etkin, Nola; Overy, David P; Lanteigne, Martin; McQuillan, Katherine; Kerr, Russell G

    2015-11-01

    Multidrug-resistant pathogens are an increasing threat to public health. In an effort to curb the virulence of these pathogens, new antimicrobial agents are sought. Here we report a new class of antimicrobial organometallic dendrimers with tunable activity against multidrug-resistant Gram-positive bacteria that included methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. Mechanistically, these redox-active, cationic organometallic dendrimers induced oxidative stress on bacteria and also disrupted the microbial cell membrane. The minimum inhibitory concentrations, which provide a quantitative measure of the antimicrobial activity of these dendrimers, were in the low micromolar range. AlamarBlue cell viability assay also confirms the antimicrobial activity of these dendrimers. Interestingly, these dendrimers were noncytotoxic to epidermal cell lines and to mammalian red blood cells, making them potential antimicrobial platforms for topical applications. PMID:26452022

  19. Intrinsic Antimicrobial Resistance Determinants in the Superbug Pseudomonas aeruginosa

    PubMed Central

    Murray, Justine L.; Kwon, Taejoon; Marcotte, Edward M.

    2015-01-01

    ABSTRACT Antimicrobial-resistant bacteria pose a serious threat in the clinic. This is particularly true for opportunistic pathogens that possess high intrinsic resistance. Though many studies have focused on understanding the acquisition of bacterial resistance upon exposure to antimicrobials, the mechanisms controlling intrinsic resistance are not well understood. In this study, we subjected the model opportunistic superbug Pseudomonas aeruginosa to 14 antimicrobials under highly controlled conditions and assessed its response using expression- and fitness-based genomic approaches. Our results reveal that gene expression changes and mutant fitness in response to sub-MIC antimicrobials do not correlate on a genomewide scale, indicating that gene expression is not a good predictor of fitness determinants. In general, fewer fitness determinants were identified for antiseptics and disinfectants than for antibiotics. Analysis of gene expression and fitness data together allowed the prediction of antagonistic interactions between antimicrobials and insight into the molecular mechanisms controlling these interactions. PMID:26507235

  20. Field Trial Evaluating the Influence of Prophylactic and Therapeutic Antimicrobial Administration on Antimicrobial Resistance of Fecal Escherichia coli in Dairy Calves

    PubMed Central

    Berge, Anna Catharina B.; Moore, Dale A.; Sischo, William M.

    2006-01-01

    The objective of this study was to describe the influence of in-feed and therapeutic antimicrobials on resistance in commensal fecal Escherichia coli isolated from preweaned calves. Four groups of 30, day-old calf-ranch calves were enrolled and raised until 4 weeks of age. Groups 1 to 3 were raised without antimicrobials in the feed. Group 1 was isolated from the other groups and received no antimicrobial therapy. Group 2 was housed on the calf ranch and did not receive antimicrobial therapy, whereas groups 3 and 4 could be treated with antimicrobials. Group 4 was fed neomycin and tetracycline HCl in the milk replacer. Fecal samples were collected from calves on days 1, 14, and 28. Three E. coli isolates per sample were evaluated for susceptibility to 12 antimicrobials. Cluster analysis was used to group isolates having similar susceptibility patterns. Cumulative logistic regression was used to evaluate factors associated with increasing levels of multiple antimicrobial resistance. In-feed antimicrobials were associated with higher levels of multiple antimicrobial resistance in fecal E. coli.f In calves not receiving in-feed antimicrobials, older calves had higher levels of resistance compared to day-old calves. Individual antimicrobial therapy increased resistance in these calves but appeared to be transient. There was no environmental influence on resistance in E. coli populations among study groups. PMID:16751491

  1. Field trial evaluating the influence of prophylactic and therapeutic antimicrobial administration on antimicrobial resistance of fecal Escherichia coli in dairy calves.

    PubMed

    Berge, Anna Catharina B; Moore, Dale A; Sischo, William M

    2006-06-01

    The objective of this study was to describe the influence of in-feed and therapeutic antimicrobials on resistance in commensal fecal Escherichia coli isolated from preweaned calves. Four groups of 30, day-old calf-ranch calves were enrolled and raised until 4 weeks of age. Groups 1 to 3 were raised without antimicrobials in the feed. Group 1 was isolated from the other groups and received no antimicrobial therapy. Group 2 was housed on the calf ranch and did not receive antimicrobial therapy, whereas groups 3 and 4 could be treated with antimicrobials. Group 4 was fed neomycin and tetracycline HCl in the milk replacer. Fecal samples were collected from calves on days 1, 14, and 28. Three E. coli isolates per sample were evaluated for susceptibility to 12 antimicrobials. Cluster analysis was used to group isolates having similar susceptibility patterns. Cumulative logistic regression was used to evaluate factors associated with increasing levels of multiple antimicrobial resistance. In-feed antimicrobials were associated with higher levels of multiple antimicrobial resistance in fecal E. coli.f In calves not receiving in-feed antimicrobials, older calves had higher levels of resistance compared to day-old calves. Individual antimicrobial therapy increased resistance in these calves but appeared to be transient. There was no environmental influence on resistance in E. coli populations among study groups. PMID:16751491

  2. Emergence of antimicrobial-resistant uropathogens isolated from pediatric patients with cystitis on daily clean intermittent catheterization.

    PubMed

    Hiyama, Yoshiki; Takahashi, Satoshi; Uehara, Teruhisa; Hashimoto, Jiro; Nishinaka, Kazuyuki; Kitamura, Hiroshi; Masumori, Naoya

    2015-10-01

    One of the major complications of clean intermittent catheterization (CIC) is urinary tract infection (UTI). Recent reports showed that community-acquired UTIs caused by antimicrobial-resistant pathogens were gradually presenting in adults. However, there have been few reports about UTIs caused by antimicrobial-resistant bacteria in pediatric patients. Therefore, we retrospectively reviewed the medical charts of 45 children with CIC due to neurogenic bladder dysfunction from January 2010 to March 2013. Sixty-two episodes of cystitis occurred in 27 patients. Seventy bacterial strains were isolated from urine samples. The rate of Gram-negative bacteria was 84.3%. Six extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli) strains were isolated from 4 patients. An ESBL-producing Proteus mirabilis strain and a methicillin-resistant Staphylococcus aureus strain were isolated from one patient each. Most of the pathogens of cystitis in the pediatric patients with CIC were Gram-negative bacilli, especially E. coli. We should be aware that ESBL producing E. coli as potential pathogens cause cystitis and regularly survey antimicrobial susceptibility to understand the resistant strains that develop. PMID:26194974

  3. Overcoming acquired resistance to kinase inhibition: the cases of EGFR, ALK and BRAF.

    PubMed

    Giroux, Simon

    2013-01-15

    In the past decade, several kinase inhibitors have been approved based on their clinical benefit for cancer patients. Unfortunately, in many cases, patients develop resistance to these agents via secondary mutations and alternative mechanisms. This review will focus on the cases of acquired resistance to EGFR and ALK inhibitors for non-small cell lung cancer patients and BRAF inhibitors for melanoma patients. I will overview the main causes of acquired resistance, and explore the chemical scaffolds as well as combination of drugs, used to tackle these major causes of resistance. PMID:23245516

  4. Managing acquired resistance in EGFR-mutated non-small cell lung cancer.

    PubMed

    Forde, Patrick M; Ettinger, David S

    2015-08-01

    Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) deliver high response rates with relatively modest toxicity in patients with advanced EGFR-mutated non-small cell lung cancer. Despite this, nearly all tumors eventually develop resistance to first-line therapy. At present, the only standard treatment option for patients with acquired resistance is cytotoxic chemotherapy. In this article, we review the latest research into methods of targeting acquired resistance to EGFR TKI therapy, including third-generation EGFR TKIs that target the T790M resistance mutation and other novel agents in development. PMID:26351816

  5. Importance of multidrug efflux pumps in the antimicrobial resistance property of clinical multidrug-resistant isolates of Neisseria gonorrhoeae.

    PubMed

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

    2014-06-01

    The contribution of drug efflux pumps in clinical isolates of Neisseria gonorrhoeae that express extensively drug-resistant or multidrug-resistant phenotypes has heretofore not been examined. Accordingly, we assessed the effect on antimicrobial resistance of loss of the three gonococcal efflux pumps associated with a known capacity to export antimicrobials (MtrC-MtrD-MtrE, MacA-MacB, and NorM) in such clinical isolates. We report that the MIC of several antimicrobials, including seven previously and currently recommended for treatment was significantly impacted. PMID:24733458

  6. Understanding bacterial resistance to antimicrobial peptides: From the surface to deep inside.

    PubMed

    Maria-Neto, Simone; de Almeida, Keyla Caroline; Macedo, Maria Ligia Rodrigues; Franco, Octávio Luiz

    2015-11-01

    Resistant bacterial infections are a major health problem in many parts of the world. The major commercial antibiotic classes often fail to combat common bacteria. Although antimicrobial peptides are able to control bacterial infections by interfering with microbial metabolism and physiological processes in several ways, a large number of cases of resistance to antibiotic peptide classes have also been reported. To gain a better understanding of the resistance process various technologies have been applied. Here we discuss multiple strategies by which bacteria could develop enhanced antimicrobial peptide resistance, focusing on sub-cellular regions from the surface to deep inside, evaluating bacterial membranes, cell walls and cytoplasmic metabolism. Moreover, some high-throughput methods for antimicrobial resistance detection and discrimination are also examined. This article is part of a Special Issue entitled: Bacterial Resistance to Antimicrobial Peptides. PMID:25724815

  7. Eight-Year Surveillance of Antimicrobial Resistance among Enterobacter Cloacae Isolated in the First Bethune Hospital

    NASA Astrophysics Data System (ADS)

    Zhou, Qi; Zhang, Man; Wang, Ailin; Xu, Jiancheng; Yuan, Ye

    This study was to investigate the antimicrobial resistance of Enterobacter cloacae isolated in 8 consecutive years in the First Bethune Hospital. Disk diffusion test was used to study the antimicrobial resistance. The data were analyzed by WHONET 5 software according to Clinical and Laboratory Standards Institute (CLSI). Most of 683 strains of Enterobacter cloacae were collected from sputum 410 (60.0%), secretions and pus 105 (15.4%), urine 69 (10.1%) during the past 8 years. No Enterobacter cloacae was resistant to imipenem and meropenem in the First Bethune Hospital. The antimicrobial resistance of Enterobacter cloacae had increased in recent 8 years. The change of the antimicrobial resistance should be investigated in order to direct rational drug usage in the clinic and prevent bacterial strain of drug resistance from b eing transmitted.

  8. Emerging resistance to newer antimicrobial agents among Shigella isolated from Finnish foreign travellers.

    PubMed

    Haukka, K; Siitonen, A

    2008-04-01

    In Finland, most cases of shigellosis are related to travel abroad. Antimicrobial drug resistance of 1814 Shigella strains isolated from Finnish patients during 1990-2005 was studied using discs of 12 antimicrobial agents. Since 2000, the E-test has been performed to determine ciprofloxacin minimum inhibitory concentrations of nalidixic acid-resistant isolates. The proportion of multi-resistant strains (resistant to >or =4 antimicrobials) was highest among isolates from China and India, but is increasing significantly in other parts of Asia. Resistance to nalidixic acid has become common among the strains from the Far East, and the first isolates also resistant to ciprofloxacin were detected during 2004-2005. All the ciprofloxacin-resistant isolates belonged to the S. flexneri 2a serotype. All the nalidixic acid-resistant S. flexneri strains had reduced susceptibility to ciprofloxacin, whereas 23% of the nalidixic acid-resistant S. sonnei strains were still completely susceptible to ciprofloxacin. PMID:17578602

  9. Acquired Antibiotic Resistance: Are We Born with It? ▿

    PubMed Central

    Zhang, Lu; Kinkelaar, Daniel; Huang, Ying; Li, Yingli; Li, Xiaojing; Wang, Hua H.

    2011-01-01

    The rapid emergence of antibiotic resistance (AR) is a major public health concern. Recent findings on the prevalence of food-borne antibiotic-resistant (ART) commensal bacteria in ready-to-consume food products suggested that daily food consumption likely serves as a major avenue for dissemination of ART bacteria from the food chain to human hosts. To properly assess the impact of various factors, including the food chain, on AR development in hosts, it is important to determine the baseline of ART bacteria in the human gastrointestinal (GI) tract. We thus examined the gut microbiota of 16 infant subjects, from the newborn stage to 1 year of age, who fed on breast milk and/or infant formula during the early stages of development and had no prior exposure to antibiotics. Predominant bacterial populations resistant to several antibiotics and multiple resistance genes were found in the infant GI tracts within the first week of age. Several ART population transitions were also observed in the absence of antibiotic exposure and dietary changes. Representative AR gene pools including tet(M), ermB, sul2, and blaTEM were detected in infant subjects. Enterococcus spp., Staphylococcus spp., Klebsiella spp., Streptococcus spp., and Escherichia coli/Shigella spp. were among the identified AR gene carriers. ART bacteria were not detected in the infant formula and infant foods examined, but small numbers of skin-associated ART bacteria were found in certain breast milk samples. The data suggest that the early development of AR in the human gut microbiota is independent of infants' exposure to antibiotics but is likely impacted by exposure to maternal and environmental microbes during and after delivery and that the ART population is significantly amplified within the host even in the absence of antibiotic selective pressure. PMID:21821748

  10. Comparison of rhizosphere bacterial communities in Arabidopsis thaliana mutants for systemic acquired resistance.

    PubMed

    Hein, John W; Wolfe, Gordon V; Blee, Kristopher A

    2008-02-01

    Systemic acquired resistance (SAR) is an inducible systemic plant defense against a broad spectrum of plant pathogens, with the potential to secrete antimicrobial compounds into the soil. However, its impact on rhizosphere bacteria is not known. In this study, we examined fingerprints of bacterial communities in the rhizosphere of the model plant Arabidopsis thaliana to determine the effect of SAR on bacterial community structure and diversity. We compared Arabidopsis mutants that are constitutive and non-inducible for SAR and verified SAR activation by measuring pathogenesis-related protein activity via a beta-glucoronidase (GUS) reporter construct driven by the beta-1-3 glucanase promoter. We used terminal restriction fragment length polymorphism (T-RFLP) analysis of MspI- and HaeIII-digested 16S rDNA to estimate bacterial rhizosphere community diversity, with Lactobacillus sp. added as internal controls. T-RFLP analysis showed a clear rhizosphere effect on community structure, and diversity analysis of both rhizosphere and bulk soil operational taxonomic units (as defined by terminal restriction fragments) using richness, Shannon-Weiner, and Simpson's diversity indices and evenness confirmed that the presence of Arabidopsis roots significantly altered bacterial communities. This effect of altered soil microbial community structure by plants was also seen upon multivariate cluster analysis of the terminal restriction fragments. We also found visible differences in the rhizosphere community fingerprints of different Arabidopsis SAR mutants; however, there was no clear decrease of rhizosphere diversity because of constitutive SAR expression. Our study suggests that SAR can alter rhizosphere bacterial communities, opening the door to further understanding and application of inducible plant defense as a driving force in structuring soil bacterial assemblages. PMID:17619212

  11. Multivariable Analysis of the Association Between Antimicrobial Use and Antimicrobial Resistance in Escherichia coli Isolated from Apparently Healthy Pigs in Japan.

    PubMed

    Makita, Kohei; Goto, Masaki; Ozawa, Manao; Kawanishi, Michiko; Koike, Ryoji; Asai, Tetsuo; Tamura, Yutaka

    2016-01-01

    The objective of this study was to investigate the association between antimicrobial agent use and antimicrobial resistance in Escherichia coli isolated from healthy pigs using data from 2004 to 2007 in the Japanese Veterinary Antimicrobial Resistance Monitoring System (JVARM). Fecal E. coli isolates from 250 pigs (one isolate each from a pig per farm) were examined for antimicrobial resistance. Information on the use of antimicrobials within preceding 6 months and types of farms recorded in JVARM was collected and statistically analyzed against the resistance patterns. In the univariate analysis, associations between both therapeutic and feed additive use of antimicrobials, and resistance to dihydrostreptomycin, gentamicin, kanamycin, ampicillin, cefazolin, ceftiofur, oxytetracycline, chloramphenicol, trimethoprim, nalidixic acid, enrofloxacin, colistin, and bicozamycin, and husbandry factors were investigated. In multivariable analysis, generalized estimating equations were used to control geographical intraclass correlation. Confounding for structurally unrelated associations was tested using generalized linear models. The results suggested direct and cross selections in the associations between use of aminoglycosides in reproduction farms and resistance to kanamycin, use of tetracyclines in larger farms and resistance to oxytetracycline, use of beta-lactams and resistance to ampicillin, use of phenicols and resistance to chloramphenicol, and use of fluoroquinolones and resistance to nalidixic acid and enrofloxacin. Coselection was suggested in the use of tetracyclines and chloramphenicol resistance. The associations between use of beta-lactams and dihydrostreptomycin resistance, use of macrolides and ampicillin and oxytetracycline resistance, and use of colistin and kanamycin resistance were significant, but were confounded by the simultaneous use of homologous antimicrobials. PMID:26296068

  12. Antimicrobial Resistance in Salmonella in the United States from 1948 to 1995.

    PubMed

    Tadesse, Daniel A; Singh, Aparna; Zhao, Shaohua; Bartholomew, Mary; Womack, Niketta; Ayers, Sherry; Fields, Patricia I; McDermott, Patrick F

    2016-04-01

    We conducted a retrospective study of 2,149 clinicalSalmonellastrains to help document the historical emergence of antimicrobial resistance. There were significant increases in resistance to older drugs, including ampicillin, chloramphenicol, streptomycin, sulfamethoxazole, and tetracycline, which were most common inSalmonella entericaserotype Typhimurium. An increase in multidrug resistance was observed for each decade since the 1950s. These data help show howSalmonellaevolved over the past 6 decades, after the introduction of new antimicrobial agents. PMID:26856840

  13. Antimicrobial resistance in Neisseria gonorrhoeae in the 21st century: past, evolution, and future.

    PubMed

    Unemo, Magnus; Shafer, William M

    2014-07-01

    Neisseria gonorrhoeae is evolving into a superbug with resistance to previously and currently recommended antimicrobials for treatment of gonorrhea, which is a major public health concern globally. Given the global nature of gonorrhea, the high rate of usage of antimicrobials, suboptimal control and monitoring of antimicrobial resistance (AMR) and treatment failures, slow update of treatment guidelines in most geographical settings, and the extraordinary capacity of the gonococci to develop and retain AMR, it is likely that the global problem of gonococcal AMR will worsen in the foreseeable future and that the severe complications of gonorrhea will emerge as a silent epidemic. By understanding the evolution, emergence, and spread of AMR in N. gonorrhoeae, including its molecular and phenotypic mechanisms, resistance to antimicrobials used clinically can be anticipated, future methods for genetic testing for AMR might permit region-specific and tailor-made antimicrobial therapy, and the design of novel antimicrobials to circumvent the resistance problems can be undertaken more rationally. This review focuses on the history and evolution of gonorrhea treatment regimens and emerging resistance to them, on genetic and phenotypic determinants of gonococcal resistance to previously and currently recommended antimicrobials, including biological costs or benefits; and on crucial actions and future advances necessary to detect and treat resistant gonococcal strains and, ultimately, retain gonorrhea as a treatable infection. PMID:24982323

  14. Antimicrobial Resistance in Neisseria gonorrhoeae in the 21st Century: Past, Evolution, and Future

    PubMed Central

    Unemo, Magnus

    2014-01-01

    SUMMARY Neisseria gonorrhoeae is evolving into a superbug with resistance to previously and currently recommended antimicrobials for treatment of gonorrhea, which is a major public health concern globally. Given the global nature of gonorrhea, the high rate of usage of antimicrobials, suboptimal control and monitoring of antimicrobial resistance (AMR) and treatment failures, slow update of treatment guidelines in most geographical settings, and the extraordinary capacity of the gonococci to develop and retain AMR, it is likely that the global problem of gonococcal AMR will worsen in the foreseeable future and that the severe complications of gonorrhea will emerge as a silent epidemic. By understanding the evolution, emergence, and spread of AMR in N. gonorrhoeae, including its molecular and phenotypic mechanisms, resistance to antimicrobials used clinically can be anticipated, future methods for genetic testing for AMR might permit region-specific and tailor-made antimicrobial therapy, and the design of novel antimicrobials to circumvent the resistance problems can be undertaken more rationally. This review focuses on the history and evolution of gonorrhea treatment regimens and emerging resistance to them, on genetic and phenotypic determinants of gonococcal resistance to previously and currently recommended antimicrobials, including biological costs or benefits; and on crucial actions and future advances necessary to detect and treat resistant gonococcal strains and, ultimately, retain gonorrhea as a treatable infection. PMID:24982323

  15. Relationship between Antimicrobial Consumption and the Incidence of Antimicrobial Resistance in Escherichia coli and Klebsiella pneumoniae Isolates

    PubMed Central

    Joseph, Noyal Mariya; Shewade, Deepak Gopal; Harish, Belgode Narasimha

    2015-01-01

    Introduction: Gram negative organisms are one of the major causes of nosocomial diseases. Development of resistance to antibiotics by these organisms increases their risk in clinical treatment of patients. It also affects morbidity and mortality hence needs to be monitored and controlled. Aim: The aim of the present study was to analyse the correlation between consumption of parenteral antibiotics and the rates of antimicrobial resistance among the Escherichia coli and Klebsiella pneumoniae isolates collected during Dec 2010 - Jun 2013 from JIPMER hospital. Materials and Methods: Consumption data of parenteral antibiotics in J01 category of Anatomical Therapeutic Chemical (ATC) in JIPMER was obtained and expressed in Defined Daily Doses (DDD) per 1000 inhabitants. Valid consumption and resistance data during the period Dec 2010 to Jun 2013 were obtained at 6 month intervals and were correlated to draw a relationship between antimicrobial consumption and its impact on drug resistance for Escherichia coli and Klebsiella pneumoniae. Results: Escherichia coli isolates showed high resistance for increased use of gentamycin and ciprofloxacin. Increase in antibiotic consumption increases the resistance for Escherichia coli except for amikacin. Among the Klebsiella isolates, meropenem and gentamycin showed high correlations followed by ceftazidime, amikacin, ceftriaxone and ciprofloxacin. Conclusion: In summary, a statistically significant association was noticed between consumption of the studied antimicrobials and resistance of Escherichia coli isolates, except for amikacin and ceftazidime. In the case of Klebsiella pneumoniae, there was a statistically significant association between the resistance rates and consumption of gentamycin, ceftazidime and meropenem. Further, a linear relationship was noted between antimicrobial consumption and resistant isolates of Escherichia coli and Klebsiella pneumoniae, except for Escherichia coli resistance to amikacin. PMID:25859453

  16. Antimicrobial resistance among Enterobacteriaceae in South America: history, current dissemination status and associated socioeconomic factors.

    PubMed

    Bonelli, Raquel Regina; Moreira, Beatriz Meurer; Picão, Renata Cristina

    2014-04-01

    South America exhibits some of the higher rates of antimicrobial resistance in Enterobactericeae worldwide. This continent includes 12 independent countries with huge socioeconomic differences, where the ample access to antimicrobials, including counterfeit ones, coexists with ineffective health systems and sanitation problems, favoring the emergence and dissemination of resistant strains. This work presents a literature review concerning the evolution and current status of antimicrobial resistance threats found among Enterobacteriaceae in South America. Resistance to β-lactams, fluoroquinolones and aminoglycosides was emphasized along with description of key epidemiological studies that highlight the success of specific resistance determinants in different parts of the continent. In addition, a discussion regarding political and socioeconomic factors possibly related to the dissemination of antimicrobial resistant strains in clinical settings and at the community is presented. Finally, in order to assess the possible sources of resistant bacteria, we compile the current knowledge about the occurrence of antimicrobial resistance in isolates in South American' food, food-producing animals and off-hospitals environments. By addressing that intensive intercontinental commerce and tourism neutralizes the protective effect of geographic barriers, we provide arguments reinforcing that globally integrated efforts are needed to decelerate the emergence and dissemination of antimicrobial resistant strains. PMID:24618111

  17. An electronic network for the surveillance of antimicrobial resistance in bacterial nosocomial isolates in Greece. The Greek Network for the Surveillance of Antimicrobial Resistance.

    PubMed Central

    Vatopoulos, A. C.; Kalapothaki, V.; Legakis, N. J.

    1999-01-01

    The present article reports an evaluation of the national electronic network for the continuous monitoring of antimicrobial resistance in Greece. The network employs a common electronic code and data format and uses WHONET software. Our four years' experience with the network confirms its practicality. A total of 22 hospitals in Greece are currently using the software, of which 19 participate in the network. Analysis of the information obtained has greatly helped in identifying the main factors responsible for the emergence of antimicrobial resistance in the participating hospitals. The data collected have also helped to identify priorities for further investigation of the genetic and molecular mechanisms responsible for the emergence of resistance and facilitated development of hospital-based empirical therapy of infections. In conclusion, the implementation of national networks for the surveillance of antimicrobial resistance should be regarded as a priority. PMID:10444883

  18. Antimicrobial resistance, infection control and planning for pandemics: the importance of knowledge transfer in healthcare resilience and emergency planning.

    PubMed

    Cole, Jennifer

    Over the last 70 years, the efficacy, ready availability and relatively low cost of antimicrobial drugs - medicines that kill microorganisms such as bacteria and viruses or inhibit their multiplication, growth and pathogenic action - has led to their considerable overuse. It is estimated that nearly 50 per cent of all antimicrobial use in hospitals is unnecessary or inappropriate1 while in neonatal care, the figure is even higher, with infection confirmed in only five per cent of neonates treated with antibiotics.2 The more antimicrobials are used, the faster the microorganisms they target evolve into new, resistant strains, a natural process of evolution that threatens to undermine the tremendous life-saving potential of these drugs. Antimicrobial resistance (AMR) is a growing concern not only for the healthcare sector3 but also, increasingly, for security and resilience. Pandemic influenza, comparable only to 'Catastrophic terrorist attacks' at the top of the UK's National Risk Register4 may well result from the emergence of a strain that cannot be treated effectively with currently available drugs or from one that quickly develops resistance to the stockpiled countermeasures. Multidrug-resistant tuberculosis impacts on immigration policy, methicillin-resistant Staphylococcus aureus (MRSA), a major cause of hospital-acquired infections is an ongoing challenge for the health sector and the increase in drug-resistant strains of malaria is problematic both in its own right and as an additional consequence of climate change. AMR places a significant burden on international governments and tackling it requires changes to thinking across a number of government departments. In 2011, the Transatlantic Taskforce on Antimicrobial Resistance (TATFAR) published Recommendations for future collaboration between the US and EU1 and both the EU and the UK's Department of Health have recently developed new AMR strategies and Action Plans. This paper will explore the cross

  19. Antimicrobial susceptibility of Staphylococcus aureus and characterization of methicillin-resistant Staphylococcus aureus isolated from bovine mastitis in Korea.

    PubMed

    Nam, Hyang-Mi; Lee, Ae-Li; Jung, Suk-Chan; Kim, Mal-Nam; Jang, Geum-Chan; Wee, Sung-Hwan; Lim, Suk-Kyung

    2011-02-01

    A total of 402 Staphylococcus aureus isolates from bovine mastitis milk collected during 2003-2009 in Korea were tested for susceptibility to 20 antimicrobial agents. All S. aureus isolates were susceptible to 11 of 20 antimicrobials tested; no resistance was observed against pirlimycin, telithromycin, novobiocin, penicillin/novobiocin, quinupristin/dalfopristin, clindamycin, rifampin, ciprofloxacin, trimethprim/sulfamethoxazol, vancomycin, and linezolid. Over 66% of the S. aureus isolates were resistant to penicillin. Resistance was also seen for gentamicin (11.9%), erythromycin (7.7%), methicillin (oxacillin and cefoxitin, 6.2%), and tetracycline (4.2%). No noticeable change was observed in penicillin, gentamicin, and erythromycin resistance over the 7-year period. Tetracycline resistance appeared to decrease consistently, whereas methicillin resistance was observed from 2005. About 2.7% (11/402) were resistant to three or more antimicrobials. Genotyping of the 17 methicillin-resistant S. aureus (MRSA) isolated from each cow revealed two staphylococcal cassette chromosome mec (SCCmec) types (IV and IVa), three spa types (t286, t324, and untypable), and two sequence types (ST1 and ST72). Eleven of 17 (64.7%) MRSA strains belonged to SCCmec IVa-t324-ST72. The rest of strains belonged to SCCmec IVa-t286-ST1 (n = 3) and SCCmec IV-untypable-ST72 (n = 3). None of the MRSA carried the Panton-Valentine leukocidin gene. These characteristics are the same as those found in community-acquired (CA) MRSA strains prevalent in humans in Korea. Three pulsed-field gel electrophoresis types (A-C) were observed among the 17 MRSA strains examined, and 14 strains belonged to the same pulsed-field gel electrophoresis pattern regardless of their geographical origin and year of isolation. The results of this study provide evidence of CA-MRSA infection in dairy cattle for the first time in Korea. PMID:21034263

  20. An Assessment of Antimicrobial Resistant Disease Threats in Canada

    PubMed Central

    Garner, Michael J.; Carson, Carolee; Lingohr, Erika J.; Fazil, Aamir; Edge, Victoria L.; Trumble Waddell, Jan

    2015-01-01

    Background Antimicrobial resistance (AMR) of infectious agents is a growing concern for public health organizations. Given the complexity of this issue and how widespread the problem has become, resources are often insufficient to address all concerns, thus prioritization of AMR pathogens is essential for the optimal allocation of risk management attention. Since the epidemiology of AMR pathogens differs between countries, country-specific assessments are important for the determination of national priorities. Objective To develop a systematic and transparent approach to AMR risk prioritization in Canada. Methods Relevant AMR pathogens in Canada were selected through a transparent multi-step consensus process (n=32). Each pathogen was assessed using ten criteria: incidence, mortality, case-fatality, communicability, treatability, clinical impact, public/political attention, ten-year projection of incidence, economic impact, and preventability. For each pathogen, each criterion was assigned a numerical score of 0, 1, or 2, and multiplied by criteria-specific weighting determined through researcher consensus of importance. The scores for each AMR pathogen were summed and ranked by total score, where a higher score indicated greater importance. A sensitivity analysis was conducted to determine the effects of changing the criteria-specific weights. Results The AMR pathogen with the highest total weighted score was extended spectrum B-lactamase-producing (ESBL) Enterobacteriaceae (score=77). When grouped by percentile, ESBL Enterobacteriaceae, Clostridium difficile, carbapenem-resistant Enterobacteriaceae, and methicillin-resistant Staphylococcus aureus were in the 80-100th percentile. Conclusion This assessment provides useful information for prioritising public health strategies regarding AMR resistance at the national level in Canada. As the AMR environment and challenges change over time and space, this systematic and transparent approach can be adapted for use by

  1. Overexpression of Specific CD44 Isoforms Is Associated with Aggressive Cell Features in Acquired Endocrine Resistance

    PubMed Central

    Bellerby, Rebecca; Smith, Chris; Kyme, Sue; Gee, Julia; Günthert, Ursula; Green, Andy; Rakha, Emad; Barrett-Lee, Peter; Hiscox, Stephen

    2016-01-01

    While endocrine therapy is the mainstay of ER+ breast cancer, the clinical effectiveness of these agents is limited by the phenomenon of acquired resistance that is associated with disease relapse and poor prognosis. Our previous studies revealed that acquired resistance is accompanied by a gain in cellular invasion and migration and also that CD44 family proteins are overexpressed in the resistant phenotype. Given the association of CD44 with tumor progression, we hypothesized that its overexpression may act to promote the aggressive behavior of endocrine-resistant breast cancers. Here, we have investigated further the role of two specific CD44 isoforms, CD44v3 and CD44v6, in the endocrine-resistant phenotype. Our data revealed that overexpression of CD44v6, but not CD44v3, in endocrine-sensitive MCF-7 cells resulted in a gain in EGFR signaling, enhanced their endogenous invasive capacity, and attenuated their response to endocrine treatment. Suppression of CD44v6 in endocrine-resistant cell models was associated with a reduction in their invasive capacity. Our data suggest that upregulation of CD44v6 in acquired resistant breast cancer may contribute to a gain in the aggressive phenotype of these cells and loss of endocrine response through transactivation of the EGFR pathway. Future therapeutic targeting of CD44v6 may prove to be an effective strategy alongside EGFR-targeted agents in delaying/preventing acquired resistance in breast cancer. PMID:27379207

  2. Community-Acquired Methicillin-Resistant "Staphylococcus aureus": Considerations for School Nurses

    ERIC Educational Resources Information Center

    Alex, Aniltta; Letizia, MariJo

    2007-01-01

    Methicillin-resistant "Staphylococcus aureus" (MRSA) is a disease-causing organism that has been present in hospital settings since the 1960s. However, a genetically distinct strain of MRSA, called community-acquired methicillin-resistant "Staphylococcus aureus" (CA-MRSA), has emerged in recent years in community settings among healthy…

  3. Antimicrobial resistance and the standards of the World Organisation for Animal Health.

    PubMed

    Orand, J P

    2012-04-01

    Antimicrobial resistance and the use of antimicrobial agents in veterinary medicine are complex issues that are currently a source of major international concern. It is therefore essential for the World Organisation for Animal Health (OIE) to consider this issue, while at the same time continuing to address the problem of zoonotic diseases. That is why the OIE has included objectives for veterinary drugs, especially antimicrobials, in its Strategic Plan. The OIE plays an active part in discussions on this subject in conjunction with other international organisations working in this field, such as the Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO). Furthermore, the OIE has adopted guidelines both for defining harmonised methodologies for antimicrobial resistance surveillance and monitoring and for helping countries to conduct a risk analysis tailored to their situation and to take appropriate management measures. The OIE has included this issue in its programme of assistance to countries by offering them structural enhancement tools: the Tool for the Evaluation of Performance of Veterinary Services (O1E PVS Tool), PVS Gap Analysis, veterinary legislation support, and training for veterinary national focal points, with the aid of its Collaborating Centres for veterinary medicinal products. Only by mobilising all countries to improve the quality of antimicrobials, to introduce antimicrobial resistance surveillance and to implement measures for the responsible and prudent use of antimicrobials, will it be possible to halt the spread of antimicrobial resistance. PMID:22849287

  4. Antimicrobial Drug Resistance of Vibrio cholerae, Democratic Republic of the Congo

    PubMed Central

    Miwanda, Berthe; Moore, Sandra; Muyembe, Jean-Jacques; Nguefack-Tsague, Georges; Kabangwa, Ickel Kakongo; Ndjakani, Daniel Yassa; Mutreja, Ankur; Thomson, Nicholas; Thefenne, Helene; Garnotel, Eric; Tshapenda, Gaston; Kakongo, Denis Kandolo; Kalambayi, Guy

    2015-01-01

    We analyzed 1,093 Vibrio cholerae isolates from the Democratic Republic of the Congo during 1997–2012 and found increasing antimicrobial drug resistance over time. Our study also demonstrated that the 2011–2012 epidemic was caused by an El Tor variant clonal complex with a single antimicrobial drug susceptibility profile. PMID:25897570

  5. EPHA2 Blockade Overcomes Acquired Resistance to EGFR Kinase Inhibitors in Lung Cancer.

    PubMed

    Amato, Katherine R; Wang, Shan; Tan, Li; Hastings, Andrew K; Song, Wenqiang; Lovly, Christine M; Meador, Catherine B; Ye, Fei; Lu, Pengcheng; Balko, Justin M; Colvin, Daniel C; Cates, Justin M; Pao, William; Gray, Nathanael S; Chen, Jin

    2016-01-15

    Despite the success of treating EGFR-mutant lung cancer patients with EGFR tyrosine kinase inhibitors (TKI), all patients eventually acquire resistance to these therapies. Although various resistance mechanisms have been described, there are currently no FDA-approved therapies that target alternative mechanisms to treat lung tumors with acquired resistance to first-line EGFR TKI agents. Here we found that EPHA2 is overexpressed in EGFR TKI-resistant tumor cells. Loss of EPHA2 reduced the viability of erlotinib-resistant tumor cells harboring EGFR(T790M) mutations in vitro and inhibited tumor growth and progression in an inducible EGFR(L858R+T790M)-mutant lung cancer model in vivo. Targeting EPHA2 in erlotinib-resistant cells decreased S6K1-mediated phosphorylation of cell death agonist BAD, resulting in reduced tumor cell proliferation and increased apoptosis. Furthermore, pharmacologic inhibition of EPHA2 by the small-molecule inhibitor ALW-II-41-27 decreased both survival and proliferation of erlotinib-resistant tumor cells and inhibited tumor growth in vivo. ALW-II-41-27 was also effective in decreasing viability of cells with acquired resistance to the third-generation EGFR TKI AZD9291. Collectively, these data define a role for EPHA2 in the maintenance of cell survival of TKI-resistant, EGFR-mutant lung cancer and indicate that EPHA2 may serve as a useful therapeutic target in TKI-resistant tumors. PMID:26744526

  6. Characterization of a human colorectal carcinoma cell line with acquired resistance to flavopiridol.

    PubMed

    Smith, V; Raynaud, F; Workman, P; Kelland, L R

    2001-11-01

    Flavopiridol is a broad-spectrum inhibitor of cyclin-dependent kinases (cdks) and represents the first in this anticancer class to enter clinical trials. In anticipation of the likelihood that, as with other cancer drugs, acquired resistance may limit the drug's efficacy, an acquired resistance model has been established by in vitro drug exposure of the human colon carcinoma cell line HCT116. This stably resistant line, possessing 8-fold resistance to flavopiridol, showed a lack of cross-resistance to the anticancer agents etoposide, doxorubicin, paclitaxel, topotecan, and cisplatin, and notably to other chemical classes of cdk inhibitors: the aminopurines roscovitine and purvalanol A, 9-nitropaullone, and hymenialdisine. Resistance did not seem to be related to differences in the levels of multidrug resistance drug efflux proteins, P-glycoprotein, and MRP1. Moreover, there were no changes in overall drug accumulation between the resistant and sensitive cell lines. Flavopiridol induced cell cycle arrest, apoptosis, and inhibition of retinoblastoma gene product phosphorylation on serine 780 in both parental and resistant lines, but the latter required 8-fold higher concentrations to achieve these effects. Cyclin E protein levels and cyclin E-associated kinase activity were increased in the resistant line, suggesting that overexpression of cyclin E may be the mechanism of resistance to flavopiridol. However, transfection of cyclin E to increase expression of this protein did not result in an increase in resistance to flavopiridol. Thus, up-regulation of cyclin E alone does not seem to cause resistance to this cdk inhibitor. PMID:11641415

  7. The Role of Flies in Disseminating Plasmids with Antimicrobial-Resistance Genes Between Farms.

    PubMed

    Usui, Masaru; Shirakawa, Takahiro; Fukuda, Akira; Tamura, Yutaka

    2015-10-01

    Dissemination of antimicrobial resistance is a major global public health concern. To clarify the role of flies in disseminating antimicrobial resistance between farms, we isolated and characterized tetracycline-resistant Escherichia coli strains isolated from flies and feces of livestock from four locations housing swine (abattoir, three farms) and three cattle farms. The percentages of isolates from flies resistant to tetracycline, dihydrostreptomycin, ampicillin, and chloramphenicol (80.8%, 61.5%, 53.8%, and 50.0%, respectively) and those from animal feces (80.5%, 78.0%, 41.5%, and 46.3%, respectively) in locations housing swine were significantly higher than those from cattle farms (p<0.05). The rates of resistance in E. coli derived from flies reflected those derived from livestock feces at the same locations, suggesting that antimicrobial resistance spreads between livestock and flies on the farms. The results of pulsed-field gel electrophoresis (PFGE) analysis showed that, with a few exceptions, all E. coli isolates differed. Two pairs of tetracycline-resistant strains harbored similar plasmids with the same tetracycline-resistance genes, although the origin (fly or feces), site of isolation, and PFGE patterns of these strains differed. Therefore, flies may disseminate the plasmids between farms. Our results suggest that flies may be involved not only in spreading clones of antimicrobial-resistant bacteria within a farm but also in the widespread dissemination of plasmids with antimicrobial resistance genes between farms. PMID:26061440

  8. The mechanism of antimicrobial activity of sophoraflavanone B against methicillin-resistant Staphylococcus aureus.

    PubMed

    Mun, Su-Hyun; Joung, Dae-Ki; Kim, Sung-Bae; Park, Sung-Joo; Seo, Yun-Soo; Gong, Ryong; Choi, Jang-Gi; Shin, Dong-Won; Rho, Jung-Rae; Kang, Ok-Hwa; Kwon, Dong-Yeul

    2014-03-01

    Sophoraflavanone B (SPF-B), a prenylated flavonoid, can be isolated from the roots of Desmodium caudatum. The aim of this study was to determine the mechanism of SPF-B's antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA). MRSA is a multidrug-resistant pathogen and the main cause of hospital- and community-acquired infections. The minimum inhibitory concentration (MIC) of SPF-B was assessed using the broth microdilution method. The mechanism of action of SPF-B on S. aureus was analyzed in combination assays incorporating detergents, ATPase inhibitors, and peptidoglycan (PGN) derived from S. aureus. Furthermore, morphological changes in the SPF-B-treated MRSA strains were investigated using transmission electron microscopy. The MIC of SPF-B for MRSA was in the range of 15.6-31.25 μg/mL. The mechanism of action of SPF-B on MRSA was investigated using combination assays with detergent and ATPase inhibitors. The optical density at 600 nm of MRSA suspensions treated with a combination of detergent and SPF-B reduced the MRSA by 63%-73%. In the SPF-B and PGN combination assay, direct binding of SPF-B with PGN from S. aureus was evident. These data may be validated for the development of new antibacterial drugs for low MRSA resistance. PMID:24601672

  9. New antimicrobial combinations: substituted chalcones- oxacillin against methicillin resistant Staphylococcus aureus

    PubMed Central

    Talia, Juan Manuel; Debattista, Nora Beatriz; Pappano, Nora Beatriz

    2011-01-01

    Staphylococcus aureus, the most virulent Staphylococcus species, is also the prevalent pathogen isolated from hospitalized patients and the second most common from patients in outpatient settings. In general, bacteria have the genetic ability to transmit and acquire resistance to drugs, which are utilized as therapeutic agents. Related studies of antimicrobial activity indicate that crude extracts containing flavonoids, triterpenes and steroids have showed significative activity against several Staphylococcus aureus strains. Combination effects between flavonoids and antibiotics also have been reported. The aim of the present work was to investigate in vitro synergism between several chalcones substituted in combination with oxacillin, an antibiotic used conventionally against S. aureus ATCC 43 300 that is resistant to meticillin, using the kinetic turbidimetric method developed earlier. The results were satisfactory for all assayed combinations and in accordance with the mechanism of bacteriostatic inhibition previously proposed, except for 2´,4´-dihydroxy-3´-methoxychalcone – oxacillin. The best combination was 2´,3´-dihydroxychalcone -oxacillin (MIC: 11.2 µg/mL). Further investigations are needed to characterize the interaction mechanism with antibiotics. Thus, chalcones – oxacillin combination could lead to the development of new antibiotics against methicillin resistant S. aureus infection. PMID:24031657

  10. Does Nonpayment for Hospital-Acquired Catheter-Associated Urinary Tract Infections Lead to Overtesting and Increased Antimicrobial Prescribing?

    PubMed Central

    Morgan, Daniel J.; Meddings, Jennifer; Saint, Sanjay; Lautenbach, Ebbing; Shardell, Michelle; Anderson, Deverick; Milstone, Aaron M.; Drees, Marci; Pineles, Lisa; Safdar, Nasia; Bowling, Jason; Henderson, David; Yokoe, Deborah; Harris, Anthony D.

    2012-01-01

    Background. On 1 October 2008, in an effort to stimulate efforts to prevent catheter-associated urinary tract infection (CAUTI), the Centers for Medicare & Medicaid Services (CMS) implemented a policy of not reimbursing hospitals for hospital-acquired CAUTI. Since any urinary tract infection present on admission would not fall under this initiative, concerns have been raised that the policy may encourage more testing for and treatment of asymptomatic bacteriuria. Methods. We conducted a retrospective multicenter cohort study with time series analysis of all adults admitted to the hospital 16 months before and 16 months after policy implementation among participating Society for Healthcare Epidemiology of America Research Network hospitals. Our outcomes were frequency of urine culture on admission and antimicrobial use. Results. A total of 39 hospitals from 22 states submitted data on 2 362 742 admissions. In 35 hospitals affected by the CMS policy, the median frequency of urine culture performance did not change after CMS policy implementation (19.2% during the prepolicy period vs 19.3% during the postpolicy period). The rate of change in urine culture performance increased minimally during the prepolicy period (0.5% per month) and decreased slightly during the postpolicy period (–0.25% per month; P < .001). In the subset of 10 hospitals providing antimicrobial use data, the median frequency of fluoroquinolone antimicrobial use did not change substantially (14.6% during the prepolicy period vs 14.0% during the postpolicy period). The rate of change in fluoroquinolone use increased during the prepolicy period (1.26% per month) and decreased during the postpolicy period (–0.60% per month; P < .001). Conclusions. We found no evidence that CMS nonpayment policy resulted in overtesting to screen for and document a diagnosis of urinary tract infection as present on admission. PMID:22700826

  11. Comparative in vitro activity of cefditoren and other antimicrobials against Enterobacteriaceae causing community-acquired uncomplicated urinary tract infections in women: a Spanish nationwide multicenter study.

    PubMed

    Cuevas, Oscar; Cercenado, Emilia; Gimeno, Mercedes; Marín, Mercedes; Coronel, Pilar; Bouza, Emilio

    2010-07-01

    Cefditoren is a third-generation orally administered cephalosporin with a broad spectrum of activity against Gram-positive and Gram-negative bacterial species. After an oral 400-mg single dose, the mean concentrations in urine are 186.5 mg/L at 2 to 4 h and 12.7 mg/L at 8 to 12 h, and it is a potential drug to be used in the treatment of urinary tract infection (UTI). We performed a multicenter nationwide study in Spain in order to determine the in vitro activity of cefditoren and other comparative agents against Enterobacteriaceae causing community-acquired uncomplicated UTI in women. From June 2008 to March 2009, 89 institutions participated in the study. A total of 2152 Enterobacteriaceae were collected and sent to a coordinating laboratory where identification and antimicrobial susceptibility testing was performed against 20 antimicrobials using an automated microdilution method (MicroScan; Siemens, Sacramento, CA). Cefditoren MICs were determined by the broth microdilution method (Clinical and Laboratory Standards Institute guidelines) using the same inoculum. Microorganisms isolated were Escherichia coli (81.8%), Klebsiella pneumoniae (7.9%), Proteus mirabilis (5.2%), and others (5.1%). A total of 51 isolates (2.4%) were extended-spectrum beta-lactamase (ESBL) producers, 3 (0.1%) produced plasmidic AmpC enzymes, and 64 (2.9%) produced chromosomal AmpC. The MIC(50)/MIC(90) (mg/L) of cefditoren against all isolates was 0.12/0.5. Cefditoren inhibited 96.5% of isolates at 1 mg/L and was uniformly active against all isolates with the exception of strains producing ESBLs or AmpC enzymes. The MIC(50)/MIC(90) of other antimicrobials were ampicillin (AMP) >16/>16, amoxicillin/clavulanic acid (A/C) 2, trimethoprim/sulfamethoxazole (SxT) 4/76, and fosfomycin (FOS) resistance were 61%, 17.2%, 5.5%, 2.3%, 20.2%, 27.4%, and 4

  12. Antimicrobial Resistance and Resistance Genes in Aerobic Bacteria Isolated from Pork at Slaughter.

    PubMed

    Li, Lili; Olsen, Rikke Heidemann; Ye, Lei; Yan, He; Nie, Qing; Meng, Hecheng; Shi, Lei

    2016-04-01

    The aim of this study was to investigate the phenotypic and genotypic antimicrobial resistance, integrons, and transferability of resistance markers in 243 aerobic bacteria recovered from pork at slaughter in the People's Republic of China. The organisms belonged to 22 genera of gram-negative bacteria (92.2%) and gram-positive bacteria (7.8%). High levels of resistance were detected to tetracycline, trimethoprim-sulfamethoxazole, and ampicillin (36.2 to 54.3%), and lower levels were detected to nitrofurantoin, cefotaxime, gentamicin, ciprofloxacin, and chloramphenicol (7.8 to 29.2%). Across species, genes conferring antimicrobial resistance were observed with the following frequencies: blaTEM, 40.7%; blaCMY-2, 15.2%; blaCTX-M, 11.5%; sul2, 27.2%; sul1, 14.4%; tet(A), 5.4%; tet(L), 5.4%; tet(M), 5.0%; tet(E), 3.7%; tet(C), 3.3%; tet(S), 2.5%; and tet(K), 0.8%. Various antimicrobial resistance genes were found in new carriers: blaTEM in Lactococcus garvieae, Myroides odoratimimus, Aeromonas hydrophila, Staphylococcus sciuri, Raoultella terrigena, Macrococcus caseolyticus, Acinetobacter ursingii, Sphingobacterium sp., and Oceanobacillus sp.; blaCMY-2 in Lactococcus lactis, Klebsiella oxytoca, Serratia marcescens, Acinetobacter baumannii, and Myroides phaeus; tet(L) in M. caseolyticus; sul1 in Vibrio cincinnatiensis; sul2 in Acinetobacter bereziniae, Acinetobacter johnsonii, and V. cincinnatiensis; and the class 1 integron and gene cassette aadA2 in V. cincinnatiensis. Approximately 6.6% of isolates contained class 1 integrons, and one isolate harbored class 2 integrons. Plasmid associated intI1 and androgen receptor- encoding genes were transferred into Escherichia coli J53 and E. coli DH5α by conjugation and transformation experiments, respectively. Our study highlights the importance of aerobic bacteria from pork as reservoirs for antimicrobial resistance genes and mobile genetic elements that can readily be transferred intra- and interspecies. PMID:27052863

  13. TEM and SHV Genes in Klebsiella pneumoniae Isolated from Cockroaches and Their Antimicrobial Resistance Pattern

    PubMed Central

    Doosti, Abbas; Pourabbas, Mohammad; Arshi, Asghar; Chehelgerdi, Mohammad; Kabiri, Hamidreza

    2014-01-01

    Objectives Klebsiella pneumoniae is a gram-negative rod bacterium, a known cause of community-acquired bacterial pneumonia and is an important hospital-acquired pathogen that causes severe morbidity and mortality. The aim of this study was to identify the TEM and SHV genes in K. pneumoniae isolated from cockroaches obtained from hospitals. Methods In this study, 250 cockroaches were collected from different hospitals in the province of Chaharmahal Va Bakhtiari, which is located in southwest Iran. The samples were examined for the presence of K. pneumoniae by plating onto a combination of culture media, and the antimicrobial susceptibility patterns of isolated K. pneumoniae from samples were evaluated using the disk diffusion test. In addition, from the culture, genomic bacterial DNA was extracted, and sequence-specific targets (TEM and SHV genes) were amplified using the polymerase chain reaction (PCR) method. Results Out of 250 cockroach samples collected from various hospitals, 179 samples (71.60%) were positive for K. pneumoniae. PCR reaction was performed using specific oligonucleotide primers (TEM-F, TEM-R and SHV-F, SHV-R) for the amplification of each gene, and amplified products were visualized on 1% agarose gel electrophoresis. Of all the specimens amplified by PCR in this research, 32 samples (17.87%) were positive for TEM and 15 samples (8.37%) were positive for SHV. Conclusion Detection of TEM and SHV genes using molecular methods and their pattern of antimicrobial resistance can provide useful information about the epidemiology of and risk factors associated with K. pneumoniae infection. PMID:25737824

  14. STROBE-AMS: recommendations to optimise reporting of epidemiological studies on antimicrobial resistance and informing improvement in antimicrobial stewardship

    PubMed Central

    Tacconelli, Evelina; Cataldo, Maria A; Paul, M; Leibovici, L; Kluytmans, Jan; Schröder, Wiebke; Foschi, Federico; De Angelis, Giulia; De Waure, Chiara; Cadeddu, Chiara; Mutters, Nico T; Gastmeier, Petra; Cookson, Barry

    2016-01-01

    Objectives To explore the accuracy of application of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) tool in epidemiological studies focused on the evaluation of the role of antibiotics in selecting resistance, and to derive and test an extension of STROBE to improve the suitability of the tool in evaluating the quality of reporting in these area. Methods A three-step study was performed. First, a systematic review of the literature analysing the association between antimicrobial exposure and acquisition of methicillin-resistant Staphylococcus aureus and/or multidrug-resistant Acinetobacter baumannii was performed. Second, articles were reviewed according to the STROBE checklist for epidemiological studies. Third, a set of potential new items focused on antimicrobial-resistance quality indicators was derived through an expert two-round RAND-modified Delphi procedure and tested on the articles selected through the literature review. Results The literature search identified 78 studies. Overall, the quality of reporting appeared to be poor in most areas. Five STROBE items, comprising statistical analysis and study objectives, were satisfactory in <25% of the studies. Informative abstract, reporting of bias, control of confounding, generalisability and description of study size were missing in more than half the articles. A set of 21 new items was developed and tested. The new items focused particularly on the study setting, antimicrobial usage indicators, and patients epidemiological and clinical characteristics. The performance of the new items in included studies was very low (<25%). Conclusions Our paper reveals that reporting in epidemiological papers analysing the association between antimicrobial usage and development of resistance is poor. The implementation of the newly developed STROBE for antimicrobial stewardship (AMS) tool should enhance appropriate study design and reporting, and therefore contribute to the improvement of

  15. Antimicrobial Resistance Incidence and Risk Factors among Helicobacter pylori–Infected Persons, United States

    PubMed Central

    Sobel, Jeremy; Pruckler, Janet M.; Song, Qunsheng; Swerdlow, David; Friedman, Cindy; Sulka, Alana; Swaminathan, Balasubra; Taylor, Tom; Hoekstra, Mike; Griffin, Patricia; Smoot, Duane; Peek, Rick; Metz, David C.; Bloom, Peter B.; Goldschmid, Steven; Parsonnet, Julie; Triadafilopoulos, George; Perez-Perez, Guillermo I.; Vakil, Nimish; Ernst, Peter; Czinn, Steve; Dunne, Donald; Gold, Ben D.

    2004-01-01

    Helicobacter pylori is the primary cause of peptic ulcer disease and an etiologic agent in the development of gastric cancer. H. pylori infection is curable with regimens of multiple antimicrobial agents, and antimicrobial resistance is a leading cause of treatment failure. The Helicobacter pylori Antimicrobial Resistance Monitoring Program (HARP) is a prospective, multicenter U.S. network that tracks national incidence rates of H. pylori antimicrobial resistance. Of 347 clinical H. pylori isolates collected from December 1998 through 2002, 101 (29.1%) were resistant to one antimicrobial agent, and 17 (5%) were resistant to two or more antimicrobial agents. Eighty-seven (25.1%) isolates were resistant to metronidazole, 45 (12.9%) to clarithromycin, and 3 (0.9%) to amoxicillin. On multivariate analysis, black race was the only significant risk factor (p < 0.01, hazard ratio 2.04) for infection with a resistant H. pylori strain. Formulating pretreatment screening strategies or providing alternative therapeutic regimens for high-risk populations may be important for future clinical practice. PMID:15207062

  16. Will antimicrobial resistance of BRD pathogens impact BRD management in the future?

    PubMed

    Brumbaugh, Gordon W

    2014-12-01

    Resistance is a qualitative interpretation of antimicrobial activity in vitro. Critical to management of bovine respiratory disease (BRD) is the clinical response in vivo. Attempts to connect activity in vitro to response in vivo have been complicated by the complexity of BRD, interpretation of antimicrobial activity in vitro, and inconsistent measures of clinical success or failure. During recent history, the discovery, development, and commercialization of antimicrobials have decreased. In response to resistance, voluntary and imposed restrictions on use of antimicrobials have been implemented. Resistance can be reversed using technology and knowledge of mechanisms of resistance. Perhaps approaches that reverse resistance will be used in clinical management of BRD in the future. The short answer to the question posed in the title is, 'yes.' Since antimicrobial drugs were discovered, resistance has been a consideration for selection of treatment of any infectious disease and BRD is not unique. In the opinion of the author, the more important question is, 'How will antimicrobial resistance of BRD pathogens impact BRD management in the future?' PMID:25410262

  17. Antimicrobial resistance in methicillin susceptible and methicillin resistant Staphylococcus pseudintermedius of canine origin: literature review from 1980 to 2013.

    PubMed

    Moodley, Arshnee; Damborg, Peter; Nielsen, Søren Saxmose

    2014-07-16

    Staphylococcus pseudintermedius is a commensal and a common opportunistic pathogen causing mainly infections of the integumentary system in dogs. The recent emergence of multidrug-resistant S. pseudintermedius isolates, in particular methicillin-resistant strains (MRSP) is a threat to small animal health and highlights the need for antimicrobial resistance surveillance to detect trends and potentially perform timeous interventions. We systematically reviewed 202 published articles to investigate temporal changes in antimicrobial resistance in clinical and commensal S. pseudintermedius isolated from dogs in 27 countries between 1980 and 2013. Resistance to the most common antimicrobials tested for in published studies and important for the treatment of staphylococcal infections in dogs were assessed separately for methicillin resistant (MRSP) and methicillin susceptible (MSSP) isolates. Stratified by MSSP and MRSP, no significant increases in antimicrobial resistance were observed over time, except for the penicillinase-labile penicillins (penicillin and ampicillin) among MSSP. However, in recent years, a few studies have reported higher-level of resistance to amikacin, gentamicin and enrofloxacin amongst MSSP. The review highlights inconsistencies between studies as a result of several factors, for example the use of different antimicrobial susceptibility testing methods and interpretation criteria. We recommend that data on susceptibility in important companion animal pathogens are collected and presented in a more harmonized way to allow more precise comparison of susceptibility patterns between studies. One way to accomplish this would be through systematic surveillance either at the country-level or at a larger scale across countries e.g. EU level. PMID:24613081

  18. Antimicrobial activity of prulifloxacin in comparison with other fluoroquinolones against community-acquired urinary and respiratory pathogens isolated in Greece.

    PubMed

    Karageorgopoulos, D E; Maraki, S; Vatopoulos, A C; Samonis, G; Schito, G C; Falagas, M E

    2013-11-01

    Prulifloxacin, the prodrug of ulifloxacin, is a broad-spectrum fluoroquinolone rather recently introduced in certain European countries. We compared the antimicrobial potency of ulifloxacin with that of other fluoroquinolones against common urinary and respiratory bacterial pathogens. The microbial isolates were prospectively collected between January 2007 and May 2008 from patients with community-acquired infections in Greece. Minimum inhibitory concentrations (MICs) were determined for ciprofloxacin, levofloxacin, moxifloxacin (for respiratory isolates only), and ulifloxacin using the E-test method. The binary logarithms of the MICs [log2(MICs)] were compared by using the Wilcoxon signed-ranks test. A total of 409 isolates were studied. Ulifloxacin had the lowest geometric mean MIC for the 161 Escherichia coli, 59 Proteus mirabilis, and 22 Staphylococcus saprophyticus urinary isolates, the second lowest geometric mean MIC for the 38 Streptococcus pyogenes respiratory isolates (after moxifloxacin), and the third lowest geometric mean MIC for the 114 Haemophilus influenzae and the 15 Moraxella catarrhalis respiratory isolates (after ciprofloxacin and moxifloxacin). Compared with levofloxacin, ulifloxacin had lower log2(MICs) against E. coli (p < 0.001), P. mirabilis (p < 0.001), S. saprophyticus (p < 0.001), and S. pyogenes (p < 0.001). Compared with ciprofloxacin, ulifloxacin had lower log2(MICs) against P. mirabilis (p < 0.001), S. saprophyticus (p = 0.008), and S. pyogenes (p < 0.001), but higher log2(MICs) against H. influenzae (p < 0.001) and M. catarrhalis (p = 0.001). In comparison with other clinically relevant fluoroquinolones, ulifloxacin had the most potent antimicrobial activity against the community-acquired urinary isolates studied and very good activity against the respiratory isolates. PMID:23686506

  19. Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib

    PubMed Central

    Kwak, Eunice L.; Sordella, Raffaella; Bell, Daphne W.; Godin-Heymann, Nadia; Okimoto, Ross A.; Brannigan, Brian W.; Harris, Patricia L.; Driscoll, David R.; Fidias, Panos; Lynch, Thomas J.; Rabindran, Sridhar K.; McGinnis, John P.; Wissner, Allan; Sharma, Sreenath V.; Isselbacher, Kurt J.; Settleman, Jeffrey; Haber, Daniel A.

    2005-01-01

    Non-small cell lung cancers (NSCLCs) with activating mutations in the kinase domain of the epidermal growth factor receptor (EGFR) demonstrate dramatic, but transient, responses to the reversible tyrosine kinase inhibitors gefitinib (Iressa) and erlotinib (Tarceva). Some recurrent tumors have a common secondary mutation in the EGFR kinase domain, T790M, conferring drug resistance, but in other cases the mechanism underlying acquired resistance is unknown. In studying multiple sites of recurrent NSCLCs, we detected T790M in only a small percentage of tumor cells. To identify additional mechanisms of acquired resistance to gefitinib, we used NSCLC cells harboring an activating EGFR mutation to generate multiple resistant clones in vitro. These drug-resistant cells demonstrate continued dependence on EGFR and ERBB2 signaling for their viability and have not acquired secondary EGFR mutations. However, they display increased internalization of ligand-activated EGFR, consistent with altered receptor trafficking. Although gefitinib-resistant clones are cross-resistant to related anilinoquinazolines, they demonstrate sensitivity to a class of irreversible inhibitors of EGFR. These inhibitors also show effective inhibition of signaling by T790M-mutant EGFR and killing of NSCLC cells with the T790M mutation. Both mechanisms of gefitinib resistance are therefore circumvented by irreversible tyrosine kinase inhibitors. Our findings suggest that one of these, HKI-272, may prove highly effective in the treatment of EGFR-mutant NSCLCs, including tumors that have become resistant to gefitinib or erlotinib. PMID:15897464

  20. A between-Species Comparison of Antimicrobial Resistance in Enterobacteria in Fecal Flora

    PubMed Central

    Österblad, Monica; Hakanen, Antti; Manninen, Raija; Leistevuo, Tiina; Peltonen, Reijo; Meurman, Olli; Huovinen, Pentti; Kotilainen, Pirkko

    2000-01-01

    Enterobacteria in fecal flora are often reported to be highly resistant. Escherichia coli is the main species; resistance data on other species are rare. To assess the effect of the host's environment, antimicrobial resistance was determined in fecal species of the family Enterobacteriaceae from three populations: healthy people (HP)(n = 125) with no exposure to antimicrobials for 3 months preceding sampling, university hospital patients (UP) (n = 159) from wards where the antibiotic use was 112 defined daily doses (DDD)/bed/month, and geriatric long-term patients (LTP) (n = 74) who used 1.8 DDD/bed/month. The mean length of hospital stay was 5 days for the UP and 22 months for the LTP. The isolates were identified to at least genus level, and MICs of 16 antimicrobials were determined. From the university hospital, resistance data on clinical Enterobacteriaceae isolates were also collected. Resistance data for on average two different isolates per sample (range, 1 to 5) were analyzed: 471 E. coli isolates and 261 other Enterobacteriaceae spp. Resistance was mainly found among E. coli; even in HP, 18% of E. coli isolates were resistant to two or more antimicrobial groups, with MIC patterns indicative of transferable resistance. Other fecal enterobacteria were generally susceptible, with little typically transferable multiresistance. Clinical Klebsiella and Enterobacter isolates were significantly more resistant than fecal isolates. The resistance patterns at both hospitals mirrored the patterns of antibiotic use, but LTP E. coli isolates were significantly more resistant than those from UP. Conditions permitting an efficient spread may have been more important in sustaining high resistance levels in the LTP. E. coli was the main carrier of antimicrobial resistance in fecal flora; resistance in other species was rare in the absence of antimicrobial selection. PMID:10817696

  1. Prevalence, Antimicrobial Resistance, and Genotypic Characterization of Vancomycin-Resistant Enterococci in Meat Preparations.

    PubMed

    Guerrero-Ramos, Emilia; Molina-González, Diana; Blanco-Morán, Sonia; Igrejas, Gilberto; Poeta, Patrícia; Alonso-Calleja, Carlos; Capita, Rosa

    2016-05-01

    A total of 160 samples of poultry (80), pork (40), and beef (40) preparations (red sausages, white sausages, hamburgers, meatballs, nuggets, minced meat, escalope, and crepes) were tested in northwestern Spain to determine the prevalence of vancomycin-resistant enterococci (VRE). VRE were detected in 38 (23.8%) samples (37.5% of poultry, 15.0% of pork, and 5.0% of beef samples). One strain per food sample was further characterized. Isolates were identified as Enterococcus faecium (14 strains), E. durans (10), E. hirae (7), E. gallinarum (5), and E. casseliflavus-E. flavescens (2). All strains showed resistance or intermediate susceptibility to three or more antimicrobials of clinical significance, in addition to vancomycin. High rates of resistance or intermediate susceptibility were observed for teicoplanin (81.6% of isolates), chloramphenicol (81.6%), erythromycin (100%), quinupristin-dalfopristin (89.5%), and ciprofloxacin (81.6%). A moderate rate of resistance or intermediate susceptibility emerged for ampicillin (34.2%) and tetracycline (36.8%). Genes encoding antimicrobial resistance and virulence were studied by PCR. The vanA, vanB, vanC-1, and vanC-2/3 genes were identified in 27, 1, 5, and 2 isolates, respectively. Other resistance genes or transposon sequences found were tet(L), tet(M), Tn5397 (tetracycline), erm(A), erm(B) (erythromycin), vat(D), and vat(E) (quinupristin-dalfopristin). Most isolates were free of virulence determinants (agg, hyl, and efaAfm genes were detected in one, one, and five strains, respectively). Strains were classified as not biofilm producers (crystal violet assay; 4 isolates) or weak biofilm producers (34 isolates). Cluster analysis (EcoRI ribotyping) suggested a strong genetic relationship among isolates from different types of meat preparations, animal species, and retail outlets. Meat preparations might play a role in the spread through the food chain of VRE with several resistance and virulence genes. PMID:27296421

  2. Serotype and Antimicrobial Resistance Patterns of Salmonella Isolates from Commercial Birds and Poultry Environment in Mississippi

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 S...

  3. Roles of Lipooligosaccharide and Capsular Polysaccharide in Antimicrobial Resistance and Natural Transformation of Campylobacter jejuni

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objectives: To investigate the roles of surface polysaccharides, such as capsular polysaccharide (CPS) and lipooligosaccharide (LOS), in modulating natural transformation and antimicrobial resistance in Campylobacter jejuni. Methods: A series of C. jejuni mutants, which are defective in either CPS ...

  4. Antimicrobial resistance and virulence of Enterococcus faecalis isolated from retail food

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although enterococci are considered opportunistic nosocomial pathogens, their contribution to food-borne illnesses via dissemination through retail food remains undefined. In this study, prevalence and association of antimicrobial resistance and virulence factors of 80 Enterococcus faecalis isolate...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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....

  6. Antimicrobial resistance in campylobacter jejuni and campylobacter coli isolated from chicken carcass rinstates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: The development of antimicrobial resistance in Campylobacter species, particularly C. jejuni and C. coli, is of public health concern. Methods: Campylobacter isolates recovered from spent chicken carcass rinsates collected at federally inspected slaughter establishments were submitted t...

  7. Effect of commercial broiler processing on prevalence and antimicrobial resistance of salmonellae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: Broiler processing includes interventions specifically designed to lessen bacterial contamination of carcasses. Purpose: This study was undertaken to determine the prevalence, serotype and antimicrobial resistance profiles of Salmonella on broiler carcasses collected from commercial pr...

  8. Erlotinib is a viable treatment for tumors with acquired resistance to cetuximab.

    PubMed

    Brand, Toni M; Dunn, Emily F; Iida, Mari; Myers, Rebecca A; Kostopoulos, Kellie T; Li, Chunrong; Peet, Chimera R; Wheeler, Deric L

    2011-09-01

    The epidermal growth factor receptor (EGFR) is a ubiquitously expressed receptor tyrosine kinase (RTK) and is recognized as a key mediator of tumorigenesis in many human tumors. Currently there are five EGFR inhibitors used in oncology, two monoclonal antibodies (panitumumab, and cetuximab) and three tyrosine kinase inhibitors (erlotinib, gefitinib, and lapatinib). Both strategies of EGFR inhibition have demonstrated clinical successes, however many tumors remain non-responsive or acquire resistance during therapy. To explore potential molecular mechanisms of acquired resistance to cetuximab we previously established a series of cetuximab-resistant clones by chronically exposing the NCI-H226 NSCLC cell line to escalating doses of cetuximab. Cetuximab-resistant clones exhibited a dramatic increase in steady-state expression of EGFR, HER2, and HER3 receptors as well as increased signaling through the MAPK and AKT pathways. RNAi studies demonstrated dependence of cetuximab-resistant clones on the EGFR signaling network. These findings prompted investigation on whether or not cells with acquired resistance to cetuximab would be sensitive to the EGFR targeted TKI erlotinib. In vitro, erlotinib was able to decrease signaling through the EGFR axis, decrease cellular proliferation, and induce apoptosis. To determine if erlotinib could have therapeutic benefit in vivo, we established cetuximab-resistant NCI-H226 mouse xenografts, and subsequently treated them with erlotinib. Mice harboring cetuximab-resistant tumors treated with erlotinib exhibited either a tumor regression or growth delay as compared to vehicle controls. Analysis of the erlotinib treated tumors demonstrated a decrease in cell proliferation and increase rates of apoptosis. The work presented herein suggests that 1) cells with acquired resistance to cetuximab maintain their dependence on EGFR and 2) tumors developing resistance to cetuximab can benefit from subsequent treatment with erlotinib, providing

  9. Antimicrobial Resistance in Non-Typhoidal Salmonella from Humans, Retail Meats and Food Animals: 2002-2007

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background. The National Antimicrobial Resistance Monitor System (NARMS) tracks antimicrobial susceptibility in enteric bacteria from humans, retail meats and food animals. We analyzed changes in ceftiofur resistance (TioR), nalidixic acid resistance (NalR) and multidrug resistance (MDR-AmpC, define...

  10. Clinical Use of Colistin Induces Cross-Resistance to Host Antimicrobials in Acinetobacter baumannii

    PubMed Central

    Napier, Brooke A.; Burd, Eileen M.; Satola, Sarah W.; Cagle, Stephanie M.; Ray, Susan M.; McGann, Patrick; Pohl, Jan; Lesho, Emil P.; Weiss, David S.

    2013-01-01

    ABSTRACT The alarming rise in antibiotic resistance has led to an increase in patient mortality and health care costs. This problem is compounded by the absence of new antibiotics close to regulatory approval. Acinetobacter baumannii is a human pathogen that causes infections primarily in patients in intensive care units (ICUs) and is highly antibiotic resistant. Colistin is one of the last-line antibiotics for treating A. baumannii infections; however, colistin-resistant strains are becoming increasingly common. This cationic antibiotic attacks negatively charged bacterial membranes in a manner similar to that seen with cationic antimicrobials of the innate immune system. We therefore set out to determine if the increasing use of colistin, and emergence of colistin-resistant strains, is concomitant with the generation of cross-resistance to host cationic antimicrobials. We found that there is indeed a positive correlation between resistance to colistin and resistance to the host antimicrobials LL-37 and lysozyme among clinical isolates. Importantly, isolates obtained before and after treatment of individual patients demonstrated that colistin use correlated with increased resistance to cationic host antimicrobials. These data reveal the overlooked risk of inducing cross-resistance to host antimicrobials when treating patients with colistin as a last-line antibiotic. PMID:23695834

  11. Endemic carbapenem-resistant Pseudomonas aeruginosa with acquired metallo-beta-lactamase determinants in European hospital.

    PubMed

    Lagatolla, Cristina; Tonin, Enrico A; Monti-Bragadin, Carlo; Dolzani, Lucilla; Gombac, Francesca; Bearzi, Claudia; Edalucci, Elisabetta; Gionechetti, Fabrizia; Rossolini, Gian Maria

    2004-03-01

    Acquired metallo-beta-lactamases (MBLs) can confer broad-spectrum beta-lactam resistance (including carbapenems) not reversible by conventional beta-lactamase inhibitors and are emerging resistance determinants of remarkable clinical importance. In 2001, multidrug-resistant Pseudomonas aeruginosa carrying bla(VIM) MBL genes were found to be widespread (approximately 20% of all P. aeruginosa isolates and 70% of the carbapenem-resistant isolates) at Trieste University Hospital. Clonal diversity and heterogeneity of resistance determinants (either bla(VIM-1)-like or bla(VIM-2)-like) were detected among MBL producers. This evidence is the first that acquired MBLs can rapidly emerge and establish a condition of endemicity in certain epidemiologic settings. PMID:15109432

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

    PubMed Central

    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. PMID:24860606

  13. Inhibition of mitochondrial glutaminase activity reverses acquired erlotinib resistance in non-small cell lung cancer

    PubMed Central

    Xie, Caifeng; Jin, Jiangbo; Bao, Xujie; Zhan, Wei-Hua; Han, Tian-Yu; Gan, Mingxi; Zhang, Chengfu; Wang, Jianbin

    2016-01-01

    The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib has been approved based on the clinical benefit in non-small cell lung cancer (NSCLC) patients over the past decade. Unfortunately, cancer cells become resistant to this agent via various mechanisms, and this limits the improvement in patient outcomes. Thus, it is urgent to develop novel agents to overcome erlotinib resistance. Here, we propose a novel strategy to overcome acquired erlotinib resistance in NSCLC by inhibiting glutaminase activity. Compound 968, an inhibitor of the glutaminase C (GAC), when combined with erlotinib potently inhibited the cell proliferation of erlotinib-resistant NSCLC cells HCC827ER and NCI-H1975. The combination of compound 968 and erlotinib not only decreased GAC and EGFR protein expression but also inhibited GAC activity in HCC827ER cells. The growth of erlotinib-resistant cells was glutamine-dependent as proved by GAC gene knocked down and rescue experiment. More importantly, compound 968 combined with erlotinib down-regulated the glutamine and glycolysis metabolism in erlotinib-resistant cells. Taken together, our study provides a valuable approach to overcome acquired erlotinib resistance by blocking glutamine metabolism and suggests that combination of EGFR-TKI and GAC inhibitor maybe a potential treatment strategy for acquired erlotinib-resistant NSCLC. PMID:26575584

  14. The human microbiome as a reservoir of antimicrobial resistance.

    PubMed

    Penders, John; Stobberingh, Ellen E; Savelkoul, Paul H M; Wolffs, Petra F G

    2013-01-01

    The gut microbiota is amongst the most densely populated microbial ecosystem on earth. While the microbiome exerts numerous health beneficial functions, the high density of micro-organisms within this ecosystem also facilitates horizontal transfer of antimicrobial resistance (AMR) genes to potential pathogenic bacteria. Over the past decades antibiotic susceptibility testing of specific indicator bacteria from the microbiome, such as Escherichia coli, has been the method of choice in most studies. These studies have greatly enlarged our understanding on the prevalence and distribution of AMR and associated risk factors. Recent studies using (functional) metagenomics, however, highlighted the unappreciated diversity of AMR genes in the human microbiome and identified genes that had not been described previously. Next to metagenomics, more targeted approaches such as polymerase chain reaction for detection and quantification of AMR genes within a population are promising, in particular for large-scale epidemiological screening. Here we present an overview of the indigenous microbiota as a reservoir of AMR genes, the current knowledge on this "resistome" and the recent and upcoming advances in the molecular diagnostic approaches to unravel this reservoir. PMID:23616784

  15. The human microbiome as a reservoir of antimicrobial resistance

    PubMed Central

    Penders, John; Stobberingh, Ellen E.; Savelkoul, Paul H. M.; Wolffs, Petra F. G.

    2013-01-01

    The gut microbiota is amongst the most densely populated microbial ecosystem on earth. While the microbiome exerts numerous health beneficial functions, the high density of micro-organisms within this ecosystem also facilitates horizontal transfer of antimicrobial resistance (AMR) genes to potential pathogenic bacteria. Over the past decades antibiotic susceptibility testing of specific indicator bacteria from the microbiome, such as Escherichia coli, has been the method of choice in most studies. These studies have greatly enlarged our understanding on the prevalence and distribution of AMR and associated risk factors. Recent studies using (functional) metagenomics, however, highlighted the unappreciated diversity of AMR genes in the human microbiome and identified genes that had not been described previously. Next to metagenomics, more targeted approaches such as polymerase chain reaction for detection and quantification of AMR genes within a population are promising, in particular for large-scale epidemiological screening. Here we present an overview of the indigenous microbiota as a reservoir of AMR genes, the current knowledge on this “resistome” and the recent and upcoming advances in the molecular diagnostic approaches to unravel this reservoir. PMID:23616784

  16. Antimicrobial treatment of nosocomial meticillin-resistant Staphylococcus aureus (MRSA) pneumonia: current and future options.

    PubMed

    Welte, Tobias; Pletz, Mathias W

    2010-11-01

    Meticillin-resistant Staphylococcus aureus (MRSA) is a frequent cause of nosocomial pneumonia. Inadequate or inappropriate antimicrobial therapy, often caused by antimicrobial resistance, is associated with increased mortality for these infections. Agents currently recommended for the treatment of MRSA pneumonia include vancomycin and linezolid in the USA, and vancomycin, linezolid, teicoplanin and quinupristin/dalfopristin in Europe. Antimicrobials such as tigecycline and daptomycin, although approved for the treatment of some MRSA infections, have not demonstrated efficacy equivalent to the approved agents for MRSA pneumonia. Further agents lack data from randomised controlled trials (e.g. fosfomycin, fusidic acid or rifampicin in combination with vancomycin). Antimicrobial agents that have recently been approved or are being investigated as treatments for MRSA infections include the lipoglycopeptides telavancin (approved for the treatment of complicated skin and skin-structure infections in the USA and Canada), dalbavancin and oritavancin, the cephalosporins ceftobiprole and ceftaroline, and the dihydrofolate reductase inhibitor iclaprim. To be an effective treatment for MRSA pneumonia, antimicrobial agents must have activity against antimicrobial-resistant S. aureus, penetrate well into the lung, have a low potential for resistance development and have a good safety profile. Here, the available data for current and potential future MRSA pneumonia antimicrobials are reviewed and discussed. PMID:20724119

  17. Molecular Characterization and Antimicrobial Resistance Profile of Methicillin-Resistant Staphylococcus aureus in Retail Chicken.

    PubMed

    Sallam, Khalid Ibrahim; Abd-Elghany, Samir Mohammed; Elhadidy, Mohamed; Tamura, Tomohiro

    2015-10-01

    The emergence of livestock-associated methicillin-resistant Staphylococcus aureus (MRSA) in food-producing animals is of increasing interest, raising questions about the presence of MRSA in food of animal origin and potential sources of transmission to humans via the food chain. In this study, the prevalence, molecular characterization, virulence factors, and antimicrobial susceptibility patterns of MRSA isolates from 200 retail raw chicken samples in Egypt were determined. MRSA was detected by positive amplification of the mecA gene in 38% (76 of 200) of chicken samples analyzed. This represents a potential public health threat in Egypt, as this contamination rate seems to be the highest among other studies reported worldwide. Furthermore, genes encoding α-hemolysin (hla) and staphylococcal enterotoxins (sea, seb, and sec) were detected in all of the 288 MRSA isolates. Nonetheless, none of the strains tested carried tst, the gene encoding toxic shock syndrome toxin 1. Antimicrobial resistance of MRSA isolates was most frequently detected against penicillin (93.4%), ampicillin (88.9%), and cloxacillin (83.3%). These results suggest that retail chicken might be a significant potential source for transmission of multidrug-resistant and toxigenic S. aureus in Egypt. This underlines the need for stricter hygienic measures in chicken production in Egypt to minimize the risk of transmission of these strains to consumers. To the best of our knowledge, this is the first study that reports the isolation and molecular characterization of MRSA in retail chicken samples in Egypt. PMID:26408138

  18. Antimicrobial resistance and molecular analysis of methicillin-resistant Staphylococcus aureus collected in a Spanish hospital.

    PubMed

    Hernández-Porto, Miriam; Lecuona, María; Aguirre-Jaime, Armando; Castro, Beatriz; Delgado, Teresa; Cuervo, Milagros; Pedroso, Yanet; Arias, Ángeles

    2015-04-01

    Clonal distribution of methicillin-resistant Staphylococcus aureus (MRSA) in hospitals may differ according to the geographic location and time period. Knowledge of MRSA clonal epidemiology in hospital settings involves much more than the study of healthcare-associated MRSA (HA-MRSA) clones. In recent years, investigators have documented the introduction of both community-associated MRSA (CA-MRSA) and livestock-associated MRSA (LA-MRSA) clones, the emergence of clones carrying Staphylococcal cassette chromosome mec (SCCmec) XI, and the genetic diversity among sporadic MRSA isolates. The allocation of certain antibiotypes to dominant MRSA clones in an institution allows their use as phenotypic markers for a preliminary search for new clones, early detection of clonal shift, and as a guide for better empirical therapy, infection control, and treatment within a particular institution. For these reasons, we identified 938 strains detected in a System of Universal Active Surveillance of MRSA in clinical samples during the period 2009-2010, obtaining the clonal distribution of MRSA at the Hospital Universitario de Canarias (Tenerife, Spain) and the relationship between antimicrobial susceptibility and three major clones present. The antibiotypes that best defined the ST5-MRSA-IV (Pediatric) clone showed resistance to tobramycin and susceptibility to clindamycin, erythromycin, gentamicin, rifampin, trimethoprim-sulfamethoxazole, vancomycin, quinupristin/dalfopristin, and linezolid, whereas the ST22-MRSA-IV clone (EMRSA-15) showed susceptibility to these antibiotics, and finally, the ST36-MRSA-II clone (EMRSA-16) was resistant to clindamycin, erythromycin, and tobramycin and susceptible to the remaining antimicrobials. Similar observations would allow the early detection of changes in clonal epidemiology by analysis of antimicrobial susceptibility of the isolates within a single institution. PMID:25365597

  19. Whole-Genome Sequencing Analysis Accurately Predicts Antimicrobial Resistance Phenotypes in Campylobacter spp.

    PubMed

    Zhao, S; Tyson, G H; Chen, Y; Li, C; Mukherjee, S; Young, S; Lam, C; Folster, J P; Whichard, J M; McDermott, P F

    2016-01-01

    The objectives of this study were to identify antimicrobial resistance genotypes for Campylobacter and to evaluate the correlation between resistance phenotypes and genotypes using in vitro antimicrobial susceptibility testing and whole-genome sequencing (WGS). A total of 114 Campylobacter species isolates (82 C. coli and 32 C. jejuni) obtained from 2000 to 2013 from humans, retail meats, and cecal samples from food production animals in the United States as part of the National Antimicrobial Resistance Monitoring System were selected for study. Resistance phenotypes were determined using broth microdilution of nine antimicrobials. Genomic DNA was sequenced using the Illumina MiSeq platform, and resistance genotypes were identified using assembled WGS sequences through blastx analysis. Eighteen resistance genes, including tet(O), blaOXA-61, catA, lnu(C), aph(2″)-Ib, aph(2″)-Ic, aph(2')-If, aph(2″)-Ig, aph(2″)-Ih, aac(6')-Ie-aph(2″)-Ia, aac(6')-Ie-aph(2″)-If, aac(6')-Im, aadE, sat4, ant(6'), aad9, aph(3')-Ic, and aph(3')-IIIa, and mutations in two housekeeping genes (gyrA and 23S rRNA) were identified. There was a high degree of correlation between phenotypic resistance to a given drug and the presence of one or more corresponding resistance genes. Phenotypic and genotypic correlation was 100% for tetracycline, ciprofloxacin/nalidixic acid, and erythromycin, and correlations ranged from 95.4% to 98.7% for gentamicin, azithromycin, clindamycin, and telithromycin. All isolates were susceptible to florfenicol, and no genes associated with florfenicol resistance were detected. There was a strong correlation (99.2%) between resistance genotypes and phenotypes, suggesting that WGS is a reliable indicator of resistance to the nine antimicrobial agents assayed in this study. WGS has the potential to be a powerful tool for antimicrobial resistance surveillance programs. PMID:26519386

  20. Whole-Genome Sequencing for Detecting Antimicrobial Resistance in Nontyphoidal Salmonella.

    PubMed

    McDermott, Patrick F; Tyson, Gregory H; Kabera, Claudine; Chen, Yuansha; Li, Cong; Folster, Jason P; Ayers, Sherry L; Lam, Claudia; Tate, Heather P; Zhao, Shaohua

    2016-09-01

    Laboratory-based in vitro antimicrobial susceptibility testing is the foundation for guiding anti-infective therapy and monitoring antimicrobial resistance trends. We used whole-genome sequencing (WGS) technology to identify known antimicrobial resistance determinants among strains of nontyphoidal Salmonella and correlated these with susceptibility phenotypes to evaluate the utility of WGS for antimicrobial resistance surveillance. Six hundred forty Salmonella of 43 different serotypes were selected from among retail meat and human clinical isolates that were tested for susceptibility to 14 antimicrobials using broth microdilution. The MIC for each drug was used to categorize isolates as susceptible or resistant based on Clinical and Laboratory Standards Institute clinical breakpoints or National Antimicrobial Resistance Monitoring System (NARMS) consensus interpretive criteria. Each isolate was subjected to whole-genome shotgun sequencing, and resistance genes were identified from assembled sequences. A total of 65 unique resistance genes, plus mutations in two structural resistance loci, were identified. There were more unique resistance genes (n = 59) in the 104 human isolates than in the 536 retail meat isolates (n = 36). Overall, resistance genotypes and phenotypes correlated in 99.0% of cases. Correlations approached 100% for most classes of antibiotics but were lower for aminoglycosides and beta-lactams. We report the first finding of extended-spectrum β-lactamases (ESBLs) (blaCTX-M1 and blaSHV2a) in retail meat isolates of Salmonella in the United States. Whole-genome sequencing is an effective tool for predicting antibiotic resistance in nontyphoidal Salmonella, although the use of more appropriate surveillance breakpoints and increased knowledge of new resistance alleles will further improve correlations. PMID:27381390

  1. Incidence of antimicrobial-resistance genes and integrons in antibiotic-resistant bacteria isolated from eels and aquaculture ponds.

    PubMed

    Lin, Mao; Wu, Xiaomei; Yan, Qingpi; Ma, Ying; Huang, Lixing; Qin, Yingxue; Xu, Xiaojin

    2016-07-01

    The overuse of antimicrobials in aquaculture has promoted the selection of antimicrobial-resistant bacteria. Here we investigated the abundance of antimicrobial-resistance genes and integrons in 108 strains of antibiotic-resistant bacteria isolated from eels and aquaculture ponds in China. Conventional PCR was implemented to examine common antibiotic-resistance genes, integrons, and their gene cassette arrays. The results showed that the antibiotic-resistance genes blaTEM, tetC, sulI, aadA, floR, and qnrB were detected at high percentages, as were a number of other resistance genes. Class I integrons were present in 79.63% of the strains, and 10 out of 108 isolates carried class II integrons. Class III integrons were not detected. Three strains carried both class I and class II integrons, and 73.26% of the class I integron-positive isolates contained the qacEΔ1/sul1 gene. Fourteen types of integron cassette arrays were found among class I integron-positive isolates. A new array, dfrB4-catB3-blaOXA-10-aadA1, was discovered in this study. The gene cassette array dfrA12-orfF-aadA2 was the most widely distributed. In summary, 23 different gene cassettes encoding resistance to 8 classes of antibiotics were identified in the class I integrons, and the main cassettes contained genes encoding resistance to aminoglycosides (aad) and trimethoprim (dfr). All class II integron-positive strains had only a single gene cassette array, viz. dfrA1-catB2-sat2-aadA1. High levels of antimicrobial-resistance genes and integrons in eels and auqauculture ponds suggest that the overuse of antimicrobials should be strictly controlled and that the levels of bacterial antimicrobial-resistance genes in aquaculture should be monitored. PMID:27409235

  2. Acquired resistance to 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin) in glioblastoma cells

    PubMed Central

    Gaspar, Nathalie; Sharp, Swee Y; Pacey, Simon; Jones, Chris; Walton, Michael; Vassal, Gilles; Eccles, Suzanne; Pearson, Andrew; Workman, Paul

    2009-01-01

    HSP90 inhibitors, such as 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin) which is currently in phase II/III clinical trials, are promising new anticancer agents. Here, we explored acquired resistance to HSP90 inhibitors in glioblastoma, a primary brain tumor with poor prognosis. Glioblastoma cells were exposed continuously to increased 17-AAG concentrations. Four 17-AAG-resistant glioblastoma cell lines were generated. High resistance levels with resistance indices (RI=resistant line IC50/parental line IC50) of 20-137 were obtained rapidly (2-8 weeks). After cessation of 17-AAG exposure, RI decreased and then stabilised. Cross-resistance was found with other ansamycin benzoquinones but not with the structurally unrelated HSP90 inhibitors, radicicol, the purine BIIB021 and the resorcinylic pyrazole/isoxazole amide compounds VER-49009, VER-50589, and NVP-AUY922. An inverse correlation between NQO1 expression/activity and 17-AAG IC50 was observed in the resistant lines. The NQO1 inhibitor ES936 abrogated the differential effects of 17-AAG sensitivity between the parental and resistant lines. NQO1 mRNA levels and NQO1 DNA polymorphism analysis indicated different underlying mechanisms: reduced expression and selection of the inactive NQO1*2 polymorphism. Decreased NQO1 expression was also observed in a melanoma line with acquired resistance to 17-AAG. No resistance was generated with VER-50589 and NVP-AUY922. In conclusion, low NQO1 activity is a likely mechanism of acquired resistance to 17-AAG in glioblastoma, melanoma and possibly other tumor types. Such resistance can be overcome with novel HSP90 inhibitors. PMID:19244114

  3. Antimicrobial resistant Escherichia coli isolates in cattle and house sparrows on two Czech dairy farms.

    PubMed

    Dolejská, M; Senk, D; Cízek, A; Rybaríková, J; Sychra, O; Literák, I

    2008-12-01

    Rectal smears of calves, cows and young bulls, as well as cloacal smears of house sparrows (Passer domesticus), from farms at the villages of Sumice and Troskotovice, Czech Republic, were examined for E. coli resistant to 12 antimicrobials. The resistant isolates were tested for antimicrobial-resistance genes and integrons. Totals of 40% (n=183), 3% (n=95), 0% (n=33), and 9% (n=54) of Escherichia coli isolates from calves, cows, young bulls and house sparrows, respectively, were antimicrobial resistant. The following genes were identified in cattle E. coli isolates: tetA, tetB (isolates resistant to tetracycline), bla(TEM) (beta-lactams), strA, aadA (streptomycin), sul1, sul2 (sulphonamides), and cat, floR (chloramphenicol). Seven of 16 antimicrobial-resistant calf isolates from the Sumice farm possessed class 1 integrons with the aadA1 gene cassette integrated, 1 kb in size. On the Troskotovice farm, eight of 57 antimicrobial-resistant calf isolates possessed class 1 integrons. Integrons of 1.5kb with the dhfr1- aadA1 gene cassette were found in four isolates, followed by a 1kb integron with the aadA1 gene found in three isolates, and a 1.7kb integron with the dhfr17-aadA5 gene cassette and the phenotype ASSuTSxtNaCipCCfG. The prevalence of resistant E. coli in calves compared to adult cattle was much higher and probably was influenced by oral antimicrobial usage in calves, feeding with milk and colostrum from treated cows, as well as mechanisms unrelated to antimicrobial drug selection. Although house sparrows lived together with the cattle and came into contact with cattle waste on the farm, they were not infected by resistant E. coli isolates with the same characteristics as those found in cattle. PMID:18471838

  4. Prevalence and Antimicrobial Resistance in Escherichia coli from Food Animals in Lagos, Nigeria.

    PubMed

    Adenipekun, Eyitayo O; Jackson, Charlene R; Oluwadun, Afolabi; Iwalokun, Bamidele A; Frye, Jonathan G; Barrett, John B; Hiott, Lari M; Woodley, Tiffanie A

    2015-06-01

    Foodborne bacteria are often associated with human infections; these infections can become more complicated to treat if the bacteria are also resistant to antimicrobials. In this study, prevalence, antimicrobial resistance, and genetic relatedness of Escherichia coli among food producing animals from Lagos, Nigeria, was investigated. From December 2012 to June 2013, E. coli were isolated from fecal samples of healthy cattle, chicken, and swine. Antimicrobial susceptibility testing against 22 antimicrobials was performed using broth microdilution with the Sensititre™ system. Clonal types were determined by pulsed-field gel electrophoresis (PFGE). From the analysis, 211/238 (88.7%), 170/210 (81%), and 136/152 (89.5%) samples from cattle, chicken, and swine, respectively, were positive for E. coli. A subset of those isolates (n=211) selected based on β-lactamase production was chosen for further study. Overall, E. coli exhibited the highest resistance to tetracycline (124/211; 58.8%), trimethoprim/sulfamethoxazole (84/211; 39.8%), and ampicillin (72/211; 34.1%). Approximately 40% of the isolates were pan-susceptible, and none of the isolates were resistant to amikacin, cefepime, ceftazidime, ertapenem, meropenem, or tigecycline. Among the resistant isolates, 28 different resistance patterns were observed; 26 of those were characterized as multi-drug resistant (MDR; resistance to ≥2 antimicrobials). One isolate was resistant to 13 different antimicrobials representing five different antimicrobial classes. Using PFGE, MDR E. coli were genetically diverse and overall did not group based on source; identical PFGE patterns were detected among isolates from different sources. These results suggest that isolates cannot be attributed to specific sources, and some may be present across all of the sources. Results from this study indicate that food-producing animals in Nigeria are a reservoir of MDR E. coli that may be transferred to humans via the food chain. PMID

  5. Diversity of Plasmids and Antimicrobial Resistance Genes in Multidrug-Resistant Escherichia coli Isolated from Healthy Companion Animals.

    PubMed

    Jackson, C R; Davis, J A; Frye, J G; Barrett, J B; Hiott, L M

    2015-09-01

    The presence and transfer of antimicrobial resistance genes from commensal bacteria in companion animals to more pathogenic bacteria may contribute to dissemination of antimicrobial resistance. The purpose of this study was to determine antimicrobial resistance gene content and the presence of genetic elements in antimicrobial resistant Escherichia coli from healthy companion animals. In our previous study, from May to August, 2007, healthy companion animals (155 dogs and 121 cats) from three veterinary clinics in the Athens, GA, USA area were sampled and multidrug-resistant E. coli (n = 36; MDR, resistance to ≥ 2 antimicrobial classes) were obtained. Of the 25 different plasmid replicon types tested by PCR, at least one plasmid replicon type was detected in 94% (34/36) of the MDR E. coli; four isolates contained as many as five different plasmid replicons. Nine replicon types (FIA, FIB, FII, I2, A/C, U, P, I1 and HI2) were identified with FIB, FII, I2 as the most common pattern. The presence of class I integrons (intI) was detected in 61% (22/36) of the isolates with eight isolates containing aminoglycoside- and/or trimethoprim-resistance genes in the variable cassette region of intI. Microarray analysis of a subset of the MDR E. coli (n = 9) identified the presence of genes conferring resistance to aminoglycosides (aac, aad, aph and strA/B), β-lactams (ampC, cmy, tem and vim), chloramphenicol (cat), sulfonamides (sulI and sulII), tetracycline [tet(A), tet(B), tet(C), tet(D) and regulator, tetR] and trimethoprim (dfrA). Antimicrobial resistance to eight antimicrobials (ampicillin, cefoxitin, ceftiofur, amoxicillin/clavulanic acid, streptomycin, gentamicin, sulfisoxazole and trimethoprim-sulfamethoxazole) and five plasmid replicons (FIA, FIB, FII, I1 and I2) were transferred via conjugation. The presence of antimicrobial resistance genes, intI and transferable plasmid replicons indicate that E. coli from companion animals may play an important role in the

  6. Imaging the urokinase plasminongen activator receptor in preclinical breast cancer models of acquired drug resistance.

    PubMed

    LeBeau, Aaron M; Sevillano, Natalia; King, Mandy L; Duriseti, Sai; Murphy, Stephanie T; Craik, Charles S; Murphy, Laura L; VanBrocklin, Henry F

    2014-01-01

    Subtype-targeted therapies can have a dramatic impact on improving the quality and quantity of life for women suffering from breast cancer. Despite an initial therapeutic response, cancer recurrence and acquired drug-resistance are commonplace. Non-invasive imaging probes that identify drug-resistant lesions are urgently needed to aid in the development of novel drugs and the effective utilization of established therapies for breast cancer. The protease receptor urokinase plasminogen activator receptor (uPAR) is a target that can be exploited for non-invasive imaging. The expression of uPAR has been associated with phenotypically aggressive breast cancer and acquired drug-resistance. Acquired drug-resistance was modeled in cell lines from two different breast cancer subtypes, the uPAR negative luminal A subtype and the uPAR positive triple negative subtype cell line MDA-MB-231. MCF-7 cells, cultured to be resistant to tamoxifen (MCF-7 TamR), were found to significantly over-express uPAR compared to the parental cell line. uPAR expression was maintained when resistance was modeled in triple-negative breast cancer by generating doxorubicin and paclitaxel resistant MDA-MB-231 cells (MDA-MB-231 DoxR and MDA-MB-231 TaxR). Using the antagonistic uPAR antibody 2G10, uPAR was imaged in vivo by near-infrared (NIR) optical imaging and (111)In-single photon emission computed tomography (SPECT). Tumor uptake of the (111)In-SPECT probe was high in the three drug-resistant xenografts (> 46 %ID/g) and minimal in uPAR negative xenografts at 72 hours post-injection. This preclinical study demonstrates that uPAR can be targeted for imaging breast cancer models of acquired resistance leading to potential clinical applications. PMID:24505235

  7. Antimicrobial Drug Use and Methicillin-resistant Staphylococcus aureus, Aberdeen, 1996–2000

    PubMed Central

    Monnet, Dominique L.; López-Lozano, José María; Beyaert, Arielle; Camacho, Máximo; Wilson, Rachel; Stuart, David; Gould, Ian M.

    2004-01-01

    Similar to many hospitals worldwide, Aberdeen Royal Infirmary has had an outbreak of methicillin-resistant Staphylococcus aureus (MRSA). In this setting, the outbreak is attributable to two major clones. The relationships between antimicrobial use and MRSA prevalence were analyzed by time-series analysis. From June 1997 to December 2000, dynamic, temporal relationships were found between monthly %MRSA and previous %MRSA, macrolide use, third-generation cephalosporin use, and fluoroquinolone use. This study suggests that use of antimicrobial drugs to which the MRSA outbreak strains are resistant may be an important factor in perpetuating the outbreak. Moreover, this study confirmed the ecologic effect of antimicrobial drug use (i.e., current antimicrobial use) may have an effect on resistance in future patients. Although these results may not be generalized to other hospitals, they suggest new directions for control of MRSA, which has thus far proved difficult and expensive. PMID:15496245

  8. Densities and antimicrobial resistance of Escherichia coli isolated from marine waters and beach sands.

    PubMed

    Andrade, Vanessa da Costa; Zampieri, Bruna Del Busso; Ballesteros, Eliete Rodrigues; Pinto, Aline Bartelochi; de Oliveira, Ana Julia Fernandes Cardoso

    2015-06-01

    Bacterial resistance is a rising problem all over the world. Many studies have showed that beach sands can contain higher concentration of microorganisms and represent a risk to public health. This paper aims to evaluate the densities and resistance to antimicrobials of Escherichia coli strains, isolated from seawater and samples. The hypothesis is that microorganisms show higher densities in contaminated beach sands and more antimicrobial resistance than the water column. Density, distribution, and antimicrobial resistance of bacteria E. coli were evaluate in seawater and sands from two recreational beaches with different levels of pollution. At the beach with higher degree of pollution (Gonzaguinha), water samples presented the highest densities of E. coli; however, higher frequency of resistant strains was observe in wet sand (71.9 %). Resistance to a larger number of antimicrobial groups was observe in water (betalactamics, aminoglycosides, macrolides, rifampicins, and tetracyclines) and sand (betagalactamics and aminoglycosids). In water samples, highest frequencies of resistance were obtain against ampicilin (22.5 %), streptomycin (15.0 %), and rifampicin (15.0 %), while in sand, the highest frequencies were observe in relation to ampicilin (36.25 %) and streptomycin (23.52 %). At the less polluted beach, Ilha Porchat, highest densities of E. coli and higher frequency of resistance were obtain in wet and dry sand (53.7 and 53.8 %, respectively) compared to water (50 %). Antimicrobial resistance in strains isolated from water and sand only occurred against betalactamics (ampicilin and amoxicilin plus clavulanic acid). The frequency and variability of bacterial resistance to antimicrobials in marine recreational waters and sands were related to the degree of fecal contamination in this environment. These results show that water and sands from beaches with a high index of fecal contamination of human origin may be potential sources of contamination by pathogens

  9. Pilot Screening to Determine Antimicrobial Synergies in a Multidrug-Resistant Bacterial Strain Library.

    PubMed

    Kim, Si-Hyun; Park, Chulmin; Chun, Hye-Sun; Lee, Dong-Gun; Choi, Jae-Ki; Lee, Hyo-Jin; Cho, Sung-Yeon; Park, Sun Hee; Choi, Su-Mi; Choi, Jung-Hyun; Yoo, Jin-Hong

    2016-07-01

    With the rise in multidrug-resistant (MDR) bacterial infections, there has been increasing interest in combinations of ≥2 antimicrobial agents with synergistic effects. We established an MDR bacterial strain library to screen for in vitro antimicrobial synergy by using a broth microdilution checkerboard method and high-throughput luciferase-based bacterial cell viability assay. In total, 39 MDR bacterial strains, including 23 carbapenem-resistant gram-negative bacteria, 9 vancomycin-intermediate Staphylococcus aureus, and 7 vancomycin-resistant Enterococcus faecalis, were used to screen for potential antimicrobial synergies. Synergies were more frequently identified with combinations of imipenem plus trimethoprim-sulfamethoxazole for carbapenem-resistant Acinetobacter baumannii in the library. To verify this finding, we tested 34 A. baumannii clinical isolates resistant to both imipenem and trimethoprim-sulfamethoxazole by the checkerboard method. The imipenem plus trimethoprim-sulfamethoxazole combination showed synergy in the treatment of 21 (62%) of the clinical isolates. The results indicate that pilot screening for antimicrobial synergy in the MDR bacterial strain library could be valuable in the selection of combination therapeutic regimens to treat MDR bacterial infections. Further studies are warranted to determine whether this screening system can be useful to screen for the combined effects of conventional antimicrobials and new-generation antimicrobials or nonantimicrobials. PMID:26974861

  10. Pilot Screening to Determine Antimicrobial Synergies in a Multidrug-Resistant Bacterial Strain Library

    PubMed Central

    Kim, Si-Hyun; Park, Chulmin; Chun, Hye-Sun; Choi, Jae-Ki; Lee, Hyo-Jin; Cho, Sung-Yeon; Park, Sun Hee; Choi, Su-Mi; Choi, Jung-Hyun; Yoo, Jin-Hong

    2016-01-01

    With the rise in multidrug-resistant (MDR) bacterial infections, there has been increasing interest in combinations of ≥2 antimicrobial agents with synergistic effects. We established an MDR bacterial strain library to screen for in vitro antimicrobial synergy by using a broth microdilution checkerboard method and high-throughput luciferase-based bacterial cell viability assay. In total, 39 MDR bacterial strains, including 23 carbapenem-resistant gram-negative bacteria, 9 vancomycin-intermediate Staphylococcus aureus, and 7 vancomycin-resistant Enterococcus faecalis, were used to screen for potential antimicrobial synergies. Synergies were more frequently identified with combinations of imipenem plus trimethoprim–sulfamethoxazole for carbapenem-resistant Acinetobacter baumannii in the library. To verify this finding, we tested 34 A. baumannii clinical isolates resistant to both imipenem and trimethoprim–sulfamethoxazole by the checkerboard method. The imipenem plus trimethoprim–sulfamethoxazole combination showed synergy in the treatment of 21 (62%) of the clinical isolates. The results indicate that pilot screening for antimicrobial synergy in the MDR bacterial strain library could be valuable in the selection of combination therapeutic regimens to treat MDR bacterial infections. Further studies are warranted to determine whether this screening system can be useful to screen for the combined effects of conventional antimicrobials and new-generation antimicrobials or nonantimicrobials. PMID:26974861

  11. Heavy metals in liquid pig manure in light of bacterial antimicrobial resistance

    SciTech Connect

    Hoelzel, Christina S.; Mueller, Christa; Harms, Katrin S.; Mikolajewski, Sabine; Schaefer, Stefanie; Schwaiger, Karin; Bauer, Johann

    2012-02-15

    Heavy metals are regularly found in liquid pig manure, and might interact with bacterial antimicrobial resistance. Concentrations of heavy metals were determined by atomic spectroscopic methods in 305 pig manure samples and were connected to the phenotypic resistance of Escherichia coli (n=613) against 29 antimicrobial drugs. Concentrations of heavy metals (/kg dry matter) were 0.08-5.30 mg cadmium, 1.1-32.0 mg chrome, 22.4-3387.6 mg copper, <2.0-26.7 mg lead, <0.01-0.11 mg mercury, 3.1-97.3 mg nickel and 93.0-8239.0 mg zinc. Associated with the detection of copper and zinc, resistance rates against {beta}-lactams were significantly elevated. By contrast, the presence of mercury was significantly associated with low antimicrobial resistance rates of Escherichia coli against {beta}-lactams, aminoglycosides and other antibiotics. Effects of subinhibitory concentrations of mercury on bacterial resistance against penicillins, cephalosporins, aminoglycosides and doxycycline were also demonstrated in a laboratory trial. Antimicrobial resistance in the porcine microflora might be increased by copper and zinc. By contrast, the occurrence of mercury in the environment might, due to co-toxicity, act counter-selective against antimicrobial resistant strains.

  12. Antibiotic Stewardship Initiatives as Part of the UK 5-Year Antimicrobial Resistance Strategy

    PubMed Central

    Johnson, Alan P.; Ashiru-Oredope, Diane; Beech, Elizabeth

    2015-01-01

    Antibiotic use is a major driver for the emergence and spread of antibiotic resistance. Antimicrobial stewardship programmes aim to improve antibiotic prescribing with the objectives of optimizing clinical outcomes while at the same time minimizing unintended consequences such as adverse effects and the selection of antibiotic resistance. In 2013, a five-year national strategy for tackling antimicrobial resistance was published in the UK. The overarching goal of the strategy is to slow the development and spread of resistance and to this end it has three strategic aims, namely to improve knowledge and understanding of resistance, to conserve and steward the effectiveness of existing treatments and to stimulate the development of new antibiotics, diagnostics and novel therapies. This article reviews the antimicrobial stewardship activities included in the strategy and describes their implementation and evaluation. PMID:27025636

  13. Insights into novel antimicrobial compounds and antibiotic resistance genes from soil metagenomes

    PubMed Central

    de Castro, Alinne P.; Fernandes, Gabriel da R.; Franco, Octávio L.

    2014-01-01

    In recent years a major worldwide problem has arisen with regard to infectious diseases caused by resistant bacteria. Resistant pathogens are related to high mortality and also to enormous healthcare costs. In this field, cultured microorganisms have been commonly focused in attempts to isolate antibiotic resistance genes or to identify antimicrobial compounds. Although this strategy has been successful in many cases, most of the microbial diversity and related antimicrobial molecules have been completely lost. As an alternative, metagenomics has been used as a reliable approach to reveal the prospective reservoir of antimicrobial compounds and antibiotic resistance genes in the uncultured microbial community that inhabits a number of environments. In this context, this review will focus on resistance genes as well as on novel antibiotics revealed by a metagenomics approach from the soil environment. Biotechnology prospects are also discussed, opening new frontiers for antibiotic development. PMID:25278933

  14. Mechanisms of antimicrobial resistance and genetic relatedness among enterococci isolated from dogs and cats in the United States

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aims: In this study, mechanisms of antimicrobial resistance and genetic relatedness among resistant enterococci from dogs and cats in the United States were determined. Methods and Results: Enterococci resistant to chloramphenicol, ciprofloxacin, erythromycin, gentamicin, kanamycin, streptomycin,...

  15. Antimicrobial resistance in faecal Escherichia coli isolates from farmed red deer and wild small mammals. Detection of a multiresistant E. coli producing extended-spectrum beta-lactamase.

    PubMed

    Alonso, C A; González-Barrio, D; Tenorio, Carmen; Ruiz-Fons, F; Torres, C

    2016-04-01

    Eighty-nine Escherichia coli isolates recovered from faeces of red deer and small mammals, cohabiting the same area, were analyzed to determine the prevalence and mechanisms of antimicrobial resistance and molecular typing. Antimicrobial resistance was detected in 6.7% of isolates, with resistances to tetracycline and quinolones being the most common. An E. coli strain carrying blaCTX-M-1 as well as other antibiotic resistant genes included in an unusual class 1 integron (Intl1-dfrA16-blaPSE-1-aadA2-cmlA1-aadA1-qacH-IS440-sul3-orf1-mef(B)Δ-IS26) was isolated from a deer. The blaCTX-M-1 gene was transferred by conjugation and transconjugants also acquired an IncN plasmid. This strain was typed as ST224, which seems to be well adapted to both clinical and environmental settings. The phylogenetic distribution of the 89 strains varied depending on the animal host. This work reveals low antimicrobial resistance levels among faecal E. coli from wild mammals, which reflects a lower selective pressure affecting these bacteria, compared to livestock. However, it is remarkable the detection of a multi-resistant ESBL-E. coli with an integron carrying clinically relevant antibiotic-resistance genes, which can contribute to the dissemination of resistance determinants among different ecosystems. PMID:27012919

  16. Synergistic Antimicrobial Activity of Camellia sinensis and Juglans regia against Multidrug-Resistant Bacteria

    PubMed Central

    Farooqui, Amber; Khan, Adnan; Borghetto, Ilaria; Kazmi, Shahana U.; Rubino, Salvatore; Paglietti, Bianca

    2015-01-01

    Synergistic combinations of antimicrobial agents with different mechanisms of action have been introduced as more successful strategies to combat infections involving multidrug resistant (MDR) bacteria. In this study, we investigated synergistic antimicrobial activity of Camellia sinensis and Juglans regia which are commonly used plants with different antimicrobial agents. Antimicrobial susceptibility of 350 Gram-positive and Gram-negative strains belonging to 10 different bacterial species, was tested against Camellia sinensis and Juglans regia extracts. Minimum inhibitory concentrations (MICs) were determined by agar dilution and microbroth dilution assays. Plant extracts were tested for synergistic antimicrobial activity with different antimicrobial agents by checkerboard titration, Etest/agar incorporation assays, and time kill kinetics. Extract treated and untreated bacteria were subjected to transmission electron microscopy to see the effect on bacterial cell morphology. Camellia sinensis extract showed higher antibacterial activity against MDR S. Typhi, alone and in combination with nalidixic acid, than to susceptible isolates.” We further explore anti-staphylococcal activity of Juglans regia that lead to the changes in bacterial cell morphology indicating the cell wall of Gram-positive bacteria as possible target of action. The synergistic combination of Juglans regia and oxacillin reverted oxacillin resistance of methicillin resistant Staphylococcus aureus (MRSA) strains in vitro. This study provides novel information about antimicrobial and synergistic activity of Camellia sinensis and Juglans regia against MDR pathogens PMID:25719410

  17. Diversity of antimicrobial resistance and virulence genes in methicillin-resistant non-Staphylococcus aureus staphylococci from veal calves.

    PubMed

    Argudín, M Angeles; Vanderhaeghen, Wannes; Butaye, Patrick

    2015-04-01

    In this study we determined whether methicillin-resistant non-Staphylococcus aureus (MRNAS) from veal calves may be a potential reservoir of antimicrobial-resistance and virulence genes. Fifty-eight MRNAS were studied by means of DNA-microarray and PCR for detection of antimicrobial resistance and virulence genes. The isolates carried a variety of antimicrobial-resistance genes [aacA-aphD, aadD, aph3, aadE, sat, spc, ampA, erm(A), erm(B), erm(C), erm(F), erm(T), lnu(A), msr(A)-msr(B), vga(A), mph(C), tet(K), tet(M), tet(L), cat, fexA, dfrA, dfrD, dfrG, dfrK, cfr, fusB, fosB, qacA, qacC, merA-merB]. Some isolates carried resistance genes without showing the corresponding resistance phenotype. Most MRNAS carried typical S. aureus virulence factors like proteases (sspP) and enterotoxins (seg) genes. Most Staphylococcus epidermidis isolates carried the arginine catabolic element, and nearly 40% of the Staphylococcus sciuri isolates carried leukocidins, and/or fibronectin-binding protein genes. MRNAS were highly multi-resistant and represent an important reservoir of antimicrobial resistance and virulence genes. PMID:25637268

  18. Analysis of antimicrobial resistance genes detected in multidrug-resistant salmonella enterica serovar typhimurium isolated from food animals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The development of multi drug resistance (MDR) in foodborne pathogens such as Salmonella enterica is a concern for both animal and human health. MDR Salmonella enterica serovar Typhimurium is the most prevalent penta-resistant serovar isolated from animals as part of the National Antimicrobial Resis...

  19. Mechanisms of β-lactam antimicrobial resistance and epidemiology of major community- and healthcare-associated multidrug-resistant bacteria.

    PubMed

    Tang, Sarah S; Apisarnthanarak, Anucha; Hsu, Li Yang

    2014-11-30

    Alexander Fleming's discovery of penicillin heralded an age of antibiotic development and healthcare advances that are premised on the ability to prevent and treat bacterial infections both safely and effectively. The resultant evolution of antimicrobial resistant mechanisms and spread of bacteria bearing these genetic determinants of resistance are acknowledged to be one of the major public health challenges globally, and threatens to unravel the gains of the past decades. We describe the major mechanisms of resistance to β-lactam antibiotics - the most widely used and effective antibiotics currently - in both Gram-positive and Gram-negative bacteria, and also briefly detail the existing and emergent pharmacological strategies to overcome such resistance. The global epidemiology of the four major types of bacteria that are responsible for the bulk of antimicrobial-resistant infections in the healthcare setting - methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, Enterobactericeae, and Acinetobacter baumannii - are also briefly described. PMID:25134490

  20. Antimicrobial resistance in commensal Escherichia coli isolated from animals at slaughter

    PubMed Central

    Wasyl, Dariusz; Hoszowski, Andrzej; Zając, Magdalena; Szulowski, Krzysztof

    2013-01-01

    Monitoring of antimicrobial resistance in commensal Escherichia coli (N = 3430) isolated from slaughtered broilers, laying hens, turkeys, swine, and cattle in Poland has been run between 2009 and 2012. Based on minimal inhibitory concentration (MIC) microbiological resistance to each of 14 tested antimicrobials was found reaching the highest values for tetracycline (43.3%), ampicillin (42.3%), and ciprofloxacin (39.0%) whereas the lowest for colistin (0.9%), cephalosporins (3.6 ÷ 3.8%), and florfenicol (3.8%). The highest prevalence of resistance was noted in broiler and turkey isolates, whereas it was rare in cattle. That finding along with resistance patterns specific to isolation source might reflect antimicrobial consumption, usage preferences or management practices in specific animals. Regression analysis has identified changes in prevalence of microbiological resistance and shifts of MIC values. Critically important fluoroquinolone resistance was worrisome in poultry isolates, but did not change over the study period. The difference (4.7%) between resistance to ciprofloxacin and nalidixic acid indicated the scale of plasmid-mediated quinolone resistance. Cephalosporin resistance were found in less than 3.8% of the isolates but an increasing trends were observed in poultry and MIC shift in the ones from cattle. Gentamycin resistance was also increasing in E. coli of turkey and cattle origin although prevalence of streptomycin resistance in laying hens decreased considerably. Simultaneously, decreasing MIC for phenicols observed in cattle and layers isolates as well as tetracycline values in E. coli from laying hens prove that antimicrobial resistance is multivariable phenomenon not only directly related to antimicrobial usage. Further studies should elucidate the scope of commensal E. coli as reservoirs of resistance genes, their spread and possible threats for human and animal health. PMID:23935596

  1. Surveillance of antimicrobial resistance in Lebanese hospitals: retrospective nationwide compiled data.

    PubMed

    Chamoun, Kamal; Farah, Maya; Araj, Georges; Daoud, Ziad; Moghnieh, Rima; Salameh, Pascale; Saade, Danielle; Mokhbat, Jacques; Abboud, Emme; Hamze, Monzer; Abboud, Edmond; Jisr, Tamima; Haddad, Antoine; Feghali, Rita; Azar, Nadim; El-Zaatari, Mohammad; Chedid, Marwan; Haddad, Christian; Zouain Dib Nehme, Mireille; Barakat, Angelique; Husni, Rola

    2016-05-01

    Antimicrobial resistance is closely linked to antimicrobial use and is a growing concern worldwide. Antimicrobial resistance increases healthcare costs substantially in many countries, including Lebanon. National data from Lebanon have, in the most part, been limited to a few academic hospitals. The Lebanese Society of Infectious Diseases conducted a retrospective study to better describe the antimicrobial susceptibility patterns of bacterial isolates in Lebanon. Data were based on records retrieved from the bacteriology laboratories of 16 different Lebanese hospitals between January 2011 and December 2013. The susceptibility results of a total 20684 Gram-positive and 55594 Gram-negative bacteria were analyzed. The prevalence rate of methicillin-resistant Staphylococcus aureus was 27.6% and of vancomycin-resistant Enterococcus spp was 1%. Streptococcus pneumoniae had susceptibilities of 46% to oxacillin, 63% to erythromycin, and 98% to levofloxacin. Streptococcus pyogenes had susceptibilities of 94% to erythromycin and 95% to clindamycin. The mean ampicillin susceptibility of Haemophilus influenzae, Salmonella spp, and Shigella spp isolates was 79%, 81.3%, and 62.2%, respectively. The extended-spectrum beta-lactamase production rate for Escherichia coli was 32.3% and for Klebsiella spp was 29.2%. Acinetobacter spp showed high resistance to most antimicrobials, with low resistance to colistin (17.1%). Pseudomonas spp susceptibilities to piperacillin-tazobactam and imipenem were lower than 80% (79.7% and 72.8%, respectively). This study provides population-specific data that are valuable in guiding antimicrobial use in Lebanon and neighbouring countries and will help in the establishment of a surveillance system for antimicrobial resistance following the implementation of a nationwide standardization of laboratory methods and data entry. PMID:26996458

  2. Antimicrobial resistance of Escherichia coli isolates from canine urinary tract infections.

    PubMed

    Chang, Shao-Kuang; Lo, Dan-Yuan; Wei, Hen-Wei; Kuo, Hung-Chih

    2015-01-01

    This study determined the antimicrobial resistance profiles of Escherichia coli isolates from dogs with a presumptive diagnosis of urinary tract infection (UTI). Urine samples from 201 dogs with UTI diagnosed through clinical examination and urinalysis were processed for isolation of Escherichia coli. Colonies from pure cultures were identified by biochemical reactions (n=114) and were tested for susceptibility to 18 antimicrobials. The two most frequent antimicrobials showing resistance in Urinary E. coli isolates were oxytetracycline and ampicillin. Among the resistant isolates, 17 resistance patterns were observed, with 12 patterns involving multidrug resistance (MDR). Of the 69 tetracycline-resistant E. coli isolates, tet(B) was the predominant resistance determinant and was detected in 50.9% of the isolates, whereas the remaining 25.5% isolates carried the tet(A) determinant. Most ampicillin and/or amoxicillin-resistant E. coli isolates carried blaTEM-1 genes. Class 1 integrons were prevalent (28.9%) and contained previously described gene cassettes that are implicated primarily in resistance to aminoglycosides and trimethoprim (dfrA1, dfrA17-aadA5). Of the 44 quinolone-resistant E. coli isolates, 38 were resistant to nalidixic acid, and 6 were resistant to nalidixic acid, ciprofloxacin and enrofloxacin. Chromosomal point mutations were found in the GyrA (Ser83Leu) and ParC (Ser80Ile) genes. Furthermore, the aminoglycoside resistance gene aacC2, the chloramphenicol resistant gene cmlA and the florfenicol resistant gene floR were also identified. This study revealed an alarming rate of antimicrobial resistance among E. coli isolates from dogs with UTIs. PMID:25720807

  3. Antimicrobial resistance of Escherichia coli isolates from canine urinary tract infections.

    PubMed

    Chang, Shao-Kuang; Lo, Dan-Yuan; Wei, Hen-Wei; Kuo, Hung-Chih

    2014-10-28

    This study determined the antimicrobial resistance profiles of Escherichia coli isolates from dogs with a presumptive diagnosis of urinary tract infection (UTI). Urine samples from 201 dogs with UTI diagnosed through clinical examination and urinalysis were processed for isolation of Escherichia coli. Colonies from pure cultures were identified by biochemical reactions (n=114) and were tested for susceptibility to 18 antimicrobials. The two most frequent antimicrobials showing resistance in Urinary E. coli isolates were oxytetracycline and ampicillin. Among the resistant isolates, 17 resistance patterns were observed, with 12 patterns involving multidrug resistance (MDR). Of the 69 tetracycline-resistant E. coli isolates, tet(B) was the predominant resistance determinant and was detected in 50.9% of the isolates, whereas the remaining 25.5% isolates carried the tet(A) determinant. Most ampicillin and/or amoxicillin-resistant E. coli isolates carried blaTEM-1 genes. Class 1 integrons were prevalent (28.9%) and contained previously described gene cassettes that are implicated primarily in resistance to aminoglycosides and trimethoprim (dfrA1, dfrA17-aadA5). Of the 44 quinolone-resistant E. coli isolates, 38 were resistant to nalidixic acid, and 6 were resistant to nalidixic acid, ciprofloxacin and enrofloxacin. Chromosomal point mutations were found in the GyrA (Ser83Leu) and ParC (Ser80Ile) genes. Furthermore, the aminoglycoside resistance gene aacC2, the chloramphenicol resistant gene cmlA and the florfenicol resistant gene floR were also identified. This study revealed an alarming rate of antimicrobial resistance among E. coli isolates from dogs with UTIs. PMID:25354649

  4. Antimicrobial resistance of Escherichia coli isolates from canine urinary tract infections

    PubMed Central

    CHANG, Shao-Kuang; LO, Dan-Yuan; WEI, Hen-Wei; KUO, Hung-Chih

    2014-01-01

    This study determined the antimicrobial resistance profiles of Escherichia coli isolates from dogs with a presumptive diagnosis of urinary tract infection (UTI). Urine samples from 201 dogs with UTI diagnosed through clinical examination and urinalysis were processed for isolation of Escherichia coli. Colonies from pure cultures were identified by biochemical reactions (n=114) and were tested for susceptibility to 18 antimicrobials. The two most frequent antimicrobials showing resistance in Urinary E. coli isolates were oxytetracycline and ampicillin. Among the resistant isolates, 17 resistance patterns were observed, with 12 patterns involving multidrug resistance (MDR). Of the 69 tetracycline-resistant E. coli isolates, tet(B) was the predominant resistance determinant and was detected in 50.9% of the isolates, whereas the remaining 25.5% isolates carried the tet(A) determinant. Most ampicillin and/or amoxicillin-resistant E. coli isolates carried blaTEM-1 genes. Class 1 integrons were prevalent (28.9%) and contained previously described gene cassettes that are implicated primarily in resistance to aminoglycosides and trimethoprim (dfrA1, dfrA17-aadA5). Of the 44 quinolone-resistant E. coli isolates, 38 were resistant to nalidixic acid, and 6 were resistant to nalidixic acid, ciprofloxacin and enrofloxacin. Chromosomal point mutations were found in the GyrA (Ser83Leu) and ParC (Ser80Ile) genes. Furthermore, the aminoglycoside resistance gene aacC2, the chloramphenicol resistant gene cmlA and the florfenicol resistant gene floR were also identified. This study revealed an alarming rate of antimicrobial resistance among E. coli isolates from dogs with UTIs. PMID:25720807

  5. Development of a DNA microarray to detect antimicrobial resistance genes identified in the national center for biotechnology information database

    Technology Transfer Automated Retrieval System (TEKTRAN)

    High density genotyping techniques are needed for investigating antimicrobial resistance especially in the case of multi-drug resistant (MDR) isolates. To achieve this all antimicrobial resistance genes in the NCBI Genbank database were identified by key word searches of sequence annotations and the...

  6. Aminoglycoside Resistance: The Emergence of Acquired 16S Ribosomal RNA Methyltransferases.

    PubMed

    Doi, Yohei; Wachino, Jun-Ichi; Arakawa, Yoshichika

    2016-06-01

    Aminoglycoside-producing Actinobacteria are known to protect themselves from their own aminoglycoside metabolites by producing 16S ribosomal RNA methyltransferase (16S-RMTase), which prevents them from binding to the 16S rRNA targets. Ten acquired 16S-RMTases have been reported from gram-negative pathogens. Most of them posttranscriptionally methylate residue G1405 of 16S rRNA resulting in high-level resistance to gentamicin, tobramycin, amikacin, and plazomicin. Strains that produce 16S-RMTase are frequently multidrug-resistant or even extensively drug-resistant. Although the direct clinical impact of high-level aminoglycoside resistance resulting from production of 16S-RMTase is yet to be determined, ongoing spread of this mechanism will further limit treatment options for multidrug-resistant and extensively drug-resistant gram-negative infections. PMID:27208771

  7. A Convenient Cell Culture Model for CML Acquired Resistance Through BCR-ABL Mutations.

    PubMed

    Wang, Zhiqiang; Chen, WenYong

    2016-01-01

    Tyrosine kinase inhibitors (TKIs) are the effective treatments for chronic myeloid leukemia (CML). However, clinical resistance to TKIs that leads to patient relapse remains a challenge. Acquisition of BCR-ABL mutations is crucial in the resistance but the underlying molecular mechanisms are poorly understood. Here we describe a cell culture model for CML acquired resistance in which blast crisis CML cells undergo initial apoptosis upon treatment with therapeutically effective doses of TKIs, but the cells regrow quickly with development of resistance through BCR-ABL mutations. This model mimics the clinical process of acquisition of BCR-ABL mutations and will be an important tool to dissect molecular mechanisms of CML drug resistance and to explore strategies to overcome resistance. PMID:27581146

  8. Genomic Insights into Intrinsic and Acquired Drug Resistance Mechanisms in Achromobacter xylosoxidans

    PubMed Central

    Hu, Yongfei; Zhu, Yuying; Ma, Yanan; Liu, Fei; Lu, Na; Yang, Xi; Luan, Chunguang; Yi, Yong

    2014-01-01

    Achromobacter xylosoxidans is an opportunistic pathogen known to be resistant to a wide range of antibiotics; however, the knowledge about the drug resistance mechanisms is limited. We used a high-throughput sequencing approach to sequence the genomes of the A. xylosoxidans type strain ATCC 27061 and a clinical isolate, A. xylosoxidans X02736, and then we used different bioinformatics tools to analyze the drug resistance genes in these bacteria. We obtained the complete genome sequence for A. xylosoxidans ATCC 27061 and the draft sequence for X02736. We predicted a total of 50 drug resistance-associated genes in the type strain, including 5 genes for β-lactamases and 17 genes for efflux pump systems; these genes are also conserved among other A. xylosoxidans genomes. In the clinical isolate, except for the conserved resistance genes, we also identified several acquired resistance genes carried by a new transposon embedded in a novel integrative and conjugative element. Our study provides new insights into the intrinsic and acquired drug resistance mechanisms in A. xylosoxidans, which will be helpful for better understanding the physiology of A. xylosoxidans and the evolution of antibiotic resistance in this bacterium. PMID:25487802

  9. The antimicrobial resistance containment and surveillance approach--a public health tool.

    PubMed Central

    Simonsen, Gunnar S.; Tapsall, John W.; Allegranzi, Benedetta; Talbot, Elizabeth A.; Lazzari, Stefano

    2004-01-01

    Antimicrobial drug resistance (AMR) is widely recognized as a global public health threat because it endangers the effectiveness of treatment of infectious diseases. In 2001 WHO issued the Global Strategy for Containment of Antimicrobial Resistance, but it has proved difficult to translate the recommendations of the Global Strategy into effective public health actions. The purpose of the Antimicrobial Resistance Containment and Surveillance (ARCS) approach is to facilitate the formulation of public health programmes and the mobilization of human and financial resources for the containment of AMR. The ARCS approach highlights the fundamental link between rational drug use and containment of AMR. Clinical management of human and animal infections should be improved through better disease control and prevention, high quality diagnostic testing, appropriate treatment regimens and consumer health education. At the same time, systems for supplying antimicrobial drugs should include appropriate regulations, lists of essential drugs, and functional mechanisms for the approval and delivery of drugs. Containment of AMR is defined in the ARCS approach as the continuous application of this package of core interventions. Surveillance of the extent and trends of antimicrobial resistance as well as the supply, selection and use of antimicrobial drugs should be established to monitor the process and outcome of containment of AMR. The ARCS approach is represented in the ARCS diagram (Fig. 2) which provides a simplified, but comprehensive illustration of the complex problem of containment and monitoring of AMR. PMID:15654407

  10. Multiple Antimicrobial Resistance of Escherichia coli Isolated from Chickens in Iran.

    PubMed

    Talebiyan, Reza; Kheradmand, Mehdi; Khamesipour, Faham; Rabiee-Faradonbeh, Mohammad

    2014-01-01

    Antimicrobial agents are used extremely in order to reduce the great losses caused by Escherichia coli infections in poultry industry. In this study, 318 pathogenic Escherichia coli (APEC) strains isolated from commercial broiler flocks with coli-septicemia were examined for antimicrobials of both veterinary and human significance by disc diffusion method. Multiple resistances to antimicrobial agents were observed in all the isolates. Resistance to the antibiotics was as follows: Tylosin (88.68%), Erythromycin (71.70%), Oxytetracycline (43.40%), Sulfadimethoxine-Trimethoprim (39.62%), Enrofloxacin (37.74%), Florfenicol (35.85%), Chlortetracycline (33.96%), Doxycycline (16.98%), Difloxacin (32.08%), Danofloxacin (28.30%), Chloramphenicol (20.75%), Ciprofloxacin (7.55%), and Gentamicin (5.66%). This study showed resistance against the antimicrobial agents that are commonly applied in poultry, although resistance against the antibiotics that are only applied in humans or less frequently used in poultry was significantly low. This study emphasizes on the occurrence of multiple drug resistant E. coli among diseased broiler chickens in Iran. The data revealed the relative risks of using antimicrobials in poultry industry. It also concluded that use of antibiotics must be limited in poultry farms in order to reduce the antibiotic resistances. PMID:25548716

  11. Multiple Antimicrobial Resistance of Escherichia coli Isolated from Chickens in Iran

    PubMed Central

    Talebiyan, Reza; Kheradmand, Mehdi; Khamesipour, Faham; Rabiee-Faradonbeh, Mohammad

    2014-01-01

    Antimicrobial agents are used extremely in order to reduce the great losses caused by Escherichia coli infections in poultry industry. In this study, 318 pathogenic Escherichia coli (APEC) strains isolated from commercial broiler flocks with coli-septicemia were examined for antimicrobials of both veterinary and human significance by disc diffusion method. Multiple resistances to antimicrobial agents were observed in all the isolates. Resistance to the antibiotics was as follows: Tylosin (88.68%), Erythromycin (71.70%), Oxytetracycline (43.40%), Sulfadimethoxine-Trimethoprim (39.62%), Enrofloxacin (37.74%), Florfenicol (35.85%), Chlortetracycline (33.96%), Doxycycline (16.98%), Difloxacin (32.08%), Danofloxacin (28.30%), Chloramphenicol (20.75%), Ciprofloxacin (7.55%), and Gentamicin (5.66%). This study showed resistance against the antimicrobial agents that are commonly applied in poultry, although resistance against the antibiotics that are only applied in humans or less frequently used in poultry was significantly low. This study emphasizes on the occurrence of multiple drug resistant E. coli among diseased broiler chickens in Iran. The data revealed the relative risks of using antimicrobials in poultry industry. It also concluded that use of antibiotics must be limited in poultry farms in order to reduce the antibiotic resistances. PMID:25548716

  12. Antimicrobial resistance in eight US hospitals along the US-Mexico border, 2000-2006.

    PubMed

    Benoit, S R; Ellingson, K D; Waterman, S H; Pearson, M L

    2014-11-01

    Antimicrobial resistance (AR) is a growing problem worldwide and international travel, cross-border migration, and antimicrobial use may contribute to the introduction or emergence of AR. We examined AR rates and trends along the US-Mexico border by analysing microbiology data from eight US hospitals in three states bordering Mexico. Microbiology data were ascertained for the years 2000-2006 and for select healthcare and community pathogens including, three Gram-negative (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae) and three Gram-positive (Staphylococcus aureus, Enterococcus, Streptococcus pneumoniae) pathogens and 10 antimicrobial-pathogen combinations. Resistance was highest in S. aureus (oxacillin resistance 45·7%), P. aeruginosa (quinolone resistance 22·3%), and E. coli (quinolone resistance 15·6%); six (60%) of the 10 antimicrobial-pathogen combinations studied had a significantly increasing trend in resistance over the study period. Potential contributing factors in the hospital and community such as infection control practices and antimicrobial use (prescription and non-prescription) should be explored further in the US-Mexico border region. PMID:24480063

  13. The future of antimicrobial therapy in the era of antibiotic resistance in cystic fibrosis pulmonary infection.

    PubMed

    McCaughey, G; Gilpin, Df; Elborn, Js; Tunney, Michael M

    2013-08-01

    Cystic fibrosis (CF) is characterised by chronic polymicrobial airway infection and inflammation, which is the major cause of morbidity and mortality. Aggressive use of antimicrobials has been fundamental in increasing the life expectancy of CF patients in recent years. However, enhanced culture and non-culture based detection methods have identified bacteria in the CF lung not previously isolated from CF patients by routine diagnostic microbiology Coupled with increasing antimicrobial resistance, the future of antimicrobial therapy in CF respiratory infection remains challenging. New strategies are needed to address these problems and ensure improvements in life expectancy are maintained. Potential future strategies include the use of new antimicrobial agents and formulations currently in clinical trials, alternative methods of selecting appropriate therapeutic regimens, determination of the pathogenicity of species newly associated with CF and the development of new antimicrobials and adjuvants for use in clinical practice. PMID:23964628

  14. Antimicrobial resistance trends among Salmonella isolates obtained from horses in the northeastern United States (2001-2013).

    PubMed

    Cummings, Kevin J; Perkins, Gillian A; Khatibzadeh, Sarah M; Warnick, Lorin D; Aprea, Victor A; Altier, Craig

    2016-05-01

    OBJECTIVE To describe the antimicrobial resistance patterns of Salmonella isolates obtained from horses in the northeastern United States and to identify trends in resistance to select antimicrobials over time. SAMPLE 462 Salmonella isolates from horses. PROCEDURES Retrospective data were collected for all Salmonella isolates obtained from equine specimens that were submitted to the Cornell University Animal Health Diagnostic Center between January 1, 2001, and December 31, 2013. Temporal trends in the prevalence of resistant Salmonella isolates were investigated for each of 13 antimicrobials by use of the Cochran-Armitage trend test. RESULTS The prevalence of resistant isolates varied among antimicrobials and ranged from 0% (imipenem) to 51.5% (chloramphenicol). During the observation period, the prevalence of resistant isolates decreased significantly for amoxicillin-clavulanic acid, ampicillin, cefazolin, cefoxitin, ceftiofur, chloramphenicol, and tetracycline and remained negligible for amikacin and enrofloxacin. Of the 337 isolates for which the susceptibility to all 13 antimicrobials was determined, 138 (40.9%) were pansusceptible and 192 (57.0%) were multidrug resistant (resistant to ≥ 3 antimicrobial classes). The most common serovar isolated was Salmonella Newport, and although the annual prevalence of that serovar decreased significantly over time, that decrease had only a minimal effect on the observed antimicrobial resistance trends. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that current antimicrobial use in horses is not promoting the emergence and dissemination of antimicrobial-resistant Salmonella strains in the region served by the laboratory. PMID:27111018

  15. Evaluation of the Enterococcus faecalis Biofilm-Associated Virulence Factors AhrC and Eep in Rat Foreign Body Osteomyelitis and In Vitro Biofilm-Associated Antimicrobial Resistance

    PubMed Central

    Frank, Kristi L.; Vergidis, Paschalis; Brinkman, Cassandra L.; Greenwood Quaintance, Kerryl E.; Barnes, Aaron M. T.; Mandrekar, Jayawant N.; Schlievert, Patrick M.; Dunny, Gary M.; Patel, Robin

    2015-01-01

    Enterococcus faecalis can cause healthcare-associated biofilm infections, including those of orthopedic devices. Treatment of enterococcal prosthetic joint infection is difficult, in part, due to biofilm-associated antimicrobial resistance. We previously showed that the E. faecalis OG1RF genes ahrC and eep are in vitro biofilm determinants and virulence factors in animal models of endocarditis and catheter-associated urinary tract infection. In this study, we evaluated the role of these genes in a rat acute foreign body osteomyelitis model and in in vitro biofilm-associated antimicrobial resistance. Osteomyelitis was established for one week following the implantation of stainless steel orthopedic wires inoculated with E. faecalis strains OG1RF, ΩahrC, and ∆eep into the proximal tibiae of rats. The median bacterial loads recovered from bones and wires did not differ significantly between the strains at multiple inoculum concentrations. We hypothesize that factors present at the infection site that affect biofilm formation, such as the presence or absence of shear force, may account for the differences in attenuation in the various animal models we have used to study the ΩahrC and ∆eep strains. No differences among the three strains were observed in the planktonic and biofilm antimicrobial susceptibilities to ampicillin, vancomycin, daptomycin, linezolid, and tetracycline. These findings suggest that neither ahrC nor eep directly contribute to E. faecalis biofilm-associated antimicrobial resistance. Notably, the experimental evidence that the biofilm attachment mutant ΩahrC displays biofilm-associated antimicrobial resistance suggests that surface colonization alone is sufficient for E. faecalis cells to acquire the biofilm antimicrobial resistance phenotype. PMID:26076451

  16. Evaluation of the Enterococcus faecalis Biofilm-Associated Virulence Factors AhrC and Eep in Rat Foreign Body Osteomyelitis and In Vitro Biofilm-Associated Antimicrobial Resistance.

    PubMed

    Frank, Kristi L; Vergidis, Paschalis; Brinkman, Cassandra L; Greenwood Quaintance, Kerryl E; Barnes, Aaron M T; Mandrekar, Jayawant N; Schlievert, Patrick M; Dunny, Gary M; Patel, Robin

    2015-01-01

    Enterococcus faecalis can cause healthcare-associated biofilm infections, including those of orthopedic devices. Treatment of enterococcal prosthetic joint infection is difficult, in part, due to biofilm-associated antimicrobial resistance. We previously showed that the E. faecalis OG1RF genes ahrC and eep are in vitro biofilm determinants and virulence factors in animal models of endocarditis and catheter-associated urinary tract infection. In this study, we evaluated the role of these genes in a rat acute foreign body osteomyelitis model and in in vitro biofilm-associated antimicrobial resistance. Osteomyelitis was established for one week following the implantation of stainless steel orthopedic wires inoculated with E. faecalis strains OG1RF, ΩahrC, and ∆eep into the proximal tibiae of rats. The median bacterial loads recovered from bones and wires did not differ significantly between the strains at multiple inoculum concentrations. We hypothesize that factors present at the infection site that affect biofilm formation, such as the presence or absence of shear force, may account for the differences in attenuation in the various animal models we have used to study the ΩahrC and ∆eep strains. No differences among the three strains were observed in the planktonic and biofilm antimicrobial susceptibilities to ampicillin, vancomycin, daptomycin, linezolid, and tetracycline. These findings suggest that neither ahrC nor eep directly contribute to E. faecalis biofilm-associated antimicrobial resistance. Notably, the experimental evidence that the biofilm attachment mutant ΩahrC displays biofilm-associated antimicrobial resistance suggests that surface colonization alone is sufficient for E. faecalis cells to acquire the biofilm antimicrobial resistance phenotype. PMID:26076451

  17. Pharmacokinetic-Pharmacodynamic Model To Evaluate Intramuscular Tetracycline Treatment Protocols To Prevent Antimicrobial Resistance in Pigs

    PubMed Central

    Ahmad, Amais; Græsbøll, Kaare; Christiansen, Lasse Engbo; Toft, Nils; Matthews, Louise

    2014-01-01

    High instances of antimicrobial resistance are linked to both routine and excessive antimicrobial use, but excessive or inappropriate use represents an unnecessary risk. The competitive growth advantages of resistant bacteria may be amplified by the strain dynamics; in particular, the extent to which resistant strains outcompete susceptible strains under antimicrobial pressure may depend not only on the antimicrobial treatment strategies but also on the epidemiological parameters, such as the composition of the bacterial strains in a pig. This study evaluated how variation in the dosing protocol for intramuscular administration of tetracycline and the composition of bacterial strains in a pig affect the level of resistance in the intestine of a pig. Predictions were generated by a mathematical model of competitive growth of Escherichia coli strains in pigs under specified plasma concentration profiles of tetracycline. All dosing regimens result in a clear growth advantage for resistant strains. Short treatment duration was found to be preferable, since it allowed less time for resistant strains to outcompete the susceptible ones. Dosing frequency appeared to be ineffective at reducing the resistance levels. The number of competing strains had no apparent effect on the resistance level during treatment, but possession of fewer strains reduced the time to reach equilibrium after the end of treatment. To sum up, epidemiological parameters may have more profound influence on growth dynamics than dosing regimens and should be considered when designing improved treatment protocols. PMID:25547361

  18. Antimicrobial Resistant E. coli from Retail Chicken Breast and Slaughter Rinsates: NARMS 2002-2005

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: The National Antimicrobial Resistance Monitoring System tracks resistance trends among non-type-specific E. coli from chicken carcasses at slaughter and chicken breast meat at retail. Methods: From 2002-2005, a monthly sampling of chicken breasts from stores in GA, MD, OR and TN yielded ...

  19. Global Antimicrobial Resistance: Where Is the Connection between Animal and Human Public Health?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Since the early 1990's, there has been increasing awareness and concern regarding the development of antimicrobial resistance among bacteria of public and animal health significance. Reports targeting zoonotic bacteria, and in particular Salmonella species, suggest that resistance is trending upwar...

  20. DNA Microarray Detection of Antimicrobial Resistance Genes in Bacteria Co-Cultured from Swine Feces

    Technology Transfer Automated Retrieval System (TEKTRAN)

    One factor leading to the spread of antimicrobial resistance (AR) in bacteria is the horizontal transfer of resistance genes. To study this, a DNA microarray was recently developed to detect these genes. To maximize the capability of this microarray, probes were designed and added to detect all AR g...

  1. Related antimicrobial resistance genes detected in different bacterial species co-isolated from swine fecal samples

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A possible factor leading to the spread of antimicrobial resistance (AR) in bacteria is the horizontal transfer of resistance genes between bacteria in animals or their environment. To investigate this, swine fecal samples were collected on-farm and cultured for Salmonella, Escherichia coli, Campylo...

  2. 76 FR 37356 - 2011 Scientific Meeting of the National Antimicrobial Resistance Monitoring System; Public...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-27

    ... Resistance Monitoring System; Public Meeting; Request for Comments AGENCY: Food and Drug Administration, HHS... Monitoring System.'' The topic to be discussed is animal and retail sampling methods for the National Antimicrobial Resistance Monitoring System (NARMS). Date and Time: The public meeting will be held on July...

  3. Microarray Analysis of Antimicrobial Resistance Genes in Salmonella enterica from Preharvest Poultry Environment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rapid detection of drug resistance profiles in Salmonella can be critical in treatment of salmonellosis. A 70-mer oligonucleotide microarray chip with 775 gene probes was used to detect antimicrobial resistance genes in 34 Salmonella isolates from a turkey production facility. The phenotypic antim...

  4. Genomic Analysis of Antimicrobial Resistant Commensal and Food Borne Pathogens Isolated from Animals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Bacterial Epidemiology and Antimicrobial Resistance Research Unit developed genomics resources to address goals including: detection of AR genes and MDR plasmid genes, development of techniques for pathogen typing and detection. These are to be used to study the epidemiology of resistant bacteri...

  5. Rapid Detection of Antimicrobial Resistance Genes in Salmonella Serovars using DNA Microarray Technology

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Selective pressure resulting from use of antimicrobials by the food animal industry and human health care may be a source for the development of resistance among food borne pathogens, such as Salmonella. Detection of drug resistance mechanisms in Salmonella serovars can be critical when treatment o...

  6. Pharmacokinetic-pharmacodynamic model to evaluate intramuscular tetracycline treatment protocols to prevent antimicrobial resistance in pigs.

    PubMed

    Ahmad, Amais; Græsbøll, Kaare; Christiansen, Lasse Engbo; Toft, Nils; Matthews, Louise; Nielsen, Søren Saxmose

    2015-03-01

    High instances of antimicrobial resistance are linked to both routine and excessive antimicrobial use, but excessive or inappropriate use represents an unnecessary risk. The competitive growth advantages of resistant bacteria may be amplified by the strain dynamics; in particular, the extent to which resistant strains outcompete susceptible strains under antimicrobial pressure may depend not only on the antimicrobial treatment strategies but also on the epidemiological parameters, such as the composition of the bacterial strains in a pig. This study evaluated how variation in the dosing protocol for intramuscular administration of tetracycline and the composition of bacterial strains in a pig affect the level of resistance in the intestine of a pig. Predictions were generated by a mathematical model of competitive growth of Escherichia coli strains in pigs under specified plasma concentration profiles of tetracycline. All dosing regimens result in a clear growth advantage for resistant strains. Short treatment duration was found to be preferable, since it allowed less time for resistant strains to outcompete the susceptible ones. Dosing frequency appeared to be ineffective at reducing the resistance levels. The number of competing strains had no apparent effect on the resistance level during treatment, but possession of fewer strains reduced the time to reach equilibrium after the end of treatment. To sum up, epidemiological parameters may have more profound influence on growth dynamics than dosing regimens and should be considered when designing improved treatment protocols. PMID:25547361

  7. Antimicrobial properties of nanomolecules: potential candidates as antibiotics in the era of multi-drug resistance

    PubMed Central

    Kandi, Venkataramana; Kandi, Sabitha

    2015-01-01

    OBJECTIVES: The emergence of multi-drug resistance among various microbial pathogens has been a cause of serious concern to the medical world, limiting the choice of antibiotics. Considering that it may take decades to synthesize new antimicrobial drugs that combat resistant pathogens, the search for alternatives to conventional antimicrobial agents has begun. METHODS: In his paper we attempted to review the physico-chemical properties of nanoparticles, their modes of action and potential use in medicine and research with special reference to antimicrobial properties. RESULTS: Nanomolecules and nanoparticles have in recent years been extensively studied for their utility not only as antibiotics but also as vehicles to carry antibiotics or other agents such as cancer chemotherapeutics to target sites and limit damage to host cells. CONCLUSION: Nanomolecules were positively evaluated for their antimicrobial activities. Anti-biofilm activities of nanoparticles, utility of nanomaterials as carrier agents of drugs signifies their importance in medicine and research. PMID:25968114

  8. Induced Bacterial Cross-Resistance toward Host Antimicrobial Peptides: A Worrying Phenomenon

    PubMed Central

    Fleitas, Osmel; Franco, Octávio L.

    2016-01-01

    Bacterial resistance to conventional antibiotics has reached alarming levels, threatening to return to the pre-antibiotic era. Therefore, the search for new antimicrobial compounds that overcome the resistance phenomenon has become a priority. Antimicrobial peptides (AMPs) appear as one of the most promising antibiotic medicines. However, in recent years several AMP-resistance mechanisms have been described. Moreover, the AMP-resistance phenomenon has become more complex due to its association with cross-resistance toward AMP effectors of the host innate immune system. In this context, the use of AMPs as a therapeutic option could be potentially hazardous, since bacteria could develop resistance toward our innate immune system. Here, we review the findings of major studies that deal with the AMP cross-resistance phenomenon. PMID:27047486

  9. Kinetics and maintenance of acquired resistance in mice to Listeria monocytogenes.

    PubMed

    Kearns, R J; Hinrichs, D J

    1977-06-01

    In the mouse system, acquired resistance to Listeria monocytogenes can only be demonstrated after immunization with viable microorganisms. A successful state of immunity cannot be elicited with formalin-killed organisms or bacterial cell-derived products. Viable, serologically cross-reactive organisms (not mouse pathogenic) do not induce a state of immunity as measured by acquired resistance. The duration of immunity, once established, is dose independent, and the absolute interval of its existence is not extended by secondary challenge with large numbers of viable organisms. The decline of immunity in actively immunized animals is not altered by antigenic challenge with formalin-killed cells or cell products. This indicates that the cellular requirements for the development of host resistance are similar for induction as well as maintenance. In vitro measurements of cellular immunity by migration inhibition indicate that formalin-killed organisms as well as cell products were recognized by actively sensitized lymphocytes obtained from immune animals. PMID:408273

  10. Incidence of community-acquired methicillin-resistant Staphylococcus aureus carrying Pantone-Valentine leucocidin gene at a referral hospital in United Arab Emirates.

    PubMed

    Dash, Nihar; Panigrahi, Debadatta; Al Zarouni, Mansour; Yassin, Faten; Al-Shamsi, Moza

    2014-04-01

    Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging pathogen in hospitalized patients worldwide. The present study was undertaken to identify CA-MRSA in hospitalized patients in a 350-bed tertiary care hospital in Sharjah, UAE over a 2-year period from January 2011 to December 2012. CA-MRSA was defined based on identification within first 48 h of admission in the hospital. Staphylococcal cassette chromosome (SCC) mec typing of the CA-MRSA isolates was carried out by multiplex polymerase chain reaction (PCR). Detection of PVL and mecA genes was done by PCR using the GenoType(®) MRSA test system (Hain Lifescience). Patient's clinical data and antimicrobial susceptibility pattern of the CA-MRSA isolates were also evaluated. Fifty seven of the 187 MRSA isolates were identified as CA-MRSA. All the CA-MRSA strains in our study belonged to SCCmecIV type and were positive for both PVL and mecA genes. The patients with CA-MRSA infections were young (median age, 32 years) and the majority of infections involved the skin and soft tissue (36%). Antimicrobial susceptibility pattern of the CA-MRSA isolates showed a better susceptibility profile to the non-beta-lactam antimicrobials with the exception of ciprofloxacin having 28% resistance. This study evidently strengthens the recent observation of an increase in CA-MRSA emergence among hospitalized patients in the UAE. PMID:23919760

  11. Data on the phylogenetic typing, integron gene cassette array analysis, multi-drug resistance analysis and correlation between antimicrobial resistance determinants in Klebsiella strains.

    PubMed

    Wu, Hao; Wang, Mingyu; Liu, Yuqing; Wang, Xinhua; Wang, Yunkun; Lu, Jinxing; Xu, Hai

    2016-09-01

    The antimicrobial resistance of Klebsiella species in the poultry industry is becoming a public concern. In support our recent publication "Characterization of antimicrobial resistance in Klebsiella species isolated from chicken broilers" (Wu et al., 2016) [1], multilocus sequence typing (MLST) and gyrA PCR-RFLP assays were conducted to identify the genetic relationships between and phylogenetic groups of the 90 antimicrobial resistant Klebsiella species isolated from a commercial broiler slaughter plant in Shandong, China. In addition, PCR-RFLP was performed to identify different gene cassette arrays in class 1 and 2 integrons, and the correlations between different antimicrobial resistance determinants were analyzed. PMID:27570806

  12. Activation of Alternate Prosurvival Pathways Accounts for Acquired Sunitinib Resistance in U87MG Glioma Xenografts

    PubMed Central

    Lv, Hua; Mazloom, Amin R.; Xu, Huilei; Ma'ayan, Avi; Gallo, James M.

    2012-01-01

    Acquired drug resistance represents a major obstacle to using sunitinib for the treatment of solid tumors. Here, we examined the cellular and molecular alterations in tumors that are associated with acquired brain tumor resistance to sunitinib by using an in vivo model. U87MG tumors obtained from nude mice that received sunitinib (40 mg/kg/day) for 30 days were classified into sunitinib-sensitive and -resistant groups based on tumor volume and underwent targeted gene microarray and protein array analyses. The expression of several angiogenesis-associated genes was significantly modulated in sunitinib-treated tumors compared with those in control tumors (p < 0.05), whereas no significant differences were observed between sunitinib-sensitive and -resistant tumors (p > 0.05). Tumor vasculature based on microvessel density, neurogenin 2 chondroitin sulfate proteoglycan density, and α-smooth muscle actin density was also similar in sunitinib-treatment groups (p > 0.05). The moderate increase in unbound sunitinib tumor-to-plasma area-under-the-curve ratio in sunitinib-resistant mice was accompanied by up-regulated ATP-binding cassette G2 expression in tumor. The most profound difference between the sunitinib-sensitive and -resistant groups was found in the expression of several phosphorylated proteins involved in intracellular signaling. In particular, phospholipase C-γ1 phosphorylation in sunitinib-resistant tumors was up-regulated by 2.6-fold compared with that in sunitinib-sensitive tumors (p < 0.05). In conclusion, acquired sunitinib resistance in U87MG tumors is not associated with revascularization in tumors, but rather with the activation of alternate prosurvival pathways involved in an escape mechanism facilitating tumor growth and possibly insufficient drug uptake in tumor cells caused by an up-regulated membrane efflux transporter. PMID:22869928

  13. Moderate Prevalence of Antimicrobial Resistance in Escherichia coli Isolates from Lettuce, Irrigation Water, and Soil

    PubMed Central

    Holvoet, Kevin; Callens, Benedicte; Dewulf, Jeroen; Uyttendaele, Mieke

    2013-01-01

    Fresh produce is known to carry nonpathogenic epiphytic microorganisms. During agricultural production and harvesting, leafy greens can become contaminated with antibiotic-resistant pathogens or commensals from animal and human sources. As lettuce does not undergo any inactivation or preservation treatment during processing, consumers may be exposed directly to all of the (resistant) bacteria present. In this study, we investigated whether lettuce or its production environment (irrigation water, soil) is able to act as a vector or reservoir of antimicrobial-resistant Escherichia coli. Over a 1-year period, eight lettuce farms were visited multiple times and 738 samples, including lettuce seedlings (leaves and soil), soil, irrigation water, and lettuce leaves were collected. From these samples, 473 isolates of Escherichia coli were obtained and tested for resistance to 14 antimicrobials. Fifty-four isolates (11.4%) were resistant to one or more antimicrobials. The highest resistance rate was observed for ampicillin (7%), followed by cephalothin, amoxicillin-clavulanic acid, tetracycline, trimethoprim, and streptomycin, with resistance rates between 4.4 and 3.6%. No resistance to amikacin, ciprofloxacin, gentamicin, or kanamycin was observed. One isolate was resistant to cefotaxime. Among the multiresistant isolates (n = 37), ampicillin and cephalothin showed the highest resistance rates, at 76 and 52%, respectively. E. coli isolates from lettuce showed higher resistance rates than E. coli isolates obtained from soil or irrigation water samples. When the presence of resistance in E. coli isolates from lettuce production sites and their resistance patterns were compared with the profiles of animal-derived E. coli strains, they were found to be the most comparable with what is found in the cattle reservoir. This may suggest that cattle are a potential reservoir of antimicrobial-resistant E. coli strains in plant primary production. PMID:23974140

  14. Changes of Antimicrobial Resistance among Coagulase-Negative Staphylococci Isolated in 8 Consecutive Years in the First Bethune Hospital

    NASA Astrophysics Data System (ADS)

    Xu, Jiancheng; Yan, Chaoying; Wang, Liqiang; Zhou, Qi

    This study was to investigate the antimicrobial resistance of coagulase-negative Staphylococci isolated in 8 consecutive years in the First Bethune Hospital. Disk diffusion test was used to study the antimicrobial resistance. The data were analyzed by WHONET 5 software according to Clinical and Laboratory Standards Institute (CLSI). Most of 2484 strains of coagulase-negative Staphylococci were collected from blood 925 (37.2%), secretions 652 (26.2%) and urine 323 (13.0%) during the past 8 years. The rates of methicillin-resistant coagulase-negative Staphylococci (MRCNS) were between 79.4% and 81.5% during the past 8 years, respectively. In recent 8 years, the antimicrobial resistance of coagulase-negative Staphylococci had increased. Monitoring the antimicrobial resistance to coagulase-negatives Staphylococci should be strengthened. The change of the antimicrobial resistance should be investigated in order to direct rational drug usage in the clinic and prevent bacterial strain of drug resistance from being transmitted.

  15. Changes of Antimicrobial Resistance among Staphylococcus Aureus Isolated in 8 Consecutive Years in the First Bethune Hospital

    NASA Astrophysics Data System (ADS)

    Xu, Wei; Zhou, Qi; Yang, Chunguang; Yao, Hanxin; Xu, Jiancheng

    This study was to investigate the antimicrobial resistance of Staphylococcus aureus isolated in 8 consecutive years in the First Bethune Hospital. Disk diffusion test was used to study the antimicrobial resistance. The data were analyzed by WHONET 5 software according to Clinical and Laboratory Standards Institute (CLSI). Most of 1469 strains of Staphylococcus aureus were collected from sputum 705 (18.0%), secretions 206 (14.0%), pus 177 (12.0%) during the past 8 years. The rates of methicillin-resistant Staphylococcus aureus (MRSA) were between 50.8% and 83.3% during the past 8 years, respectively. In recent 8 years, the antimicrobial resistance of Staphylococcus aureus had increased. Monitoring the antimicrobial resistance to Staphylococcus aureus should be strengthened. The change of the antimicrobial resistance should be investigated in order to direct rational drug usage in the clinic and prevent bacterial strain of drug resistance from being transmitted.

  16. Serotypes and antimicrobial resistance of Salmonella enterica ssp in central Thailand, 2001-2006.

    PubMed

    Sirichote, Pantip; Bangtrakulnonth, Aroon; Tianmanee, Kanokwan; Unahalekhaka, Aekkawat; Oulai, Amonrat; Chittaphithakchai, Patcharee; Kheowrod, Wachirapa; Hendriksen, Rene S

    2010-11-01

    This study was carried out to elucidate the epidemiological trends and antimicrobial susceptibilities against Salmonella serovars among Thai patients and asymptomatic carriers during 2001-2006 in central Thailand. A total of 1,401 human and 260 non-human isolates from various sources were included. The isolates were characterized using serotyping and antimicrobial susceptibility testing. The most common serovars in patients submitting stool samples were S. Weltevreden, S. Stanley, S. Anatum, and S. Rissen. Significantly higher odds ratios were observed in blood samples versus stool sample for S. Choleraesuis, S. Enteritidis, S. Typhimurium, and S. Typhi. Children under five years old suffered the most frequently from gastroenteritis. The patients most commonly infected with an invasive serovar were children and people from 26 to 55 years of age. Antimicrobial susceptibility data revealed that S. Schwarzengrund, S. Choleraesuis, S. Anatum, S. Stanley, S. Rissen, and S. Typhimurium were the most resistant serovars observed. The invasive serovar, S. Choleraesuis was resistant to cefotaxime and norfloxacin. Antimicrobial resistance to cefotaxime, was observed in S. Agona, S. Rissen, S. Typhimurium, S. Anatum, and S. Weltevreden. An alarmingly high frequency of resistance to third generation cephalosporins was observed. We recommend Thai authorities take action in order to prevent spread of resistant S. Choleraesuis and other serovars among animals and humans by enforcing a more strict policy on the use of antimicrobials in food animals. PMID:21329317

  17. Dairy farm age and resistance to antimicrobial agents in Escherichia coli isolated from dairy topsoil.

    PubMed

    Jones, Suzanna E; Burgos, Jonathan M; Lutnesky, Marvin M F; Sena, Johnny A; Kumar, Sanath; Jones, Lindsay M; Varela, Manuel F

    2011-04-01

    Antimicrobial agent usage is common in animal agriculture for therapeutic and prophylactic purposes. Selective pressure exerted by these antimicrobials on soil bacteria could result in the selection of strains that are resistant due to chromosomal- or plasmid-derived genetic components. Multiple antimicrobial resistances in Escherichia coli and the direct relationship between antimicrobial agent use over time has been extensively studied, yet the relationship between the age of an animal agriculture environment such as a dairy farm and antibiotic resistance remains unclear. Therefore, we tested the hypothesis that antimicrobial-resistance profiles of E. coli isolated from dairy farm topsoil correlate with dairy farm age. E. coli isolated from eleven dairy farms of varying ages within Roosevelt County, NM were used for MIC determinations to chloramphenicol, nalidixic acid, penicillin, tetracycline, ampicillin, amoxicillin/clavulanic acid, gentamicin, trimethoprim/sulfamethoxazole, cefotaxime, and ciprofloxacin. The minimum inhibitory concentration values of four antibiotics ranged 0.75 to >256 μg/ml, 1 to >256 μg/ml, 12 to >256 μg/ml, and 0.75 to >256 μg/ml for chloramphenicol, nalidixic acid, penicillin, and tetracycline, respectively. The study did not show a direct relationship between antibiotic resistance and the age of dairy farms. PMID:21153729

  18. Combating multidrug-resistant Gram-negative bacteria with structurally nanoengineered antimicrobial peptide polymers.

    PubMed

    Lam, Shu J; O'Brien-Simpson, Neil M; Pantarat, Namfon; Sulistio, Adrian; Wong, Edgar H H; Chen, Yu-Yen; Lenzo, Jason C; Holden, James A; Blencowe, Anton; Reynolds, Eric C; Qiao, Greg G

    2016-01-01

    With the recent emergence of reports on resistant Gram-negative 'superbugs', infections caused by multidrug-resistant (MDR) Gram-negative bacteria have been named as one of the most urgent global health threats due to the lack of effective and biocompatible drugs. Here, we show that a class of antimicrobial agents, termed 'structurally nanoengineered antimicrobial peptide polymers' (SNAPPs) exhibit sub-μM activity against all Gram-negative bacteria tested, including ESKAPE and colistin-resistant and MDR (CMDR) pathogens, while demonstrating low toxicity. SNAPPs are highly effective in combating CMDR Acinetobacter baumannii infections in vivo, the first example of a synthetic antimicrobial polymer with CMDR Gram-negative pathogen efficacy. Furthermore, we did not observe any resistance acquisition by A. baumannii (including the CMDR strain) to SNAPPs. Comprehensive analyses using a range of microscopy and (bio)assay techniques revealed that the antimicrobial activity of SNAPPs proceeds via a multimodal mechanism of bacterial cell death by outer membrane destabilization, unregulated ion movement across the cytoplasmic membrane and induction of the apoptotic-like death pathway, possibly accounting for why we did not observe resistance to SNAPPs in CMDR bacteria. Overall, SNAPPs show great promise as low-cost and effective antimicrobial agents and may represent a weapon in combating the growing threat of MDR Gram-negative bacteria. PMID:27617798

  19. Amphibians acquire resistance to live and dead fungus overcoming fungal immunosuppression.

    PubMed

    McMahon, Taegan A; Sears, Brittany F; Venesky, Matthew D; Bessler, Scott M; Brown, Jenise M; Deutsch, Kaitlin; Halstead, Neal T; Lentz, Garrett; Tenouri, Nadia; Young, Suzanne; Civitello, David J; Ortega, Nicole; Fites, J Scott; Reinert, Laura K; Rollins-Smith, Louise A; Raffel, Thomas R; Rohr, Jason R

    2014-07-10

    Emerging fungal pathogens pose a greater threat to biodiversity than any other parasitic group, causing declines of many taxa, including bats, corals, bees, snakes and amphibians. Currently, there is little evidence that wild animals can acquire resistance to these pathogens. Batrachochytrium dendrobatidis is a pathogenic fungus implicated in the recent global decline of amphibians. Here we demonstrate that three species of amphibians can acquire behavioural or immunological resistance to B. dendrobatidis. Frogs learned to avoid the fungus after just one B. dendrobatidis exposure and temperature-induced clearance. In subsequent experiments in which B. dendrobatidis avoidance was prevented, the number of previous exposures was a negative predictor of B. dendrobatidis burden on frogs and B. dendrobatidis-induced mortality, and was a positive predictor of lymphocyte abundance and proliferation. These results suggest that amphibians can acquire immunity to B. dendrobatidis that overcomes pathogen-induced immunosuppression and increases their survival. Importantly, exposure to dead fungus induced a similar magnitude of acquired resistance as exposure to live fungus. Exposure of frogs to B. dendrobatidis antigens might offer a practical way to protect pathogen-naive amphibians and facilitate the reintroduction of amphibians to locations in the wild where B. dendrobatidis persists. Moreover, given the conserved nature of vertebrate immune responses to fungi and the fact that many animals are capable of learning to avoid natural enemies, these results offer hope that other wild animal taxa threatened by invasive fungi might be rescued by management approaches based on herd immunity. PMID:25008531

  20. Isolation, Virulence, and Antimicrobial Resistance of Methicillin-Resistant Staphylococcus aureus (MRSA) and Methicillin Sensitive Staphylococcus aureus (MSSA) Strains from Oklahoma Retail Poultry Meats

    PubMed Central

    Abdalrahman, Lubna S.; Stanley, Adriana; Wells, Harrington; Fakhr, Mohamed K.

    2015-01-01

    Staphylococcus aureus is one the top five pathogens causing domestically acquired foodborne illness in the U.S. Only a few studies are available related to the prevalence of S. aureus and MRSA in the U.S. retail poultry industry. The objectives of this study were to determine the prevalence of S. aureus (MSSA and MRSA) in retail chicken and turkey meats sold in Tulsa, Oklahoma and to characterize the recovered strains for their antimicrobial resistance and possession of toxin genes. A total of 167 (114 chicken and 53 turkey) retail poultry samples were used in this study. The chicken samples included 61 organic samples while the rest of the poultry samples were conventional. The overall prevalence of S. aureus was 57/106 (53.8%) in the conventional poultry samples and 25/61 (41%) in the organic ones. Prevalence in the turkey samples (64.2%) was higher than in the chicken ones (42.1%). Prevalence of S. aureus did not vary much between conventional (43.4%) and organic chicken samples (41%). Two chicken samples 2/114 (1.8%) were positive for MRSA. PFGE identified the two MRSA isolates as belonging to PFGE type USA300 (from conventional chicken) and USA 500 (from organic chicken) which are community acquired CA-MRSA suggesting a human based source of contamination. MLST and spa typing also supported this conclusion. A total of 168 Staphylococcus aureus isolates (101 chicken isolates and 67 turkey isolates) were screened for their antimicrobial susceptibility against 16 antimicrobials and their possession of 18 different toxin genes. Multidrug resistance was higher in the turkey isolates compared to the chicken ones and the percentage of resistance to most of the antimicrobials tested was also higher among the turkey isolates. The hemolysin hla and hld genes, enterotoxins seg and sei, and leucocidins lukE-lukD were more prevalent in the chicken isolates. The PVL gene lukS-lukF was detected only in chicken isolates including the MRSA ones. In conclusion, S. aureus is

  1. Changing antimicrobial resistance profiles among Neisseria gonorrhoeae isolates in Italy, 2003 to 2012.

    PubMed

    Carannante, Anna; Renna, Giovanna; Dal Conte, Ivano; Ghisetti, Valeria; Matteelli, Alberto; Prignano, Grazia; Impara, Giampaolo; Cusini, Marco; D'Antuono, Antonietta; Vocale, Caterina; Antonetti, Raffaele; Gaino, Marina; Busetti, Marina; Latino, Maria Agnese; Mencacci, Antonella; Bonanno, Carmen; Cava, Maria Carmela; Giraldi, Cristina; Stefanelli, Paola

    2014-10-01

    The emergence of Neisseria gonorrhoeae isolates displaying resistance to antimicrobial agents is a major public health concern and a serious issue related to the occurrence of further untreatable gonorrhea infections. A retrospective analysis on 1,430 N. gonorrhoeae isolates, collected from 2003 through 2012, for antimicrobial susceptibility by Etest and molecular characterization by Neisseria gonorrhoeae multiantigen sequence typing (NG-MAST) was carried out in Italy. Azithromycin-resistant gonococci decreased from 14% in 2007 to 2.2% in 2012. Similarly, isolates with high MICs to cefixime (>0.125 mg/liter) decreased from 11% in 2008 to 3.3% in 2012. The ciprofloxacin resistance rate remains quite stable, following an increasing trend up to 64% in 2012. The percentage of penicillinase-producing N. gonorrhoeae (PPNG) significantly declined from 77% in 2003 to 7% in 2012. A total of 81 multidrug-resistant (MDR) gonococci were identified, showing 11 different antimicrobial resistance patterns. These were isolated from men who have sex with men (MSM) and from heterosexual patients. Two sequence types (STs), ST661 and ST1407, were the most common. Genogroup 1407, which included cefixime-, ciprofloxacin-, and azithromycin-resistant isolates, was found. In conclusion, a change in the antimicrobial resistance profiles among gonococci was identified in Italy together with a percentage of MDR isolates. PMID:25070110

  2. Increased survival of experimentally evolved antimicrobial peptide-resistant Staphylococcus aureus in an animal host

    PubMed Central

    Dobson, Adam J; Purves, Joanne; Rolff, Jens

    2014-01-01

    Antimicrobial peptides (AMPs) have been proposed as new class of antimicrobial drugs, following the increasing prevalence of bacteria resistant to antibiotics. Synthetic AMPs are functional analogues of highly evolutionarily conserved immune effectors in animals and plants, produced in response to microbial infection. Therefore, the proposed therapeutic use of AMPs bears the risk of ‘arming the enemy’: bacteria that evolve resistance to AMPs may be cross-resistant to immune effectors (AMPs) in their hosts. We used a panel of populations of Staphylococcus aureus that were experimentally selected for resistance to a suite of individual AMPs and antibiotics to investigate the ‘arming the enemy’ hypothesis. We tested whether the selected strains showed higher survival in an insect model (Tenebrio molitor) and cross-resistance against other antimicrobials in vitro. A population selected for resistance to the antimicrobial peptide iseganan showed increased in vivo survival, but was not more virulent. We suggest that increased survival of AMP-resistant bacteria almost certainly poses problems to immune-compromised hosts. PMID:25469169

  3. Prevalence and characterization of antimicrobial-resistant Escherichia coli isolated from conventional and organic vegetables.

    PubMed

    Kim, Sara; Woo, Gun-Jo

    2014-10-01

    To compare the characteristics and to identify the epidemiological relationships of Escherichia coli isolated from organic and conventional vegetables, the antimicrobial resistance and genetic properties of E. coli were investigated from 2010 to 2011. E. coli was isolated from 1 of 111 (0.9%) organic vegetables and from 20 of 225 (8.9%) conventional vegetables. The majority of strains were isolated from the surrounding farming environment (n=27/150 vs. 49/97 in organic vs. conventional samples). The majority of the vegetable strains were isolated from the surrounding farming environments. E. coli isolated from organic vegetables showed very low antimicrobial resistance rates except for cephalothin, ranging from 0% to 17.9%, while the resistance rates to cephalothin (71%) were extremely high in both groups. E. coli isolates expressed various resistance genes, which most commonly included blaTEM, tet(A), strA, strB, and qnrS. However, none of the isolates harbored tet(D), tet(E), tet(K), tet(L), tet(M), or qnrA. The transferability of tet gene, tet(A), and tet(B) was identified in tetracycline-resistant E. coli, and the genetic relationship was confirmed in a few cases from different sources. With regard to the lower antimicrobial resistance found in organic produce, this production mode seems able to considerably reduce the selection of antimicrobial-resistant bacteria on vegetables. PMID:25140978

  4. Antimicrobial Resistance and Virulence: a Successful or Deleterious Association in the Bacterial World?

    PubMed Central

    Beceiro, Alejandro; Tomás, María

    2013-01-01

    SUMMARY Hosts and bacteria have coevolved over millions of years, during which pathogenic bacteria have modified their virulence mechanisms to adapt to host defense systems. Although the spread of pathogens has been hindered by the discovery and widespread use of antimicrobial agents, antimicrobial resistance has increased globally. The emergence of resistant bacteria has accelerated in recent years, mainly as a result of increased selective pressure. However, although antimicrobial resistance and bacterial virulence have developed on different timescales, they share some common characteristics. This review considers how bacterial virulence and fitness are affected by antibiotic resistance and also how the relationship between virulence and resistance is affected by different genetic mechanisms (e.g., coselection and compensatory mutations) and by the most prevalent global responses. The interplay between these factors and the associated biological costs depend on four main factors: the bacterial species involved, virulence and resistance mechanisms, the ecological niche, and the host. The development of new strategies involving new antimicrobials or nonantimicrobial compounds and of novel diagnostic methods that focus on high-risk clones and rapid tests to detect virulence markers may help to resolve the increasing problem of the association between virulence and resistance, which is becoming more beneficial for pathogenic bacteria. PMID:23554414

  5. Does the adoption of EUCAST susceptibility breakpoints affect the selection of antimicrobials to treat acute community-acquired respiratory tract infections?

    PubMed Central

    2012-01-01

    Background In several European Countries, by the end of 2012, CLSI guidelines will be replaced by EUCAST. We compared antimicrobial susceptibility results of a large number of respiratory pathogens using both EUCAST and previously adopted CLSI criteria to evaluate the impact on susceptibility patterns and the possible consequences that could occur in clinical practice due to this replacement. For S. pyogenes and S. aureus, the interpretation of susceptibility data using the EUCAST criteria did not produce relevant changes in comparison to CLSI. Against S. pneumoniae, more restrictive EUCAST breakpoints could lead to increased benzylpenicillin and/or amoxicillin-clavulanate resistance rates, which in turn could translate in increased dosages of these antibiotics or usage of alternative agents for respiratory tract infections. Against S. pneumoniae, M. catarrhalis and H. influenzae, cefuroxime-axetil and cefaclor produced the most divergent results depending on the breakpoints adopted and these striking differences could lead to the revision of those guidelines suggesting these two cephalosporins as alternatives in the management of upper respiratory tract infections. Discussion Many differences exist between CLSI and EUCAST breakpoints. However, only in a few cases do these differences translate in major interpretive category discrepancies. In countries adopting more restrictive EUCAST breakpoints, clinicians should be aware of these discrepancies and that they could be faced with antibiotic-resistant respiratory pathogens more frequently than before. Summary The interpretive discrepancies between EUCAST and CLSI suggest that the discussion on the management of community-acquired respiratory tract infections is still open and further studies are desirable to better define the role of some antibiotics. PMID:22866984

  6. Population-Based Surveillance of Neisseria meningitidis Antimicrobial Resistance in the United States

    PubMed Central

    Harcourt, Brian H.; Anderson, Raydel D.; Wu, Henry M.; Cohn, Amanda C.; MacNeil, Jessica R.; Taylor, Thomas H.; Wang, Xin; Clark, Thomas A.; Messonnier, Nancy E.; Mayer, Leonard W.

    2015-01-01

    Background. Antimicrobial treatment and chemoprophylaxis of patients and their close contacts is critical to reduce the morbidity and mortality and prevent secondary cases of meningococcal disease. Through the 1990's, the prevalence of antimicrobial resistance to commonly used antimicrobials among Neisseria meningitidis was low in the United States. Susceptibility testing was performed to ascertain whether the proportions of isolates with reduced susceptibility to antimicrobials commonly used for N meningitidis have increased since 2004 in the United States. Methods. Antimicrobial susceptibility testing was performed by broth microdilution on 466 isolates of N meningitidis collected in 2004, 2008, 2010, and 2011 from an active, population-based surveillance system for susceptibility to ceftriaxone, ciprofloxacin, penicillin G, rifampin, and azithromycin. The molecular mechanism of reduced susceptibility was investigated for isolates with intermediate or resistant phenotypes. Results. All isolates were susceptible to ceftriaxone and azithromycin, 10.3% were penicillin G intermediate (range, 8% in 2008–16.7% in 2010), and <1% were ciprofloxacin, rifampin, or penicillin G resistant. Of the penicillin G intermediate or resistant isolates, 63% contained mutations in the penA gene associated with reduced susceptibility to penicillin G. All ciprofloxacin-resistant isolates contained mutations in the gyrA gene associated with reduced susceptibility. Conclusions. Resistance of N meningitidis to antimicrobials used for empirical treatment of meningitis in the United States has not been detected, and resistance to penicillin G and chemoprophylaxis agents remains uncommon. Therapeutic agent recommendations remain valid. Although periodic surveillance is warranted to monitor trends in susceptibility, routine clinical testing may be of little use. PMID:26357666

  7. Antimicrobial resistance among Clostridium perfringens isolated from various sources in Thailand.

    PubMed

    Tansuphasiri, Unchalee; Matra, Wiriya; Sangsuk, Leelaowadee

    2005-07-01

    Antimicrobial resistance among Clostnridium perfringens isolated from feces of humans and pigs, food and other environmental sources was examined by testing of 201 PCR-confirmed strains for resistance to 7 antimicrobial agents. The minimal inhibitory concentrations (MICs) were determined by the agar dilution method. Overall, C. perfringens showed the highest resistance to tetracycline (56.2%), followed by imipenem (24.9%), metronidazole (9.5%), penicillin G (9%), vancomycin (4.5%), chloramphenicol (3%) and ceftriaxone (1%). The majority of the isolated strains from pig feces (77.8%), environment (72.7%), human feces (44.9%) and food (28%) showed resistance to tetracycline. Strains isolated from human feces only showed low resistance to ceftriaxone (2.5%) and vancomycin (10.1%). Penicillin G had high activity, with overall MIC50 and MIC90 of 0.06 and 1.0 microg/ml, respectively, and low rate of resistance (10-12% for strains isolated from humans, animals and food). Among 62.7% of antimicrobial resistant strains, 39.3% were resistant to a single drug and 23.4% were multiple-drug resistant (MDR). Of overall 47 MDR strains, 63.8% were derived from human feces and were resistant to two to six drugs. PMID:16295551

  8. Clinical Significance of Community- and Healthcare-Acquired Carbapenem-Resistant Enterobacteriaceae Isolates

    PubMed Central

    Tang, Hung-Jen; Hsieh, Cheng-Fang; Chang, Ping-Chin; Chen, Jyh-Jou; Lin, Yu-Hsiu; Lai, Chih-Cheng; Chao, Chien-Ming; Chuang, Yin-Ching

    2016-01-01

    This study was conducted to investigate the clinical significance, manifestations, microbiological characteristics and outcomes of carbapenem-resistant Enterobacteriaceae (CRE) isolates, and compare the clinical features of community- and healthcare-acquired CRE isolates. A total of 78 patients were identified to have CRE. Klebsiella pneumoniae was the most common pathogens (n = 42, 53.8%), followed by Enterobacter cloacae (n = 24, 30.8%), and Escherichia coli (n = 11, 14.1%). Most of the patients acquired CRE from healthcare settings (n = 55, 70.5%), and other cases got CRE from community settings (n = 23, 29.5%). Nine cases (11.5%) were classified as CRE colonization. Among the remaining 69 cases of CRE infections, pneumonia (n = 28, 40.6%) was the most common type of infections, followed by urinary tract infection (n = 24, 34.8%), and intra-abdominal infection (n = 16, 23.2%). The patients acquired CRE from community settings were more likely to be elderly, female, and had more urinary tract infections than from healthcare settings. In contrast, the patients acquired CRE from healthcare settings had more intra-abdominal infections, intra-abdominal surgery, and presence of indwelling device than from community settings. In conclusion, community-acquired CRE are not rare, and their associated clinical presentations are different from healthcare-acquired CRE. PMID:26999356

  9. Characterization of in vivo-acquired resistance to macrolides of Mycoplasma gallisepticum strains isolated from poultry

    PubMed Central

    2011-01-01

    The macrolide class of antibiotics, including tylosin and tilmicosin, is widely used in the veterinary field for prophylaxis and treatment of mycoplasmosis. In vitro susceptibility testing of 50 strains of M. gallisepticum isolated in Israel during the period 1997-2010 revealed that acquired resistance to tylosin as well as to tilmicosin was present in 50% of them. Moreover, 72% (13/18) of the strains isolated from clinical samples since 2006 showed acquired resistance to enrofloxacin, tylosin and tilmicosin. Molecular typing of the field isolates, performed by gene-target sequencing (GTS), detected 13 molecular types (I-XIII). Type II was the predominant type prior to 2006 whereas type X, first detected in 2008, is currently prevalent. All ten type X strains were resistant to both fluoroquinolones and macrolides, suggesting selective pressure leading to clonal dissemination of resistance. However, this was not a unique event since resistant strains with other GTS molecular types were also found. Concurrently, the molecular basis for macrolide resistance in M. gallisepticum was identified. Our results revealed a clear-cut correlation between single point mutations A2058G or A2059G in domain V of the gene encoding 23S rRNA (rrnA, MGA_01) and acquired macrolide resistance in M. gallisepticum. Indeed, all isolates with MIC ≥ 0.63 μg/mL to tylosin and with MIC ≥ 1.25 μg/mL to tilmicosin possess one of these mutations, suggesting an essential role in decreased susceptibility of M. gallisepticum to 16-membered macrolides. PMID:21810258

  10. Characterization of in vivo-acquired resistance to macrolides of Mycoplasma gallisepticum strains isolated from poultry.

    PubMed

    Gerchman, Irena; Levisohn, Sharon; Mikula, Inna; Manso-Silván, Lucía; Lysnyansky, Inna

    2011-01-01

    The macrolide class of antibiotics, including tylosin and tilmicosin, is widely used in the veterinary field for prophylaxis and treatment of mycoplasmosis. In vitro susceptibility testing of 50 strains of M. gallisepticum isolated in Israel during the period 1997-2010 revealed that acquired resistance to tylosin as well as to tilmicosin was present in 50% of them. Moreover, 72% (13/18) of the strains isolated from clinical samples since 2006 showed acquired resistance to enrofloxacin, tylosin and tilmicosin. Molecular typing of the field isolates, performed by gene-target sequencing (GTS), detected 13 molecular types (I-XIII). Type II was the predominant type prior to 2006 whereas type X, first detected in 2008, is currently prevalent. All ten type X strains were resistant to both fluoroquinolones and macrolides, suggesting selective pressure leading to clonal dissemination of resistance. However, this was not a unique event since resistant strains with other GTS molecular types were also found. Concurrently, the molecular basis for macrolide resistance in M. gallisepticum was identified. Our results revealed a clear-cut correlation between single point mutations A2058G or A2059G in domain V of the gene encoding 23S rRNA (rrnA, MGA_01) and acquired macrolide resistance in M. gallisepticum. Indeed, all isolates with MIC ≥ 0.63 μg/mL to tylosin and with MIC ≥ 1.25 μg/mL to tilmicosin possess one of these mutations, suggesting an essential role in decreased susceptibility of M. gallisepticum to 16-membered macrolides. PMID:21810258

  11. Resistance of gram-negative bacilli as related to hospital use of antimicrobial agents.

    PubMed Central

    Ma, M Y; Goldstein, E J; Friedman, M H; Anderson, M S; Mulligan, M E

    1983-01-01

    The development of resistance of gram-negative bacilli, which are common nosocomial pathogens, is an increasing problem. It is generally accepted that this resistance may directly reflect the frequency of use of various antimicrobial agents. Because our institution experienced in 1976 a dramatic change in the pattern of antimicrobial use, primarily a marked decrease in prescribing cephalosporins, we attempted to evaluate retrospectively the effects of this change upon the resistance of gram-negative bacilli that are common nosocomial pathogens. Susceptibilities of Klebsiella and Providencia spp., Pseudomonas aeruginosa, and Serratia marcescens were determined for the years 1975 to 1979. Not unexpectedly, we observed a substantial decrease in cephalosporin resistance. An unexpected finding was a decrease in aminoglycoside resistance, despite increased use of these agents. The possibility that decreased cephalosporin use may lead to decreased aminoglycoside resistance is an intriguing and provocative thesis which can only be speculative at this time but which would seem worthy of additional formal investigation. PMID:6638994

  12. Temporal Prevalence of Antimicrobial Resistance in Campylobacter spp. from Beef Cattle in Alberta Feedlots†

    PubMed Central

    Inglis, G. D.; Morck, D. W.; McAllister, T. A.; Entz, T.; Olson, M. E.; Yanke, L. J.; Read, R. R.

    2006-01-01

    Antimicrobial resistance (AMR) was temporally assessed in campylobacters isolated from beef cattle (7,738 fecal samples from 2,622 animals) in four commercial feedlots in Alberta. All calves were administered chlortetracycline and oxytetracycline in feed, and a majority of the animals (93%) were injected with long-acting oxytetracycline upon arrival at the feedlot. Fecal samples from individual animals were collected upon arrival (i.e., entry sample), 69 days (standard deviation [SD] = 3 days) after arrival (i.e., interim sample), and 189 days (SD = 33 days) after arrival (i.e., exit sample) at the feedlot. In total, 1,586 Campylobacter isolates consisting of Campylobacter coli (n = 154), Campylobacter fetus (n = 994), Campylobacter jejuni (n = 431), Campylobacter hyointestinalis (n = 4), and Campylobacter lanienae (n = 3) were recovered and characterized. The administration of antimicrobials did not decrease carriage rates of campylobacters, and minimal resistance (≤4%) to azithromycin, ciprofloxacin, enrofloxacin, gentamicin, and meropenem was observed. In contrast, substantive increases in the prevalence of isolates resistant to tetracycline and doxycycline (56 to 89%) for C. coli, C. fetus, and C. jejuni, as well as in the number of animals (7 to 42%) from which resistant isolates were recovered, were observed during the feedlot period. Increased resistance to erythromycin (total isolates and carriages rates) was also observed in isolates of C. coli over the three isolation times. The majority of C. fetus isolates recovered were resistant to nalidixic acid, but this was independent of when they were isolated. A relatively limited number of multidrug-resistant isolates were recovered and consisted primarily of C. coli resistant to tetracyclines and erythromycin (10% of isolates). Over the course of the feedlot period, considerable increases in antimicrobial resistance were observed in C. coli, C. fetus, and C. jejuni, but with the exception of erythromycin

  13. Increased Mitochondrial DNA Induces Acquired Docetaxel Resistance in Head and Neck Cancer Cells

    PubMed Central

    Mizumachi, T; Suzuki, S; Naito, A; Carcel-Trullols, J; Evans, TT; Spring, PM; Oridate, N; Furuta, Y; Fukuda, S; Higuchi, M

    2008-01-01

    Docetaxel is one of the most effective chemotherapeutic agents against cancer; nevertheless, some patients develop resistance. Unfortunately, their causes and mechanisms remain unknown. We created docetaxel-resistant DRHEp2 from human laryngeal cancer HEp2 and investigated the roles of mitochondrial DNA (mtDNA) and ROS on docetaxel resistance. DRHEp2 had greatly increased mtDNA content. Reduction of mtDNA content in DRHEp2 by ethidium bromide treatment reduced the resistance. These results indicate the possible roles of mtDNA-coded enzymes in mitochondrial respiratory chain (MRC) in resistant mechanisms. Oligomycin A, an Fo-ATPase inhibitor, eliminated docetaxel resistance in DRHEp2. In contrast, inhibitors of other MRC did not. RNA interference targeted to Fo-ATPase d-subunit restored docetaxel-induced cytotoxicity to DRHEp2. These results indicate the roles of Fo-ATPase for resistant mechanisms. Docetaxel induced ROS generation in HEp2 but not in DRHEp2 and antioxidant pyrrolidine dithiocarbamate eliminated docetaxel-induced cytotoxicity, suggesting roles of ROS in docetaxel-induced cell death. Furthermore, inhibition of Fo-ATPase by Oligomycin A induced docetaxel–mediated ROS generation in DRHEp2. Taken together, DRHEp2 acquired docetaxel resistance through increasing Fo-ATPase, which led to diminish docetaxel-induced ROS generation and subsequently inhibited cell death. In conclusion, mtDNA plays an important role in developing docetaxel resistance through the reduction of ROS generation by regulating Fo-ATPase. PMID:17637738

  14. Identification and Antimicrobial Resistance of Bacteria Isolated from Probiotic Products Used in Shrimp Culture.

    PubMed

    Noor Uddin, Gazi Md; Larsen, Marianne Halberg; Christensen, Henrik; Aarestrup, Frank M; Phu, Tran Minh; Dalsgaard, Anders

    2015-01-01

    Probiotics are increasingly used in aquaculture to control diseases and improve feed digestion and pond water quality; however, little is known about the antimicrobial resistance properties of such probiotic bacteria and to what extent they may contribute to the development of bacterial resistance in aquaculture ponds. Concerns have been raised that the declared information on probiotic product labels are incorrect and information on bacterial composition are often missing. We therefore evaluated seven probiotics commonly used in Vietnamese shrimp culture for their bacterial species content, phenotypic antimicrobial resistance and associated transferable resistance genes. The bacterial species was established by 16S rRNA sequence analysis of 125 representative bacterial isolates. MIC testing was done for a range of antimicrobials and whole genome sequencing of six multiple antimicrobial resistant Bacillus spp. used to identify resistance genes and genetic elements associated with horizontal gene transfer. Thirteen bacterial species declared on the probiotic products could not be identified and 11 non-declared Bacillus spp. were identified. Although our culture-based isolation and identification may have missed a few bacterial species present in the tested products this would represent minor bias, but future studies may apply culture independent identification methods like pyro sequencing. Only 6/60 isolates were resistant to more than four antimicrobials and whole genome sequencing showed that they contained macrolide (ermD), tetracycline (tetL), phenicol (fexA) and trimethoprim (dfrD, dfrG and dfrK) resistance genes, but not known structures associated with horizontal gene transfer. Probiotic bacterial strains used in Vietnamese shrimp culture seem to contribute with very limited types and numbers of resistance genes compared to the naturally occurring bacterial species in aquaculture environments. Approval procedures of probiotic products must be strengthened

  15. Identification and Antimicrobial Resistance of Bacteria Isolated from Probiotic Products Used in Shrimp Culture

    PubMed Central

    Noor Uddin, Gazi Md.; Larsen, Marianne Halberg; Christensen, Henrik; Aarestrup, Frank M.; Phu, Tran Minh; Dalsgaard, Anders

    2015-01-01

    Probiotics are increasingly used in aquaculture to control diseases and improve feed digestion and pond water quality; however, little is known about the antimicrobial resistance properties of such probiotic bacteria and to what extent they may contribute to the development of bacterial resistance in aquaculture ponds. Concerns have been raised that the declared information on probiotic product labels are incorrect and information on bacterial composition are often missing. We therefore evaluated seven probiotics commonly used in Vietnamese shrimp culture for their bacterial species content, phenotypic antimicrobial resistance and associated transferable resistance genes. The bacterial species was established by 16S rRNA sequence analysis of 125 representative bacterial isolates. MIC testing was done for a range of antimicrobials and whole genome sequencing of six multiple antimicrobial resistant Bacillus spp. used to identify resistance genes and genetic elements associated with horizontal gene transfer. Thirteen bacterial species declared on the probiotic products could not be identified and 11 non-declared Bacillus spp. were identified. Although our culture-based isolation and identification may have missed a few bacterial species present in the tested products this would represent minor bias, but future studies may apply culture independent identification methods like pyro sequencing. Only 6/60 isolates were resistant to more than four antimicrobials and whole genome sequencing showed that they contained macrolide (ermD), tetracycline (tetL), phenicol (fexA) and trimethoprim (dfrD, dfrG and dfrK) resistance genes, but not known structures associated with horizontal gene transfer. Probiotic bacterial strains used in Vietnamese shrimp culture seem to contribute with very limited types and numbers of resistance genes compared to the naturally occurring bacterial species in aquaculture environments. Approval procedures of probiotic products must be strengthened

  16. Inherent and Acquired Resistance to Paclitaxel in Hepatocellular Carcinoma: Molecular Events Involved

    PubMed Central

    Meena, Avtar Singh; Sharma, Aanchal; Kumari, Ratna; Mohammad, Naoshad; Singh, Shivendra Vikram; Bhat, Manoj Kumar

    2013-01-01

    Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and is a major cause of cancer related deaths worldwide. Only 10 to 20% of HCC can be surgically excised. Therefore, chemotherapeutic intervention and treatment is essential for achieving favorable prognosis. However, therapeutic outcome of chemotherapy is generally poor owing to inherent resistance of cancer cells to the treatment or due to development of acquired resistance. To differentiate and delineate the molecular events, we developed drug resistant Hep3B cells (DRC) by treating cells with the increasing concentration of paclitaxel. We also developed a unique single cell clone of Hep3B cells (SCC) by selecting single cell colonies and screening them for resistant phenotype. Interestingly, both DRC and SCC were resistant to paclitaxel in comparison to parental Hep3B cells. We analyzed the contributory factors that may be involved in the development of resistance. As expected, level of P-glycoprotein (P-gp) was elevated in DRC. In addition, Caveolin-1 (Cav-1), Fatty acid synthase (FASN) and Cytochrome P450 (CYP450) protein levels were elevated in DRC whereas in SCC, FASN and CYP450 levels were elevated. Downregulation of these molecules by respective siRNAs and/or by specific pharmacological inhibitors resensitized cells to paclitaxel. Interestingly, these drug resistant cells were also less sensitive to vinblastine, doxorubicin and methotrexate with the exception of cisplatin. Our results suggested that differential levels of P-gp, Cav-1 and FASN play a major role in acquired resistant phenotype whereas FASN level was associated with the presentation of inherent resistant phenotype in HCC. PMID:23613870

  17. PP2A inhibition overcomes acquired resistance to HER2 targeted therapy

    PubMed Central

    2014-01-01

    Background HER2 targeted therapies including trastuzumab and more recently lapatinib have significantly improved the prognosis for HER2 positive breast cancer patients. However, resistance to these agents is a significant clinical problem. Although several mechanisms have been proposed for resistance to trastuzumab, the mechanisms of lapatinib resistance remain largely unknown. In this study we generated new models of acquired resistance to HER2 targeted therapy and investigated mechanisms of resistance using phospho-proteomic profiling. Results Long-term continuous exposure of SKBR3 cells to low dose lapatinib established a cell line, SKBR3-L, which is resistant to both lapatinib and trastuzumab. Phospho-proteomic profiling and immunoblotting revealed significant alterations in phospho-proteins involved in key signaling pathways and molecular events. In particular, phosphorylation of eukaryotic elongation factor 2 (eEF2), which inactivates eEF2, was significantly decreased in SKBR3-L cells compared to the parental SKBR3 cells. SKBR3-L cells exhibited significantly increased activity of protein phosphatase 2A (PP2A), a phosphatase that dephosphorylates eEF2. SKBR3-L cells showed increased sensitivity to PP2A inhibition, with okadaic acid, compared to SKBR3 cells. PP2A inhibition significantly enhanced response to lapatinib in both the SKBR3 and SKBR3-L cells. Furthermore, treatment of SKBR3 parental cells with the PP2A activator, FTY720, decreased sensitivity to lapatinib. The alteration in eEF2 phosphorylation, PP2A activity and sensitivity to okadaic acid were also observed in a second HER2 positive cell line model of acquired lapatinib resistance, HCC1954-L. Conclusions Our data suggests that decreased eEF2 phosphorylation, mediated by increased PP2A activity, contributes to resistance to HER2 inhibition and may provide novel targets for therapeutic intervention in HER2 positive breast cancer which is resistant to HER2 targeted therapies. PMID:24958351

  18. Susceptibility of Clostridium difficile Isolates of Varying Antimicrobial Resistance Phenotypes to SMT19969 and 11 Comparators

    PubMed Central

    Freeman, Jane; Vernon, Jonathan; Vickers, Richard

    2015-01-01

    We determined the in vitro activity of SMT19969 and 11 comparators, including metronidazole, vancomycin, and fidaxomicin, against 107 C. difficile isolates of different antimicrobial resistance phenotypes. Fidaxomicin and SMT19969 were the most active. The fidaxomicin and SMT19969 geometric mean MICs were highest in ribotypes known to show multiple resistance. Coresistance to linezolid and moxifloxacin was evident in ribotypes 001, 017, 027, and 356. The high-level ceftriaxone resistance in ribotypes 356 and 018 was location linked. PMID:26552981

  19. Antimicrobial resistance in Escherichia coli isolates from food animals, animal food products and companion animals in China.

    PubMed

    Lei, Tao; Tian, Wei; He, Liu; Huang, Xian-Hui; Sun, Yong-Xue; Deng, Yu-Ting; Sun, Yan; Lv, Dian-Hong; Wu, Cong-Ming; Huang, Liang-Zong; Shen, Jian-Zhong; Liu, Jian-Hua

    2010-11-20

    One thousand and thirty Escherichia coli isolates from food animals, animals-derived foods, and companion animals between 2007 and 2008 in Southern China were used to investigate their antimicrobial susceptibility to 14 different antimicrobials by the standard agar dilution method. More than 70% of isolates showed resistance to tetracycline, trimethoprim-sulphamethoxazole, nalidixic acid, and ampicillin. In general, resistance was less frequent in companion animal isolates vs food animals isolates, but cephalosporin and amikacin resistance was more frequent in companion animal isolates, 42.6% to 56.2% vs 14.1% to 24.3%, and 28.5% vs 18.8%, respectively, which was most likely due to the common use of these antimicrobials as treatment in pet animals. Fluoroquinolones resistance was high in all animal isolates (>50%). Food products showed lowest resistance among isolates from these three resources. PFGE analysis indicated that a majority of multidrug-resistant E. coli isolates showed unique, unrelated PFGE profiles and were unlikely to be the spread of a specific clone. This study provides useful information about the prevalence of antimicrobial resistance in E. coli isolated from animals and food products in China and provided evidence of the linkage of the use of antimicrobials in animals and its selection of antimicrobial resistance in bacterial isolates. The data from this study further warns the prudent use of antimicrobials in food and pet animals to reduce the risks of transmission of antimicrobial resistance zoonotic pathogen to humans. PMID:20605690

  20. In vitro antimicrobial activity of five essential oils on multidrug resistant Gram-negative clinical isolates

    PubMed Central

    Sakkas, Hercules; Gousia, Panagiota; Economou, Vangelis; Sakkas, Vassilios; Petsios, Stefanos; Papadopoulou, Chrissanthy

    2016-01-01

    Aim/Background: The emergence of drug-resistant pathogens has drawn attention on medicinal plants for potential antimicrobial properties. The objective of the present study was the investigation of the antimicrobial activity of five plant essential oils on multidrug resistant Gram-negative bacteria. Materials and Methods: Basil, chamomile blue, origanum, thyme, and tea tree oil were tested against clinical isolates of Acinetobacter baumannii (n = 6), Escherichia coli (n = 4), Klebsiella pneumoniae (n = 7), and Pseudomonas aeruginosa (n = 5) using the broth macrodilution method. Results: The tested essential oils produced variable antibacterial effect, while Chamomile blue oil demonstrated no antibacterial activity. Origanum, Thyme, and Basil oils were ineffective on P. aeruginosa isolates. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration values ranged from 0.12% to 1.50% (v/v) for tea tree oil, 0.25-4% (v/v) for origanum and thyme oil, 0.50% to >4% for basil oil and >4% for chamomile blue oil. Compared to literature data on reference strains, the reported MIC values were different by 2SD, denoting less successful antimicrobial activity against multidrug resistant isolates. Conclusions: The antimicrobial activities of the essential oils are influenced by the strain origin (wild, reference, drug sensitive, or resistant) and it should be taken into consideration whenever investigating the plants’ potential for developing new antimicrobials. PMID:27366345

  1. Use and misuse of antimicrobial drugs in poultry and livestock: Mechanisms of antimicrobial resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Food safety begins on the farm with management practices that contribute to an abundant, safe, and affordable food supply. To attain this goal, antimicrobials have been used in all stages of food animal production in the United States and elsewhere around the world at one time or another. Among fo...

  2. In vitro activities of antibiotics and antimicrobial cationic peptides alone and in combination against methicillin-resistant Staphylococcus aureus biofilms.

    PubMed

    Mataraci, Emel; Dosler, Sibel

    2012-12-01

    Methicillin-resistant Staphylococcus aureus (MRSA) strains are most often found as hospital- and community-acquired infections. The danger of MRSA infections results from not only the emergence of multidrug resistance but also the occurrence of bacteria that form strong biofilms. We investigated the in vitro activities of antibiotics (daptomycin, linezolid, teichoplanine, azithromycin, and ciprofloxacin) and antimicrobial cationic peptides {AMPs; indolicidin, CAMA [cecropin (1-7)-melittin A (2-9) amide], and nisin} alone or in combination against MRSA ATCC 43300 biofilms. The MICs and minimum biofilm eradication concentrations (MBECs) were determined by the broth microdilution technique. Antibiotic and AMP combinations were assessed using the checkerboard technique. For MRSA planktonic cells, MICs of antibiotics and AMPs ranged between 0.125 and 512 and 8 and 16 mg/liter, respectively, and the MBEC values were between 512 and 5,120 and 640 mg/liter, respectively. With a fractional inhibitory concentration of ≤0.5 as the borderline, synergistic interactions against MRSA biofilms were frequent with almost all antibiotic-antibiotic and antibiotic-AMP combinations. Against planktonic cells, they generally had an additive effect. No antagonism was observed. All of the antibiotics, AMPs, and their combinations were able to inhibit the attachment of bacteria at 1/10 MIC and biofilm formation at 1× MIC. Biofilm-associated MRSA was not affected by therapeutically achievable concentrations of antimicrobial agents. Use of a combination of antimicrobial agents can provide a synergistic effect, which rapidly enhances antibiofilm activity and may help prevent or delay the emergence of resistance. AMPs seem to be good candidates for further investigations in the treatment of MRSA biofilms, alone or in combination with antibiotics. PMID:23070152

  3. Multilocus Sequence Typing and Antimicrobial Resistance of Campylobacter jejuni Isolated from Dairy Calves in Austria.

    PubMed

    Klein-Jöbstl, Daniela; Sofka, Dmitri; Iwersen, Michael; Drillich, Marc; Hilbert, Friederike

    2016-01-01

    Human campylobacteriosis is primarily associated with poultry but also cattle. In this study, 55 Campylobacter jejuni strains isolated from 382 dairy calves' feces were differentiated by multilocus sequence typing and tested for antimicrobial resistance. The most prevalent sequence type (ST) was ST883 (20.0%), followed by ST48 (14.5%), and ST50 (9.1%). In contrast to ST48 and ST50, ST883 has rarely been described in cattle previously. Furthermore, risk factor analysis was performed for the presence of the most prevalent STs in these calves. Multiple regression analysis revealed that the type of farm (organic vs. conventional) and calf housing (place, and individual vs. group) were identified as significantly (p < 0.05) associated with the presence of ST883 in calves, and ST50 was associated with calf diarrhea. Antimicrobial resistance was detected in 58.2% of the isolates. Most of the resistant isolates (81.3%) were resistant to more than one antimicrobial. Most frequently, resistance to ciprofloxacin (49.1%), followed by nalidixic acid (42.8%), and tetracycline (14.5%) was observed. The results of the present study support the hypothesis that dairy calves may serve as a potential reservoir for C. jejuni and pose a risk for transmission, including antimicrobial resistant isolates to the environment and to humans. PMID:26870027

  4. Nationwide surveillance of antimicrobial resistance among Enterobacteriaceae in intensive care units in Taiwan.

    PubMed

    Jean, S-S; Hsueh, P-R; Lee, W-S; Chang, H-T; Chou, M-Y; Chen, I-S; Wang, J-H; Lin, C-F; Shyr, J-M; Ko, W-C; Wu, J-J; Liu, Y-C; Huang, W-K; Teng, L-J; Liu, C-Y

    2009-02-01

    To determine the antimicrobial resistance profiles among clinical isolates of Enterobacteriaceae in Taiwanese intensive care units (ICUs), a national surveillance of antibiotic resistance among important Enterobacteriaceae was conducted from September 2005 through November 2005 at the ICUs of ten major teaching hospitals in Taiwan. A total of 574 Enterobacteriaceae isolates recovered from various clinical samples of our ICU patients were submitted for in vitro test. Minimum inhibitory concentrations (MICs) of these isolates to 18 antimicrobial agents were determined by the broth microdilution method. The prevalences of Enterobacteriaceae isolates with phenotypic extended-spectrum beta-lactamase (ESBL) production were 26% in Klebsiella pneumoniae, 16% in Serratia marcescens, 14% in Escherichia coli, and 13% in Proteus mirabilis, in which a significantly rising prevalence of ESBL production among K. pneumoniae was noted (p = 0.002) when compared with a previous Taiwanese survey in 2000. Heterogeneous resistance to various fluoroquinolones was found among our Enterobacteriaceae isolates, except for Enterobacter cloacae. Emergence of ertapenem-resistant isolates of E. coli, K. pneumoniae, E. cloacae, and S. marcescens was noted. Gradually increasing rates of drug-resistant Enterobacteriaceae were noted in Taiwanese ICUs. Periodic surveillance of the evolutionary trend of antimicrobial resistance among ICU isolates is crucial for starting appropriately empirical antimicrobial therapy in the future. PMID:18716805

  5. Multilocus Sequence Typing and Antimicrobial Resistance of Campylobacter jejuni Isolated from Dairy Calves in Austria

    PubMed Central

    Klein-Jöbstl, Daniela; Sofka, Dmitri; Iwersen, Michael; Drillich, Marc; Hilbert, Friederike

    2016-01-01

    Human campylobacteriosis is primarily associated with poultry but also cattle. In this study, 55 Campylobacter jejuni strains isolated from 382 dairy calves’ feces were differentiated by multilocus sequence typing and tested for antimicrobial resistance. The most prevalent sequence type (ST) was ST883 (20.0%), followed by ST48 (14.5%), and ST50 (9.1%). In contrast to ST48 and ST50, ST883 has rarely been described in cattle previously. Furthermore, risk factor analysis was performed for the presence of the most prevalent STs in these calves. Multiple regression analysis revealed that the type of farm (organic vs. conventional) and calf housing (place, and individual vs. group) were identified as significantly (p < 0.05) associated with the presence of ST883 in calves, and ST50 was associated with calf diarrhea. Antimicrobial resistance was detected in 58.2% of the isolates. Most of the resistant isolates (81.3%) were resistant to more than one antimicrobial. Most frequently, resistance to ciprofloxacin (49.1%), followed by nalidixic acid (42.8%), and tetracycline (14.5%) was observed. The results of the present study support the hypothesis that dairy calves may serve as a potential reservoir for C. jejuni and pose a risk for transmission, including antimicrobial resistant isolates to the environment and to humans. PMID:26870027

  6. Antimicrobial Resistance Profiles in Escherichia coli O157 Isolates from Northern Colorado Dairies.

    PubMed

    McConnel, Craig S; Stenkamp-Strahm, Chloe M; Rao, Sangeeta; Linke, Lyndsey M; Magnuson, Roberta J; Hyatt, Doreene R

    2016-03-01

    Escherichia coli O157 (EcO157) infections can lead to serious disease and death in humans. Although the ecology of EcO157 is complex, ruminant animals serve as an important reservoir for human infection. Dairy cattle are unique because they may be a source of contamination for milk, meat, and manure-fertilized crops. Foodborne dairy pathogens such as EcO157 are of primary importance to public health. Antimicrobial resistance (AMR) is a complex phenomenon that complicates the treatment of serious bacterial infections and is of increasing concern. In the face of recommended use restrictions for antimicrobial agents in livestock operations, current AMR patterns in known foodborne pathogens should be documented. The objective of this study was to document AMR patterns in EcO157 isolates from dairies in northern Colorado using antimicrobial agents commonly found on dairies and representative of medically important antimicrobial drug classes. Seventy-five EcO157 isolates were recovered from three dairies. Six isolates were resistant to at least 1 of the 10 tested antimicrobial agents: four were resistant to streptomycin, sulfisoxazole, and tetracycline; one was resistant to streptomycin and tetracycline; and one was resistant to only tetracycline. All resistant isolates were from a single dairy. Overall, a low prevalence (8%) of AMR was observed among the 75 EcO157 isolates. No significant effects on AMR profiles due to virulence genes, parity, or previous antimicrobial treatments within the current lactation period were detected. The results of this study provide background information for future comparative studies investigating AMR trends. Future studies should include more participating farms and more samples and should control for potential confounding factors of AMR that may underlie individual farm variation. PMID:26939660

  7. Dissipation of Antimicrobial Resistance Determinants in Composted and Stockpiled Beef Cattle Manure.

    PubMed

    Xu, Shanwei; Sura, Srinivas; Zaheer, Rahat; Wang, George; Smith, Alanna; Cook, Shaun; Olson, Andrew F; Cessna, Allan J; Larney, Francis J; McAllister, Tim A

    2016-03-01

    Windrow composting or stockpiling reduces the viability of pathogens and antimicrobial residues in manure. However, the impact of these manure management practices on the persistence of genes coding for antimicrobial resistance is less well known. In this study, manure from cattle administered 44 mg of chlortetracycline kg feed (dry wt. basis) (CTC), 44 mg of CTC and 44 mg of sulfamethazine kg feed (CTCSMZ), 11 mg of tylosin kg feed (TYL), and no antimicrobials (control) were composted or stockpiled over 102 d. Temperature remained ≥55°C for 35 d in compost and 2 d in stockpiles. Quantitative PCR was used to measure levels of 16S rRNA genes and tetracycline [(B), (C), (L), (M), (W)], erythromycin [(A), (B), (F), (X)], and sulfamethazine [(1), (2)] resistance determinants. After 102 d, 16S rRNA genes and all resistance determinants declined by 0.5 to 3 log copies per gram dry matter. Copies of 16S rRNA genes were affected ( < 0.05) by antimicrobials with the ranking of control > CTC = TYL > CTCSMZ. Compared with the control, antimicrobials did not increase the abundance of resistance genes in either composted or stockpiled manure, except (M) and (2) in CTCSMZ ( < 0.05). The decline in 16S rRNA genes and resistance determinants was higher ( < 0.05) in composted than in stockpiled manure. We conclude that composting may be more effective than stockpiling in reducing the introduction of antimicrobial resistance genes into the environment before land application of manure. PMID:27065400

  8. Antimicrobial resistance and genetic diversity of Escherichia coli isolated from humans and foods

    PubMed Central

    Melo, Daniela Benevides; Menezes, Ana Paula de Oliveira; Reis, Joice Neves; Guimarães, Alaíse Gil

    2015-01-01

    Antibiotic resistance has increased in recent years, raising the concern of public health authorities. We conducted a study of Escherichia coli isolates obtained from human and food samples to assess the prevalence of antimicrobial resistance and to determine the genotype and clonal relationship of 84 E. coli isolates (48 from humans and 36 from foods). An antimicrobial susceptibility test was performed using the disk diffusion method. Virulence factors were evaluated by multiplex PCR, and the clonal relationship among the resistant isolates was studied by Pulsed Field Gel Electrophoresis (PFGE). All isolates were susceptible to ceftriaxone. Overall, 26%, 20.2%, 15.4% and 6% of the isolates were resistant to tetracycline, ampicillin, sulfamethoxazole/trimethoprim and cephalotin, respectively. Twenty two percent of the isolates exhibited resistance to more than one antimicrobial agent. Multiple-drug resistance was mostly observed in the human isolates and involved the antibiotics ampicillin and tetracycline. None of the six virulence genes were identified among the isolates. Analysis of genetic diversity by PFGE of 31 resistant isolates, revealed 29 distinct restriction patterns. In conclusion, E. coli from humans and foods are resistant to commonly used antibiotics and are highly genetically diverse. In this setting, inappropriate use of antibiotics may be a cause of high resistance rate instead of clonal spread. PMID:26691477

  9. Overcoming acquired BRAF inhibitor resistance in melanoma via targeted inhibition of Hsp90 with ganetespib.

    PubMed

    Acquaviva, Jaime; Smith, Donald L; Jimenez, John-Paul; Zhang, Chaohua; Sequeira, Manuel; He, Suqin; Sang, Jim; Bates, Richard C; Proia, David A

    2014-02-01

    Activating BRAF kinase mutations serve as oncogenic drivers in over half of all melanomas, a feature that has been exploited in the development of new molecularly targeted approaches to treat this disease. Selective BRAF(V600E) inhibitors, such as vemurafenib, typically induce initial, profound tumor regressions within this group of patients; however, durable responses have been hampered by the emergence of drug resistance. Here, we examined the activity of ganetespib, a small-molecule inhibitor of Hsp90, in melanoma lines harboring the BRAF(V600E) mutation. Ganetespib exposure resulted in the loss of mutant BRAF expression and depletion of mitogen-activated protein kinase and AKT signaling, resulting in greater in vitro potency and antitumor efficacy compared with targeted BRAF and MAP-ERK kinase (MEK) inhibitors. Dual targeting of Hsp90 and BRAF(V600E) provided combinatorial benefit in vemurafenib-sensitive melanoma cells in vitro and in vivo. Importantly, ganetespib overcame mechanisms of intrinsic and acquired resistance to vemurafenib, the latter of which was characterized by reactivation of extracellular signal-regulated kinase (ERK) signaling. Continued suppression of BRAF(V600E) by vemurafenib potentiated sensitivity to MEK inhibitors after acquired resistance had been established. Ganetespib treatment reduced, but not abolished, elevations in steady-state ERK activity. Profiling studies revealed that the addition of a MEK inhibitor could completely abrogate ERK reactivation in the resistant phenotype, with ganetespib displaying superior combinatorial activity over vemurafenib. Moreover, ganetespib plus the MEK inhibitor TAK-733 induced tumor regressions in vemurafenib-resistant xenografts. Overall these data highlight the potential of ganetespib as a single-agent or combination treatment in BRAF(V600E)-driven melanoma, particularly as a strategy to overcome acquired resistance to selective BRAF inhibitors. PMID:24398428

  10. [A mathematical model for the chemical control of Aedes aegypti (Diptera: Culicidae) having acquired chemical resistance].

    PubMed

    Restrepo-Alape, Leonardo D; Toro-Zapata, Hernán D; Muñoz-Loaiza, Aníbal

    2010-12-01

    Dengue fever is a common vector-borne disease in tropical and subtropical areas. It is transmitted to humans by the bite of an infected female Aedes mosquito. Since no vaccines are currently available which can protect against infection, disease control relies on controlling the mosquito population. This work was aimed at modelling such mosquito's population dynamics regarding chemical control of the adult population and its acquired resistance to chemicals. The model was analysed by using classical dynamic system theory techniques and mosquito growth threshold was determined as this establishes when a particular population may prosper in the environment or when it is likely to disappear. A suitable chemical control strategy was developed from such threshold. Simulations were made in control and non-control scenarios; this determined the degree of control application effectiveness against different levels of acquired resistance. PMID:22030690

  11. Naturally occurring dominant drug resistance mutations occur infrequently in the setting of recently acquired hepatitis C

    PubMed Central

    Applegate, Tanya L; Gaudieri, Silvana; Plauzolles, Anne; Chopra, Abha; Grebely, Jason; Lucas, Michaela; Hellard, Margaret; Luciani, Fabio; Dore, Gregory J; Matthews, Gail V

    2014-01-01

    Background Directly Acting Antivirals (DAAs) are predicted to transform hepatitis C (HCV) therapy, yet little is known about the prevalence of naturally occurring resistance mutations in recently acquired HCV. This study aimed to determine the prevalence and frequency of drug resistance mutations in the viral quasispecies among HIV positive and negative individuals with recent HCV. Methods The NS3 protease, NS5A and NS5B polymerase genes were amplified from fifty genotype 1a participants of the Australian Trial in Acute Hepatitis C. Amino acid variations at sites known to be associated with possible drug resistance were analysed by ultra-deep pyrosequencing. Results Twelve percent of individuals harboured dominant resistance mutations, while 36% demonstrated non dominant resistant variants below that detectable by bulk sequencing (ie < 20%) but above a threshold of 1%. Resistance variants (< 1%) were observed at most sites associated with DAA resistance from all classes, with the exception of sofosbuvir. Conclusions Dominant resistant mutations were uncommonly observed in the setting of recent HCV. However, low level mutations to all DAA classes were observed by deep sequencing at the majority of sites, and in most individuals. The significance of these variants and impact on future treatment options remains to be determined. PMID:25105742

  12. Resistance to antimicrobial agents of Campylobacter spp. strains isolated from animals in Poland.

    PubMed

    Krutkiewicz, A; Sałamaszyńska-Guz, A; Rzewuska, M; Klimuszko, D; Binek, M

    2009-01-01

    A total of 69 Campylobacter jejuni and 16 Campylobacter coli strains isolated from chicken, dog and pig stool samples were characterized based on their resistance to five antimicrobial agents and on plasmid pTet profiles. Antimicrobials used in this study were: amoxicillin/clavulanic acid, ciprofloxacin, erythromycin, tetracycline and trimethoprim/sulfamethoxazole. Among the isolates studied, 91.7% were resistant to one or more antimicrobial agent. The highest level of resistance for the whole test group was to trimethoprim/sulfamethoxazole (57.6%), followed by ciprofloxacin (44.2%) and tetracycline (20%). All isolates were susceptible to amoxicillin/clavulanic acid. Strains isolated from chickens were susceptible to erythromycin. Few erythromycin-resistant strains were isolated from dogs and pigs (5.8%). C. coli strains exhibited a higher antibiotic resistance than C. jejuni strains, excluding resistance to trimethoprim/sulfamethoxazole. The pTet plasmid harboring the tet(O) gene was detected in 14 Campylobacter spp. strains. Our studies demonstrate that the majority (71.4%) of tetracycline-resistant isolates carry a plasmid-borne tet(O) gene, particularly strains for which the minimum inhibitory concentration (MIC) are > or = 256 microg/ml. In conclusion, we have found high-level trimethoprim/sulfamethoxazole, ciprofloxacin and tetracycline resistance in Polish strains isolated from different sources. This study has demonstrated that resistance of Campylobacter species differs depending on both the bacterial species and animal origins. All strains that displayed resistance to four antimicrobial agents were isolated from pigs. Localization of the tet(O) gene on either plasmid or chromosome was not found to be correlated with tetracycline resistance. PMID:20169919

  13. A family cluster of tuberculosis cases, including a case of acquired multidrug resistant tuberculosis.

    PubMed

    Holden, Julie; Trachtman, Louis

    2012-01-01

    Although the number of tuberculosis cases in the US is at an all-time low, with progressive declines seen for the past 17 years, many goals in the tuberculosis elimination process remain unrealized. This report describes a cluster of four tuberculosis cases in a family, including one case of acquired multidrug resistant tuberculosis. It also underscores some important issues in tuberculosis control today, including significant disparities in the foreign-born population with multidrug resistant tuberculosis as a looming problem, as well as utilization of therapeutic drug level monitoring in complicated cases. PMID:22533114

  14. Acquired PIK3CA amplification causes resistance to selective phosphoinositide 3-kinase inhibitors in breast cancer.

    PubMed

    Huw, L-Y; O'Brien, C; Pandita, A; Mohan, S; Spoerke, J M; Lu, S; Wang, Y; Hampton, G M; Wilson, T R; Lackner, M R

    2013-01-01

    Agents targeting the PI3K/mTOR signaling axis have shown promise in early-phase clinical trials and are currently being studied in later stages of clinical development in multiple indications. Experience with other targeted agents suggests that clinical responses may be short-lived because of acquired resistance to therapy. Here, we report preclinical modeling of acquired resistance in a HER2-positive, PIK3CA mutant breast cancer cell line, KPL-4. We identified a heretofore-unreported mechanism of resistance, specifically high-level amplification of the mutant allele of PIK3CA, which resulted in a marked upregulation of PI3K signaling, enabling resistant cells to regain proliferative capacity at clinically relevant concentrations of the PI3K inhibitor, GDC-0941. We show that knockdown of the amplified PIK3CA mutant allele in these cells by small interfering RNA restored pathway signaling and sensitivity to PI3K inhibition at levels comparable to parental cells. These novel preclinical findings suggest that, in addition to assessment of other previously reported mechanisms of resistance, evaluation of PI3K copy number variation should be integrated into the exploratory analysis of biopsies obtained at disease progression. PMID:24366379

  15. Physiological and Molecular Characteristics of Elicitin-Induced Systemic Acquired Resistance in Tobacco.

    PubMed Central

    Keller, H.; Blein, J. P.; Bonnet, P.; Ricci, P.

    1996-01-01

    Elicitins are low molecular weight proteins secreted by all Phytophthora species analyzed so far. Application of the purified proteins to tobacco Nicotiana tabacum leads to the induction of resistance to subsequent inoculations with the black shank-causing agent, Phytophthora parasitica var nicotianae. In this paper, we describe the systemic characteristics of elicitin-induced acquired resistance in tobacco. Elicitin application is followed by the rapid translocation of the protein in the plant. The basic elicitin, cryptogein, induces necrosis formation in the leaves, which results from accumulation of the protein in these organs. Necrosis does not seem to be essential for the establishment of systemic acquired resistance (SAR), since resistance induced by the acidic elicitin, capsicein, is not accompanied by the development of visible symptoms on the leaves. Both elicitins trigger the coordinate accumulation of transcripts from nine genes, previously described to be expressed during establishment of SAR. Additionally, elicitin treatment leads to the activation of the multiple response gene str 246. In leaves, transcript accumulation was found to be higher in all cases in response to cryptogein compared to capsicein treatment. These results, along with northern hybridization analysis following infiltration of leaves with cryptogein, indicate that SAR genes appear to be expressed locally, corresponding to necrosis formation as well as systemically during induction of resistance. To our knowledge, elicitins are the only well-characterized, pathogen-derived molecules that trigger SAR in a plant. PMID:12226188

  16. Epidermal growth factor receptor cooperates with Src family kinases in acquired resistance to cetuximab.

    PubMed

    Wheeler, Deric L; Iida, Mari; Kruser, Tim J; Nechrebecki, Meghan M; Dunn, Emily F; Armstrong, Eric A; Huang, Shyhmin; Harari, Paul M

    2009-04-01

    The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that plays a major role in oncogenesis. Cetuximab is an EGFR-blocking antibody that is FDA approved for use in patients with metastatic colorectal cancer (mCRC) and head and neck squamous cell carcinoma (HNSCC). Although cetuximab has shown strong clinical benefit for a subset of cancer patients, most become refractory to cetuximab therapy. We reported that cetuximab-resistant NSCLC line NCI-H226 cells have increased steady-state expression and activity of EGFR secondary to altered trafficking/degradation and this increase in EGFR expression and activity lead to hyper-activation of HER3 and down stream signals to survival. We now present data that Src family kinases (SFKs) are highly activated in cetuximab-resistant cells and enhance EGFR activation of HER3 and PI(3)K/Akt. Studies using the Src kinase inhibitor dasatinib decreased HER3 and PI(3)K/Akt activity. In addition, cetuximab-resistant cells were resensitized to cetuximab when treated with dasatinib. These results indicate that SFKs and EGFR cooperate in acquired resistance to cetuximab and suggest a rationale for clinical strategies that investigate combinatorial therapy directed at both the EGFR and SFKs in patients with acquired resistance to cetuximab. PMID:19276677

  17. Antimicrobial Stewardship

    PubMed Central

    Doron, Shira; Davidson, Lisa E.

    2011-01-01

    Antimicrobial resistance is increasing; however, antimicrobial drug development is slowing. Now more than ever before, antimicrobial stewardship is of the utmost importance as a way to optimize the use of antimicrobials to prevent the development of resistance and improve patient outcomes. This review describes the why, what, who, how, when, and where of antimicrobial stewardship. Techniques of stewardship are summarized, and a plan for implementation of a stewardship program is outlined. PMID:22033257

  18. Narrow grass hedges reduce tylosin and associated antimicrobial resistance genes in agricultural runoff.

    PubMed

    Soni, Bhavneet; Bartelt-Hunt, Shannon L; Snow, Daniel D; Gilley, John E; Woodbury, Bryan L; Marx, David B; Li, Xu

    2015-05-01

    Agricultural runoff from areas receiving livestock manure can potentially contaminate surface water with antimicrobials and antimicrobial resistance genes (ARGs). The objective of this study was to investigate the effectiveness of narrow grass hedges (NGHs) on reducing the transport of antimicrobials and ARGs in runoff after land application of swine manure slurry. Plot-scale rainfall simulation tests were conducted on 0.75 m by 4.0 m plots designed to test three treatment factors: manure amendment (control plots receiving no manure vs. amended plots receiving manure based on 3 times N requirement), NGH (plots with a NGH vs. plots without a NGH), and rainfall events (days 1-3). Runoff generated during three 30-min simulated rainfall events was sampled and analyzed for antimicrobials and ARGs. Manure amendment was responsible for the presence of antimicrobial tylosin ( < 0.0001) and tylosin resistance gene (B) ( < 0.0001) in runoff. Narrow grass hedges proved to be effective in reducing tylosin ( < 0.0001) and (B) ( < 0.0347) in runoff. Manure amendment was responsible for the introduction of tylosin ( < 0.0482) and (B) ( = 0.0128) into the soil; however, it had no significant impact on the abundance of the 16S rRNA gene in soil. Results from this study suggest that NGHs could be a best management practice to control the transport of antimicrobials and ARGs in agricultural runoff. PMID:26024269

  19. Chitosan Microparticles Exert Broad-Spectrum Antimicrobial Activity against Antibiotic-Resistant Micro-organisms without Increasing Resistance.

    PubMed

    Ma, Zhengxin; Kim, Donghyeon; Adesogan, Adegbola T; Ko, Sanghoon; Galvao, Klibs; Jeong, Kwangcheol Casey

    2016-05-01

    Antibiotic resistance is growing exponentially, increasing public health concerns for humans and animals. In the current study, we investigated the antimicrobial features of chitosan microparticles (CM), engineered from chitosan by ion gelation, seeking potential application for treating infectious disease caused by multidrug resistant microorganisms. CM showed excellent antimicrobial activity against a wide range of microorganisms, including clinically important antibiotic-resistant pathogens without raising resistant mutants in serial passage assays over a period of 15 days, which is a significantly long passage compared to tested antibiotics used in human and veterinary medicine. In addition, CM treatment did not cause cross-resistance, which is frequently observed with other antibiotics and triggers multidrug resistance. Furthermore, CM activity was examined in simulated gastrointestinal fluids that CM encounter when orally administered. Antimicrobial activity of CM was exceptionally strong to eliminate pathogens completely. CM at a concentration of 0.1 μg/mL killed E. coli O157:H7 (5 × 10(8) CFU/mL) completely in synthetic gastric fluid within 20 min. Risk assessment of CM, in an in vitro animal model, revealed that CM did not disrupt the digestibility, pH or total volatile fatty acid production, indicating that CM likely do not affect the functionality of the rumen. Given all the advantages, CM can serve as a great candidate to treat infectious disease, especially those caused by antibiotic-resistant pathogens without adverse side effects. PMID:27057922

  20. Antimicrobial Resistance and Virulence Characterization among Escherichia coli Clinical Isolates Causing Severe Obstetric Infections in Pregnant Women

    PubMed Central

    Guiral, Elisabet; Sáez-López, Emma; Bosch, Jordi; Goncé, Anna; López, Marta; Sanz, Sergi; Vila, Jordi

    2015-01-01

    The virulence markers and the antimicrobial resistance profiles of 78 Escherichia coli isolates causing obstetric infections accompanied by sepsis or not were studied. Adhesion-related virulence factors were the most prevalent markers. Low rates of resistance to the antimicrobial agents used as first-line therapy suggest their correct implementation in stewardship guidelines. PMID:25740771

  1. Genotypic and Phenotypic Characterization of Antimicrobial-Resistant Escherichia coli from Farm-Raised Diarrheic Sika Deer in Northeastern China

    PubMed Central

    Li, Rui; He, Liang; Hao, Lili; Wang, Qi; Zhou, Yu; Jiang, Hongchen

    2013-01-01

    In China, overuse and/or abuse of antimicrobials are common in stockbreeding, which possess high risks of antimicrobial-resistant contaminations. The serogroups, major virulence genes, and antimicrobial resistant patterns of the antimicrobial-resistant Escherichia coli (E. coli) were investigated in the feces of diarrheic farm-raised sika deer from 50 farms in three Northeastern provinces of China. A total of 220 E. coli isolates were obtained and characterized. Twenty-eight O serogroups were identified from the obtained E. coli isolates with O2, O26, O128, O142 and O154 being dominant. Nearly all the isolates were resistant to at least four of the tested antimicrobials. More than 90% of the E. coli isolates carried at least one of the tested virulence genes. About 85% of the E. coli isolates carried one or more antimicrobial-resistant genes responsible for resistant phenotypes of sulfonamides, streptomycin/spectionomycin or tetracycline. The antimicrobial resistant level and pathogenic group occurrences of the obtained E. coli isolates were higher than that of livestock and wild animals reported in some developed countries. Thus, the fecal-carrying antimicrobial-resistant E. coli from the farm-raised sika deer is potentially a significant contamination source for freshwater systems and food chain, and may pose great health risks for human and animals in Northeastern China. PMID:24039919

  2. Genotypic and phenotypic characterization of antimicrobial-resistant Escherichia coli from farm-raised diarrheic sika deer in Northeastern China.

    PubMed

    Li, Rui; He, Liang; Hao, Lili; Wang, Qi; Zhou, Yu; Jiang, Hongchen

    2013-01-01

    In China, overuse and/or abuse of antimicrobials are common in stockbreeding, which possess high risks of antimicrobial-resistant contaminations. The serogroups, major virulence genes, and antimicrobial resistant patterns of the antimicrobial-resistant Escherichia coli (E. coli) were investigated in the feces of diarrheic farm-raised sika deer from 50 farms in three Northeastern provinces of China. A total of 220 E. coli isolates were obtained and characterized. Twenty-eight O serogroups were identified from the obtained E. coli isolates with O2, O26, O128, O142 and O154 being dominant. Nearly all the isolates were resistant to at least four of the tested antimicrobials. More than 90% of the E. coli isolates carried at least one of the tested virulence genes. About 85% of the E. coli isolates carried one or more antimicrobial-resistant genes responsible for resistant phenotypes of sulfonamides, streptomycin/spectionomycin or tetracycline. The antimicrobial resistant level and pathogenic group occurrences of the obtained E. coli isolates were higher than that of livestock and wild animals reported in some developed countries. Thus, the fecal-carrying antimicrobial-resistant E. coli from the farm-raised sika deer is potentially a significant contamination source for freshwater systems and food chain, and may pose great health risks for human and animals in Northeastern China. PMID:24039919

  3. Development and Validation of an Oligonucleotide Microarray for Detection of Multiple Virulence and Antimicrobial Resistance Genes in Escherichia coli†

    PubMed Central

    Bruant, Guillaume; Maynard, Christine; Bekal, Sadjia; Gaucher, Isabelle; Masson, Luke; Brousseau, Roland; Harel, Josée

    2006-01-01

    An oligonucleotide microarray detecting 189 Escherichia coli virulence genes or markers and 30 antimicrobial resistance genes was designed and validated using DNA from known reference strains. This microarray was confirmed to be a powerful diagnostic tool for monitoring emerging E. coli pathotypes and antimicrobial resistance, as well as for environmental, epidemiological, and phylogenetic studies including the evaluation of genome plasticity. PMID:16672535

  4. Antimicrobial resistance and molecular epidemiology of vancomycin-resistant enterococci from North America and Europe: a report from the SENTRY antimicrobial surveillance program.

    PubMed

    Deshpande, Lalitagauri M; Fritsche, Thomas R; Moet, Gary J; Biedenbach, Douglas J; Jones, Ronald N

    2007-06-01

    Increases in prevalence of vancomycin-resistant enterococci (VRE) have been documented globally since its emergence in the 1980s. A SENTRY Antimicrobial Surveillance Program (2003) objective monitored VRE isolates with respect to antimicrobial susceptibility trends, geographic resistance variability, and clonal dissemination. In 2003, VRE isolates from North America (United States and Canada, n = 839, 26 sites) and Europe (n = 56, 10 sites) were susceptibility tested using Clinical and Laboratory Standards Institute (CLSI) reference methodologies. Based on resistance profiles, 155 isolates displayed similar multidrug-resistant (MDR) profiles and were temporally related; these were subsequently submitted for typing by pulsed-field gel electrophoresis (PFGE). Most of the submitted isolates were Enterococcus faecium (91.0%) and Enterococcus faecalis (7.8%). Among VRE, the VanA phenotype was more prevalent in North America (76%) than Europe (40%), and all isolates had elevated resistance rates to other antimicrobial classes including the following: 1) chloramphenicol resistance among E. faecalis being greater in North America than in Europe (28.6% versus 7.1%, respectively) but reversed among E. faecium (0.5% and 15.0%, the latter due to clonal occurrences); 2) ciprofloxacin resistance in North America >99% for both species and in Europe varying from 85.7% to 87.5%; 3) rare occurrences of linezolid resistance in North America (0.8% to 1.8%) due to G2576U ribosomal mutation; 4) higher quinupristin/dalfopristin resistance observed among European E. faecium strains (10.0% versus 0.6%); and 5) higher rifampin resistance rates among European E. faecalis (21.4% versus 5.4%). Thirty-five MDR epidemic clusters were identified by PFGE in 21 North American and 2 European medical centers including the following: 1) VanA (20 sites, 27 clonal occurrences) and VanB (1 site, 2 clonal occurrences); 2) elevated quinupristin/dalfopristin MIC results (not vatD/E, 3 sites); and 3

  5. Understanding the contribution of environmental factors in the spread of antimicrobial resistance.

    PubMed

    Fletcher, Stephanie

    2015-07-01

    The overuse and abuse of antibiotics have contributed to the global epidemic of antibiotic resistance. Current evidence suggests that widespread dependency on antibiotics and complex interactions between human health, animal husbandry and veterinary medicine, have contributed to the propagation and spread of resistant organisms. The lack of information on pathogens of major public health importance, limited surveillance, and paucity of standards for a harmonised and coordinated approach, further complicates the issue. Despite the widespread nature of antimicrobial resistance, limited focus has been placed on the role of environmental factors in propagating resistance. There are limited studies that examine the role of the environment, specifically water, sanitation and hygiene factors that contribute to the development of resistant pathogens. Understanding these elements is necessary to identify any modifiable interactions to reduce or interrupt the spread of resistance from the environment into clinical settings. This paper discusses some environmental issues that contribute to antimicrobial resistance, including soil related factors, animal husbandry and waste management, potable and wastewater, and food safety, with examples drawn mainly from the Asian region. The discussion concludes that some of the common issues are often overlooked and whilst there are numerous opportunities for environmental factors to contribute to the growing burden of antimicrobial resistance, a renewed focus on innovative and traditional environmental approaches is needed to tackle the problem. PMID:25921603

  6. Analysis of antimicrobial resistance and plasmid profiles in Salmonella serovars associated with tropical seafood of India.

    PubMed

    Kumar, Rakesh; Surendran, P K; Thampuran, Nirmala

    2009-06-01

    A total of 256 Salmonella strains consisting of 29 Salmonella serovars isolated from seafood of Cochin (India) were analyzed for resistance to antimicrobials commonly used in human and veterinary medicines as therapeutic agents. The 10 most predominant Salmonella serovars in seafood were also characterized for presence of plasmids using the alkaline lysis method. Antimicrobial susceptibility studies highlighted a comparatively high resistance in Salmonella isolates to sulfamethizol and carbenicillin, and moderate resistance to nalidixic acid and oxytetracycline. Nevertheless, antimicrobial resistance was not observed against ampicillin, ciprofloxacin, chloramphenicol, gentamicin, and kanamycin in different Salmonella serovars. Fifty percent of the Salmonella isolates, comprising 16 Salmonella serovars, were resistant to sulfamethizol followed by 39% resistant to carbenicillin and 14% resistant to oxytetracycline. Multidrug resistance was detected in 39.4%, 14.4%, 12.1%, and 1.5% of Salmonella isolates towards two drugs (sulfamethizol and carbenicillin), three drugs (sulfamethizol, carbenicillin, and oxytetracycline), four drugs (sulfamethizol, carbenicillin, oxytetracycline, and nalidixic acid), and five drugs (sulfamethizol, carbenicillin, oxytetracycline, nalidixic acid, and streptomycin), respectively. Plasmid profiling highlighted the presence of nine plasmid profiles in Salmonella serovars and plasmids that were not detected in Salmonella enterica subsp. enterica Weltevreden, Salmonella Rissen, Salmonella Bareilly, Salmonella Irumu, Salmonella Ohio, Salmonella Oslo, and Salmonella Typhi isolated from seafood. PMID:19422307

  7. Salmonella contamination, serovars and antimicrobial resistance profiles of cattle slaughtered in South Africa.

    PubMed

    Madoroba, Evelyn; Kapeta, Daniel; Gelaw, Awoke K

    2016-01-01

    Antimicrobial resistant Salmonella are among the leading causes of foodborne infections. Our aim was to determine Salmonella contamination during cattle slaughter in South African rural abattoirs (n = 23) and environmental samples. Furthermore, antimicrobial resistance patterns of the Salmonella isolates were determined. Samples of cattle faeces (n = 400), carcass sponges (n = 100), intestinal contents (n = 62), hides (n = 67), and water from the abattoirs (n = 75) were investigated for Salmonella species using microbiological techniques and species-specific polymerase chain reaction targeting the invA gene. In total 92 Salmonella species isolates were recovered. The Salmonella mean frequency of occurrence on hides, carcasses, and intestinal contents was 35.37% (n = 81). Eleven faecal samples (2.75%) tested positive for Salmonella. The predominant serovar was Salmonella Enteritidis. Diverse serovars that were identified on carcasses were not necessarily found on the hides and intestinal contents. The inconsistent occurrence of the diverse Salmonella serovars on hides, carcasses, and intestinal contents implies that in addition to carriage on hides and in intestinal contents, other external factors also play an important role regarding carcass contamination. The 92 Salmonella were serotyped and tested for susceptibility towards the following antimicrobials: ampicillin, cefotaxime, enrofloxacin, kanamycin, and oxytetracycline using the disk diffusion method. Most Salmonella (n = 66; 71.7%) isolates were resistant to at least one antimicrobial with highest resistance observed towards oxytetracycline (51.90%), which highlights the need for strict hygiene during slaughter and prudent antimicrobial use during animal production. In conclusion, cattle slaughtered in South African rural abattoirs harbour diverse Salmonella serovars that are resistant to antimicrobials, which could be a public health risk. The findings should assist policymakers with improving implementation

  8. Characterization of antimicrobial resistance in Salmonella enterica strains isolated from Brazilian poultry production.

    PubMed

    Mattiello, Samara P; Drescher, Guilherme; Barth, Valdir C; Ferreira, Carlos A S; Oliveira, Sílvia D

    2015-11-01

    Antimicrobial resistance profiles and presence of resistance determinants and integrons were evaluated in Salmonella enterica strains from Brazilian poultry. The analysis of 203 isolates showed that those from the poultry environment (88 isolates) were significantly more resistant to antimicrobials than isolates from other sources, particularly those isolated from poultry by-product meal (106 isolates). Thirty-seven isolates were resistant to at least three antimicrobial classes. Class 1 integrons were detected in 26 isolates, and the analysis of the variable region between the 5' conserved segment (CS) and 3' CS of each class 1 integron-positive isolate showed that 13 contained a typical 3' CS and 14 contained an atypical 3' CS. One Salmonella Senftenberg isolate harbored two class 1 integrons, showing both typical and atypical 3' CSs. The highest percentage of resistance was found to sulfonamides, and sul genes were detected in the majority of the resistant isolates. Aminoglycoside resistance was detected in 50 isolates, and aadA and aadB were present in 28 and 32 isolates, respectively. In addition, strA and strB were detected in 78.1 and 65.6% isolates resistant to streptomycin, respectively. Twenty-one isolates presented reduced susceptibility to β-lactams and harbored bla(TEM), bla(CMY), and/or bla(CTX-M). Forty isolates showed reduced susceptibility to tetracycline, and most presented tet genes. These results highlight the importance of the environment as a reservoir of resistant Salmonella, which may enable the persistence of resistance determinants in the poultry production chain, contributing, therefore, to the debate regarding the impacts that <