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HMW PBPs, which are bifunctional enzymes containing transglycosylase and transpeptidase domains, are categorized into class A, and PBPs lacking the transglycosylase domain are categorized into class B. We found 2 SNPs in the genes coding for 2 high molecular weight (HMW) penicillin-binding proteins (PBPs) ( Figure 1). Through whole-genome sequencing, we found 13 single-nucleotide polymorphisms (SNPs) that differentiated the imipenem-resistant and imipenem-susceptible RT017 isolates ( Table 2 Figure 1 Technical Appendix). The domains and conserved motifs SXXK, SXN, and KTG are shown for the following. Amino acid substitutions in 2 PBPs predicted to be associated with imipenem resistance in Clostridium difficile, Portugal. Multidrug resistance to noncarbapenem antimicrobial drugs correlated with the presence of several genetic determinants, many located in mobile genetic elements ( Figure 1 online Technical Appendix), in line with the idea that multidrug-resistant strains have a selective advantage ( 4) and that horizontal gene transfer plays a major role in the evolution of this pathogen ( 11).įigure 2. In this study, the 22 RT017 imipenem-resistant isolates were also found to be resistant to all of these antimicrobial drugs and showed higher meropenem and ertapenem MICs than those of the RT017 imipenem-susceptible isolates ( Table 1 Technical Appendix Technical Appendix Figure). difficile strains are frequently resistant to clindamycin, erythromycin, moxifloxacin, tetracycline, or rifampin (individually or in combination) ( 8, 10). A) Core genome single-nucleotide polymorphism–based neighbor-joining phylogeny of 25 RT017 C. Phylogeny of Clostridium difficile RT017 isolates from hospitals A and B and genetic determinants of antimicrobial drug resistance, Portugal. In another study, isolates collected in a South Korea hospital during 2000–2009 were analyzed, and a resistance rate to imipenem of 8% (12% among RT017 isolates) was found ( 10).įigure 1. difficile strains, the overall rate of resistance to imipenem, an antimicrobial drug of the carbapenem class, currently widely used as a last-line drug to treat infections by gram-negative bacteria, was found to be 7.41%, and the geometric mean (GM) MIC of imipenem for RT017 strains was 5.91 mg/L ( 8). In particular, RT017, the most common toxin A–negative, toxin B–positive ribotype, is widespread in Asia and is common in Europe ( 7– 9). Strains of other ribotypes, including RT078 and RT017, which have enhanced virulence, have emerged ( 6). This shift was mainly associated with the dissemination of fluoroquinolone-resistant PCR ribotype (RT) 027, which has been responsible for hospital outbreaks worldwide. In past decades, CDI prominence has increased because of a sudden rise in outbreaks and an increase in disease severity and death ( 5). difficile strains determinants of resistance are often found in horizontally transferable mobile genetic elements ( 4). Multidrug resistance is frequently found in epidemic C. Multiple antimicrobial drugs can promote CDI, and cephalosporins and fluoroquinolones have been associated with a higher risk for CDI ( 3). CDI is mainly mediated by the TcdA and TcdB toxins, though some strains additionally produce a binary toxin. difficile spores to germinate in the colon and providing a selective advantage to nonsusceptible strains ( 3). Antimicrobial drugs disrupt the protective gut microbiota, enabling ingested C.
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difficile infection (CDI) usually develops in previously hospitalized persons with a recent history of antimicrobial drug use and causes illness with symptoms ranging from mild diarrhea to potentially lethal pseudomembranous colitis ( 2). Clostridium difficile, a toxin-producing, spore-forming bacillus, is a main cause of nosocomial antimicrobial drug–associated diarrhea in industrialized countries ( 1).