Extended-spectrum beta-lactamases (ESBLs) are one of the most common defence mechanisms of gram-negative bacteria against beta-lactam antibiotics. Treatment options for infections with ESBL-producing Enterobacteriaceae are limited. Most of ESBL enzymes can be inhibited by clavulanate and tazobactam, in-vitro. In many clinical studies, beta-lactam beta-lactamase inhibitor (BLBLI) combinations have been compared with type-2 carbapenems (e.g. imipenem or meropenem), as gold standard antibiotics for the treatment of infections caused by ESBL-producing organisms. Nevertheless, the results of these trials have been somewhat conflicting.Cefepime was another alternative for the treatment of these infections owing to its relative resistance to hydrolysis by ESBLs as compared with other cephalosporins. However, some ESBLs have high hydrolysing capabilities against cefepime (e.g. CTX-M-type) and BLBLI combinations (e.g. SHV-type). Additionally, microorganisms containing ESBLs can harbour other types of beta-lactamases (narrow spectrum oxacillinases [e.g. OXA-1] and AmpCtype beta-lactamases) and non-beta-lactamase resistance mechanisms (e.g. porin loss mutations, efflux pumps). Overall, bacteria can reduce their susceptibility or become fully resistant against cephalosporins, BLBLI combinations and even carbapenems when the simultaneous expression of these mechanisms exists. These bacteria can also have resistance genes on the same plasmid encoding ESBLs. They can become insusceptible to a variety of antibiotics, including fluoroquinolones, trimethoprim-sulfamethoxazole and aminoglycosides, thus further limiting therapeutic alternatives. Rapid dissemination of ESBL genes in the community and increasing prevalence of community-onset infections caused by ESBL-producing organisms have recently become a critical public health threat. A variety of infections, including urinary tract infections and bloodstream infections, can be seen in the community setting with these bacteria. International travel, urban wastewater, food animals, companion animals and contaminated drinking waters have been identified as possible sources for transmission of ESBL-producing organisms to humans in the community. Overall, these conditions result in a significant challenge to administer appropriate empirical antimicrobial therapy for patients in the community and hospital settings.Extended-spectrum β-lactamase-Producing Enterobacteriaceae Aslan et al.
Peer-review: Externally peer-reviewedAuthor Contributions: Concept -A.T.A., M.A.; Design -A.T.A, M.A.; Supervision -A.T.A., M.A.; Data Collection and/or Processing -A.T.A.; Analysis and/or Interpretation -A.T.A.; Literature Review -A.T.A.; Writer -A.T.A, M.A.; Critical Reviews -A.T.A, M.A. Conflict of Interest: The authors have no conflict of interest to declare.