Emergence of carbapenem resistance in Bacteroides fragilis in China

Abstract

The antimicrobial resistance crisis makes it critically important for laboratories to closely monitor trends and mechanisms of emerging antimicrobial resistance in clinical isolates. Bacteroides fragilis is an anaerobic pathogen that causes several serious infections and is increasingly resistant to antimicrobial agents. However, data from China regarding antimicrobial resistance in B. fragilis are limited. In this work, the mechanism underlying carbapenem resistance in 44 B. fragilis isolates collected from a Chinese hospital was investigated. Antimicrobial susceptibility testing for 13 antimicrobial agents was performed by the agar dilution method, and the contribution of efflux pumps to carbapenem resistance was analysed. Genetic relatedness of the isolates was determined by PFGE. Outer membrane porins were analysed in isolates with reduced carbapenem susceptibility. Potential carbapenemase-encoding genes were identified, and the location and environment of the cfiA gene was analysed. Among the 44 isolates, 18.2%, 29.5%, 22.7%, 100%, 100%, 29.5%, 15.9%, 81.8%, 88.6% and 47.7% were resistant to imipenem, meropenem, ertapenem, penicillin, ampicillin, amoxicillin/clavulanic acid, piperacillin/tazobactam, clindamycin, tetracycline and moxifloxacin, respectively. None of the isolates were resistant to metronidazole, cefoxitin or chloramphenicol. A chromosomally located gene (cfiA) encoding a metallo-β-lactamase was identified in 16 isolates (36.4%). A conserved insertion sequence of IS1187 or IS613 was upstream of cfiA in eight isolates with high-level carbapenem resistance. The insertion sequences were associated with increased carbapenem resistance in B. fragilis by upregulating the expression of cfiA as shown by RT-qPCR. This is the first study to describe a mechanism of carbapenem resistance in B. fragilis in mainland China.