Cefmetazole Resistance Mechanism for Including ESBL-Producing Strains.

PURPOSE

Cefmetazole (CMZ), a cephamycin antibiotic, is primarily used as a definitive therapy for Extended Spectrum β-Lactamase (ESBL)-producing infections. However, the mechanism of CMZ resistance in is still unknown. To elucidate the resistance mechanism and to determine combined drugs for prevention of resistance acquisition.

METHODS

Clinical isolates of 14 ESBL-producing and non-producing 12 isolates were used in in vitro testing of CMZ resistance acquisition. After 10-day of CMZ exposure (1st subculture), these strains were incubated in an antibacterial-free medium for 14-day. These strains were again exposed to CMZ for 10-day (2nd subculture) and confirmed for changes in MIC. For each strain detected after 1st subculture, each mRNA expression level of porin, chromosomal , and drug-efflux pump was measured using real-time RT-PCR. Relebactam (REL) has the potency to recover antimicrobial activity against carbapenem-resistant that has porin deficiency. REL was added to the CMZ dilution series, and MIC changes and those of porin were confirmed.

RESULTS

Of these 26 strains, 15 strains (57.7%) acquired resistance after 1st subculture, but after passage culture on the antibacterial-free medium, 11 strains recovered susceptibility. These 11 strains showed resistance after 2nd subculture. The expression levels of and were significantly decreased in these strains (<0.05). When REL was added, all strains suppressed resistance acquisition after 1st subculture. The mechanism was the activation of .

CONCLUSION

Our results showed that the mRNA expression levels of genes encoding porin were decreased in the strains that acquired resistance due to CMZ exposure, and that and in particular were thought to be involved in the acquisition of resistance. The CMZ acquisition of resistance was also suppressed by the concomitant use of REL and actually suppressed the decrease in mRNA expression in . It was confirmed that porin reactivated by REL.