Insights into collateral susceptibility and collateral resistance in Acinetobacter baumannii during antimicrobial adaptation

초록

The susceptibility of Acinetobacter baumannii exposed to primary antibiotic can be either increased or decreased when exposed to secondary antibiotic. This study was designed to assess the relative fitness, collateral susceptibility and collateral resistance of polymyxin B- (PMB-) adapted A. baumannii to ciprofloxacin (CIP), meropenem (MER), PMB, tetracycline (TET) and tobramycin (TOB). Strains of wild-type A. baumannii KACC 12454 (AB(KACC)), wild-type A. baumannii CCARM 12088 (AB(CCARM)), PMB-adapted AB(KACC), PMB-adapted AB(CCARM), stabilized AB(KACC) and stabilized AB(CCARM) were used in this study. Compared to the wild-type AB(KACC), the MICs of PMB were increased from 2 to 128 mu g ml(-1) against PMB-adapted AB(KACC), while MICs of CIP, MER, TET and TOB were decreased from 2 to 1 mu g ml(-1), 16 to 1 mu g ml(-1), 16 to 2 mu g ml(-1) and 64 to 16 mu g ml(-1), respectively. The PMB-adapted AB(CCARM) was resistant to CIP (32 mu g ml(-1)) and PMB (64 mu g ml(-1)) compared to the wild-type AB(CCARM). The resistance of stabilized AB(KACC) and AB(CCARM) to all antibiotics was lost after antibiotic-free culture in the exception of CIP and TET. The susceptibilities of wild-type, PMB-adapted and stabilized AB(KACC) and AB(CCARM) to CIP, MER, PMB, TET and TOB were increased in the presence of beta-lactamase and efflux pump inhibitors. The high levels of relative fitness were observed for stabilized AB(KACC), PMB-adapted AB(CCARM) and stabilized AB(CCARM). The stabilized AB(KACC) and PMB-adapted AB(CCARM) were highly heteroresistance to PMB and TET, respectively. The PMB-adapted AB(KACC) and AB(CCARM) showed various antibiotic patterns, known as collateral susceptibility and collateral resistance. The results provide useful information for designing effective antibiotic regimens that can enhance the antibiotic activity against A. baumannii infections.

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