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

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 (ABKACC ), wild-type A. baumannii CCARM 12088 (ABCCARM ), PMB-adapted ABKACC , PMB-adapted ABCCARM , stabilized ABKACC and stabilized ABCCARM were used in this study. Compared to the wild-type ABKACC , the MICs of PMB were increased from 2 to 128 μg ml-1 against PMB-adapted ABKACC , while MICs of CIP, MER, TET and TOB were decreased from 2 to 1 μg ml-1 , 16 to 1 μg ml-1 , 16 to 2 μg ml-1 and 64 to 16 μg ml-1 , respectively. The PMB-adapted ABCCARM was resistant to CIP (32 μg ml-1 ) and PMB (64 μg ml-1 ) compared to the wild-type ABCCARM . The resistance of stabilized ABKACC and ABCCARM 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 ABKACC and ABCCARM to CIP, MER, PMB, TET and TOB were increased in the presence of β-lactamase and efflux pump inhibitors. The high levels of relative fitness were observed for stabilized ABKACC , PMB-adapted ABCCARM and stabilized ABCCARM . The stabilized ABKACC and PMB-adapted ABCCARM were highly heteroresistance to PMB and TET, respectively. The PMB-adapted ABKACC and ABCCARM 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.