Colistin heteroresistance in carbapenem-resistantAcinetobacter baumanniiclinical isolates from a Thai university hospital

Colistin is the last resort for the treatment of infections with carbapenem-resistant (CR) Gram-negative bacteria particularlyAcinetobacter baumannii(CRAB). Currently, both colistin-resistant and -heteroresistantA. baumanniiisolates have been reported globally. We therefore investigated the colistin heteroresistance rate in 75 non-duplicate colistin-susceptible CRAB clinical isolates from a Thai university collected in 2016. Minimum inhibitory concentrations (MICs) of colistin for all isolates were determined by broth microdilution method and carbapenemase genes were detected by PCR methods. All isolates were genotyped by ERIC-PCR method and screened for colistin heteroresistance by modified population analysis profile (PAP) method. The colistin MIC range for the 75 isolates was 0.5-2 mu g/mL, with MIC(50)and MIC(90)of 1 and 2 mu g/mL, respectively. Thirty-three isolates (44%) were considered colistin-heteroresistant with subpopulations growing at 3-8 mu g/mL of colistin. After three daily passages of the subpopulations on antibiotic-free medium, their colistin MICs ranged from 4 to > 32 mu g/mL, with MIC(50)and MIC(90)of 32 and > 32 mu g/mL, respectively. Eight different ERIC-PCR profiles were obtained among the 33 isolates and all carriedbla(OXA-23-like). The high rate of colistin heteroresistance in the CRAB isolates highlights the possibility of treatment failure of CRAB infections by colistin due to the selection of colistin-resistant subpopulations.