Colistin can be used in patients infected with carbapenem-resistant Acinetobacter baumannii complex (CR-ABC), but recently resistance to colistin and heteroresistance have been reported. In this study we aimed to investigate the colistin heteroresistance rates and the effects of colistin and its combinations on colistin heteroresistance/resistance development in CR-ABC strains in our hospital. Materials and Methods: Heteroresistance analysis was performed on CR-ABC isolates and standard ABC strain [American Type Culture Collection (ATCC) 19606)] strain. To investigate hidden heteroresistance, the isolates were exposed to colistin at sub-inhibitory concentrations. 'Time-kill' study was performed on the standard strain and a clinical strain for colistin. Serial passage test was performed to investigate the effects of drug combinations on heteroresistance/resistance development. Results: In the first heteroresistance analysis test, all strains were found to be non-heteroresistant. However, after sub-inhibitory exposure to colistin, colistin heteroresistance/resistance developed in all isolates. In serial passages, colistin-rifampicin and colistin-tigecycline (Col+Tig) combinations were found to be effective and prevented growth of colistin-resistant sub-populations even at sub-inhibitory doses. Colistin-gentamicin (Col+Gen) combination was not found to be effective against the clinical isolate while it was effective on ATCC strain. Colistin-fluconazole combination was found to be ineffective at all concentrations.
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Gazel et al. (2018) studied this question.
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