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Ann Clin Microbiol Antimicrob. 2013 Jul 2;12:15. doi: 10.1186/1476-0711-12-15.

Hetero- and adaptive resistance to polymyxin B in OXA-23-producing carbapenem-resistant Acinetobacter baumannii isolates.



Resistance rates to polymyxin B in surveillance studies have been very low despite its increasing use worldwide as the last resort therapy for multidrug-resistant Gram-negative bacilli. However, two other resistance phenotypes, hetero- and adaptive resistance, have been reported to polymyxin. We aimed to investigate the presence of polymyxin B hetero- and adaptive resistance and evaluate its stability in carbapenem-resistant Acinetobacter baumannii (CRAB) clinical isolates.


CRAB isolates were recovered from hospitalized patients at three Brazilian hospitals. Hetero-resistance was determined by population analysis profile (PAP). Adaptive resistance was evaluated after serial daily passages of isolates in Luria-Bertani broth containing increasing polymyxin B concentrations. MICs of polymyxin B of colonies growing at the highest polymyxin B concentration were further determined after daily sub-cultured in antibiotic-free medium and after storage at -80°C, in some selected isolates.


Eighty OXA-23-producing CRAB isolates were typed resulting in 15 distinct clones. Twenty-nine randomly selected isolates (at least one from each clone) were selected for hetero- resistance evaluation: 26 (90%) presented growth of subpopulations with higher polymyxin B MIC than the original one in PAP. No isolate has grown at polymyxin B concentrations higher than 2 mg/L. Polymyxin B MICs of subpopulations remained higher than the original population after daily passages on antibiotic-free medium but returned to the same or similar levels after storage. Twenty-two of the 29 isolates (at least one from each clone) were evaluated for adaptive resistance: 12 (55%) presented growth in plates containing 64 mg/L of polymyxin B. Polymyxin B MICs decreased after daily passages on antibiotic-free medium and returned to the same levels after storage.


The presence of subpopulations with higher polymyxin B MIC was extremely common and high-level adaptive resistance was very frequent in CRAB isolates.

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