Hetero- and adaptive resistance to polymyxin B in OXA-23-producing carbapenem-resistant Acinetobacter baumannii isolates
1 Post-Graduate Medical Sciences Program, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
2 Biomedicine School, IPA, Porto Alegre, Brazil
3 School of Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
4 Clinical Pathology Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
5 Infectious Diseases Service, Hospital de Clínicas de Porto Alegre, 2350 Ramiro Barcelos St, Porto Alegre 90.035-903, Brazil
Annals of Clinical Microbiology and Antimicrobials 2013, 12:15 doi:10.1186/1476-0711-12-15Published: 2 July 2013
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.