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Open Access Research

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

Juliana Barin1, Andreza Francisco Martins2, Bianca Lucia Heineck3, Afonso Luis Barth4 and Alexandre Prehn Zavascki5*

Author Affiliations

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

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Annals of Clinical Microbiology and Antimicrobials 2013, 12:15  doi:10.1186/1476-0711-12-15

Published: 2 July 2013

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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

Keywords:
Acinetobacter baumannii; Polymyxins; Polymyxin B; Colistin; Hetero-resistance; Adaptive resistance; Multidrug-resistance; Carbapenemase