Abstract
BackgroundResistance 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.MethodsCRAB 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.ResultsEighty 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.ConclusionsThe presence of subpopulations with higher polymyxin B MIC was extremely common and high-level adaptive resistance was very frequent in CRAB isolates.
Highlights
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
Hetero-resistance has been recently described for colistin in some carbapenem-resistant A. baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae isolates [8,9,10], and other studies have demonstrated the presence of adaptive resistance to polymyxins, mainly in P. aeruginosa [7]
MIC of polymyxin B ranged from ≤0.125 mg/L to ≥64 mg/L
Summary
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. 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. The increasing worldwide prevalence of multi-drug resistant, Acinetobacter baumannii, a major nosocomial pathogen, carbapenem-resistant strains, is of great concern, since treatment becomes restricted to very few options [1]. Polymyxins, both B and E (colistin), are “old” polypeptide antibiotics that re-emerged in clinical practice as the last resort therapy against multidrugresistant Gram-negative bacteria; many, including A. baumannii, are only susceptible to these drugs [2]. The aim of this study was to assess the occurrence of these phenomena and evaluate its stability in CRAB clinical isolates
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