Abstract
The worldwide increase in the emergence of carbapenem resistant Acinetobacter baumannii (CRAB) calls for the investigation into alternative approaches for treatment. This study aims to evaluate colistin-carbapenem combinations against Acinetobacter spp., in order to potentially reduce the need for high concentrations of antibiotics in therapy. This study was conducted on 100 non-duplicate Acinetobacter isolates that were collected from different patients admitted at Saint George Hospital-University Medical Center in Beirut. The isolates were identified using API 20NE strips, which contain the necessary agents to cover a panel of biochemical tests, and confirmed by PCR amplification of blaOXA−51−like. Activities of colistin, meropenem and imipenem against Acinetobacter isolates were determined by ETEST and microdilution methods, and interpreted according to the guidelines of the Clinical and Laboratory Standards Institute. In addition, PCR amplifications of the most common beta lactamases contributing to carbapenem resistance were performed. Tri locus PCR–typing was also performed to determine the international clonality of the isolates. Checkerboard, ETEST and time kill curves were then performed to determine the effect of the colistin-carbapenem combinations. The synergistic potential of the combination was then determined by calculating the Fractional Inhibitory Concentration Index (FICI), which is an index that indicates additivity, synergism, or antagonism between the antimicrobial agents. In this study, 84% of the isolates were resistant to meropenem, 78% to imipenem, and only one strain was resistant to colistin. 79% of the isolates harbored blaOXA−23−like and pertained to the International Clone II. An additive effect for the colistin-carbapenem combination was observed using all three methods. The combination of colistin-meropenem showed better effects as compared to colistin-imipenem (p < 0.05). The colistin-meropenem and colistin-imipenem combinations also showed a decrease of 2.6 and 2.8-fold, respectively in the MIC of colistin (p < 0.001). Time kill assays additionally showed synergistic effects for a few isolates, and no bacterial re-growth was detected following a 24 h incubation. Our study showed that the combination of colistin with carbapenems could be a promising antimicrobial strategy in treating CRAB infections and potentially lowering colistin toxicity related to higher doses used in colistin monotherapy.
Highlights
Acinetobacter spp. are organisms that could be found almost ubiquitously in nature
In terms of the susceptibility patterns determined by the disc diffusion method, 84% of the isolates were resistant to meropenem and 78% were resistant to imipenem. 88% of the isolates were classified as Multi-Drug Resistant (MDR) since they showed resistance to at least three categories of antimicrobial agents
The disc diffusion method showed a 19% resistance to colistin (Figure 2), the microdilution method showed that only one isolate was resistant to colistin
Summary
Acinetobacter spp. are organisms that could be found almost ubiquitously in nature. some species, especially Acinetobacter baumannii and its closely related species, have a great clinical significance in hospital environments since they are often associated with outbreaks and nosocomial infections (Towner, 2009; Howard et al, 2012). Multi-Drug Resistant (MDR) Acinetobacter baumannii is being increasingly implicated with infecting critically ill patients. The emergence of Carbapenem Resistant Acinetobacter baumannii (CRAB) strains and their detection in several regions across the world makes their treatment increasingly challenging (Towner, 2009; Howard et al, 2012). A wide range of broad-spectrum antimicrobial agents have been used in the treatment of infections caused by MDR organisms. Of these agents, carbapenems are often resorted to due to their low toxicity and high efficacy (El-Herte et al, 2012). The overuse and misuse of carbapenems led to an increase in resistance rates against this potent class of antimicrobial agents (El-Herte et al, 2012)
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