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      In vitro synergism of combinations of colistin with selected antibiotics against colistin-resistant Acinetobacter baumannii Translated title: In-vitro-Synergismus von Kombinationen von Colistin mit ausgewählten Antibiotika gegen Colistin-resistente Acinetobacter baumannii

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          Abstract

          Aim: The in vitro activity of colistin in combination with sulbactam, netilmicin, and vancomycin against colistin-resistant A. baumannii strains was investigated. Furthermore, the clonal relationship of the strains was analyzed.

          Methods: Clonal relationship was investigated using rep-PCR. To screen for synergysm, the fractional inhibitory concentration index (FICI) was calculated using checkerboard assay. The killing kinetics of the combination of colistin with vancomycin was assessed using time-kill assay.

          Results: Three different clones were found among 10 clinical isolates of colistin-resistant A. baumannii strains. Thereof, 8 strains were susceptible to netilmicin. Synergistic interaction was detected in 1 strain with the combination of colistin-netilmicin, in 5 strains with colistin-sulbactam, and in 9 strains with colistin-vancomycin. None of combinations had antagonistic activity. Colistin-vancomycin combination resulted in rapid bactericidal activity.

          Conclusion: These results show a distinct in vitro synergism between colistin and vancomycin, which might be useful to treat infection with multiple-resistant strains, prevent emergence of resistant strains, and to lower doses for both antibiotics to be used.

          Zusammenfassung

          Ziel: Die Kombination von Colistin mit Sulbactam, Netilmicin und Vancomycin wurde in vitro gegen Colistin-resistente A. baumannii-Stämme untersucht und die klonale Verwandtschaft der Stämme analysiert.

          Methoden: Die klonale Verwandtschaft wurde mittels rep-PCR untersucht. Der Fractional Inhibitory Concentration Index (FICI) Bruch wurde mit dem Checkerboard-Assay berechnet. Die Abtötungskinetik Colistin-Vancomycin-Kombination wurde mit dem Zeit-Kill-Assay ermittelt.

          Ergebnisse: Es wurden 3 verschiedene Klone identifiziert. Alle Isolate waren resistent gegen Colistin, 8 Stämme waren empfindlich gegen Netilmicin. Eine synergistische Wechselwirkung wurde für einen Stamm mit der Kombination Colistin-Netilmicin, für 5 Stämme mit der Kombination Colistin-Sulbactam und für 9 Stämme mit der Kombination Colistin-Vancomycin festgestellt. Bei keiner Kombination trat Antagonismus auf. Die Kombination von Colistin mit Vancomycin ergab eine rasche bakterizide Aktivität.

          Fazit: Die In-vitro-Ergebnisse zeigen einen Synergismus für die Kombination von Colistin mit Vancomycin. Damit ist die Möglichkeit gegeben, Infektionen durch multipel-resistente Erreger zu behandeln und der Entstehung resistenter Stämme entgegen zu wirken. Zugleich kann die Dosis für beide Antibiotika gesenkt werden.

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          Peptide antibiotics.

          R. Hancock (1997)
          The era of the "classical antibiotic" may be over. The emergence of resistance has seen to that. Yet no truly novel class of antibacterial agent has come on the market in the past 30 years. Currently there is great interest in peptide antibiotics, especially the cationic peptides. Thousands of such molecules have been synthesised and just a few are entering clinical trials. Because they kill bacteria quickly by the physical disruption of cell membranes, peptide antibiotics may not face the rapid emergence of resistance.
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            Performance standards for antimicrobial susceptibility testing

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              Global assessment of the antimicrobial activity of polymyxin B against 54 731 clinical isolates of Gram-negative bacilli: report from the SENTRY antimicrobial surveillance programme (2001-2004).

              In total, 54 731 Gram-negative bacilli isolated worldwide between 2001 and 2004 from diverse sites of infection were tested for susceptibility to polymyxin B by the broth reference microdilution method, with interpretation of results according to CLSI (formerly NCCLS) guidelines. Polymyxin B showed excellent potency and spectrum against 8705 Pseudomonas aeruginosa and 2621 Acinetobacter spp. isolates (MIC50, 98% susceptible) against Citrobacter spp., Escherichia coli and Klebsiella spp., but activity was more variable against Enterobacter spp. (MIC50, 8 mg/L) against Burkholderia cepacia (11.8% susceptible), Serratia spp. (5.4% susceptible), indole-positive Proteus spp. (1.3% susceptible) and Proteus mirabilis (0.7% susceptible).
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                Author and article information

                Journal
                GMS Hyg Infect Control
                GMS Hyg Infect Control
                GMS Hyg Infect Control
                GMS Hygiene and Infection Control
                German Medical Science GMS Publishing House
                2196-5226
                19 August 2014
                2014
                : 9
                : 2
                : Doc14
                Affiliations
                [1 ]Department of Microbiology, Faculty of Medicine, Erciyes University, Kayseri, Turkey
                [2 ]Department of Microbiology, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey
                [3 ]Department of Infectious Diseases and Clinical Microbiology, Yozgat State Hospital, Yozgat, Turkey
                Author notes
                *To whom correspondence should be addressed: Duygu Percin, Department of Microbiology, Faculty of Medicine, Erciyes University, 38039 Kayseri, Turkey, Phone: +90 352 2076666 (extension:23383), Fax: +90 532 2053860, E-mail: duygu.percin@ 123456hotmail.com
                Article
                dgkh000234 Doc14 urn:nbn:de:0183-dgkh0002345
                10.3205/dgkh000234
                4141631
                25152859
                8d41b1fc-d6e4-43ca-81cb-f3639468cc1e
                Copyright © 2014 Percin et al.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by-nc-nd/3.0/). You are free to copy, distribute and transmit the work, provided the original author and source are credited.

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                Article

                acinetobacter baumannii,colistin resistance,fractional inhibitory concentration index (fici),time-kill assay,synergism,vancomycin,sulbactam,netilmicin

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