In-vitro activity of polymyxin B, rifampicin, tigecycline alone and in combination against carbapenem-resistant Acinetobacter baumannii in Singapore

Tze-Peng Lim, Thean-Yen Tan, Winnie Lee, S Sasikala, Thuan-Tong Tan, Li-Yang Hsu, Andrea L Kwa, Tze-Peng Lim, Thean-Yen Tan, Winnie Lee, S Sasikala, Thuan-Tong Tan, Li-Yang Hsu, Andrea L Kwa

Abstract

Objective: Carbapenem-resistant Acinetobacter baumannii (CR-AB) is an emerging cause of nosocomial infections worldwide. Combination therapy may be the only viable option until new antibiotics become available. The objective of this study is to identify potential antimicrobial combinations against CR-AB isolated from our local hospitals.

Methods: AB isolates from all public hospitals in Singapore were systematically collected between 2006 and 2007. MICs were determined according to CLSI guidelines. All CR-AB isolates were genotyped using a PCR-based method. Clonal relationship was elucidated. Time-kill studies (TKS) were conducted with polymyxin B, rifampicin and tigecycline alone and in combination using clinically relevant (achievable) unbound concentrations.

Results: 31 CR AB isolates were identified. They are multidrug-resistant, but are susceptible to polymyxin B. From clonal typing, 8 clonal groups were identified and 11 isolates exhibited clonal diversity. In single TKS, polymyxin B, rifampicin and tigecycline alone did not exhibit bactericidal activity at 24 hours. In combination TKS, polymyxin plus rifampicin, polymyxin B plus tigecycline and tigecycline plus rifampicin exhibited bactericidal killing in 13/31, 9/31 and 7/31 isolates respectively at 24 hours. Within a clonal group, there may be no consensus with the types of antibiotics combinations that could still kill effectively.

Conclusion: Monotherapy with polymyxin B may not be adequate against polymyxin B susceptible AB isolates. These findings demonstrate that in-vitro synergy of antibiotic combinations in CR AB may be strain dependant. It may guide us in choosing a pre-emptive therapy for CR AB infections and warrants further investigations.

Conflict of interest statement

Competing Interests: Transparency Declaration: on other occasions TTY and HLY have received funding for research from, and have been an invited as speakers for Wyeth Pharmaceuticals and Pfizer. ALK, WL and LTP have received funding for research from Janssen-Cilag and Merck Sharp & Dohme (I.A.) Corp. None of these companies provided any funding for this particular study. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.

Figures

Figure 1. Phylogenetic Tree Diagram showing *…
Figure 1. Phylogenetic Tree Diagram showing * clonal groups.
A yellow oval, denote a clonal group after applying a similarity index of 90% to PCR typing results.

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