Abstract
ObjectiveCarbapenem-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.MethodsAB 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.Results31 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.ConclusionMonotherapy 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.
Highlights
Acinetobacter baumannii is a successful pathogen that has evoked scientific and public interest worldwide.[1]
All isolates were resistant to meropenem, imipenem, ampicillin/sulbactam, ciprofloxacin, gentamicin, aztreonam, piperacillin/tazobactam, ceftazidime, cefepime and amikacin. But they were susceptible to polymyxin B (MIC range 0.5–2 mg/L)
The Minimum inhibitory concentrations (MIC) of rifampicin and tigecycline ranged from 1–$64 mg/L and 0.5–$32 mg/L respectively (Table 1)
Summary
Acinetobacter baumannii is a successful pathogen that has evoked scientific and public interest worldwide.[1] It is increasingly multidrug-resistant due to its wide repertoire of antimicrobial resistance mechanisms and its innate ability to acquire new resistance determinants.[2] As a frequently occurring pathogen associated with serious nosocomial infections, A. baumannii had been shown to be associated with unfavourable clinical outcomes.[3,4]. Carbapenems, members of a potent broad-spectrum antimicrobial class, are increasingly being used as first-line therapy in institutions where there is a high prevalence of multidrug-resistant bacterial infections. With the advent of increasing usage and poor infection control, carbapenem resistance has emerged worldwide and there has been a surge in recent reports of outbreaks involving multidrug-resistant A. baumannii that are carbapenem-resistant (CR-AB).[5,6] This phenomena has resulted in the revival of the polymyxins, which are increasingly used as the last line of defence against such difficult-to-treat infections
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