title: In-vitro activity of polymyxin B, rifampicin, tigecycline alone and in combination against carbapenem-resistant Acinetobacter baumannii in Singapore.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacy, Singapore General Hospital, Singapore, Singapore.
authors.forename: Tze-Peng
authors.initials: TP
authors.lastname: Lim
authors.forename: Thean-Yen
authors.initials: TY
authors.lastname: Tan
authors.forename: Winnie
authors.initials: W
authors.lastname: Lee
authors.forename: S
authors.initials: S
authors.lastname: Sasikala
authors.forename: Thuan-Tong
authors.initials: TT
authors.lastname: Tan
authors.forename: Li-Yang
authors.initials: LY
authors.lastname: Hsu
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Kwa
mesh_terms: D040981:Acinetobacter baumannii / Q000145:classification / Q000187:drug effects*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015780:Carbapenems / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D066298:In Vitro Techniques; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology; D011112:Polymyxin B / Q000494:pharmacology*; D012293:Rifampin / Q000494:pharmacology*; D012846:Singapore; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D000078304:Tigecycline; D008911:Minocycline; D011112:Polymyxin B; D012293:Rifampin