title: Extensively drug-resistant Acinetobacter baumannii in a Thai hospital: a molecular epidemiologic analysis and identification of bactericidal Polymyxin B-based combinations.
abstract: BACKGROUND
  Limited knowledge of the local molecular epidemiology and the paucity of new effective antibiotics has resulted in an immense challenge in the control and treatment of extensively drug-resistant (XDR) Acinetobacter baumannii infections in Thailand. Antimicrobial combination regimens may be the only feasible treatment option in such cases. We sought to characterize the local molecular epidemiology and assess the bactericidal activity of various antibiotics individually and in combination against XDR A. baumannii in a Thai hospital.
  
  
  METHODS
  All XDR A. baumannii isolates from Thammasat University Hospital were collected between October 2010 and May 2011. Susceptibility testing was conducted according to reference broth dilution methods. Pulse-field gel electrophoresis was used to genotype the isolates. Carbapenemase genes were detected using polymerase chain reaction. In vitro testing of clinically-relevant concentrations of imipenem, meropenem, doripenem, rifampicin and tigecycline alone and in combination with polymyxin B was conducted using multiple combination bactericidal testing.
  
  
  RESULTS
  Forty-nine polymyxin B-susceptible XDR A. baumannii isolates were identified. bla OXA-23 and bla OXA-51 genes were detected in all isolates. Eight clonally related clusters were identified, resulting in the initiation of several infection control measures. Imipenem, meropenem, doripenem, rifampicin, and tigecycline in combination with PB respectively, exhibited bactericidal killing in 100%, 100%, 98.0%, 100% and 87.8% isolates respectively at 24 hours.
  
  
  CONCLUSIONS
  Molecular epidemiologic analysis can aid the early detection of infection outbreak within the institution, resulting in the rapid containment of the outbreak. Imipenem/meropenem/rifampicin in combination with polymyxin B demonstrated consistent bactericidal effect against 49 bla OXA-23-harbouring XDR A. baumannii clinical isolates, suggesting a role of combination therapy in the treatment of these infections.
authors: Department of Pharmacy, Singapore General Hospital, Outram Road, Singapore, 169608 Singapore.
authors: Jocelyn
authors: J
authors: Teo
authors: Department of Pharmacy, Singapore General Hospital, Outram Road, Singapore, 169608 Singapore.|Division of Infectious Diseases, Department of Medicine, 1E Kent Ridge Road, NUHS, Yong Loo Lin School of Medicine, National University of Singapore, Tower Block, Level 9, Singapore, 119228 Singapore.
authors: Tze-Peng
authors: TP
authors: Lim
authors: Division of Infectious Diseases, Department of Medicine, 1E Kent Ridge Road, NUHS, Yong Loo Lin School of Medicine, National University of Singapore, Tower Block, Level 9, Singapore, 119228 Singapore.
authors: Li-Yang
authors: LY
authors: Hsu
authors: Department of Laboratory Medicine, Changi General Hospital, 2 Simei St 3, Singapore, 529889 Singapore.
authors: Thean-Yen
authors: TY
authors: Tan
authors: Department of Pharmacy, Singapore General Hospital, Outram Road, Singapore, 169608 Singapore.|Current address: AStar, Biopolis, 31 Biopolis Way, Singapore, 138668 Singapore.
authors: Suranthran
authors: S
authors: Sasikala
authors: Division of Infectious Diseases, Department of Medicine, 1E Kent Ridge Road, NUHS, Yong Loo Lin School of Medicine, National University of Singapore, Tower Block, Level 9, Singapore, 119228 Singapore.|Current address: Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore, 308433 Singapore.
authors: Pei-Yun
authors: PY
authors: Hon
authors: Department of Pharmacy, Singapore General Hospital, Outram Road, Singapore, 169608 Singapore.|Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore, 169857 Singapore.
authors: Andrea L
authors: AL
authors: Kwa
authors: Division of Infectious Diseases, Faculty of Medicine, Thammasat University Hospital, Pathumthani, 12120 Thailand.
authors: Anucha
authors: A
authors: Apisarnthanarak
keywords: Acinetobacter baumannii; Carbapenem resistance; Combination therapy
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