title: In Vitro Synergistic Effects of Antimicrobial Combinations on Extensively Drug-Resistant Pseudomonas aeruginosa and Acinetobacter baumannii Isolates.
abstract: BACKGROUND
  Extensively drug-resistant (XDR) Pseudomonas aeruginosa and Acinetobacter baumannii are a threat to hospitalized patients. We evaluated the effects of antimicrobial combinations on XDR P. aeruginosa and A. baumannii isolates.
  
  
  METHODS
  P. aeruginosa and A. baumannii isolates, which were resistant to all antibiotics except colistin (CL), were collected from eight hospitals in Korea. Genes encoding metallo-β-lactamases (MBLs) and OXA carbapenemases were detected by PCR in eight P. aeruginosa and 30 A. baumannii isolates. In vitro synergy of antimicrobial combinations was tested by using the checkerboard method.
  
  
  RESULTS
  Minimum inhibitory concentrations of β-lactams, aminoglycosides, and fluoroquinolones were very high, while that of CL was low for majority of XDR P. aeruginosa and A. baumannii isolates. Antimicrobial combinations including Imipenem (IPM)-CL, ceftazidime (CAZ)-CL, and rifampin (RIF)-CL exerted only additive/indifferent effects on majority of XDR P. aeruginosa isolates. Proportions of XDR A. baumannii isolates that showed synergistic and additive/indifferent inhibition after treatment with antimicrobial combinations used are as follows: IPM-ampicillin-sulbactam (AMS), 17% and 80% isolates, respectively; IPM-rifampin (RIF), 13% and 81% isolates, respectively; IPM-CL, 13% and 87% isolates, respectively; and RIF-COL, 20% and 73% isolates, respectively. Significant proportion (19%) of XDR P. aeruginosa isolates produced MBLs, and majority (82%) of A. baumannii isolates produced either MBLs or OXA-23.
  
  
  CONCLUSIONS
  Our results suggest that combinations of IPM-AMS, IPM-RIF, IPM-CL, and RIF-CL are more useful than individual drugs for treating 13-20% of XDR A. baumannii infections.
authors.affiliation: Department of Laboratory Medicine, International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon, Korea.
authors.forename: Hyukmin
authors.initials: H
authors.lastname: Lee
authors.affiliation: Seegene Institute of Life Sciences, Seoul, Korea.
authors.forename: Kyung Ho
authors.initials: KH
authors.lastname: Roh
authors.affiliation: Department of Laboratory Medicine, Bundang CHA Hospital, Pochon CHA University College of Medicine, Seongnam, Korea.
authors.forename: Seong Geun
authors.initials: SG
authors.lastname: Hong
authors.affiliation: Department of Laboratory Medicine, Soonchunhyang Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea.
authors.forename: Hee Bong
authors.initials: HB
authors.lastname: Shin
authors.affiliation: Department of Laboratory Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Seok Hoon
authors.initials: SH
authors.lastname: Jeong
authors.affiliation: Department of Laboratory Medicine, Gangnam Sacred Hospital, Hallym University College of Medicine, Seoul, Korea.
authors.forename: Wonkeun
authors.initials: W
authors.lastname: Song
authors.affiliation: Department of Laboratory Medicine, Wonju Severance Christian Hospital, Yonsei University, Wonju College of Medicine, Wonju, Korea.
authors.forename: Young
authors.initials: Y
authors.lastname: Uh
authors.affiliation: Department of Laboratory Medicine, Severance Hospital Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Dongeun
authors.initials: D
authors.lastname: Yong
authors.affiliation: Department of Laboratory Medicine, Severance Hospital Yonsei University College of Medicine, Seoul, Korea. leekcp@yuhs.ac.
authors.forename: Kyungwon
authors.initials: K
authors.lastname: Lee
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D000617:Aminoglycosides / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D004357:Drug Synergism; D024841:Fluoroquinolones / Q000494:pharmacology; D015378:Imipenem / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D016133:Polymerase Chain Reaction; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism
chemical_list: D000617:Aminoglycosides; D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D024841:Fluoroquinolones; D015378:Imipenem; D001618:beta-Lactamases; C063912:carbapenemase
keywords: Acinetobacter baumannii; Combination chemotherapy; In vitro synergy; Pseudomonas aeruginosa