Ann Lab Med.  2016 Mar;36(2):138-144. 10.3343/alm.2016.36.2.138.

In Vitro Synergistic Effects of Antimicrobial Combinations on Extensively Drug-Resistant Pseudomonas aeruginosa and Acinetobacter baumannii Isolates

  • 1Department of Laboratory Medicine, International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon, Korea.
  • 2Seegene Institute of Life Sciences, Seoul, Korea.
  • 3Department of Laboratory Medicine, Bundang CHA Hospital, Pochon CHA University College of Medicine, Seongnam, Korea.
  • 4Department of Laboratory Medicine, Soonchunhyang Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea.
  • 5Department of Laboratory Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
  • 6Department of Laboratory Medicine, Gangnam Sacred Hospital, Hallym University College of Medicine, Seoul, Korea.
  • 7Department of Laboratory Medicine, Wonju Severance Christian Hospital, Yonsei University, Wonju College of Medicine, Wonju, Korea.
  • 8Department of Laboratory Medicine, Severance Hospital Yonsei University College of Medicine, Seoul, Korea.


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.
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-beta-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.
Minimum inhibitory concentrations of beta-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.
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.


In vitro synergy; Combination chemotherapy; Pseudomonas aeruginosa; Acinetobacter baumannii

MeSH Terms

Acinetobacter baumannii/*drug effects/genetics/isolation & purification
Anti-Infective Agents/*pharmacology
Bacterial Proteins/genetics/metabolism
Drug Resistance, Multiple, Bacterial/*drug effects
Drug Synergism
Microbial Sensitivity Tests
Polymerase Chain Reaction
Pseudomonas aeruginosa/*drug effects/genetics/isolation & purification
Anti-Infective Agents
Bacterial Proteins
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