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

• Lee H
• Roh KH
• Hong SG
• Shin HB
• Jeong SH
• Song W
• Uh Y
• Yong D
• Lee K

• KMID: 2373513
• DOI: http://doi.org/10.3343/alm.2016.36.2.138

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-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.
RESULTS
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.
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.

Keyword

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

MeSH Terms

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

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