In Vitro Synergistic Activity of Antimicrobial Agents in Combination against Clinical Isolates of Colistin-Resistant Acinetobacter baumannii.

Seongman Bae, Min-Chul Kim, Su-Jin Park, Hee Sueng Kim, Heungsup Sung, Mi-Na Kim, Sung-Han Kim, Sang-Oh Lee, Sang-Ho Choi, Jun Hee Woo, Yang Soo Kim, Yong Pil Chong
Author Information
  1. Seongman Bae: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  2. Min-Chul Kim: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  3. Su-Jin Park: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  4. Hee Sueng Kim: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  5. Heungsup Sung: Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  6. Mi-Na Kim: Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  7. Sung-Han Kim: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  8. Sang-Oh Lee: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  9. Sang-Ho Choi: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  10. Jun Hee Woo: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  11. Yang Soo Kim: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  12. Yong Pil Chong: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea drchong@amc.seoul.kr.

Abstract

Emerging resistance to colistin in clinical Acinetobacter baumannii isolates is of growing concern. Since current treatment options for these strains are extremely limited, we investigated the in vitro activities of various antimicrobial combinations against colistin-resistant A. baumannii Nine clinical isolates (8 from bacteremia cases and 1 from a pneumonia case) of colistin-resistant A. baumannii were collected in Asan Medical Center, Seoul, South Korea, between January 2010 and December 2012. To screen for potential synergistic effects, multiple combinations of two antimicrobials among 12 commercially available agents were tested using the multiple-combination bactericidal test (MCBT). Checkerboard tests were performed to validate these results. Among the 9 colistin-resistant strains, 6 were pandrug resistant and 3 were extensively drug resistant. With MCBT, the most effective combinations were colistin-rifampin and colistin-teicoplanin; both combinations showed synergistic effect against 8 of 9 strains. Colistin-aztreonam, colistin-meropenem, and colistin-vancomycin combinations showed synergy against seven strains. Colistin was the most common constituent of antimicrobial combinations that were active against colistin-resistant A. baumannii Checkerboard tests were then conducted in colistin-based combinations. Notably, colistin-rifampin showed synergism against all nine strains (100%). Both colistin-vancomycin and colistin-teicoplanin showed either synergy or partial synergy. Colistin combined with another β-lactam agent (aztreonam, ceftazidime, or meropenem) showed a relatively moderate effect. Colistin combined with ampicillin-sulbactam, tigecycline, amikacin, azithromycin, or trimethoprim-sulfamethoxazole demonstrated limited synergism. Using MCBT and checkerboard tests, we found that only colistin-based combinations, particularly those with rifampin, glycopeptides, or β-lactams, may confer therapeutic benefits against colistin-resistant A. baumannii.

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MeSH Term

Acinetobacter Infections
Acinetobacter baumannii
Anti-Bacterial Agents
Aztreonam
Bacteremia
Ceftazidime
Colistin
Drug Combinations
Drug Resistance, Multiple, Bacterial
Drug Synergism
Humans
Meropenem
Microbial Sensitivity Tests
Pneumonia, Bacterial
Retrospective Studies
Rifampin
Teicoplanin
Thienamycins
Vancomycin

Chemicals

Anti-Bacterial Agents
Drug Combinations
Thienamycins
Teicoplanin
Vancomycin
Ceftazidime
Meropenem
Aztreonam
Rifampin
Colistin

Word Cloud

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