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JAC Advance Access originally published online on October 29, 2003
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Journal of Antimicrobial Chemotherapy (2003) 52, 911-914
© 2003 The British Society for Antimicrobial Chemotherapy

In vitro effects of combinations of antipseudomonal agents against seven strains of multidrug-resistant Pseudomonas aeruginosa

Shigeharu Oie1, Toshinari Uematsu1, Akihiro Sawa1, Hidekazu Mizuno2, Masaaki Tomita3, Shiro Ishida4, Yoshiro Okano4 and Akira Kamiya1,*

1 Department of Pharmacy and 2 Clinical Laboratory, Yamaguchi University Hospital, 1-1-1 Minamikogushi, Ube 755-8505; 3 Yamaguchi Prefectural Research Institute of Public Health, 2-5-67 Aoi, Yamaguchi 753-0821; 4 Department of Pharmaceutical Care and Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, 180 Yamashiro-cho, Tokushima-shi, Tokushima 770-8514, Japan

Received 10 June 2003; returned 16 July 2003; revised 16 September 2003; accepted 20 September 2003

Objectives: The aim of this study was to evaluate the combined effects of antibiotic combinations by agar incorporation inhibitory tests and by time–kill tests on seven geographically and epidemiologically distinct isolates of multidrug-resistant Pseudomonas aeruginosa. All seven strains were resistant to piperacillin, meropenem, ceftazidime, cefoperazone-sulbactam, aztreonam, amikacin and ciprofloxacin.

Methods: Strains were distinguished by pulsed-field gel electrophoresis after DNA extraction and restriction with SpeI. MICs of the seven antibiotics listed above were determined by agar dilution. The effect of combinations of these agents was determined by agar incorporation tests and by time–kill studies.

Results: Among the two-drug combinations, the combination aztreonam and amikacin was the most effective, inhibiting proliferation in five of the seven strains. Among the three-drug combinations, the combinations of piperacillin, ceftazidime and amikacin, and that of ceftazidime, aztreonam and amikacin were the most effective, inhibiting proliferation in all seven strains. In the killing tests, the three-drug combination of ceftazidime, aztreonam and amikacin was the most effective. This three-drug combination had bacteriostatic effects on all seven strains 2, 4, 6 and 24 h after drug addition, synergic effects on 2–3 strains and bactericidal effects on 1–2 strains after 4, 6 and 24 h.

Conclusions: The three-drug combination of ceftazidime, aztreonam and amikacin may be effective against P. aeruginosa resistant to all commonly used antipseudomonal drugs, and deserves further study.

Keywords: P. aeruginosa, antimicrobial agents, combined effects, ceftazidime, aztreonam, amikacin

* Corresponding author. Tel: +81-836-22-2665; Fax: +81-836-22-2673; E-mail: akira-ygc{at}umin.ac.jp


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