JAC Advance Access published online on October 29, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg478
© 2003 by The British Society for Antimicrobial Chemotherapy
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Original article
1 Department of Pharmacy, Yamaguchi University Hospital, 1-1-1 Minamikogushi,
Ube 755-8505;
* Corresponding author. E-mail: akira-ygc{at}umin.ac.jp.
Received 10 June 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
In vitro effects of combinations
of antipseudomonal agents against seven strains of multidrug-resistant Pseudomonas aeruginosa
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
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