In vitro activity of ciprofloxacin in combination with ceftazidime, aztreonam, and azlocillin against multiresistant isolates of Pseudomonas aeruginosa

Abstract

The combinations of ciprofloxacin plus ceftazidime, ciprofloxacin plus aztreonam, and ciprofloxacin plus azlocillin were evaluated for the presence of synergy against multiresistant isolates of Pseudomonas aeruginosa. The frequency of synergy was dependent on antibiotic susceptibilities. If the organism was resistant to ciprofloxacin, synergy was observed in more than 50% of the isolates; however, if the organism was resistant to the beta-lactam (with the exception of ceftazidime), synergy was generally observed in less than 10% of the isolates. Antagonism was not observed with any of the combinations. These results may be helpful in making clinical decisions in treating P. aeruginosa infections.A number of studies have reported on the presence of synergy for combinations of ciprofloxacin and antipseudomonal beta-lactam antibiotics (1-7). Few studies, however, have investigated the activities of these combinations against multiresistant isolates.We have completed an extensive evaluation of the activities of combinations of ciprofloxacin with three beta-lactam agents against clinical isolates of Pseudomonas aeruginosa, many of which were resistant to ciprofloxacin, the betalactam antibiotic, or both.(This work was presented in part at the 87th Annual Meeting of the American Society for Microbiology, Atlanta, Ga., 1 to 6 March 1987.)A total of 108 clinical isolates of P. aeruginosa recovered from patients treated at the University of Maryland Cancer Center were studied. The three ciprofloxacin-beta-lactam combinations consisted of ciprofloxacin plus ceftazidime, ciprofloxacin plus aztreonam, and ciprofloxacin plus azlocillin. The ranges of the antibiotic concentrations tested were as follows: ciprofloxacin, 0.002 to 4 ,ug/ml; azlocillin, 0.004 to 64 ,ug/ml; aztreonam, 0.004 to 64 ,ug/ml; and ceftazidime, 0.004 to 64 ,ug/ml. The inoculum was -5 x 105 CFU/ml, as determined by McFarland standards and colony counts. MICs were determined and the presence of synergy was assessed by the checkerboard microtiter dilution method with the MIC 2000 system (Dynatech Laboratories, Inc., Alexandria, Va.).The fractional inhibitory indices were determined. Synergy was defined by fractional inhibitory index of s0.5, and antagonism was defined by a fractional inhibitory index of >4. Antibiotic resistance was defined as follows: ciprofloxacin MIC, >2 ,g/ml; azlocillin MIC, >64 ,ug/ml; aztreonam MIC, >16 ,ug/ml; and ceftazidime MIC, >16 ,ug/ml.The antibiotic susceptibilities of the strains studied are shown in 2. When P. aeruginosa was resistant to ciprofloxacin but susceptible to the beta-lactam in the combination, synergy was demonstrated for all three combinations in greater than 50% of the isolates. In contrast, for isolates resistant to aztreonam or azlocillin but susceptible to ciprofloxacin, synergy was rarely demonstrated (<5%). When the organism was resistant to ceftazidime but susceptible to ciprofioxacin, synergy was observed in 75% of the isolates (9 of 12). When the organism was susceptible to both antibiotics in the comb...

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