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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...

The combinations of imipenem plus ciprofloxacin and imipenem plus amikacin were investigated for their activity against Pseudomonas aeruginosa and other bacterial pathogens. For imipenem-susceptible P. aeruginosa, synergy of imipenem plus ciprofloxacin and imipenem plus amikacin was observed against 36 and 45% of the strains, respectively. The incidence of synergy against imipenem-resistant isolates of P. aeruginosa was 10% for both combinations. Antagonism was not observed with either combination.

We evaluated the microbiologic characteristics including MIC determinations, synergy plate assays and serum bactericidal activity for two regimens being examined as empiric antibiotic therapy for febrile granulocytopenic cancer patients. The regimens consisted of moxalactam (4 g.i.v. q12h) plus piperacillin (75 mg/kg i.v. q6h) or moxalactam (as above) plus amikacin (levels adjusted to one hour post-infusion levels of 25 mg/l and troughs of 6-8 mg/l). Detailed pharmacokinetics were ascertained for the beta lactams. All drugs were active against a panel of 11 strains each of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus. The pharmacokinetic profile showed serum levels sufficient to provide good antimicrobial activity throughout the dosing interval. Both regimens displayed synergistic or partially synergistic activity in the main for the test organisms; moxalactam plus piperacillin produced good results against S. aureus and P. aeruginosa. In the serum bactericidal assays, the moxalactam-piperacillin combination produced significantly higher mean titers at both peak and trough when compared to the moxalactam-amikacin regimen. This may be because moxalactam acts as a beta lactamase inhibitor for both staphylococcal beta lactamase, as well as the Sabath-Abraham Id type beta lactamase carried by P. aeruginosa (among others). Moxalactam-piperacillin deserves extensive evaluation as empiric therapy for the febrile neutropenic cancer patients.