The antibacterial activity of imipenem combined with norfloxacin, ciprofloxacin, or ofloxacin against 43 gram-positive cocci and 53 aerobic gram-negative rods isolated from hospitalized patients was determined by the checkerboard method and compared to results obtained with the combination of imipenem with amikacin. Synergistic antibacterial action (defined as FIC index ≤ 0.5) was found for 28% of strains with imipenem/amikacin and imipenem/norfloxacin, in 23% with imipenem/ofloxacin, and in 18% with imipenem/ciprofloxacin. Antagonistic activity (FIC index > 1.0) was found in 21, 21, 32, and 23% respectively. These rates were not statistically different for gram-positive and gram-negative isolates. Antagonistic activity seemed to occur more frequently with Pseudomonas spp. and enterococci than with staphylococci or Entero-bacteriaceae. A tendency for increased rates of antagonism was noted in strains with higher MIC values. Clinically significant and meaningful positive interactions (defined as a decrease of imipenem MICs to below 2.0 (μg/ml) were found with imipenem/amikacin against several Pseudomonas spp., with imipenem/ofloxacin or ciprofloxacin against Streptococcus faecium and with all combinations against Proteus spp. We conclude that continuous treatment with newer quinolone derivatives for selective decontamination in neutropenic patients receiving imipenem antibacterial therapy for treatment of infection should not be regarded as effective combination therapy.

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