Killing of gram-negative bacteria by ciprofloxacin within both healthy human neutrophils and neutrophils with inactivated O2-dependent bactericidal mechanisms.
The intraphagocytic killing of Escherichia coli, Serratia marcescens, Pseudomonas aeruginosa, and Salmonella typhi by ciprofloxacin (0.1, 1 and 5 microg/ml) within human neutrophils with intact and impaired (by phenylbutazone treatment) O2-dependent killing mechanisms was studied and compared with the extracellular killing in the same medium of the intraphagocytic killing, but omitting neutrophils. The MIC/MBC of ciprofloxacin in vitro (assays performed according to NCCLS specifications) were: 0.015/0.06 for E. coli, 0.12/32 for S. marcescens, 1/16 for P. aeruginosa, and 0.007/0.06 for S. typhi. Ciprofloxacin showed bactericidal activity both extracellular and within phenylbutazone-treated and untreated neutrophils. The minimum concentration of ciprofloxacin to kill 90% of phagocytosed bacteria within neutrophils with normal O2-dependent killing power after 30 min was: 0.1 microg/ml for E. coli, and S. typhi, 1 microg/ml for P. aeruginosa, and 5 microg/ml for S. marcescens. In contrast, exposure for 60 min was required to reach this percentage within phenylbutazone treated neutrophils. The minimum concentration to kill 90% of extracellular bacteria after 30 min was: 0.1 microg/ml for E. coli, P. aeruginosa and S. typhi, and 5 microg/ml, for S. marcescens. A positive interaction between ciprofloxacin and the O2-dependent mechanisms of phagocytes was found. The reactive oxygen metabolites produced in the respiratory burst did not affect the intraphagocytic activity of ciprofloxacin. Phenylbutazone treatment of phagocytes would be a good experimental model to study the intraphagocytic killing of drugs in situations such as AIDS and chronic granulomatous disease where inefficient oxidative mechanisms of neutrophils exist.
Servicio de Microbiología, Centro de Investigación, Hospital Universitario La Fe, Valencia, Spain.
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Cantón
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Peman
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Cabrera
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Velert
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Orero
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Pastor
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Gobernado
D000890:Anti-Infective Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D009504:Neutrophils / Q000187:drug effects* / Q000382:microbiology; D010100:Oxygen / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects; D012016:Reference Values
D000890:Anti-Infective Agents; D002939:Ciprofloxacin; D006861:Hydrogen Peroxide; D010100:Oxygen