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.
Cantón
E
E
Servicio de Microbiología, Centro de Investigación, Hospital Universitario La Fe, Valencia, Spain.
Peman
J
J
Cabrera
E
E
Velert
M
M
Orero
A
A
Pastor
A
A
Gobernado
M
M
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