Comparative efficacy of ciprofloxacin, azlocillin, imipenem/cilastatin and tobramycin in a model of experimental septicemia due to Pseudomonas aeruginosa in neutropenic mice.
The in vivo activity of ciprofloxacin against Pseudomonas aeruginosa was studied in a septicemia model in neutropenic mice and compared to that of other antibiotics with established activity against P. aeruginosa. When given as a single agent, ciprofloxacin proved to be as effective as imipenem/cilastatin, whereas azlocillin and tobramycin were rather ineffective. After infection with higher challenge inocula, combinations of two (synergistic) antibiotics were more effective than single agent therapy in most instances. The combination of ciprofloxacin with azlocillin was at least as effective as that of imipenem/cilastatin with tobramycin. Selection of mutants with decreased sensitivity to ciprofloxacin occurred during therapy, however, post-therapy MICs of ciprofloxacin did not exceed a level of 1 mg/l and rises of MICs did not detrimentally influence treatment outcome. Taken together with the results of earlier studies, our data encourage the use of ciprofloxacin in gram-negative septicemia in neutropenic patients.
Ulrich
E
E
Institut für Medizinische Mikrobiologie, Freie Universität Berlin, FR Germany.
Trautmann
M
M
Krause
B
B
Bauernfeind
A
A
Hahn
H
H
D000380:Agranulocytosis / Q000150:complications*; D000818:Animals; D001390:Azlocillin / Q000493:pharmacokinetics / Q000592:standards* / Q000627:therapeutic use; D015377:Cilastatin / Q000592:standards; D002939:Ciprofloxacin / Q000493:pharmacokinetics / Q000592:standards* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination / Q000592:standards; D008297:Male; D051379:Mice; D009503:Neutropenia / Q000150:complications*; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000209:etiology; D018805:Sepsis / Q000188:drug therapy* / Q000209:etiology; D014031:Tobramycin / Q000592:standards
D015377:Cilastatin; D002939:Ciprofloxacin; D001390:Azlocillin; D014031:Tobramycin