title: Impact of the duration of infection on the activity of ceftazidime, gentamicin and ciprofloxacin in Klebsiella pneumoniae pneumonia and septicemia in leukopenic rats.
abstract: An experimental Klebsiella pneumoniae pneumonia and septicemia in leukopenic rats was used to study the impact of the duration of infection on the bactericidal activity of ceftazidime, gentamicin and ciprofloxacin. It appeared that the number of bacteria persisting after a single intravenous injection progressively increased with delay of antibiotic administration up to 3 h after bacterial inoculation with each of the drugs tested. This effect was most pronounced for ciprofloxacin. An inoculum effect could not explain this decrease in bacterial killing. It was also observed that a single injection with a particular dose of each of the respective drugs did not kill all the Klebsiella pneumoniae organisms in the lung. Persisting bacteria did not represent a preexisting less susceptible subpopulation selected after antibiotic administration. In further experiments the impact of delay of the start of treatment on the efficacy of ceftazidime or ciprofloxacin after administration for a period of four days with intramuscular injections at 6 h intervals was investigated. Treatment was started at 5, 12 or 24 h after bacterial inoculation. The therapeutic efficacy of both drugs decreased with the increase of duration of infection, which may be at least in part due to the progressive number of bacteria persisting after antibiotic administration. These data underline the need to start antimicrobial treatment as soon as possible.
authors.affiliation: Department of Clinical Microbiology, Academic Hospital Free University, Amsterdam, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Roosendaal
authors.forename: I A
authors.initials: IA
authors.lastname: Bakker-Woudenberg
authors.forename: M
authors.initials: M
authors.lastname: van den Berghe-van Raffe
authors.forename: J C
authors.initials: JC
authors.lastname: Vink-van den Berg
authors.forename: M F
authors.initials: MF
authors.lastname: Michel
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000188:drug therapy; D002442:Ceftazidime / Q000627:therapeutic use*; D002939:Ciprofloxacin / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D005839:Gentamicins / Q000627:therapeutic use*; D007710:Klebsiella Infections / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000187:drug effects*; D007970:Leukopenia / Q000150:complications*; D011014:Pneumonia / Q000188:drug therapy; D051381:Rats; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors
chemical_list: D005839:Gentamicins; D002939:Ciprofloxacin; D002442:Ceftazidime