Continuous versus intermittent administration of ceftazidime in experimental Klebsiella pneumoniae pneumonia in normal and leukopenic rats - PubMed (original) (raw)

Continuous versus intermittent administration of ceftazidime in experimental Klebsiella pneumoniae pneumonia in normal and leukopenic rats

R Roosendaal et al. Antimicrob Agents Chemother. 1986 Sep.

Abstract

Experimental Klebsiella pneumoniae pneumonia was used to study the influence of cyclophosphamide-induced leukopenia on the relative therapeutic efficacy of continuous and intermittent (6-h intervals) administration of ceftazidime. The antimicrobial response was evaluated with respect to the calculated daily dose that protected 50% of the animals from death (PD50) until 16 days after the termination of a 4-day treatment. When ceftazidime was administered intermittently to leukopenic rats, the PD50 was 24.37 mg/kg per day, 70 times (P less than 0.001) the PD50 of 0.35 mg/kg per day for normal rats. Continuous administration of ceftazidime to leukopenic rats resulted in a PD50 of 1.52 mg/kg per day, four times (P less than 0.001) the PD50 of 0.36 mg/kg per day for normal rats. Continuous administration of ceftazidime in daily doses that protected 100% of normal and leukopenic rats from death resulted in serum levels of 0.06 and 0.38 micrograms/ml, respectively, whereas the MIC for the infecting K. pneumoniae strain was 0.2 micrograms of ceftazidime per ml. The effect of the duration of ceftazidime treatment by continuous infusion on the therapeutic efficacy in relation to the persistence of leukopenia was then investigated in leukopenic rats. The administration of 3.75 mg of ceftazidime/kg per day for 4 days protected all leukopenic rats from death, provided the circulating leukocytes returned at the end of antibiotic treatment. When leukopenia persisted for 8 days this ceftazidime treatment schedule resulted in the mortality of rats (P less than 0.05). However, when ceftazidime treatment was continued for 8 days, until the return of the leukocytes, there was no significant mortality (P greater than 0.05).

PubMed Disclaimer

Cited by

Effect of treatment duration on pharmacokinetic/pharmacodynamic indices correlating with therapeutic efficacy of ceftazidime in experimental Klebsiella pneumoniae lung infection.
Bakker-Woudenberg IA, ten Kate MT, Goessens WH, Mouton JW. Bakker-Woudenberg IA, et al. Antimicrob Agents Chemother. 2006 Sep;50(9):2919-25. doi: 10.1128/AAC.00859-05. Antimicrob Agents Chemother. 2006. PMID: 16940082 Free PMC article.
Impact of dosage schedule of antibiotics on the treatment of serious infections.
Bakker-Woudenberg IA, Roosendaal R. Bakker-Woudenberg IA, et al. Intensive Care Med. 1990;16 Suppl 3:S229-34. doi: 10.1007/BF01709706. Intensive Care Med. 1990. PMID: 2289996 Review.
Pharmacodynamics of fluconazole in a murine model of systemic candidiasis.
Louie A, Drusano GL, Banerjee P, Liu QF, Liu W, Kaw P, Shayegani M, Taber H, Miller MH. Louie A, et al. Antimicrob Agents Chemother. 1998 May;42(5):1105-9. doi: 10.1128/AAC.42.5.1105. Antimicrob Agents Chemother. 1998. PMID: 9593135 Free PMC article.
Pharmacodynamic effects of subinhibitory concentrations of beta-lactam antibiotics in vitro.
Odenholt-Tornqvist I, Löwdin E, Cars O. Odenholt-Tornqvist I, et al. Antimicrob Agents Chemother. 1991 Sep;35(9):1834-9. doi: 10.1128/AAC.35.9.1834. Antimicrob Agents Chemother. 1991. PMID: 1952854 Free PMC article.
Impact of the dosage schedule on the efficacy of ceftazidime, gentamicin and ciprofloxacin in Klebsiella pneumoniae pneumonia and septicemia in leukopenic rats.
Roosendaal R, Bakker-Woudenberg IA, van den Berghe-van Raffe M, Vink-van den Berg JC, Michel BM. Roosendaal R, et al. Eur J Clin Microbiol Infect Dis. 1989 Oct;8(10):878-87. doi: 10.1007/BF01963774. Eur J Clin Microbiol Infect Dis. 1989. PMID: 2512132

References

1. Zentralbl Bakteriol A. 1981 Mar;249(1):43-52 - PubMed
1. Rev Infect Dis. 1981 Jan-Feb;3(1):28-37 - PubMed
1. J Antimicrob Chemother. 1981 Jan;7(1):71-9 - PubMed
1. Rev Infect Dis. 1981 Jan-Feb;3(1):4-11 - PubMed
1. Appl Microbiol. 1966 Mar;14(2):170-7 - PubMed

Continuous versus intermittent administration of ceftazidime in experimental Klebsiella pneumoniae pneumonia in normal and leukopenic rats - PubMed (original) (raw)