Lung deposition of continuous and intermittent intravenous ceftazidime in experimental Pseudomonas aeruginosa bronchopneumonia
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Lung tissue deposition of intravenous ceftazidime administered either continuously or intermittently was compared in ventilated piglets with experimental bronchopneumonia.
Prospective experimental study
Eighteen anesthetized and ventilated piglets
Bronchopneumonia was produced by the intrabronchial inoculation of Pseudomonas aeruginosa characterized by an impaired sensitivity to ceftazidime (MIC 16 mg/l). Ceftazidime was administered either through a continuous infusion of 90 mg/kg per 24 h after a bolus of 30 mg/kg or by an intermittent infusion of 30 mg/kg per 8 h.
Measurements and results
Piglets were killed 24 h after the initiation of continuous ceftazidime (n = 6), and 1 h (peak, n = 6) and 8 h (trough, n = 6) after the third dose following intermittent administration. Lung tissue concentrations of ceftazidime, measured by HPLC, and lung bacterial burden were assessed on multiple postmortem lung specimens. During continuous administration ceftazidime lung tissue concentrations were 9.7 ± 3.8 μg/g. Following intermittent administration peak and trough lung tissue concentrations were, respectively, 7.1 ± 2.4 μg/g and 0.6 ± 1 μg/g. Lung bacterial burden was different after continuous and intermittent administration (median 7.103 vs. 4.102 cfu/g).
Continuous infusion of ceftazidime maintained higher tissue concentrations than intermittent administration.
KeywordsCeftazidime Continuous infusion Pseudomonas aeruginosa Bronchopneumonia Mechanical ventilation
- 1.Rubinstein E, Green M, Modan M, Amit P, Bernstein L, Rubinstein A (1989) The effects of nosocomial infections on the length and costs of hospital stay. J Antimicrob Chemother 9 [Suppl A]:93–100Google Scholar
- 3.Cavallo JD, Leblanc F, Fabre R (2000) Surveillance of Pseudomonas aeruginosa sensitivity to antibiotics in France and distribution of beta-lactam resistance mechanisms: 1998 GERPB study. Pathol Biol (Paris) 48:472–477Google Scholar
- 28.Roosendaal R, Bakker-Woudenberg IA, van den Berghe-van Raffe M, Vink-van den Berg JC, Michel BM (1989) Impact of the dosage schedule on the efficacy of ceftazidime, gentamicin and ciprofloxacin in Klebsiella pneumoniae pneumonia and septicemia in leukopenic rats. Eur J Clin Microbiol Infect Dis 8:878–887PubMedCrossRefGoogle Scholar
- 29.Robaux MA, Dube L, Caillon J, Bugnon D, Kergueris MF, Navas D, Le Conte P, Baron D, Potel G (2001) In vivo efficacy of continuous infusion versus intermittent dosing of ceftazidime alone or in combination with amikacin relative to human kinetic profiles in a Pseudomonas aeruginosa rabbit endocarditis model. J Antimicrob Chemother 47:617–622PubMedCrossRefGoogle Scholar
- 30.Cappelletty DM, Kang SL, Palmer SM, Rybak MJ (1995) Pharmacodynamics of ceftazidime administered as continuous infusion or intermittent bolus alone and in combination with single daily-dose amikacin against Pseudomonas aeruginosa in an in vitro infection model. Antimicrob Agents Chemother 39:1797–1801PubMedGoogle Scholar