JAC Advance Access originally published online on January 28, 2003
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Journal of Antimicrobial Chemotherapy (2003) 51, 659-664
© 2003 The British Society for Antimicrobial Chemotherapy
Optimizing ceftazidime pharmacodynamics in patients with acute exacerbation of severe chronic bronchitis
Zentralklinik Emil v. Behring, Department Lungenklinik Heckeshorn, 1 Pneumologie I and 2 Institute of Medical Microbiology and Immunology, affil. Freie Universität Berlin, Zum Heckeshorn 33, D-14109 Berlin; 3 Department of Internal Medicine, Kreiskrankenhaus Lüdenscheid, Paulmannshöher Str. 14, 58515 Lüdenscheid; 4 Klinikum Nord, Medizinische Klinik I, Department of Pneumologie, Prof.-Ernst-Nathan-Str. 1, 90419 Nürnberg; 5 Medizinische Klinik und Poliklinik, Universitätsklinikum Magdeburg, Otternweg 7, 39120 Magdeburg, Germany
Received 19 June 2002; returned 25 August 2002; revised 5 October 2002; accepted 3 December 2002
Objectives: Implementation of current pharmacodynamic knowledge could enhance clinical results, avoid resistance development and reduce treatment costs. In this open, randomized, multicentre study, we evaluated the clinical and bacteriological outcome and pharmacokinetic as well as pharmacodynamic parameters of two ceftazidime therapy regimens in patients with acute exacerbation of severe chronic bronchitis (AECB).
Methods: Eighty-one patients (56 males, 25 females, age 65.3 ± 10.1 years) with AECB were included. A subgroup of 21 patients underwent pharmacokinetic and pharmacodynamic examination. The patients received either ceftazidime 2 g every 8 h (C3 x 2) or ceftazidime 2 g as a loading dose, followed by ceftazidime 2 g over 7 h every 12 h (C2 x 2) for 8–14 days. Clinical and bacteriological responses were monitored at day 8 or 9, and 72 h after the end of therapy (EOT).
Results: At EOT, clinical success was recorded in 90% and 90.2% of clinically evaluable patients receiving C3 x 2 and C2 x 2, respectively. Bacteriological success at EOT was achieved in 87.5% and 90.2% of evaluable patients treated with C3 x 2 and C2 x 2, respectively. Cmax (mg/L) varied between 168.9 ± 34.1 and 144.0 ± 9.8 in the C3 x 2 group, and between 60.1 ± 34.1 and 54.2 ± 30.4 at steady-state in the C2 x 2 group. Minimal concentrations were between 9.1 and 13.4 mg/L in the C3 x 2 group, and between 16.6 and 17.7 mg/L in the C2 x 2 group. Concentrations >4–5 x MIC were seen in all pathogens, except Staphylococcus aureus, during 100% of infusion time.
Conclusion: The 2 x 7 h infusion of ceftazidime 2 g (C2 x 2) was clinically and bacteriologically as effective as the usual 3 x 2 g ceftazidime short-term infusion in the treatment of AECB, and demonstrated advantages in terms of pharmacodynamic parameters compared with the C3 x 2 regimen.
Keywords: ceftazidime, AECB, pharmacokinetic, pharmacodynamic
* Corresponding author. Tel: +49-30-8002-2222; Fax: +49-30-8002-2623; E-mail: haloheck{at}zedat.fu-berlin.de