JAC Advance Access published online on January 28, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg111
© 2003 by The British Society for Antimicrobial Chemotherapy
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Original article
1 Zentralklinik Emil v. Behring, Department Lungenklinik Heckeshorn, Pneumologie I, affil. Freie Universität Berlin, Zum Heckeshorn
33, D-14109 Berlin
* Corresponding author. E-mail: haloheck{at}zedat.fu-berlin.de.
Received 19 June 2002
; revised 25 August 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
Optimizing ceftazidime pharmacodynamics in patients
with acute exacerbation of severe chronic bronchitis
2 Zentralklinik Emil v. Behring, Department Lungenklinik Heckeshorn, 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
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