Optimizing ceftazidime pharmacodynamics in patients with acute exacerbation of severe chronic bronchitis.
OBJECTIVE
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. C(max) (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.


CONCLUSIONS
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.
Lubasch
Annette
A
Zentralklinik Emil v. Behring, Department Lungenklinik Heckeshorn, Pneumologie I, Freie Universität Berlin, Zum Heckeshorn 33, D-14109 Berlin.
Lück
Stefan
S
Lode
Hartmut
H
Mauch
Harald
H
Lorenz
Joachim
J
Bölcskei
Pal
P
Welte
Tobias
T
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D029481:Bronchitis, Chronic / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D002442:Ceftazidime / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
D002442:Ceftazidime