Witowski, Andrea and Palmowski, Lars and Minichmayr, Iris K. and Zeitlinger, Markus and Dorn, Christoph and Lier, Constantin and Adamzik, Michael and Nowak, Hartmuth and Rahmel, Tim (2024) Concentrations of ceftazidime and avibactam in bile fluid-a prospective phase IIb study. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 79 (12). pp. 3297-3302. ISSN 0305-7453, 1460-2091
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Background: The rise in carbapenem-resistant bacteria and the limited number of effective antibiotics pose a major health-care threat. The combination of ceftazidime (CAZ) and avibactam (AVI) represents an approved treatment option for carbapenem-resistant intra-abdominal infections. However, data on the pharmacokinetic profile of AVI in the hepatobiliary compartment is lacking. Objectives: To provide clinical in vivo data on the concentration of AVI in bile fluid as a surrogate for hepatobiliary excretion. Methods: A single dose of 2000/500 mg CAZ/AVI was administered prolonged over 2 h to 10 patients prior to abdominal surgery, with bile samples available in nine patients in this phase IIb study (DRKS-ID: DRKS00023533). Antibiotic concentrations in plasma (0-8 h), bile (after resection) and pharmacodynamic parameters were determined. Results: The mean concentration across individuals in bile was 33.5 mg/L (+/- 20.5 mg/L) for CAZ and 7.1 mg/L (+/- 3.5 mg/L) for AVI, resulting in bile/plasma ratios of 0.58 (+/- 0.26) and 0.61 (+/- 0.18). The Cmax in plasma was 87.2 mg/L (+/- 25.0 mg/L) for CAZ and 18.6 mg/L (+/- 6.29 mg/L) for AVI, with AUC0-infinity values of 351 h<middle dot>mg/L (+/- 104 h<middle dot>mg/L) and 72.1 h<middle dot>mg/L (+/- 32.1 h<middle dot>mg/L), respectively. Plasma concentrations of both CAZ and AVI remained more than 50% of the dosing interval above the minimum inhibitory concentrations (T>MIC > 50%; MICCAZ = 8 mg/L, MICAVI = 1 mg/L) in all patients. No antibiotic-associated side effects were reported during the 30-day follow-up. Conclusions: The concentrations of CAZ and AVI in bile suggest their potential as a valuable therapeutic option for multi-resistant biliary infections.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PLASMA |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Group Clinical Pharmacy (Dr. Dorn) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Jan 2026 10:41 |
| Last Modified: | 22 Jan 2026 10:41 |
| URI: | https://pred.uni-regensburg.de/id/eprint/64845 |
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