Erschienen in:
01.08.2015 | Original Paper
Pharmacokinetic variability of clindamycin and influence of rifampicin on clindamycin concentration in patients with bone and joint infections
verfasst von:
Emmanuel Curis, Vincent Pestre, Vincent Jullien, Luc Eyrolle, Denis Archambeau, Philippe Morand, Laure Gatin, Matthieu Karoubi, Nicolas Pinar, Valérie Dumaine, Jean-Claude Nguyen Van, Antoine Babinet, Philippe Anract, Dominique Salmon
Erschienen in:
Infection
|
Ausgabe 4/2015
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Abstract
Purpose
Clindamycin, a lincosamide antibiotic with a good penetration into bone, is widely used for treating bone and joint infections by Gram-positive pathogens. To be active against Staphylococcus spp, its concentration at the infection site, C, must be higher than 2× the minimal inhibitory concentration (MIC). The aims of the work were to study the determinants of plasma clindamycin trough concentration, C
min, especially the effect of co-treatment with rifampicin, and the consequences on clinical outcome.
Methods
An observational study was performed, involving patients hospitalized for a bone and joint infection who received clindamycin as part of their antibiotic treatment. Target C
min was 1.7 mg/L, to reach the desired bone concentration/MIC >2, assuming a 30 % diffusion into bone and MIC = 2.5 mg/L.
Results
Sixty one patients (mean age: 56.8 years, 57.4 % male) were included between 2007 and 2011. 72.1 % underwent a surgery on a foreign material, and 91.1 % were infected by at least a Gram-positive micro-organism. Median C
min value was 1.39 mg/L, with 58 % of the values below the threshold value of 1.7 mg/L. Median C
min was significantly lower for patients taking rifampicin (0.46 vs 1.52 mg/L, p = 0.034). No patient with rifampicin co-administration reached the target concentration (maximal C
min: 0.85 mg/L). After a median follow-up of 17 months (1.5–38 months), 4 patients relapsed, 2 died and 47 (88.7 % of the patients with known outcome) were cured, independently of association with rifampicin.
Conclusions
This study shows the high inter-variability of plasma clindamycin concentration and confirms that co-treatment with rifampicin significantly decreases clindamycin trough concentrations.