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- Title
Pharmacokinetic variability of clindamycin and influence of rifampicin on clindamycin concentration in patients with bone and joint infections.
- Authors
Curis, Emmanuel; Pestre, Vincent; Jullien, Vincent; Eyrolle, Luc; Archambeau, Denis; Morand, Philippe; Gatin, Laure; Karoubi, Matthieu; Pinar, Nicolas; Dumaine, Valérie; Van, Jean-Claude; Babinet, Antoine; Anract, Philippe; Salmon, Dominique
- 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, 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 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 value was 1.39 mg/L, with 58 % of the values below the threshold value of 1.7 mg/L. Median C 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: 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.
- Subjects
BIOLOGICAL assay; BONE diseases; COMBINATION drug therapy; CLINDAMYCIN; CONFIDENCE intervals; FISHER exact test; HIGH performance liquid chromatography; JOINT diseases; MULTIVARIATE analysis; PROBABILITY theory; QUESTIONNAIRES; REGRESSION analysis; RIFAMPIN; STATISTICS; COMORBIDITY; LOGISTIC regression analysis; BODY mass index; TREATMENT effectiveness; DATA analysis software; ODDS ratio
- Publication
Infection, 2015, Vol 43, Issue 4, p473
- ISSN
0300-8126
- Publication type
Article
- DOI
10.1007/s15010-015-0773-y