Pharmacokinetic variability of clindamycin and influence of rifampicin on clindamycin concentration in patients with bone and joint infections

• DOI: 10.1007/s15010-015-0773-y
• Publication Date: 2015-04-03T14:03:33Z
• Authors: Emmanuel Curis; Vincent Pestre; Vincent Jullien; Luc Eyrolle; Denis Archambeau; Philippe Morand; Laure Gatin; Matthieu Karoubi; Nicolas Pinar; Valérie Dumaine; Jean-Claude Nguye...; Antoine Babinet; Philippe Anract; Dominique Salmon
• Keywords: Bone Infection

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.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.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.This study shows the high inter-variability of plasma clindamycin concentration and confirms that co-treatment with rifampicin significantly decreases clindamycin trough concentrations.