title: Pharmacokinetic variability of clindamycin and influence of rifampicin on clindamycin concentration in patients with bone and joint infections.
abstract: OBJECTIVE
  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.
authors.affiliation: Laboratoire de biomathématiques, Faculté de pharmacie, Université Paris Descartes, Sorbonne Paris Cité, 4, avenue de l'Observatoire, 75006, Paris, France, emmanuel.curis@parisdescartes.fr.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Curis
authors.forename: Vincent
authors.initials: V
authors.lastname: Pestre
authors.forename: Vincent
authors.initials: V
authors.lastname: Jullien
authors.forename: Luc
authors.initials: L
authors.lastname: Eyrolle
authors.forename: Denis
authors.initials: D
authors.lastname: Archambeau
authors.forename: Philippe
authors.initials: P
authors.lastname: Morand
authors.forename: Laure
authors.initials: L
authors.lastname: Gatin
authors.forename: Matthieu
authors.initials: M
authors.lastname: Karoubi
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pinar
authors.forename: Valérie
authors.initials: V
authors.lastname: Dumaine
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Nguyen Van
authors.forename: Antoine
authors.initials: A
authors.lastname: Babinet
authors.forename: Philippe
authors.initials: P
authors.lastname: Anract
authors.forename: Dominique
authors.initials: D
authors.lastname: Salmon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002981:Clindamycin / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010019:Osteomyelitis / Q000097:blood / Q000188:drug therapy*; D012293:Rifampin / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D002981:Clindamycin; D012293:Rifampin
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