Dramatic reduction of clindamycin serum concentration in staphylococcal osteoarticular infection patients treated with the oral clindamycin-rifampicin combination.
OBJECTIVE
Pharmacokinetics of clindamycin in combination with rifampicin or levofloxacin were prospectively evaluated for the oral treatment of severe staphylococcal osteo articular infections.


METHODS
Thirty-four patients (25 males, 9 females), with a mean age of 52.4 ± 17 years (range, 24-81 years), were randomly assigned either to the clindamycin-rifampicin or to the clindamycin-levofloxacin arm (control), following surgical debridement and intravenous adapted treatment. Trough and peak serum concentrations of clindamycin were measured at day-1 (D1), D15 and D30 of oral treatment. Cure was evaluated at a minimum of one year after the initiation of treatment.


RESULTS
The oral treatment was interrupted in 4 cases because of adverse events. Mean trough and peak serum concentrations of clindamycin in the clindamycin-rifampicin arm were lower than in the clindamycin-levofloxacin arm during the time of oral antibiotic regimen (0.79 ± 0.3 μg/ml vs 4.7 ± 1.2 μg/ml, p < 0.001, and 3.48 ± 1.1 μg/ml vs 10.2 ± 1.8 μg/ml, p < 0.001, respectively). A consistent decrease in clindamycin serum concentration was observed at each time-point of follow-up. At a mean of 23 ± 7.8 months (range, 12-47 months), 24 patients were available for clinical evaluation. No difference could be detected in the cure rates between the groups.


CONCLUSIONS
Our results indicate a significant influence of rifampicin on clindamycin pharmacokinetics using the oral route. Clindamycin serum concentrations (trough and peak) were systematically below the recommended therapeutic ranges when associated with rifampicin, as opposed to the control. Considering the potential risk of selection of mutant resistant to clindamycin, we do not recommend the clindamycin-rifampicin combination in the oral treatment of severe staphylococcal osteoarticular infection, unless clindamycin serum concentration is thoroughly controlled. The study has been registered on the clinicaltrials.gov website under the number NCT 01500837.
Service de Pharmacie, Hôpital Européen Georges Pompidou, AP-HP, 75015 Paris, France.
Aurélie
A
Bernard
Department of Traumatology and Orthopaedic Surgery, European Hospital of Paris, Medical School Paris 5 René Descartes, AP-HP, Paris, France.
Gwénolé
G
Kermarrec
Unité Mobile de Microbiologie Clinique, Service de Microbiologie, Hôpital Européen Georges Pompidou, AP-HP, 75015 Paris, France.
Perrine
P
Parize
Service de Pharmacie, Hôpital Européen Georges Pompidou, AP-HP, 75015 Paris, France.
Thibaut
T
Caruba
Service de Pharmacie, Hôpital Européen Georges Pompidou, AP-HP, 75015 Paris, France.
Anaïs
A
Bouvet
Unité Mobile de Microbiologie Clinique, Service de Microbiologie, Hôpital Européen Georges Pompidou, AP-HP, 75015 Paris, France; UMRS 1138, Laboratoire de Recherche Moléculaire sur les Antibiotiques, Equipe 12 du Centre de Recherche des Cordeliers, Université Paris Descartes et Université Pierre-et-Marie-Curie, 75006 Paris, France.
Jean-Luc
JL
Mainardi
Service de Pharmacie, Hôpital Européen Georges Pompidou, AP-HP, 75015 Paris, France; Inserm UMR 1138, Equipe 22 « Systèmes d'information et médecine personnalisée », Centre de Recherche des Cordeliers, Université Paris Descartes et Université Pierre-et-Marie-Curie, 75006 Paris, France.
Brigitte
B
Sabatier
Department of Traumatology and Orthopaedic Surgery, European Hospital of Paris, Medical School Paris 5 René Descartes, AP-HP, Paris, France. Electronic address: chrnich@gmail.com.
Christophe
C
Nich
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002981:Clindamycin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000188:drug therapy*; D011446:Prospective Studies; D012293:Rifampin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D044967:Serum / Q000737:chemistry*; D013203:Staphylococcal Infections / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
D000900:Anti-Bacterial Agents; D002981:Clindamycin; D012293:Rifampin
Clindamycin; Osteoarticular infection; Pharmacokinetics; Rifampicin; Staphylococcal infection