Clindamycin-rifampin Drug Interaction in the Treatment of Bone and Joint Infections
Status:
Completed
Trial end date:
2019-12-01
Target enrollment:
Participant gender:
Summary
Treatment of bone and joint infections remains difficult and variable according to centres
and countries. Clindamycin given intravenously and followed by an oral route is recommended
for the treatment of staphylococcal, streptococcal and anaerobes bone and joint infections by
the French Society for Infectious Diseases. For staphylococcal bone and implant infections,
rifampin is a major drug, as it remains active in bacterial biofilm and on quiescent
staphylococci. For that reasons, clindamycin-rifampin combination therapy is frequently used
in these infections.Clindamycin is metabolized by the P450 3A4 cytochrome, an enzyme strongly
inducible by rifampin. A retrospective study published in 2010 on 70 patients treated for
bone and joint infections showed that clindamycin serum concentrations were significantly
lower when clindamycin was combined with rifampin (5.3 mg/liter vs 8.9 mg/liter; p<0.02).
This drug interaction could even be stronger with the oral route, because of hepatic
first-past effect, ending up with very low clindamycin serum concentration, a risk of
selecting resistant microorganisms and treatment failure. This latter point is an important
issue, because clindamycin has an excellent oral bioavailability and is frequently used in
oral regimens. In the above study, a wide variability of clindamycin serum concentration was
observed in the group of patients treated with combination therapy (1-12mg/l) suggesting
interindividual variability. Rifampin induction of CYP 450 3A4/A5 depends on different
receptor (PXR, RXR, LXRalpha) submitted to genetic polymorphism. Hypothesis: Plasma clearance
of clindamycin (CLclin) combined with rifampicin (CLclinrif) is higher when clindamycin is
administered by the oral route (CLclinrif OR) compared with IV administration (CLclinrif IV).
Details
Lead Sponsor:
Fondation Ophtalmologique Adolphe de Rothschild Groupe Hospitalier Diaconesses Croix Saint-Simon
Collaborators:
Fondation Ophtalmologique Adolphe de Rothschild Groupe Hospitalier Diaconesses Croix Saint-Simon