The oral combination of clindamycin and rifampicin is relevant for the treatment of staphylococcal osteoarticular infections (SOAI). However, rifampicin induces CYP3A4, suggesting a pharmacokinetic (PK) interaction with clindamycin with unknown PK/pharmacodynamic (PD) consequences.
To quantify clindamycin PK/PD markers before and during rifampicin co-administration in OAI.
Patients with SOAI were included (NCT02782078). After an initial intravenous antistaphylococcal treatment, oral therapy was started with clindamycin (600 or 750 mg tid), followed by the addition of rifampicin 36 hours after. Population PK analysis was performed using the SAEM algorithm. PKPD markers were compared with and without rifampicin co-administration, each patient being his own control.
In 19 patients, Clindamycin Median (min-max) through concentrations were 2.7 (0.3-8.9) and <0.05 (<0.05-0.3) mg/L, before and during rifampicin administration, respectively. Rifampicin co-administration increased clindamycin clearance by a factor 16 and reduced the AUC /MIC by a factor 15 (p 60, even with high dose of clindamycin.
Rifampicin co-administration with clindamycin has high impact on clindamycin exposure and PKPD targets in SOAI, which could result in clinical failures, even for a fully susceptible strain.
Copyright © 2023. Published by Elsevier Ltd.
