Pharmacokinetic interaction between rifampicin and clindamycin in staphylococcal osteoarticular infections

被引：7

作者：

Goulenok, T. ^{[1
,11
]}

Seurat, J. ^{[2
]}

de La Selle, A. ^{[3
]}

Jullien, V. ^{[4
]}

Leflon-Guibout, V. ^{[5
]}

Grall, N. ^{[2
,6
]}

Lescure, F. X. ^{[2
,7
]}

Lepeule, R. ^{[8
,9
]}

Bertrand, J. ^{[2
]}

Fantin, B. ^{[2
]}

Burdet, C. ^{[2
,10
]}

Lefort, A. ^{[2
,3
]}

机构：

[1] Univ Paris, Hop Bichat Claude Bernard, GHU APHP Nord, Dept Med Interne, Paris, France

[2] Univ Paris Cite, INSERM 1137, IAME, F-75018 Paris, France

[3] Univ Paris, Hop Beaujon, GHU APHP Nord, Dept Med Interne, Paris, France

[4] Univ Sorbonne Paris Nord, Hop Jean Verdier, UF Pharmacol, F-93141 Bondy, France

[5] Univ Paris, Hop Beaujon, GHU APHP Nord, Serv Microbiol, Paris, France

[6] Univ Paris, Hop Bichat Claude Bernard, GHU APHP Nord, Serv Bacteriol, Paris, France

[7] Univ Paris, Hop Bichat Claude Bernard, GHU APHP Nord, Serv Malad Infect & Trop, Paris, France

[8] Hop Univ Henri Mondor, APHP, Unite Rransversale Traitement Infect, F-94010 Creteil, France

[9] Univ Paris Est Creteil, EA Dynamyc 7380, EnvA, UPEC, F-94000 Creteil, France

[10] Univ Paris, Hop Bichat Claude Bernard, GHU APHP Nord, Biostat & Rech Clin,Dept Epidemiol, Paris, France

[11] Hop Bichat Claude Bernard, Dept Med Interne, 46 Rue Henri Huchard, F-75018 Paris, France

来源：

INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS | 2023年 / 62卷 / 02期

关键词：

Clindamycin; Rifampicin; Bone and joint infection; Pharmacokinetics; Drug interaction; DRAMATIC REDUCTION; OSTEOMYELITIS; COMBINATION; LEVOFLOXACIN; EFFICACY; THERAPY; BONE;

D O I：

10.1016/j.ijantimicag.2023.106885

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

Objectives: Oral combination of clindamycin and rifampicin is relevant for the treatment of staphylococcal osteoarticular infection (SOAIs). However, rifampicin induces CYP3A4, suggesting a pharmacokinetic interaction with clindamycin with unknown pharmacokinetic/pharmacodynamic (PK/PD) consequences. This study aimed to quantify clindamycin PK/PD markers before and during rifampicin co-administration in SOAI. Methods: Patients with SOAI were included. After initial intravenous antistaphylococcal treatment, oral therapy was started with clindamycin (600 or 750 mg t.i.d.), followed by addition of rifampicin 36 h later. Population PK analysis was performed using the SAEM algorithm. PK/PD markers were compared with and without rifampicin co-administration, each patient being his own control. Results: In 19 patients, clindamycin median (range) trough concentrations were 2.7 (0.3-8.9) mg/L 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 0-8h/MIC by a factor 15 (P < 0.005). Clindamycin plasma concentrations were simulated for 1000 individuals, without and with rifampicin. Against a susceptible Staphylococcus aureus strain (clindamycin MIC 0.0625 mg/L), >80% of individuals would reach all proposed PK/PD targets without co-administration of rifampicin, even with low clindamycin dose. For the same strain, when rifampicin was co-administered, the probability to reach clindamycin PK/PD targets dropped to 1% for %fT(>MIC) = 100% and to 6% for AUC(0-24h)/MIC > 60, even with high clindamycin dose. Conclusion: Rifampicin co-administration with clindamycin has a high impact on clindamycin exposure and PK/PD targets in SOAI, which could result in clinical failure even for fully susceptible strains. (c) 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.

引用

页数：8

共 37 条

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