Skip to main content
SpringerLink
Log in

Pharmacokinetic variability of clindamycin and influence of rifampicin on clindamycin concentration in patients with bone and joint infections

  • Original Paper
  • Published:
Infection Aims and scope Submit manuscript

Abstract

Purpose

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. LaPlante KL, Leonard SN, Andes DR, Craig WA, Rybak MJ. Activities of clindamycin, daptomycin, doxycycline, linezolid, trimethoprim-sulfamethoxazole, and vancomycin against community-associated methicillin-resistant Staphylococcus aureus with inducible clindamycin resistance in murine thigh infection and in vitro pharmacodynamic models. Antimicrob Agents Chemother. 2008;52:2156–62.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Klepser ME, Nicolau DP, Quintiliani R, Nightingale CH. Bactericidal activity of low-dose clindamycin administered at 8- and 12-hour intervals against Staphylococcus aureus, Streptococcus pneumoniae, and Bacteroides fragilis. Antimicrob Agents Chemother. 1997;41:630–5.

    CAS  PubMed Central  PubMed  Google Scholar 

  3. Zabransky RJ, Johnston JA, Hauser KJ. Bacteriostatic and bactericidal activities of various antibiotics against Bacteroides fragilis. Antimicrob Agents Chemother. 1973;3:152–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Klepser ME, Banevicius MA, Quintiliani R, Nightingale CH. Characterization of bactericidal activity of clindamycin against Bacteroides fragilis via kill curve methods. Antimicrob Agents Chemother. 1996;40:1941–4.

    CAS  PubMed Central  PubMed  Google Scholar 

  5. Panzer JD, Brown DC, Epstein WL, Lipson RL, Mahaffey HW, Atkinson WH. Clindamycin levels in various body tissues and fluids. J Clin Pharmacol New Drugs. 1972;12:259–62.

    Article  CAS  PubMed  Google Scholar 

  6. Schurman DJ, Johnson BL Jr, Finerman G, Amstutz HC. Antibiotic bone penetration. Concentrations of methicillin and clindamycin phosphate in human bone taken during total hip replacement. Clin Orthop Relat Res. 1975;111:142–6.

    Article  PubMed  Google Scholar 

  7. Nicholas P, Meyers BR, Levy RN, Hirschman SZ. Concentration of clindamycin in human bone. Antimicrob Agents Chemother. 1975;8:220–1.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Dornbusch K, Carlström A, Hugo H, Lidströlm A. Antibacterial activity of clindamycin and lincomycin in human bone. J Antimicrob Chemother. 1977;3:153–60.

    Article  CAS  PubMed  Google Scholar 

  9. Summersgill JT, Schupp LG, Raff MJ. Comparative penetration of metronidazole, clindamycin, chloramphenicol, cefoxitin, ticarcillin, and moxalactam into bone. Antimicrob Agents Chemother. 1982;21:601–3.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Duckworth C, Fisher JF, Carter SA, Newman CL, Cogburn C, Nesbit RR. Tissue penetration of clindamycin in diabetic foot infections. J Antimicrob Chemother. 1993;31:581–4.

    Article  CAS  PubMed  Google Scholar 

  11. Plott MA, Roth H. Penetration of clindamycin into synovial fluid. Clin Pharmacol Ther. 1970;11:577–80.

    CAS  PubMed  Google Scholar 

  12. Geddes AM, Dwyer NS, Ball AP, Amos RS. Clindamycin in bone and joint infections. J Antimicrob Chemother. 1977;3:501–7.

    Article  CAS  PubMed  Google Scholar 

  13. El Samad Y, Havet E, Bentayeb H, Olory B, Canarelli B, Lardanchet JF, Douadi Y, Rousseau F, Lescure FX, Mertl P, Eb F, Schmit JL. Treatment of osteoarticular infections with clindamycin in adults. Med Mal Infect. 2008;38:465–70.

    Article  PubMed  Google Scholar 

  14. Mader JT, Shirtliff ME, Bergquist SC, Calhoun J. Antimicrobial treatment of chronic osteomyelitis. Clin Orthop Relat Res. 1999;360:47–65.

    Article  PubMed  Google Scholar 

  15. Darley ES, MacGowan AP. Antibiotic treatment of gram-positive bone and joint infections. J Antimicrob Chemother. 2004;53:928–35.

    Article  CAS  PubMed  Google Scholar 

  16. Feigin RD, Pickering LK, Anderson D, Keeney RE, Shakleford PG. Clindamycin treatment of osteomyelitis and septic arthritis in children. Pediatrics. 1975;55:213–23.

    CAS  PubMed  Google Scholar 

  17. Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antimicrobial dosing of mice and men. Clin Infect Dis. 1998;26:1–12.

    Article  CAS  PubMed  Google Scholar 

  18. Ambrose PG, Bhavnani SM, Rubino CM, Louie A, Gumbo T, Forrest A, Drusano GL. Pharmacokinetics-pharmacodynamics of antimicrobial therapy: it’s not just for mice anymore. Clin Infect Dis. 2007;44:79–86.

    Article  CAS  PubMed  Google Scholar 

  19. Weinstein MP, Stratton CW, Hawley HB, Ackley A, Reller LB. Multicenter collaborative evaluation of a standardized serum bactericidal test as a predictor of therapeutic efficacy in acute and chronic osteomyelitis. Am J Med. 1987;83:218–22.

    Article  CAS  PubMed  Google Scholar 

  20. Flaherty JF, Rodondi LC, Guglielmo BJ, Fleishaker JC, Townsend RJ, Gambertoglio JG. Comparative pharmacokinetics and serum inhibitory activity of clindamycin in different dosing regimens. Antimicrob Agents Chemother. 1988;32:1825–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Plaisance KI, Drusano GL, Forrest A, Townsend RJ, Standiford HC. Pharmacokinetic evaluation of two dosage regimens of clindamycin phosphate. Antimicrob Agents Chemother. 1989;33:618–20.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Gatti G, Flaherty J, Bubp J, White J, Borin M, Gambertoglio J. Comparative study of bioavailabilities and pharmacokinetics of clindamycin in healthy volunteers and patients with AIDS. Antimicrob Agents Chemother. 1993;37:1137–43.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. del Carrasco-Portugal MC, Lujan M, Flores-Murrieta FJ. Evaluation of gender in the oral pharmacokinetics of clindamycin in humans. Biopharm Drug Dispos. 2008;29:427–30.

    Article  CAS  Google Scholar 

  24. Muller AE, Mouton JW, Oostvogel PM, Dorr PJ, Voskuyl RA, DeJongh J, Steegers EA, Danhof M. Pharmacokinetics of clindamycin in pregnant women in the peripartum period. Antimicrob Agents Chemother. 2010;54:2175–81.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Zeller V, Dzeing-Ella A, Kitzis MD, Ziza JM, Mamoudy P, Desplaces N. Continuous clindamycin infusion, an innovative approach to treating bone and joint infections. Antimicrob Agents Chemother. 2010;54:88–92.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Niemi M, Backman JT, Fromm MF, Neuvonen PJ, Kivistö KT. Pharmacokinetic interactions with rifampin: clinical relevance. Clin Pharmacokinet. 2003;42:819–50.

    Article  CAS  PubMed  Google Scholar 

  27. Sousa M, Pozniak A, Boffito M. Pharmacokinetics and pharmacodynamics of drug interactions involving rifampicin, rifabutin and antimalarial drugs. J Antimicrob Chemother. 2008;62:872–8.

    Article  CAS  PubMed  Google Scholar 

  28. Wynalda MA, Hutzler JM, Koets MD, Podoll T, Wienkers LC. In vitro metabolism of clindamycin in human liver and intestinal microsomes. Drug Metab Dispos. 2003;31:878–87.

    Article  CAS  PubMed  Google Scholar 

  29. Czekaj J, Dinh AL, Moldovan A, Vaudaux P, Gras G, Hoffmeyer P, Lew D, Bernard L, Uçkay I. Efficacy of a combined oral clindamycin? rifampicin regimen for therapy of staphylococcal osteoarticular infections. Scand J Infect Dis. 2011;43:962–7.

    Article  CAS  PubMed  Google Scholar 

  30. Hothorn T, Bretz F, Westfall P. Simultaneous inference in general parametric models. Biometrical Journal. 2008;50:346–63.

    Article  PubMed  Google Scholar 

  31. Fox J, Weisberg S. An R companion to applied regression, 2nd edn. Thousand Oaks: Sage, 2011. URL:http://www.socserv.socsci.mcmaster.ca/jfox/Books/Companion.

  32. McLellan RA, Drobitch RK, Monshouwer M, Renton KW. Fluoroquinolone antibiotics inhibit cytochrome P450-mediated microsomal drug metabolism in rat and human. Drug Metab Dispos. 1996;24:1134–8.

    CAS  PubMed  Google Scholar 

  33. Marculescu CE, Cantey JR. Polymicrobial prosthetic joint infections: risk factors and outcome. Clin Orthop Relat Res. 2008;466:1397–404.

    Article  PubMed Central  PubMed  Google Scholar 

  34. Zeller V, Lavigne M, Biau D, et al. Outcome of group B streptococcal prosthetic hip infections compared to that of other bacterial infections. Joint Bone Spine. 2009;76:491–6.

    Article  PubMed  Google Scholar 

  35. Lee J, Kang CI, Lee JH, Joung M, Moon S, Wi YM, Chung DR, Ha CW, Song JH, Peck KR. Risk factors for treatment failure in patients with prosthetic joint infections. J Hosp Infect. 2010;75:273–6.

    Article  CAS  PubMed  Google Scholar 

  36. Senneville E, Joulie D, Legout L, Valette M, Dezèque H, Beltrand E, Roselé B, d’Escrivan T, Loïez C, Caillaux M, Yazdanpanah Y, Maynou C, Migaud H. Outcome and predictors of treatment failure in total hip/knee prosthetic joint infections due to Staphylococcus aureus. Clin Infect Dis. 2011;53:334–40.

    Article  PubMed Central  PubMed  Google Scholar 

  37. Peel TN, Buising KL, Dowsey MM, Aboltins CA, Daffy JR, Stanley PA, Choong PF. Outcome of debridement and retention in prosthetic joint infections by methicillin-resistant staphylococci, with special reference to rifampin and fusidic acid combination therapy. Antimicrob Agents Chemother. 2013;57:350–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Peddie BA, Dann E, Bailey RR. The effect of impairment of renal function and dialysis on the serum and urine levels of clindamycin. Aust NZ J Med. 1975;5:198–202.

    Article  CAS  Google Scholar 

  39. Roberts AP, Eastwood JB, Gower PE, Fenton CM, Curtis JR. Serum and plasma concentrations of clindamycin following a single intramuscular injection of clindamycin phosphate in maintenance haemodialysis patients and normal subjects. Eur J Clin Pharmacol. 1978;14:435–9.

    Article  CAS  PubMed  Google Scholar 

  40. Eastwood JB, Gower PE. A study of the pharmacokinetics of clindamycin in normal subjects and patients with chronic renal failure. Postgrad Med J. 1974;50:710–2.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Conflict of interest

No author had conflict of interest; no Grant or funding was raised for this study.

Author information

Author notes

    Authors and Affiliations

    1. Laboratoire de biomathématiques, Faculté de pharmacie, Université Paris Descartes, Sorbonne Paris Cité, 4, avenue de l’Observatoire, 75006, Paris, France

      Emmanuel Curis

    2. Infectious Diseases Unit, Assistance Publique Hôpitaux de Paris, Cochin Hospital, Université Paris Descartes, Sorbonne Paris Cité, Paris, France

      Vincent Pestre & Dominique Salmon

    3. Pharmacology Department, Assistance Publique Hôpitaux de Paris, Cochin Hospital, Université Paris Descartes, Sorbonne Paris Cité, Paris, France

      Vincent Jullien

    4. Anaesthesiology Department, Assistance Publique Hôpitaux de Paris, Cochin Hospital, Paris, France

      Luc Eyrolle & Denis Archambeau

    5. Bacteriology Department, Assistance Publique Hôpitaux de Paris, Cochin Hospital, Université Paris Descartes, Sorbonne Paris Cité, Paris, France

      Philippe Morand

    6. Orthopaedic Surgery Department, Assistance Publique Hôpitaux de Paris, Cochin Hospital, Université Paris Descartes, Sorbonne Paris Cité, Paris, France

      Laure Gatin, Matthieu Karoubi, Nicolas Pinar, Valérie Dumaine, Antoine Babinet & Philippe Anract

    7. Service de chirurgie orthopédique, Institut hospitalier franco-Britanique, Levallois, France

      Nicolas Pinar

    8. Laboratoire de microbiologie médicale, Fondation hôpital Saint-Joseph, Paris, France

      Jean-Claude Nguyen Van

    Authors
    1. Emmanuel Curis
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Vincent Pestre
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Vincent Jullien
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Luc Eyrolle
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Denis Archambeau
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Philippe Morand
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Laure Gatin
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Matthieu Karoubi
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Nicolas Pinar
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Valérie Dumaine
      View author publications

      You can also search for this author in PubMed Google Scholar

    11. Jean-Claude Nguyen Van
      View author publications

      You can also search for this author in PubMed Google Scholar

    12. Antoine Babinet
      View author publications

      You can also search for this author in PubMed Google Scholar

    13. Philippe Anract
      View author publications

      You can also search for this author in PubMed Google Scholar

    14. Dominique Salmon
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Emmanuel Curis or Dominique Salmon.

    Additional information

    E. Curis and V. Pestre contributed equally to this manuscript.

    Electronic supplementary material

    Below is the link to the electronic supplementary material.

    Supplementary material 1 (DOC 38 kb)

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Curis, E., Pestre, V., Jullien, V. et al. Pharmacokinetic variability of clindamycin and influence of rifampicin on clindamycin concentration in patients with bone and joint infections. Infection 43, 473–481 (2015). https://doi.org/10.1007/s15010-015-0773-y

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s15010-015-0773-y

    Keywords

    Search

    Navigation