Skip to main content
SpringerLink
Log in

Influence of daily dosage and frequency of administration of rifampicin–levofloxacin therapy on tolerance and effectiveness in 154 patients treated for prosthetic joint infections

  • Article
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

Data on the tolerance and effectiveness of rifampicin–levofloxacin combination therapy (RLCT) in patients treated for prosthetic joint infections (PJIs) according to daily dosage are lacking. A review of the clinical data from patients treated with RLCT for PJIs in a French referent center for PJIs was conducted. A total of 154 patients (75 F/79 M), with a median age of 64.1 years and median body weight of 83.1 kg, were included. The median daily dosages of rifampicin and levofloxacin were, respectively, 1,200 mg (range 300–2,100) and 750 mg (range 500–1,500), corresponding to a mean daily dose per kg of, respectively, 16.2 ± 4.3 mg/kg and 10.1 ± 3.0 mg/kg. After a mean follow-up period of 55.6 ± 27.1 months (range 24–236), 127 patients (82.5 %) were in remission. Adverse events attributable to rifampicin and levofloxacin were reported in 48 (31.2 %) and 13 (8.4 %) patients (p < 0.001), respectively. Patients who experienced rifampicin-related adverse events had been given higher rifampicin daily doses than the other patients (p = 0.04). The rifampicin daily dosage did not influence patient outcome and nor did the levofloxacin daily dosage on both tolerance and patient outcome. Our results suggest that adjusting rifampicin daily doses to the patient total body weight when combined with levofloxacin for the treatment of PJIs is associated with a poor tolerance. High daily doses of rifampicin (>600 mg) and levofloxacin (750 mg) do not improve patient outcome when compared to lower daily doses in this setting.

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. Chuard C, Herrmann M, Vaudaux P et al (1991) Successful therapy of experimental chronic foreign-body infection due to methicillin-resistant Staphylococcus aureus by antimicrobial combinations. Antimicrob Agents Chemother 35:2611–2616

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Lucet JC, Herrmann M, Rohner P et al (1990) Treatment of experimental foreign body infection caused by methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 34:2312–2317

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Zimmerli W, Widmer AF, Blatter M et al (1998) Role of rifampin for treatment of orthopedic implant-related staphylococcal infections: a randomized controlled trial. Foreign-Body Infection (FBI) Study Group. JAMA 279:1537–1541

    Article  CAS  PubMed  Google Scholar 

  4. El Helou OC, Berbari EF, Lahr BD et al (2010) Efficacy and safety of rifampin containing regimen for staphylococcal prosthetic joint infections treated with debridement and retention. Eur J Clin Microbiol Infect Dis 29:961–967

    Article  PubMed  Google Scholar 

  5. Senneville E, Joulie D, Legout L et al (2011) Outcome and predictors of treatment failure in total hip/knee prosthetic joint infections due to Staphylococcus aureus. Clin Infect Dis 53:334–340

    Article  PubMed Central  PubMed  Google Scholar 

  6. Lora-Tamayo J, Murillo O, Iribarren JA et al (2013) A large multicenter study of methicillin-susceptible and methicillin-resistant Staphylococcus aureus prosthetic joint infections managed with implant retention. Clin Infect Dis 56:182–194

    Article  PubMed  Google Scholar 

  7. Kaye KS, Engemann JJ, Fraimow HS et al (2004) Pathogens resistant to antimicrobial agents: epidemiology, molecular mechanisms, and clinical management. Infect Dis Clin North Am 18:467–511

    Article  PubMed  Google Scholar 

  8. Spratt BG (1994) Resistance to antibiotics mediated by target alterations. Science 264:388–393

    Article  CAS  PubMed  Google Scholar 

  9. Grosset J, Leventis S (1983) Adverse effects of rifampicin. Rev Infect Dis 5(Suppl 3):S440–S450

    Article  CAS  PubMed  Google Scholar 

  10. Finch CK, Chrisman CR, Baciewicz AM et al (2002) Rifampin and rifabutin drug interactions: an update. Arch Intern Med 162:985–992

    Article  CAS  PubMed  Google Scholar 

  11. Roblot F, Besnier JM, Giraudeau B et al (2007) Lack of association between rifampicin plasma concentration and treatment-related side effects in osteoarticular infections. Fundam Clin Pharmacol 21:363–369

    Article  CAS  PubMed  Google Scholar 

  12. Nijland HM, Ruslami R, Suroto AJ et al (2007) Rifampicin reduces plasma concentrations of moxifloxacin in patients with tuberculosis. Clin Infect Dis 45:1001–1007

    Article  CAS  PubMed  Google Scholar 

  13. Drancourt M, Stein A, Argenson JN et al (1993) Oral rifampin plus ofloxacin for treatment of Staphylococcus-infected orthopedic implants. Antimicrob Agents Chemother 37:1214–1218

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Osmon DR, Berbari EF, Berendt AR et al; Infectious Diseases Society of America (2013) Executive summary: diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 56:1–10

    Article  PubMed  Google Scholar 

  15. Frippiat F, Meunier F, Derue G (2004) Place of newer quinolones and rifampicin in the treatment of Gram-positive bone and joint infections. J Antimicrob Chemother 54:1158

    Article  CAS  PubMed  Google Scholar 

  16. Zimmerli W, Trampuz A, Ochsner PE (2004) Prosthetic-joint infections. N Engl J Med 351:1645–1654

    Article  CAS  PubMed  Google Scholar 

  17. Steckelberg JM, Osmon DR (2000) Prosthetic joint infections. In: Waldvogel FA, Bisno AL (eds) Infections associated with indwelling medical devices, 3rd edn. ASM Press, Washington, pp 173–209

    Chapter  Google Scholar 

  18. Westrich GH, Salvati EA, Brause B (1999) Postoperative infection. In: Bono JV, McCarthy JC, Thornhill TS, Bierbaum BE, Turner RH (eds) Revision total hip arthroplasty. Springer-Verlag, New York, pp 371–390

    Chapter  Google Scholar 

  19. Ure KJ, Amstutz HC, Nasser S et al (1998) Direct-exchange arthroplasty for the treatment of infection after total hip replacement. An average ten-year follow-up. J Bone Joint Surg Am 80:961–968

    CAS  PubMed  Google Scholar 

  20. Tsukayama DT, Estrada R, Gustilo RB (1996) Infection after total hip arthroplasty. A study of the treatment of one hundred and six infections. J Bone Joint Surg Am 78:512–523

    CAS  PubMed  Google Scholar 

  21. Schoifet SD, Morrey BF (1990) Treatment of infection after total knee arthroplasty by debridement with retention of the components. J Bone Joint Surg Am 72:1383–1390

    CAS  PubMed  Google Scholar 

  22. Byren I, Bejon P, Atkins BL et al (2009) One hundred and twelve infected arthroplasties treated with ‘DAIR’ (debridement, antibiotics and implant retention): antibiotic duration and outcome. J Antimicrob Chemother 63:1264–1271

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Lewin CS, Amyes SG (1989) The bactericidal activity of DR-3355, an optically active isomer of ofloxacin. J Med Microbiol 30:227–231

    Article  CAS  PubMed  Google Scholar 

  24. Ruslami R, Nijland H, Aarnoutse R et al (2006) Evaluation of high- versus standard-dose rifampin in Indonesian patients with pulmonary tuberculosis. Antimicrob Agents Chemother 50:822–823

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Drancourt M, Stein A, Argenson JN et al (1997) Oral treatment of Staphylococcus spp. infected orthopaedic implants with fusidic acid or ofloxacin in combination with rifampicin. J Antimicrob Chemother 39:235–240

    Article  CAS  PubMed  Google Scholar 

  26. Société de Pathologie Infectieuse de Langue Française (SPILF); Collège des Universitaires de Maladies Infectieuses et Tropicales (CMIT); Groupe de Pathologie Infectieuse Pédiatrique (GPIP); Société Française d’Anesthésie et de Réanimation (SFAR); Société Française de Chirurgie Orthopédique et Traumatologique (SOFCOT); Société Française d’Hygiène Hospitalière (SFHH); Société Française de Médecine Nucléaire (SFMN); Société Française de Médecine Physique et de Réadaptation (SOFMER); Société Française de Microbiologie (SFM); Société Française de Radiologie (SFR-Rad); Société Française de Rhumatologie (SFR-Rhu) (2009) Recommendations for clinical practice. Osteo-articular infection therapy according to materials used (prosthesis, implants, osteosynthesis). Med Mal Infect 39:745–774

    Article  Google Scholar 

  27. Valour F, Karsenty J, Bouaziz A et al (2014) Antimicrobial-related severe adverse events during treatment of bone and joint infection due to methicillin-susceptible Staphylococcus aureus. Antimicrob Agents Chemother 58:746–755

    Article  PubMed Central  PubMed  Google Scholar 

  28. Erstad BL (2002) Which weight for weight-based dosage regimens in obese patients? Am J Health Syst Pharm 59:2105–2110

    PubMed  Google Scholar 

  29. Morris AB, Kanyok TP, Scott J et al (1998) Rifamycins. In: Yu VL, Merigan TC, Barriere SL (eds) Antimicrobial therapy and vaccines. Lippincott Williams & Wilkins, Philadelphia, pp 901–962

    Google Scholar 

  30. Gumbo T, Louie A, Deziel MR et al (2007) Concentration-dependent Mycobacterium tuberculosis killing and prevention of resistance by rifampin. Antimicrob Agents Chemother 51:3781–3788

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Kucers A, Crowe S, Grayson ML et al (1997) Rifampicin (rifampin). In: Kucers A, Crowe S, Grayson ML (eds) The use of antibiotics. A clinical review of antibacterial, antifungal and antiviral drugs, 5th edn. Butterworth-Heinemann, Oxford, pp 676–708

  32. Soriano A, García S, Bori G et al (2006) Treatment of acute post-surgical infection of joint arthroplasty. Clin Microbiol Infect 12:930–933

    Article  CAS  PubMed  Google Scholar 

  33. Peloquin CA, Jaresko GS, Yong CL et al (1997) Population pharmacokinetic modeling of isoniazid, rifampin, and pyrazinamide. Antimicrob Agents Chemother 41:2670–2679

    CAS  PubMed Central  PubMed  Google Scholar 

  34. Acocella G (1983) Pharmacokinetics and metabolism of rifampin in humans. Rev Infect Dis 5(Suppl 3):S428–S432

    Article  CAS  PubMed  Google Scholar 

  35. Spellberg B, Lipsky BA (2012) Systemic antibiotic therapy for chronic osteomyelitis in adults. Clin Infect Dis 54:393–407

    Article  PubMed Central  PubMed  Google Scholar 

  36. Murillo O, Pachón ME, Euba G et al (2008) Antagonistic effect of rifampin on the efficacy of high-dose levofloxacin in staphylococcal experimental foreign-body infection. Antimicrob Agents Chemother 52:3681–3686

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

Acknowledgments go to Mrs. Khadija Amrani and Mr. Philippe Choisy for their technical assistance.

Funding

None.

Conflict of interest

No potential conflicts of interest relevant to this article were reported.

Author contributions

SN and ES wrote the manuscript. MT, CL OB, and K. Amrani collected the clinical and biological data. MV and P. Choisy performed the statistical analyses. CL, EB, and HM contributed to the discussion. ES is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Author information

Authors and Affiliations

  1. Infectious Diseases Department, Gustave Dron Hospital, 135 rue du Président Coty, 59200, Tourcoing, France

    S. Nguyen, O. Robineau, N. Blondiaux, M. Valette & E. Senneville

  2. Laboratory of Microbiology, University Hospital of Lille, Lille, France

    M. Titecat & C. Loiez

  3. Orthopaedic Surgery Unit, Gustave Dron Hospital, Tourcoing, France

    E. Beltrand

  4. Orthopedic Surgery Unit, Roger Salengro Hospital, University Hospital of Lille, Lille, France

    H. Migaud

  5. French Reference Center for Complex Osteoarticular Infections (CRIOAC Lille-Tourcoing), Faculty of Medicine Lille University 2, Lille, France

    E. Senneville

Authors
  1. S. Nguyen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. O. Robineau
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Titecat
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N. Blondiaux
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Valette
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C. Loiez
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. E. Beltrand
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. H. Migaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. E. Senneville
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E. Senneville.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nguyen, S., Robineau, O., Titecat, M. et al. Influence of daily dosage and frequency of administration of rifampicin–levofloxacin therapy on tolerance and effectiveness in 154 patients treated for prosthetic joint infections. Eur J Clin Microbiol Infect Dis 34, 1675–1682 (2015). https://doi.org/10.1007/s10096-015-2404-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-015-2404-z

Keywords

Search

Navigation