Risk factors for treatment failure in orthopedic device-related methicillin-resistant Staphylococcus aureus infection

  • T. FerryEmail author
  • I. Uçkay
  • P. Vaudaux
  • P. François
  • J. Schrenzel
  • S. Harbarth
  • F. Laurent
  • L. Bernard
  • F. Vandenesch
  • J. Etienne
  • P. Hoffmeyer
  • D. Lew


The purpose of this study was to determine the clinical and microbiological risk factors for treatment failure of methicillin-resistant Staphylococcus aureus (MRSA) orthopedic device-related infection (ODRI). A retrospective cohort study of patients with MRSA ODRI who were treated at Geneva University Hospitals between 2000 and 2008 was undertaken. Stored MRSA isolates were retrieved for genetic characterization and determination of the vancomycin minimum inhibitory concentration (MIC). Fifty-two patients were included, of whom 23 (44%) had joint arthroplasty and 29 (56%) had osteosynthesis. All 41 of the retrieved MRSA isolates were susceptible to vancomycin (MIC ≤ 2 mg/L) and 35 (85%) shared genetic characteristics of the South German clone (ST228). During a median follow-up of 391 days (range, 4–2,922 days), 18 patients (35%) experienced treatment failure involving MRSA persistence or recurrence. Microbiological factors such as infection with the predominant clone and a vancomycin MIC of 2 mg/L were not associated with treatment failure. Using a Cox proportional hazards model, implant retention (hazard ratio [HR], 4.9; 95% confidence interval [CI], 1.3–18.2; P = 0.017) and single-agent antimicrobial therapy (HR, 4.4; 95% CI, 1.2–16.3; P = 0.025) were independent predictors of treatment failure after debridement. Therapy using a combination of antimicrobials should be considered for patients with MRSA ODRI, especially when implant removal is not feasible.


Vancomycin Treatment Failure Fusidic Acid Prosthetic Joint Infection SCCmec Type 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by Fondation pour la Recherche Médicale, Paris, France. We are indebted to Elzbieta Huggler, Myriam Girard, Hélène Meugnier, Michele Bes, Colette Nicollier, Christine Courtier, Christine Cardon, Céline Spinelli, and Caroline Bouveron for the isolate characterization. We thank Nathalie Vallier for assistance with the statistical analysis, Abel Ferry for technical assistance, and David Young for editorial guidance.


  1. 1.
    Lew DP, Waldvogel FA (2004) Osteomyelitis. Lancet 364:369–379CrossRefPubMedGoogle Scholar
  2. 2.
    Widmer AF (2001) New developments in diagnosis and treatment of infection in orthopedic implants. Clin Infect Dis 33(Suppl 2):S94–S106CrossRefPubMedGoogle Scholar
  3. 3.
    Zimmerli W, Trampuz A, Ochsner PE (2004) Prosthetic-joint infections. N Engl J Med 351:1645–1654CrossRefPubMedGoogle Scholar
  4. 4.
    Gristina AG (1987) Biomaterial-centered infection: microbial adhesion versus tissue integration. Science 237:1588–1595CrossRefPubMedGoogle Scholar
  5. 5.
    Kilgus DJ, Howe DJ, Strang A (2002) Results of periprosthetic hip and knee infections caused by resistant bacteria. Clin Orthop Relat Res 404:116–124CrossRefPubMedGoogle Scholar
  6. 6.
    Proctor RA, von Eiff C, Kahl BC et al (2006) Small colony variants: a pathogenic form of bacteria that facilitates persistent and recurrent infections. Nat Rev Microbiol 4:295–305CrossRefPubMedGoogle Scholar
  7. 7.
    Tsukayama DT, Wicklund B, Gustilo RB (1991) Suppressive antibiotic therapy in chronic prosthetic joint infections. Orthopedics 14:841–844PubMedGoogle Scholar
  8. 8.
    Wilson MG, Kelley K, Thornhill TS (1990) Infection as a complication of total knee-replacement arthroplasty. Risk factors and treatment in sixty-seven cases. J Bone Joint Surg Am 72:878–883PubMedGoogle Scholar
  9. 9.
    Berbari EF, Hanssen AD, Duffy MC et al (1998) Risk factors for prosthetic joint infection: case–control study. Clin Infect Dis 27:1247–1254CrossRefPubMedGoogle Scholar
  10. 10.
    Betsch BY, Eggli S, Siebenrock KA et al (2008) Treatment of joint prosthesis infection in accordance with current recommendations improves outcome. Clin Infect Dis 46:1221–1226CrossRefPubMedGoogle Scholar
  11. 11.
    Lentino JR (2003) Prosthetic joint infections: bane of orthopedists, challenge for infectious disease specialists. Clin Infect Dis 36:1157–1161CrossRefPubMedGoogle Scholar
  12. 12.
    Salgado CD, Dash S, Cantey JR et al (2007) Higher risk of failure of methicillin-resistant Staphylococcus aureus prosthetic joint infections. Clin Orthop Relat Res 461:48–53PubMedGoogle Scholar
  13. 13.
    Soriano A, Marco F, Martínez JA et al (2008) Influence of vancomycin minimum inhibitory concentration on the treatment of methicillin-resistant Staphylococcus aureus bacteremia. Clin Infect Dis 46:193–200CrossRefPubMedGoogle Scholar
  14. 14.
    Ferry T, Bes M, Dauwalder O et al (2006) Toxin gene content of the Lyon methicillin-resistant Staphylococcus aureus clone compared with that of other pandemic clones. J Clin Microbiol 44:2642–2644CrossRefPubMedGoogle Scholar
  15. 15.
    Oliveira DC, Tomasz A, de Lencastre H (2002) Secrets of success of a human pathogen: molecular evolution of pandemic clones of meticillin-resistant Staphylococcus aureus. Lancet Infect Dis 2:180–189CrossRefPubMedGoogle Scholar
  16. 16.
    Amaral MM, Coelho LR, Flores RP et al (2005) The predominant variant of the Brazilian epidemic clonal complex of methicillin-resistant Staphylococcus aureus has an enhanced ability to produce biofilm and to adhere to and invade airway epithelial cells. J Infect Dis 192:801–810CrossRefPubMedGoogle Scholar
  17. 17.
    Charlson ME, Pompei P, Ales KL et al (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40:373–383CrossRefPubMedGoogle Scholar
  18. 18.
    Zimmerli W, Ochsner PE (2003) Management of infection associated with prosthetic joints. Infection 31:99–108CrossRefPubMedGoogle Scholar
  19. 19.
    Clinical and Laboratory Standards Institute (CLSI) (2007) Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard M7-S17, Wayne, PAGoogle Scholar
  20. 20.
    Francois P, Huyghe A, Charbonnier Y et al (2005) Use of an automated multiple-locus, variable-number tandem repeat-based method for rapid and high-throughput genotyping of Staphylococcus aureus isolates. J Clin Microbiol 43:3346–3355CrossRefPubMedGoogle Scholar
  21. 21.
    Dauwalder O, Lina G, Durand G et al (2008) Epidemiology of invasive methicillin-resistant Staphylococcus aureus clones collected in France in 2006 and 2007. J Clin Microbiol 46:3454–3458CrossRefPubMedGoogle Scholar
  22. 22.
    Jarraud S, Mougel C, Thioulouse J et al (2002) Relationships between Staphylococcus aureus genetic background, virulence factors, agr groups (alleles), and human disease. Infect Immun 70:631–641CrossRefPubMedGoogle Scholar
  23. 23.
    Kondo Y, Ito T, Ma XX et al (2007) Combination of multiplex PCRs for staphylococcal cassette chromosome mec type assignment: rapid identification system for mec, ccr, and major differences in junkyard regions. Antimicrob Agents Chemother 51:264–274CrossRefPubMedGoogle Scholar
  24. 24.
    François P, Harbarth S, Huyghe A et al (2008) Methicillin-resistant Staphylococcus aureus, Geneva, Switzerland, 1993–2005. Emerg Infect Dis 14:304–307CrossRefPubMedGoogle Scholar
  25. 25.
    Sax H, Posfay-Barbe K, Harbarth S et al (2006) Control of a cluster of community-associated, methicillin-resistant Staphylococcus aureus in neonatology. J Hosp Infect 63:93–100CrossRefPubMedGoogle Scholar
  26. 26.
    Concato J, Feinstein AR, Holford TR (1993) The risk of determining risk with multivariable models. Ann Intern Med 118:201–210PubMedGoogle Scholar
  27. 27.
    Moise PA, Sakoulas G, Forrest A et al (2007) Vancomycin in vitro bactericidal activity and its relationship to efficacy in clearance of methicillin-resistant Staphylococcus aureus bacteremia. Antimicrob Agents Chemother 51:2582–2586CrossRefPubMedGoogle Scholar
  28. 28.
    Knudsen JD, Fuursted K, Raber S et al (2000) Pharmacodynamics of glycopeptides in the mouse peritonitis model of Streptococcus pneumoniae or Staphylococcus aureus infection. Antimicrob Agents Chemother 44:1247–1254CrossRefPubMedGoogle Scholar
  29. 29.
    Peetermans WE, Hoogeterp JJ, Hazekamp-van Dokkum AM et al (1990) Antistaphylococcal activities of teicoplanin and vancomycin in vitro and in an experimental infection. Antimicrob Agents Chemother 34:1869–1874PubMedGoogle Scholar
  30. 30.
    Brandt CM, Sistrunk WW, Duffy MC et al (1997) Staphylococcus aureus prosthetic joint infection treated with debridement and prosthesis retention. Clin Infect Dis 24:914–919PubMedGoogle Scholar
  31. 31.
    Marculescu CE, Berbari EF, Hanssen AD et al (2006) Outcome of prosthetic joint infections treated with debridement and retention of components. Clin Infect Dis 42:471–478CrossRefPubMedGoogle Scholar
  32. 32.
    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 279:1537–1541CrossRefPubMedGoogle Scholar
  33. 33.
    Widmer AF, Frei R, Rajacic Z et al (1990) Correlation between in vivo and in vitro efficacy of antimicrobial agents against foreign body infections. J Infect Dis 162:96–102PubMedGoogle Scholar
  34. 34.
    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 39:235–240CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • T. Ferry
    • 1
    • 2
    • 3
    • 4
    • 10
    Email author
  • I. Uçkay
    • 1
    • 5
  • P. Vaudaux
    • 1
  • P. François
    • 6
  • J. Schrenzel
    • 1
    • 6
    • 7
  • S. Harbarth
    • 1
    • 8
  • F. Laurent
    • 3
    • 4
  • L. Bernard
    • 9
  • F. Vandenesch
    • 3
    • 4
  • J. Etienne
    • 3
    • 4
  • P. Hoffmeyer
    • 5
  • D. Lew
    • 1
  1. 1.Infectious Diseases UnitGeneva University Hospitals and Faculty of MedicineGenevaSwitzerland
  2. 2.Infectious and Tropical Diseases UnitCroix-Rousse HospitalHospices Civils de LyonFrance
  3. 3.INSERM U851LyonFrance
  4. 4.Université Claude BernardLyon 1France
  5. 5.Orthopaedic Surgery UnitGeneva University Hospitals and Faculty of MedicineGenevaSwitzerland
  6. 6.Genomic Research LaboratoryGeneva University Hospitals and Faculty of MedicineGenevaSwitzerland
  7. 7.Central Laboratory of BacteriologyGeneva University Hospitals and Faculty of MedicineGenevaSwitzerland
  8. 8.Infection Control ProgramGeneva University Hospitals and Faculty of MedicineGenevaSwitzerland
  9. 9.Infectious Diseases UnitBretonneau University Hospital, CHRU of ToursToursFrance
  10. 10.Service de Maladies Infectieuses et TropicalesHôpital de la Croix-RousseLyonFrance

Personalised recommendations