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S02.KL1 PROSTHETIC JOINT INFECTIONS: FROM ANIMAL STUDIES TO CLINICAL EXPERIENCE



Abstract

Implants are highly susceptible to infection [1]. The infection rate is 0.5–2% after hip or knee arthroplasty [2]. Periprosthetic joint infections are hard to eradicate. Until recently, two-stage exchange or life-long antibiotic suppression therapy has been the rule. However, novel treatment concepts evolved. Whereas no controlled trials on the surgical management of prosthetic-joint associated infection are available, much is known about the optimal antimicrobial therapy. Modern treatment concepts are based on animal studies, in vitro data, observational studies and one single controlled trial comparing two different antimicrobial regimens in patients with orthopaedic device-associated infections [2]. The tissue-cage guinea pig model is especially suitable to analyse the role of antibiotics in device-related infections [3]. In this model, different aspects of implant-associated infections have been studied, namely

  1. host-defense mechanisms around implants [1],

  2. risk of hematogeneous infection of extravascular devices [4],

  3. efficacy of prevention or antibiotic treatment [512],

  4. correlation between efficacy of treatment in vivo and in vitro [11,12], and the role of biofilm formation on the activity of antibiotics [11].

Taken together, these experiments showed that an agent acting on slow-growing and adhering microorganism is needed to eradicate device-associated infection. This requirement is only fulfilled by rifamycins in staphylococcal infection and by fluoroquinolones in infections caused by gram-negative bacilli [512]. We could show that even new drugs against methicillin-resistant staphylococci (MRSA), such as linezolid and daptomycin, were not able to eradicate experimental foreign-body infections, when used as single agents. In contrast, in combination with rifampin linezolid cured 60%, and daptomycin 67% of the implant-associated MRSA-infections [9,10]. Based on these in vitro and animal data, observational studies were performed in patients with staphylococcal infections associated to orthopedic devices. We developed an algorithm allowing to choose the optimal therapeutic option for each patient [2]. This algorithm has been validated in cohort studies [13,14]. Finally, in a randomized double-blind controlled trial, the benefit of a rifampin-quinolone combination as compared to quinolone monotherapy has been proven in patients with acute orthopedic implant associated staphylococcal infection undergoing debridement with retention [15].

In conclusion, the favorable role of rifampin has been proven in vitro, in animals and in human studies. Also the newest antistaphylococcal agents must be given in combination with rifampin in order to eliminate infection without removal of the device.

Correspondence should be addressed to Vienna Medical Academy, Alser Strasse 4, A-1090 Vienna, Austria. Phone: +43 1 4051383 0, Fax: +43 1 4078274, Email: ebjis2009@medacad.org

1 Zimmerli W, Lew PD and Waldvogel FA. Pathogenesis of foreign body infection: Evidence for a local granulocyte defect. J Clin Invest1984; 73:1191–1200. Google Scholar

2 Zimmerli W, Trampuz A and Ochsner PE. Prosthetic joint-associated infection. N Engl J Med2004;351:1645–1654. Google Scholar

3 Zimmerli W. Animal models in the investigation of device-related infections. J Antimicrob Chemother1993; 31 (Suppl D): 97–102. Google Scholar

4 Zimmerli W, Zak O, Vosbeck K. Experimental hematogenous infection of subcutaneously implanted foreign bodies. Scand J Infecti Dis1985;17: 303–310. Google Scholar

5 Tshefu K, Zimmerli W, Waldvogel FA. Short-term rifampin administration in the prevention/eradication of foreign body infection. Rev Infect Dis1983; 5: S474–480. Google Scholar

6 Widmer AF, Frei R, Raijacic Z, Zimmerli W. Correlation between in vivo and in vitro efficacy of antimicrobial agents against foreign-doy infections. J Infect Dis1990; 96–102. Google Scholar

7 Widmer AF, Wiestner A, Frei R and Zimmerli W. Killing of nongrowing and adherent Escherichia coli determines drug efficacy in device-related infections. Antimicrob Agents Chemother1991; 35:741–746. Google Scholar

8 Trampuz A, Murphy CK, Rothstein DM, et al. Efficacy of a novel rifamycin derivative, ABI-0043, against Staphylococcus aureus in an experimental model of foreign-body infection. Antimicrob Agents Chemother2007; 51:2540–2545. Google Scholar

9 Baldoni D, Haschke M, Rajacic Z et al. Linezolid alone or combined with rifampin against methicillin-resistant Staphylococcus aureus in experimental foreign-body infection. Antimicrob Agents Chemother2009; 53:1142–1148. Google Scholar

10 John A-K, Baldoni D, Haschke M et al. Efficacy of daptomycin in implant-associated infection due to methicillin-resistant Staphylococcus aureus: Importance of combination with rifampin. Antimicrob Agents Chemother2009; 53:2719–2724. Google Scholar

11 Schwank S, Rajacic Z, Zimmerli W, Blaser J. Impact of bacterial biofilm formation on in vitro and in vivo activities of antibiotics. Antimicrob Agents Chemother1998; 42:895–898. Google Scholar

12 Zimmerli W, Frei R, Widmer AF, Rajacic Z. Microbiological tests to predict treatment outcome in experimental device-related infections due to Staphylococcus aureus. J Antimicrob Chemother1994; 33: 959–967. Google Scholar

13 Giulieri SG, Graber P, Ochsner PE and Zimmerli W. Management of infection associated with total hip arthroplasty according to a treatment algorithm. Infection2004; 32:222–228. Google Scholar

14 Laffer R, Graber P, Ochsner PE and Zimmerli W. Outcome of prosthetic knee-associated infection: evaluation of 40 consecutive episodes of a single center. Clin Microbiol Infect Dis2006; 12:433–439. Google Scholar

15 Zimmerli W, Widmer AF, Blatter M, et al. Role of rifampin for treatment of orthopedic implant-related staphylococcal infections: a randomized controlled trial. Foreign-Body Infection (FBI) Study Group. JAMA1998;279:1537–1541. Google Scholar