A Retrospective Review of the Clinical Experience of Linezolid with or Without Rifampicin in Prosthetic Joint Infections Treated with Debridement and Implant Retention

Laura Morata, Eric Senneville, Louis Bernard, Sophie Nguyen, Rodolphe Buzelé, Jérome Druon, Eduard Tornero, Josep Mensa, Alex Soriano, Laura Morata, Eric Senneville, Louis Bernard, Sophie Nguyen, Rodolphe Buzelé, Jérome Druon, Eduard Tornero, Josep Mensa, Alex Soriano

Abstract

Introduction: Debridement and prosthesis retention, combined with a prolonged antibiotic regimen including rifampicin, is an accepted therapeutic approach when the duration of symptoms is less than 4 weeks and there are no radiological signs of loosening. The outcome of patients managed with this strategy has been previously assessed in several articles with success rates of 60-90%. This study aims to review the clinical experience with linezolid in 3 different hospitals from Spain and France in patients with prosthetic joint infection (PJI) managed with debridement, retention of the implant and treated with linezolid with or without rifampicin.

Methods: Patients with an acute PJI who underwent open debridement with implant retention treated with linezolid for more than 7 days in 3 hospitals from Barcelona, Tours and Lille between 2005 and 2011 were retrospectively reviewed. Relevant information about demographics, co-morbidity, type of implant, surgical treatment, microorganism isolated, antimicrobial therapy, adverse events (AEs) and outcomes were recorded from patients.

Results: A total of 39 patients were retrospectively reviewed. The mean age (SD) was 70.5 (8.8) years and 9 patients had diabetes mellitus (23%). There were 25 (64%) knee prostheses, 13 (33%) hips and 1 shoulder (3%). The median interquartile range (IQR) days from arthroplasty to infection diagnosis was 17 (19-48) and 33 (85%) cases were diagnosed within the first 60 days. The median (IQR) duration of antibiotic treatment was 70.5 (34-96) days and the median (IQR) number of days on linezolid treatment was 44.5 (30-81). AEs were observed in 15 patients (38%), with gastrointestinal complaints in 8 cases and anemia in 5 being the most frequent. After a median (IQR) follow-up of 2.5 (1.8-3.6) years, there were 11 failures (28%) (8 relapses and 3 new infections). The failure rate was higher in the rifampicin group (36% vs. 18%) mainly due to a higher relapse rate (27% vs. 12%) although differences were not statistically significant.

Conclusion: Management of acute PJIs with debridement and retention of the implant linezolid, with or without rifampicin, is associated with a high remission rate and it is an alternative treatment for infections due to fluoroquinolone and/or rifampicin-resistant staphylococci.

Keywords: Debridement; Infectious diseases; Linezolid; Prosthetic joint infection; Rifampicin; Treatment outcome.

Figures

Fig. 1
Fig. 1
The cumulative probability of being in remission according to whether the patient received concomitant rifampicin or not (Log-Rank test, P = 0.25)

References

    1. Cobo J, Miguel LGS, Euba G, et al. Early prosthetic joint infection: outcomes with debridement and implant retention followed by antibiotic therapy. Clin Microbiol Infect. 2011;17:1632–1637. doi: 10.1111/j.1469-0691.2010.03333.x.
    1. Vilchez F, Martínez-Pastor JC, Garcia-Ramiro S, et al. Outcome and predictors of treatment failure in early post-surgical prosthetic joint infections due to Staphylococcus aureus treated with debridement. Clin Microbiol Infect. 2011;17:439–444. doi: 10.1111/j.1469-0691.2010.03244.x.
    1. Zimmerli W, Widmer AF, Blatter M, Frei R, Ochsner PE. Role of rifampin for treatment of orthopedic implant-related staphylococcal infections: a randomized controlled trial. Foreign-Body Infection (FBI) Study Group. JAMA. 1998;279:1537–1541. doi: 10.1001/jama.279.19.1537.
    1. Lora-Tamayo J, Murillo O, Iribarren JA, et al. A large multicenter study of methicillin susceptible- and methicillin resistant-Staphylococcus aureus prosthetic joint infections managed with implant retention. Clin Infect Dis. 2012;56:182–194. doi: 10.1093/cid/cis746.
    1. Senneville E, Joulie D, Legout L, et al. Outcome and predictors of treatment failure in total hip/knee prosthetic joint infections due to Staphylococcus aureus. Clin Infect Dis. 2011;53:334–340. doi: 10.1093/cid/cir402.
    1. Bernard L, Legout L, Zürcher-Pfund L, et al. Six weeks of antibiotic treatment is sufficient following surgery for septic arthroplasty. J Infect. 2010;61:125–132. doi: 10.1016/j.jinf.2010.05.005.
    1. Livermore DM. Linezolid in vitro: mechanism and antibacterial spectrum. J Antimicrob Chemother. 2003;51(Suppl 2):ii9–ii16.
    1. MacGowan AP. Pharmacokinetic and pharmacodynamic profile of linezolid in healthy volunteers and patients with Gram-positive infections. J Antimicrob Chemother. 2003;51(Suppl 2):ii17–ii25.
    1. Kutscha-Lissberg F, Hebler U, Muhr G, Köller M. Linezolid penetration into bone and joint tissues infected with methicillin-resistant staphylococci. Antimicrob Agents Chemother. 2003;47:3964–3966. doi: 10.1128/AAC.47.12.3964-3966.2003.
    1. Baldoni D, Haschke M, Rajacic Z, Zimmerli W, Trampuz A. Linezolid alone or combined with rifampin against methicillin-resistant Staphylococcus aureus in experimental foreign-body infection. Antimicrob Agents Chemother. 2009;53:1142–1148. doi: 10.1128/AAC.00775-08.
    1. Gandelman K, Zhu T, Fahmi OA, et al. Unexpected effect of rifampin on the pharmacokinetics of linezolid. In silico and in vitro approaches to explain its mechanism. J Clin Pharmacol. 2011;51:229–236. doi: 10.1177/0091270010366445.
    1. Egle H, Trittler R, Kümmerer K, Lemmen SW. Linezolid and rifampin: drug interaction contrary to expectations? Clin Pharmacol Ther. 2005;77:451–453. doi: 10.1016/j.clpt.2005.01.020.
    1. Hoyo I, Martínez-Pastor J, Garcia-Ramiro S, et al. Decreased serum linezolid concentrations in two patients receiving linezolid and rifampicin due to bone infections. Scand J Infect Dis. 2012;44:548–550. doi: 10.3109/00365548.2012.663931.
    1. Tornero E, García-Oltra E, García-Ramiro S, et al. Prosthetic joint infections due to Staphylococcus aureus and coagulase-negative staphylococci. Int J Artif Organs. 2012;35:884–892.
    1. Bassetti M, Vitale F, Melica G, et al. Linezolid in the treatment of Gram-positive prosthetic joint infections. J Antimicrob Chemother. 2005;55:387–390. doi: 10.1093/jac/dki016.
    1. Rao N, Hamilton CW. Efficacy and safety of linezolid for Gram-positive orthopedic infections: a prospective case series. Diagn Microbiol Infect Dis. 2007;59:173–179. doi: 10.1016/j.diagmicrobio.2007.04.006.
    1. Bradbury T, Fehring TK, Taunton M, et al. The fate of acute methicillin-resistant Staphylococcus aureus periprosthetic knee infections treated by open debridement and retention of components. J Arthroplasty. 2009;24:101–104. doi: 10.1016/j.arth.2009.04.028.
    1. Legout L, Valette M, Dezeque H, et al. Tolerability of prolonged linezolid therapy in bone and joint infection: protective effect of rifampicin on the occurrence of anaemia? J Antimicrob Chemother. 2010;65:2224–2230. doi: 10.1093/jac/dkq281.
    1. Soriano A, Gómez J, Gómez L, et al. Efficacy and tolerability of prolonged linezolid therapy in the treatment of orthopedic implant infections. Eur J Clin Microbiol Infect Dis. 2007;26:353–356. doi: 10.1007/s10096-007-0289-1.
    1. 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 Chemother. 1994;33:959–967. doi: 10.1093/jac/33.5.959.
    1. Nguyen S, Pasquet A, Legout L, et al. Efficacy and tolerance of rifampicin-linezolid compared with rifampicin-cotrimoxazole combinations in prolonged oral therapy for bone and joint infections. Clin Microbiol Infect. 2009;15:1163–1169. doi: 10.1111/j.1469-0691.2009.02761.x.
    1. Gómez J, Canovas E, Baños V, et al. Linezolid plus rifampin as a salvage therapy in prosthetic joint infections treated without removing the implant. Antimicrob Agents Chemother. 2011;55:4308–4310. doi: 10.1128/AAC.00352-11.
    1. Brandt CM, Sistrunk WW, Duffy MC, et al. Staphylococcus aureus prosthetic joint infection treated with debridement and prosthesis retention. Clin Infect Dis. 1997;24:914–919. doi: 10.1093/clinids/24.5.914.
    1. Craig WA. Basic pharmacodynamics of antibacterials with clinical applications to the use of beta-lactams, glycopeptides, and linezolid. Infect Dis Clin North Am. 2003;17:479–501. doi: 10.1016/S0891-5520(03)00065-5.
    1. Jones RN, Kohno S, Ono Y, Ross JE, Yanagihara K. ZAAPS International Surveillance Program (2007) for linezolid resistance: results from 5591 Gram-positive clinical isolates in 23 countries. Diagn Microbiol Infect Dis. 2009;64:191–201. doi: 10.1016/j.diagmicrobio.2009.03.001.
    1. Cattaneo D, Orlando G, Cozzi V, et al. Linezolid plasma concentrations and occurrence of drug-related hematological toxicity in patients with Gram-positive infections. Int J Antimicrob Agents. 2013;41:586–589. doi: 10.1016/j.ijantimicag.2013.02.020.
    1. Pea F, Viale P, Cojutti P, Del Pin B, Zamparini E, Furlanut M. Therapeutic drug monitoring may improve safety outcomes of long-term treatment with linezolid in adult patients. J Antimicrob Chemother. 2012;67:2034–2042. doi: 10.1093/jac/dks153.

Source: PubMed

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