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

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          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.

          Electronic supplementary material

          The online version of this article (doi:10.1007/s40121-014-0032-z) contains supplementary material, which is available to authorized users.

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          Most cited references27

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          Role of rifampin for treatment of orthopedic implant-related staphylococcal infections: a randomized controlled trial. Foreign-Body Infection (FBI) Study Group.

          Rifampin-containing regimens are able to cure staphylococcal implant-related infections based on in vitro and in vivo observations. However, this evidence has not been proven by a controlled clinical trial. To evaluate the clinical efficacy of a rifampin combination in staphylococcal infections associated with stable orthopedic devices. A randomized, placebo-controlled, double-blind trial conducted from 1992 through 1997. Two infectious disease services in tertiary care centers in collaboration with 5 orthopedic surgeons in Switzerland. A total of 33 patients with culture-proven staphylococcal infection associated with stable orthopedic implants and with a short duration of symptoms of infection (exclusion limit <1 year; actual experience 0-21 days). Initial debridement and 2-week intravenous course of flucloxacillin or vancomycin with rifampin or placebo, followed by either ciprofloxacin-rifampin or ciprofloxacin-placebo long-term therapy. Cure was defined as (1) lack of clinical signs and symptoms of infection, (2) C-reactive protein level less than 5 mg/L, and (3) absence of radiological signs of loosening or infection at the final follow-up visit at 24 months. Failure was defined as (1) persisting clinical and/or laboratory signs of infection or (2) persisting or new isolation of the initial microorganism. A total of 18 patients were allocated to ciprofloxacin-rifampin and 15 patients to the ciprofloxacin-placebo combination. Twenty-four patients fully completed the trial with a follow-up of 35 and 33 months. The cure rate was 12 (100%) of 12 in the ciprofloxacin-rifampin group compared with 7 (58%) of 12 in the ciprofloxacin-placebo group (P=.02). Nine of 33 patients dropped out due to adverse events (n=6), noncompliance (n=1), or protocol violation (n=2). Seven of the 9 patients who dropped out were subsequently treated with rifampin combinations, and 5 of them were cured without removal of the device. Among patients with stable implants, short duration of infection, and initial debridement, patients able to tolerate long-term (3-6 months) therapy with rifampin-ciprofloxacin experienced cure of the infection without removal of the implant.
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            A large multicenter study of methicillin-susceptible and methicillin-resistant Staphylococcus aureus prosthetic joint infections managed with implant retention.

            Several series predicting the prognosis of staphylococcal prosthetic joint infection (PJI) managed with debridement, antibiotics, and implant retention (DAIR) have been published, but some of their conclusions are controversial. At present, little is known regarding the efficacy of the different antibiotics that are used or their ability to eliminate methicillin-resistant S. aureus (MRSA) infection. This was a retrospective, multicenter, observational study of cases of PJI by S. aureus that were managed with DAIR (2003-2010). Cases were classified as failures when infection persistence/relapse, death, need for salvage therapy, or prosthesis removal occurred. The parameters that predicted failure were analyzed with logistic and Cox regression. Out of 345 episodes (41% men, 73 years), 81 episodes were caused by MRSA. Fifty-two were hematogenous, with poorer prognoses, and 88% were caused by methicillin-susceptible S. aureus (MSSA). Antibiotics were used for a median of 93 days, with similar use of rifampin-based combinations in MSSA- and MRSA-PJI. Failure occurred in 45% of episodes, often early after debridement. The median survival time was 1257 days. There were no overall prognostic differences between MSSA- and MRSA-PJI, but there was a higher incidence of MRSA-PJI treatment failure during the period of treatment (HR 2.34), while there was a higher incidence of MSSA-PJI treatment failure after therapy. Rifampin-based combinations exhibited an independent protective effect. Other independent predictors of outcome were polymicrobial, inflammatory, and bacteremic infections requiring more than 1 debridement, immunosuppressive therapy, and the exchange of removable components of the prosthesis. This is the largest series of PJI by S. aureus managed with DAIR reported to date. The success rate was 55%. The use of rifampin may have contributed to homogenizing MSSA and MRSA prognoses, although the specific rifampin combinations may have had different efficacies.
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              Basic pharmacodynamics of antibacterials with clinical applications to the use of β-lactams, glycopeptides, and linezolid

              Infectious Disease Clinics of North America, 17(3), 479-501
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                Author and article information

                Contributors
                lmorata@clinic.ub.es
                Journal
                Infect Dis Ther
                Infect Dis Ther
                Infectious Diseases and Therapy
                Springer Healthcare (Heidelberg )
                2193-8229
                2193-6382
                20 August 2014
                20 August 2014
                December 2014
                : 3
                : 2
                : 235-243
                Affiliations
                [ ]Bone and Joint Infection Unit, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic of Barcelona, C/Villarroel 170, 08036 Barcelona, Spain
                [ ]Lille-Tourcoing French Referent Center for Osteo-articular Infection, Lille University Hospital, Lille, France
                [ ]Infectious Diseases Unit, Tours University Hospital, Tours Cedex, France
                [ ]Regional French Referent Center for Osteo-articular Infection, Tours Cedex, France
                Article
                32
                10.1007/s40121-014-0032-z
                4269635
                25139552
                c4aaf1f9-a8ae-432c-9199-0bc2293809fb
                © The Author(s) 2014
                History
                : 18 June 2014
                Categories
                Original Research
                Custom metadata
                © Springer Healthcare 2014

                debridement,infectious diseases,linezolid,prosthetic joint infection,rifampicin,treatment outcome

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