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      Rates and Predictors of Treatment Failure in Staphylococcus aureus Prosthetic Joint Infections According to Different Management Strategies: A Multinational Cohort Study—The ARTHR-IS Study Group

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      1 , 31 , 2 , 3 , 4 , 5 , 3 , 4 , 5 , 6 , 7 , 7 , 8 , 9 , 10 , 11 , 11 , 12 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 2 , 2 , 2 , 19 , 28 , 29 , 30 , 19 , 28 , 29 , 30 , , The ARTHR-IS Group
      Infectious Diseases and Therapy
      Springer Healthcare
      Prosthetic joint infection, Staphylococcus aureus, Outcome, Clinical failure, Functional failure

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          Abstract

          Introduction

          Guidelines have improved the management of prosthetic joint infections (PJI). However, it is necessary to reassess the incidence and risk factors for treatment failure (TF) of Staphylococcus aureus PJI (SA-PJI) including functional loss, which has so far been neglected as an outcome.

          Methods

          A retrospective cohort study of SA-PJI was performed in 19 European hospitals between 2014 and 2016. The outcome variable was TF, including related mortality, clinical failure and functional loss both after the initial surgical procedure and after all procedures at 18 months. Predictors of TF were identified by logistic regression. Landmark analysis was used to avoid immortal time bias with rifampicin when debridement, antibiotics and implant retention (DAIR) was performed.

          Results

          One hundred twenty cases of SA-PJI were included. TF rates after the first and all surgical procedures performed were 32.8% and 24.2%, respectively. After all procedures, functional loss was 6.0% for DAIR and 17.2% for prosthesis removal. Variables independently associated with TF for the first procedure were Charlson ≥ 2, haemoglobin < 10 g/dL, bacteraemia, polymicrobial infection and additional debridement(s). For DAIR, TF was also associated with a body mass index (BMI) > 30 kg/m 2 and delay of DAIR, while rifampicin use was protective. For all procedures, the variables associated with TF were haemoglobin < 10 g/dL, hip fracture and additional joint surgery not related to persistent infection.

          Conclusions

          TF remains common in SA-PJI. Functional loss accounted for a substantial proportion of treatment failures, particularly after prosthesis removal. Use of rifampicin after DAIR was associated with a protective effect. Among the risk factors identified, anaemia and obesity have not frequently been reported in previous studies.

          Trial registration

          This study is registered at clinicaltrials.gov, registration no. NCT03826108.

          Graphical abstract

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s40121-022-00701-0.

          Plain Language Summary

          Staphylococcus aureus is one of the most virulent bacteria and frequently causes prosthetic joint infections.

          Knowledge of the treatment of this type of infection has advanced in recent years, and treatment guidelines have led to improved management. Typically, the successful treatment of these infections has been determined by clinical cure, that is, the symptoms of infection have disappeared, but has not taken into account loss of function (such as significant difficulties walking), which is critical for the patient’s quality of life. Our aim in this study was to evaluate the success of current management strategies for S. aureus prosthetic joint infection, including recovery of functionality, and the factors that predict why some of these infections are not cured, to identify areas for improvement.

          In a multinational cohort of 128 patients with S. aureus prosthetic joint infection, rates of treatment failure were found to be high, with significant rates of loss of function, especially when the prosthesis needed to be removed. Loss of function was less frequent when the infection was initially treated with surgical cleaning without removal of the prosthesis, even when this procedure failed at first. We found that anaemia and obesity were associated with lower treatment success, and that the probability of treatment success increased when surgical cleaning without prosthesis removal was performed early, and when the antibiotic rifampicin was used in combination with another antibiotic.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s40121-022-00701-0.

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          Most cited references1

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          Prosthetic joint infection.

          Prosthetic joint infection (PJI) is a tremendous burden for individual patients as well as the global health care industry. While a small minority of joint arthroplasties will become infected, appropriate recognition and management are critical to preserve or restore adequate function and prevent excess morbidity. In this review, we describe the reported risk factors for and clinical manifestations of PJI. We discuss the pathogenesis of PJI and the numerous microorganisms that can cause this devastating infection. The recently proposed consensus definitions of PJI and approaches to accurate diagnosis are reviewed in detail. An overview of the treatment and prevention of this challenging condition is provided.
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            Author and article information

            Contributors
            mdeltoro@us.es
            Journal
            Infect Dis Ther
            Infect Dis Ther
            Infectious Diseases and Therapy
            Springer Healthcare (Cheshire )
            2193-8229
            2193-6382
            15 October 2022
            15 October 2022
            December 2022
            : 11
            : 6
            : 2177-2203
            Affiliations
            [1 ]GRID grid.411375.5, ISNI 0000 0004 1768 164X, Infectious Diseases and Microbiology Clinical Unit, , Hospital Universitario Virgen Macarena, ; Seville, Spain
            [2 ]GRID grid.425088.3, GlaxoSmithKline (GSK), ; Siena, Italy
            [3 ]GRID grid.413396.a, ISNI 0000 0004 1768 8905, Infectious Diseases Unit, , Hospital de la Santa Creu i Sant Pau, ; Barcelona, Spain
            [4 ]GRID grid.420258.9, ISNI 0000 0004 1794 1077, Sant Pau Institute for Biomedical Research, ; Barcelona, Spain
            [5 ]GRID grid.7080.f, ISNI 0000 0001 2296 0625, Department of Medicine, , Universitat Autònoma de Barcelona, ; Barcelona, Spain
            [6 ]GRID grid.6292.f, ISNI 0000 0004 1757 1758, Department of Medical and Surgical Sciences, , University of Bologna, ; Bologna, Italy
            [7 ]GRID grid.6292.f, ISNI 0000 0004 1757 1758, Infectious Diseases Unit, , IRCCS Azienda Ospedaliero Universitaria di Bologna, ; Bologna, Italy
            [8 ]Department of Orthopaedic Surgery and Trauma, Máxima MC, Eindhoven, The Netherlands
            [9 ]GRID grid.20522.37, ISNI 0000 0004 1767 9005, Department of Infectious Diseases, Hospital del Mar, , Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), ; Barcelona, Spain
            [10 ]GRID grid.5612.0, ISNI 0000 0001 2172 2676, Universitat Pompeu Fabra, ; Barcelona, Spain
            [11 ]GRID grid.411129.e, ISNI 0000 0000 8836 0780, Department of Infectious Diseases, , Hospital Universitari Bellvitge, IDIBELL, ; Barcelona, Spain
            [12 ]GRID grid.461589.7, ISNI 0000 0001 0224 3960, Bone Infection Unit, , Nuffield Orthopaedic Centre, Oxford University Hospitals NHS Foundation Trust, ; Oxford, UK
            [13 ]GRID grid.413711.1, ISNI 0000 0004 4687 1426, Department of Infection Control, , Amphia Hospital, ; Breda, The Netherlands
            [14 ]GRID grid.5477.1, ISNI 0000000120346234, Department of Medical Microbiology, , University Medical Center Utrecht, Utrecht University, ; Utrecht, The Netherlands
            [15 ]GRID grid.417728.f, ISNI 0000 0004 1756 8807, Prosthetic-Joint Replacement Unit, , Humanitas Research Hospital, ; Milan, Italy
            [16 ]GRID grid.275559.9, ISNI 0000 0000 8517 6224, Center for Infectious Diseases and Infection Control, , Jena University Hospital, ; Jena, Germany
            [17 ]GRID grid.416391.8, ISNI 0000 0004 0400 0120, Department of Orthopaedics, , Norfolk and Norwich University Hospital, ; Norwich, UK
            [18 ]GRID grid.411347.4, ISNI 0000 0000 9248 5770, Department of Infectious Diseases, , Hospital Universitario Ramón y Cajal, ; Madrid, Spain
            [19 ]GRID grid.413448.e, ISNI 0000 0000 9314 1427, Centro de Investigación en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, ; Madrid, Spain
            [20 ]GRID grid.411154.4, ISNI 0000 0001 2175 0984, Department of Infectious Diseases, , Centre Hospitalier Universitaire de Rennes, ; Rennes, France
            [21 ]GRID grid.413306.3, ISNI 0000 0004 4685 6736, Orthopedic Surgery Department, , Croix Rousse Hospital, ; Lyon, France
            [22 ]GRID grid.42399.35, ISNI 0000 0004 0593 7118, Department of Infectious and Tropical Diseases, , Centre Hospitalier Universitaire de Bordeaux, ; Bordeaux, France
            [23 ]GRID grid.413532.2, ISNI 0000 0004 0398 8384, Department of Orthopaedic Surgery and Trauma, , Catharina Hospital, ; Eindhoven, The Netherlands
            [24 ]Department of Orthopaedic Surgery and Trauma, Máxima MC, Eindhoven, The Netherlands
            [25 ]GRID grid.411171.3, ISNI 0000 0004 0425 3881, Department of Internal Medicine, , Hospital Universitario, ; 12 de Octubre, Madrid, Spain
            [26 ]GRID grid.411109.c, ISNI 0000 0000 9542 1158, Clinical Unit of Infectious Diseases and Microbiology, , Hospital Universitario Virgen del Rocío, ; Seville, Spain
            [27 ]GRID grid.416450.2, ISNI 0000 0004 0400 7971, Infectious Diseases Unit, , North Manchester General Hospital, ; Manchester, UK
            [28 ]GRID grid.411375.5, ISNI 0000 0004 1768 164X, Infectious Diseases and Microbiology Clinical Unit, , Hospital Universitario Virgen Macarena, ; Avda Dr Fedriani 3, 41009 Seville, Spain
            [29 ]GRID grid.9224.d, ISNI 0000 0001 2168 1229, Department of Medicine, School of Medicine, , University of Sevilla, ; Seville, Spain
            [30 ]Biomedicine Institute of Sevilla (IBiS), Seville, Spain
            [31 ]GRID grid.412800.f, ISNI 0000 0004 1768 1690, Present Address: Hospital Universitario de Valme, ; Seville, Spain
            Author information
            http://orcid.org/0000-0001-6410-013X
            http://orcid.org/0000-0001-9546-2811
            http://orcid.org/0000-0003-1938-3905
            http://orcid.org/0000-0002-0455-0785
            http://orcid.org/0000-0001-8157-2753
            http://orcid.org/0000-0001-6732-9001
            http://orcid.org/0000-0002-4935-8754
            Article
            701
            10.1007/s40121-022-00701-0
            9669291
            36242742
            c4b16629-9cb6-47f5-9b70-595f211fa472
            © The Author(s) 2022

            Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

            History
            : 23 June 2022
            : 20 September 2022
            Funding
            Funded by: FundRef http://dx.doi.org/10.13039/501100010767, Innovative Medicines Initiative;
            Award ID: 115523
            Categories
            Original Research
            Custom metadata
            © The Author(s) 2022

            prosthetic joint infection,staphylococcus aureus,outcome,clinical failure,functional failure

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