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da Cruz VF, Machinski E, da Silva Oliveira Filho AR, Conde RA, Varone BB, Gobbi RG, Helito CP, Leal DP. Effectiveness of intra-articular vancomycin in preventing prosthetic joint infections in hip and knee arthroplasty: A systematic review and meta-analysis of RCT's. J Orthop 2025; 66:25-33. [PMID: 39872993 PMCID: PMC11763160 DOI: 10.1016/j.jor.2024.12.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Accepted: 12/23/2024] [Indexed: 01/30/2025] Open
Abstract
Introduction This study aimed to evaluate the effectiveness and safety of intra-articular vancomycin powder in reducing prosthetic joint infections (PJIs) in primary hip and knee arthroplasty through a meta-analysis of randomized controlled trials (RCTs). Methods A research in Pubmed, Embase and Cochrane databases was performed to identify randomized clinical trials comparing intra-articular vancomycin use to conventional antibiotic prophylaxis in total hip or knee arthroplasty patients, assessing postoperative infection rates, adverse drug reactions, and venous thrombotic events. Statistical analysis was performed using R (RStudio 2024.04.2), and heterogeneity was assessed with the I2 test. Results A total of 1485 patients from five randomized clinical trials were included, with 737 receiving intra-articular vancomycin. The infection rate was 0.54 % in the intervention group and 1.73 % in the control group (RR 0.37; 95 % CI 0.02-8.95; p = 0.369; I2 = 49 %), showing no statistically significant difference between the groups. Adverse reactions to the glycopeptide were reported in six cases (0.8 %) in the intervention group compared to four cases (0.5 %) in the control group (RR 1.50; 95 % CI 1.50-150; p = 0.001; I2 = 0 %). Regarding thrombotic events, there was one case in 647 patients in the intervention group and three cases in 660 patients in the control group (RR 0.45; 95 % CI 0.03-7.02; p = 0.169; I2 = 0 %). Conclusion Although no significant difference was found, the intervention group showed a trend toward lower infection rates. Additional RCTs with larger sample sizes are required to confirm these findings. Trial registration The prospective registration of the meta-analysis was conducted on PROSPERO in July 2024 with the protocol number 565988.
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Affiliation(s)
| | - Elcio Machinski
- Universidade Estadual de Ponta Grossa (UEPG), Ponta Grossa, Brazil
| | | | - Rodrigo Arruda Conde
- Fundación Barceló - Instituto Universitario de Ciencias de la Salud, Buenos Aires, Argentina
| | - Bruno Butturi Varone
- Instituto de Ortopedia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
| | - Riccardo Gomes Gobbi
- Instituto de Ortopedia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
- HCor, Hospital do Coração, São Paulo, SP, Brazil
| | - Camilo Partezani Helito
- Instituto de Ortopedia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
| | - Daniel Peixoto Leal
- Instituto de Ortopedia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
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Vuotto F, Bru JP, Canoui E, Caseris M, Chopin MCC, Cohen R, Diamantis S, Dinh A, Fillatre P, Gauzit R, Gillet Y, Jonville-Bera AP, Lafaurie M, Lesprit P, Lorrot M, Lourtet J, Maulin L, Poitrenaud D, Pariente A, Raymond J, Strady C, Stahl JP, Varon E, Welker Y, Bonnet E. The latest updates on the proper use of fluoroquinolones - Actualisation 2025 update by the SPILF and the GPIP. Infect Dis Now 2025; 55:105062. [PMID: 40216161 DOI: 10.1016/j.idnow.2025.105062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2025] [Accepted: 04/08/2025] [Indexed: 04/27/2025]
Affiliation(s)
- F Vuotto
- Maladies Infectieuses, CHU Lille, Hôpital Huriez, 59 000 Lille, France.
| | - J P Bru
- Maladies Infectieuses, CH Annecy Genevois, 74374 Pringy, France
| | - E Canoui
- Équipe mobile d'infectiologie, CHU Cochin, APHP, 75014 Paris, France
| | - M Caseris
- Équipe Opérationnelle d'Infectiologie, Hôpital mère enfant Robert Debré, APHP, 75019 Paris, France
| | - M C C Chopin
- Service de Maladies Infectieuses, CH Boulogne-sur-Mer, 62321 Boulogne-sur-Mer, France
| | - R Cohen
- Unité Petits Nourrissons, CHI, 94000 Créteil, France
| | - S Diamantis
- Maladies Infectieuses et Tropicales, groupe hospitalier Sud Ile de France, 77000 Melun, France
| | - A Dinh
- Maladies Infectieuses et Tropicales, Hôpitaux R. Poincaré-A. Paré, 92380 Garches, France
| | - P Fillatre
- Service de Réanimation Polyvalente, CH Yves Le Foll, 22000 Saint Brieuc, France
| | - R Gauzit
- Infectiologie transversale, CHU Cochin, APHP, 75014 Paris, France
| | - Y Gillet
- Service d'urgences et réanimation pédiatrique, équipe mobile d'infectiologie pédiatrique, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Université Claude Bernard Lyon 1, 69229 Lyon, France
| | | | - M Lafaurie
- Service des Maladies Infectieuses, Hôpital Saint-Louis, APHP, 75010 Paris, France
| | - P Lesprit
- Université Grenoble Alpes, Maladies Infectieuses et tropicales, CHU Grenoble Alpes, Grenoble, France
| | - M Lorrot
- Service de Pédiatrie Générale et Equipe d'infectiologie, Hôpital Armand Trousseau, AP-HP, Sorbonne Université. URMS 1123 ECEVE, 75019 Paris, France
| | - J Lourtet
- Service de Bactériologie, Hôpital Saint Antoine, 75012 Paris, France
| | - L Maulin
- Maladies Infectieuses et Tropicales, CHIAP, 13616 Aix en Provence, France
| | - D Poitrenaud
- Unité fonctionnelle d'Infectiologie Régionale, CH Ajaccio 20303 Ajaccio, France
| | - A Pariente
- Pharmacoépidémiologie et Bon Usage du Médicament, Service de Pharmacologie Médicale, Pôle de Santé Publique, CHU de Bordeaux, France
| | - J Raymond
- Bactériologie : Centre Hospitalier Bicêtre, 94270 Kremlin- Bicêtre, France
| | - C Strady
- Maladies Infectieuses et Tropicales, groupe hospitalier Sud Ile de France, 77000 Melun, France
| | - J P Stahl
- Infectiologie, Université Grenoble Alpes, 38700 La Tronche, France
| | - E Varon
- Laboratoire de Biologie Médicale et Centre National de Référence des Pneumocoques, France
| | - Y Welker
- Maladies Infectieuses, CHI, 78100 Saint Germain en Laye, France
| | - E Bonnet
- Maladies Infectieuses et Tropicales, CHU Toulouse, Hôpital Purpan, 31300 Toulouse, France
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Hewlett AL, Kildow BJ, Cortés-Penfield NW. Periprosthetic Joint Infections. Infect Dis Clin North Am 2025:S0891-5520(25)00015-7. [PMID: 40413113 DOI: 10.1016/j.idc.2025.02.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/27/2025]
Abstract
Periprosthetic joint infection (PJI) is a dreaded and devastating complication of total joint arthroplasty. The clinical presentation of PJI is dependent on multiple factors, but typically involves pain, swelling, warmth and erythema of the affected joint. The management of PJI is complex, with both the medical and surgical approach being scenario specific. The importance of interdisciplinary collaboration to manage these complicated infections cannot be overstated. This review, aimed at the practicing infectious diseases clinician, details the background, microbiology, clinical presentation, diagnosis and both surgical and medical treatment of PJI.
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Affiliation(s)
- Angela L Hewlett
- Department of Internal Medicine, Division of Infectious Diseases, Section of Orthopedic Infectious Diseases, University of Nebraska Medical Center, 985400 Nebraska Medical Center, Omaha, NE 68198-5400, USA.
| | - Beau J Kildow
- Department of Orthopaedic Surgery and Rehabilitation, University of Nebraska Medical Center, 981080 Nebraska Medical Center, Omaha, NE 68198-1080, USA
| | - Nicolás W Cortés-Penfield
- Department of Internal Medicine, Division of Infectious Diseases, Section of Orthopedic Infectious Diseases, University of Nebraska Medical Center, 985400 Nebraska Medical Center, Omaha, NE 68198-5400, USA
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Schreiner G, Fucaloro S, Meija J, Krivicich L, Salzler M. Oral antibiotics demonstrate similar rates of success and complications compared to parenteral antibiotics for bone and joint infections: a systematic review and meta-analysis. Infection 2025:10.1007/s15010-025-02517-9. [PMID: 40372606 DOI: 10.1007/s15010-025-02517-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2025] [Accepted: 03/17/2025] [Indexed: 05/16/2025]
Abstract
PURPOSE Bone and joint infections (BJIs) cause significant morbidity, and current guidelines suggest treatment with parenteral antibiotics for 4-6 weeks. However, utility of oral antibiotics as a potential alternative has yet to be thoroughly investigated. To provide a statistical appraisal of literature comparing treatment success and complication rates of oral antibiotics to parenteral antibiotics for BJIs. METHODS PubMed, Embase, Cochrane, and Web of Science databases were queried for studies published by November 12, 2024. Randomized controlled trials (RCTs) comparing parenteral to oral regimens for the entire treatment duration were included, as well as comparative studies evaluating "early switch" therapy, defined as switching from parenteral to oral antibiotics within 28 days. Data was pooled and sub-analyzed according to design (RCTs or early switch cohorts). Treatment successes and complications for parenteral and oral groups were assessed via DerSimonian-Laird binary random-effects modeling with a p-value < 0.05 indicating significance. RESULTS Six RCTs (1,310 patients) compared treatment success of parenteral or oral regimens for the duration of the infection treatment, and six retrospective cohort studies (1,106 patients) compared parenteral therapy to early switch therapy. Meta-analysis of RCTs demonstrated no significant difference for treatment success rates for oral versus parenteral antibiotics (OR 1.09 [0.79-1.51], p = 0.93, I2 = 0.00%). Six early switch cohort studies demonstrated that oral antibiotics had significantly higher success (OR = 1.70 [1.13-2.54], p = 0.01, I2 = 0.00%). Meta-data of both RCTs and early switch cohort studies demonstrated no significant difference in complication rates. CONCLUSION No difference in treatment success rates or complication rates was found when comparing oral and parenteral antibiotics. Oral antibiotics are a possible option for treatment of BJIs.
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Affiliation(s)
| | | | - Jesus Meija
- Tufts University School of Medicine, Boston, MA, USA
| | - Laura Krivicich
- Department of Orthopaedic Surgery, Tufts Medical Center, Boston, MA, USA
| | - Matthew Salzler
- Department of Orthopaedic Surgery, Tufts Medical Center, Boston, MA, USA.
- , Biewend Building, 260 Tremont St, Boston, MA, 02111, USA.
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Fröschen FS, Greber L, Molitor E, Hischebeth GTR, Franz A, Randau TM. The PJI-TNM Classification as Predictor for Revision-Free Implant Survival Rates in Patients with Periprosthetic Joint Infection of the Hip or Knee Joint. Infect Dis Rep 2025; 17:54. [PMID: 40407656 PMCID: PMC12101191 DOI: 10.3390/idr17030054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2025] [Revised: 04/24/2025] [Accepted: 05/13/2025] [Indexed: 05/26/2025] Open
Abstract
BACKGROUND Periprosthetic joint infections (PJIs) remain a major challenge in arthroplasty. This study tries to evaluate the PJI-TNM classification as predictor for the revision-free implant survival in patients with PJI of the hip or knee joint. METHODS To this end, we perform a retrospective study of all consecutive patients with PJI of an inlying hip or knee arthroplasty between January 2015 and December 2019. RESULTS A total of 443 cases (hip: n = 247; knee n = 196) were identified. In total, 439 patients underwent surgery (DAIR: n = 138 cases (31%), explantation: n = 272 (61%), irrigation with debridement without exchange of implant components: n = 29 (6.5%)). Four patients refused surgical treatment and 39.5% were lost to follow-up. In total, 78 patients died during follow-up and 27 deaths were directly related to PJI/complications during treatment. Patients with inlying "standard"-implants (p < 0.001) and without previous history of PJI (p = 0.002) displayed a significantly higher postoperative revision-free implant survival. In terms of the PJI-TNM subclassification, patients with loosened implants but without soft-tissue defects (T1) displayed the highest revision-free implant survival. In contrast, patients classified as M3 (no surgical treatment possible) displayed an inferior outcome compared to M0, M1, or M2. Patients with different N-subclassifications ("non-human cells"/causative pathogen) did not display differences in revision-free implant survival. CONCLUSIONS The PJI-TNM classification is well suited to classify PJIs. Its complexity allows for more than 500 different combinations of classifications. Further validation data are needed, but to us, the PJI-TNM classification seems to offer the possibility of comparing patients with PJIs. It may, therefore, be a very valuable tool in order to compare cohorts with PJIs and provide individual data for patient specific outcomes.
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Affiliation(s)
- Frank Sebastian Fröschen
- Department of Orthopaedics and Trauma Surgery, University Hospital Bonn, 53127 Bonn, Germany; (L.G.); (A.F.); (T.M.R.)
| | - Lisa Greber
- Department of Orthopaedics and Trauma Surgery, University Hospital Bonn, 53127 Bonn, Germany; (L.G.); (A.F.); (T.M.R.)
| | - Ernst Molitor
- Institute of Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, 53127 Bonn, Germany; (E.M.); (G.T.R.H.)
| | | | - Alexander Franz
- Department of Orthopaedics and Trauma Surgery, University Hospital Bonn, 53127 Bonn, Germany; (L.G.); (A.F.); (T.M.R.)
- Department of Trauma and Orthopedic Surgery, BG Klinik Ludwigshafen, 67071 Ludwigshafen, Germany
| | - Thomas Martin Randau
- Department of Orthopaedics and Trauma Surgery, University Hospital Bonn, 53127 Bonn, Germany; (L.G.); (A.F.); (T.M.R.)
- Clinic for Orthopedics, Special Orthopedic Surgery and Sports Medicine, Augustinian Sisters Hospital, 51109 Cologne, Germany
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Sabater-Martos M, Clauss M, Ribau A, Sousa R, on behalf of the Leukocyte Count Synovial Fluid working group for the Unified PJI definition task force. Differential synovial fluid white blood cell count for the diagnosis of chronic peri-prosthetic joint infection - a systematic review and meta-analysis. J Bone Jt Infect 2025; 10:165-184. [PMID: 40385309 PMCID: PMC12082335 DOI: 10.5194/jbji-10-165-2025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2025] [Accepted: 05/05/2025] [Indexed: 05/20/2025] Open
Abstract
Introduction: Peri-prosthetic joint infection (PJI) is a significant complication of arthroplasty, lacking a single gold standard diagnostic test. Synovial fluid white blood cell (WBC) count and polymorphonuclear neutrophil (PMN) proportion are widely used diagnostic tools, but their optimal cutoffs remain unclear, particularly for chronic PJI. Material and methods: This systematic review and meta-analysis included 74 studies published between 2000 and 2024. Data on diagnostic performance (sensitivity, specificity, and diagnostic odds ratios - DORs) of WBC count and PMN proportions were analysed. Sub-group analyses and heterogeneity assessments were performed, and optimal cutoffs for diagnostic accuracy were identified. Results: The meta-analysis revealed a WBC count summary DOR of 58.38 (95 % CI - confidence interval: 48.48-70.32) with an area under the curve (AUC) of the summarized receiver operating characteristic curve of 0.952. The PMN proportion showed a DOR of 43.17 (95 % CI: 35.31-52.79) and an AUC of 0.941. Optimal diagnostic thresholds for chronic PJI were WBC count > 2600 cells per microlitre and PMN > 70 %. Rule-in thresholds (specificity > 95 %) were WBC count ≥ 3000 cells per microlitre and PMN ≥ 75 %, while rule-out thresholds (sensitivity > 95 %) were WBC count ≤ 1500 cells per microlitre and PMN ≤ 65 %. Confounding conditions such as fractures, inflammatory arthritis, and metal-related reactions reduced test accuracy. Conclusions: Synovial fluid analysis remains a critical diagnostic tool for chronic PJI. Thresholds of WBC count < 1500 and > 3000 cells per microlitre and PMN < 65 % and > 75 % provide reliable negative and positive predictive values. A standardized diagnostic framework is essential for addressing remaining controversies and ensuring consistent interpretation across clinical settings.
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Affiliation(s)
- Marta Sabater-Martos
- Orthopedic and Traumatology Department, Clínic Barcelona. Carrer Villarroel 170, 08036 Barcelona, Spain
| | - Martin Clauss
- Center for Musculoskeletal Infections (ZMSI), University Hospital Basel, Basel, Switzerland
- Department for Orthopaedics and Trauma Surgery, University Hospital Basel, Basel, Switzerland
| | - Ana Ribau
- Unidade Local de Sáude do Médio Ave, Famalicao, Portugal
| | - Ricardo Sousa
- Porto Bone and Joint Infection Group (GRIP), ULS Santo António – Porto and CUF hospitals, Porto and Lisbon, Portugal
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Roškar S, Mihalič R, Mihelič A, Trebše R. Synovial fluid viscosity with synovial fluid cell count, valuable diagnostic marker of prosthetic joint infections. Sci Rep 2025; 15:16223. [PMID: 40346265 PMCID: PMC12064731 DOI: 10.1038/s41598-025-00760-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Accepted: 04/30/2025] [Indexed: 05/11/2025] Open
Abstract
In the absence of standard criteria for prosthetic joint infections (PJI), several diagnostic modalities have been proposed mostly concentrating on novel biochemical markers. The physical chemistry markers received scarce attention. Synovial fluid (SF) viscosity could be considered as marker for PJI, however, its diagnostic value of PJI remains unknown. Our study aimed to determine the potential of SF viscosity as a diagnostic marker of PJI and compare it to SF cell count with differential (CCD). We prospectively analysed 123 SF samples (58 septic and 65 aseptic) for viscosity and CCD of SF obtained during hip and knee revision procedures. The diagnosis of PJI based on EBJIS criteria. The viscosity cut-off for PJI was calculated and the diagnostic power was compared to CCD. The mean SF viscosity in the PJI group was 8.5 ± 0.4 mPa s and 103.2 ± 18.8 mPa s in the aseptic group (p < 0.05). SF viscosity achieved 100% sensitivity and 85.3% specificity, with AUC 0.832 (95% CI 0.739, 0.925). Combination of SF viscosity and CCD achieved AUC 0.951 (95% CI 0.919, 0.987). SF viscosity is more sensitive but slightly less specific in diagnosing PJI than SF CCD. Best diagnostic value is achieved combining SF viscosity with CCD in detection of PJI.
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Affiliation(s)
- Samo Roškar
- Valdoltra Orthopaedic Hospital, Jadranska Cesta 31, 6280, Ankaran, Slovenia
- Faculty of Medicine, University of Ljubljana, Zaloška Cesta 9, 1000, Ljubljana, Slovenia
| | - René Mihalič
- Valdoltra Orthopaedic Hospital, Jadranska Cesta 31, 6280, Ankaran, Slovenia
- Faculty of Medicine, University of Ljubljana, Zaloška Cesta 9, 1000, Ljubljana, Slovenia
| | - Anže Mihelič
- Valdoltra Orthopaedic Hospital, Jadranska Cesta 31, 6280, Ankaran, Slovenia
| | - Rihard Trebše
- Valdoltra Orthopaedic Hospital, Jadranska Cesta 31, 6280, Ankaran, Slovenia.
- Faculty of Medicine, University of Ljubljana, Zaloška Cesta 9, 1000, Ljubljana, Slovenia.
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Sendi P, Trebse R, Zimmerli W. Debridement, antibiotics and implant retention: are all approaches to periprosthetic joint infection equal? Same procedures, different outcomes. Clin Microbiol Infect 2025:S1198-743X(25)00219-8. [PMID: 40339793 DOI: 10.1016/j.cmi.2025.04.037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2025] [Revised: 04/23/2025] [Accepted: 04/26/2025] [Indexed: 05/10/2025]
Abstract
BACKGROUND The reported success rate of debridement, antibiotics, and implant retention (DAIR) for periprosthetic joint infection varies considerably between studies, despite institutions reporting use of the same procedure. In this narrative review, we aim to delineate the differences between the various DAIR approaches and highlight why they influence the outcome. OBJECTIVES We performed a PubMed and internet search investigating the different approaches for DAIR and their associated outcomes. SOURCES Twenty-two studies with defined infection criteria, consisting of 50 or more periprosthetic joint infection cases and a follow-up of 1 year or longer, were included. CONTENT Most studies did not report whether the presence of a sinus tract was a criterion for not performing DAIR, and the use of biofilm-active agents for curative DAIR was only reported in a few studies. The duration of infection as criterion for early postoperative and acute haematogenous infection varied between studies. The epidemiology of host factors and microorganisms, healthcare systems, patient-doctor interactions, and decision-making processes for surgical interventions vary worldwide, and so do the indications for DAIR. IMPLICATIONS Studies should precisely declare the indication for DAIR, the variables that influence decision-making for treatment options, the surgical technique applied, and the type and duration of antimicrobial therapy. Such an approach will increase the quality of research data and allow the development of recognized subcategories of DAIR.
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Affiliation(s)
- Parham Sendi
- Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
| | - Rihard Trebse
- Valdoltra Orthopaedic Hospital, Ankaran, Slovenia; Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Werner Zimmerli
- Interdisciplinary Unit for Orthopedic Infections, Kantonsspital Baselland, University of Basel, Liestal, Switzerland
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Kremers HM, Wyles CC, Slusser JP, O’Byrne TJ, Sagheb E, Lewallen DG, Berry DJ, Osmon DR, Sohn S, Kremers WK. Data-Driven Approach to Development of a Risk Score for Periprosthetic Joint Infections in Total Joint Arthroplasty Using Electronic Health Records. J Arthroplasty 2025; 40:1308-1316.e13. [PMID: 39489386 PMCID: PMC11985314 DOI: 10.1016/j.arth.2024.10.129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Revised: 10/22/2024] [Accepted: 10/24/2024] [Indexed: 11/05/2024] Open
Abstract
BACKGROUND Periprosthetic joint infection (PJI) is an uncommon, but serious complication in total joint arthroplasty. Personalized risk prediction and risk factor management may allow better preoperative assessment and improved outcomes. We evaluated different data-driven approaches to develop surgery-specific PJI prediction models using large-scale data from the electronic health records (EHRs). METHODS A large institutional arthroplasty registry was leveraged to collect data from 58,574 procedures of 41,844 patients who underwent at least one primary and/or revision hip and/or knee arthroplasty between 2000 and 2019. The registry dataset was augmented with additional clinical, procedural, and laboratory data from the EHRs for more than 100 potential predictor variables. The main outcome was PJI within the first year after surgery. We implemented both traditional and machine learning methods for model development (lasso regression, relaxed lasso regression, ridge regression, random forest, stepwise regression, extreme gradient boosting, neural network) and used 10-fold cross-validation to calculate measures of model performance in terms of discrimination (c-statistic) and calibration. RESULTS All models discriminated similarly in predicting PJI risk, with negligible differences of less than 0.08 between the best- and worst-performing models. The relaxed and fully relaxed lasso models using the Cox model structure outperformed the other models with concordances of 0.787 in primary hip arthroplasty and 0.722 in revision hip arthroplasty, with the number of predictors ranging from nine to 41. The concordances with the relaxed lasso models were 0.681 in primary and 0.699 in revision knee arthroplasty, with a higher number of predictors in the models. Predictors included in the models varied substantially across the four surgical groups. CONCLUSIONS The incorporation of additional data from the EHRs offers limited improvement in PJI risk stratification. Furthermore, improvement in PJI risk prediction was modest with the machine learning approaches and may not justify the added complexity.
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Affiliation(s)
- Hilal Maradit Kremers
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota
| | - Cody C. Wyles
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota
| | - Joshua P. Slusser
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota
| | - Thomas J. O’Byrne
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota
| | - Elham Sagheb
- Department of Artificial Intelligence and Informatics, Mayo Clinic, Rochester, Minnesota
| | | | - Daniel J. Berry
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota
| | - Douglas R. Osmon
- Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Sunghwan Sohn
- Department of Artificial Intelligence and Informatics, Mayo Clinic, Rochester, Minnesota
| | - Walter K. Kremers
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota
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10
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DeBiase JM. A Clinical Review of Prosthetic Joint Infections. Med Clin North Am 2025; 109:615-623. [PMID: 40185550 DOI: 10.1016/j.mcna.2024.12.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/07/2025]
Abstract
Prosthetic arthroplasties are continuing to increase in the United States. While prosthetic joint infections are a less common adverse event, they can have a devastating impact on the patient as well as have a large economic burden on the health care industry. Prosthetic joint infections can be surgically managed by debridement, antibiotics, and implant retention, 1-stage revisions, 2-stage revisions, resection arthroplasties, arthrodesis, and amputations. Antimicrobial therapy typically includes 4 to 6 weeks of parenteral or highly bioavailable oral agents. Suppressive and chronic oral antimicrobial therapy may be pursued depending on the pathogen, clinical scenario, and retention of the prosthesis.
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Affiliation(s)
- Joseph M DeBiase
- Macon & Joan Brock Virginia Health Sciences Eastern Virginia Medical School at Old Dominion University, Hofheimer Hall, 4th Floor, 825 Fairfax Avenue, Norfolk, VA 23507, USA.
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11
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Grant AR, Nin DZ, Chen YW, Niu R, Esantsi M, Talmo CT, Hollenbeck BL, Chang DC, Mattingly DA, Smith EL. The Fate of the DAIR, Outcomes after 1 Year: A Large Database Study. J Knee Surg 2025; 38:282-289. [PMID: 39667407 DOI: 10.1055/a-2501-1024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2024]
Abstract
Debridement with antibiotics and implant retention (DAIR) is commonly utilized for treatment of prosthetic joint infection (PJI) in total knee arthroplasty (TKA), particularly in cases of acute PJI. Reported success rates of DAIR have been highly variable, but the overall success rate of DAIR cohort studies is approximately 70 to 80%. However, no large database studies have investigated the success rate of DAIR. Therefore, we seek to provide a framework for large-database analysis of PJI interventions and their outcomes and to assess the success rate of DAIR. We queried the MarketScan Database for patients who underwent a DAIR (CPT 27310 and/or CPT 27486) procedure for indication of PJI (ICD-10 T84.53 OR T84.54) between January 1, 2017 and December 31, 2021. We identified reoperations (i.e., stage 1 revision, amputation, or arthrodesis) indicating failure of DAIR. Failure of DAIR treatment was defined by subsequent reoperation. We also identified prescriptions of suppression antibiotics more than 6 months after DAIR. We identified 1,018 patients who underwent a DAIR procedure for PJI. Of these patients, 195 (19.2%) underwent reoperation within 1 year and an additional 178 (17.5%) were prescribed suppressive antibiotics. For 780 patients with a minimum of 2 years of follow-up, 164 (21%) underwent reoperation and an additional 179 (22.9%) were prescribed suppressive antibiotics. Patients with obesity and patients younger than 60 years had significantly higher rates of having reoperation or suppressive antibiotics at 1 year following DAIR. DAIR is a viable option in the treatment of PJI, with an approximately 19% rate of reoperation at 2 years. Our findings are consistent with that of previously published literature.
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Affiliation(s)
- Andrew R Grant
- Department of Orthopaedics, New England Baptist Hospital, Boston, Massachusetts
| | - Darren Z Nin
- Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - Ya-Wen Chen
- Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - Ruijia Niu
- Department of Research, New England Baptist Hospital, Boston, Massachusetts
| | - Michael Esantsi
- Department of Orthopaedics, Tufts Medical Center, Boston, Massachusetts
| | - Carl T Talmo
- Department of Orthopedic Surgery, New England Baptist Hospital, Boston, Massachusetts
| | - Brian L Hollenbeck
- Department of Infectious Diseases, New England Baptist Hospital, Boston, Massachusetts
| | - David C Chang
- Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - David A Mattingly
- Department of Orthopedic Surgery, New England Baptist Hospital, Boston, Massachusetts
| | - Eric L Smith
- Department of Arthroplasty, New England Baptist Hospital, Boston, Massachusetts
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12
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Saadana J, Abdeljelil M, Khemili K, Chaouch F, Saad L, Belgacem H, Jellali M, Fekih A, Toumi A, Abid A. Strategies for periprosthetic joint infection management in resource-limited settings: the applicability of EBJIS criteria. INTERNATIONAL ORTHOPAEDICS 2025; 49:1027-1035. [PMID: 40053070 DOI: 10.1007/s00264-025-06478-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/21/2024] [Accepted: 02/23/2025] [Indexed: 04/17/2025]
Abstract
BACKGROUND AND PURPOSE Periprosthetic joint infection (PJI) is a significant and challenging healthcare issues. Accurate diagnosis is essential for effective treatment. The aim of our study is to underscore the usefulness of the new EBJIS definition and criteria when applied in a developing country department. METHODS We conducted a retrospective analysis of a single-center cohort of consecutive revision arthroplasties (January 2018-June 2024). This study was carried out at the Department of Orthopedics and Trauma Surgery in the University Hospital Fattouma Bourguiba in Monastir, Tunisia. Were included in our research patients who underwent revision surgery for arthroplasties due to septic failure. Exclusion criteria were: surgery performed within the previous six weeks, antibiotic-loaded bone cement spacer in place, the second step of a two-stage revision and periprosthetic fractures. RESULTS A total of 46 patients were included in the study. According to the EBJIS criteria, our cohort was divided into two groups: "likely infection" including 12 patients (26.1%) and "confirmed infection" with 34 patients (73.9%). Clinical signs like inflammation (Se 85.3%, PPV 76.32%) and pain (Se 76.47%, PPV 70.27%) demonstrate higher sensitivity but low specificity. Among paraclinical tests, a CRP level > 10 mg/dL is highly sensitive (97.06%), while PMN > 80% shows perfect specificity (100%). Tissue samples with more than two positives and cultures with the same microorganism exhibit high sensitivity (96.66% and 80%) and PPV (84.85% and 85.71%). CONCLUSION Establishing PJI diagnosis is challenging and depends on paraclinical testing. We highlight the lack of important diagnostic instruments in settings with limited resources.
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Affiliation(s)
- J Saadana
- Orthopaedic Surgery Department, Monastir University Hospital, Monastir, Tunisia
| | - Meriam Abdeljelil
- Infectious diseases Department, Monastir University Hospital, Monastir, Tunisia.
| | - K Khemili
- Emergency Department, Kairouan University Hospital, Kairouan, Tunisia
| | - F Chaouch
- Orthopaedic Surgery Department, Monastir University Hospital, Monastir, Tunisia
| | - L Saad
- Infectious diseases Department, Monastir University Hospital, Monastir, Tunisia
| | - H Belgacem
- Orthopaedic Surgery Department, Monastir University Hospital, Monastir, Tunisia
| | - M Jellali
- Orthopaedic Surgery Department, Monastir University Hospital, Monastir, Tunisia
| | - A Fekih
- Orthopaedic Surgery Department, Monastir University Hospital, Monastir, Tunisia
| | - A Toumi
- Infectious diseases Department, Monastir University Hospital, Monastir, Tunisia
| | - A Abid
- Orthopaedic Surgery Department, Monastir University Hospital, Monastir, Tunisia
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13
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Freller K, Punz H, Schopper C, Gotterbarm T, Klasan A, Stevoska S. The Accuracy of Empirical Antibiotic Treatment for Periprosthetic Joint Infections in Total Shoulder and Knee Arthroplasties. Antibiotics (Basel) 2025; 14:447. [PMID: 40426514 PMCID: PMC12108516 DOI: 10.3390/antibiotics14050447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2025] [Revised: 04/22/2025] [Accepted: 04/26/2025] [Indexed: 05/29/2025] Open
Abstract
Introduction: Periprosthetic joint infections (PJIs) remain a major challenge in orthopedic and trauma surgeries. The microbial resistance profiles and the optimal choice of empirical antibiotic therapy in shoulder arthroplasty revision are less well characterized compared to those in knee or hip arthroplasty revision. Materials and Methods: This retrospective study constitutes a novel comparative analysis, providing valuable insights into the presence of joint-specific pathogen resistance and the empirical treatment accuracy of shoulder and knee arthroplasties. A review of all the revision cases following primary shoulder and knee arthroplasties conducted between January 2012 and December 2023 was performed. Cases that required revision because of PJIs were identified, and microbial cultures were analyzed to determine the presence of pathogens and their resistance profiles. Results: The most administered postoperative empirical antibiotics were cefuroxime and amoxicillin-sulbactam. A statistically significant difference in the prevalence of anerobic pathogens was observed between total shoulder arthroplasty and knee arthroplasty. Furthermore, a statistically significant difference was observed in the sensitivities of pathogens to metronidazole (p < 0.001) and erythromycin (p = 0.014). Conclusions: This study demonstrates microbiological and antimicrobial resistance differences between PJI TSA and TKA cases.
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Affiliation(s)
- Katrin Freller
- Faculty of Medicine, Johannes Kepler University Linz, 4040 Linz, Austria; (H.P.); (C.S.); (T.G.); (A.K.)
- Department for Orthopedics and Traumatology, Kepler University Hospital GmbH, 4020 Linz, Austria
| | - Hannah Punz
- Faculty of Medicine, Johannes Kepler University Linz, 4040 Linz, Austria; (H.P.); (C.S.); (T.G.); (A.K.)
| | - Clemens Schopper
- Faculty of Medicine, Johannes Kepler University Linz, 4040 Linz, Austria; (H.P.); (C.S.); (T.G.); (A.K.)
- Department for Orthopedics and Traumatology, Kepler University Hospital GmbH, 4020 Linz, Austria
| | - Tobias Gotterbarm
- Faculty of Medicine, Johannes Kepler University Linz, 4040 Linz, Austria; (H.P.); (C.S.); (T.G.); (A.K.)
- Department for Orthopedics and Traumatology, Kepler University Hospital GmbH, 4020 Linz, Austria
| | - Antonio Klasan
- Faculty of Medicine, Johannes Kepler University Linz, 4040 Linz, Austria; (H.P.); (C.S.); (T.G.); (A.K.)
- AUVA UKH Steiermark, 8020 Graz, Austria
| | - Stella Stevoska
- Faculty of Medicine, Johannes Kepler University Linz, 4040 Linz, Austria; (H.P.); (C.S.); (T.G.); (A.K.)
- Department for Orthopedics and Traumatology, Kepler University Hospital GmbH, 4020 Linz, Austria
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14
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Valour F, Miot O, Batailler C, Goutelle S, Ferry T. Management of Gram-positive multiresistant bacteria prosthetic joint infection: a narrative review on current and innovative strategies. Clin Microbiol Infect 2025:S1198-743X(25)00184-3. [PMID: 40294870 DOI: 10.1016/j.cmi.2025.04.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Revised: 04/04/2025] [Accepted: 04/21/2025] [Indexed: 04/30/2025]
Abstract
BACKGROUND Prosthetic joint infection (PJI) is a devastating complication of arthroplasty surgery, mostly caused by Gram-positive pathogens, including Staphylococcus aureus and coagulase-negative staphylococci. Multidrug resistance is of major concern in this setting: (a) it can negatively impact outcome, restricting the use of the most effective antimicrobials; (b) it may influence the choice of surgical strategies; and (c) it restrains the therapeutic options to newly labelled antimicrobials with limited experience in PJI. OBJECTIVES To provide a comprehensive overview of the clinical impact of antimicrobial resistance in Gram-positive PJI and on current and innovative therapeutic strategies. SOURCES The review is based on PubMed searches for relevant topics, including multiresistant staphylococci PJI and the discussed specific therapeutic approaches. Given the very few randomized trials in this setting, discussion is mostly based on observational studies and the experience and opinion of the authors. CONTENT Methicillin resistance is an important concern in staphylococcal PJI, especially in coagulase-negative staphylococci. However, its impact on the outcome is controversial. Conversely, rifampicin and/or fluoroquinolone resistance are associated with worse prognosis and might be considered when defining difficult-to-treat pathogens in the PJI setting. There is very little experience with recently developed anti-Gram-positive antimicrobial in PJI, but evaluations of their antibiofilm activities are promising, and some of them might represent significant advances regarding antimicrobial tolerance (such as tedizolid) or pharmacokinetic profiles (such as dalbavancin) during long-term treatment required for PJI. Evaluation of innovative strategies in this setting is crucial, including repositioning of current surgical options using local antimicrobial delivery, pharmacokinetic monitoring and modelling to optimize antimicrobial therapy, suppressive antimicrobial treatment and/or phage-based approaches. IMPLICATIONS PJIs caused by resistant Gram-positive bacteria-including rifampicin- and/or fluoroquinolone-resistant staphylococci-may be associated with a poorer prognosis. It is therefore essential to optimize medical and surgical management, and to find new therapeutic alternatives.
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Affiliation(s)
- Florent Valour
- Reference Centre for the Management of Complex Bone and Joint Infection (CRIOAc Lyon, www.crioac-lyon.fr), Hospices Civils de Lyon, Lyon, France; Department of Infectious Diseases, Hospices Civils de Lyon, Lyon, France; Centre International de Recherche en Infectiologie (CIRI), Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Univ Lyon, Lyon, France.
| | - Olivier Miot
- Reference Centre for the Management of Complex Bone and Joint Infection (CRIOAc Lyon, www.crioac-lyon.fr), Hospices Civils de Lyon, Lyon, France; Department of Infectious Diseases, Hospices Civils de Lyon, Lyon, France
| | - Cécile Batailler
- Reference Centre for the Management of Complex Bone and Joint Infection (CRIOAc Lyon, www.crioac-lyon.fr), Hospices Civils de Lyon, Lyon, France; Orthopedic Surgery Department, Croix-Rousse Hospital, Hospices Civils de Lyon, Lyon, France; Institut français des sciences et technologies des transports, de l'aménagement et des réseaux (IFSTTAR), Laboratoire de biomécanique et mécanique des chocs (LBMC), Université de Lyon, Université Claude Bernard Lyon 1, UMR_T9406, Lyon, France
| | - Sylvain Goutelle
- Reference Centre for the Management of Complex Bone and Joint Infection (CRIOAc Lyon, www.crioac-lyon.fr), Hospices Civils de Lyon, Lyon, France; Pharmacy Department, Croix-Rousse Hospital, Hospices Civils de Lyon, Lyon, France; Laboratoire de biométrie et biologie évolutive (LBBE), CNRS, UMR 5558, Université Lyon 1, Villeurbanne, France
| | - Tristan Ferry
- Reference Centre for the Management of Complex Bone and Joint Infection (CRIOAc Lyon, www.crioac-lyon.fr), Hospices Civils de Lyon, Lyon, France; Department of Infectious Diseases, Hospices Civils de Lyon, Lyon, France; Laboratoire de biométrie et biologie évolutive (LBBE), CNRS, UMR 5558, Université Lyon 1, Villeurbanne, France
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15
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Herren SC, Karau MJ, Koscianski C, Greenwood-Quaintance KE, Mandrekar JN, Wang W, Patel R. Activity of contezolid against methicillin-resistant Staphylococcus aureus in a rat model of foreign body osteomyelitis. Microbiol Spectr 2025:e0237224. [PMID: 40277362 DOI: 10.1128/spectrum.02372-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/26/2025] Open
Abstract
Contezolid has activity against methicillin-resistant Staphylococcus aureus (MRSA), a common cause of orthopedic infection. In a rat model of foreign body osteomyelitis, 1.3 log10 cfu/g bone and 0.5 log10 cfu/k-wire reduction in MRSA was found in tibiae (P = 0.0186) and K-wires, respectively, of contezolid-treated compared to untreated rats. No MRSA was recovered from animals receiving rifampin alone or in combination with contezolid or vancomycin. There was no emergence of resistance to contezolid, vancomycin, or rifampin.
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Affiliation(s)
- Sebastian C Herren
- Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Melissa J Karau
- Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Christina Koscianski
- Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Kerryl E Greenwood-Quaintance
- Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Jayawant N Mandrekar
- Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA
| | - Wen Wang
- Department of Biology, MicuRx Pharmaceuticals Inc., Shanghai, China
| | - Robin Patel
- Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
- Division of Public Health, Infectious Diseases, and Occupational Medicine, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
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16
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Wahl P, Schläppi M, Loganathan A, Uçkay I, Hodel S, Fritz B, Scheidegger J, Djebara S, Leitner L, McCallin S. Bacteriophage therapy created the necessary conditions for successful antibiotic suppression in a periprosthetic hip joint infection: a Case Report. Front Med (Lausanne) 2025; 12:1564369. [PMID: 40351470 PMCID: PMC12061668 DOI: 10.3389/fmed.2025.1564369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Accepted: 04/08/2025] [Indexed: 05/14/2025] Open
Abstract
Introduction Treatment failure remains an issue in periprosthetic joint infection (PJI). Bacteriophages offer new treatment options. However, there is still a lack of evidence to better define their usefulness and administration. We report a case in which antibiotic suppression was successful only after administration of bacteriophages. Case description Antibiotic suppression was the only option for a 94-year-old male with methicillin-resistant Staphylococcus aureus (MRSA) PJI of the hip and of the knee. As the hip PJI could not be suppressed adequately, bacteriophages were administered locally and systemically together with daptomycin. This combined approach led to sufficient clinical improvement for further oral antibiotic suppression, although without infection eradication. Conclusion The administration of bacteriophages may be a valuable, less-invasive adjunct therapy to successfully suppress PJI. Bacteriophage selection, preparation and administration, however, remains associated with administrative obstacles, greatly limiting availability and practicability. Nevertheless, research and developments in this domain should be pursued, particularly considering issues with future antibiotic limitations and cost associated with treatment failure in PJI.
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Affiliation(s)
- Peter Wahl
- Division of Orthopaedics and Traumatology, Cantonal Hospital Winterthur, Winterthur, Switzerland
- Faculty of Medicine, University of Bern, Bern, Switzerland
| | - Michel Schläppi
- Division of Orthopaedics and Traumatology, Cantonal Hospital Winterthur, Winterthur, Switzerland
| | - Archana Loganathan
- Department of Neuro-Urology, Balgrist University Hospital, University of Zurich, Zürich, Switzerland
| | - Ilker Uçkay
- Unit of Clinical and Applied Research, Infectiology, Balgrist University Hospital, University of Zurich, Zürich, Switzerland
| | - Sandro Hodel
- Department of Orthopedics, Balgrist University Hospital, University of Zurich, Zürich, Switzerland
| | - Benjamin Fritz
- Department of Radiology, Balgrist University Hospital, University of Zurich, Zürich, Switzerland
| | - Jens Scheidegger
- Department of Neuro-Urology, Balgrist University Hospital, University of Zurich, Zürich, Switzerland
| | - Sarah Djebara
- Center for Infectious Diseases, Queen Astrid Military Hospital, Brussels, Belgium
| | - Lorenz Leitner
- Department of Neuro-Urology, Balgrist University Hospital, University of Zurich, Zürich, Switzerland
| | - Shawna McCallin
- Department of Neuro-Urology, Balgrist University Hospital, University of Zurich, Zürich, Switzerland
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17
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Tedeschi S, Giannitsioti E, Mayer C. Emerging Concepts for the Treatment of Biofilm-Associated Bone and Joint Infections with IV Fosfomycin: A Literature Review. Microorganisms 2025; 13:963. [PMID: 40431135 PMCID: PMC12114314 DOI: 10.3390/microorganisms13050963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2025] [Revised: 04/02/2025] [Accepted: 04/16/2025] [Indexed: 05/29/2025] Open
Abstract
Due to the involvement of biofilms in the pathogenesis of bone and joint infections (BJI), the treatment of these infections is often challenging, especially when multidrug- or extensively drug-resistant (MDR/XDR) pathogens are involved. Intravenous fosfomycin (FOS) is a phosphoenolpyruvate analogue with a unique mode of action and broad-spectrum activity against both Gram-positive (GP) and Gram-negative (GN) pathogens. It is used in various severe and deep-seated infections, including BJIs. This review article focuses on preclinical and clinical data surrounding the use of FOS for biofilm-related BJIs. Data from several in vitro and animal models of infection demonstrated that FOS, especially in combination with other antibiotics, is effective against biofilms of (methicillin-resistant) Staphylococcus spp., (vancomycin-resistant) Enterococcus spp., carbapenem-resistant and extended-spectrum beta-lactamase-producing Enterobacterales, and MDR Pseudomonas aeruginosa. Data from clinical studies, mostly retrospective observational studies and case reports/case series, revealed that FOS was typically used in combination with other antibiotics for the treatment of various BJI, including acute and chronic osteomyelitis, prosthetic joint infections, and fracture-related infections, in adult and pediatric patients. Success rates often exceeded 80%. FOS exhibits good and fast penetration into bone tissue and is generally well tolerated, with only a few adverse drug reactions, such as gastrointestinal disorders and electrolyte imbalances. Collectively, the data indicate that FOS is a valuable option as part of combination regimens for the treatment of BJIs caused by both GP and GN bacteria.
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Affiliation(s)
- Sara Tedeschi
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy
- Infectious Diseases Unit, Department of Integrated Infectious Risk Management, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Efthymia Giannitsioti
- 1st Department of Propaedeutic and Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, 11527 Athens, Greece;
| | - Christian Mayer
- InfectoPharm Arzneimittel und Consilium GmbH, 64646 Heppenheim, Germany;
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18
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Kang YR, Park JY, Chung DR, Kang M, Ko JH, Huh K, Cho SY, Kang CI, Peck KR. Enhanced Biofilm Disruption in Methicillin-Resistant Staphylococcus aureus Using Rifampin and Fluoroquinolone Combinations. Pathogens 2025; 14:404. [PMID: 40430725 PMCID: PMC12113996 DOI: 10.3390/pathogens14050404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2025] [Revised: 04/18/2025] [Accepted: 04/21/2025] [Indexed: 05/29/2025] Open
Abstract
Staphylococcus aureus biofilms complicate the treatment of device-related infections. We hypothesized that combining rifampin with fluoroquinolones could eradicate biofilms even in antimicrobial-resistant S. aureus strains. We determined the synergistic interactions of these combinations in a biofilm model. Thirty methicillin-resistant S. aureus (MRSA) isolates with varying susceptibility profiles were evaluated. Minimum biofilm eradication concentrations (MBECs) were determined using the Calgary Biofilm Device, and the synergy was assessed using the fractional biofilm eradication concentration (FBEC) index. Scanning electron microscopy (SEM) was performed on one strain, and confocal laser scanning microscopy (CLSM) was conducted on four strains for visualizing and evaluating the biofilm viability. The MBEC90 for rifampin and levofloxacin were 512 mg/L and 256 mg/L, respectively, and exceeded 1024 mg/L for ciprofloxacin. Synergy was observed in 56.7% of strains for both the rifampin + ciprofloxacin and rifampin + levofloxacin combinations, with no difference between the combinations. A higher ciprofloxacin MBEC (≥16 mg/L) increased the likelihood of synergy with rifampin by 18-fold. SEM and CLSM analyses in a subset of strains confirmed the enhanced biofilm disruption with rifampin + ciprofloxacin compared to ciprofloxacin alone. Our findings suggest that rifampin combined with ciprofloxacin or levofloxacin may synergistically eradicate MRSA biofilms, offering a potential treatment option for device-related infections when alternatives are limited.
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Affiliation(s)
- Yu Ri Kang
- Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea; (Y.R.K.); (J.-H.K.); (K.H.); (S.Y.C.); (C.-I.K.); (K.R.P.)
- Asia Pacific Foundation for Infectious Diseases (APFID), Seoul 06367, Republic of Korea
| | - Joo-Young Park
- Department of Data Science, School of Software Convergence, Myongji University, Seoul 03674, Republic of Korea;
| | - Doo Ryeon Chung
- Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea; (Y.R.K.); (J.-H.K.); (K.H.); (S.Y.C.); (C.-I.K.); (K.R.P.)
- Asia Pacific Foundation for Infectious Diseases (APFID), Seoul 06367, Republic of Korea
| | - Minhee Kang
- Biomedical Engineering Research Center, Smart Healthcare Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea;
| | - Jae-Hoon Ko
- Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea; (Y.R.K.); (J.-H.K.); (K.H.); (S.Y.C.); (C.-I.K.); (K.R.P.)
| | - Kyungmin Huh
- Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea; (Y.R.K.); (J.-H.K.); (K.H.); (S.Y.C.); (C.-I.K.); (K.R.P.)
- Asia Pacific Foundation for Infectious Diseases (APFID), Seoul 06367, Republic of Korea
| | - Sun Young Cho
- Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea; (Y.R.K.); (J.-H.K.); (K.H.); (S.Y.C.); (C.-I.K.); (K.R.P.)
| | - Cheol-In Kang
- Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea; (Y.R.K.); (J.-H.K.); (K.H.); (S.Y.C.); (C.-I.K.); (K.R.P.)
| | - Kyong Ran Peck
- Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea; (Y.R.K.); (J.-H.K.); (K.H.); (S.Y.C.); (C.-I.K.); (K.R.P.)
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19
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Chen F, Schiffer NE, Song J. Animal Models of Orthopedic Implant-Associated Infections and Revisions. ACS Biomater Sci Eng 2025; 11:2052-2068. [PMID: 40125564 PMCID: PMC11996597 DOI: 10.1021/acsbiomaterials.4c02331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/25/2025]
Abstract
Orthopedic implant-associated infections such as prosthetic joint infections (PJIs) lead to devastating complications for patients and impose significant financial burdens on the healthcare systems. Although the primary orthopedic implant associated infection rate is relatively low (0.3-9%), the reinfection rate after implant revisions can be as high as 20% to 40%. To evaluate novel therapeutic strategies for preventing and treating infections associated with primary and revision implants, it is essential to develop appropriate animal models that closely emulate clinical realities. Here we discuss existing animal models developed for orthopedic implant revision surgeries including small animal models in rats and mice, and larger animal models in rabbits, sheep, and mini-pigs. While larger animal models offer the advantage of more closely mimicking human surgical procedures, implant dimensions, and infection treatment protocols, rodent models are more cost-effective and better suited for screening experimental prophylaxes and therapeutics. Existing animal revision models have focused on primary infections established by Staphylococcal aureus (S. aureus) and revisions involving both one-stage and two-stage procedures. Further development of smaller animal implant revision models that implement more clinically relevant surgical procedures and recapitulate polymicrobial infections could facilitate the discovery and more rigorous evaluation of novel implant coating prophylaxes and therapeutics for reducing reinfection rates following implant revisions.
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Affiliation(s)
- Feiyang Chen
- Department of Orthopedics and Physical Rehabilitation, Department of Biochemistry and Molecular Biotechnology, UMass Chan Medical School, Worcester, Massachusetts 01655, United States
| | - Naomi E. Schiffer
- Department of Orthopedics and Physical Rehabilitation, Department of Biochemistry and Molecular Biotechnology, UMass Chan Medical School, Worcester, Massachusetts 01655, United States
| | - Jie Song
- Department of Orthopedics and Physical Rehabilitation, Department of Biochemistry and Molecular Biotechnology, UMass Chan Medical School, Worcester, Massachusetts 01655, United States
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20
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Cortés-Penfield NW, Justo JA, McCreary EK, Ryder JH. Optimizing Antibiotic Therapy in Musculoskeletal Infections. Infect Dis Clin North Am 2025:S0891-5520(25)00014-5. [PMID: 40221230 DOI: 10.1016/j.idc.2025.02.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/14/2025]
Abstract
Research into the optimal antibiotic management of musculoskeletal infections has advanced tremendously over the past quarter century, including over a dozen randomized controlled trials and numerous observational studies. This review examines the rationale for and evidence base supporting modern approaches to antibiotic decision making and stewardship in orthopedic infections. Specific practice advances discussed include the increased and earlier use of oral antibiotics, other principles of antibiotic selection (eg, the notion of "bone penetration" and novel local antimicrobial strategies), individualizing durations of therapy, and increasingly selective approaches to empiric antipseudomonal therapy, suppressive antibiotic therapy, and periprocedural antimicrobial prophylaxis following arthroplasty.
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Affiliation(s)
| | - Julie Ann Justo
- Department of Pharmacy, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
| | - Erin K McCreary
- Division of Infectious Diseases, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Jonathan H Ryder
- Division of Infectious Diseases, University of Nebraska Medical Center, Omaha, NE, USA
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21
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Macaux L, Levavasseur B, Kerroumi Y, Aubert T, Prunel M, Heym B, Marmor S, Zeller V. Hip-resection arthroplasty: A valuable treatment for complex hip prosthetic joint infection? Orthop Traumatol Surg Res 2025:104243. [PMID: 40220784 DOI: 10.1016/j.otsr.2025.104243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Revised: 03/27/2025] [Accepted: 04/09/2025] [Indexed: 04/14/2025]
Abstract
INTRODUCTION Management of recurrent hip prosthetic joint infection (PJI) is challenging. Hip-resection arthroplasty is a last-choice rescue strategy for complex PJI. The main objective was to assess prospectively the mid-term infectious and functional PJI outcomes of patients managed with hip-resection arthroplasty. HYPOTHESIS In complex multi-operated PJI, hip-resection arthroplasty may cure the infection without any major impact on hip function, which is often already very limited. MATERIAL AND METHODS This prospective cohort study conducted in a French Referral Center for bone-and-joint infections included all hip PJIs treated with hip-resection arthroplasty from 2004 to 2019. Patients were followed for at least 2 years, with recording of the following events: reinfection, including relapse or new infection, and PJI-related death. Hip functional status was assessed with the modified Merle d'Aubigné-Postel (mMAP) score. The primary outcome was 2-year event-free survival (EFS). The secondary outcomes were the 4- and 6-year EFS rates and hip functional status at 2 years. RESULTS We included 30 patients: median age, 65 years; 39% women. Median [IQR] PJI duration was 15 [4-39] months and patients underwent a median of 5 surgical procedures before resection arthroplasty. The 2-year reinfection free-survival was 89.2% (95% CI: 70.2-96.4). After a median follow-up of 70 [32-103] months, we observed: 1 relapse, 4 new infections, 7 revisions for mechanical reasons and 1 PJI-related death. Median mMAP score 2 years postsurgery was 12, versus 7 before; pain reduction was the main benefit of resection arthroplasty. DISCUSSION Hip-resection arthroplasty achieves sepsis and pain control, and can be a valuable last-line rescue strategy for patients with complex or recurrent hip PJIs. LEVEL OF EVIDENCE II; monocentric prospective cohort.
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Affiliation(s)
- Lou Macaux
- Centre de Référence des Infections Ostéo-Articulaires Complexes, Groupe Hospitalier Diaconesses Croix Saint-Simon, 125 rue d'Avron, 75020 Paris, France; Laboratoire des Centres de Santé et Hôpitaux Île-de-France, Groupe Hospitalier Diaconesses Croix Saint-Simon, 125 rue d'Avron, 75020 Paris, France
| | - Benjamin Levavasseur
- Centre de Référence des Infections Ostéo-Articulaires Complexes, Groupe Hospitalier Diaconesses Croix Saint-Simon, 125 rue d'Avron, 75020 Paris, France
| | - Younes Kerroumi
- Centre de Référence des Infections Ostéo-Articulaires Complexes, Groupe Hospitalier Diaconesses Croix Saint-Simon, 125 rue d'Avron, 75020 Paris, France
| | - Thomas Aubert
- Centre de Référence des Infections Ostéo-Articulaires Complexes, Groupe Hospitalier Diaconesses Croix Saint-Simon, 125 rue d'Avron, 75020 Paris, France; Service de Chirurgie Osseuse et Traumatologique, Groupe Hospitalier Diaconesses Croix Saint-Simon, 125 rue d'Avron, 75020 Paris, France
| | - Maiwenn Prunel
- Centre de Référence des Infections Ostéo-Articulaires Complexes, Groupe Hospitalier Diaconesses Croix Saint-Simon, 125 rue d'Avron, 75020 Paris, France
| | - Beate Heym
- Centre de Référence des Infections Ostéo-Articulaires Complexes, Groupe Hospitalier Diaconesses Croix Saint-Simon, 125 rue d'Avron, 75020 Paris, France; Laboratoire des Centres de Santé et Hôpitaux Île-de-France, Groupe Hospitalier Diaconesses Croix Saint-Simon, 125 rue d'Avron, 75020 Paris, France
| | - Simon Marmor
- Centre de Référence des Infections Ostéo-Articulaires Complexes, Groupe Hospitalier Diaconesses Croix Saint-Simon, 125 rue d'Avron, 75020 Paris, France; Service de Chirurgie Osseuse et Traumatologique, Groupe Hospitalier Diaconesses Croix Saint-Simon, 125 rue d'Avron, 75020 Paris, France
| | - Valérie Zeller
- Centre de Référence des Infections Ostéo-Articulaires Complexes, Groupe Hospitalier Diaconesses Croix Saint-Simon, 125 rue d'Avron, 75020 Paris, France.
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22
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Frank FA, Müller AM, Morgenstern M, Kuehl R, Clauss M. Current Concepts in Shoulder Periprosthetic Joint Infections-Are Shoulders the Same as Hips and Knees? J Clin Med 2025; 14:2578. [PMID: 40283408 PMCID: PMC12028255 DOI: 10.3390/jcm14082578] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Revised: 03/28/2025] [Accepted: 04/07/2025] [Indexed: 04/29/2025] Open
Abstract
Background/Objectives: The vast amount of research and data on periprosthetic joint infection (PJI) is focussed on infections in hip and knee replacements. This article aims to highlight the special features of PJI in shoulders. Methods: This narrative review is based on the recent and most relevant literature regarding PJI in general, and in shoulders in particular. Results: While the majority of findings for PJI in hips and knees can be transferred to infected shoulder arthroplasties, shoulder PJI represents a unique entity with a different microbial profile and its own diagnostic challenges. Conclusions: As profound evidence for shoulder PJI is lacking, diagnostic and therapeutic algorithms should be transferred from those for PJI in hips and knees. Further research is necessary to determine optimal management of shoulder PJI.
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Affiliation(s)
- Florian August Frank
- Center for Musculoskelettal Infections (ZMSI), University Hospital Basel, 4031 Basel, Switzerland; (F.A.F.); (M.M.); (R.K.)
- Department of Orthopaedic Surgery and Traumatology, University Hospital Basel, 4031 Basel, Switzerland;
| | - Andreas Marc Müller
- Department of Orthopaedic Surgery and Traumatology, University Hospital Basel, 4031 Basel, Switzerland;
| | - Mario Morgenstern
- Center for Musculoskelettal Infections (ZMSI), University Hospital Basel, 4031 Basel, Switzerland; (F.A.F.); (M.M.); (R.K.)
- Department of Orthopaedic Surgery and Traumatology, University Hospital Basel, 4031 Basel, Switzerland;
| | - Richard Kuehl
- Center for Musculoskelettal Infections (ZMSI), University Hospital Basel, 4031 Basel, Switzerland; (F.A.F.); (M.M.); (R.K.)
- Department of Infectious Diseases, University Hospital Basel, 4031 Basel, Switzerland
| | - Martin Clauss
- Center for Musculoskelettal Infections (ZMSI), University Hospital Basel, 4031 Basel, Switzerland; (F.A.F.); (M.M.); (R.K.)
- Department of Orthopaedic Surgery and Traumatology, University Hospital Basel, 4031 Basel, Switzerland;
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23
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Cartau T, Michon J, Verdon R, Baldolli A. Oral tetracyclines for bone and joint infections: what do we know? J Bone Jt Infect 2025; 10:143-154. [PMID: 40385556 PMCID: PMC12082486 DOI: 10.5194/jbji-10-143-2025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Accepted: 05/12/2025] [Indexed: 05/20/2025] Open
Abstract
Background and aim: Complex bone and joint infections (BJIs), including prosthetic joint infections (PJIs) and infections associated with osteosynthetic materials, present significant treatment challenges that often require surgical intervention and prolonged antibiotic therapy. In France, the incidence of PJIs in knee and hip arthroplasties ranges from 0.79 % to 2.4 %, with staphylococci being the primary pathogens involved. Recent studies have suggested that oral antibiotic therapy may be as effective as intravenous therapy and that 12 weeks of antibiotic treatment are needed. Tetracyclines, particularly doxycycline and minocycline, are of interest because of their broad-spectrum activities, good oral bioavailability, and potential efficacy in treating BJIs. We aimed to provide a literature review on the role of oral tetracyclines in the management of BJIs. Method: We performed a systematic review of the literature identified via an electronic search of PubMed and ScienceDirect. Results: A total of 648 articles were screened, and 31 studies were included. Pharmacological studies demonstrated that the bone to blood penetration ratio ranged from 0.06 to 0.75. Less than 20 % of strains implicated in BJIs exhibited resistance to oral tetracyclines. Four studies demonstrated potential inhibition of strain growth. Eight studies that included 62 patients reported curative treatment, with a success rate ranging from 82 % to 100 % for PJIs regardless of the surgical management. For suppressive therapy, 10 studies that included 201 patients reported success rates ranging from 57 % to 100 %. The rate of adverse effects ranged from 0 % to 14 % for curative treatment and from 0 % to 57 % for suppressive treatment, leading to treatment discontinuation in less than 20 % of cases. Conclusion: This review highlights that the number of studies supporting the use of oral tetracyclines for the treatment of BJIs is limited. More robust pharmacological and clinical studies are needed to confirm the safety and efficacy profiles of oral tetracyclines for the treatment of BJIs.
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Affiliation(s)
- Tom Cartau
- CHU de Caen, Infectious Diseases Department, Avenue de la Côte de Nacre, Caen, 14000 France
- Reference Center for Complex Bone and Joint Infection, Avenue de la Côte de Nacre, Caen, 14000 France
| | - Jocelyn Michon
- CHU de Caen, Infectious Diseases Department, Avenue de la Côte de Nacre, Caen, 14000 France
- Reference Center for Complex Bone and Joint Infection, Avenue de la Côte de Nacre, Caen, 14000 France
| | - Renaud Verdon
- CHU de Caen, Infectious Diseases Department, Avenue de la Côte de Nacre, Caen, 14000 France
- Reference Center for Complex Bone and Joint Infection, Avenue de la Côte de Nacre, Caen, 14000 France
- Calvados, Normandie University, UNICAEN, CHU de Caen Normandie, Caen, Normandy, 14000 France
- INSERM U1311 DynaMicURe, Normandie University, UNICAEN, UNIROUEN, Caen, France
| | - Aurelie Baldolli
- CHU de Caen, Infectious Diseases Department, Avenue de la Côte de Nacre, Caen, 14000 France
- Reference Center for Complex Bone and Joint Infection, Avenue de la Côte de Nacre, Caen, 14000 France
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Sebastian S, Parvizi J, Hofstaetter JG. Diagnostic Guidelines for Periprosthetic Joint Infection: Know the Differences. J Arthroplasty 2025:S0883-5403(25)00320-1. [PMID: 40189076 DOI: 10.1016/j.arth.2025.03.084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2025] [Revised: 03/26/2025] [Accepted: 03/27/2025] [Indexed: 05/12/2025] Open
Affiliation(s)
- Sujeesh Sebastian
- Michael Ogon Laboratory for Orthopedic Research, Orthopedic Hospital Vienna Speising, Vienna, Austria
| | - Javad Parvizi
- Department of International Joint Center, Acibadem Maslak Hospital, Acibadem University, Maslak, Istanbul, Turkey
| | - Jochen G Hofstaetter
- Michael Ogon Laboratory for Orthopedic Research, Orthopedic Hospital Vienna Speising, Vienna, Austria; Second Department, Orthopedic Hospital Vienna Speising, Vienna, Austria
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25
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Ludwig M, Fuchs M, Trappe O, Oltmanns M, Reichel H, Freitag T. Unexpected Positive Cultures During Aseptic Hip and Knee Revision Arthroplasty: Substantial Discrepancies in Laboratory Analyses. Antibiotics (Basel) 2025; 14:372. [PMID: 40338268 PMCID: PMC12023968 DOI: 10.3390/antibiotics14040372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2025] [Revised: 03/05/2025] [Accepted: 03/31/2025] [Indexed: 05/09/2025] Open
Abstract
Background: Microbial analysis of tissue samples represents an important diagnostic tool in the course of revision total joint arthroplasty. Currently, unexpected positive intraoperative cultures are commonly observed during presumed aseptic revision surgery and evoke a degree of uncertainty among physicians. To date, it is unclear if there are deviations in pathogen detection between certified laboratories. Methods: Tissue samples of sixty consecutive patients undergoing presumably aseptic total hip and knee revision surgery were sent to two different internationally certified accredited laboratories and tested for any microbial growth as well as pathogen differentiation. Results: Each laboratory analyzed 300 samples. Laboratory 1 observed an unexpected positive culture rate of 16.7%; laboratory 2 indicated that 18.3% of all processed specimens showed pathogen growth. In comparison, a consistent microbial evaluation was only present in one patient. The kappa correlation coefficient showed a poor correlation between the two laboratories in all evaluated categories. Coagulase-negative staphylococci represented the most common pathogens of laboratory 1, while laboratory 2 predominantly observed cutibacterium acnes species. Within a mean follow-up period of 17.6 ± 18.6 months (range: 0-63 months), there was no revision due to periprosthetic joint infection. Conclusions: Unexpected positive culture results during presumed aseptic revision surgery remain a significant clinical challenge. This study is the first of its kind to evaluate the convergence of laboratory findings in the context of aseptic revision surgery. Our results suggest that even established and certified laboratories show substantial discrepancies. Thus, a careful interpretation of unexpected bacterial cultures after revision surgery is mandatory. Given the uncertainty inherent in laboratory findings, a precise clinical and histopathological evaluation of this patient cohort should be ensured.
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Affiliation(s)
| | | | | | | | | | - Tobias Freitag
- Department of Orthopedic Surgery, University of Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany
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26
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Cojutti PG, Gatti M, Tedeschi S, Zamparini E, Meschiari M, Danzi M, Menegotto G, Cotrufo M, Soavi L, Chiari E, Ripa M, Mazzitelli M, Crapis M, Cattelan A, Parruti G, Russo A, Zammarchi L, Tascini C, Viale P, Pea F. Usefulness of a hub and spoke TDM-guided expert clinical pharmacological advice program of dalbavancin for optimizing very long-term curative or suppressive treatment of chronic staphylococcal infections. Antimicrob Agents Chemother 2025; 69:e0183024. [PMID: 39992102 PMCID: PMC11963596 DOI: 10.1128/aac.01830-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Accepted: 01/17/2025] [Indexed: 02/25/2025] Open
Abstract
A hub and spoke model for optimizing long-term treatment of chronic staphylococcal infections with dalbavancin based on therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) was implemented. This multicentric retrospective cohort study included patients receiving dalbavancin monotherapy lasting >6 weeks at different spoke hospitals having treatment optimized by means of a TDM-guided ECPA program at a hub hospital. Optimal pharmacokinetic/pharmacodynamic target against staphylococci with an MIC up to 0.125 mg/L was defined as dalbavancin concentrations >8.04 mg/L. Patients received dalbavancin therapy for curative (curative group) or suppressive (suppressive group) purposes. Clinical outcome was assessed by means of repeated ambulatory visits. A total of 12 spoke hospitals applied for 414 TDM-based ECPA for 101 patients, of whom 64.4% (65/101) were treated for curative and 35.6% (36/101) were for suppressive purposes. In the curative and suppressive groups, TDM-based ECPA optimized treatment for up to 14 and 28 months, respectively, and ensured median optimal exposure of 95.7% and 100%, respectively. In the curative group, having <70% of treatment time with concentrations above the optimal target increased failure risk [odds ratio (OR), 6.71; confidence interval (CI), 0.97-43.3; P = 0.05]. In the suppressive group, infective endocarditis was associated with an increased risk of ineffective treatment (OR, 8.65; CI, 1.29-57.62; P = 0.046). Mild adverse events were reported in 4.5% (5/101) of cases. A hub and spoke TDM-guided ECPA program of dalbavancin may be cost-effective for optimizing long-term treatment of chronic staphylococcal infections and for patients admitted to hospitals lacking in-house MD clinical pharmacologists.
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Affiliation(s)
- Pier Giorgio Cojutti
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
- Clinical Pharmacology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Milo Gatti
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
- Clinical Pharmacology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Sara Tedeschi
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
- Infectious Diseases Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Eleonora Zamparini
- Infectious Diseases Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Marianna Meschiari
- Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Maria Danzi
- Unit of Infectious Diseases, Santa Chiara Hospital, APSS, Trento, Italy
| | - Giacomo Menegotto
- Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Marco Cotrufo
- Infectious Diseases Clinic, Santa Maria della Misericordia University Hospital of Udine, ASUFC, Udine, Italy
| | - Laura Soavi
- UOC Malattie Infettive, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Erika Chiari
- Division of Infectious and Tropical Diseases, ASST Spedali Civili, Brescia, Italy
| | - Marco Ripa
- Infectious Diseases Unit, Vita-Salute San Raffaele University, Milan, Italy
- Infectious Diseases Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Maria Mazzitelli
- Infectious and Tropical Diseases Unit, Padua University Hospital, Padua, Italy
| | - Massimo Crapis
- Infectious Diseases Unit, S. Maria degli Angeli Hospital, Pordenone, Italy
| | - Annamaria Cattelan
- Infectious and Tropical Diseases Unit, Padua University Hospital, Padua, Italy
| | - Giustino Parruti
- Infectious Diseases Unit, Pescara General Hospital, Pescara, Italy
| | - Alessandro Russo
- Department of Medical and Surgical Sciences, "Magna Graecia" University, Catanzaro, Italy
- Infectious and Tropical Disease Unit, "Renato Dulbecco" Teaching Hospital, Catanzaro, Italy
| | - Lorenzo Zammarchi
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
- Department of Infectious and Tropical Diseases, Azienda Ospedaliero Universitaria Careggi, Florence, Italy
| | - Carlo Tascini
- Infectious Diseases Clinic, Santa Maria della Misericordia University Hospital of Udine, ASUFC, Udine, Italy
- Department of Medical Area, University of Udine, Udine, Italy
| | - Pierluigi Viale
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
- Infectious Diseases Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Federico Pea
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
- Clinical Pharmacology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
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Putnam NE, Charles DW, Doub JB, Johnson JK. Broad-range polymerase chain reaction and sequencing for the diagnosis of infectious diseases. Microbiol Spectr 2025; 13:e0250524. [PMID: 40042284 PMCID: PMC11960090 DOI: 10.1128/spectrum.02505-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Accepted: 01/22/2025] [Indexed: 04/03/2025] Open
Abstract
Broad-range polymerase chain reaction (BR-PCR) identifies molecular signatures of microorganisms directly from clinical specimens without requiring microbial growth in culture. BR-PCR may be a powerful tool to reveal microbial causes of infectious diseases, but the impact on diagnosis and clinical management has yet to be fully defined. Consequently, the aims here were to investigate how bacterial, fungal, and mycobacterial (AFB) BR-PCR perform compared to microbiology culture methods in detecting microorganisms and to assess clinical utility, defined as the ability of the results to change antimicrobial therapy or treatment duration. Between 2018 and 2021, 348 unique specimens were sent from 327 patients seen within the University of Maryland Medical System (UMMS). Patient charts were reviewed retrospectively. Organisms identified by BR-PCR were compared to bacterial (n = 302), fungal (n = 137), and AFB (n = 111) cultures to determine concordance and were evaluated to determine if they led to a change in clinical management. Agreement in organism(s) reported by BR-PCR and culture was considered concordant for calculating performance data. Sensitivity of BR-PCR compared to concordant culture results was 30.9% for bacteria (25/81; 95% CI: 21.8-41.6%), 18.8% for fungi (3/16; 95% CI: 5.8-43.8%), and 33.3% for AFB (1/3; 95% CI: 5.6-79.8%) detection. The bacterial negative percent agreement of 80.1% (165/206) may reflect antibiotic pretreatment or detection of fastidious organisms. Despite longer turnaround times, BR-PCR results changed clinical care in 6% of cases. Based on these findings herein, the clinical use of BR-PCR would be best utilized when fastidious organisms are suspected, or specimens remain culture negative, but should not replace routine culture methods at this time.IMPORTANCEDetermining infectious etiology can be challenging in patients with chronic presentation and in those receiving empiric therapy. In addition to the standard of care (microbiology cultures), providers can order a broad-range polymerase chain reaction and sequencing (BR-PCR) test to identify microorganisms directly from clinical specimens and independently from culture. While studies have been done from individual hospitals or systems, there is a lack of broadly applicable clinical evidence detailing clinical scenarios in which BR-PCR should be utilized. This study adds to the growing body of literature surrounding BR-PCR clinical usage, examining assay performance and clinical utility of BR-PCR test results. Although BR-PCR and culture had low concordance among organisms identified, it was shown to complement the standard of care for uncommonly isolated and fastidious organisms. Overall, BR-PCR results changed clinical management in 6% of cases, which is similar to other studies that include a broad representation of specimen types.
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Affiliation(s)
- Nicole E. Putnam
- Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland, USA
- Clinical Microbiology Laboratory, Laboratories of Pathology, University of Maryland Medical Center, Baltimore, Maryland, USA
| | - Drew W. Charles
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland, USA
- Division of Infectious Disease, Medical University of South Carolina, Charleston, South Carolina, USA
| | - James B. Doub
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - J. Kristie Johnson
- Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland, USA
- Clinical Microbiology Laboratory, Laboratories of Pathology, University of Maryland Medical Center, Baltimore, Maryland, USA
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Fu FS, Chen HH, Chen Y, Yuan Y, Zhao Y, Yu A, Zhang XZ. Engineered bacillus subtilis enhances bone regeneration via immunoregulation and anti-Infection. Bioact Mater 2025; 46:503-515. [PMID: 39868074 PMCID: PMC11760808 DOI: 10.1016/j.bioactmat.2025.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2024] [Revised: 12/18/2024] [Accepted: 01/02/2025] [Indexed: 01/28/2025] Open
Abstract
Chronic osteomyelitis caused by implant infections is a common complication following orthopedic surgery. Preventing bacterial infection and simultaneously improving bone regeneration are the key for osteomyelitis. Current treatments include systemic antibiotics and multiple surgical interventions, but the strategies available for treatment are limited. In this study, a multifunctional engineered Bacillus subtilis (B. sub) hydrogel with sulfasalazine (SSZ) is developed to treat methicillin-resistant Staphylococcus aureus (MRSA) infection and anti-inflammatory and promote bone regeneration. B. sub in alginate hydrogels protects B. sub from being cleared by the host immune system while allowing the release of its bioactive substances, including antibacterial peptides and anti-inflammatory agents such as SSZ. The results show that the engineered probiotic hydrogels exhibit excellent antibacterial efficacy against MRSA (97 %) and prevent the development of bacterial resistance. The antibacterial effect is primarily mediated through the secretion of bioactive peptides by B. sub, which not only inhibit MRSA growth but also reduce the likelihood of resistance development. Meanwhile, the probiotic hydrogel has a greater ability to induce M2 polarization of macrophages and promote angiogenesis, resulting in enhanced osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs) and thus enhancing bone regeneration. This engineered probiotic hydrogel offers a promising strategy by simultaneously combating bacterial infection and enhancing osteogenic differentiation for chronic osteomyelitis.
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Affiliation(s)
- Fang-Sheng Fu
- Department of Orthopedic Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, PR China
| | - Huan-Huan Chen
- Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan, 430072, PR China
- State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Key Laboratory of Industrial Biotechnology, School of Life Sciences, Hubei University, Wuhan, 430062, PR China
| | - Yu Chen
- Department of Orthopedic Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, PR China
| | - Ying Yuan
- Department of Orthopedic Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, PR China
| | - Yong Zhao
- Department of Orthopedic Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, PR China
| | - Aixi Yu
- Department of Orthopedic Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, PR China
| | - Xian-Zheng Zhang
- Department of Orthopedic Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, PR China
- Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan, 430072, PR China
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29
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Guo X, Ji B, Zhang X, Li Y, Chen Q, Cao L. High-Dose Compound Betamethasone Used in Local Infiltration Analgesia Does Not Increase Reinfection Rates Following Periprosthetic Joint Infection Treatment. J Arthroplasty 2025; 40:1028-1033. [PMID: 39370016 DOI: 10.1016/j.arth.2024.09.042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Revised: 09/26/2024] [Accepted: 09/27/2024] [Indexed: 10/08/2024] Open
Abstract
BACKGROUND Cocktails containing glucocorticoids for local infiltration analgesia (LIA) are highly advocated and effective in managing pain in total joint arthroplasty (TJA). However, it remains ambiguous whether this protocol maintains its safety and efficacy in the treatment of periprosthetic joint infection (PJI), a devastating complication of TJA. METHODS A retrospective study was conducted on 299 single-stage revision cases for PJI spanning the years 2010 to 2021. Of these, 127 received LIAs containing high-dose compound betamethasone (CB) were termed the CB group, and the other 172 were termed the non-CB group. The rates of re-infection and other postoperative complications, along with postoperative visual analog scale (VAS) scores, and opioid consumption were compared. RESULTS During minimum 2-year follow-up, there was no significant difference in the re-infection rate between the non-CB and CB groups (9.3 versus 8.7%; P = 0.85), consistent within the subsets of hip (8.4 versus 4.5%; P = 0.51) and knee (10.4 versus 13.3%; P = 0.60) PJIs individually. The administration of high-dose CB was neither an independent risk factor for reinfection (P > 0.05; 95% CI [confidence interval] including 1) nor was it associated with the occurrence of reinfection (P > 0.05). The incidence of postoperative nausea and vomiting (PONV) was significantly lower in the CB group (P < 0.05). In the first 48-hour postoperative period, the CB group exhibited lower mean scores in both resting and movement VAS evaluations (P < 0.05). For knees, the movement VAS scores of the CB group remained lower even at 72 hours post-surgery (P < 0.001). Furthermore, within the first 72 hours post-surgery, the CB group required less additional opioid analgesics than the non-CB group (P < 0.05). CONCLUSIONS A LIA with a high-dose CB reduces postoperative pain, opioid consumption, and the incidence of PONV following a single-stage revision without affecting reinfection and other complication rates.
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Affiliation(s)
- Xiaobin Guo
- Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Baochao Ji
- Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Xiaogang Zhang
- Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Yicheng Li
- Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Quan Chen
- Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Li Cao
- Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
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Trebše A, Roškar S, Mihelič A, Trebše R. Good Results for PJI Caused by Corynebacterium spp. After Algorithmic Surgical Approach and Rifampicin Combination in Implant Retention. Open Forum Infect Dis 2025; 12:ofaf146. [PMID: 40160343 PMCID: PMC11953024 DOI: 10.1093/ofid/ofaf146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Accepted: 03/06/2025] [Indexed: 04/02/2025] Open
Abstract
Background Corynebacterium spp. is a rare culprit in periprosthetic joint infections (PJIs), with limited data available on outcomes and appropriate treatment course. The aim of this study was to evaluate the success rate of a clinical cohort of patients with PJI, where Corynebacterium spp. was the causative organism (CPJI), treated according to an institutional algorithm based upon European Bone and Joint Infection Society guidelines. Methods From the institutional bone infection registry, 44 patients treated for CPJI between 2007 and 2023 were identified. CPJIs were divided into 2 groups according to the isolated microbes: monomicrobial (14 [32%]) and polymicrobial (30 [68%]). Patients were treated with debridement, antibiotics, and implant retention (DAIR; 14 [32%]) or with 1- or 2-stage implant exchange (reimplantation group; 30 [68%]). In 13 (30%) cases, antibiotic combination with rifampicin was used. Results Out of 44 patients, 4 required further treatment. In monomicrobial CPJI, the treatment course was successful in all patients, whereas in polymicrobial CPJI it was successful in 87%. Antibiotic combination including rifampicin was used in 4 monomicrobial cases (29%) and 9 polymicrobial (30%) cases. In the polymicrobial group, DAIR was successful in 90% (9/10), while the reimplantation group had an 85% (17/20) success rate. Conclusions In contrast with the previously published papers on CPJI, the results in our cohort were good, with the total cure rate being 91%. The cure rate was slightly lower in the polymicrobial group compared with the monomicrobial: 87% and 100%, respectively. Surgical therapy according to the established institutional algorithm resulted in a high success rate.
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Affiliation(s)
- Ana Trebše
- University Medical Centre Ljubljana, Ljubljana, Slovenia
| | - Samo Roškar
- Valdoltra Orthopaedic Hospital, Ankaran, Slovenia
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Anže Mihelič
- Valdoltra Orthopaedic Hospital, Ankaran, Slovenia
| | - Rihard Trebše
- Valdoltra Orthopaedic Hospital, Ankaran, Slovenia
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
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Lorenzo MP, Adams KK, Housman ST. Common Bacterial Infections in Persons Who Inject Drugs. MEDICINES (BASEL, SWITZERLAND) 2025; 12:8. [PMID: 40265354 PMCID: PMC12015887 DOI: 10.3390/medicines12020008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Revised: 03/17/2025] [Accepted: 03/21/2025] [Indexed: 04/24/2025]
Abstract
Opioid use in the United States has increased dramatically. Bacterial infections are common among persons who inject drugs (PWID), and there is a disparity in the care these individuals receive. As such, outcomes associated with these infections can be poor. Healthcare providers can address these disparities through optimal pharmacotherapy recommendations and assistance with changing approaches to the management of PWID.
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Affiliation(s)
| | - Kathleen K. Adams
- School of Pharmacy, University of Connecticut, Storrs, CT 06269, USA;
| | - Seth T. Housman
- Baystate Medical Center, Springfield, MA 01199, USA;
- College of Pharmacy and Health Sciences, Western New England University, Springfield, MA 01119, USA
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Li P, Wang Y, Zhao R, Hao L, Chai W, Jiying C, Feng Z, Ji Q, Zhang G. The Application of artificial intelligence in periprosthetic joint infection. J Adv Res 2025:S2090-1232(25)00199-7. [PMID: 40158619 DOI: 10.1016/j.jare.2025.03.039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2025] [Revised: 03/06/2025] [Accepted: 03/20/2025] [Indexed: 04/02/2025] Open
Abstract
Periprosthetic joint infection (PJI) represents one of the most devastating complications following total joint arthroplasty, often necessitating additional surgeries and antimicrobial therapy, and potentially leading to disability. This significantly increases the burden on both patients and the healthcare system. Given the considerable suffering caused by PJI, its prevention and treatment have long been focal points of concern. However, challenges remain in accurately assessing individual risk, preventing the infection, improving diagnostic methods, and enhancing treatment outcomes. The development and application of artificial intelligence (AI) technologies have introduced new, more efficient possibilities for the management of many diseases. In this article, we review the applications of AI in the prevention, diagnosis, and treatment of PJI, and explore how AI methodologies might achieve individualized risk prediction, improve diagnostic algorithms through biomarkers and pathology, and enhance the efficacy of antimicrobial and surgical treatments. We hope that through multimodal AI applications, intelligent management of PJI can be realized in the future.
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Affiliation(s)
- Pengcheng Li
- Department of Orthopaedics, General Hospital of Chinese People's Liberation Army, Beijing 100853, China
| | - Yan Wang
- Department of Orthopaedics, General Hospital of Chinese People's Liberation Army, Beijing 100853, China
| | - Runkai Zhao
- Department of Orthopaedics, General Hospital of Chinese People's Liberation Army, Beijing 100853, China
| | - Lin Hao
- Department of Orthopaedics, General Hospital of Chinese People's Liberation Army, Beijing 100853, China
| | - Wei Chai
- Department of Orthopaedics, General Hospital of Chinese People's Liberation Army, Beijing 100853, China
| | - Chen Jiying
- Department of Orthopaedics, General Hospital of Chinese People's Liberation Army, Beijing 100853, China
| | - Zeyu Feng
- Department of Orthopaedics, General Hospital of Chinese People's Liberation Army, Beijing 100853, China
| | - Quanbo Ji
- Department of Orthopaedics, General Hospital of Chinese People's Liberation Army, Beijing 100853, China; Beijing National Research Center for Information Science and Technology (BNRist), Beijing, China; Department of Automation, Tsinghua University, Beijing, China.
| | - Guoqiang Zhang
- Department of Orthopaedics, General Hospital of Chinese People's Liberation Army, Beijing 100853, China.
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Varin-Simon J, Haney EF, Colin M, Velard F, Gangloff SC, Hancock REW, Reffuveille F. D-enantiomeric antibiofilm peptides effective against anaerobic Cutibacterium acnes biofilm. Microbiol Spectr 2025; 13:e0252324. [PMID: 40130849 PMCID: PMC12053997 DOI: 10.1128/spectrum.02523-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Accepted: 01/27/2025] [Indexed: 03/26/2025] Open
Abstract
The emergence of antibiotic resistance, biofilm formation, and internalization by host cells contribute to a high risk of chronic infections, highlighting the necessity to develop novel therapeutic strategies. Identification of natural host defense peptides (HDPs) with promising antimicrobial and antibiofilm activities led to the development of synthetic peptides with broad-spectrum efficacy. However, few studies have examined their effect on anaerobic bacterial species. This study aimed to test the effect of synthetic HDPs on Cutibacterium acnes, an anaerobe species involved in 10% of prosthesis joint infections (PJI). A preliminary screen identified three peptides (DJK5, AB009-D, and AB101-D) with promising activity against four C. acnes strains (two of which were isolated from PJI). A bactericidal effect was observed for the three peptides with 50% of planktonic bacteria killing for AB009-D and AB101-D after only 3 hours of contact. DJK5 and AB009-D inhibited the C. acnes adhesion on plastic and titanium supports with a 2-log decrease in bacterial cells. In the presence of peptides, the morphology of C. acnes cells was altered with an increase in cell length observed, especially for one of the non-PJI-related strains. Against mature biofilms, AB101-D was the most effective with an approximate 2-log decrease in adhered CFUs, indicating the induction of bacterial dispersion or death. DJK5 also inhibited C. acnes internalization by osteoblasts, with a reduction of the internalized bacteria quantity for three strains. Overall, this study demonstrates that synthetic HDPs are effective against anaerobic bacteria and hold promise as novel therapeutic candidates to prevent or treat C. acnes PJIs.IMPORTANCEThe emergence of antibiotic tolerance highlights the necessity to develop novel therapeutic strategies with promising antimicrobial but also antibiofilm activities. In this study, we tested the effect of synthetic host defense peptides (HDPs) on Cutibacterium acnes, an anaerobic species, rarely studied, whereas involved in 10% of prosthesis joint infections (PJI). In our study, we demonstrate that the selected synthetic HDPs are effective against this anaerobic bacteria, both as a preventive treatment (effect on planktonic growth, bacterial adhesion, and biofilm formation) and against internalization of C. acnes by osteoblasts, revealing that these peptides are promising as novel therapeutic candidates to prevent or treat C. acnes PJIs.
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Affiliation(s)
- Jennifer Varin-Simon
- Université de Reims Champagne-Ardenne, BIOS, Reims, Grand Est, France
- Université de Reims Champagne-Ardenne, UFR Pharmacie, Reims, Grand Est, France
| | - Evan F. Haney
- Asep Medical Inc./ABT Innovations Inc., Victoria, British Columbia, Canada
- Department of Microbiology and Immunology, Center for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, British Columbia, Canada
| | - Marius Colin
- Université de Reims Champagne-Ardenne, BIOS, Reims, Grand Est, France
- Université de Reims Champagne-Ardenne, UFR Pharmacie, Reims, Grand Est, France
| | - Frédéric Velard
- Université de Reims Champagne-Ardenne, BIOS, Reims, Grand Est, France
| | - Sophie C. Gangloff
- Université de Reims Champagne-Ardenne, BIOS, Reims, Grand Est, France
- Université de Reims Champagne-Ardenne, UFR Pharmacie, Reims, Grand Est, France
| | - Robert E. W. Hancock
- Asep Medical Inc./ABT Innovations Inc., Victoria, British Columbia, Canada
- Department of Microbiology and Immunology, Center for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, British Columbia, Canada
| | - Fany Reffuveille
- Université de Reims Champagne-Ardenne, BIOS, Reims, Grand Est, France
- Université de Reims Champagne-Ardenne, UFR Pharmacie, Reims, Grand Est, France
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Johns B, Loewenthal M, Dewar D, Manning L, Davis J. Comparison of surgical treatments for hip and knee periprosthetic joint infections using the desirability of outcome ranking in a prospective multicentre study. J Bone Jt Infect 2025; 10:73-84. [PMID: 40271507 PMCID: PMC12015177 DOI: 10.5194/jbji-10-73-2025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2024] [Accepted: 01/13/2025] [Indexed: 04/25/2025] Open
Abstract
Introduction: In periprosthetic joint infection (PJI), there is a paucity of prospective data comparing debridement, antibiotics and implant retention (DAIR) with two-stage revision while also accounting for time since the initial arthroplasty. Additionally, comparisons often lack patient-centred measures. A desirability of outcome ranking for PJI (DOOR-PJI) unifies joint function, infection cure and mortality into one outcome. We aimed to describe the DOOR-PJI distribution in a large patient cohort and use it to compare DAIR and two-stage revision. Methods: Adults with a newly diagnosed hip or knee PJI from the prospective Prosthetic joint Infection in Australia and New Zealand Observational (PIANO) study were analysed. Patients from 27 hospitals were included. PJI was classified as "early" or "late". The primary outcome was the novel DOOR-PJI at the 2-year follow-up. Results were expressed using win ratio (WR) values. A WR > 1.0 indicates that two-stage revision was superior to DAIR. Results: A DOOR was available for 533 patients. The most common treatments were DAIR (297 patients, 56 %) and two-stage revision (139 patients, 26 %). In early PJI, DAIR was superior to two-stage revision (WR 0.51, 95 % confidence interval (CI) [0.30-0.86], p = 0.012). In late PJI, two-stage revision was superior to DAIR (WR 1.61, 95 % CI [1.11-2.33], p = 0.012). These findings persisted following stratification by comorbidities, affected joint, symptom duration and a sensitivity analysis applying the initial (rather than the main) surgical strategy at day 90. Conclusions: In the first application of a DOOR in orthopaedics, DAIR was superior to two-stage revision for early PJI. Conversely, two-stage revision was superior compared with DAIR for late PJI. These findings were independent of comorbidities and symptom duration.
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Affiliation(s)
- Brenton P. Johns
- The Bone and Joint Institute, Royal Newcastle Centre, Newcastle, NSW, Australia
- School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
| | - Mark R. Loewenthal
- Department of Immunology and Infectious Diseases, Royal Newcastle Centre, Newcastle, NSW, Australia
- School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
| | - David C. Dewar
- The Bone and Joint Institute, Royal Newcastle Centre, Newcastle, NSW, Australia
- School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
| | - Laurens A. Manning
- Faculty of Health and Medical Sciences, University of Western Australia, Perth, WA, Australia
- Department of Infectious Diseases, Fiona Stanley Hospital, Murdoch, WA, Australia
| | - Joshua S. Davis
- Department of Immunology and Infectious Diseases, Royal Newcastle Centre, Newcastle, NSW, Australia
- School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
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Battistella L, Kireche R, Ricco JB, Boisroux T, Shourick J, Chaufour X, Canaud L, Hostalrich A. Outcomes of native or graft abdominal aortic infection managed with orthotopic xeno pericardial grafts or cryopreserved allograft: A French bicentric comparative study. J Vasc Surg 2025:S0741-5214(25)00613-5. [PMID: 40122311 DOI: 10.1016/j.jvs.2025.03.182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2025] [Revised: 03/03/2025] [Accepted: 03/14/2025] [Indexed: 03/25/2025]
Abstract
BACKGROUND The ideal substitute for in situ reconstruction of aortic graft or native aortic infection has yet to be defined. Though recognized as resistant to infection, cryopreserved arterial allograft (Allograft) presents problems of availability when treating emergent cases, with the risk of long-term aneurysmal degeneration. Commercially available bovine pericardial substitutes (Pericard) seems to be an alternative, with promising results in the recent literature. The goal of this study was to compare the results of these two substitutes. METHODS Between January 2010 and December 2023, we conducted a retrospective observational study in two tertiary centers, including all patients having undergone in situ surgery for aortic graft or native aortic infections with reconstruction by Allograft or Pericard. Survival, reinterventions and reinfections were analyzed according to the Kaplan-Meier method and Cox regression model. RESULTS All in all, 169 patients were included in the study with 103 aortic graft infections (60.9%), 33 aortic endograft infections (19.5%), and 33 native aortic infections (19.5%). Allograft was used in 111 patients (65.7%) and Pericard in 58 (34.3%). The two groups were comparable as regards preoperative risk factors, types of index surgery, and infectious agents, with 41 patients (24.8%) with an aortoenteric fistula. There was no significant difference in postoperative complications. The median follow-up was 18 months (interquartile range, 4-44 months). At 24 months, survival was comparable, with 68 ± 4% for Allograft and 68 ± 6 for Pericard, as was reinfection-free survival with 80 ± 4% for Allograft vs 83 ± 6% for Pericard (P = .722). Reintervention-free survival at 2 years was likewise comparable: 86 ± 4% for Allograft vs 77 ± 8% for Pericard (P = .419). CONCLUSIONS A pericardial substitute offers the possibility of in situ aortic reconstruction without the problems of availability and with midterm results comparable with those achieved with aortic allografts. Further studies with long-term follow-up are needed to validate the absence of late reinfection and to confirm pericardial substitute patency.
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Affiliation(s)
- Lucas Battistella
- Department of Vascular Surgery, University Hospital of Rangueil, Toulouse, France
| | - Ramla Kireche
- Department of Vascular Surgery, University Hospital of Montpellier, Montpellier, France
| | - Jean Baptiste Ricco
- Department of Vascular Surgery, University Hospital of Rangueil, Toulouse, France
| | - Thibaut Boisroux
- Department of Vascular Surgery, University Hospital of Rangueil, Toulouse, France
| | - Jason Shourick
- UMR 1295 CERPOP, Inserm, Université Toulouse III - Paul Sabatier, Toulouse, France
| | - Xavier Chaufour
- Department of Vascular Surgery, University Hospital of Rangueil, Toulouse, France
| | - Ludovic Canaud
- Department of Vascular Surgery, University Hospital of Montpellier, Montpellier, France
| | - Aurélien Hostalrich
- Department of Vascular Surgery, University Hospital of Rangueil, Toulouse, France.
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Harley JD, Braman JP, Harrison AK, Rao AJ. A novel process to reduce the cost of admission for treatment of infected shoulder arthroplasty. J Shoulder Elbow Surg 2025:S1058-2746(25)00250-2. [PMID: 40120640 DOI: 10.1016/j.jse.2025.02.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 01/28/2025] [Accepted: 02/10/2025] [Indexed: 03/25/2025]
Abstract
BACKGROUND With the rapidly increasing volume of total joint arthroplasty procedures, the incidence of periprosthetic joint infection (PJI) and its associated economic burden are expected to rise. Two-stage reimplantation, a common strategy for PJI management, is costly, as it requires multiple surgeries and hospitalizations, with total costs ranging from $35,000 to $42,000. Given the long hospital stays required for these patients, a quality improvement project was undertaken at the authors' institution to reduce cost of admission (COA) and length of stay (LOS). METHODS We conducted a retrospective review of patients treated for PJI of the shoulder at a single hospital within a large health system. Patients were included if they had a biopsy-proven shoulder PJI treated with 1 of 2 protocols: a conventional, inpatient focused approach or a new, outpatient focused approach. Conventional management involved prosthesis explantation with intraoperative cultures, antibiotic spacer placement, inpatient infectious disease consultation, and inpatient peripherally inserted central catheter placement. The new protocol consisted of outpatient infectious disease clinic referral and peripherally inserted central catheter placement prior to explantation and spacer placement. COA and LOS were compared between the 2 groups. RESULTS Sixteen patients were included, 8 in each group. Patients managed with the outpatient-focused protocol had a significantly reduced COA ($17,711 ± 4078) compared to the conventional protocol ($24,233 ± 4967) with a mean difference of $6521, representing a 26.9% cost reduction per patient (P = .006). LOS was significantly reduced in the outpatient-focused group (median: 1.35 days; interquartile range: 1.21-1.89) compared to the conventional protocol group (median: 2.52 days; interquartile range: 1.81-3.21) (U = 10.50; Z = -2.26; P = .024). CONCLUSIONS The pilot quality improvement initiative resulted in a 27% reduction in COA and a significantly reduced LOS for patients with shoulder PJI. This has broad implications across orthopedics for the management of periprosthetic joint replacement and potential for tremendous impact of reducing healthcare costs.
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Affiliation(s)
- Jonathan D Harley
- Department of Orthopaedic Surgery, University of Minnesota, Minneapolis, MN, USA.
| | - Jonathan P Braman
- Department of Orthopaedic Surgery, Henry Ford Hospital, Detroit, MI, USA
| | - Alicia K Harrison
- Department of Orthopaedic Surgery, University of Minnesota, Minneapolis, MN, USA
| | - Allison J Rao
- Department of Orthopaedic Surgery, University of Minnesota, Minneapolis, MN, USA
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Sebastian S, Mitterer JA, Ahmed Y, Frank BJH, Simon S, Hofstaetter JG. Synovial absolute polymorphonuclear neutrophil cell count: A simple and inexpensive marker for diagnosing periprosthetic hip and knee joint infections. Knee Surg Sports Traumatol Arthrosc 2025. [PMID: 40100925 DOI: 10.1002/ksa.12652] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Revised: 02/28/2025] [Accepted: 03/04/2025] [Indexed: 03/20/2025]
Abstract
PURPOSE This study aimed to establish the optimal cutoff value for synovial absolute polymorphonuclear neutrophil (APMN) count in distinguishing between septic and aseptic hip and knee revision arthroplasties. We also investigated its effectiveness as an indicator in revision arthroplasties with challenging microbiological findings, including (i) aseptic cases with a single unexpected positive intraoperative culture (UPICs), (ii) septic cases with unexpected negative ICs (UNICs) and (iii) infections caused by high- and low-virulent pathogens. METHODS A total of 616 revision arthroplasties (177:hip, 439:knee) included. Using European Bone and Joint Infection Society (EBJIS) criteria, 325 (52.8%) were classified as infection confirmed, 271 (44%) infection unlikely and 20 (3.2%) as infection likely. International Consensus Meeting (ICM) 2018 criteria classified 308 (50%) as infected, 269 (43.7%) not infected, and 39 (6.3%) as inconclusive. Diagnostic accuracy was assessed through receiver operating characteristic curves and area under the curve (AUC). RESULTS Optimal APMN count thresholds using EBJIS criteria in hip and knee joints were 783.6 cells/µL (AUC: 0.92) and 549 cells/µL (AUC: 0.91), respectively. With the ICM criteria, its optimal cutoff values remained unchanged, except for the knee, which shifted to 594.2 cells/µL. Comparing UPICs to other aseptic cases showed no significant median APMN count differences when both criteria's applied, potentially ruling out infection suspicion. In septic cases, APMN counts differed between UNICs and culture positives but were statistically significant with EBJIS criteria (Hip:p = 0.01, Knee:p = 0.03) but not with ICM (p = 0.08). Median APMN counts were significantly elevated in high-virulent compared to low-virulent organisms, with similar trends in most of the other markers. Compared to alpha-defensin, APMN count exhibited better AUC, sensitivity and negative predictive value. CONCLUSIONS The APMN count represents a simple and inexpensive method that may serve as a complementary diagnostic marker in hip and knee revision arthroplasties with challenging microbiological findings. LEVEL OF EVIDENCE Level III, retrospective study.
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Affiliation(s)
- Sujeesh Sebastian
- Michael Ogon Laboratory for Orthopedic Research, Orthopedic Hospital Vienna Speising, Vienna, Austria
| | - Jennyfer A Mitterer
- Michael Ogon Laboratory for Orthopedic Research, Orthopedic Hospital Vienna Speising, Vienna, Austria
| | - Youssef Ahmed
- Michael Ogon Laboratory for Orthopedic Research, Orthopedic Hospital Vienna Speising, Vienna, Austria
| | - Bernhard J H Frank
- Michael Ogon Laboratory for Orthopedic Research, Orthopedic Hospital Vienna Speising, Vienna, Austria
| | - Sebastian Simon
- Michael Ogon Laboratory for Orthopedic Research, Orthopedic Hospital Vienna Speising, Vienna, Austria
| | - Jochen G Hofstaetter
- Michael Ogon Laboratory for Orthopedic Research, Orthopedic Hospital Vienna Speising, Vienna, Austria
- Second Department, Orthopedic Hospital Vienna Speising, Vienna, Austria
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You TY, Lee NY, Yang TH, Chen PL, Li MC, Su SL, Hsu YW, Ko WC. Culture-negative orthopedic implant-associated infection due to Mycoplasma hominis: A case report. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2025:S1684-1182(25)00069-6. [PMID: 40122737 DOI: 10.1016/j.jmii.2025.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 03/09/2025] [Accepted: 03/15/2025] [Indexed: 03/25/2025]
Affiliation(s)
- Tian-Yu You
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Center for Infection Control, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Nan-Yao Lee
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Center for Infection Control, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Tai-Hua Yang
- Department of Orthopedics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Po-Lin Chen
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Center for Infection Control, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ming-Chi Li
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Center for Infection Control, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Shu-Li Su
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yu-Wei Hsu
- Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Wen-Chien Ko
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Center for Infection Control, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
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Harrabi H, Meyer E, Dournon N, Bouchand F, Kilu CM, Perronne V, Jaffal K, d’Anglejan E, Duran C, Dinh A. Suppressive Antibiotic Therapy in Prosthetic Joint Infections: A Contemporary Overview. Antibiotics (Basel) 2025; 14:277. [PMID: 40149088 PMCID: PMC11939255 DOI: 10.3390/antibiotics14030277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2025] [Revised: 03/03/2025] [Accepted: 03/06/2025] [Indexed: 03/29/2025] Open
Abstract
The management of prosthetic joint infections (PJIs) poses significant challenges, requiring a multidisciplinary approach involving surgical, microbiological, and pharmacological expertise. Suppressive antibiotic therapy (SAT) has emerged as a viable option in cases where curative interventions are deemed unfeasible. This review provides an updated synthesis of recent evidence on SAT, including its indications, efficacy, practical considerations, and associated challenges. We aim to highlight the nuances of this therapeutic approach, discuss the factors influencing its success, and offer future directions for research to optimize patient outcomes.
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Affiliation(s)
- Hajer Harrabi
- Infectious Disease Department, University Hospital R. Poincaré, Assistance Publique des Hôpitaux de Paris, Versailles Paris Saclay University, 104 Bd R. Poincaré, 92380 Garches, France; (E.M.); (F.B.); (C.M.K.); (V.P.); (K.J.); (E.d.); (C.D.)
| | | | | | | | | | | | | | | | | | - Aurélien Dinh
- Infectious Disease Department, University Hospital R. Poincaré, Assistance Publique des Hôpitaux de Paris, Versailles Paris Saclay University, 104 Bd R. Poincaré, 92380 Garches, France; (E.M.); (F.B.); (C.M.K.); (V.P.); (K.J.); (E.d.); (C.D.)
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Jackson K, Veillette JJ, Olson J, Seibert AM, Webb BJ. Evaluation of serial erythrocyte sedimentation rate and C-reactive protein monitoring in infectious disease outpatient parenteral antimicrobial therapy patients. ANTIMICROBIAL STEWARDSHIP & HEALTHCARE EPIDEMIOLOGY : ASHE 2025; 5:e73. [PMID: 40109915 PMCID: PMC11920914 DOI: 10.1017/ash.2025.15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Revised: 12/17/2024] [Accepted: 12/20/2024] [Indexed: 03/22/2025]
Abstract
Of 313 patients whose outpatient parenteral antimicrobial therapy was managed by an ID physician, only 39 [12.5%, 95% CI (8.8%-16.1%)] had clinical decisions influenced by erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), or both. ESR/CRP ordering was associated with $530 in excess cost per treatment course (average duration 5.1 weeks) representing a diagnostic stewardship opportunity.
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Affiliation(s)
- Katarina Jackson
- Department of Pharmacy, Intermountain Medical Center, Murray, UT, USA
| | - John J Veillette
- Department of Pharmacy, Intermountain Medical Center, Murray, UT, USA
- Infectious Diseases Telehealth Service, Intermountain Health, Murray, UT, USA
| | - Jared Olson
- Department of Pharmacy, Primary Children's Hospital, Salt Lake City, UT, USA
- Division of Infectious Diseases, Department of Pediatrics, University of Utah, Salt Lake City, UT, USA
| | - Allan M Seibert
- Division of Infectious Diseases and Clinical Epidemiology, Intermountain Health, Salt Lake City, UT, USA
| | - Brandon J Webb
- Division of Infectious Diseases and Clinical Epidemiology, Intermountain Health, Salt Lake City, UT, USA
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Huang J, Li X, Chen Y, Zhang M, Gao Z, Dai Z, Liu T, Jin Y. Diagnostic value of ratio of blood inflammation to coagulation markers in periprosthetic joint infection. Open Med (Wars) 2025; 20:20251150. [PMID: 40028264 PMCID: PMC11868709 DOI: 10.1515/med-2025-1150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Revised: 12/23/2024] [Accepted: 12/29/2024] [Indexed: 03/05/2025] Open
Abstract
Introduction Assess the feasibility of utilizing the ratio of blood inflammation to coagulation markers as a potential periprosthetic joint infection (PJI) diagnostic tool. Materials and methods A retrospective analysis was conducted, involving 133 PJI and 93 aseptic loosening patients. Levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), platelet count, mean platelet volume, fibrinogen, D-dimer, and ratios of CRP to fibrinogen, ESR to fibrinogen, platelet count and mean platelet volume ratio (PC/MPV), and D-dimer were compared. Receiver operating characteristic curves and Youden's index were employed to assess the diagnostic efficacy of these biomarkers. Results PJI patients had significantly higher levels of CRP, ESR, PC/MPV ratio, fibrinogen, D-dimer, CRP/(PC/MPV) ratio (CPR), CRP/D-dimer, CRP/fibrinogen (CFR), ESR/(PC/MPV) ratio, ESR/D-dimer, and ESR/fibrinogen. Area under the curve (AUC) values for fibrinogen, CRP, and ESR in diagnosing PJI were comparable. AUC values for CPR and CFR were akin to those of ESR. AUC values for combined CRP and CPR, combined CRP and fibrinogen, combined CRP and CFR, and combined ESR and fibrinogen in diagnosing PJI were akin to that of combined CRP and ESR. Conclusions Fibrinogen, CPR, CFR, combined CRP and CPR, combined CRP and fibrinogen, combined CRP and CFR, and combined ESR and fibrinogen could be considered as new adjunct markers for diagnosing PJI.
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Affiliation(s)
- Jincheng Huang
- Department of Orthopedics, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, Henan, 450003, P. R. China
| | - Xu Li
- Department of Orthopedics, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, Henan, 450003, P. R. China
| | - Yajun Chen
- Department of SICU, Zhengzhou First People’s Hospital, Zhengzhou, Henan, 450000, P. R. China
| | - Meng Zhang
- Department of Orthopedics, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, Henan, 450003, P. R. China
| | - Zongyan Gao
- Department of Orthopedics, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, Henan, 450003, P. R. China
| | - Zhipeng Dai
- Department of Orthopedics, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, Henan, 450003, P. R. China
| | - Tao Liu
- Department of Orthopedics, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, No. 7, Road Weiwu, Zhengzhou, Henan, 450003, P. R. China
| | - Yi Jin
- Department of Orthopedics, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, No. 7, Road Weiwu, Zhengzhou, Henan, 450003, P. R. China
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Olearo F, Zein SE, Portillo ME, Zapf A, Rohde H, Berbari EF, Wouthuyzen-Bakker M. Diagnostic accuracy of 16S rDNA PCR, multiplex PCR and metagenomic next-generation sequencing in periprosthetic joint infections: a systematic review and meta-analysis. Clin Microbiol Infect 2025:S1198-743X(25)00083-7. [PMID: 40023316 DOI: 10.1016/j.cmi.2025.02.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Revised: 01/28/2025] [Accepted: 02/20/2025] [Indexed: 03/04/2025]
Abstract
BACKGROUND The diagnostic accuracy of 16S rDNA PCR, multiplex PCR (mPCR), and metagenomic next-generation sequencing (mNGS) in periprosthetic joint infections (PJIs) remains unclear. OBJECTIVES This study aims to evaluate the diagnostic accuracy of 16S rDNA PCR, mPCR, and mNGS in PJI. METHODS Data sources: Data sources included PubMed and Embase (January 1, 2000-March 1, 2024), with no language restrictions. STUDY ELIGIBILITY CRITERIA Studies containing sufficient data to construct a 2 × 2 contingency table allowing for sensitivity and specificity calculation were considered. PARTICIPANTS Participants included adults (≥18 years) with PJI and appropriate control groups. TESTS Tests included 16S rDNA PCR, mPCR, and mNGS. REFERENCE STANDARD Diagnosis required adherence to Musculoskeletal Infection Society, Infectious Diseases Society of America, International Consensus Meeting, European Bone and Joint Infection Society criteria. Studies employing alternative author-defined criteria were included only if they did not rely solely on positive cultures to define PJI. ASSESSMENT OF RISK OF BIAS Quality Assessment of Diagnostic Accuracy Studies 2 was used. METHODS OF DATA SYNTHESIS A bivariate model calculated pooled diagnostic odds ratios (DORs), sensitivities, and specificities, each with 95% CIs. RESULTS Seventy-nine studies were included, comprising 3940 PJI cases and 4700 uninfected controls. Pooled sensitivity/specificity were 80.0% (95% CI, 75.4-84.3%)/94.0% (95% CI, 91-96%) for 16S rDNA PCR; 62.2% (52.5-70.9%)/96.2% (93.2-97.9%) for mPCR; and 88.6% (83.3-92.4%)/93.2% (89.5-95.6%) for mNGS. Notably, mNGS had the highest DOR (105.9; 95% CI, 60-186.9). A sensitivity analysis excluding lower-quality studies resulted in increased DORs for all methods. DISCUSSION These molecular techniques display strong diagnostic accuracy for identifying PJI. Although mNGS yielded the highest DOR, numerous technical and practical challenges preclude its routine use for PJI diagnosis. Significant heterogeneity across studies warrants cautious interpretation and underscores the need for future comparative research.
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Affiliation(s)
- Flaminia Olearo
- Department of Microbiology, Institute for Medical Microbiology, Virology and Hygiene, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
| | - Said El Zein
- Division of Public Health, Infectious Diseases and Occupational Medicine, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Maria Eugenia Portillo
- Department of Clinical Microbiology, University Hospital of Navarra, Instituto de Investigación Sanitaria de Navarra-CIBERESP, Pamplona, Spain
| | - Antonia Zapf
- Department of Microbiology, Institute of Medical Biometry and Epidemiology, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
| | - Holger Rohde
- Department of Microbiology, Institute for Medical Microbiology, Virology and Hygiene, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
| | - Elie F Berbari
- Division of Public Health, Infectious Diseases and Occupational Medicine, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Marjan Wouthuyzen-Bakker
- Department of Medical Microbiology and Infection Prevention, The University Medical Center Groningen, The University of Groningen, Groningen, The Netherlands.
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Azamgarhi T, Gerrand C, Warren S. Rethinking antibiotic prophylaxis in orthopaedic oncology: insights from a cohort study of endoprosthetic infections. J Bone Jt Infect 2025; 10:33-39. [PMID: 40331134 PMCID: PMC12050981 DOI: 10.5194/jbji-10-33-2025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 05/06/2024] [Indexed: 05/08/2025] Open
Abstract
Introduction: Endoprosthetic replacement (EPR) is the preferred limb salvage method for musculoskeletal tumours involving bone; however, infection rates range from 8 % to 12 %. We investigated the impact of antibiotic prophylaxis at primary implantation on the development of prosthetic joint infection (PJI). Methods: We conducted a retrospective analysis of patients who underwent primary EPRs between 2010 and 2021. Prosthetic joint infections were identified and classified according to criteria from the European Bone and Joint Infection Society (EBJIS). The follow-up period extended until an infection was identified, subsequent surgery for non-infectious reasons occurred or the last known follow-up was conducted. For all primary procedures, we collected details of postoperative complications at the surgical site, including superficial wound infections, delayed wound healing and wound dehiscence. PJIs were divided into two groups. The first group included patients with an uncomplicated postoperative course, while the second comprised those with either postoperative wound problems or infections from an identifiable source. Results: Out of 1064 patients, 73 (6.9 %) developed PJI within a median follow-up of 25.6 months (IQR 8.8-52.7). A total of 26 % of PJIs were attributed to primary implantation, while 74 % of PJIs were due to secondary causes, with 47 % having wound complications and 27 % presenting acutely. The microbiological profiles between groups differed significantly, with infections from skin flora related to primary implantation and a high proportion of other bacteria (Gram-negatives and enterococci) linked to secondary infections. Conclusions: Skin flora are likely responsible for infections related to the primary procedure, and antibiotic prophylaxis should be optimised accordingly. Additional measures are needed to prevent secondary infections.
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Affiliation(s)
- Tariq Azamgarhi
- Pharmacy Department, Royal National Orthopaedic Hospital NHS Trust, Brockley Hill, Stanmore, HA7 4LP, UK
| | - Craig Gerrand
- Division of Orthopaedic Oncology, Royal National Orthopaedic Hospital NHS Trust, Sarcoma Unit, Brockley Hill, Stanmore, HA7 4LP, UK
| | - Simon Warren
- Bone Infection Unit, Royal National Orthopaedic Hospital NHS Trust, Brockley Hill, Stanmore, HA7 4LP, UK
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Dinh A, McNally M, D’Anglejan E, Mamona Kilu C, Lourtet J, Ho R, Scarborough M, Dudareva M, Jesuthasan G, Ronde Oustau C, Klein S, Escolà-Vergé L, Rodriguez Pardo D, Delobel P, Lora-Tamayo J, Mancheño-Losa M, Sorlí Redó ML, Barbero Allende JM, Arvieux C, Vaznaisiène D, Bauer T, Roux AL, Noussair L, Corvec S, Fernández-Sampedro M, Rossi N, Lemaignen A, Costa Salles MJ, Cunha Ribeiro T, Mazet J, Sasso M, Lavigne JP, Sotto A, Canouï E, Senneville É, Thill P, Lortholary O, Lanternier F, Morata L, Soriano A, Giordano G, Fourcade C, Frank BJH, Hofstaetter JG, Duran C, Bonnet E. Prosthetic Joint Infections due to Candida Species: A Multicenter International Study. Clin Infect Dis 2025; 80:347-355. [PMID: 39189831 PMCID: PMC11848259 DOI: 10.1093/cid/ciae395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Indexed: 08/28/2024] Open
Abstract
BACKGROUND Prosthetic joint infection (PJI) caused by Candida spp is a severe complication of arthroplasty. We investigated the outcomes of Candida PJI. METHODS This was a retrospective observational multinational study including patients diagnosed with Candida-related PJI between 2010 and 2021. Treatment outcome was assessed at 2-year follow-up. RESULTS A total of 269 patients were analyzed. Median age was 73.0 (interquartile range [IQR], 64.0-79.0) years; 46.5% of patients were male and 10.8% were immunosuppressed. Main infection sites were hip (53.0%) and knee (43.1%), and 33.8% patients had fistulas. Surgical procedures included debridement, antibiotics, and implant retention (DAIR) (35.7%), 1-stage exchange (28.3%), and 2-stage exchange (29.0%). Candida spp identified were Candida albicans (55.8%), Candida parapsilosis (29.4%), Candida glabrata (7.8%), and Candida tropicalis (5.6%). Coinfection with bacteria was found in 51.3% of cases. The primary antifungal agents prescribed were azoles (75.8%) and echinocandins (30.9%), administered for a median of 92.0 (IQR, 54.5-181.3) days. Cure was observed in 156 of 269 (58.0%) cases. Treatment failure was associated with age >70 years (OR, 1.811 [95% confidence interval {CI}: 1.079-3.072]), and the use of DAIR (OR, 1.946 [95% CI: 1.157-3.285]). Candida parapsilosis infection was associated with better outcome (OR, 0.546 [95% CI: .305-.958]). Cure rates were significantly different between DAIR versus 1-stage exchange (46.9% vs 67.1%, P = .008) and DAIR versus 2-stage exchange (46.9% vs 69.2%, P = .003), but there was no difference comparing 1- to 2-stage exchanges (P = .777). CONCLUSIONS Candida PJI prognosis seems poor, with high rate of failure, which does not appear to be linked to immunosuppression, use of azoles, or treatment duration.
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Affiliation(s)
- Aurélien Dinh
- Infectious Disease Department, Raymond-Poincaré University Hospital, Paris Saclay University, Assistance Publique-Hôpitaux de Paris, Garches, France
| | - Martin McNally
- Oxford Bone Infection Unit, Nuffield Orthopaedic Centre, Oxford University Hospitals, Oxford, United Kingdom
| | - Emma D’Anglejan
- Infectious Disease Department, Raymond-Poincaré University Hospital, Paris Saclay University, Assistance Publique-Hôpitaux de Paris, Garches, France
| | - Christel Mamona Kilu
- Infectious Disease Department, Raymond-Poincaré University Hospital, Paris Saclay University, Assistance Publique-Hôpitaux de Paris, Garches, France
| | - Julie Lourtet
- Clinical Microbiology Laboratory, Saint-Joseph Hospital, Paris
| | - Rosemary Ho
- Oxford Bone Infection Unit, Nuffield Orthopaedic Centre, Oxford University Hospitals, Oxford, United Kingdom
| | - Matthew Scarborough
- Oxford Bone Infection Unit, Nuffield Orthopaedic Centre, Oxford University Hospitals, Oxford, United Kingdom
| | - Maria Dudareva
- Oxford Bone Infection Unit, Nuffield Orthopaedic Centre, Oxford University Hospitals, Oxford, United Kingdom
| | - Gerald Jesuthasan
- Oxford Bone Infection Unit, Nuffield Orthopaedic Centre, Oxford University Hospitals, Oxford, United Kingdom
| | - Cecile Ronde Oustau
- Orthopedic Surgery Department, Strasbourg University Hospital, Strasbourg, France
| | - Stéphane Klein
- Orthopedic Surgery Department, Strasbourg University Hospital, Strasbourg, France
| | - Laura Escolà-Vergé
- Infectious Disease Department, Vall d’Hebron University Hospital, Barcelona, Spain
| | | | - Pierre Delobel
- Infectious Disease Department, Toulouse University Hospital, Toulouse, France
| | - Jaime Lora-Tamayo
- Internal Medicine Department, Hospital Universitario 12 de Octubre, Madrid
| | | | | | - José María Barbero Allende
- Internal Medicine Department, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain
| | - Cédric Arvieux
- Infectious Disease Department, Rennes University Hospital, Rennes, France
| | - Danguole Vaznaisiène
- Infectious Disease Department, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | | | - Anne-Laure Roux
- Microbiology Department, Raymond-Poincaré University Hospital, Paris Saclay University, Assistance Publique-Hôpitaux de Paris, Garches
| | - Latifa Noussair
- Microbiology Department, Raymond-Poincaré University Hospital, Paris Saclay University, Assistance Publique-Hôpitaux de Paris, Garches
| | - Stéphane Corvec
- Infectious Disease Department, Nantes University Hospital, Nantes, France
| | - Marta Fernández-Sampedro
- Internal Medicine Department, Marques de Valdecilla Hospital, Instituto de Investigación Sanitaria Valdecilla (IDIVAL), Centro De Investigación Biomédica En Red Enfermedades Infecciosas (CIBERINFEC), Santander, Spain
| | - Nicolò Rossi
- Orthopedic Surgery Department, Sant’Orsola Polyclinic, Bologna, Italy
| | - Adrien Lemaignen
- Infectious Disease Department, Bretonneau University Hospital, Tours, France
| | - Mauro José Costa Salles
- Infectious Disease Department, Faculdade de Ciências Médicas Santa Casa de São Paulo, São Paulo, Brazil
| | - Taiana Cunha Ribeiro
- Infectious Disease Department, Faculdade de Ciências Médicas Santa Casa de São Paulo, São Paulo, Brazil
| | - Julien Mazet
- Infectious Disease Department, Caremeau University Hospital, Nîmes
| | - Milène Sasso
- Infectious Disease Department, Caremeau University Hospital, Nîmes
| | | | - Albert Sotto
- Infectious Disease Department, Caremeau University Hospital, Nîmes
| | - Etienne Canouï
- Infectious Disease Department, Cochin University Hospital, Assistance Publique-Hôpitaux de Paris, Paris
| | - Éric Senneville
- Infectious Disease Department, Lille University Hospital, Lille
| | - Pauline Thill
- Infectious Disease Department, Lille University Hospital, Lille
| | - Olivier Lortholary
- Necker-Pasteur Center for Infectious Diseases and Tropical Medicine, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Paris
- Mycology Department, Institut Pasteur, Centre National de Référence Mycoses Invasives et Antifongiques, Paris Cité University, Groupe de Recherche Translationnelle en Mycologie, Paris, France
| | - Fanny Lanternier
- Necker-Pasteur Center for Infectious Diseases and Tropical Medicine, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Paris
- Mycology Department, Institut Pasteur, Centre National de Référence Mycoses Invasives et Antifongiques, Paris Cité University, Groupe de Recherche Translationnelle en Mycologie, Paris, France
| | - Laura Morata
- Infectious Disease Department, Hospital Clínic de Barcelona, Barcelona, Spain
| | - Alex Soriano
- Infectious Disease Department, Hospital Clínic de Barcelona, Barcelona, Spain
| | - Gérard Giordano
- Orthopedic surgery department, Joseph Ducuing Hospital, Toulouse, France
| | - Camille Fourcade
- Infectious Disease Department, Joseph Ducuing Hospital, Toulouse, France
| | - Bernhard J H Frank
- Michael Ogon Laboratory for Orthopaedic Research, Orthopaedic Hospital Vienna, Speising, Austria
| | - Jochen G Hofstaetter
- Michael Ogon Laboratory for Orthopaedic Research, Orthopaedic Hospital Vienna, Speising, Austria
| | - Clara Duran
- Infectious Disease Department, Raymond-Poincaré University Hospital, Paris Saclay University, Assistance Publique-Hôpitaux de Paris, Garches, France
| | - Eric Bonnet
- Infectious Disease Department, Joseph Ducuing Hospital, Toulouse, France
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Motta L, Stroffolini G, Marocco S, Bertoli G, Piovan G, Povegliano L, Zorzi C, Gobbi F. Evaluation of the Use of Preventive Antibiotic Therapy in Patients Undergoing One-Step Prosthetic Revision Surgery with Low Preoperative Infectious Risk. Antibiotics (Basel) 2025; 14:224. [PMID: 40149036 PMCID: PMC11939302 DOI: 10.3390/antibiotics14030224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Revised: 02/17/2025] [Accepted: 02/19/2025] [Indexed: 03/29/2025] Open
Abstract
Introduction: The prosthetic knee infection (PKI) rate in most centers ranges from 0.5 to 2% for knee replacements, depending on risk factors. Current PKI definitions may miss the identification of both early and late complications. There is no consensus on preventive or early empiric antibiotic therapy (EEAT) in the one-step exchange strategy for low-risk patients pending microbiology results. The aim of the study was to evaluate the potential role of EEAT in patients with comorbidities in preventing PKI and to evaluate differences in septic failure at 3, 6 and 9 months after prosthetic revision between patients undergoing EEAT and patients not undergoing EEAT. Methods: All adult patients undergoing one-step knee revision surgery at IRCCS Sacro-Cuore Don Calabria Negrar, from January 2018 to February 2021, were retrospectively included in a cohort observational study. Patients on antibiotic therapy before surgery or with preoperative ascertained PKI were excluded. Demographic characteristics, Charlson score, comorbidities, inflammatory markers, microbiological tests, imaging, infectious disease risk score and EEAT data were collected. Any postoperative complication or modification of antibiotic therapy at 14, 30, 90, 180 and 270 days after surgery was collected. Results: A total of 227 patients were included: 114 comorbid low-risk patients received EEAT after surgery, pending microbiological results; while 113 non-comorbid low-risk patients did not receive any antibiotic therapy in the postoperative period. Among the EEAT group, 16 were diagnosed with PKI, compared with 10 in the untreated group. Regarding septic failure during the 9-month follow-up after revision surgery, we registered nine cases in the EEAT arm and four in the untreated arm. In three out of nine cases treated with EEAT who had a post-revision septic failure, the causative microorganism was not successfully empirically targeted by EEAT; in the untreated group, two out of four cases had a post-revision septic failure, despite the targeted treatment of intraoperatively identified causative microorganisms. Conclusions: According to our results, EEAT after revision surgery in patients with comorbidities, who are at higher risk of infection, did not prevent prosthetic knee infections. There was also no evidence of a reduction in subsequent septic failure within nine months of revision surgery between groups. More accurate risk-defining scores are needed to identify patients at risk of PKI complications.
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Affiliation(s)
- Leonardo Motta
- Department of Infectious-Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar, 37024 Verona, Italy; (L.M.); (S.M.); (G.B.); (F.G.)
| | - Giacomo Stroffolini
- Department of Infectious-Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar, 37024 Verona, Italy; (L.M.); (S.M.); (G.B.); (F.G.)
| | - Stefania Marocco
- Department of Infectious-Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar, 37024 Verona, Italy; (L.M.); (S.M.); (G.B.); (F.G.)
| | - Giulia Bertoli
- Department of Infectious-Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar, 37024 Verona, Italy; (L.M.); (S.M.); (G.B.); (F.G.)
| | - Gianluca Piovan
- Department of Orthopaedic and Traumatology, S. Cuore-Don Calabria Hospital, Negrar, 37024 Verona, Italy; (G.P.); (L.P.); (C.Z.)
| | - Lorenzo Povegliano
- Department of Orthopaedic and Traumatology, S. Cuore-Don Calabria Hospital, Negrar, 37024 Verona, Italy; (G.P.); (L.P.); (C.Z.)
| | - Claudio Zorzi
- Department of Orthopaedic and Traumatology, S. Cuore-Don Calabria Hospital, Negrar, 37024 Verona, Italy; (G.P.); (L.P.); (C.Z.)
| | - Federico Gobbi
- Department of Infectious-Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar, 37024 Verona, Italy; (L.M.); (S.M.); (G.B.); (F.G.)
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Robinet S, Parisot F, Clavé A. A nine-year retrospective study of bacterial epidemiology and culture optimization in four orthopaedic surgery departments. Orthop Traumatol Surg Res 2025:104193. [PMID: 39986537 DOI: 10.1016/j.otsr.2025.104193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 02/17/2025] [Accepted: 02/19/2025] [Indexed: 02/24/2025]
Abstract
BACKGROUND Management of device-associated bone and joint infections combines surgical treatment and antibiotic therapy. Immediate postoperative broad-spectrum empiric treatment is often recommended pending complete microbiology results. The probabilistic antibiotics often used are not harmless, and expose the patient to the selection of resistant bacteria and changes in bacterial ecology within the healthcare units. The aim of this study was to answer the following questions: (1) Have the pathogenic bacteria isolated in osteoarticular infections and/or their antibiotic susceptibility profile changed over a 9-year period at our center, with possible implications for antibiotic therapy protocols? (2) Is there a way to optimize the incubation time for microbiological cultures while still being acceptable for slow growing pathogens? HYPOTHESIS Our hypothesis was that no difference in microbial epidemiology and antibiotic resistance rates would be found over this 9-year period, confirming antibiotic protocols. MATERIALS AND METHODS We conducted a retrospective study describing a nine-year bacterial epidemiology in four traumatology and orthopedic surgery departments. Bacteria identified, site of infection, and antibiotic resistance were evaluated. Antibiotics for use in probabilistic protocols and after documentation of infection were selected for follow-up. Bacterial species were isolated after a maximum incubation period of 15 days up to 2020, and 10 days from 2021 with the addition of a solid culture medium that promotes anaerobic bacterial growth. RESULTS Of the 648 clinical situations, 824 bacteria were identified. Gram-positive cocci accounted for 61.4% (506/824) of the strains, including 291/824 (35.3%) Staphylococcus aureus and 136/824 (16.5%) coagulase-negative staphylococci. For the latter, fluoroquinolone resistance remained stable at 7.3% (18/291 (p = 0.086)) and 22.8% (34/136 (p = 0.432)), respectively. Resistance to rifampicin was also stable for Staphylococcus aureus (1.2%,4/291 (p = 0.486)) and for coagulase-negative staphylococci (10.7%, 15/136 (p = 0.596)). Enterobacteriaceae accounted for 148/824 (18.0%) of identifications and were more resistant to piperacillin/tazobactam (15.1%, 24/148) than to cefepime (5.6%,9/148 (p = 0.006)). There was no significant difference between the 15-day and 10-day culture protocols in the proportion of anaerobic bacteria isolated from shoulder (p = 0.721), hip and knee (p = 0.530) prosthesis infections and spinal device-associated infections (p = 0.373). A microbiological diagnosis was made within five days using the 10-day culture protocol in 333/344 (96.8%) cases. DISCUSSION The increase in Cutibacterium acnes isolates is mainly explained by the increased number of patients recruited for shoulder arthroplasty. No change in antibiotic resistance was observed in our retrospective study. This is probably related to the use of some precautions when prescribing antibiotic therapy. For gram-negative bacilli, cefepime is the beta-lactam of choice for probabilistic treatment when combined with an antibiotic that is particularly effective against methicillin-resistant staphylococci. An incubation period limited to 10 days seems to be sufficient for the culture of slow-growing organisms, as epidemiological analysis has not shown any negative effects. LEVEL OF EVIDENCE Level IV. Retrospective cohort study.
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Affiliation(s)
- Sylvain Robinet
- Laboratory of Medical Microbiology, Eurofins - Clinical Diagnostics, 2 rue Eugène Coste, 06300 Nice, France.
| | - François Parisot
- Laboratory of Medical Microbiology, Eurofins - Clinical Diagnostics, 2 rue Eugène Coste, 06300 Nice, France
| | - Arnaud Clavé
- Department of Traumatology and Orthopedics, Clinique Saint George, 2 Avenue de Rimiez, 06105 Nice, France
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Morreel ERL, van Dessel HA, Geurts J, Savelkoul PHM, van Loo IHM. Prolonged incubation time unwarranted for acute periprosthetic joint infections. J Clin Microbiol 2025; 63:e0114324. [PMID: 39817758 PMCID: PMC11837491 DOI: 10.1128/jcm.01143-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 11/02/2024] [Indexed: 01/18/2025] Open
Abstract
Current laboratory protocols for periprosthetic joint infections (PJIs) involve a standard 10- to 14-day incubation period. However, recent evidence indicates considerable variability in the time to diagnosis (TTD) between acute and chronic PJIs. TTD is also influenced by the employed culture media and sample types. Enriched liquid media, such as broths and blood culture bottles, along with sonication fluid culture, are commonly used, though their incremental benefit for PJI diagnosis remains debated. We retrospectively analyzed 187 confirmed hip and knee PJIs, each with at least three intraoperative samples. Comparison of TTD among early acute (n = 68), late acute (n = 52), and late chronic (n = 67) PJIs revealed a significant difference, particularly between late acute and late chronic infections (P < 0.004). Early acute and late acute PJIs were diagnosed within 5 days in 97.1% and 98.1% of cases, respectively, contrasting with 14 days required for 97.1% of late chronic PJIs. Enriched liquid media significantly improved species detection, especially in polymicrobial and anaerobic infections. Pediatric and anaerobic blood culture bottles demonstrated superior efficacy over thioglycolate broths for diagnostic confirmation. Sonication fluid culture was essential for confirming diagnoses in 17.6% of cases. Our findings highlight that clinical presentation, rather than time since primary arthroplasty, should guide incubation duration: both early acute and late acute PJIs can be diagnosed within 5 days. Medical microbiology laboratories should consider shorter incubation times for acute PJIs to optimize diagnostic efficiency. The use of blood culture bottles and sonication fluid culture proves invaluable for accurate PJI diagnosis. IMPORTANCE While molecular techniques are becoming increasingly employed, culture remains the gold standard for diagnosing periprosthetic joint infections. However, guidance for laboratory protocols is limited and highly variable. This article aims to increase diagnostic efficiency by providing concrete recommendations for medical microbiology laboratories.
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Affiliation(s)
- E. R. L. Morreel
- Department of Medical Microbiology, Infectious Diseases and Infection Prevention, Maastricht University Medical Centre, Maastricht, the Netherlands
- Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, the Netherlands
| | - H. A. van Dessel
- Department of Medical Microbiology, Infectious Diseases and Infection Prevention, Maastricht University Medical Centre, Maastricht, the Netherlands
- Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, the Netherlands
| | - J. Geurts
- Department of Orthopedic Surgery, Maastricht University Medical Centre (MUMC+), Maastricht, the Netherlands
| | - P. H. M. Savelkoul
- Department of Medical Microbiology, Infectious Diseases and Infection Prevention, Maastricht University Medical Centre, Maastricht, the Netherlands
- Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, the Netherlands
| | - I. H. M. van Loo
- Department of Medical Microbiology, Infectious Diseases and Infection Prevention, Maastricht University Medical Centre, Maastricht, the Netherlands
- Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, the Netherlands
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48
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Levin BR, Gil-Gil T, Berryhill BA, Woodworth MH. A theoretical exploration of protocols for treating prosthetic joint infections with combinations of antibiotics and bacteriophage. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.02.16.638499. [PMID: 39990355 PMCID: PMC11844561 DOI: 10.1101/2025.02.16.638499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 02/25/2025]
Abstract
With the increase in the placement of prosthetic joints and other hardware in the body has come an increase in associated infections. These infections are particularly difficult to treat due to the underlying bacteria generating matrices which resist clearance by immune system effectors or antibiotics. These matrices, biofilms, have two primary ways of being eradicated, either by physical removal by debridement or by killing the underlying bacteria. The viruses which kill bacteria, bacteriophage, are readily capable of entering into biofilms and eradicating the bacteria therein. Therefore, bacteriophage have therapeutic potential as a supplement to antibiotics for the treatment of prosthetic joint infections. In this investigation, we generate a mathematical-computer simulation model to explore the contributions of the innate immune system with antibiotics, bacteriophage, and the joint action thereof in the control of biofilm-associated infections. Our results question the proposition that bacteriophage are an effective addition in the treatment of prosthetic joint infections.
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Affiliation(s)
- Bruce R. Levin
- Department of Biology, Emory University; Atlanta, Georgia, 30322, USA
| | - Teresa Gil-Gil
- Department of Biology, Emory University; Atlanta, Georgia, 30322, USA
| | - Brandon A. Berryhill
- Department of Biology, Emory University; Atlanta, Georgia, 30322, USA
- Program in Microbiology and Molecular Genetics, Graduate Division of Biological and Biomedical Sciences, Laney Graduate School, Emory University; Atlanta, GA, 30322, USA
| | - Michael H. Woodworth
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 49 Jesse Hill JR. Drive, Atlanta, GA, 30303, USA
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49
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Nguyen VD, Côté A, Marsot A. External Evaluation of Longitudinal Population Pharmacokinetic Models of Vancomycin in Patients With Osteoarticular Infections. Ther Drug Monit 2025:00007691-990000000-00316. [PMID: 39937437 DOI: 10.1097/ftd.0000000000001303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Accepted: 12/04/2024] [Indexed: 02/13/2025]
Abstract
BACKGROUND Osteoarticular infections pose a challenge for therapeutic drug monitoring of vancomycin because they often require prolonged treatment. Given the extensive renal elimination of vancomycin, its pharmacokinetic properties are difficult to predict in the later stages of treatment because the risk of nephrotoxicity increases with the duration of treatment. In this study, published longitudinal population pharmacokinetic (popPK) models were externally evaluated in a cohort of patients with osteoarticular infections. METHODS A literature search was performed in PubMed/EMBASE and published reviews. The predictive performance of the selected models was assessed through prediction- and simulation-based diagnostics using NONMEM software. Data were collected during both the retrospective and prospective phases, during which prospectively recruited patients provided additional vancomycin concentrations. RESULTS The external validation dataset comprised 525 vancomycin concentrations obtained from 73 patients treated for osteoarticular infections at Montréal General Hospital. Two published popPK models that provided different approaches for integrating a longitudinal structure were identified. Both failed to meet the clinically acceptable threshold of imprecision in population predictions. The weighted median absolute prediction error ranged from 34.9% to 48.3% before re-estimation of model parameters and from 33.5% to 35.2% after re-estimation. The re-estimated models tended to underpredict vancomycin concentrations in the later stages of treatment. CONCLUSIONS The 2 evaluated models showed poor predictive performance in our local study population. Further studies should explore new strategies to incorporate a longitudinal component and consider other relevant clinical covariates to develop improved longitudinal popPK models for vancomycin.
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Affiliation(s)
- Van Dong Nguyen
- Pharmacy Department, McGill University Health Centre, Montréal, Quebec, Canada
- Université de Montréal, Pavillon Jean-Coutu, Montréal, Quebec, Canada
- Laboratoire de Suivi Thérapeutique Pharmacologique et Pharmacocinétique, Faculté de Pharmacie, Université de Montréal, Pavillon Jean-Coutu, Montréal, Quebec, Canada; and
| | - Alice Côté
- Pharmacy Department, McGill University Health Centre, Montréal, Quebec, Canada
- Université de Montréal, Pavillon Jean-Coutu, Montréal, Quebec, Canada
- Laboratoire de Suivi Thérapeutique Pharmacologique et Pharmacocinétique, Faculté de Pharmacie, Université de Montréal, Pavillon Jean-Coutu, Montréal, Quebec, Canada; and
| | - Amélie Marsot
- Université de Montréal, Pavillon Jean-Coutu, Montréal, Quebec, Canada
- Laboratoire de Suivi Thérapeutique Pharmacologique et Pharmacocinétique, Faculté de Pharmacie, Université de Montréal, Pavillon Jean-Coutu, Montréal, Quebec, Canada; and
- Centre de recherche du CHU Ste-Justine, Centre hospitalier universitaire Ste-Justine, Montréal, Quebec, Canada
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50
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Durham SH, Covington EW, Roberts MZ, Chahine EB. Rifampin in device-related infections: Assessing the modern evidence. Am J Health Syst Pharm 2025; 82:184-202. [PMID: 39324584 DOI: 10.1093/ajhp/zxae263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Indexed: 09/27/2024] Open
Abstract
PURPOSE Rifampin is commonly used to treat device-related infections (DRIs) due to its activity against biofilms, despite a history of limited clinical evidence to support its use. Evidence published since 2011 regarding rifampin use for DRIs is reviewed to describe the contemporary findings and ongoing considerations for rifampin use in these infections. SUMMARY A literature review was performed by searching PubMed and Google Scholar to identify relevant studies evaluating systemic rifampin use for the treatment of DRIs published from 2011 to 2023. References of identified studies were also screened for additional pertinent studies. Sixty-eight studies were identified, and 48 met the inclusion criteria. Rifampin efficacy was evaluated as both a primary outcome for cardiac device infections (n = 3) and prosthetic joint infections (n = 21) and as a nonprimary outcome (n = 24). Overall, the studies were primarily retrospective (n = 36) and small, with sample sizes ranging from 14 to 842 patients, and varied greatly with respect to prosthesis site, surgical intervention, pathogen, infection time frame, and antibiotic combination and duration. Efficacy outcome results varied greatly, with statistically significant evidence for the efficacy of rifampin combination in DRIs limited to a single study of prosthetic vascular graft infections and 13 studies of prosthetic joint infections. CONCLUSION The modern literature provides conflicting results regarding the benefit and lack of benefit with rifampin combination therapy in DRIs. Additional, robust research is imperative to solidify the ongoing role of rifampin in DRIs.
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Affiliation(s)
- Spencer H Durham
- Auburn University Harrison College of Pharmacy, Huntsville, AL, USA
| | | | - Megan Z Roberts
- Auburn University Harrison College of Pharmacy, Huntsville, AL, USA
| | - Elias B Chahine
- Gregory School of Pharmacy, Palm Beach Atlantic University, West Palm Beach, FL, USA
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