{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:47:02Z","timestamp":1790858822605,"version":"4.1.0"},"reference-count":63,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Prosthetic joint infections (PJI) remain among the most devastating complications in orthopedic surgery, with increasing incidence paralleling the growth in arthroplasty procedures worldwide. While treatment protocols are well-established, evidence supporting current approaches is lacking, and outcomes remain suboptimal, highlighting the need for improved therapeutic strategies. The objective of this study is to review ongoing and recently completed randomized controlled trials (RCTs) investigating novel approaches to PJI prevention and treatment. We searched PubMed and ClinicalTrials.gov databases for RCTs that focused on PJI management, and that are ongoing or completed within the 6 months preceding February 28, 2025. We included investigator-initiated trials, studies of novel therapeutic agents, and studies on infection prevention strategies. We extracted and reviewed data regarding trial design, interventions, and outcomes. We identified significant advances in three key areas: (i) investigator-initiated trials exploring optimization of current surgical and antimicrobial treatment strategies, including the ROADMAP adaptive platform trial (ii); novel therapeutic agents, including engineered antibacterial peptides, monoclonal antibodies, and new-generation antibiotics specifically targeting biofilm-associated infections; and (iii) prevention strategies, particularly focusing on perioperative antibiotic protocols. Recent trials demonstrate promising approaches to reducing antibiotic exposure while maintaining efficacy, novel mechanisms for biofilm disruption, and strategies for optimizing perioperative prophylaxis. Investigator-initiated trials like ROADMAP and SOLARIO are challenging traditional paradigms, particularly in antibiotic duration, while novel therapeutics targeting biofilm through various mechanisms show promise in early-phase trials. Future research should prioritize cost-effectiveness analyses, targeted studies for specific patient subgroups, and evaluation of combination therapeutic approaches.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00338-25","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T14:41:38Z","timestamp":1755182498000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["Advancing the management of prosthetic joint infections: a review of randomized controlled trials and emerging evidence"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1362-2434","authenticated-orcid":true,"given":"Burcu","family":"Isler","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00rqy9422","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Queensland Centre for Clinical Research","place":["Brisbane, Australia"]},{"name":"Department of Infectious Diseases, Gold Coast University Hospital","place":["Gold Coast, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenya","family":"Welyczko","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04mqb0968","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Orthopaedic Surgery, Princess Alexandra Hospital","place":["Brisbane, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Jorgensen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04mqb0968","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Orthopaedic Surgery, Princess Alexandra Hospital","place":["Brisbane, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9864-5699","authenticated-orcid":true,"given":"Joshua","family":"Davis","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0020x6414","id-type":"ROR","asserted-by":"publisher"}],"name":"Infection Research Program, Hunter Medical Research Institute, University of Newcastle","place":["New Lambton Heights, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Paterson","sequence":"additional","affiliation":[{"name":"ADVANCE-ID, Saw Swee Hock School of Public Health and Yong Loo Lin School of Medicine, National University of Singapore","place":["Singapore, Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-017-1569-2"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arth.2018.08.021"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2020198"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.106B10.BJJ-2024-0106.R1"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arth.2020.12.005"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.5694\/mja2.52228"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofaa068"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics12101486"},{"key":"e_1_3_1_10_2","unstructured":"ROADMAP Trial. 2025. Available from: https:\/\/www.roadmaptrial.com\/investigators\/resource-documents. Retrieved 06 Jun 2025."},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13063-019-3832-3"},{"key":"e_1_3_1_12_2","unstructured":"BONESUPPORT. Additional data from SOLARIO study reveals further positive insights. Available from: https:\/\/www.bonesupport.com\/en-us\/media\/press-releases\/additional-data-from-solario-study-reveals-further-positive-insights\/. Retrieved 04 Jun 2025."},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1302\/1358-992X.2024.19.019"},{"key":"e_1_3_1_14_2","unstructured":"Rifampicin combination therapy versus targeted antimicrobial monotherapy in the oral antimicrobial treatment phase of staphylococcal prosthetic joint infection. clinicaltrials.gov. Available from: https:\/\/clinicaltrials.gov\/study\/NCT06172010. Retrieved 04 Jun 2025."},{"key":"e_1_3_1_15_2","unstructured":"Rifabutin versus rifampicin for treatment of staphylococcal PJI treated with DAIR. clinicaltrials.gov. Available from: https:\/\/clinicaltrials.gov\/study\/NCT04672525. Retrieved 04 Jun 2025."},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11999-011-2102-9"},{"key":"e_1_3_1_17_2","unstructured":"Interim results show similar efficacy of one- and two-stage treatment for PJI. Available from: https:\/\/www.healio.com\/news\/orthopedics\/20240214\/interim-results-show-similar-efficacy-of-one-and-twostage-treatment-for-pji. Retrieved 06 Mar 2025."},{"key":"e_1_3_1_18_2","volume-title":"Presented at the American Academy of Orthopaedic Surgeons Annual Meeting","author":"Fehring TK","year":"2024","unstructured":"Fehring TK, Otero JE, Fehring K, Curtin BM, Springer BD, Ready A, Rowe TM, Odum SM. 2024. One-stage versus two-stage treatment for prosthetic joint infection: a prospective, randomized clinical trial. Abstract TPA-10203. Presented at the American Academy of Orthopaedic Surgeons Annual Meeting, San Francisco, CA."},{"key":"e_1_3_1_19_2","unstructured":"Controlled trial of omadacycline randomized treatment given for bone and joint infection (CORGI). clinicaltrials.gov. Available from: https:\/\/clinicaltrials.gov\/study\/NCT05753215. Retrieved 06 Jun 2025."},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofae631.274"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/os.14262"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2022-071487"},{"key":"e_1_3_1_23_2","unstructured":"Overgaard S. The effect of single vs multiple prophylactic antibiotic doses on PJI following primary THA in patients with a fracture: a cross-over cluster randomized controlled non-inferiority trial based on national quality databases: ProHipQ-F. clinicaltrials.gov. Available from: https:\/\/clinicaltrials.gov\/study\/NCT05530174. Retrieved 04 Jun 2025."},{"key":"e_1_3_1_24_2","unstructured":"Antibiotic prophylaxis in patients undergoing elective TKA-multi-center trial. clinicaltrials.gov. Available from: https:\/\/clinicaltrials.gov\/study\/NCT03283878. Retrieved 04 Jun 2025."},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2022-071281"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.5435\/JAAOS-D-24-00013"},{"key":"e_1_3_1_27_2","unstructured":"A phase 1 open-label safety study of VT-X7. clinicaltrials.gov. Available from: https:\/\/clinicaltrials.gov\/study\/NCT03721328. Retrieved 04 Jun 2025."},{"key":"e_1_3_1_28_2","unstructured":"A second randomized controlled trial of alternating irrigation of vancomycin hydrochloride and tobramycin sulfate in patients undergoing two-stage exchange arthroplasty for periprosthetic joint infection of the hip or knee. clinicaltrials.gov. Available from: https:\/\/clinicaltrials.gov\/study\/NCT05607030. Retrieved 06 Mar 2025."},{"key":"e_1_3_1_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arth.2024.03.069"},{"key":"e_1_3_1_30_2","unstructured":"A phase 1b open-label dose-escalating study to evaluate the safety and tolerability of PLG0206 in patients undergoing debridement antibiotics and implant retention (DAIR) for treatment of a periprosthetic joint infection (PJI) occurring after total knee arthroplasty (TKA). clinicaltrials.gov. Available from: https:\/\/clinicaltrials.gov\/study\/NCT05137314. Retrieved 04 Jun 2025."},{"key":"e_1_3_1_31_2","unstructured":"Peptilogics reports positive 180-day top line interim data from phase 1b trial of PLG0206 in patients with periprosthetic joint infection (PJI). Available from: https:\/\/peptilogics.com\/news\/peptilogics-reports-positive-180-day-top-line-interim-data-from-phase-1b-trial-of-plg0206-in-patients-with-periprosthetic-joint-infection-pji\/. Retrieved 04 Jun 2025."},{"key":"e_1_3_1_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00655-24"},{"key":"e_1_3_1_33_2","unstructured":"Phase 2 study to evaluate the efficacy and safety of TRL1068 for the treatment of chronic prosthetic joint infection of the knee or hip without exchange arthroplasty. clinicaltrials.gov. Available from: https:\/\/clinicaltrials.gov\/study\/NCT06621251. Retrieved 04 Jun 2025."},{"key":"e_1_3_1_34_2","unstructured":"An open-label study to evaluate tissue distribution plasma pharmacokinetics safety and tolerability after a single intravenous dose of TNP-2092 in adult participants undergoing primary total hip or knee arthroplasty. clinicaltrials.gov. Available from: https:\/\/clinicaltrials.gov\/study\/NCT04294862. Retrieved 04 Jun 2025."},{"key":"e_1_3_1_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofae631.1303"},{"key":"e_1_3_1_36_2","unstructured":"A phase 1 single-center randomized double-blind placebo-controlled dose-escalation clinical trial to evaluate the safety tolerability and pharmacokinetics of single-dose and multiple-dose continuous intravenous infusions of TNP-2092 for injection in healthy chinese participants. clinicaltrials.gov. Available from: https:\/\/clinicaltrials.gov\/study\/NCT06394518. Retrieved 04 Jun 2025."},{"key":"e_1_3_1_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofae631.1253"},{"key":"e_1_3_1_38_2","unstructured":"PHAXIAM Therapeutics. Available from: https:\/\/live.euronext.com\/en\/product\/equities\/FR001400K4B1-XPAR#CompanyPressRelease-12711403. Retrieved 04 Jun 2025."},{"key":"e_1_3_1_39_2","unstructured":"A pilot multicenter randomized non-comparative double-blind study of phage therapy in patients with hip or knee prosthetic joint infection due to Staphylococcus aureus treated with DAIR and antibiotic therapy. clinicaltrials.gov. Available from: https:\/\/clinicaltrials.gov\/study\/NCT05369104. Retrieved 04 Jun 2025."},{"key":"e_1_3_1_40_2","unstructured":"A phase II proof of concept multicenter randomized double-blind study to assess the safety and efficacy of phage therapy in patients with hip or knee prosthetic joint infection due to Staphylococcus aureus treated by DAIR. clinicaltrials.gov. Available from: https:\/\/clinicaltrials.gov\/study\/NCT06605651. Retrieved 04 Jun 2025."},{"key":"e_1_3_1_41_2","unstructured":"Osteal therapeutics announces first subject enrollment in second phase 2 clinical trial of VT-X7 combination product for treatment of periprosthetic joint infection. GlobeNewswire News Room. 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Available from: https:\/\/www.tennorx.com\/en\/NewsD.html?id=504. Retrieved 04 Jun 2025."},{"key":"e_1_3_1_57_2","unstructured":"Wittke F Tacheron A Grossmann M Hussaini A Fuhr R Etter AL Nicolas V. 2017. IV and oral drug development of the staphylococcal-specific antibiotic Debio 1450: results from formulation finding and multiple ascending dose studies"},{"key":"e_1_3_1_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00250-20"},{"key":"e_1_3_1_59_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofae631.1411"},{"key":"e_1_3_1_60_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofae631.272"},{"key":"e_1_3_1_61_2","unstructured":"PHAXIAM provides an update on the deployment of its strategy to maximize the development potential of phage therapy. Available from: https:\/\/www.businesswire.com\/news\/home\/20250130268564\/en\/PHAXIAM-Provides-An-Update-On-The-Deployment-Of-Its-Strategy-To-Maximize-The-Development-Potential-Of-Phage-Therapy. 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