ROADMAP Clinical Trial

Inclusion Criteria: 1. "Confirmed" or "Likely" Prosthetic joint infection of a large joint according to European Bone and Joint Infection Society (EBJIS) criteria (2021) 2. Physically present at participating hospital at time of eligibility assessment 3. "Current" prosthetic joint infection, meaning symptoms and/or signs of the PJI are present at the time of eligibility assessment. Exclusion Criteria: Potentially eligible participants meeting any of the following criteria at the time of eligibility assessment for platform entry will be excluded from the randomised platform (but may still participate in the registry): 1. The index prosthetic joint is a shoulder, elbow, wrist or ankle. 2. Known previous participation in the randomised ROADMAP randomised platform for the index joint. 3. Known previous participation in the randomised ROADMAP platform for a joint other than the index joint within the 12 months prior to eligibility assessment 4. Treating clinician believes that death is imminent and inevitable. 5. Treatment is not with curative intent. 6. Patient is not classifiable into one of the three defined silos. 7. Patient is unlikely to be accessible for follow up over the 12 months following platform entry. 8. Treating team deems enrolment in the study is not in the best interests of the patient. To be included in any of the following Domains the participant must be eligible for the PLATFORM ( as listed above) and none of the platform-level exclusion criteria AND all of the domain-level inclusion and none of the domain-level exclusion criteria. Domain-specific eligibility criteria Each domain may have additional criteria for eligibility. Participants who fulfil the above criteria will be assessed for enrolment into all domains active at a participating site. At least 2 interventions (which may include standard of care) within a domain must be available to an eligible participant in order for that participant to enter the domain. The minimum number of interventions within a domain is two. The availability of interventions within domains will be region- and site-specific, although the default position is that all interventions within a domain will be available at all sites. Surgical Strategy Domain: Late Acute Silo inclusion criteria Patient is in the Late Acute silo, meaning all of the following 3 criteria are met: 1. Onset of symptoms is \>30 days after implantation of the index joint 2. Treating team feel that either DAIR or revision is appropriate for this patient. 3. The infected prosthesis is a primary arthroplasty. Surgical Strategy Domain: Late Acute Silo exclusion criteria <!-- --> 1. Any previous episode of native joint septic arthritis or PJI in the index joint 2. A definitive DAIR has already occurred for this episode of infection. 3. A revision has already occurred for this episode of infection 4. Loosening or instability of any component of the prosthesis 5. Predicted inadequate soft tissue coverage for wound closure 6. One or more of the causative organisms is a fungus or a "difficult to treat" bacterium. 7. Treating team deems enrolment in this domain is not in the best interests of the patient. Antibiotic Choice Domain inclusion criteria 1. The time of eligibility assessment is between 48h and 7 days following initial surgical treatment. 2. One or more of the causative organisms is a Gram-positive of interest OR the infection is culture negative. Antibiotic Choice Domain exclusion criteria <!-- --> 1. Previous hypersensitivity reaction to rifampicin 2. The patient is receiving a concomitant medication with an expected clinically significant drug interaction with rifampicin, which cannot be ceased, substituted for an alternative agent, or mitigated by dose adjustment. 3. One or more causative Gram-positive organisms of interest have in-vitro evidence of resistance to rifampicin 4. Known pregnancy or breastfeeding 5. Treating team deems enrolment in this domain is not in the best interests of the patient. Antibiotic Duration Part A Domain inclusion criteria 1. A single stage revision procedure has been performed For the purposes of this domain, the definition of a single stage revision procedure is as follows: A one-stage revision means: • Arthrotomy • Removal of all prosthetic components • Comprehensive synovectomy • Placement of "definitive" new components * could be primary or revision components • With no plans for a second stage operation Additional recommended elements (not part of definition, but considered 'ideal' elements of this procedure): * Removal of all loose cement; well-fixed cement may be retained. * Double set up (using a separate set of sterile instruments and drapes for the reimplantation) Antibiotic Duration Part A Domain exclusion criteria Patients will be excluded from this domain if, at the time of eligibility assessment, they have any of the following: <!-- --> 1. Any causative organism is a fungus or a 'difficult-to-treat' bacterium at the time of platform entry 2. Treating team deems enrolment in this domain is not in the best interests of the patient 3. The single stage revision was \>7 days ago 4. Patient no longer willing to participate in the domain Antibiotic Duration Part B Domain Eligibility assessment and allocation reveal will be performed at day 7 (+/- 3 days) from the time of the reimplantation operation - i.e. between 4 and 10 days following the reimplantation operation. The purpose of this time frame is to confirmation of negative reimplantation cultures. Antibiotic Duration Part B Domain inclusion criteria 1. A two-stage revision procedure has been performed For the purposes of this domain, the definition of two-stage revision and reimplantation procedures are defined as follows: A two-stage revision means: • Removal of all existing prosthetic components (including metal, ceramic, polyethylene) and any loose cement * Placement of a temporary prosthesis or spacer with the intention to replace this at a later time point with a permanent prosthesis * The intention to subsequently replace of the temporary spacer with a definitive prosthesis at a reimplantation operation in the future Additional recommended elements (not part of definition, but encouraged): • Use of antibiotic-loaded cement as the spacer * Use of an articulating spacer which is capable of withstanding weight-bearing A reimplantation procedure as the second stage of a two-stage revision means: • Removal of the temporary prosthesis and all associated cement * Implantation of a new prosthesis; considered the 'destination prosthesis' 2. The infected prosthesis was a primary (not revision) arthroplasty 3. At least 6 weeks of antibiotics have been received following the first stage revision, intended as treatment of the index infection 4. The reimplantation operation was done 4-10 days ago Antibiotic Duration Part B Domain exclusion criteria 1. \>6 months has passed since platform entry 2. One or more of the causative organisms is a fungus or a 'difficult-to-treat' bacterium 3. No perioperative tissue or fluid cultures were collected at the reimplantation operation 4. Perioperative cultures collected at reimplantation grow a significant organism (s) 5. Long-term antibiotic suppressive therapy is planned following the reimplantation operation 6. Treating team deems enrolment in this domain is not in the best interests of the patient 7. Patient no longer willing to participate in the domain