Short Against Long Antibiotic Therapy for Infected Orthopedic Sites

Study Overview
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Brief Summary
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The investigators will perform two concomitant RCTs, depending on the presence of infected osteosynthesis material at enrolment: - SALATIO 1. Infected implant not removed (or new material inserted): Randomization 6 vs. 12 weeks (+/- 5 days) of total antibiotic therapy counted since the first debridement for infection. Early switch to oral targeted therapy. - SALATIO 2. Infected implant without residual material (definitive removal or within the interval of a two-stage exchange): Randomization 3 vs. 6 weeks (+/- 5 days) of total antibiotic therapy counted since the first debridement for infection. Early switch to oral targeted therapy.

Detailed Description
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The optimal duration of postoperative, systemic antibiotic therapy for implant-related orthopedic infections, with or without implant removal, is unknown. Retrospective studies suggest that a maximum duration of 6 weeks is not inferior to longer administrations; even if the infected implants are kept in place or during a one-stage exchange. Prospective-randomized trials (RCT) suggest that even shorter durations, such 3 or 4 weeks, are possible, when the implant is removed. Likewise, in prospective studies, 6 or 8 weeks of systemic antibiotics are not inferior to the current 12 weeks during DAIR (debridement, antibiotic and implant retention), or during the one-stage exchange; except for one single RCT suggesting a better outcome for 12 weeks in the substrata of arthroplasty infections undergoing the DAIR procedure. However, these RCTs concern selected branches of orthopedic surgery; especially prosthetic joint infections. The investigators intend to expand these evaluations to all fields of orthopedic and hand surgery. The only exceptions would be spine surgery, for which a multicenter, separate RCT is already under way (SASI-trials). The second exception would be the treatment of implant-free diabetic foot infections, for which two RCTs are underway.

Official Title
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Short Against Long Antibiotic Therapy for Infected Orthopedic Sites

Conditions
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Orthopedic Devices Associated With Misadventures, Infection, Surgical Site, Antibiotic Side Effect

Intervention / Treatment
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* Drug: Antibiotic


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years on admission Orthopedic bone and implant infections including musculoskeletal grafts Intraoperative debridement with any surgical technique 12 months of scheduled follow-up from hospitalization Bacterial orthopedic infections of any nature First or second episode of infection Exclusion Criteria: Mycobacterial, fungal, nocardial, and Actinomyces infections Purely soft tissue infections Non-resected cancer in the infection site Purely intrasynovial infections (native joint septic arthritis) More than three debridements performed for infection Absence of at least one surgical intraoperative debridement Spine infections (investigated in another trial)10 Diabetic foot infections (investigated in another trial)7 Documented endocarditis according to the Duke criteria At least 2 prior infection episodes at the actual infection site

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The investigators will perform two concomitant RCTs, depending on the presence of infected osteosynthesis material at enrolment: - SALATIO 1. Infected implant not removed (or new material inserted): Randomization 6 vs. 12 weeks (+/- 5 days) of total antibiotic therapy counted since the first debridement for infection. Early switch to oral targeted therapy. - SALATIO 2. Infected implant without residual material (definitive removal or within the interval of a two-stage exchange): Randomization 3 vs. 6 weeks (+/- 5 days) of total antibiotic therapy counted since the first debridement for infection. Early switch to oral targeted therapy.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Long Antibiotic Arm<br>Without implant material in place: 6 weeks of systemic post-surgical antibiotic therapy With mateial in place 12 weeks of systemic post-surgical antibiotic therapy | Drug: Antibiotic<br>* The investigators will perform two concomitant RCTs, depending on the presence of infected osteosynthesis material at enrolment: - SALATIO 1. Infected implant not removed (or new material inserted): Randomization 6 vs. 12 weeks (+/- 5 days) of total antibiotic therapy counted since the first debridement for infection. Early switch to oral targeted therapy. - SALATIO 2. Infected implant without residual material (definitive removal or within the interval of a two-stage exchange): Randomization 3 vs. 6 weeks (+/- 5 days) of total antibiotic therapy counted since the first debridement for infection. Early switch to oral targeted therapy.<br>|
| Experimental: Short Antibiotic Arm<br>Without implant material in place: 3 weeks of systemic post-surgical antibiotic therapy With mateial in place 6 weeks of systemic post-surgical antibiotic therapy | Drug: Antibiotic<br>* The investigators will perform two concomitant RCTs, depending on the presence of infected osteosynthesis material at enrolment: - SALATIO 1. Infected implant not removed (or new material inserted): Randomization 6 vs. 12 weeks (+/- 5 days) of total antibiotic therapy counted since the first debridement for infection. Early switch to oral targeted therapy. - SALATIO 2. Infected implant without residual material (definitive removal or within the interval of a two-stage exchange): Randomization 3 vs. 6 weeks (+/- 5 days) of total antibiotic therapy counted since the first debridement for infection. Early switch to oral targeted therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical remission related to the duration of total, postdebridement, antibiotic use | Clinical assessment during routine surgical controls. Definition of clinical failure accoding to to sandard criteria in the literature (surgical revision, pain, local inflammation, discharge, several deep intraoperative bacterial tissue samples) | 6 weeks postoperatively, or 1 year postoperatively in case of implant-related orthopedic surgery | 
| Microbiological recurrence in relation to the total, postdebridement, antibiotic use | Recurrence of infection, with the same pathogens, after completing the antibiotic treatment for the index infection | 6 weeks postoperatively, or 1 year postoperatively in case of implant-related orthopedic surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Description of all clinical failures of any sort | Need for hospitalisation or revision surgery for any non-infectious failures related to the operation wound (hematoma, seroma, internal (closed) fractures, dislocation of implants) | 6 weeks postoperatively, or 1 year postoperatively in case of implant-related orthopedic surgery | 
| Adverse events in each study arm, and in relation to the antibiotics used | All adverse events during the therapy and follow-up time , with an emphasis on antibiotic-related adverse events (according to medical judgement). Numbers and descriptions. | 6 weeks postoperatively, or 1 year postoperatively in case of implant-related orthopedic surgery | 
| Length of hospital stay in acute care surgery (without rehabilitation) | The duration of the hospital stay for every episode in both randomizing arm | 6 weeks postoperatively, or 1 year postoperatively in case of implant-related orthopedic surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Orthopedic infectionsT, Duration, Antibiotic Therapy, Randomized-Controlled Trial