Broad-spectrum antibiotic prophylaxis in tumor and infected orthopedic surgery-the prospective-randomized, microbiologist-blinded, stratified, superiority trials: BAPTIST Trials

Abstract

Background: The perioperative antibiotic prophylaxis with 1st or 2nd generation cephalosporins is evidence-based in orthopedic surgery. There are, however, situations with a high risk of prophylaxis-resistant surgical site infections (SSI).

Methods: We perform a superiority randomized controlled trial with a 10% margin and a power of 90% in favor of the broad-spectrum prophylaxis. We will randomize orthopedic interventions with a high risk for SSI due to selection of resistant pathogens (open fractures, surgery under therapeutic antibiotics, orthopedic tumor surgery, spine surgery with American Society of Anesthesiologists (ASA) score ≥ 3 points) in a prospective-alternating scheme (1:1, standard prophylaxis with cefuroxime versus a broad-spectrum prophylaxis of a combined single-shot of vancomycin 1 g and gentamicin 5 mg/kg parenterally). The primary outcome is "remission" at 6 weeks for most orthopedic surgeries or at 1 year for surgeries with implant. Secondary outcomes are the risk for prophylaxis-resistant SSI pathogens, revision surgery for any reason, change of antibiotic therapy during the treatment of infection, adverse events, and the postoperative healthcare-associated infections other than SSI within 6 weeks (e.g., urine infections or pneumonia). With event-free surgeries to 95% in the broad-spectrum versus 85% in the standard prophylaxis arm, we need 2 × 207 orthopedic surgeries.

Discussion: In selected patients with a high risk for infections due to selection of prophylaxis-resistant SSI, a broad-spectrum combination with vancomycin and gentamycin might prevent SSIs (and other postoperative infections) better than the prophylaxis with cefuroxime.

Trial registration: ClinicalTrial.gov NCT05502380. Registered on 12 August 2022. Protocol version: 2 (3 June 2022).

Keywords: Broad-spectrum antibiotic prophylaxis; Orthopedic surgery; Postoperative healthcare-associated infections; Randomized-controlled trial; Surgical site infections.

Fig. 1

Study criteria

Fig. 2

Main study flowchart

Fig. 3

SPIRIT flowchart of enrolments and assessments during the trials. Visit times related to the Allocation (Inclusion) day: V₁ = Day =, start of therapy, V₂ = Day 14 (+/- 3 days; end-of-treatment visit), V₃ = Day 42 (+/- 14 days; test-of-cure visit). Baseline variables: age, sex, known immune-suppression (diabetes mellitus, renal dialysis, cirrhosis, pregnancy, medicamentous immune-suppression, untreated HIV disease, agranulocytosis, active cancer), American Society of Anesthesiologists’ (ASA)-Score Surgery specific baseline data: number and type of surgeries for the actual problem, agent, dose and duration of pre-surgical antibiotic therapy, local antibiotics used in the bone, cell count (if any), initial serum CRP level, presence of initial bacteremia. Anatomical localization of surgery, type of surgery, microbiological results, histology (facultative). Control and outcome variables: number of surgeries to treat infection, total duration of antibiotic therapy, duration, agent and dose of intravenous and oral antibiotic therapy, wound healing problems, presence and duration of vacuum-assisted negative pressure therapy, adverse events, clinical or and microbiological recurrence, date and reasons for re-hospitalization and re-treatment, follow-up data, fatalities. Administrative data: total hospitalization length, BioBanking of infected tissues at the Balgrist Campus *The visits are all standard. The data is collected from the medical record