Should we use post-operative antibiotics following surgery for patients with mandible fractures? The MANTRA trial (MANdibular TRauma and Antibiotic use)

Research Question: Are post-operative antibiotics required following surgery for patients with mandible fractures?

Background: Mandible fractures are the commonest facial fractures needing surgery and account for a significant percentage of the acute workload in OMFS units. The UK records >6000 new cases per year. Patients having surgery for mandible fractures have a theoretical risk of developing surgical site infection, due to the proximity of the fracture lines to the oral cavity microbes and the presence of foreign body (titanium fixation miniplates).

For this reason, clinicians often prescribe antibiotics after surgery, to reduce the risk of infection. Previous systematic reviews and a multicentre cohort study by this team, revealed significant clinical variation in post-operative antibiotic prescription amongst UK OMFS clinicians and the presence of clinical equipoise. Antibiotic overuse can lead to antibiotic resistance and other antibiotic-related side effects; judicious antibiotic use and stewardship is of paramount importance

Aim: To determine whether postoperative antibiotics are required at all, following surgery for mandible fractures, and, if so, what is the most clinically- and cost-effective regimen Primary Objective:

To conduct a Randomized Controlled Trial (MANTRA) in order to establish the non-inferiority (or not) of not giving postoperative antibiotics versus 2 other postoperative antibiotic regimens. An internal pilot phase will optimise recruitment and retention Secondary Objectives: • Measure the cost-effectiveness of the proposed antibiotic pathways

• Assess patient and clinician acceptability to change clinical practice • Process evaluation to inform dissemination and implementation

Methods: We designed and propose the MANTRA RCT to compare 3 post-operative antibiotic approaches to prevent Surgical Site Infections (SSIs) following surgery for mandible fractures. The MANTRA trial is a large open label, multicentre study in NHS OMFS units. The 3 study arms represent the most common clinical pathways in the UK based on our previous work; the control group is the approach prescribed by most UK OMFS clinicians.

All patients will receive 1 dose of IV antibiotics (co-amoxiclav 1.2g, if no penicillin allergy), on induction of anaesthesia, prior to surgery The participants will be randomised to the following (1:1:1): Group A: No further antibiotics Group B: 2 further postoperative IV doses of co-amoxiclav 1.2g

Group C: 2 further postoperative IV doses (as above), followed by a 5-day course of oral co-amoxiclav 625mg every 8 hours if no penicillin allergy (Control)

Trial processes will be optimised by an internal pilot phase ensuring we recruit, randomise and retain participants with clear progression criteria. We will also conduct cost-effectiveness analyses and process evaluation for dissemination and implementation Timeline: Start of grant: First Day of Month 1

Start of RCT/pilot: First Day of Month 7 End of pilot: Last Day of Month 12 End of recruitment: Last Day of Month 42 End of follow-up: Last Day of Month 48 Completion: Last Day of Month 54 Impact and dissemination:

• Practice changing outputs that standardise the use of antibiotics in mandible fractures and provide a framework for other surgical prophylaxis research • A bespoke clinical dissemination plan via an engagement and training legacy • Cost-effectiveness data to inform policy making • A research legacy and change of culture in the OMFS specialty