Safety of routine antimicrobial prophylaxis for surgery (SAPPHIRE): a prospective multi-centre cohort study

Background: Prophylactic antimicrobial drugs are routinely administered for most surgical procedures worldwide. However, the benefit may be modest and supported by low-certainty evidence, while little is known about safety in contemporary practice. Methods: Observational study in 26 UK hospitals between 2022 and 2024. Eligible patients were aged ≥18 years undergoing any of six common surgical procedures. The exposure was the number of antimicrobial doses administered before, during or after surgery to prevent infection. The primary outcome was surgical site infection (SSI) within 30 days after surgery. Secondary outcomes were antimicrobial side effects (diarrhoea, hearing loss, tinnitus, vertigo, acute kidney injury), all post-operative infections and all post-operative complications. Data are presented as mean (SD), median (IQR) or risk differences (RD) with 95% confidence intervals. Findings: Of 13,720 patients, 13,646 were included in the analysis. Mean age was 59 (20) years and 9059/13,646 (66%) patients were women. 13,246/13,646 (97.1%) patients received antimicrobial prophylaxis (median of 2 (1-2) doses). 1097/13,646 (8.0%) patients experienced an SSI. Increasing number of antimicrobial prophylaxis doses was not associated with a reduction in SSI (1 dose: RD -0.2% [-2.5 to 2.2]; to >10 doses: 0.6% [-2.4 to 3.6]). There was a dose-related increase in antimicrobial side effects (1 dose: RD -1.4% [-3.9 to 1.0], to >10 doses: 4.2% [0.4-7.9]) and complications (1 dose: RD -0.2% [-4.2 to 3.8], to >10 doses: 6.2% [0.5-11.8]). 875/13,646 (6.4%) patients experienced antimicrobial-related side effects compared to an expected incidence of 2.2%. Overall infection rates did not differ with increasing antimicrobial doses. Study registration: ISRCTN15775657. Interpretation: In this study, increasing doses of antimicrobial prophylaxis did not improve SSI prevention. Antimicrobial side effect rates were much higher than expected, especially among patients receiving more doses. Adherence to antimicrobial prophylaxis protocols could improve side effect rates without an increase in the incidence of SSI. Funding: British Journal of Anaesthesia (WKR0-2020-0020); National Institute for Health and Care Research (NIHR): (CL-2021-19-501), (NIHR305701), (DRF-2020-301454), (DRF-2018-11-ST2-062), (NIHR RP-PG-0218-20001).