European Network for Optimization of Veterinary Antimicrobial Therapy (ENOVAT) guidelines for antimicrobial and non-steroidal anti-inflammatory drug use in bovine respiratory disease

<ns5:p> Background Bovine respiratory disease (BRD) is a major cause of morbidity, mortality, impaired welfare, production loss, and antimicrobial use in cattle. These European Network for Optimization of Veterinary Antimicrobial Therapy (ENOVAT) guidelines provide evidence-based recommendations for antimicrobial and non-steroidal anti-inflammatory drug (NSAID) use in cattle with acute, undifferentiated BRD, balancing animal-level outcomes with antimicrobial stewardship. Methods Recommendations were developed using the GRADE approach and Evidence-to-Decision frameworks, following ENOVAT procedures and RIGHT reporting guidance. Evidence came from two prespecified systematic reviews and meta-analyses of randomized controlled trials evaluating individual treatment of clinical BRD: one comparing antimicrobial classes head-to-head and one evaluating NSAIDs as adjunctive treatment or monotherapy. Metaphylaxis and prophylaxis were excluded. Certainty of evidence was assessed with GRADE. Panel judgments incorporated stakeholder-derived thresholds for clinically meaningful differences in short-term therapeutic failure, defined as need for antimicrobial re-treatment, and a merged stewardship perspective based on WHO antimicrobial importance and EMA AMEG categories. Results Across antimicrobial comparisons, no class showed a clinically meaningful advantage in reducing short-term re-treatment sufficient to override stewardship considerations. The panel conditionally suggests penicillin G, oxytetracycline, or florfenicol as first-line empirical treatment, guided by local susceptibility data, herd treatment history, product authorization, withdrawal periods, and suspicion of <ns5:italic>Mycoplasmopsis bovis</ns5:italic> infection. Macrolides are conditionally suggested as second-line treatment, preferably guided by culture and susceptibility testing or documented treatment failure. Fluoroquinolones are recommended against as primary or secondary treatment, except in exceptional, justified circumstances consistent with regulations. Adding NSAIDs to antimicrobials did not meaningfully reduce antimicrobial re-treatment; the panel recommends against NSAID use for this specific purpose. Evidence was insufficient to recommend for or against NSAIDs for welfare-related outcomes or as antimicrobial substitutes. Conclusions These guidelines prioritize effective BRD treatment while reducing unnecessary use of higher-priority antimicrobials. Local adoption or adaptation using GRADE-ADOLOPMENT is recommended. </ns5:p>