Alternatives to antibiotics for bovine mastitis management: a systematic review and meta-analysis of efficacy and translational evidence.

Nanoparticles and phytochemicals show in vitro promise, but lack in vivo validation for clinical mastitis use.

This systematic review and meta-analysis evaluated the antimicrobial efficacy and translational relevance of alternatives to antibiotics for bovine mastitis management, following PRISMA guidelines. Sixty eligible studies published between January 2020 and June 2025, spanning 28 countries and 11 intervention types, were included. Phytochemicals and nanoparticles were the most extensively studied alternatives, though the majority of evidence derives from in vitro experiments rather than in vivo or clinical trials. Using a multilevel random-effects model, the pooled minimum inhibitory concentration (log MIC) estimates were 2.83 µg/ml (95% CI: 2.36–3.30) against Staphylococcus aureus and 2.89 µg/ml (95% CI: 2.27–3.51) against Escherichia coli. Substantial between-study heterogeneity was identified (τ² > 0.8, I² > 95%), and a wide prediction interval (0.45–5.21 µg/ml) underscores the variability across studies. Meta-regression demonstrated that nanoparticles exhibited significantly greater antimicrobial potency than phytochemicals against S. aureus (β = -0.131, p < 0.0001). The authors conclude that while promising alternatives exist, inconsistent research methodologies and a predominance of in vitro data limit clinical applicability. Harmonised study designs and robust in vivo validation are necessary before these alternatives can reliably contribute to sustainable mastitis management and antimicrobial resistance mitigation in dairy production.

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