review · The Veterinary Journal
Bovine mastitis and rising antimicrobial resistance present serious challenges to dairy production and food security, driving interest in non-antibiotic treatments. A systematic review and meta-analysis evaluating research from January 2020 to June 2025 synthesised evidence across sixty studies, eleven intervention categories, and twenty-eight countries. Phytochemicals and nanoparticles emerged as the most frequently evaluated approaches, with laboratory in vitro experiments dominating the existing literature. Pooled estimates of antimicrobial potency showed comparable overall minimum inhibitory concentrations against Staphylococcus aureus and Escherichia coli, alongside substantial variation across studies. Meta-regression showed that nanoparticles exhibited significantly higher potency against Staphylococcus aureus than phytochemicals. However, the predominance of laboratory testing and pronounced study heterogeneity highlight that current alternatives require harmonised experimental methodologies and robust animal validation before they can effectively replace conventional antibiotics in dairy herds.
Antimicrobial resistance in dairy cattle threatens animal welfare, milk production, and broader food security. Finding functional alternatives to antibiotics for bovine mastitis is vital to reducing reliance on standard drugs. Synthesising global efficacy data clarifies which emerging treatments show measurable antimicrobial impact, helping veterinary scientists and dairy industry stakeholders focus future validation efforts on the most viable candidates.
The findings are relevant to veterinary pharmaceutical developers and livestock health companies seeking non-antibiotic mastitis therapies, with nanoparticles presenting the strongest immediate potency. However, the technology sits at an early stage of development, as the evidence base is almost entirely restricted to in vitro experiments. Substantial in vivo validation and standardised testing protocols are necessary before viable commercial formulations can reach dairy producers.
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The impact of antimicrobial resistance (AMR) on diary production and global food security due to bovine mastitis raises the need to develop new alternatives to reduce reliance on antibiotics. While an increasing number of alternatives are being evaluated, a comprehensive quantitative synthesis of their potential is scarce. We conducted a systematic review and meta-analysis following PRISMA guidelines to evaluate antimicrobial potency and translational relevance of the current alternatives. Relevant studies, published between January 2020 and June 2025, were identified and screened for eligibility. Quantitative outcome data were analysed using a multilevel random-effects model and meta-regression. All statistical analyses were performed using R software. Sixty eligible studies, spanning 28 countries and 11 intervention types, were included. Among other alternatives, phytochemicals and nanoparticles were most extensively evaluated, with overall dominance of in vitro experiments. Based on the minimum inhibitory concentration (log 10 MIC) data, the overall pooled estimate of the alternatives was 2.83 µg/ml (95% CI: 2.36–3.30) for Staphylococcus aureus , and 2.89 µg/ml (95% CI: 2.27–3.51) for Escherichia coli . Substantial between-study heterogeneity (τ² > 0.8, I² > 95%, p < 0.0001) and a wide p rediction interval (0.45–5.21 µg/ml) were observed. Meta-regression analysis indicated significantly higher antimicrobial potency in nanoparticles than phytochemicals against Staphylococcus aureus , with lower log 10 MIC values (β = -0.131, p < 0.0001). In conclusion, prioritising harmonised research methodologies and robust in vivo validation of the most promising alternatives are needed before emerging alternatives can contribute meaningfully to sustainable mastitis management and AMR mitigation.
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DOI: 10.1016/j.tvjl.2026.106844
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