Antibiotic Use, Bacterial Co-Infection, and Antimicrobial Resistance in Adults Hospitalized with COVID-19, Influenza, or RSV: A Systematic Review and Meta-Analysis

Background: Adults hospitalized with COVID-19, influenza A/B, or respiratory syncytial virus (RSV) frequently receive empirical antibiotics, but antibiotic prescribing, confirmed bacterial co-infection, antimicrobial resistance (AMR), and outcomes have not been jointly synthesized across these infections. Methods: We conducted a PRISMA 2020 systematic review and meta-analysis of 39 studies including 839,531 hospitalized adults. Random-effects models with Freeman–Tukey double-arcsine transformation pooled prevalence estimates; sensitivity and publication-bias analyses were performed where appropriate. Results: Pooled antibiotic use was 62.56% (95% CI, 53.75–70.97%) for COVID-19, 57.48% (25.76–86.09%) for influenza A/B, and 76.03% (67.62–83.53%) for RSV, with very high heterogeneity. Confirmed bacterial co-infection was lower: 5.31% (3.43–7.56%), 18.66% (9.98–29.30%), and 24.36% (18.53–30.70%), respectively. Prescribing-to-confirmed infection ratios ranged from 3.0 to 46.2. AMR evidence was restricted to COVID-19 studies and was dominated by carbapenem-resistant Gram-negative organisms, mainly in secondary, ICU-associated, or healthcare-associated infections. Confirmed bacterial complications were associated with ICU admission, longer hospitalization, and higher mortality. Conclusions: Antibiotic prescribing exceeded confirmed bacterial infection across all viral groups, but estimates require cautious interpretation due to heterogeneity, diagnostic uncertainty, observational evidence, and the absence of low-risk-of-bias studies. The evidence base was dominated by COVID-19 cohorts, while influenza A/B and RSV data, especially virus-specific AMR evidence, remain limited. COVID-19-specific AMR findings should not be generalized to influenza A/B or RSV. Virus-specific stewardship should prioritize rapid diagnostics, systematic sampling, reassessment, and de-escalation when bacterial infection is not confirmed.