H. Bott, R. Pei, M. E. Murphy, T. Shi, A. Ho
Background Bacterial co-infection contributes substantially to influenza-associated morbidity and mortality. Patterns of viral circulation, diagnostic testing and antimicrobial use changed markedly during the COVID-19 pandemic, yet contemporary estimates of bacterial co-infection and antimicrobial use in influenza have not been synthesised. Objectives To estimate the pooled prevalence of microbiologically confirmed bacterial co-infection among hospital-attended patients with laboratory-confirmed influenza. Secondary objectives were to characterise co-infecting bacterial pathogens, quantify antimicrobial prescribing overall and across key subgroups. This study was registered with PROSPERO (CRD420251072782). Data sources and eligibility We searched Embase (Ovid), MEDLINE, PubMed, Scopus, and Web of Science to 15th June 2025 for studies including [≥]50 hospital-attended patients with laboratory-confirmed influenza and reporting bacterial co-infection. Methods Pooled prevalence estimates and antimicrobial prescription proportions were calculated using a generalised linear mixed model with logit link. Subgroup analyses included age group, clinical setting, and seasonal vs. pandemic influenza. Risk of bias was assessed using JBI Critical Appraisal tools and certainty of evidence using GRADE. Results Ninety-seven studies from 30 countries, comprising 116,273 patients with influenza, met inclusion criteria; 10,880 had confirmed bacterial co-infection. The pooled prevalence was 16.7% (95%CI 13.9-20.0%; I2=99.0%). Prevalence was higher in ICU compared to non-ICU settings (27.6% vs. 13.4%). The most frequently identified bacterial pathogens were Streptococcus pneumoniae (35.7%) and Staphylococcus aureus (30.3%). Antimicrobial use, reported in 38 studies, was high (pooled prevalence 88.1%, 95%CI 76.0-94.5%; I2=99.9%), and was more common in adults than children (97.8% vs 65.0%), and in ICU compared with non-ICU settings (96% vs 81%). Conclusions Bacterial co-infection was identified in approximately one in six hospital-attended influenza cases, yet antimicrobial prescribing is near-universal. Substantial heterogeneity and diagnostic variability constraint interpretation but underscore persistent challenges in clinical decision-making. These findings support strengthened diagnostic capacity and antimicrobial stewardship to optimise management of suspected influenza-associated bacterial co-infection.