Background Hospital-acquired infections (HAIs) represent a major global health concern, contributing substantially to increased morbidity, mortality, and healthcare costs. The rising prevalence of multidrug-resistant (MDR) organisms further complicates patient management worldwide. This systematic review aimed to synthesize global evidence on the prevalence of major HAIs and to characterize their associated microbial etiology and antimicrobial resistance patterns. Methods A systematic literature search was conducted in Medline (via PubMed), Embase, and Web of Science to identify studies published between January 2000 and December 2025. Studies reporting the prevalence of HAIs in human populations and providing sufficient demographic and microbiological data were included. Two independent reviewers screened titles, abstracts, and full texts, extracted relevant data, and assessed study quality using the Joanna Briggs Institute (JBI) checklist. Data on HAI prevalence, infection types, bacterial and fungal pathogens, and antimicrobial resistance patterns were synthesized. Results The overall observed prevalence across the included studies was 15.72%, but substantial heterogeneity (I² = 99%) precluded formal meta-analytic pooling, with the highest prevalence reported in Asia (43.04%) and Africa (34.07%). India exhibited the highest national prevalence (24.28%). The most frequently identified pathogens included Staphylococcus aureus , Escherichia coli ( E. coli ), Pseudomonas aeruginosa ( P. aeruginosa ), Klebsiella pneumoniae ( K. pneumoniae ), and Acinetobacter baumannii ( A. baumannii ), many of which demonstrated multidrug resistance. Among 300 S. aureus isolates assessed for vancomycin susceptibility, 35 (11.66%) were reported as VRSA; however, this proportion reflects only the isolates evaluated in the contributing studies and should not be interpreted as the global prevalence of VRSA. Respiratory tract infections, urinary tract infections, and surgical site infections were the most common HAI types, particularly among patients admitted to intensive care units (ICUs). Conclusion Hospital-acquired infections remain a significant global health challenge, with the greatest burden observed in Asia and Africa. The high prevalence of MDR pathogens, particularly S. aureus , E. coli , and P. aeruginosa , complicates clinical management, especially in ICU settings. Strengthening infection prevention and control measures, antimicrobial stewardship programs, and global surveillance systems is essential to reduce the burden of HAIs and improve patient outcomes. Due to insufficient and inconsistent reporting across the included studies, colistin resistance could not be comprehensively evaluated.
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