Multimodal Hand Hygiene Interventions and Clinical Healthcare-Associated Infection Outcomes in Acute Care Hospitals: A Systematic Review of Quasi-Experimental Studies

Background/Objectives: Hand hygiene is a cornerstone of infection prevention, yet the extent to which multimodal institutional hand hygiene interventions translate into measurable reductions in healthcare-associated infections (HAIs) remains uncertain. This systematic review aimed to evaluate the association between hospital-wide or multi-ward multimodal hand hygiene interventions and clinical HAI outcomes in acute care hospitals. Methods: A structured literature search was conducted in PubMed, Scopus, Embase, and Google Scholar using a combination of Medical Subject Headings (MeSH) and free-text terms related to hand hygiene, healthcare-associated infections, hospital settings, and intervention strategies. Eligible studies were quasi-experimental designs, including before–after, controlled before–after, and interrupted time-series studies, evaluating multimodal hand hygiene interventions implemented at hospital-wide or multi-ward level and reporting clinical HAI outcomes. Two reviewers independently assessed risk of bias using the ROBINS-I tool, and certainty of evidence across major outcome categories was summarized using GRADE. Results: twelve studies met the inclusion criteria. Overall, multimodal hand hygiene interventions were generally associated with favorable directional trends in clinical outcomes. Reductions were most consistent for broader institutional HAI measures and some device-associated infections, particularly central line-associated bloodstream infections. In contrast, organism-specific outcomes, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and Clostridioides difficile, were more heterogeneous across studies and settings. All included studies were judged to be at serious or critical overall risk of bias, primarily because of confounding, lack of contemporaneous controls, co-interventions, and phased implementation. Conclusions: Multimodal hand hygiene programs in acute care hospitals may be associated with improvement in selected clinically relevant HAI outcomes, particularly at the institutional level. However, the overall certainty of evidence remains low to very low, and the strength of inference is limited by the non-randomized nature of the available studies and the difficulty of isolating the independent effect of hand hygiene within complex infection-prevention strategies.