Healthcare-Associated Infections (HAIs) are among the leading causes of morbidity and mortality in critically ill patients admitted to intensive care units. The growing spread of multidrug-resistant (MDR), extensively drug-resistant (XDR), and totally drug-resistant (TDR) microorganisms is making the clinical management of sepsis and septic shock increasingly complex. AIM: We conducted an uncontrolled retrospective before-and-after study comparing ICU patients admitted before and after implementation of the P-GRISS protocol (Prevention and Rapid Management of Infections and Sepsis), based on four integrated strategies: environmental prevention, microbiota restoration, rapid point-of-care molecular diagnostics, and early targeted antimicrobial therapy. Methods: We carried out a retrospective study between 1 January 2015 and 31 March 2019 at the Anesthesia and Intensive Care Unit of Sora Hospital, Italy. Results: The introduction of advanced air purification systems led to a 64% reduction in healthcare-associated Acinetobacter baumannii infections and a 76% reduction in Pseudomonas infections, with no cases of cross-transmission of Staphylococcus or Clostridioides difficile reported during the observation period. The use of the FilmArray molecular platform allowed pathogen identification in about one hour, facilitating the early initiation of targeted therapies. Sepsis-attributable mortality (calculated on the total ICU-admitted population, including deaths occurring outside the ICU) decreased from 13.5% to 7.0% (p < 0.004). Conclusions: The implementation of the P-GRISS bundle was associated with a reduction in HAIs. However, the relative contribution of environmental purification, rapid diagnostics, microbiota restoration, and antimicrobial optimization cannot be determined from the present study.
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