Management of Multidrug-Resistant Infections in ICUs: A Narrative Review of Pharmacological and Non-pharmacological...

Multidrug-resistant (MDR) infections in ICUs are a growing global health challenge associated with increased morbidity, mortality, prolonged hospitalization, and rising healthcare costs. Critically ill patients are particularly vulnerable because of immune dysfunction, invasive procedures, prolonged ICU stays, and frequent exposure to broad-spectrum antibiotics, all of which increase susceptibility to MDR infections and antimicrobial selection pressure. Common MDR pathogens in ICU settings include Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), and carbapenem-resistant Enterobacterales. Major resistance mechanisms include β-lactamase and carbapenemase production, efflux pump overexpression, reduced membrane permeability, target modification, biofilm formation, and horizontal gene transfer. Effective management of MDR infections in ICUs requires an integrated, evidence-based approach combining early recognition, microbiological diagnosis, optimized antimicrobial therapy, and strict infection-prevention strategies. Pharmacological management relies on appropriate empiric therapy, antimicrobial stewardship, therapeutic drug monitoring, and pharmacokinetic/pharmacodynamic optimization to improve treatment efficacy while minimizing toxicity and resistance development. Newer antimicrobial agents, including β-lactam/β-lactamase inhibitor combinations and cefiderocol, have expanded treatment options for resistant resistant Gram-negative infections. Non-pharmacological interventions such as hand hygiene, environmental disinfection, surveillance cultures where indicated, contact precautions, and multidisciplinary infection-control programs remain essential in reducing transmission. Emerging innovations, including artificial intelligence-guided antimicrobial selection, rapid diagnostic technologies, microbiome-based therapies, and bacteriophage therapy, show promise for future management. A multidisciplinary strategy integrating prevention, stewardship, and ongoing research is essential to reduce the MDR burden in ICUs and preserve antimicrobial effectiveness.