Management of MDR/XDR severe infections in the critically ill

Purpose of review This review aims to summarize current recommendations for the management of serious infections, such as bloodstream infections (BSIs) and ventilator-associated pneumonia, caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) pathogens, focusing on evidence from randomized controlled trials (RCTs) and emerging treatment options. Recent findings Vancomycin, linezolid, and daptomycin represent the main therapeutic options for the management of methicillin-resistant Staphylococcus aureus infections; among newer agents, ceftobiprole has recently gained approval for BSI treatment. For vancomycin-resistant Enterococcus faecium BSIs, linezolid and daptomycin remain commonly employed despite the lack of comparative RCTs guiding treatment decisions. The management of MDR/XDR Gram-negative infections is challenging, owing to sparse clinical trials for robust guidance and rapid emergence of diverse resistance mechanisms. New beta-lactam/beta-lactamase inhibitor combinations remain the cornerstone of treatment for carbapenem-resistant Enterobacterales and carbapenem-resistant Pseudomonas aeruginosa . Cefiderocol and the combination of ceftazidime-avibactam plus aztreonam represent the current last-resort options for metallo-β-lactamase producers. For carbapenem-resistant Acinetobacter baumannii , sulbactam–durlobactam has demonstrated at least comparable activity compared to colistin but is unavailable in most countries. Summary Optimal management of serious infections by MDR/XDR pathogens requires up-to-date knowledge of evolving treatment options and resistance mechanisms. Further high-quality clinical trials are needed to guide evidence-based therapy.