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Published on: August 30, 2018
Management of MDR/XDR severe infections in the critically ill
Luca Mezzadri1,2, Ya-Ting Chang1,3, David L Paterson1,4
1ADVANCE-ID, Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
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.
Insights
Managing serious infections from multidrug-resistant (MDR) and extensively drug-resistant (XDR) pathogens requires updated knowledge of treatments and resistance. High-quality clinical trials are crucial for evidence-based therapy against these challenging infections.
Area of Science:
- Infectious Diseases
- Clinical Microbiology
- Pharmacology
Background:
- Serious infections caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) pathogens pose a significant global health challenge.
- Current treatment guidelines are often limited by a lack of robust clinical trial data for these difficult-to-treat organisms.
Purpose of the Study:
- To review current recommendations for managing serious infections caused by MDR/XDR pathogens.
- To focus on evidence from randomized controlled trials (RCTs) and highlight emerging therapeutic options.
Main Methods:
- Systematic review of randomized controlled trials (RCTs) and recent clinical data.
- Analysis of treatment strategies for specific MDR/XDR pathogens, including Gram-positive and Gram-negative bacteria.
Main Results:
- For methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs), vancomycin, linezolid, and daptomycin are primary options, with ceftobiprole as a newer agent.
- Management of vancomycin-resistant Enterococcus faecium BSIs relies on linezolid and daptomycin.
- Treatment of MDR/XDR Gram-negative infections is challenging; new beta-lactam/beta-lactamase inhibitor combinations are key for carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa.
- Cefiderocol and ceftazidime-avibactam plus aztreonam are last-resort options for metallo-β-lactamase producers.
- Sulbactam-durlobactam shows promise for carbapenem-resistant Acinetobacter baumannii but has limited availability.
Conclusions:
- Effective management of serious MDR/XDR infections necessitates continuous updates on treatment options and resistance patterns.
- There is a critical need for more high-quality clinical trials to establish evidence-based therapeutic guidelines.
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