All-cause mortality rates in adults with carbapenem-resistant Gram-negative bacterial infections: a comprehensive review of pathogen-focused, prospective, randomized, interventional clinical studies

Expert Rev Anti Infect Ther. 2021 Dec 23. doi: 10.1080/14787210.2022.2020099. Online ahead of print.ABSTRACTINTRODUCTION: Pathogen-focused, randomized, controlled trials (PF-RCT) are important in the fight against carbapenem-resistant (CR) Gram-negative infections. Some recently approved antibiotics and older generic antibiotics with activity against CR Gram-negative bacteria were investigated in PF-RCTs in a variety of infections.AREAS COVERED: We searched Pubmed, Cochrane database and international clinical trial databases for PF-RCTs for the period between 2005 and 2020 and compared the study designs, patient populations, infection types, pathogens, and Day-28 all-cause mortality (ACM).EXPERT OPINION: PF-RCTs are particularly challenging to quantitatively assess and compare due to the heterogeneity in infection types, pathogens, CR mechanism, inclusion/exclusion criteria, and endpoints. Data interpretation is further complicated by lack of formal statistical analysis plans and/or non-inferiority design, and limited power across most PF-RCTs. The studies with new antibiotics (i.e. plazomicin, meropenem/vaborbactam, cefiderocol) ranked lower regarding feasibility, with relatively small sample sizes (analyzed: 37-118) versus the comparative effectiveness studies of older generic drugs (analyzed: 94-406). ACM ranged between 11.8% and 40% for CR Enterobacterales, 17.7% and 57.4% for CR Acinetobacter spp., and 20.0% and 30.8% for CR Pseudomonas aeruginosa. The information gather...
Source: Expert Review of Anti-Infective Therapy - Category: Infectious Diseases Authors: Source Type: research