1. Patient outcomes by baseline pathogen resistance phenotype and genotype in CERTAIN-1, a Phase 3 study of cefepime-taniborbactam versus meropenem in adults with complicated urinary tract infection.
- Author
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Moeck G, Gasink LB, Mendes RE, Woosley LN, Dorr M, Chen H, Wagenlehner FM, Henkel T, and McGovern PC
- Subjects
- Humans, Adult, Female, Male, Pseudomonas aeruginosa drug effects, Pseudomonas aeruginosa genetics, Middle Aged, Double-Blind Method, Bacterial Proteins genetics, Genotype, Phenotype, Aged, Escherichia coli drug effects, Escherichia coli genetics, Treatment Outcome, Borinic Acids, Carboxylic Acids, Meropenem therapeutic use, Meropenem pharmacology, Cefepime therapeutic use, Cefepime pharmacology, Anti-Bacterial Agents therapeutic use, Anti-Bacterial Agents pharmacology, Urinary Tract Infections drug therapy, Urinary Tract Infections microbiology, Cephalosporins therapeutic use, Cephalosporins pharmacology, Microbial Sensitivity Tests, beta-Lactamases genetics
- Abstract
CERTAIN-1 was a Phase 3, double-blind, randomized, parallel group study of the efficacy and safety of cefepime-taniborbactam versus meropenem in the treatment of adults with complicated urinary tract infection (cUTI), including acute pyelonephritis. We determined susceptibility of Enterobacterales and Pseudomonas aeruginosa baseline pathogens to cefepime-taniborbactam and comparators and characterized β-lactam resistance mechanisms. Microbiologic response and clinical response were assessed in patient subsets defined by baseline pathogens that were of cefepime-, multidrug-, or carbapenem-resistant phenotype or that carried β-lactamase genes. Among Enterobacterales baseline pathogens, 26.8%, 4.1%, and 3.0% carried genes for extended-spectrum β-lactamases (ESBLs), AmpC, and carbapenemases, respectively. Within each treatment group, while composite success rates at Test of Cure in resistant subsets by pathogen species were similar to those by pathogen overall, composite success rates in meropenem patients were numerically lower for cefepime-resistant Escherichia coli (9/19; 47.4%) and ESBL E. coli (13/25; 52.0%) compared with E. coli overall (62/100; 62.0%). Cefepime-taniborbactam achieved composite success in 7/8 (87.5%) patients with carbapenem-resistant Enterobacterales and 8/9 (88.9%) patients with Enterobacterales with a carbapenemase gene (5 OXA-48-group; 2 KPC-3; 2 NDM-1). Cefepime-taniborbactam also achieved composite success in 8/16 (50.0%) patients and clinical success in 13/16 (81.3%) patients with P. aeruginosa ; corresponding rates were 4/7 (57.1%) and 6/7 (85.7%) for meropenem. Cefepime-taniborbactam demonstrated efficacy in adult cUTI patients with cefepime-, multidrug-, and carbapenem-resistant pathogens including pathogens with ESBL, AmpC, and carbapenemase genes., Clinical Trials: This study is registered with ClinicalTrials.gov as NCT03840148.
- Published
- 2024
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