Venatorx Pharmaceuticals, Inc., Malvern, Pennsylvania, USA.
LBG Consulting, LLC, Saint Davids, Pennsylvania, USA.
Antimicrob Agents Chemother. 2024 Jul 9;68(7):e0023624. doi: 10.1128/aac.00236-24. Epub 2024 May 23.
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 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 (9/19; 47.4%) and ESBL (13/25; 52.0%) compared with 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 ; 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.
This study is registered with ClinicalTrials.gov as NCT03840148.
CERTAIN-1 是一项 3 期、双盲、随机、平行分组研究，旨在评估头孢吡肟-他唑巴坦与美罗培南治疗复杂性尿路感染（cUTI）成人患者（包括急性肾盂肾炎）的疗效和安全性。我们确定了肠杆菌科细菌对头孢吡肟-他唑巴坦和对照药物的敏感性，并对基线病原体的β-内酰胺耐药机制进行了特征分析。根据基线病原体的表型对患者亚组进行评估，这些病原体对头孢吡肟、多药耐药或碳青霉烯类耐药，或携带β-内酰胺酶基因。在肠杆菌科细菌的基线病原体中，分别有 26.8%、4.1%和 3.0%携带超广谱β-内酰胺酶（ESBLs）、AmpC 和碳青霉烯酶基因。在每个治疗组中，耐药亚组的治疗后临床疗效评估中，复合成功率按病原体种类与总体复合成功率相似，但美罗培南患者中，头孢吡肟耐药（19 例中有 9 例；47.4%）和 ESBL（25 例中有 13 例；52.0%）的复合成功率低于总体（100 例中有 62 例；62.0%）。头孢吡肟-他唑巴坦在 8 例耐碳青霉烯类肠杆菌科细菌患者（87.5%）和 9 例携带碳青霉烯酶基因的肠杆菌科细菌患者（5 例 OXA-48 组；2 例 KPC-3；2 例 NDM-1）中均达到复合成功率。头孢吡肟-他唑巴坦在 16 例携带头孢吡肟、多药耐药和碳青霉烯类耐药病原体的患者中达到复合成功率（8/16，50.0%）和临床成功率（13/16，81.3%），相应的美罗培南为 4/7（57.1%）和 6/7（85.7%）。头孢吡肟-他唑巴坦在治疗成人 cUTI 患者中，对携带 ESBL、AmpC 和碳青霉烯酶基因的头孢吡肟、多药耐药和碳青霉烯类耐药病原体具有疗效。
本研究在 ClinicalTrials.gov 上注册，编号为 NCT03840148。
