念珠菌血症和/或侵袭性念珠菌病由念珠菌属引起的临床和真菌学结果以及抗真菌药敏性：瑞扎芬净与卡泊芬净两项随机试验的汇总分析

Clinical and mycological outcomes of candidaemia and/or invasive candidiasis by Candida spp. and antifungal susceptibility: pooled analyses of two randomized trials of rezafungin versus caspofungin.

作者信息

Soriano Alex, Locke Jeffrey B, Cornely Oliver A, Roilides Emmanuel, Ramos-Martinez Antonio, Honoré Patrick M, Castanheira Mariana, Carvalhaes Cecilia G, Nseir Saad, Bassetti Matteo, Manamley Nick, Sandison Taylor, Arendrup Maiken C

机构信息

Hospital Clínic de Barcelona, IDIBAPS, CIBERINF, University of Barcelona, Barcelona, Spain.

Microbiology, Cidara Therapeutics, Inc., San Diego, CA, USA.

出版信息

Clin Microbiol Infect. 2025 Feb;31(2):250-257. doi: 10.1016/j.cmi.2024.11.029. Epub 2024 Nov 22.

DOI:10.1016/j.cmi.2024.11.029

PMID:39581541

Abstract

OBJECTIVES

A post hoc analysis used pooled STRIVE/ReSTORE trial data to determine outcomes with rezafungin versus caspofungin by Candida species and antifungal susceptibility.

METHODS

The efficacy and safety of once weekly rezafungin 400/200 mg versus once daily caspofungin 70/50 mg was demonstrated in the randomized, double-blind phase 2 STRIVE (NCT02734862) and phase 3 ReSTORE (NCT03667690) trials involving adults with candidaemia and/or invasive candidiasis. In this analysis, data were pooled for patients with a documented Candida infection within 96 hours of randomization who also received ≥1 dose of study drug. Treatment outcomes were evaluated by Candida species and baseline MICs. Susceptibility was determined using European Committee on Antimicrobial Susceptibility Testing E.Def 7.4 broth microdilution methodology, with Tween 20-supplemented medium for rezafungin.

RESULTS

A total of 294 patients were included (rezafungin: N = 139, caspofungin: N = 155). Susceptibility testing at baseline identified three rezafungin non-susceptible isolates. Day 14 global cure rates were numerically similar between groups for C. albicans (rezafungin: 61.0% [36/59], caspofungin: 65.2% [45/69]) and C. tropicalis (rezafungin: 70.4% [19/27], caspofungin: 63.6% [14/22]), but higher with rezafungin than caspofungin for C. glabrata (rezafungin: 71.1% [27/38], caspofungin: 60.0% [21/35]) and C. parapsilosis (rezafungin: 78.6% [11/44], caspofungin: 55.6% [15/27]). Day 30 all-cause mortality rates were numerically similar between groups for C. albicans (rezafungin: 22.0% [13/59], caspofungin: 18.8% [13/69]) and C. glabrata (rezafungin: 15.8% [6/38], caspofungin: 11.4% [4/35]), but higher with caspofungin than rezafungin for C. tropicalis (rezafungin: 18.5% [5/27], caspofungin: 31.8% [2/22]) and C. parapsilosis (rezafungin: 7.1% [1/14], caspofungin: 29.6% [8/27]). Day 5/14 mycological eradication rates were numerically similar between treatments for C. albicans and C. parapsilosis, but higher with rezafungin for C. glabrata and C. tropicalis. Outcomes by Candida species were not associated with treatment-specific MICs.

DISCUSSION

Rezafungin appears to be an effective treatment for candidaemia/invasive candidiasis irrespective of baseline Candida species.

摘要

目的

一项事后分析使用STRIVE/ReSTORE试验汇总数据，按念珠菌种类和抗真菌药敏情况确定瑞扎芬净与卡泊芬净的治疗结果。

方法

在涉及念珠菌血症和/或侵袭性念珠菌病成人患者的随机、双盲2期STRIVE试验（NCT02734862）和3期ReSTORE试验（NCT03667690）中，证明了每周一次400/200mg瑞扎芬净与每日一次70/50mg卡泊芬净的疗效和安全性。在该分析中，汇总了随机分组后96小时内有记录的念珠菌感染且接受了≥1剂研究药物的患者的数据。根据念珠菌种类和基线最低抑菌浓度（MIC）评估治疗结果。使用欧洲抗菌药物敏感性试验委员会E.Def 7.4肉汤微量稀释法测定药敏情况，瑞扎芬净使用添加吐温20的培养基。

结果

共纳入294例患者（瑞扎芬净组：N = 139，卡泊芬净组：N = 155）。基线药敏试验鉴定出3株对瑞扎芬净不敏感的菌株。白色念珠菌组（瑞扎芬净：61.0% [36/59]，卡泊芬净：65.2% [45/69]）和热带念珠菌组（瑞扎芬净：70.4% [19/27]，卡泊芬净：63.6% [14/22]）第14天的总体治愈率在两组间数值相近，但光滑念珠菌组（瑞扎芬净：71.1% [27/38]，卡泊芬净：60.0% [21/35]）和近平滑念珠菌组（瑞扎芬净：78.6% [11/44]，卡泊芬净：55.6% [15/27]）中瑞扎芬净组的治愈率高于卡泊芬净组。白色念珠菌组（瑞扎芬净：22.0% [13/59]，卡泊芬净：18.8% [13/69]）和光滑念珠菌组（瑞扎芬净：15.8% [6/38]，卡泊芬净：11.4% [4/35]）第30天的全因死亡率在两组间数值相近，但热带念珠菌组（瑞扎芬净：18.5% [5/27]，卡泊芬净：31.8% [2/22]）和近平滑念珠菌组（瑞扎芬净：7.1% [1/14]，卡泊芬净：29.6% [8/27]）中卡泊芬净组的死亡率高于瑞扎芬净组。白色念珠菌和近平滑念珠菌的治疗间第5/14天真菌清除率数值相近，但光滑念珠菌和热带念珠菌中瑞扎芬净组的清除率更高。按念珠菌种类划分的治疗结果与治疗特异性MIC无关。