Arns Beatriz, Horvath Jaqueline Driemeyer C, Rech Gabriela Soares, Sesin Guilhermo Prates, Agani Crepin Aziz Jose Oluwafoumi, da Rosa Bruna Silveira, Dos Santos Tiago Marcon, Brochier Liliane Spencer Bittencourt, Cavalcanti Alexandre Biasi, Tomazini Bruno Martins, Pereira Adriano Jose, Veiga Viviane Cordeiro, Nascimento Giovana Marssola, Kalil Andre C, Zavascki Alexandre P
Responsabilidade Social-PROADI, Hospital Moinhos de Vento, Porto Alegre, RS, Brazil.
Infectious Diseases and Infection Control Service, Hospital Moinhos de Vento, 910 Ramiro Barcelos St, Porto Alegre, RS, 90035-000, Brazil.
Infect Dis Ther. 2024 Jan;13(1):237-250. doi: 10.1007/s40121-023-00897-9. Epub 2023 Dec 16.
Shorter courses of antimicrobials have been shown to be non-inferior to longer, "traditional" duration of therapies, including for some severe healthcare-associated infections, with a few exceptions. However, evidence is lacking regarding shorter regimes against severe infections by multidrug-resistant Gram-negative bacteria (MDR-GNB), which are often caused by distinct strains and commonly treated with second-line antimicrobials. In the duratiOn of theraPy in severe infecTIons by MultIdrug-reSistant gram-nEgative bacteria (OPTIMISE) trial, we aim to assess the non-inferiority of 7-day versus 14-day antimicrobial therapy in critically ill patients with severe infections caused by MDR-GNB.
This is a randomized, multicenter, open-label, parallel controlled trial to assess the non-inferiority of 7-day versus 14-day of adequate antimicrobial therapy for intensive care unit (ICU)-acquired severe infections by MDR-GNB. Adult patients with severe infections by MDR-GNB initiated after 48 h of ICU admission are screened for eligibility. Patients are eligible if they proved to be hemodynamically stable and without fever for at least 48 h on the 7th day of adequate antimicrobial therapy. After consenting, patients are 1:1 randomized to discontinue antimicrobial therapy on the 7th (± 1) day or to continue for a total of 14th (± 1) days.
The primary outcome is treatment failure, defined as death or relapse of infection within 28 days after randomization. Non-inferiority will be achieved if the upper edge of the two-tailed 95% confidence interval of the difference between the clinical failure rate in the 7-day and the 14-day group is not higher than 10%.
The OPTIMISE trial is the first randomized controlled trial specifically designed to assess the duration of antimicrobial therapy in patients with severe infections by MDR-GNB.
ClinicalTrials.gov, NCT05210387. Registered on 27 January 2022. Seven Versus 14 Days of Antibiotic Therapy for Multidrug-resistant Gram-negative Bacilli Infections (OPTIMISE).
抗菌药物疗程缩短已被证明不劣于更长的“传统”疗程，包括一些严重的医疗保健相关感染，但有少数例外情况。然而，对于由多重耐药革兰氏阴性菌（MDR-GNB）引起的严重感染，缺乏关于较短疗程的证据，这些感染通常由不同菌株引起，且常用二线抗菌药物治疗。在多重耐药革兰氏阴性菌引起的严重感染的治疗疗程（OPTIMISE）试验中，我们旨在评估在患有MDR-GNB引起的严重感染的重症患者中，7天与14天抗菌治疗的非劣效性。
这是一项随机、多中心、开放标签、平行对照试验，旨在评估7天与14天充分抗菌治疗对重症监护病房（ICU）获得性MDR-GNB严重感染的非劣效性。筛选入住ICU 48小时后发生MDR-GNB严重感染的成年患者是否符合条件。如果患者在充分抗菌治疗第7天时被证明血流动力学稳定且至少48小时无发热，则符合条件。在获得同意后，患者按1:1随机分为在第7（±1）天停止抗菌治疗或总共持续至第14（±1）天。
主要结果是治疗失败，定义为随机分组后28天内死亡或感染复发。如果7天组和14天组临床失败率差异的双侧95%置信区间的上限不高于10%，则可实现非劣效性。
OPTIMISE试验是首个专门设计用于评估MDR-GNB严重感染患者抗菌治疗疗程的随机对照试验。
ClinicalTrials.gov，NCT05210387。于2022年1月27日注册。多重耐药革兰氏阴性杆菌感染的7天与14天抗生素治疗（OPTIMISE）。
