Momčilović Mirna, Šitum Ivan, Erceg Ante, Siroglavić Marko, Lovrić Mila, Nižić Nodilo Laura, Hafner Anita, Lovrić Jasmina, Turčić Petra, Fabijanović Dora, Marinić Ana, Nedeljković Vanja, Pašalić Marijan, Perčin Luka, Šipuš Dubravka, Miličić Davor, Lovrić Daniel
Department of Cardiovascular Diseases, University Hospital Centre Zagreb, Zagreb, Croatia.
Department of Anesthesiology, Reanimatology, Intensive Medicine and Pain Therapy, University Hospital Centre Zagreb, Zagreb, Croatia.
Front Pharmacol. 2025 Aug 7;16:1618987. doi: 10.3389/fphar.2025.1618987. eCollection 2025.
Ceftazidime/avibactam (CZA) is an essential treatment option for managing infections caused by multidrug-resistant (MDR) Gram-negative (G-) bacteria, including OXA-48 and carbapenem-resistant . Growing evidence indicates that critically ill intensive care unit (ICU) patients often exhibit altered pharmacokinetics (PK) of CZA, which may compromise the achievement of optimal PK/pharmacodynamic (PD) targets with standard dosing regimens. The primary hypothesis of this study is that continuous infusion (CI) of CZA improves microbiological success compared to intermittent dosing (ID) in critically ill ICU patients with severe infections caused by OXA-48 or .
This is a single-center, randomized, open-label trial with a 1:1 allocation ratio, conducted at the University Hospital Centre Zagreb, a tertiary care hospital in Croatia. A total of 140 critically ill ICU patients with severe infections due to OXA-48 or requiring CZA treatment will be randomized to receive either ID of CZA (2 g/0.5 g/8 h over 2 h) or the same total daily dose in CI (6 g/1.5 g over 24 h). The study is powered to demonstrate the superiority of CI over ID of CZA in terms of microbiological success.
The primary outcome will be microbiological success rate, chosen as a key indicator of pathogen eradication that is directly influenced by PK/PD target attainment. Secondary outcomes will include clinical success rate, time to symptoms improvement, length of ICU stay, length of hospital stay, all-cause 28-day mortality, pathogen recurrence rate on day 28, time to weaning from mechanical ventilation, cumulative vasoactive-inotropic score, adverse events, and the ratio of ceftazidime plasma concentration to the pathogen's minimum inhibitory concentration (C/MIC).
This trial will provide evidence on optimal CZA administration regimen in critically ill ICU patients with severe infections due to MDR G-pathogens.
clinicaltrials.gov, identifier NCT06811727.
头孢他啶/阿维巴坦（CZA）是治疗多重耐药（MDR）革兰氏阴性（G-）菌感染的重要治疗选择，这些细菌包括产OXA-48酶菌和耐碳青霉烯类细菌。越来越多的证据表明，重症监护病房（ICU）的重症患者常表现出CZA药代动力学（PK）改变，这可能会影响标准给药方案实现最佳PK/药效学（PD）目标。本研究的主要假设是，对于由产OXA-48酶菌或耐碳青霉烯类细菌引起严重感染的重症ICU患者，与间歇给药（ID）相比，持续输注（CI）CZA可提高微生物学治愈率。
这是一项在克罗地亚萨格勒布大学医院中心进行的单中心、随机、开放标签试验，分配比例为1:1。共有140例因产OXA-48酶菌或耐碳青霉烯类细菌引起严重感染且需要CZA治疗的重症ICU患者将被随机分组，分别接受CZA的ID（2g/0.5g/8小时，静脉滴注2小时）或相同每日总剂量的CI（6g/1.5g，持续静脉滴注24小时）。该研究旨在证明CI在微生物学治愈率方面优于CZA的ID。
主要结局将是微生物学治愈率，这是作为直接受PK/PD目标达成影响的病原体清除关键指标。次要结局将包括临床治愈率、症状改善时间、ICU住院时间、住院时间、全因28天死亡率、第28天病原体复发率、机械通气撤机时间、累积血管活性-正性肌力评分、不良事件以及头孢他啶血浆浓度与病原体最低抑菌浓度的比值（C/MIC）。
本试验将为因MDR G-病原体引起严重感染的重症ICU患者提供最佳CZA给药方案的证据。
clinicaltrials.gov，标识符NCT06811727。
