Continuous infusion versus intermittent dosing of ceftazidime/avibactam in critically ill patients with OXA-48 or infections: a single-center randomized open-label trial (ZAVICONT). Rationale and design.

Objective: 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 .

Methods: 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.

Outcomes: 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).

Conclusion: This trial will provide evidence on optimal CZA administration regimen in critically ill ICU patients with severe infections due to MDR G-pathogens.

Clinica Trial Registration: clinicaltrials.gov, identifier NCT06811727.