Ceftazidime Plus Fosfomycin Versus Ceftazidime Alone for Severe Gram-negative Infections: a Triple-blind, Placebo-controlled Randomized Clinical Trial

What this Trial Is About

Researchers are evaluating whether combining ceftazidime (with or without avibactam) and fosfomycin leads to better clinical outcomes compared to ceftazidime alone in adults hospitalized with suspected severe Gram-negative bacterial infections. This phase 3 clinical trial aims to see if adding fosfomycin shortens the time to recovery as measured by normalization of quick Sequential Organ Failure Assessment (qSOFA) parameters and a significant drop in C-reactive protein (CRP), a marker of inflammation. The study also monitors the safety of this combination treatment. Participants will be randomly assigned to one of two groups. The intervention group receives intravenous ceftazidime with or without avibactam plus fosfomycin, while the control group receives ceftazidime with or without avibactam plus a placebo infusion. Treatment is given for about three days, typically three times daily, with adjustments based on kidney function. The addition of avibactam depends on the presence of resistant bacteria as determined by the physician. Fosfomycin or placebo is given alongside in matching schedules. During the study, participants will provide extra blood samples to measure CRP levels and will be monitored in hospital or contacted by phone after discharge up to day 28 for follow-up questions. Researchers measure the time from treatment start until qSOFA parameters normalize and CRP levels decrease by half. Safety is closely watched by tracking adverse events during treatment and shortly afterward. The total participation spans the initial treatment and follow-up period to assess recovery and tolerability.

A Combination Therapy With Ceftazidime and Fosfomycin Will be Compared to Ceftazidime Alone in Hospitalized Adult Patients With Suspected Severe Gram-negative Bacterial Infections