Gram Negative Infections

The ACT-FAST study aims to compare commercially available Rapid Antimicrobial Susceptibility Testing (R-AST) tools with the current standard of care for patients with Bloodstream Infections (BSI). The primary objective is to evaluate whether "early targeted" antibiotic prescriptions, guided by these rapid tests, can improve antimicrobial stewardship and patient clinical outcomes. To facilitate the evaluation of various diagnostic tools-including those currently on the market and those emerging in the near future-this study utilizes an adaptive clinical trial platform. This flexible design allows for the continuous assessment of different R-AST technologies within a single master protocol, ensuring that the most effective diagnostic strategies are identified efficiently.

A multicenter international prospective observational pharmacological study in adult patients (≥18 years) treated with ceftazidime/avibactam (CAZ/AVI) alone or with CAZ/AVI plus fosfomycin (FOS) for infection due to carbapenem-resistant Enterobacterales (CRE) (KPC and/or OXA-48).

The goal of this clinical trial is to assess the pharmacokinetic (PK) and safety and tolerability of Vaborem (fixed combination of meropenem and vaborbactam) in the paediatric population aged from birth to \< 18 years with suspected or confirmed Gram negative infections in need of hospitalisation and intravenous (IV) antibiotic administration. All participants will receive Vaborem IV every 8 hours to treat the suspected or confirmed Gram negative infections for 10 up to 14 days; switch to stepdown oral antibiotic is allowed after a minimum of 3 days of Vaborem. PK sample collection will occur after at least 6 doses administration. Participant's clinical conditions will be monitored during the entire duration of the hospitalization and during scheduled visit/s after the completion of the treatment.

The goal of this clinical trial is to learn if a personalized duration of antibiotic therapy, based on clinical stability, is as effective as a standard duration of at least 10 days in hospitalized patients with hematologic malignancies (such as leukemia or lymphoma) who develop febrile neutropenia and Gram-negative bacteraemia. The main questions it aims to answer are: * Can a personalized antibiotic duration increase the number of days free from anti-Gram-negative therapy within 28 days without compromising patient safety? * How does the duration of antibiotic therapy (short vs. prolonged) affect the rate and modality of gut microbiota reconstitution? Researchers will compare: * Group A (Personalized Duration): Antibiotics are stopped after the patient maintains clinical stability (no fever and stable vital signs) for 72 consecutive hours. * Group B (Standard of Care): Antibiotics are continued for a standard duration, typically at least 10 days, based on current clinical surveys and physician decision. Participants will: * Be randomized to receive either the personalized or the standard duration of antibiotic therapy once a Gram-negative infection is confirmed in the blood. * Be monitored for 28 days to assess for new fever episodes, recurrence of infection, and overall survival. * If participating in the microbiological sub-study, provide biological samples (blood, feces, and rectal swabs) at specific time points (at the onset of fever, at the end of treatment, and at day 28). * Undergo specialized laboratory testing (Whole Metagenomic Sequencing) on the collected samples to evaluate the evolution of their intestinal and blood microbiota and the presence of antibiotic-resistant genes.

The goal of this clinical trial is to : 1. Test whether the combination of CAZ±AVI and FOS leads to superior clinical outcomes in patients with severe suspected Gram-negative bacterial infection, as demonstrated by a shorter time to normalization of quick Sequential Organ Failure Assessment (qSOFA) parameters and reduction in C-reactive protein (CRP) compared to standard of care (CAZ±AVI alone) 2. to further characterize the safety profile of this combination therapy In the presence of such an infection, standard treatment is to start intravenous antibiotic therapy. Ceftazidime (Fortam®), or ceftazidime-avibactam (Zavicefta®), is a standard antibiotic commonly used for this purpose (for very resistant bacteria, the compound avibactam is included to protect ceftazidime from being broken down by bacteria). Researchers will compare ceftazidime (or ceftazdime-avibactam) plus fosfomycin versus ceftazidime alone with placebo (i.e. a look-alike substance given with no drug) to examine whether the addition of another intravenous antibiotic, fosfomycin, would lead to faster recovery from severe infection and evaluate the tolerability of this combination. Participants will: * Be randomly assigned to either the intervention group or the control group. * The intervention group will receive ceftazidime (with avibactam if multidrug resistant bacteria are suspected, per routine practice) and intravenous fosfomycin, and the control group will receive ceftazidime (with avibactam if multidrug resistant bacteria are suspected) and placebo. * Either treatment will be given for 3 days, three times daily (or less frequently, depending on renal function). * Provide a few extra blood samples (for CRP measurement, a protein marker of inflammation) during the first few days of the study. * Be contacted in the hospital or by phone if discharged on day 28 to be asked a few questions.