PK/PD Relationship of CAZ/AVI and FOS in the Treatment of Patients With Infections Due to CRE

Gram-negative infections, particularly those caused by carbapenem-resistant Enterobacterales (CRE), have a dramatic impact on patient survival. Despite the introduction of new drugs in the last years have improved the outcome of patients with CRE infections, mortality and relapse rates are still relevant, especially in patients with high-risk source as pneumonia, and those in which the attainment of optimal exposure could be reduced by underlying renal disease. The use of combination regimen in these scenarios has been proposed. However, a standardized approach is still missing. Since several in vitro studies have highlighted the synergistic effect of fosfomycin (FOS) with different antibiotic classes, including cephalosporins such drug could be an appealing option in combination therapy for the management of CRE infections. In particular, the primary aim of the study is to assess the probability of achieving a pre-defined target of efficacy in patients treated with ceftazidime/avibactam (CAZ/AVI) and/or FOS according to different modes of drug administration in patients with CRE infections. Secondary aim is to assess the association between plasma drug concentration of both CAZ/AVI and FOS and patient response.