CEFtolozane-Tazobactam for the Empiric Anti-bacterial Treatment of Neutropenic Fever in Hematology Patients

The role of early appropriate empiric anti-bacterial therapy in reducing morbidity and mortality in patients with prolonged neutropenia has long being documented. The National Center for Cancer Care and Research (NCCCR) antibiograms for recent years showed increasing rates of ESBL-producing E. coli and K. pneumoniae, as well as reduced susceptibility of P. aeruginosa isolates to piperacillin-tazobactam. Ceftolozane-tazobactam is a newer β-lactam-β-lactamase inhibitor combination with a broad in-vitro spectrum that includes ESBL and AmpC-producing Enterobacterales, as well as multidrug resistant P. aeruginosa. The clinical efficacy and safety of ceftolozane-tazobactam was demonstrated in registrational randomized clinical trials in multiple settings. However, clinical experience with ceftolozane-tazobactam in patients with hematological malignancy or HSCT is very limited. The aim of this study is to explore the potential role of ceftolozane-tazobactam as empiric treatment for hematology patients with neutropenic fever of unknown origin. The primary objective is to assess the efficacy of ceftolozane-tazobactam as empiric anti-bacterial therapy for neutropenic fever in patients with hematological malignancy or HSCT. The study will be a prospective, non-comparative, single-arm, single center, open-label interventional study. Patients admitted to NCCCR with a malignant hematological diagnosis and/or HSCT will be screened daily for possible inclusion in the study. Participants will receive empiric therapy with ceftolozane-tazobactam intravenously. All remaining care will be consistent with standard clinical care for patients with neutropenic fever. The Primary endpoint will be treatment success at 72 hours of ceftolozane-tazobactam therapy without modification of anti-bacterial therapy. Treatment success is defined as a composite of defervescence, resolution of any baseline clinical signs of infection, microbiological eradication of any baseline bacterial pathogen, and no modification of anti-bacterial therapy by addition of or switch to an agent with microbiological activity against Enterobacterales or P. aeruginosa (except the addition of sulfamethoxazole-trimethoprim for P. jiroveci prophylaxis). The study will be conducted in full conformance with principles of the "Declaration of Helsinki", Good Clinical Practice (GCP), and within the laws and regulations of Ministry of Public Health in Qatar. Participation will be subject to written informed consent. The study is sponsored by Hamad Medical Corporation. Funding and medication supply is provided by Merck \& Co (MSD) through its Investigator Initiated Studies Program. MSD will not have any role in data collection, data analysis or driving study conclusions.