Ceftolozane/Tazobactam and Ceftazidime/Avibactam: An Italian Multi-center Retrospective Analysis of Safety and Efficacy in Children With Hematologic Malignancies and Multi-drug Resistant Gram-negative Bacteria Infections

ne major issue in pediatric hemato-oncologic patients is the emergence of multi-drug resistant (MDR) Gram-negative bacteria (GNB) infections. 1 A history of previous MDR-GNB infection or colonization is in itself a major predictor of sepsis and poor outcome. 2 Soon after autologous or allogeneic stem cell transplantation, MDR-GNB infections, particularly in the bloodstream, are predictive of increased morbidity and mortality. 3 Better outcomes of MDR-GNB sepsis were achieved with Ceftolozane/Tazobactam (C/T) and Ceftazidime/Avibactam (C/A) antibiotic therapy. 4 These new antibiotic combinations are directed against carbapenem-resistant Enterobacteriacee (CRE) and CR- Pseudomonas aeruginosa (PA). Limited data are, however, available on their use in children with hemato-oncologic disorders, as only C/A has recently been authorized infection, due to HSCT or chemotherapy. HSCT patients developed infection at a median of 10 days after graft infusion when they were profoundly neutropenic and particularly susceptible to this kind of infection. The present study also demonstrated that, even as a 3rd-line treatment after failure of empirical and/or second-line antibiotic therapy, C/A and C/T were otherwise safe and effective in 20/22 children with MDR-GNB sepsis and/or colonization. These patients were at very high risk to die of MDR-GNB infections, but most of them survived after C/A or C/T treatment. The infection resolved in >90% of cases and no significant side effects were recorded.