Ceftazidime/avibactam (CAZ/AVI) is an antibiotic combination approved for the treatment of several infections caused by multi-drug resistant (MDR) Gram-negative bacteria. Neonates admitted to the Neonatal Intensive Care Unit (NICU) are at high risk of developing bacterial infections, and the choice of appropriate antibiotics is crucial. However, the use of antibiotics in neonates carries risks such as antibiotic resistance and disruption of gut microbiota. This study aimed to assess the safety and efficacy of CAZ/AVI in preterm infants admitted to the NICU. Retrospective data from preterm infants with Klebsiella pneumoniae bacteremia who received CAZ/AVI were analyzed. Clinical and microbiological responses, adverse events, and outcomes were evaluated. Eight patients were included in the study, all of whom showed clinical improvement and achieved microbiological cure with CAZ/AVI treatment. No adverse drug reactions were reported. Previous antibiotic therapies failed to improve the neonates’ condition, and CAZ/AVI was initiated based on clinical deterioration and epidemiological considerations. The median duration of CAZ/AVI treatment was 14 days, and combination therapy with fosfomycin or amikacin was administered. Previous case reports have also shown positive outcomes with CAZ/AVI in neonates. However, larger trials are needed to further investigate the safety and efficacy of CAZ/AVI in this population.