Use of Ceftazidime–Avibactam in a Late-Preterm Newborn with Multidrug-Resistant Enterobacter hormaechei Sepsis

Background: Neonatal sepsis caused by multidrug-resistant (MDR) Gram-negative pathogens poses significant therapeutic challenges in neonatal intensive care units (NICUs), particularly in surgical neonates. Ceftazidime-avibactam (CAZ-AVI), a novel β-lactam/β-lactamase inhibitor combination, offers activity against extended-spectrum β-lactamases (ESBLs), AmpC, and serine carbapenemases, but neonatal experience remains limited. Methods and Results: We present a 35-week preterm neonate with long-gap esophageal atresia who developed late-onset sepsis caused by MDR Enterobacter hormaechei, including a KPC-producing carbapenem-resistant isolate, during postoperative recovery. After a multidisciplinary review, the patient received off-label CAZ-AVI at 25 mg/kg/dose (20/5 mg/kg) every 8 h, infused over 2 h, informed by available neonatal pharmacokinetic evidence and weight-adjusted dosing recommendations. Amikacin was administered contextually. Consecutive blood cultures obtained 48–72 h after dual antibiotic therapy initiation became negative and remained sterile, with concordant decline in inflammatory biomarkers, confirming rapid microbiological clearance. Unfortunately, the newborn died in the hours immediately following the final surgery performed to repair the esophageal atresia via end-to-end anastomosis; the cause was complications (hemothorax) unrelated to infectious diseases, although the onset of such severe sepsis may have compromised an already impaired immunological status. Discussion: This case shows mechanism-concordant antimicrobial selection and the feasibility of neonatal dosing when MDR Enterobacterales drive invasive infection. Our experience supports prospective evaluation of CAZ-AVI in carefully selected septic newborns while emphasizing the importance of rapid carbapenemase genotyping, susceptibility testing, and multidisciplinary oversight.