2890. Pharmacokinetics, Safety, and Efficacy of Ceftazidime-Avibactam in Neonates and Young Infants with Bacterial Infections: Results from a Phase 2a, 2-Part, Open-label, Non-randomized, Multicenter Trial

Abstract Background Antibiotic resistance in pediatrics, including neonates and infants, is increasing globally. Ceftazidime-avibactam (CAZ-AVI) is approved for use in pediatric patients (age ≥ 3 months) with Gram-negative bacterial infections. This study evaluated pharmacokinetics (PK), safety, and efficacy of CAZ-AVI in hospitalized neonates and young infants (from 26 weeks gestation, up to 3 months of age) with suspected/confirmed infections due to Gram-negative pathogens requiring intravenous (IV) antibiotic treatment (Tx). Methods This Phase 2a study was conducted at 39 sites in 9 countries (Jan2020-Dec2022; EudraCT 2018-002800-16). Hospitalized neonates and infants received single (Part A) or multiple doses (Part B) of IV CAZ-AVI (Figure 1). PK (CAZ and AVI), safety (adverse events [AEs], serious AEs, deaths), and efficacy (Part B: clinical outcomes [cure/improvement], microbiological response) were assessed. The study was not powered for inferential statistical analysis, descriptive methods were used to summarize all data. Results In total, 46 participants were administered CAZ-AVI, aged 2 to 89 days and 31 to ≥ 37 weeks gestation (Table 1). Overall, sepsis (39.1%) and urinary tract infection (15.2%) were the most common primary infectious diagnoses. In Part B, 60% of the baseline pathogens isolated were Escherichia coli. Median duration of CAZ-AVI Tx in Part B was 7.0 days. Plasma concentrations of CAZ and AVI were similar to those in previous pediatric studies (Figure 2). Overall, 50% (n=23) of participants had treatment-emergent AEs (TEAEs); the majority were mild/moderate in severity. SAEs (n=8) and deaths (due to necrotizing enterocolitis and septic shock, n=1; sepsis, n=1) were not related to study Tx. Most participants had favorable clinical outcomes and microbiological response at test of cure. Conclusion Plasma concentrations of CAZ and AVI after single and multiple doses of CAZ-AVI were similar to previous pediatric studies. Single and multiple doses of CAZ-AVI were safe and well tolerated in hospitalized neonates and young infants with suspected/confirmed bacterial infections. TEAEs were mild/moderate in severity and no new safety concerns were identified. Disclosures Emmanuel Roilides, MD, PhD, Gilead: Advisor/Consultant|GSK: Grant/Research Support|MSD: Advisor/Consultant|MSD: Grant/Research Support|Mundipharma: Advisor/Consultant|Pfizer: Grant/Research Support|Scynexis: Grant/Research Support Richard England, MD, PhD, Pfizer: Employee of Pfizer|Pfizer: Stocks/Bonds Margaret Tawadrous, MD, MS, Pfizer: Employee of Pfizer|Pfizer: Stocks/Bonds Jean Yan, M.S., Pfizer: Employee of Pfizer|Pfizer: Stocks/Bonds Elena Soto, PhD, Pfizer: Employee of Pfizer|Pfizer: Stocks/Bonds Gregory Stone, PhD, Pfizer: Employee of Pfizer|Pfizer: Stocks/Bonds Shweta Kamat, MD, Pfizer: Employee of Pfizer|Pfizer: Stocks/Bonds