1143. Safety and Efficacy of Ceftolozane/Tazobactam Versus Meropenem in Neonatal and Pediatric Participants With Complicated Urinary Tract Infection, Including Pyelonephritis: A Phase 2, Randomized, Clinical Trial. (4th December 2021)

• Record Type: Journal Article
• Authors: Roilides, Emmanuel; Ashouri, Negar; Bradley, John S; Johnson, Matthew G; Lonchar, Julia; Su, Feng-Hsiu; Huntington, Jennifer A; Popejoy, Myra W; Bensaci, Mekki; De Anda, Carisa S; Rhee, Elizabeth G; Bruno, Christopher
• Is Part Of: Open forum infectious diseases. Volume 8(2021)Supplement 1
• Page Start: S663
• Page End: S664
• Publication Date: 2021-12-04
• Subjects: Communicable diseases -- Periodicals; Medical microbiology -- Periodicals; Infection -- Periodicals; 616.9
• DOI: 10.1093/ofid/ofab466.1336
• Languages: English
• ISSNs: 2328-8957

Abstract

Abstract: Background: Ceftolozane/tazobactam (C/T) is a cephalosporin–β-lactamase inhibitor combination approved to treat complicated urinary tract infections (cUTI), complicated intra-abdominal infections, and nosocomial pneumonia in adults. Safety and efficacy of C/T in neonatal and pediatric participants with cUTI was assessed. Methods: This phase 2, randomized, double-blind study (NCT03230838) compared C/T with meropenem (MEM) for treatment of cUTI, including pyelonephritis in participants from birth to 18 years of age. Treatment duration was 7-14 days. After 3 days of intravenous therapy, optional oral step-down therapy was allowed. Participants were stratified and dosed by age group (Table 1). The primary objective was to evaluate the safety and tolerability of C/T compared with MEM, and key secondary end points included clinical response and per-participant microbiologic response at end of treatment (EOT) and test of cure (TOC). Results: Participants were randomized 3:1 and treated with C/T (n=100) or MEM (n=33). The microbiologic modified intent-to-treat population (mMITT) included 95 participants in the C/T (n=71) and MEM (n=24) arms; the most common reason for mMITT exclusion was lack of a qualifying baseline uropathogen (28.4%). Pyelonephritis was the most common baseline diagnosis (83.2%), and Escherichia coli was the most common qualifying baseline uropathogen (77.9%). Overall mean treatment duration was comparable in both arms (C/T, 10.2 days; MEM, 10.7); a total of 50 (70.4%) and 20 (83.3%) participants switched to optional oral step-down therapy in the C/T and MEM arms, respectively, both for a mean of approximately 6 days. The overall incidence of adverse events (AE; all and drug related), serious AE (SAE), and AE leading to discontinuation was comparable between C/T and MEM arms. There were no AE leading to death, drug-related SAE, or discontinuations due to drug-related AE or SAE (Table 2). For C/T and MEM, rates of clinical cure and microbiologic eradication at EOT and TOC were high (Figure). Conclusion: In this study, C/T was well tolerated with a safety profile comparable to MEM and to the previously reported safety profile for C/T in adults with cUTI. C/T achieved high clinical cure and microbiologic eradication rates and is a potential new treatment option for children with cUTI. Disclosures: Emmanuel Roilides, MD, PhD, FIDSA, FAAM, FESCMID, Merck Sharp & Dohme Corp. (Consultant, Grant/Research Support) Negar Ashouri, MD, Merck Sharp & Dohme Corp. (Grant/Research Support) Matthew G. Johnson, MD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee) Julia Lonchar, MSc, Merck Sharp & Dohme Corp. (Employee, Shareholder) Feng-Hsiu Su, MPH, MBA, Merck Sharp & Dohme Corp. (Employee, Shareholder) Jennifer A. Huntington, PharmD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee) Myra W. Popejoy, PharmD, Merck Sharp & Dohme Corp. (Employee) Mekki Bensaci, PhD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee) Carisa S. De Anda, PharmD, Merck Sharp & Dohme Corp. (Employee, Shareholder) Elizabeth G. Rhee, MD, Merck Sharp & Dohme Corp (Employee, Shareholder) Christopher Bruno, MD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee)