Shigeru Kohno1, Hiroyuki Bando2, Fumihiko Yoneyama3, Hiroaki Kikukawa4, Kazuya Kawahara5, Masayoshi Shirakawa6, Norihiro Aoyama6, Michelle Brown7, Amanda Paschke7, Akiko Takase8. 1. Nagasaki University, 1-14 Bunkyou-machi, Nagasaki, Nagasaki, 852-8521, Japan. 2. Ishikawa Prefectural Central Hospital, 2-1 Kuratsukihigashi, Kanazawa, Ishikawa, 920-8530, Japan. 3. Nagoya Ekisaikai Hospital, 4-66 Shonen-cho, Nakagawa-ku, Nagoya, Aichi, 454-8502, Japan. 4. National Hospital Organization Kumamoto Medical Center, 1-5 Ninomaru, Chuo-ku, Kumamoto, Kumamoto, 860-0008, Japan. 5. Kawahara Clinic, 73-3 Nishimochida, Aira, Kagoshima, 899-5431, Japan. 6. Japan Development, MSD K.K., 1-13-12 Kudan-kita, Chiyoda-ku, Tokyo, 102-8667, Japan. 7. Global Clinical Development, Merck & Co., Inc., Kenilworth, NJ, USA. 8. Japan Development, MSD K.K., 1-13-12 Kudan-kita, Chiyoda-ku, Tokyo, 102-8667, Japan. Electronic address: akiko.takase@merck.com.
Abstract
INTRODUCTION: Relebactam, a novel class A/C β-lactamase inhibitor developed as a fixed-dose combination with imipenem/cilastatin, restores imipenem activity against imipenem-nonsusceptible gram-negative pathogens. METHODS: This phase 3, multicenter, open-label, noncomparative study (NCT03293485) evaluated relebactam/imipenem/cilastatin (250 mg/500 mg/500 mg) dosed every 6 h for 5-14 days in Japanese patients with complicated intra-abdominal infections (cIAIs) or complicated urinary tract infections (cUTIs), including those with secondary sepsis. Sepsis was defined as an infection-induced systemic inflammatory response syndrome, with a documented positive blood culture; patients meeting these protocol-defined criteria were evaluated for efficacy against sepsis. RESULTS: Of 83 patients enrolled, 81 patients (cIAI, n = 37; cUTI, n = 44) received ≥1 dose of study treatment. Escherichia coli was the most common baseline pathogen isolated in both patients with cIAI and cUTI. Adverse events (AEs) were reported in 74.1% (n = 60/81) of patients, and drug-related AEs occurred in 18.5% (n = 15/81). The most common AEs were diarrhea and nausea (8.6%). Serious AEs occurred in nine patients, including one death, but none were considered treatment related. The primary efficacy endpoint for patients with cIAI was clinical response at end of treatment (EOT) in the microbiologically evaluable (ME) population, and for patients with cUTI was microbiological response at EOT in the ME population. The proportion of cIAI and cUTI patients achieving favorable responses were 85.7% (n = 24/28) and 100.0% (n = 39/39), respectively. All patients with sepsis (cIAI, n = 1; cUTI, n = 5) achieved a favorable composite clinical and microbiological response at EOT. CONCLUSIONS: A favorable safety and efficacy profile for relebactam/imipenem/cilastatin was observed in Japanese patients with cIAI and cUTI.
INTRODUCTION:Relebactam, a novel class A/C β-lactamase inhibitor developed as a fixed-dose combination with imipenem/cilastatin, restores imipenem activity against imipenem-nonsusceptible gram-negative pathogens. METHODS: This phase 3, multicenter, open-label, noncomparative study (NCT03293485) evaluated relebactam/imipenem/cilastatin (250 mg/500 mg/500 mg) dosed every 6 h for 5-14 days in Japanese patients with complicated intra-abdominal infections (cIAIs) or complicated urinary tract infections (cUTIs), including those with secondary sepsis. Sepsis was defined as an infection-induced systemic inflammatory response syndrome, with a documented positive blood culture; patients meeting these protocol-defined criteria were evaluated for efficacy against sepsis. RESULTS: Of 83 patients enrolled, 81 patients (cIAI, n = 37; cUTI, n = 44) received ≥1 dose of study treatment. Escherichia coli was the most common baseline pathogen isolated in both patients with cIAI and cUTI. Adverse events (AEs) were reported in 74.1% (n = 60/81) of patients, and drug-related AEs occurred in 18.5% (n = 15/81). The most common AEs were diarrhea and nausea (8.6%). Serious AEs occurred in nine patients, including one death, but none were considered treatment related. The primary efficacy endpoint for patients with cIAI was clinical response at end of treatment (EOT) in the microbiologically evaluable (ME) population, and for patients with cUTI was microbiological response at EOT in the ME population. The proportion of cIAI and cUTI patients achieving favorable responses were 85.7% (n = 24/28) and 100.0% (n = 39/39), respectively. All patients with sepsis (cIAI, n = 1; cUTI, n = 5) achieved a favorable composite clinical and microbiological response at EOT. CONCLUSIONS: A favorable safety and efficacy profile for relebactam/imipenem/cilastatin was observed in Japanese patients with cIAI and cUTI.
Authors: Munjal Patel; Francesco Bellanti; Naveen M Daryani; Nadia Noormohamed; David W Hilbert; Katherine Young; Pooja Kulkarni; William Copalu; Ferdous Gheyas; Matthew L Rizk Journal: Clin Transl Sci Date: 2021-10-27 Impact factor: 4.689
Authors: Nicholas Rebold; Taylor Morrisette; Abdalhamid M Lagnf; Sara Alosaimy; Dana Holger; Katie Barber; Julie Ann Justo; Kayla Antosz; Travis J Carlson; Jeremy J Frens; Mark Biagi; Wesley D Kufel; William J Moore; Nicholas Mercuro; Brian R Raux; Michael J Rybak Journal: Open Forum Infect Dis Date: 2021-12-09 Impact factor: 3.835