John E Mazuski1, Florian Wagenlehner2, Antoni Torres3, Yehuda Carmeli4, Joseph W Chow5, Dalia Wajsbrot6, Gregory G Stone7, Paurus Irani8, David Bharucha9, Karen Cheng10, Margaret Tawadrous11. 1. Department of Surgery, Washington University School of Medicine, St Louis, MO, USA. 2. Department of Urology, Pediatric Urology and Andrology, Justus-Liebig-University, Giessen, Germany. 3. Department of Pulmonology, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERES, ICREA, Barcelona, Spain. 4. Division of Epidemiology, National Institute for Antibiotic Resistance and Infection Control, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. 5. Global Product Development, Pfizer, Collegeville, PA, USA. 6. Biostatistics, Pfizer, New York, NY, USA. 7. Microbiology, Internal Medicine, Pfizer, Groton, CT, USA. 8. Global Medical Affairs, Pfizer, Tadworth, Surrey, UK. 9. Clinical Development, AbbVie, Madison, NJ, USA. 10. Safety Surveillance and Risk Management, Pfizer, Sandwich, Kent, UK. 11. Global Product Development, Pfizer, Inc, 445 Eastern Point Road, Groton, CT, 06340, USA. Margaret.Tawadrous@pfizer.com.
Abstract
INTRODUCTION: This exploratory analysis assessed efficacy and safety outcomes in patients with Gram-negative bacteremia treated withceftazidime-avibactam or comparator across five phase 3, randomized, controlled, multi-center trials in adults with complicated intra-abdominal infection (cIAI), complicated urinary tract infection (cUTI)/pyelonephritis, hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP). METHODS: In each trial, RECLAIM and RECLAIM 3 (cIAI; NCT01499290/NCT01726023), REPRISE (cIAI/cUTI; NCT01644643), RECAPTURE (cUTI; NCT01595438/NCT01599806), and REPROVE (HAP/VAP; NCT01808092), patients were randomized 1:1 to intravenous ceftazidime-avibactam (plus metronidazole for those with cIAI) or comparators (carbapenems in > 97% patients) for 5-21 days. Efficacy assessments included clinical and microbiological responses at the test-of-cure visit in the pooled Gram-negative extended microbiologically evaluable (GNeME) population (bacteremia subset). Safety outcomes were summarized for patients with positive bacterial blood culture(s) at baseline who received ≥ 1 dose of study treatment. RESULTS: The overall safety population included 4050 patients (ceftazidime-avibactam, n = 2024; comparator, n = 2026). The GNeME population (bacteremia subset) comprised 101 patients (ceftazidime-avibactam, n = 54; comparator, n = 47). Clinical cure rates (all indications combined) were 47/54 (87.0%) for ceftazidime-avibactam and 39/47 (83.0%) for comparators; favorable microbiological response rates were 43/54 (79.6%) and 32/47 (68.1%), respectively. Clinical and microbiological responses in the bacteremia subset were generally similar to those in the overall set. The pattern of adverse events in patients with bacteremia was similar between treatment groups and was consistent with the known safety profile of ceftazidime-avibactam. CONCLUSION: This analysis provides supportive evidence of the efficacy and safety of ceftazidime-avibactam in patients with Gram-negative bacteremia associated with cIAI, cUTI/pyelonephritis, or HAP/VAP.
RCT Entities:
INTRODUCTION: This exploratory analysis assessed efficacy and safety outcomes in patients with Gram-negative bacteremia treated with ceftazidime-avibactam or comparator across five phase 3, randomized, controlled, multi-center trials in adults with complicated intra-abdominal infection (cIAI), complicated urinary tract infection (cUTI)/pyelonephritis, hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP). METHODS: In each trial, RECLAIM and RECLAIM 3 (cIAI; NCT01499290/NCT01726023), REPRISE (cIAI/cUTI; NCT01644643), RECAPTURE (cUTI; NCT01595438/NCT01599806), and REPROVE (HAP/VAP; NCT01808092), patients were randomized 1:1 to intravenous ceftazidime-avibactam (plus metronidazole for those with cIAI) or comparators (carbapenems in > 97% patients) for 5-21 days. Efficacy assessments included clinical and microbiological responses at the test-of-cure visit in the pooled Gram-negative extended microbiologically evaluable (GNeME) population (bacteremia subset). Safety outcomes were summarized for patients with positive bacterial blood culture(s) at baseline who received ≥ 1 dose of study treatment. RESULTS: The overall safety population included 4050 patients (ceftazidime-avibactam, n = 2024; comparator, n = 2026). The GNeME population (bacteremia subset) comprised 101 patients (ceftazidime-avibactam, n = 54; comparator, n = 47). Clinical cure rates (all indications combined) were 47/54 (87.0%) for ceftazidime-avibactam and 39/47 (83.0%) for comparators; favorable microbiological response rates were 43/54 (79.6%) and 32/47 (68.1%), respectively. Clinical and microbiological responses in the bacteremia subset were generally similar to those in the overall set. The pattern of adverse events in patients with bacteremia was similar between treatment groups and was consistent with the known safety profile of ceftazidime-avibactam. CONCLUSION: This analysis provides supportive evidence of the efficacy and safety of ceftazidime-avibactam in patients with Gram-negative bacteremia associated with cIAI, cUTI/pyelonephritis, or HAP/VAP.
Authors: Wright W Nichols; Gregory G Stone; Paul Newell; Helen Broadhurst; Angela Wardman; Merran MacPherson; Katrina Yates; Todd Riccobene; Ian A Critchley; Shampa Das Journal: Antimicrob Agents Chemother Date: 2018-10-24 Impact factor: 5.191
Authors: Maria Di Pietrantonio; Lucia Brescini; Jennifer Candi; Morroni Gianluca; Francesco Pallotta; Sara Mazzanti; Paolo Mantini; Bianca Candelaresi; Silvia Olivieri; Francesco Ginevri; Giulia Cesaretti; Sefora Castelletti; Emanuele Cocci; Rosaria G Polo; Elisabetta Cerutti; Oriana Simonetti; Oscar Cirioni; Marcello Tavio; Andrea Giacometti; Francesco Barchiesi Journal: Antibiotics (Basel) Date: 2022-02-28