A Randomized, Double-blind, Multicenter Trial Comparing Efficacy and Safety of Imipenem/Cilastatin/Relebactam Versus
Ivan Titov1, Richard G Wunderink2, Antoine Roquilly3
1Department of Anesthesiology and Intensive Care, Ivano-Frankivsk Regional Clinical Hospital, Ivano-Frankivsk, Ukraine.
Background:
Imipenem combined with the β-lactamase inhibitor relebactam has broad antibacterial activity, including against carbapenem-resistant gram-negative pathogens. We evaluated efficacy and safety of imipenem/cilastatin/relebactam in treating hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP).
Methods:
This was a randomized, controlled, double-blind phase 3 trial. Adults with HABP/VABP were randomized 1:1 to imipenem/cilastatin/relebactam 500 mg/500 mg/250 mg or piperacillin/tazobactam 4 g/500 mg, intravenously every 6 hours for 7-14 days. The primary endpoint was day 28 all-cause mortality in the modified intent-to-treat (MITT) population (patients who received study therapy, excluding those with only gram-positive cocci at baseline). The key secondary endpoint was clinical response 7-14 days after completing therapy in the MITT population.
Results:
Of 537 randomized patients (from 113 hospitals in 27 countries), the MITT population comprised 264 imipenem/cilastatin/relebactam and 267 piperacillin/tazobactam patients; 48.6% had ventilated HABP/VABP, 47.5% APACHE II score ≥15, 24.7% moderate/severe renal impairment, 42.9% were ≥65 years old, and 66.1% were in the intensive care unit. The most common baseline pathogens were Klebsiella pneumoniae (25.6%) and Pseudomonas aeruginosa (18.9%). Imipenem/cilastatin/relebactam was noninferior (P < .001) to piperacillin/tazobactam for both endpoints: day 28 all-cause mortality was 15.9% with imipenem/cilastatin/relebactam and 21.3% with piperacillin/tazobactam (difference, -5.3% [95% confidence interval {CI}, -11.9% to 1.2%]), and favorable clinical response at early follow-up was 61.0% and 55.8%, respectively (difference, 5.0% [95% CI, -3.2% to 13.2%]). Serious adverse events (AEs) occurred in 26.7% of imipenem/cilastatin/relebactam and 32.0% of piperacillin/tazobactam patients; AEs leading to treatment discontinuation in 5.6% and 8.2%, respectively; and drug-related AEs (none fatal) in 11.7% and 9.7%, respectively.
Conclusions:
Imipenem/cilastatin/relebactam is an appropriate treatment option for gram-negative HABP/VABP, including in critically ill, high-risk patients.
Clinical Trials Registration:
NCT02493764.
More Related Videos
11:17Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
05:39Author Spotlight: A Non-Intubated Video-Assisted Thoracoscopic Surgery with Multimodal Analgesia and Sevoflurane Inhalation Anesthesia
Published on: May 26, 2023
Related Concept Videos
01:28Pneumonia IV: Management
Bacterial Pneumonia Treatment
For bacterial pneumonia, antibiotics serve as the cornerstone of therapy. Initial treatment often begins with empirical antibiotics, tailored to the anticipated causative organism and adjusted based on culture results. Key antibiotic choices include:
01:28Acute Pyelonephritis II: Diagnostic Studies and Management
01:30Pneumonia III: Complications and Assessment
01:30Pneumonia I: Introduction
Risk Factors
Various factors influence the likelihood of developing pneumonia. Age plays a crucial role, with infants, children under two, and individuals over 65 at increased risk due to their...