TOPLINE:
In a multinational phase 3 trial, imipenem-cilastatin-relebactam demonstrated noninferiority to piperacillin-tazobactam in treating critically ill patients with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP), with a comparable safety profile.
METHODOLOGY:
- This multinational phase 3 trial, conducted between September 2018 and July 2022, compared imipenem-cilastatin-relebactam with piperacillin-tazobactam for HABP and VABP to support its use across multiple countries.
- Overall, 270 patients with HABP or VABP (mean age, 57.6 years; 73.3% men) were randomly assigned to receive either intravenous imipenem-cilastatin-relebactam (500 mg/250 mg) or piperacillin-tazobactam (4000 mg/500 mg) every 6 hours over 30 minutes for 7-14 days.
- Both treatment groups included critically ill patients, with 54.5% and 55.1% of patients in the imipenem-cilastatin-relebactam and piperacillin-tazobactam groups, respectively, having an Acute Physiology and Chronic Health Evaluation II score ≥ 15.
- The primary outcome was the 28-day all-cause mortality; secondary outcomes included the rates of clinical and microbiological responses, as well as the incidence of adverse events.
TAKEAWAY:
- Imipenem-cilastatin-relebactam was noninferior to piperacillin-tazobactam in terms of 28-day all-cause mortality (adjusted difference, 5.2%; 95% CI, −1.5-12.4; P = .024 for noninferiority).
- At the end of treatment, the rates of a favorable clinical response were comparable between the imipenem-cilastatin-relebactam (71.6%) and piperacillin-tazobactam (68.4%) groups.
- After treatment, microbiological response rates were 48.8% in the imipenem-cilastatin-relebactam group, whereas the rates were 47.9% in the piperacillin-tazobactam group.
- The incidence of drug-related adverse events was similar across the treatment groups, with diarrhea, increased levels of alanine aminotransferase and aspartate aminotransferase, and abnormal hepatic function being the most common events.
IN PRACTICE:
“These results support the use of IMI/REL [imipenem-cilastatin-relebactam] in MDR [multidrug-resistant] infections globally, including to expand the range of available treatments for critically ill patients with HABP/VABP in China, and provide additional data to inform the World Health Organization’s MDR pathogen strategy,” the authors wrote.
SOURCE:
This study was led by Junjie Li, Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. It was published online on December 12, 2024, in the International Journal of Infectious Diseases.
LIMITATIONS:
This study excluded patients with immunosuppression and those on intermittent hemodialysis, limiting the generalizability of the results to these populations.
DISCLOSURES:
This study was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey. Some authors served as employees of Merck Sharp & Dohme LLC, New Jersey, and MSD, China.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.