mk-7655 and Pneumonia--Ventilator-Associated

Imipenem combined with beta-lactamase inhibitor relebactam (IMI/REL) has an extensive bactericidal activity against Gram-negative pathogens producing class A or class C beta-lactamases, not active against class B and class D. The phase 3 clinical trial (RESTORE-IMI-2), double-blind, randomized, evaluated IMI/REL vs. piperacillin-tazobactam (PIP/TAZ) for treatment of hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), demonstrated non-inferiority at all-cause mortality at 28 days (15.9% vs 21.3%), favorable clinical response at 7-14 days end of treatment (61% vs 59.8%) and with minor serious adverse effects (26.7% vs 32%). IMI/REL is a therapeutic option in HAP and VAP at approved dosage imipenem 500 mg, cilastatin 500 mg and relebactam 250 mg once every 6h, by an IV infusion over 30 min.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Cilastatin; Clinical Trials, Phase III as Topic; Drug Therapy, Combination; Humans; Imipenem; Patient Acuity; Pneumonia, Ventilator-Associated; Randomized Controlled Trials as Topic

The article describes the use of the last-resort carbapenem antibiotic imipenem in combination with relebactam, a novel b-lactamase inhibitor, in the treatment of ventilator-associated pneumonia developing after SARS-CoV-2 infection in a young pregnant patient. The introduction briefly describes the mechanism and spectrum of activity of the antibiotic, including its dosage.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Cilastatin, Imipenem Drug Combination; COVID-19; Humans; Imipenem; Microbial Sensitivity Tests; Pneumonia, Ventilator-Associated; SARS-CoV-2

The β-lactamase inhibitor relebactam inactivates class A β-lactamases, including KPC-type carbapenemases, and class C β-lactamases. Relebactam combined with imipenem is in clinical development for several indications, including hospital-acquired and ventilator-associated pneumonia. Employing CLSI-defined broth microdilution methodology, we evaluated the activities of imipenem-relebactam (using imipenem MIC breakpoints) and comparators against non-Proteeae Enterobacteriaceae (n=853) and Pseudomonas aeruginosa (n=598) isolated from lower respiratory tract infection samples in 20 hospital laboratories in the United States participating in the 2015 SMART (Study for Monitoring Antimicrobial Resistance Trends) global surveillance program. Imipenem-relebactam and imipenem susceptibilities were 97.2% and 91.6% for non-Proteeae Enterobacteriaceae and 93.1% and 68.1% for P. aeruginosa. Relebactam restored imipenem susceptibility to 66.7% and 78.5% of imipenem-non-susceptible non-Proteeae Enterobacteriaceae isolates (n=72) and P. aeruginosa (n=191), respectively. Further development of imipenem-relebactam as therapy for lower respiratory tract infections is warranted given relebactam's ability to restore activity to imipenem against non-susceptible non-Proteeae Enterobacteriaceae and P. aeruginosa.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; beta-Lactamase Inhibitors; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Imipenem; Microbial Sensitivity Tests; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; United States