Background: Relebactam (REL), formerly MK-7655, is a β-lactamase inhibitor of class A and C β-lactamases that is in development in combination with imipenem (IMI). In this study, we evaluated the activity of IMI/REL against recent clinical isolates of gram-negative bacilli (GNB) collected globally as part of the SMART surveillance program.
Methods: In 2017, 188 hospitals in 54 countries each collected up to 100 consecutive gram-negative aerobic or facultatively anaerobic pathogens from lower respiratory tract infections, 75 from intra-abdominal infections, and 75 from urinary tract infections. MICs were determined for 41,319 GNB, including 30,864 Enterobacteriaceae and 6,933 P. aeruginosa isolates, using CLSI broth microdilution and interpreted with CLSI breakpoints; for comparison purposes, IMI susceptible breakpoints were applied to IMI/REL.
Results: Susceptibilities to IMI/REL and comparators of the 10 most commonly found Enterobacteriaceae species and P. aeruginosa are shown below.
IMI/REL showed activity >90% against 7 of the top 10 Enterobacteriaceae species, typically ~5 to 35 percentage points higher than the β-lactam comparators, and it was active against 89% of P. aeruginosa, ~15 to 25 percentage points higher than the β-lactam comparators. Only amikacin and colistin showed similar or higher activity for most species, with colistin showing little activity against Proteeae and Serratia.
Conclusion: IMI/REL could provide an important treatment option against infections with gram-negative pathogens, especially since amikacin and colistin are associated with significant morbidity, including nephrotoxicity and ototoxicity, and amikacin is typically used in combination with another antibiotic.
D. Hoban, IHMA, Inc.: Employee , Salary . Merck: Consultant , Consulting fee .
M. Hackel, IHMA, Inc.: Employee , Salary . Merck: Consultant , Consulting fee .
K. Young, Merck: Employee and Shareholder , Dividends and Salary .
M. Motyl, Merck: Employee and Shareholder , Dividends and Salary .
D. Sahm, IHMA, Inc.: Employee , Salary . Merck: Consultant , Consulting fee .