Meropenem/Vaborbactam: A Review in Complicated Urinary Tract Infections

摘要

The global threat of the spread of carbapenem resistance in Enterobacteriaceae has led to the search for new antibacterials. Intravenous meropenem/vaborbactam (Vabomere™) is the first carbapenem/β-lactamase inhibitor combination approved in the USA for use in patients with complicated urinary tract infections (cUTIs), including pyelonephritis. Vaborbactam is a potent inhibitor of class A serine carbapenemases, which, when combined with the antibacterial meropenem, restores the activity of meropenem against β-lactamase producing Enterobacteriaceae, particularly Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae. Meropenem/vaborbactam demonstrated excellent in vitro activity against Gram-negative clinical isolates, including KPC- and extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. In the phase 3, noninferiority TANGO I trial in patients with cUTIs, intravenous meropenem/vaborbactam was noninferior to intravenous piperacillin/tazobactam for overall success (composite of clinical cure and microbial eradication; FDA primary endpoint) and microbial eradication (EMA primary endpoint). In subsequent superiority testing, meropenem/vaborbactam was superior to piperacillin/tazobactam for overall success. Meropenem/vaborbactam was generally well tolerated, with a tolerability profile generally similar to that of piperacillin/tazobactam. TANGO I did not assess the efficacy of meropenem/vaborbactam for the treatment of infections caused by carbapenem-resistant Enterobacteriaceae and meropenem/vaborbactam is currently not indicated for these patients. Available evidence indicates that meropenem/vaborbactam is a useful treatment option for patients with cUTIs.