Meropenem-Vaborbactam Effective for Complicated Urinary Tract Infection

By Will Boggs MD

NEW YORK (Reuters Health) - The combination meropenem-vaborbactam is at least as effective as piperacillin-tazobactam for treating complicated urinary tract infection, including acute pyelonephritis, according to results from the TANGO trial.

"Meropenem-vaborbactam’s most important attribute is its activity against carbapenem-resistant Enterobacteriaceae (CRE), notably those that produce KPC (Klebsiella pneumoniae carbapenemase),” Dr. Keith S. Kaye from University of Michigan Medical School, Ann Arbor, told Reuters Health by email. “When KPC-producers are suspected or confirmed, meropenem-vaborbactam is a good choice.”

Vaborbactam broadly inhibits serine beta-lactamases, including KPC, and in combination with meropenem restores the activity of meropenem against KPC-producing CRE.

Dr. Kaye and colleagues from 60 sites in 17 countries compared meropenem-vaborbactam versus piperacillin-tazobactam in a randomized trial of 550 adults with complicated urinary tract infection, including acute pyelonephritis. The findings were reported online February 27 in JAMA.

The researchers used different primary efficacy endpoints based on criteria from the U.S. Food and Drug Administration (overall success, a composite of clinical cure and microbial eradication at the end of intravenous treatment visit) and the European Medicines Agency (microbial eradication at the test-of-cure visit).

For both endpoints, noninferiority was met for the comparison between meropenem-vaborbactam and piperacillin-tazobactam. Statistical superiority of meropenem-vaborbactam also was observed for the primary endpoint of overall success.

The overall success rate was 98.4% with meropenem-vaborbactam and 94.0% with piperacillin-tazobactam, a significant difference. However, significance did not persist in subgroup analyses of patients with acute pyelonephritis and in patients with complicated urinary tract infection and a removable or a nonremovable source of infection.

“I was not surprised that meropenem-vaborbactam performed well but was surprised that statistical superiority was achieved over piperacillin-tazobactam, a trusted excellent-performing antibiotic,” Dr. Kaye said.

Microbial eradication at test of cure was 74.2% in the meropenem-vaborbactam group and 63.4% in the piperacillin-tazobactam group, a nonsignificant difference that persisted in the subgroup analyses.

The treatment groups did not differ significantly in the proportions of patients who experienced an adverse event, study drug-related adverse event, severe adverse event, or life-threatening adverse event.

“Meropenem-vaborbactam is a welcomed and important addition to physicians’ antimicrobial armamentarium, particularly due to its activity against many strains of CRE,” Dr. Kaye said.

“A publication detailed meropenem-vaborbactam compared to best alternative therapy for treatment of CRE infection is in preparation and should be of interest to clinicians,” he added.

SOURCE: https://bit.ly/2EXbcuH

JAMA 2018.

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