Clinical trial findings support the use of once-daily plazomicin for complicated urinary tract infections (UTIs), including acute pyelonephritis, investigators concluded.

In the EPIC (Evaluating Plazomicin in cUTI) phase 3 multicenter, randomized trial, patients treated with plazomicin, an aminoglycoside, had higher rates of microbiologic eradication and composite cure (clinical and microbiologic eradication) at test-of-cure visits compared with those treated with meropenem.

At late follow-up, defined as 24 to 32 days after initiation of therapy, a significantly smaller proportion of patients in the plazomicin than meropenem treatment arm had microbiologic recurrence (3.7% vs 8.1%) or clinical relapse (1.6% vs 7.1%), Florian M.E. Wagenlehner, MD, of Justus Liebig University in Giessen, Germany, and colleagues reported in The New England Journal of Medicine.

“The lower incidence of microbiologic recurrence and clinical relapse in the plazomicin group than in the meropenem group at late follow-up suggests that the greater microbiologic eradication with plazomicin has additional clinical benefit for patients with complicated UTIs, including acute pyelonephritis,” Dr Wagenlehner’s team wrote.

Plazomicin is an aminoglycoside with bactericidal activity against multidrug-resistant Enterbacteriaceae. Meropenem is a carbapenem antibiotic. The investigators noted that carbapenems are being used increasingly to treat complicated UTIs. “The incidence of multidrug resistance has continued to increase—and now includes carbapenem resistance; therefore, alternative treatment options are needed,” the authors stated.

In EPIC, investigators randomly assigned patients to receive intravenous (IV) plazomicin (15 mg per kilogram of body weight once daily) or meropenem (1 g every 8 hours) for 7 to 10 days. The plazomicin and meropenem arms had 191 and 197 patients, respectively. Of these, 84 (44.0%) and 78 (39.6%) had acute pyelonephritis, respectively.

At day 5, the investigators observed composite cure in similar proportions of patients in the plazomicin and meropenem groups: 88.0% and 91.4%, respectively. At the test-of-cure visit, Dr Wagenlehner and colleagues observed composite cure in a significantly higher proportion of patients in the plazomicin arm (81.7% vs 70.1%). Also at the test-of-cure visit, a significantly higher proportion of patients in the plazomicin than meropenem arm had microbiologic eradication, including eradication of Enterobacteriaceae that were not susceptible to aminoglycosides (78.8% vs 68.6%) as well as Enterobacteriaceae that produce extended-spectrum beta-lactamases (82.4% vs 75.0%).

The trial was funded by Achaogen and the Biomedical Advanced Research and Development Authority.

Reference

Wagenlehner FME, Cloutier DJ, Komirenko AS, et al. Once-daily plazomicin for complicated urinary tract infectionsN Engl J Med. 2019; published online ahead of print.