A daily dose of the aminoglycoside Zemdri was noninferior to meropenem for the treatment of complicated UTIs and acute pyelonephritis caused by Enterobacteriaceae, including multidrug-resistant strains, according to findings recently published in The New England Journal of Medicine.
Last year, the FDA approved Zemdri (plazomicin, Achaogen) to treat UTIs, including pyelonephritis, caused by certain Enterobacteriaceae in adult patients who have limited or no alternative treatment options.
“The previous mainstays of empirical therapy for complicated UTIs, such as fluoroquinolones and cephalosporins, are not widely recommended because of concerns about resistance,” Florian M.E. Wagenlehner, MD, of the Justus Liebig University, Giessen, Germany and colleagues wrote.
“Carbapenems, which have been traditionally reserved for the treatment of multidrug-resistant infections, are increasingly being used to treat complicated UTIs. The incidence of multidrug resistance has continued to increase — and now includes carbapenem resistance; therefore, alternative treatment options are needed,” they added.
Researchers randomly assigned 609 patients with complicated UTIs, including acute pyelonephritis, in a 1:1 ratio to receive either IV plazomicin (15 mg/kg of body weight daily) or meropenem (1 g every 8 hours). Patients could choose to receive oral step-down therapy after at least 4 days of IV therapy for a maximum of 10 days of therapy.
Wagenlehner and colleagues found that at day 5, composite cure was observed in 88% of the patients receiving plazomicin and 91.4% of patients receiving meropenem. A test-of-cure visit showed composite cure in 81.7% of those receiving plazomicin vs. 70.1% of those receiving meropenem. The researchers also found that 78.8% of patients receiving plazomicin had microbiologic eradication, including eradication of Enterobacteriaceae that were not susceptible to aminoglycosides, vs. 68.6% of those taking meropenem. Enterobacteriaceae that produce extended-spectrum beta-lactamases were observed in 82.4% of those receiving plazomicin vs. 75% of those receiving meropenem.
In addition, fewer patients who received plazomicin had microbiologic recurrence or clinical relapse 24 to 32 days after the start of their therapy.
“Findings from this trial suggest that additional data should be generated to guide approaches for managing asymptomatic bacteriuria in patients at risk for recurrent complicated UTIs,” Wagenlehner and colleagues wrote. – by Janel Miller
Disclosures: Wagenlehner reports receiving advisory board fees and participating in a study for Achaogen, Bionorica, OM Pharma/Vifor Pharma, and Shionogi; receiving advisory board fees from AstraZeneca, GlaxoSmithKline, Janssen, Leo Pharma, MerLion, MSD, Pfizer, RosenPharma and VenatoRx; and participating in a study for Deutsches Zentrum für Infektionsforschung, Enteris BioPharma and Helperby Therapeutics. Please see the study for all other authors’ relevant financial disclosures.