Journal article

Publication year: 2019

Pages: 729-740

Journal: New England Journal of Medicine

Volume number: 380

Issue number: 8

ISSN: 0028-4793

eISSN: 1533-4406

Open access status: Bronze

DOI Link: https://doi.org/10.1056/NEJMoa1801467

Publisher: Massachusetts Medical Society

Abstract: 

BACKGROUND

The increasing multidrug resistance among gram-negative uropathogens necessitates new treatments for serious infections. Plazomicin is an aminoglycoside with bactericidal activity against multidrug-resistant (including carbapenem-resistant) Enterobacteriaceae.

METHODS

We randomly assigned 609 patients with complicated urinary tract infections (UTIs), including acute pyelonephritis, in a 1: 1 ratio to receive intravenous plazomicin (15 mg per kilogram of body weight once daily) or meropenem (1 g every 8 hours), with optional oral step-down therapy after at least 4 days of intravenous therapy, for a total of 7 to 10 days of therapy. The primary objective was to show the noninferiority of plazomicin to meropenem in the treatment of complicated UTIs, including acute pyelonephritis, with a noninferiority margin of 15 percentage points. The primary end points were composite cure (clinical cure and microbiologic eradication) at day 5 and at the test-of-cure visit (15 to 19 days after initiation of therapy) in the microbiologic modified intention-to-treat population.

RESULTS

Plazomicin was noninferior to meropenem with respect to the primary efficacy end points. At day 5, composite cure was observed in 88.0% of the patients (168 of 191 patients) in the plazomicin group and in 91.4% (180 of 197 patients) in the meropenem group (difference, -3.4 percentage points; 95% confidence interval [CI], -10.0 to 3.1). At the test-of-cure visit, composite cure was observed in 81.7% (156 of 191 patients) and 70.1% (138 of 197 patients), respectively (difference, 11.6 percentage points; 95% CI, 2.7 to 20.3). At the test-of-cure visit, a higher percentage of patients in the plazomicin group than in the meropenem group were found to have microbiologic eradication, including eradication of Enterobacteriaceae that were not susceptible to aminoglycosides (78.8% vs. 68.6%) and Enterobacteriaceae that produce extended-spectrum beta-lactamases (82.4% vs. 75.0%). At late follow-up (24 to 32 days after initiation of therapy), fewer patients in the plazomicin group than in the meropenem group had microbiologic recurrence (3.7% vs. 8.1%) or clinical relapse (1.6% vs. 7.1%). Increases in serum creatinine levels of 0.5 mg or more per deciliter (>= 40 mu mol per liter) above baseline occurred in 7.0% of patients in the plazomicin group and in 4.0% in the meropenem group.

CONCLUSIONS

Once-daily plazomicin was noninferior to meropenem for the treatment of complicated UTIs and acute pyelonephritis caused by Enterobacteriaceae, including multidrug-resistant strains. (Funded by Achaogen and the Biomedical Advanced Research and Development Authority; EPIC ClinicalTrials.gov number, NCT02486627.)

Harvard Citation style: Wagenlehner, F., Cloutier, D., Komirenko, A., Cebrik, D., Krause, K., Keepers, T., et al. (2019) Once-Daily Plazomicin for Complicated Urinary Tract Infections, New England Journal of Medicine, 380(8), pp. 729-740. https://doi.org/10.1056/NEJMoa1801467

APA Citation style: Wagenlehner, F., Cloutier, D., Komirenko, A., Cebrik, D., Krause, K., Keepers, T., Connolly, L., Miller, L., Friedland, I., & Dwyer, J. (2019). Once-Daily Plazomicin for Complicated Urinary Tract Infections. New England Journal of Medicine. 380(8), 729-740. https://doi.org/10.1056/NEJMoa1801467