Once-Daily Plazomicin for Complicated Urinary Tract Infections
| Autor: | Florian M E, Wagenlehner, Daniel J, Cloutier, Allison S, Komirenko, Deborah S, Cebrik, Kevin M, Krause, Tiffany R, Keepers, Lynn E, Connolly, Loren G, Miller, Ian, Friedland, Jamie P, Dwyer, Robert, Poirier |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male medicine.medical_specialty Urinary system Administration Oral Drug resistance Microbial Sensitivity Tests 030204 cardiovascular system & hematology Plazomicin Meropenem Drug Administration Schedule 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Enterobacteriaceae Internal medicine Drug Resistance Multiple Bacterial medicine Humans 030212 general & internal medicine Aged Extramural business.industry Aminoglycoside Enterobacteriaceae Infections Patient Acuity General Medicine Middle Aged Anti-Bacterial Agents Multiple drug resistance chemistry Urinary Tract Infections Sisomicin Administration Intravenous Female Once daily business medicine.drug |
| Zdroj: | The New England journal of medicine. 380(8) |
| ISSN: | 1533-4406 |
| Popis: | 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.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.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 β-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 μmol per liter) above baseline occurred in 7.0% of patients in the plazomicin group and in 4.0% in the meropenem group.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.). |
| Databáze: | OpenAIRE |
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