RT Journal Article
T1 Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections: A Randomized Clinical Trial.
A1 Sojo-Dorado, Jesus
A1 Lopez-Hernandez, Inmaculada
A1 Rosso-Fernandez, Clara
A1 Morales, Isabel M
A1 Palacios-Baena, Zaira R
A1 Hernandez-Torres, Alicia
A1 Merino-de-Lucas, Esperanza
A1 Escola-Verge, Laura
A1 Bereciartua, Elena
A1 Garcia-Vazquez, Elisa
A1 Pintado, Vicente
A1 Boix-Palop, Lucía
A1 Natera-Kindelan, Clara
A1 Sorli, Luisa
A1 Borrell, Nuria
A1 Giner-Oncina, Livia
A1 Amador-Prous, Concha
A1 Shaw, Evelyn
A1 Jover-Saenz, Alfredo
A1 Molina, Jose
A1 Martinez-Alvarez, Rosa M
A1 Dueñas, Carlos J
A1 Calvo-Montes, Jorge
A1 Silva, Jose T
A1 Cardenes, Miguel A
A1 Lecuona, Maria
A1 Pomar, Virginia
A1 Valiente-de-Santis, Lucía
A1 Yagüe-Guirao, Genoveva
A1 Lobo-Acosta, Maria Angeles
A1 Merino-Bohorquez, Vicente
A1 Pascual, Alvaro
A1 Rodriguez-Baño, Jesus
K1 Aged, 80 and over
K1 Anti-Bacterial Agents
K1 Bacteremia
K1 Drug Resistance, Multiple, Bacterial
AB The consumption of broad-spectrum drugs has increased as a consequence of the spread of multidrug-resistant (MDR) Escherichia coli. Finding alternatives for these infections is critical, for which some neglected drugs may be an option. To determine whether fosfomycin is noninferior to ceftriaxone or meropenem in the targeted treatment of bacteremic urinary tract infections (bUTIs) due to MDR E coli. This multicenter, randomized, pragmatic, open clinical trial was conducted at 22 Spanish hospitals from June 2014 to December 2018. Eligible participants were adult patients with bacteremic urinary tract infections due to MDR E coli; 161 of 1578 screened patients were randomized and followed up for 60 days. Data were analyzed in May 2021. Patients were randomized 1 to 1 to receive intravenous fosfomycin disodium at 4 g every 6 hours (70 participants) or a comparator (ceftriaxone or meropenem if resistant; 73 participants) with the option to switch to oral fosfomycin trometamol for the fosfomycin group or an active oral drug or parenteral ertapenem for the comparator group after 4 days. The primary outcome was clinical and microbiological cure (CMC) 5 to 7 days after finalization of treatment; a noninferiority margin of 7% was considered. Among 143 patients in the modified intention-to-treat population (median [IQR] age, 72 [62-81] years; 73 [51.0%] women), 48 of 70 patients (68.6%) treated with fosfomycin and 57 of 73 patients (78.1%) treated with comparators reached CMC (risk difference, -9.4 percentage points; 1-sided 95% CI, -21.5 to ∞ percentage points; P = .10). While clinical or microbiological failure occurred among 10 patients (14.3%) treated with fosfomycin and 14 patients (19.7%) treated with comparators (risk difference, -5.4 percentage points; 1-sided 95% CI, -∞ to 4.9; percentage points; P = .19), an increased rate of adverse event-related discontinuations occurred with fosfomycin vs comparators (6 discontinuations [8.5%] vs 0 discontinuations; P = .006). In an exploratory analysis among a subset of 38 patients who underwent rectal colonization studies, patients treated with fosfomycin acquired a new ceftriaxone-resistant or meropenem-resistant gram-negative bacteria at a decreased rate compared with patients treated with comparators (0 of 21 patients vs 4 of 17 patients [23.5%]; 1-sided P = .01). This study found that fosfomycin did not demonstrate noninferiority to comparators as targeted treatment of bUTI from MDR E coli; this was due to an increased rate of adverse event-related discontinuations. This finding suggests that fosfomycin may be considered for selected patients with these infections. ClinicalTrials.gov Identifier: NCT02142751.
PB American Medical Association
YR 2022
FD 2022-01-13
LK http://hdl.handle.net/10668/21939
UL http://hdl.handle.net/10668/21939
LA en
NO Sojo-Dorado J, López-Hernández I, Rosso-Fernandez C, Morales IM, Palacios-Baena ZR, Hernández-Torres A, et al. Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections: A Randomized Clinical Trial. JAMA Netw Open. 2022 Jan 4;5(1):e2137277
DS RISalud
RD Apr 7, 2025