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dc.contributor.authorSojo Dorado, Jesús
dc.contributor.authorLópez Hernández, Inmaculada
dc.contributor.authorRosso Fernández, Clara
dc.contributor.authorMorales, Isabel M.
dc.contributor.authorPalacios Baena, Zaira R.
dc.contributor.authorHernández Torres, Alicia
dc.contributor.authorMerino de Lucas, Esperanza
dc.contributor.authorEscolà Vergé, Laura
dc.contributor.authorBereciartua, Elena
dc.contributor.authorGarcía Vázquez, Elisa
dc.contributor.authorPintado, Vicente
dc.contributor.authorBoix Palop, Lucía
dc.contributor.authorNatera Kindelán, Clara
dc.contributor.authorSorlí, Luisa
dc.contributor.authorBorrell, Nuria
dc.contributor.authorGiner Oncina, Livia
dc.contributor.authorAmador Prous, Concha
dc.contributor.authorShaw, Evelyn
dc.contributor.authorJover, Alfredo
dc.contributor.authorMolina, Jose
dc.contributor.authorMartínez Álvarez, Rosa M.
dc.contributor.authorDueñas, Carlos J.
dc.contributor.authorCalvo Montes, Jorge
dc.contributor.authorSilva, Jose T.
dc.contributor.authorCárdenes, Miguel A.
dc.contributor.authorLecuona, María
dc.contributor.authorPomar, Virginia
dc.contributor.authorValiente de Santis, Lucía
dc.contributor.authorYagüe Guirao, Genoveva
dc.contributor.authorLobo Acosta, María Angeles
dc.contributor.authorMerino Bohórquez, Vicente
dc.contributor.authorPascual, Álvaro
dc.contributor.authorRodríguez Baño, Jesús
dc.description.abstractImportance 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. Objective 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. Design, Setting, and Participants 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. Interventions 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. Main Outcomes and Measures The primary outcome was clinical and microbiological cure (CMC) 5 to 7 days after finalization of treatment; a noninferiority margin of 7% was considered. Results 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). Conclusions and Relevance 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.ca_ES
dc.description.sponsorshipThe study was funded by grants RD16/0016/0001, 0002, 0003, 0005, 0007, 0008, 0009,0011, 0012, and 0015 from Plan Nacional de Investigación, Desarrollo e Innovación (I+D+i) 2013 to 2016 and theInstituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI); PT13/0002/0010 and PT17/0017/0012 from the Spanish Clinical Research and Clinical Trials Platform (SCReN); and PI 13/01282co-financed by the European Development Regional Fund “A Way to Achieve Europe” and Operative ProgramIntelligence Growth 2014 to 2020.ca_ES
dc.publisherAmerican Medical Associationca_ES
dc.relation.isformatofReproducció del document publicat a:
dc.relation.ispartofJournal of the American Medical Association (JAMA) Netw Open, 2022,vol. 5, núm. 1ca_ES
dc.rightscc-by (c)American Medical Association, 2022ca_ES
dc.titleEffectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections: A Randomized Clinical Trialca_ES

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