Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections

Autor: Sojo Dorado, Jesús, López Hernández, Inmaculada, Rosso Fernández, Clara, Morales, Isabel M., Palacios Baena, Zaira R., Hernández Torres, Alicia, Merino de Lucas, Esperanza, Escolà Vergé, Laura, Bereciartua, Elena, García Vázquez, Elisa, Pintado, Vicente, Boix Palop, Lucía, Natera Kindelán, Clara, Sorlí, Luisa, Borrell, Nuria, Giner Oncina, Livia, Amador Prous, Concha, Shaw, Evelyn, Jover Saenz, Alfredo, Molina, Jose, Martínez Álvarez, Rosa M., Dueñas, Carlos J., Calvo Montes, Jorge, Silva, Jose T., Cárdenes, Miguel A., Lecuona, María, Pomar, Virginia, Valiente de Santis, Lucía, Yagüe Guirao, Genoveva, Lobo Acosta, María Angeles, Merino Bohórquez, Vicente, Pascual, Alvaro, Rodríguez Baño, Jesús, Almirante, Benito, Fernández, Mario, Paño Pardo, José Ramón, Cueto, Marina de, Retamar Gentil, Pilar, López Cortés, Luis Eduardo, Gutiérrez Gutiérrez, Belén, Docobo, Fernando, Borreguero, Irene, Camean, Manuel, Moral Escudero, Encarnación, Pareja Rodríguez de Vera, Ana, Martínez Toldos, María del Carmen, Blázquez Abellán, Ana, Belles Belles, Alba, Ramírez Hidalgo, María Fernanda, Mirelis, Beatriz, Calbo, Esther, Xercavins, Mariona, Gracia Ahufinger, Irene, Cano Yuste, Angela M., Guío, Laura, Hernandez, Jose Luis, Pigrau Serrallach, Carlos, Viñado Pérez, Belen, Puig Asensio, Mireia, Ardanuy, Carmen, Pujol, Miquel, García Rosado, Dácil, Gil Anguita, Concepción, Siverio, Ana, Gimeno Gascón, Adelina, Boix Martínez, Vicente, Reus Bañuls, Sergio, Agea Durán, Iván, Fariñas, Carmen, Palop, Begoña, Vilchez, Helem, Lepe, José Antonio, Gil Navarro, María Victoria, San Juan, Rafael, Chaves, Fernando, Escudero, Rosa, Gioia, Francesca, Sánchez Díaz, Ana María, Cañas Pedrosa, Ana, Sangil Monroy, Nayra, Toyas Miazza, Carla, Reipi Geiras Forest Group
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Dipòsit Digital de la UB
Universidad de Barcelona
Popis: IMPORTANCE 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 pa renteral 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 infinity 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. -infinity 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.
Databáze: OpenAIRE
Externí odkaz: