Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections: A Randomized Clinical Trial.

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 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. Trial Registration: ClinicalTrials.gov Identifier: NCT02142751.

Un programa de prevención primaria en una escuela secundaria de Panamá / A primary prevention program in a high school in Panamá

Se presentan los resultados de un programa de intervención con énfasis en la prevención primaria desarrollado por el equipo de Salud Mental del Programa de Adolescentes de la Caja de Seguro Social, el cual se llevó a cabo en el Instituto Bolívar, por un período de 3 años. De una muestra que varió cada año entre 400 y 500 estudiantes fueron seleccionados 33,55 y 66 alumnos de primer ciclo, a quienes sus profesores identificaron, a través de una Encuesta de Adaptación Socio-Ecolar, como portadores de problemas de disciplina y bajo rendimento escolástico. Estos estudiantes fueron sometidos a terapia de grupo y sus padres recibieron charlas, lo mismo que sus profesores. Se observó que muchos de los alumnos mostraron mejoría conductual al término del programa, y que tanto los padres como los profesores manifestaron interés en la continuidad del mismo. Paralelamente se fué adiestrando al personal de orientación de la institución en el manejo de técnicas de terapia de grupo y se les hizo particular inicialmnete como observadores, posteriormente como coterapeutas y finalmente, ya en el tercer año del programa, como terapeutas de grupo. Para concluir, se trabajó en la identificación de las formas de manejo de los problemas de conducta dentro de institución, y se efectuó una revisión completa y ulterior modificación del reglamento interno de disciplina