Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections : A Randomized Clinical Trial
Sojo-Dorado, Jesús (Universidad de Sevilla)
López-Hernández, I. (Universidad de Sevilla)
Rosso-Fernandez, C. (Hospital Universitario Virgen Macarena (Sevilla, Andalusia))
Palacios-Baena, Z.R. (Universidad de Sevilla)
Hernández-Torres, A. (Hospital Clínico Universitario Virgen de la Arrixaca (El Palmar, Múrcia))
Merino De Lucas, E. (Hospital General Universitario de Alicante (Alacant, País Valencià))
Escolà-Vergé, Laura (Hospital Universitari Vall d'Hebron)
Bereciartua, Elena (Hospital Universitario de Cruces (Barakaldo, País Basc))
García-Vázquez, E. (Hospital Clínico Universitario Virgen de la Arrixaca (El Palmar, Múrcia))
Pintado, Vicente (Hospital Universitario Ramón y Cajal (Madrid))
Boix-Palop, Lucía (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Natera-Kindelán, C. (Hospital Universitario Reina Sofía (Còrdova, Espanya))
Sorlí, Luisa (Institut Hospital del Mar d'Investigacions Mèdiques)
Borrell, Nuria (Hospital Universitari Son Espases (Palma de Mallorca, Balears))
Giner-Oncina, L. (Hospital General Universitario de Alicante (Alacant, País Valencià))
Amador-Prous, C. (Hospital Marina Baixa (La Vila Joiosa, Alacant))
Shaw, Evelyn (Institut d'Investigació Biomèdica de Bellvitge)
Jover-Saenz, A. (Hospital Universitari Arnau de Vilanova)
Molina, J. (Universidad de Sevilla)
Martínez-Alvarez, R.M. (Hospital Universitario Miguel Servet (Saragossa))
Dueñas, C.J. (Hospital Clínico Universitario de Valladolid)
Calvo-Montes, J. (Hospital Universitario Marqués de Valdecilla (Santander, Cantabria))
Silva, J.T. (Hospital 12 de Octubre (Madrid))
Cárdenes, M.A. (Hospital Universitario de Gran Canaria Dr. Negrín)
Lecuona, M. (Hospital Universitario de Canarias (La Laguna))
Pomar, Virginia (Institut d'Investigació Biomèdica Sant Pau)
Valiente De Santis, L. (Hospital Regional Universitario de Málaga)
Yagüe-Guirao, G. (Hospital Clínico Universitario Virgen de la Arrixaca (El Palmar, Múrcia))
Lobo-Acosta, M.A. (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Merino-Bohórquez, V. (Hospital Universitario Virgen Macarena (Sevilla, Andalusia))
Pascual, A. (Universidad de Sevilla)
Rodríguez-Baño, J. (Universidad de Sevilla)
Almirante Gragera, Benito (Hospital Universitari Vall d'Hebron)
Mirelis, Beatriz (Institut d'Investigació Biomèdica Sant Pau)
Pigrau, Carlos (Hospital Universitari Vall d'Hebron)
Viñado, Belén (Hospital Universitari Vall d'Hebron)
Puig-Asensio, Mireia (Hospital Universitari Vall d'Hebron)
Ardanuy, Carmen (Hospital Universitari de Bellvitge)
Pujol, Miquel (Hospital Universitari de Bellvitge)
Universitat Autònoma de Barcelona

Date:	2022
Abstract:	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. 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. 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. 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.
Grants:	Ministerio de Economía y Competitividad RD16/0016/0001 Ministerio de Economía y Competitividad RD16/0016/0002 Ministerio de Economía y Competitividad RD16/0016/0003 Ministerio de Economía y Competitividad RD16/0016/0005 Ministerio de Economía y Competitividad RD16/0016/0007 Ministerio de Economía y Competitividad RD16/0016/0008 Ministerio de Economía y Competitividad RD16/0016/0009 Ministerio de Economía y Competitividad RD16/0016/0011 Ministerio de Economía y Competitividad RD16/0016/0012 Ministerio de Economía y Competitividad RD16/0016/0015 Ministerio de Economía y Competitividad PT13/0002/0010 Ministerio de Economía y Competitividad PI13/01282
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	JAMA network open, Vol. 5 Núm. 1 (13 2022) , p. 37277, ISSN 2574-3805

DOI: 10.1001/jamanetworkopen.2021.37277
PMID: 35024838

14 p, 1016.9 KB

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