Portal de Periódicos da CAPES

Efficacy and safety of a structured de-escalation from antipseudomonal β-lactams in bloodstream infections due to Enterobacterales (SIMPLIFY): an open-label, multicentre, randomised trial

2024; Elsevier BV; Volume: 24; Issue: 4 Linguagem: Inglês

10.1016/s1473-3099(23)00686-2

1474-4457

Luis Eduardo López-Cortés, Mercedes Delgado-Valverde, Elisa Moreno-Mellado, Josune Goikoetxea Aguirre, Laura Guío Carrión, María José Blanco Vidal, Leyre Mónica López Soria, Pérez Rodríguez, Lucía Martínez Lamas, Francisco Arnaíz de las Revillas, Carlos Armiñanzas, Carlos Ruiz de Alegría Puig, Patricia Jiménez Aguilar, María del Carmen Martínez-Rubio, Carmen Sáez-Bejar, Carmen de las Cuevas, Andrés Martín-Aspas, Fátima Galán‐Sánchez, José Ramón Yuste, José Leiva, Germán Bou, Patricia Capón González, Lucía Boix-Palop, Mariona Xercavins-Valls, Miguel Ángel Goenaga-Sánchez, Diego Vicente Anza, Juan José Castón, Manuel Recio, Esperanza Merino, Juan Carlos Rodrı́guez, Belén Loeches, Guillermo Cuervo, María José Guerra Palmero, Antonio Plata, Salvador Pérez Cortés, Pablo López Mato, José Luis Sierra Monzón, Clara Rosso-Fernández, José María Bravo-Ferrer, Pilar Retamar, Jesús Rodríguez‐Baño, Marina de Cueto, Irene Borreguero, Javier Nieto Aranda, Adrián Sousa Domínguez, Claudia González-Rico, María Carmen Fariñas, María Luisa Fernández Ávila, Alberto Romero-Palacios, Francisca María Guerrero Sánchez, Marta Rúa Gómez, Idoia Bilbao del Olmo, Esther Calbo, Beatriz Dietl, Maialen Ibarguren Pinilla, Marta Gómez-Ruiz de Arbulo, Isabel Torres Beceiro, Isabel Machuca, Ángela Cano, Livia Giner, Héctor Pinargote Celorio, Emilio Cendejas‐Bueno, María Pilar Romero‐Gómez, Adrián Argüelles Curto, José María Reguero, M. Díaz-López, José Ramón Paño,

Antibiotic Resistance in Bacteria

Background De-escalation from broad-spectrum to narrow-spectrum antibiotics is considered an important measure to reduce the selective pressure of antibiotics, but a scarcity of adequate evidence is a barrier to its implementation. We aimed to determine whether de-escalation from an antipseudomonal β-lactam to a narrower-spectrum drug was non-inferior to continuing the antipseudomonal drug in patients with Enterobacterales bacteraemia. Methods An open-label, pragmatic, randomised trial was performed in 21 Spanish hospitals. Patients with bacteraemia caused by Enterobacterales susceptible to one of the de-escalation options and treated empirically with an antipseudomonal β-lactam were eligible. Patients were randomly assigned (1:1; stratified by urinary source) to de-escalate to ampicillin, trimethoprim–sulfamethoxazole (urinary tract infections only), cefuroxime, cefotaxime or ceftriaxone, amoxicillin–clavulanic acid, ciprofloxacin, or ertapenem in that order according to susceptibility (de-escalation group), or to continue with the empiric antipseudomonal β-lactam (control group). Oral switching was allowed in both groups. The primary outcome was clinical cure 3–5 days after end of treatment in the modified intention-to-treat (mITT) population, formed of patients who received at least one dose of study drug. Safety was assessed in all participants. Non-inferiority was declared when the lower bound of the 95% CI of the absolute difference in cure rate was above the –10% non-inferiority margin. This trial is registered with EudraCT (2015-004219-19) and ClinicalTrials.gov (NCT02795949) and is complete. Findings 2030 patients were screened between Oct 5, 2016, and Jan 23, 2020, of whom 171 were randomly assigned to the de-escalation group and 173 to the control group. 164 (50%) patients in the de-escalation group and 167 (50%) in the control group were included in the mITT population. 148 (90%) patients in the de-escalation group and 148 (89%) in the control group had clinical cure (risk difference 1·6 percentage points, 95% CI –5·0 to 8·2). The number of adverse events reported was 219 in the de-escalation group and 175 in the control group, of these, 53 (24%) in the de-escalation group and 56 (32%) in the control group were considered severe. Seven (5%) of 164 patients in the de-escalation group and nine (6%) of 167 patients in the control group died during the 60-day follow-up. There were no treatment-related deaths. Interpretation De-escalation from an antipseudomonal β-lactam in Enterobacterales bacteraemia following a predefined rule was non-inferior to continuing the empiric antipseudomonal drug. These results support de-escalation in this setting. Funding Plan Nacional de I+D+i 2013–2016 and Instituto 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; Spanish Clinical Research and Clinical Trials Platform, co-financed by the EU; European Development Regional Fund "A way to achieve Europe", Operative Program Intelligence Growth 2014–2020.