Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• The Lancet infectious diseases, 2024-04, Vol.24 (4), p.375-385

Ort / Verlag

United States: Elsevier Ltd

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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. 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. 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. 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.