José Molina1, Enrique Montero-Mateos2, Julia Praena-Segovia1, Eva León-Jiménez3, Clara Natera4, Luis E López-Cortés5, Lucía Valiente6, Clara M Rosso-Fernández7, Marta Herrero1, Ana I Aller-García3, Ángela Cano4, Belén Gutiérrez-Gutiérrez5, Ignacio Márquez-Gómez6, Rocío Álvarez-Marín1, Carmen Infante1, Cristina Roca1, Adoración Valiente-Méndez5, Jerónimo Pachón8, José María Reguera6, Juan Enrique Corzo-Delgado3, Julián Torre-Cisneros9, Jesús Rodríguez-Baño10, José Miguel Cisneros11. 1. Unit of Infectious Diseases, Microbiology and Preventive Medicine, Virgen del Rocío University Hospital, Seville, Spain; Institute of Biomedicine of Seville (IBiS), Virgen del Rocío and Virgen Macarena University Hospitals/CSIC/University of Seville, Seville, Spain. 2. Department of Pathology and Institute of Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca, Salamanca, Spain. 3. Unit of Infectious Diseases and Microbiology, Virgen de Valme University Hospital, Seville, Spain. 4. Maimonides Institute for Research in Biomedicine of Córdoba (IMIBIC), Service of Infectious Diseases. Reina Sofia University Hospital, Córdoba, Spain. 5. Institute of Biomedicine of Seville (IBiS), Virgen del Rocío and Virgen Macarena University Hospitals/CSIC/University of Seville, Seville, Spain; Clinical Unit of Infectious Diseases and Microbiology, Virgen Macarena University Hospital, Seville, Spain. 6. Unit of Infectious Diseases, Microbiology and Preventive Medicine, Málaga Regional University Hospital, Málaga, Spain. 7. Institute of Biomedicine of Seville (IBiS), Virgen del Rocío and Virgen Macarena University Hospitals/CSIC/University of Seville, Seville, Spain; Spanish Clinical Research Network, Virgen del Rocío University Hospital, Seville, Spain. 8. Institute of Biomedicine of Seville (IBiS), Virgen del Rocío and Virgen Macarena University Hospitals/CSIC/University of Seville, Seville, Spain; Department of Medicine, University of Seville, Seville, Spain. 9. Maimonides Institute for Research in Biomedicine of Córdoba (IMIBIC), Service of Infectious Diseases. Reina Sofia University Hospital, Córdoba, Spain; Department of Medical and Surgical Sciences, University of Córdoba (UCO), Córdoba, Spain. 10. Institute of Biomedicine of Seville (IBiS), Virgen del Rocío and Virgen Macarena University Hospitals/CSIC/University of Seville, Seville, Spain; Clinical Unit of Infectious Diseases and Microbiology, Virgen Macarena University Hospital, Seville, Spain; Department of Medicine, University of Seville, Seville, Spain. 11. Unit of Infectious Diseases, Microbiology and Preventive Medicine, Virgen del Rocío University Hospital, Seville, Spain; Institute of Biomedicine of Seville (IBiS), Virgen del Rocío and Virgen Macarena University Hospitals/CSIC/University of Seville, Seville, Spain; Department of Medicine, University of Seville, Seville, Spain. Electronic address: jmcisnerosh@gmail.com.
Abstract
OBJECTIVE: To prove that 7-day courses of antibiotics for bloodstream infections caused by members of the Enterobacterales (eBSIs) allow a reduction in patients' exposure to antibiotics while achieving clinical outcomes similar to those of 14-day schemes. METHODS: A randomized trial was performed. Adult patients developing eBSI with appropriate source control were assigned to 7 or 14 days of treatment, and followed 28 days after treatment cessation; treatments could be resumed whenever necessary. The primary endpoint was days of treatment at the end of follow-up. Clinical outcomes included clinical cure, relapse of eBSI and relapse of fever. A superiority margin of 3 days was set for the primary endpoint, and a non-inferiority margin of 10% was set for clinical outcomes. Efficacy and safety were assessed together with a DOOR/RADAR (desirability of outcome ranking and response adjusted for duration of antibiotic risk) analysis. RESULTS: 248 patients were assigned to 7 (n = 119) or 14 (n = 129) days of treatment. In the intention-to-treat analysis, median days of treatment at the end of follow-up were 7 and 14 days (difference 7, 95%CI 7-7). The non-inferiority margin was also met for clinical outcomes, except for relapse of fever (-0.2%, 95%CI -10.4 to 10.1). The DOOR/RADAR showed that 7-day schemes had a 77.7% probability of achieving better results than 14-day treatments. CONCLUSIONS: 7-day schemes allowed a reduction in antibiotic exposure of patients with eBSI while achieving outcomes similar to those of 14-day schemes. The possibility of relapsing fever in a limited number of patients, without relevance to final outcomes, may not be excluded, but was overcome by the benefits of shortening treatments.
OBJECTIVE: To prove that 7-day courses of antibiotics for bloodstream infections caused by members of the Enterobacterales (eBSIs) allow a reduction in patients' exposure to antibiotics while achieving clinical outcomes similar to those of 14-day schemes. METHODS: A randomized trial was performed. Adult patients developing eBSI with appropriate source control were assigned to 7 or 14 days of treatment, and followed 28 days after treatment cessation; treatments could be resumed whenever necessary. The primary endpoint was days of treatment at the end of follow-up. Clinical outcomes included clinical cure, relapse of eBSI and relapse of fever. A superiority margin of 3 days was set for the primary endpoint, and a non-inferiority margin of 10% was set for clinical outcomes. Efficacy and safety were assessed together with a DOOR/RADAR (desirability of outcome ranking and response adjusted for duration of antibiotic risk) analysis. RESULTS: 248 patients were assigned to 7 (n = 119) or 14 (n = 129) days of treatment. In the intention-to-treat analysis, median days of treatment at the end of follow-up were 7 and 14 days (difference 7, 95%CI 7-7). The non-inferiority margin was also met for clinical outcomes, except for relapse of fever (-0.2%, 95%CI -10.4 to 10.1). The DOOR/RADAR showed that 7-day schemes had a 77.7% probability of achieving better results than 14-day treatments. CONCLUSIONS: 7-day schemes allowed a reduction in antibiotic exposure of patients with eBSI while achieving outcomes similar to those of 14-day schemes. The possibility of relapsing fever in a limited number of patients, without relevance to final outcomes, may not be excluded, but was overcome by the benefits of shortening treatments.
Authors: Robin M E Janssen; Anke J M Oerlemans; Johannes G Van Der Hoeven; Jaap Ten Oever; Jeroen A Schouten; Marlies E J L Hulscher Journal: J Antimicrob Chemother Date: 2022-07-28 Impact factor: 5.758