• Beatriz Arns, Andre C Kalil, Guilherme G L Sorio, Emerson Boschi, AntonioAna Carolina PeçanhaACP0000-0001-6146-1247Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil., Juliana Peçanha Antonio, Daniella Cunha Birriel, Daniel Haase Lanziotti, Frederico da Cunha Abbott, Glecia Carla Rocha, Vanildes de Fátima Fernandes, de Souza DantasVicente CésVCHospital Naval Marcílio Dias, Rio de Janeiro, Brazil., Graciele Fátima da Silva Medeiros, Verônica de França Diniz Rocha, Francielle Constantino Pereira, GobattoAndré Luiz NunesALNHospital da Cidade, Salvador, Brazil., Valéria Paes Lima, Fábio Holanda Lacerda, Cláudia Maria Dantas de Maio Carrilho, Kairo Daniel Nunes de Oliveira Cardozo, Vivian Menezes Irineu, Pedro Kurtz, Jaqueline Driemeyer Correia Horvath, Guilhermo Prates Sesin, Crepin Aziz Jose Oluwafoumi Agani, Tiago Marcon Dos Santos, Liliane Spencer Bittencourt Brochier, Bruna Silveira da Rosa, TomaziniBruno MartinsBM0000-0001-6763-6132HCor Research Institute, HCor, São Paulo, SP, Brazil., BesenBruno Adler Maccagnan PinheiroBAMP0000-0002-3516-9696Diretoria de Compromisso Social, Hospital Sírio Libanês, São Paulo, Brazil., Adriano Jose Pereira, Viviane Cordeiro Veiga, Giovana Marssola Nascimento, Alexandre P Zavascki, and OPTIMISE Study Group.
• Infectious Diseases and Infection Control Service, Hospital Moinhos de Vento, 910 Ramiro Barcelos St, Porto Alegre, RS, 90035-000, Brazil. beatriz.arns@hmv.org.br.
• Crit Care. 2024 Dec 18; 28 (1): 412412.

BackgroundShorter courses of antimicrobial therapy have been shown to be non-inferior to longer durations for the management of several infections. However, data on critically ill patients with severe infections by multidrug-resistant Gram-negative bacteria (MDR-GNB) are scarce. In the duratiOn of theraPy in severe infecTIons by MultIdrug-reSistant gram-nEgative bacteria (OPTIMISE) trial, we assessed the non-inferiority of 7-day versus 14-day antimicrobial therapy for patients with intensive care unit (ICU)-acquired severe infections by MDR-GNB.MethodsThis was a randomised multicenter, open-label, parallel controlled, non-inferiority trial. Adult patients with severe infections by MDR-GNB initiated ≥ 48 h of ICU admission were eligible if they were hemodynamically stable and without fever > 48 h on the 7th day of appropriate antimicrobial therapy. Patients were 1:1 randomised to discontinue antimicrobial therapy on the 7th (± 1) day or to continue for a total of 14 (± 1) days. The primary outcome was clinical failure, defined as death or relapse of infection within 28 days of randomisation. An upper edge of the two-tailed 95% confidence interval (CI) of the delta between the clinical failure rate in the 7- and the 14-day lower than 10% in both intention-to-treat (ITT) and per protocol (PP) analyses was set as the non-inferiority criteria.ResultsA total of 106 patients composed the ITT population: 59 and 47 allocated to 7- and 14-day groups, respectively. The PP population included 75 patients: 47 and 28 in the 7- and 14-day groups, respectively. Clinical failure occurred in 42.4% and 44.7% of the ITT population in 7- and 14-day groups, respectively, (risk difference (RD) - 2.3, 95%CI - 21.3 to 16.7), and in 46.8% and 50.0% of the PP population in 7- and 14-day groups, respectively (RD - 3.2, 95%CI - 26.6 to 20.2).  Most infections were of the respiratory tract (73/68.9%) and caused by carbapenem-resistant Enterobacterales (42/39.6%). The study was interrupted before reaching planned sample size due to low recruitment rate.ConclusionThe OPTIMISE trial could not determine the non-inferiority of 7-day compared to 14-day therapy for severe infections caused by MDR-GNB due to early termination related to the low recruitment rate.Trial RegistrationNCT05210387 on January 13, 2022.© 2024. The Author(s).

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