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. 2024 Jan;13(1):237-250.
doi: 10.1007/s40121-023-00897-9. Epub 2023 Dec 16.

A Randomized, Open-Label, Non-inferiority Clinical Trial Assessing 7 Versus 14 Days of Antimicrobial Therapy for Severe Multidrug-Resistant Gram-Negative Bacterial Infections: The OPTIMISE Trial Protocol

Beatriz Arns  1   2 , Jaqueline Driemeyer C Horvath  1 , Gabriela Soares Rech  1 , Guilhermo Prates Sesin  1 , Crepin Aziz Jose Oluwafoumi Agani  1 , Bruna Silveira da Rosa  1 , Tiago Marcon Dos Santos  1 , Liliane Spencer Bittencourt Brochier  1 , Alexandre Biasi Cavalcanti  3 , Bruno Martins Tomazini  3 , Adriano Jose Pereira  4 , Viviane Cordeiro Veiga  5 , Giovana Marssola Nascimento  6 , Andre C Kalil  7 , Alexandre P Zavascki  8   9
Affiliations

A Randomized, Open-Label, Non-inferiority Clinical Trial Assessing 7 Versus 14 Days of Antimicrobial Therapy for Severe Multidrug-Resistant Gram-Negative Bacterial Infections: The OPTIMISE Trial Protocol

Beatriz Arns et al. Infect Dis Ther. 2024 Jan.

Abstract

Introduction: Shorter courses of antimicrobials have been shown to be non-inferior to longer, "traditional" duration of therapies, including for some severe healthcare-associated infections, with a few exceptions. However, evidence is lacking regarding shorter regimes against severe infections by multidrug-resistant Gram-negative bacteria (MDR-GNB), which are often caused by distinct strains and commonly treated with second-line antimicrobials. In the duratiOn of theraPy in severe infecTIons by MultIdrug-reSistant gram-nEgative bacteria (OPTIMISE) trial, we aim to assess the non-inferiority of 7-day versus 14-day antimicrobial therapy in critically ill patients with severe infections caused by MDR-GNB.

Methods: This is a randomized, multicenter, open-label, parallel controlled trial to assess the non-inferiority of 7-day versus 14-day of adequate antimicrobial therapy for intensive care unit (ICU)-acquired severe infections by MDR-GNB. Adult patients with severe infections by MDR-GNB initiated after 48 h of ICU admission are screened for eligibility. Patients are eligible if they proved to be hemodynamically stable and without fever for at least 48 h on the 7th day of adequate antimicrobial therapy. After consenting, patients are 1:1 randomized to discontinue antimicrobial therapy on the 7th (± 1) day or to continue for a total of 14th (± 1) days.

Planned outcomes: The primary outcome is treatment failure, defined as death or relapse of infection within 28 days after randomization. Non-inferiority will be achieved if the upper edge of the two-tailed 95% confidence interval of the difference between the clinical failure rate in the 7-day and the 14-day group is not higher than 10%.

Conclusion: The OPTIMISE trial is the first randomized controlled trial specifically designed to assess the duration of antimicrobial therapy in patients with severe infections by MDR-GNB.

Trial registration: ClinicalTrials.gov, NCT05210387. Registered on 27 January 2022. Seven Versus 14 Days of Antibiotic Therapy for Multidrug-resistant Gram-negative Bacilli Infections (OPTIMISE).

Keywords: Acinetobacter baumannii; Antimicrobial resistance; Antimicrobial therapy; Enterobacterales; Gram-negative bacilli; Klebsiella pneumoniae; Pseudomonas aeruginosa.

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Conflict of interest statement

All authors confirm that they have no conflicts of interest to declare. Alexandre P. Zavascki is a research fellow of the National Council for Scientific and Technological Development (CNPq), Ministry of Science and Technology, Brazil.

Figures

Fig. 1
Fig. 1
Participant timeline. ATM antimicrobial, D day of the study, ICF informed consent form
See this image and copyright information in PMC

References

    1. Tacconelli E, Carrara E, Savoldi A, et al. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis. 2018;18(3):318–327. doi: 10.1016/S1473-3099(17)30753-3. - DOI - PubMed
    1. Review on antimicrobial resistance. Tackling drug-resistant infections globally: final report and recommendations (2016). https://amr-review.org/sites/default/files/160518_Final%20paper_with%20c.... Accessed 9 Sept 2023.
    1. WHO. Antimicrobial resistance. https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance. Accessed 29 Sep 2023.
    1. Antimicrobial Resistance Collaborators Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022;399(10325):629–655. doi: 10.1016/S0140-6736(21)02724-0. - DOI - PMC - PubMed
    1. Stewardson AJ, Marimuthu K, Sengupta S, et al. Effect of carbapenem resistance on outcomes of bloodstream infection caused by Enterobacteriaceae in low-income and middle-income countries (PANORAMA): a multinational prospective cohort study. Lancet Infect Dis. 2019;19(6):601–610. doi: 10.1016/S1473-3099(18)30792-8. - DOI - PubMed

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