Seven Versus 14 Days of Antibiotic Therapy for Multidrug-resistant Gram-negative Bacilli Infections (OPTIMISE)

Hospital Moinhos de Vento

Status: Terminated

Conditions: Acinetobacter Infections; Bacteremia; Bloodstream Infection; Carbapenem-Resistant Enterobacteriaceae Infection; Severe Infection; Carbapenem Resistant Bacterial Infection; Gram-Negative Bacterial Infections; Pseudomonas Aeruginosa; Human; Sepsis

Treatments: Other: Duration of therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT05210387

47366621.1.1001.5330

Details and patient eligibility

About

Antimicrobial resistance is a major global problem, particularly in hospital-acquired infections (HAIs). Gram-negative bacilli (GNB), including Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii, are among the most common pathogens associated with multidrug resistance and HAIs. These bacteria are of special concern because few therapeutic options are available.

Traditionally, the duration of treatment for severe multidrug-resistant (MDR)-GNB infections is 14 days. Studies of severe infections by GNB, regardless of susceptibility profile, have shown that shorter antimicrobial treatments are not inferior to traditional durations of therapy and are associated with a lower incidence of adverse effects. However, there are currently no studies assessing whether shorter duration of antimicrobial treatment is effective for MDR-GNB.

This open-label, randomized clinical trial aims to assess the non-inferiority of 7-day antibiotic therapy compared to conventional 14-day treatment in severe infections by MDR-GNB.

Enrollment: 107 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria

• Infection's diagnosis while in the ICU
• Severe infection in any site (defined as the presence of sepsis/septic shock or bloodstream infection or pneumonia) associated with a positive culture by MRD-GNB (Acinetobacter baumannii complex, Pseudomonas aeruginosa, and Enterobacterales bacteria, only susceptible to carbapenems and/or polymyxins)
• Hemodynamically stable and afebrile (axillary temperature less than 37.8ºC) for at least 48 hours on day 7 of adequate antibiotic therapy
• Consent of the team providing care to the patient regarding their inclusion in the research

Exclusion criteria

• Inclusion in other experimental studies involving antimicrobial therapy
• Infections that have as the primary site: endocarditis/endovascular infection, necrotizing fasciitis, osteomyelitis, abdominal abscess or other abdominal infections requiring surgical intervention (except infections that have been treated surgically, with curative character within the first 3 days of appropriate antimicrobial therapy), central nervous system Infections, empyema, prosthetic infection;
• Immunosuppression defined as: neutrophil cells <1000/mm³ in the current hospitalization, HIV/AIDS diagnosis with last CD4 count <200/mm³, solid organ transplantation in the last year and/or need for increased immunosuppression due to acute rejection in the last year, hematopoietic stem cell transplantation in the last year, and/or current therapy for chronic graft-versus-host disease
• Positive blood cultures for the same pathogen within 48 hours prior to randomization, when collected
• Uncontrolled concomitant infection with another GNB (regardless of susceptibility profile)
• Previous inclusion in this study
• Known pregnancy
• Patient in palliative care who has already decided not to restart antimicrobials, if necessary, or hemodynamic support measures.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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107 participants in 2 patient groups

7-day adequate antibiotic therapy

Experimental group

Description:

Adequate antibiotic therapy is defined as antimicrobial treatment with at least one agent with in vitro susceptibility.

Treatment:

Other: Duration of therapy

14-day adequate antibiotic therapy

Active Comparator group

Description:

Adequate antibiotic therapy is defined as antimicrobial treatment with at least one agent with in vitro susceptibility.

Treatment:

Other: Duration of therapy