Emulating a Target Trial of Shorter Compared to Longer Course of Antibiotic Therapy for Gram-Negative Bacteremia.

Bibliographic Details
Title: Emulating a Target Trial of Shorter Compared to Longer Course of Antibiotic Therapy for Gram-Negative Bacteremia.
Authors: Tingsgård, Sandra, Israelsen, Simone Bastrup, Østergaard, Christian, Benfield, Thomas
Source: Clinical Infectious Diseases; 2/15/2024, Vol. 78 Issue 2, p292-300, 9p
Subject Terms: BACTEREMIA, CAUSES of death, CONFIDENCE intervals, TREATMENT duration, TREATMENT effectiveness, RANDOMIZED controlled trials, COMPARATIVE studies, COMMUNITY-acquired infections, DESCRIPTIVE statistics, RESEARCH funding, GRAM-negative bacterial diseases, STATISTICAL sampling, ANTIBIOTICS
Geographic Terms: DENMARK
Abstract: Background Despite the availability of antimicrobial therapies, gram-negative bacteremia remains a significant cause of morbidity and mortality on a global level. Recent randomized controlled trials support shorter antibiotic treatment duration for individuals with uncomplicated gram-negative bacteremia. The target trial framework using the cloning approach utilizes real-world data but eliminates the issue of immortal time bias seen in observational studies by emulating the analysis of randomized trials with full adherence. Method A hypothetical target trial allocating individuals with gram-negative bacteremia to either short antibiotic treatment duration (5–7 days) or longer antibiotic treatment duration (8–14 days) was specified and emulated using the cloning, censoring, and weighting approach. The primary outcome was 90-day all-cause mortality. Secondary outcome was a composite endpoint of clinical and microbiological relapse. The emulated trial included individuals from four hospitals in Copenhagen from 2018 through 2021. Results In sum, 1040 individuals were included. The median age of the cohort was 76 years, the majority were male (54%), had community-acquired gram-negative bacteremia (86%), urinary tract infection as the source of the infection (78%), and Escherichia coli as the pathogen of the infection (73%). The adjusted 90-day risk difference in all-cause mortality was 1.3% (95% confidence interval [CI]: −.7, 3.3), and the risk ratio was 1.12 (95% CI:.89, 1.37). The adjusted 90-day risk difference in relapse was 0.7% (95% CI: −2.3, 3.8), and the risk ratio was 1.07 (95% CI:.71, 1.45). Conclusions We found comparative outcomes for shorter treatment duration compared to longer treatment duration in patients with gram-negative bacteremia. [ABSTRACT FROM AUTHOR]
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Database: Complementary Index
More Details
ISSN:10584838
DOI:10.1093/cid/ciad670
Published in:Clinical Infectious Diseases
Language:English