TY - JOUR

T1 - Emulating a Target Trial of Shorter Compared to Longer Course of Antibiotic Therapy for Gram-Negative Bacteremia

AU - Tingsgård, Sandra

AU - Israelsen, Simone Bastrup

AU - Østergaard, Christian

AU - Benfield, Thomas

N1 - Publisher Copyright: © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved.

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

KW - antibiotic stewardship

KW - bloodstream infections

KW - gram-negative bacteremia

KW - target trial emulation

KW - treatment duration

U2 - 10.1093/cid/ciad670

DO - 10.1093/cid/ciad670

M3 - Journal article

C2 - 37949816

AN - SCOPUS:85182874663

VL - 78

SP - 292

EP - 300

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 2

ER -