Clin Infect Dis. 2023 Nov 9:ciad670. doi: 10.1093/cid/ciad670. Online ahead of print.
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: 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% CI -0.7, 3.3), and the risk ratio was 1.12 (95% CI 0.89, 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 0.71, 1.45).
CONCLUSION: We found comparative outcomes for shorter treatment duration compared to longer treatment duration in patients with Gram-negative bacteremia.
PMID:37949816 | DOI:10.1093/cid/ciad670