Observational versus randomized controlled trials to inform antibiotic treatment durations: a narrative review. (February 2023)

• Record Type: Journal Article
• Authors: McDonald, Emily G.; Prosty, Connor; Hanula, Ryan; Bortolussi-Courval, Émilie; Albuquerque, Arthur M.; Tong, Steven Y.C.; Hamilton, Fergus; Lee, Todd C.
• Is Part Of: Clinical microbiology and infection. Volume 29:Number 2(2023)
• Page Start: 165
• Page End: 170
• Publication Date: 2023-02
• Subjects: Antibiotics -- High-value care -- Infectious diseases -- Treatment duration; Medical microbiology -- Periodicals; Diagnostic microbiology -- Periodicals; Communicable diseases -- Periodicals; Infection -- Periodicals; 616.01
• DOI: 10.1016/j.cmi.2022.09.002
• Languages: English
• ISSNs: 1198-743X

Abstract

Abstract: Background: Studies comparing shorter and longer antibiotic treatment durations are increasingly common. Randomized controlled trials (RCTs) are an ideal methodological approach to study antibiotic treatment durations; however, these trials can be logistically and financially challenging to conduct. Objectives: In this narrative review, we sought to compare the strengths and limitations of observational study data with those of RCT data in evaluating antibiotic treatment durations. We used uncomplicated Gram-negative bacteraemia as an illustrative case example because several published RCTs and observational studies have been conducted in similar patient populations. Sources: We searched MEDLINE for articles comparing treatment durations for gram-negative bacteremia from inception to June 9th, 2022. We included studies reporting on all-cause mortality and/or relapse at day 28-30. Data comparing short- versus long-course therapy were pooled by Bayesian random effects meta-analyses to assess the odds ratios (OR) of all-cause mortality and relapse at 30 days, stratified by study design. Parameters were summarized with median and 95% highest-density credible intervals (CrI). Posterior probabilities of OR > 1.0 were estimated. Observational studies were further examined to determine if and how they addressed potential sources of bias. Content: We identified 1671 unique records and included 10 studies (seven observational and three RCTs). With respect to 30-day mortality, the Bayesian posterior probability that a longer course of therapy was better (i.e. OR >1.0) was 42% in RCTs (OR, 0.94; 95% CrI, 0.51–1.68) and 91% in observational studies (OR, 1.25; 95% CrI, 0.88–1.73). No observational study fully addressed all potential sources of bias. Implications: On the basis of our findings, we discuss future directions for antibiotic treatment duration trials, including approaches to limit sources of bias in observation data and novel trial designs.