Observational versus randomized controlled trials to inform antibiotic treatment durations: a narrative review

Emily G McDonald*, Connor Prosty, Ryan Hanula, Émilie Bortolussi-Courval, Arthur M Albuquerque, Steven Y C Tong, Fergus Hamilton, Todd C Lee

*Corresponding author for this work

Research output: Contribution to journalReview article (Academic Journal)peer-review

8 Citations (Scopus)
53 Downloads (Pure)


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.

Original languageEnglish
Pages (from-to)165-170
Number of pages6
JournalClinical Microbiology and Infection
Issue number2
Early online date12 Sept 2022
Publication statusPublished - 1 Feb 2023

Bibliographical note

Funding Information:
EGM and TCL receive research salary support from the Fonds de recherche du Québec-Santé.

Publisher Copyright:
© 2022 European Society of Clinical Microbiology and Infectious Diseases


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