Research in context
bacterial infections, death, tuberculosis
BACTERIAL INFECTIONS, TUBERCULOSIS, TUBERCULOSIS

Tuberculosis diagnostic algorithms often recommend prescription of broad-spectrum antibiotics for patients whose initial sputum tests are negative (trial-of-antibiotics), assuming that post-antibiotic symptom improvement rules out tuberculosis. We searched MEDLINE, Embase, and Global Health on Feb 18, 2023, using the combined terms for “tuberculosis”, “antibiotic treatment”, terms for diagnostic accuracy (“sensitivity”, “specificity”, and “predictive value”), and a filter for randomised trials. We searched for randomised trials published from database inception to Feb 18, 2023, with no language restrictions, and found no relevant publications. Our systematic review and meta-analysis that pooled available observational data (only eight studies), concluded that trial-of-antibiotics was yet to be supported by evidence, and the meta-analysis suggested that diagnostic performance was low. Not one of the identified studies systematically assessed the effect on other clinical outcomes and antimicrobial resistance.
To our knowledge, this study is the first randomised trial to investigate the diagnostic, clinical, and the effect on antimicrobial resistance of trial-of-antibiotics to rule out tuberculosis. Compared with standard of care, trial-of-antibiotics with either azithromycin or amoxicillin modestly improved diagnostic specificity for mycobacteriologically confirmed tuberculosis, and provided weak evidence for increased risk of antimicrobial resistance. There was no effect on the composite clinical outcome (coprimary) of missed tuberculosis diagnosis, hospitalisation, or death.
These results confirm the limited benefit of trial-of-antibiotics in tuberculosis screening algorithms, presenting an opportunity for discontinuation of routine prescription of trial-of-antibiotics and improved antimicrobial stewardship, without affecting clinical outcomes. National tuberculosis and antimicrobial stewardship programmes should restrict prescription of empirical broad-spectrum antibiotics to patients in which strong clinical or microbiological indication exists. New affordable and point-of-care diagnostics for tuberculosis and other respiratory pathogens are urgently needed to address the unmet clinical need.In addition to uncertain diagnostic performance and concerns about antimicrobial resistance, patient safety and effectiveness in improving clinical outcomes are key underinvestigated considerations when trials-of-antibiotics are used in tuberculosis diagnostic algorithms. The potential for clinical benefit is based on the high risk of bacterial infections in patients undergoing tuberculosis investigations.