Clostridium difficile and other adverse events from overprescribed antibiotics for acute upper respiratory infection

Background: Guidelines widely recommend avoiding antibiotics for many acute upper respiratory infections (aURIs) to avert adverse events in the absence of likely benefit. However, the extent of harm from these antibiotics remains a subject of debate and could inform patient-centered decision-making. Prior estimates finding a number needed to harm (NNH) between 8 and 10 rely on patient-reported adverse events of any severity. In this analysis, we sought to estimate adverse events by only measuring comparatively severe events that require subsequent clinical evaluation.

Methods: We constructed a retrospective cohort, including 51 million patient encounters. Using logistic regression models, we determined the adjusted odds ratio (aOR) of clinically detectable adverse events following antibiotic use compared with events among unexposed individuals with aURIs. Our outcomes included candidiasis, diarrhea, Clostridium difficile infection (CDI), and a composite outcome.

Findings: From our analysis, 62.4% of the population received antibiotics in an aURI encounter. Observed adverse events in the antibiotic-exposed group were 54,279 and 46,936 for diarrhea and candidiasis, respectively, yielding an aOR of 1.24 and 1.61, and an NNH of 3,126 and 1,975. Observed events of CDI in the exposed group were 30,133, and aORs of isolated CDI and combined adverse events were 1.07 and 1.30, resulting in an NNH of 17,695 and 1,150, respectively. Females were more likely to be diagnosed with any adverse event. Overall antibiotics were found to result in 5.7 additional cases of CDI per 100,000 outpatient prescriptions following an upper respiratory tract infection.

Interpretation: Despite higher NNH than previous methods of analysis, we find substantial iatrogenic harm associated with prescribing antibiotics in aURIs.