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For most patients hospitalized for community-acquired pneumonia, guidelines recommend empirical therapy with a β-lactam antibiotic plus atypical bacterial coverage with azithromycin; doxycycline is recommended only as an alternative, when azithromycin is contraindicated (NEJM JW Gen Med Dec 1 2019 and Am J Respir Crit Care Med 2019; 200:e45). Because of doxycycline's antitoxin activity and postulated lower effect on gut flora, investigators evaluated its association with Clostridioides difficile infection (CDI; confirmed by PCR testing) in a retrospective analysis of 156,000 patients hospitalized in U.S. Veterans Affairs hospitals for community-acquired pneumonia. All patients received a β-lactam antimicrobial plus either azithromycin (87%)…