Doxycycline for Legionella Pneumonia: Expanding Treatment Horizons Through a Case Series and Narrative Review

Abstract

Background: Legionella pneumonia is a significant cause of community-acquired pneumonia that often requires timely and effective treatment. While fluoroquinolones and macrolides are the recommended first-line therapies, doxycycline offers an alternative with favorable pharmacokinetics, safety, and minimal drug-drug interactions. Methods: We describe three hospitalized patients with Legionella pneumonia who received doxycycline monotherapy.Clinical outcomes, including symptom resolution and survival, were assessed at 60 days. A literature review was also performed for studies published between 1980 and 2025 that evaluated doxycycline for Legionella infection. Results: All three patients achieved clinical improvement with doxycycline monotherapy, with resolution of presenting symptoms and survival at 60 days post-hospitalization. The literature review identified limited clinical data on doxycycline for Legionella pneumonia. In vitro data suggested that doxycycline may have lower bactericidal activity than fluoroquinolones, although its pharmacological profile and tolerability support its consideration in select cases. Conclusion: Doxycycline monotherapy was associated with favorable outcomes in three cases of Legionella pneumonia. Although the evidence remains sparse, doxycycline may represent a viable alternative when first-line therapy is contraindicated. Further research is required to define its role in the treatment of Legionella pneumonia.