Azithromycin as Host-Directed Therapy for Pulmonary Tuberculosis: A Randomized Pilot Trial

Abstract

Background. Adjunctive host-directed therapies that modulate host immune responses to reduce excessive inflammation and prevent tissue damage in tuberculosis are being investigated. Macrolides, including azithromycin, were shown to possess anti-inflammatory and immune-modulatory effects in addition to their antibacterial effects. In the current trial, we investigated whether azithromycin enhances resolution of systemic and pulmonary inflammation and decreases extracellular matrix-related tissue turnover in tuberculosis patients. Methods. An open-label, randomized, controlled trial was performed. Adult patients with drug-susceptible, pulmonary tuberculosis aged above 18 years were randomly assigned to receive standard antituberculosis care or azithromycin 250â mg orally once daily in addition to standard care (SOC) for 28 days. Results. Twenty-eight patients were included within 4 weeks after initiating antituberculosis treatment. Twelve patients in both arms completed the trial. Participants were mostly young, male, had a history of smoking, and had no comorbidities. No differences in baseline characteristics were observed between the study arms. In blood, azithromycin treatment significantly enhanced the reduction of the tuberculosis marker interferon-γ-induced protein-10 (SOC plus azithromycin,-38% vs SOC alone,-24% vs SOC, P