Azithromycin as host-directed therapy for pulmonary tuberculosis – a randomized pilot trial

Abstract

Background Adjunctive host-directed therapies are investigated that modulate host immune responses to reduce excessive inflammation and prevent tissue damage in tuberculosis (TB). 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 TB patients. Methods An open label, randomised controlled trial was performed. Adult patients with drug-susceptible, pulmonary TB aged above 18 years were randomly assigned to receive standard anti-TB care or azithromycin 250 mg orally once daily on top of standard care (SoC) for 28 days. Results Twenty-eight patients were included within 4 weeks after initiating anti-TB treatment. Twelve patients in both arms completed the trial. Participants were mostly young, male, had a smoking history and had no co-morbidities. No differences in baseline characteristics were observed between both arms. In blood, azithromycin treatment significantly reduced the TB marker interferon gamma-induced protein-10 (-38% vs -24% vs SoC, P<0.05) and the collagen type IV degradation product C4M (-26% vs -11%, P<0.05). In sputum, treatment with azithromycin significantly reduced neutrophils (-24% vs 0%, P<0.001), neutrophil elastase (-88% vs 75%, P<0.01), and transforming growth factor-β (-86% vs -68%, P<0.05). No significant effects were observed on other parameters. Treatment with azithromycin appeared to be safe. Conclusions The addition of azithromycin to standard anti-TB treatment appears to diminish excess neutrophilic inflammation in patients with pulmonary TB.