A pilot randomised controlled trial of oral doxycycline after endoscopic sinus surgery and its effects on the sinonasal microbiome

Background: Oral antibiotics are commonly prescribed after endoscopic sinus surgery (ESS) despite minimal clinical data supporting this practice. We aim to assess the effect of post-ESS doxycycline on clinical outcomes and on the diversity and composition of the sinonasal microbiome. Methods: Samples from the middle meatus were collected from twelve patients undergoing ESS to treat chronic rhinosinusitis. Patients were double-blind randomised to receive either oral doxycycline or placebo in the post-operative period. Further samples were collected at two weeks and three months post-operatively. The sinonasal microbiome was characterized using 16S ribosomal RNA (rRNA) gene amplicon sequencing. SNOT-22 scores, Lund Mackay scores, and Modified Lund Mackay Endoscopic Scores (MLMES) were collected. Results: After ESS, bacterial diversity increased while SNOT-22 score decreased for both treatments. Microbiome composition diverged between treatments, and random forest analysis identified nine taxa that may distinguish treatment groups. There was no significant difference in SNOT-22 score, 3-month MLMES or bacterial diversity between the placebo and doxycycline groups. The trends for all of these measures favour placebo. Conclusion: In this pilot study, we detected no significant difference between placebo and antibiotic treatments in clinical outcome. As patient symptoms improved after ESS, we detected a concurrent increase in the diversity of the sinonasal microbiome. Our data highlight the need for and facilitate the design of future larger studies to explore the relationship between prophylactic antibiotics and post-ESS recovery.