Sinonasal and gastrointestinal bacterial composition and abundance are stable after one week of oral antibiotic treatment for CRS: a randomised trial

Background: Despite their limited efficacy, antibiotics are widely prescribed for the treatment of chronic rhinosinusitis (CRS) and appear to have limited penetration into the sinonasal mucosa in an initial report by this group. Their adverse effects on non-target sites are also rarely reported. We aimed to investigate the short-term effects of antibiotics on the sinus and gut microbiota as well as any relationships these had with drug distribution.Methods: Thirty subjects undergoing functional endoscopic sinus surgery for CRS were randomized to one of three groups: 1) doxycycline (100 mg daily for seven days) 2) roxithromycin (300 mg daily for seven days) and 3) control (no antibiotics given). Sinonasal and stool samples collected before and after treatment were analyzed using 16S rRNA gene-targeted amplicon sequencing and Droplet Digital PCR for bacterial community composition and the quantification of bacterial DNA respectively. Sinonasal mucus, tissue and serum drug concentration published in our initial published report were analyzed in relation to microbiological data and clinical outcome scores.Results: Significant bacterial community shifts or changes in bacterial diversity and load were not observed for the three patient groups. The relative abundance of Staphylococcus ASV129 in sinus samples reduced with increasing mucus doxycycline levels (p= 0.01). For the roxithromycin group, sinonasal bacterial diversity was negatively correlated with serum drug levels and reduced overall compared to controls (p< 0.05.)Conclusions: The limited sinonasal mucosal penetration of oral antibiotics may be one of the factors contributing to the poor efficacy of these agents in the treatment of CRS.