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Antibiotic concentrations in the sinonasal secretions and tissue in CRS patients after oral therapy: a randomized trial

By Joey Siu, Lilian Klingler, Yi Wang, Cheung-Tak Hung, Soo Hee Jeong, Susan Smith, Malcolm Tingle, Brett Wagner Mackenzie, Kristi Biswas, Richard Douglas

Posted 18 Jun 2020
bioRxiv DOI: 10.1101/2020.06.17.158535

Background: Despite the widespread prescription of antibiotics for patients with chronic rhinosinusitis (CRS), the extent to which drug distribution to the sinonasal mucosa influences their efficacy remains largely undefined. Methods: Thirty subjects undergoing functional endoscopic sinus surgery (FESS) for bilateral 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). Drug levels were measured using liquid chromatography-tandem mass spectrometry in sinonasal secretions, sinonasal tissues and serum at steady state. Nasal endoscopy (Modified Lund-Kennedy) and Gastrointestinal Symptom Rating Scale (GSRS) scores were recorded. Results: Antibiotic concentrations in the nasal secretions were significantly lower compared to those in the serum and tissue (mean mucus/serum ratio at steady state = 0.16 and 0.37 for doxycycline and roxithromycin respectively; p<0.01). A short course of antibiotic intake did not correlate with any difference in clinical outcomes except where slightly higher GSRS scores were reported in the roxithromycin group (p=0.04). Conclusions: Although the efficacy of doxycycline and roxithromycin in sinonasal mucus in vivo cannot be predicted solely from reported minimum inhibitory concentrations, given the added complication of bacterial biofilm antimicrobial tolerance, these results suggest that low mucosal penetration of antibiotics may be one of the factors contributing to the limited efficacy of these agents in the treatment of CRS.

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