Oral antibiotics used in the treatment of chronic rhinosinusitis have limited penetration into the sinonasal mucosa: a randomized trial
Creators: name: Siu, Joey
name: Klingler, Lilian
name: Wang, Yi
name: Hung, Cheung-Tak
name: Jeong, Soo Hee
name: Smith, Susan
name: Tingle, Malcolm Drummond
name: Mackenzie, Brett Wagner
name: Biswas, Kristi
name: Douglas, Richard George
Publisher: name: Taylor & Francis
Year: 2020
Subjects: subject: Biochemistry
subject: Space Science
subject: Medicine
subject: Microbiology
subject: FOS: Biological sciences
subject: Cell Biology
subject: Physiology
subject: Pharmacology
subject: Biotechnology
subject: Chemical Sciences not elsewhere classified
subject: Virology

description: Despite the widespread prescription of antibiotics for patients with chronic rhinosinusitis (CRS), the extent to which drug distribution to the sinonasal mucosa occurs remains largely undefined.Twenty subjects undergoing functional endoscopic sinus surgery (FESS) for CRS were randomized to one of two groups: 1) doxycycline (100 mg daily for seven days) 2) roxithromycin (300 mg daily for seven days). Drug levels were measured using liquid chromatography-tandem mass spectrometry in sinonasal mucus, sinonasal tissues and serum at steady state.Doxycycline concentrations measured in the mucus were significantly lower compared to that in the serum (mean mucus/serum ratio = 0.16, <i>p</i> &lt; 0.001) and the tissue (mean mucus/tissue ratio = 0.18, <i>p</i> &lt; 0.0001). Roxithromycin concentrations in the mucus were also significantly lower compared to that in the serum (mean mucus/serum ratio = 0.37, <i>p</i> = 0.002) and the tissue (mean mucus/tissue ratio = 0.60, <i>p</i> &lt; 0.001).Although the efficacy of doxycycline and roxithromycin in sinonasal mucus in vivo cannot be predicted solely from reported minimum inhibitory concentrations, given the added complexity 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. Despite the widespread prescription of antibiotics for patients with chronic rhinosinusitis (CRS), the extent to which drug distribution to the sinonasal mucosa occurs remains largely undefined. Twenty subjects undergoing functional endoscopic sinus surgery (FESS) for CRS were randomized to one of two groups: 1) doxycycline (100 mg daily for seven days) 2) roxithromycin (300 mg daily for seven days). Drug levels were measured using liquid chromatography-tandem mass spectrometry in sinonasal mucus, sinonasal tissues and serum at steady state. Doxycycline concentrations measured in the mucus were significantly lower compared to that in the serum (mean mucus/serum ratio = 0.16, <i>p</i> &lt; 0.001) and the tissue (mean mucus/tissue ratio = 0.18, <i>p</i> &lt; 0.0001). Roxithromycin concentrations in the mucus were also significantly lower compared to that in the serum (mean mucus/serum ratio = 0.37, <i>p</i> = 0.002) and the tissue (mean mucus/tissue ratio = 0.60, <i>p</i> &lt; 0.001). Although the efficacy of doxycycline and roxithromycin in sinonasal mucus in vivo cannot be predicted solely from reported minimum inhibitory concentrations, given the added complexity 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.