Oral antibiotics used in the treatment of chronic rhinosinusitis have limited penetration into the sinonasal mucosa: a randomized trial

Abstract

1. 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.

2. 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.

3. Doxycycline concentrations measured in the mucus were significantly lower compared to that in the serum (mean mucus/serum ratio = 0.16, p < 0.001) and the tissue (mean mucus/tissue ratio = 0.18, p < 0.0001). Roxithromycin concentrations in the mucus were also significantly lower compared to that in the serum (mean mucus/serum ratio = 0.37, p = 0.002) and the tissue (mean mucus/tissue ratio = 0.60, p < 0.001).

4. 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.

Keywords:

• Sinusitis
• Bacteria
• Microbiota
• Antibiotics
• Antibiotic resistance
• Macrolides
• Tetracyclines

Acknowledgements

Laboratory and technical assistance were provided by the microbiology laboratory in Labtests Auckland, and the research and development team in Zenith Technology Corporation. This study was supported by a grant from the Garnett Passe and Rodney Williams Memorial Foundation.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported by a grant from the Garnett Passe and Rodney Williams Memorial Foundation.