Oral Antibiotic Use in CRS Patients has Limited Drug Penetration into the Sinonasal Mucosa: A Randomized Trial
Authors List
Siu, J., Department of Surgery, The University of Auckland, Auckland, New Zealand
Mackenzie, B., Department of Surgery, The University of Auckland, Auckland, New Zealand
Klingler, L., Research and Development, Zenith Technology Corporation Limited, Dunedin, New Zealand
Biswas, K., Department of Surgery, The University of Auckland, Auckland, New Zealand
Hung, C., Research and Development, Zenith Technology Corporation Limited, Dunedin, New Zealand
Tingle, M., Department of Pharmacology and Clinical Pharmacology, The University of Auckland, Auckland, New Zealand
Douglas, R., Department of Surgery, The University of Auckland, Auckland, New Zealand
Introduction: Despite the widespread prescription of antibiotics for patients with chronic rhinosinusitis (CRS), the extent to which the drug penetrates the sinonasal mucosa remains largely undefined. The adverse effects of oral antibiotics on sites apart from the target site are also rarely reported.
Aims: To investigate the relationships between antibiotic distribution and microbiota in the sinuses and gastrointestinal tract.
Methods: Thirty subjects undergoing functional endoscopic sinus surgery (FESS) 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). Drug levels in sinonasal secretions, sinonasal tissues and serum at steady state were measured using liquid chromatography-tandem mass spectrometry. Sinonasal and stool samples collected before and after treatment were analysed using 16S rRNA gene-targeted amplicon sequencing and Droplet Digital™ PCR (ddPCR) for bacterial community composition and the quantification of bacterial DNA respectively.
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). Significant changes in bacterial community diversity and bacterial load were not observed for the three groups. The relative abundance of Staphylococcus ASV129 in sinus samples reduced with increasing mucus doxycycline concentrations (p=0.01). The alpha-diversity of sinus samples reduced with increasing serum roxithromycin concentrations (p<0.05). A short course of antibiotic intake was associated with slightly higher gastrointestinal symptom (GSRS) scores in the roxithromycin group (p=0.04).
Conclusions: These results suggest that sinonasal mucosal penetration of antibiotics may be one of the factors contributing to the limited efficacy of these agents in the treatment of CRS.
Siu, J., Department of Surgery, The University of Auckland, Auckland, New Zealand
Mackenzie, B., Department of Surgery, The University of Auckland, Auckland, New Zealand
Klingler, L., Research and Development, Zenith Technology Corporation Limited, Dunedin, New Zealand
Biswas, K., Department of Surgery, The University of Auckland, Auckland, New Zealand
Hung, C., Research and Development, Zenith Technology Corporation Limited, Dunedin, New Zealand
Tingle, M., Department of Pharmacology and Clinical Pharmacology, The University of Auckland, Auckland, New Zealand
Douglas, R., Department of Surgery, The University of Auckland, Auckland, New Zealand
Introduction: Despite the widespread prescription of antibiotics for patients with chronic rhinosinusitis (CRS), the extent to which the drug penetrates the sinonasal mucosa remains largely undefined. The adverse effects of oral antibiotics on sites apart from the target site are also rarely reported.
Aims: To investigate the relationships between antibiotic distribution and microbiota in the sinuses and gastrointestinal tract.
Methods: Thirty subjects undergoing functional endoscopic sinus surgery (FESS) 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). Drug levels in sinonasal secretions, sinonasal tissues and serum at steady state were measured using liquid chromatography-tandem mass spectrometry. Sinonasal and stool samples collected before and after treatment were analysed using 16S rRNA gene-targeted amplicon sequencing and Droplet Digital™ PCR (ddPCR) for bacterial community composition and the quantification of bacterial DNA respectively.
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). Significant changes in bacterial community diversity and bacterial load were not observed for the three groups. The relative abundance of Staphylococcus ASV129 in sinus samples reduced with increasing mucus doxycycline concentrations (p=0.01). The alpha-diversity of sinus samples reduced with increasing serum roxithromycin concentrations (p<0.05). A short course of antibiotic intake was associated with slightly higher gastrointestinal symptom (GSRS) scores in the roxithromycin group (p=0.04).
Conclusions: These results suggest that sinonasal mucosal penetration of antibiotics may be one of the factors contributing to the limited efficacy of these agents in the treatment of CRS.
