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.

摘要

1. 尽管针对慢性鼻-鼻窦炎（CRS）患者使用了广泛的抗生素处方，但药物在鼻窦粘膜中分布的程度仍然不确定。

2. 将接受CRS的功能性内窥镜鼻窦手术（FESS）的20名受试者随机分为两组：1）强力霉素（每天100 mg，连续7天）2）罗红霉素（每天300 mg，连续7天）。使用液相色谱-串联质谱法在稳态下测量鼻窦粘液，鼻窦组织和血清中的药物水平。

3. 与血清（平均黏液/血清比= 0.16，p  <0.001）和组织（平均黏液/组织比= 0.18，p  <0.0001）相比，在黏液中测出的强力霉素浓度显着降低。黏液中罗红霉素的浓度也显着低于血清（黏液/血清平均比= 0.37，p  = 0.002）和组织（黏液/组织平均比= 0.60，p  <0.001）。

4. 尽管仅根据报告的最低抑菌浓度不能单独预测强力霉素和罗红霉素在体内鼻窦粘液的疗效，但鉴于细菌生物膜抗微生物耐受性的增加，该结果表明，低黏膜渗透性的抗生素可能是造成细菌性鼻炎的因素之一。这些药物在治疗CRS中的疗效有限。