Efficacy and Safety of Long-Term Low-Dose Clarithromycin in Patients With Refractory Chronic Sinusitis After Endoscopic Sinus Surgery: A Prospective Clinical Trial

Abstract

Objective: To observe the efficacy and safety of postoperative long-term low-dose oral administration of clarithromycin in patients with refractory chronic rhinosinusitis (RCRS), to explore the characteristics of postoperative microbiota in the nasal cavity in patients with RCRS, and to compare the differences and changes in microbiota in the nasal cavity before and after medication. Methods: This was a prospective, self-controlled study. Eighteen patients with RCRS who had persistent symptoms after endoscopic sinus surgery and standard therapy with normal immunoglobulin E and eosinophil level were included. Low dose (250 mg, once daily) clarithromycin was orally administrated for 12 weeks. Symptom severity and endoscopic findings were evaluated before, after 4 weeks, and 12 weeks of treatment, and nasal cavity microbiota was analyzed simultaneously. Results: A total of 18 patients with RCRS were enrolled and 17 patients completed the study. Four weeks after oral administration of clarithromycin, significant improvement was observed in subjective symptoms including nasal congestion, rhinorrhea, postnasal drip, and general discomfort, as well as endoscopic findings including general surgical cavity condition, rhinedema, and rhinorrhea ( P < .05). After continuous treatment to the 12th week, symptoms showed significant improvement compared with baseline, and endoscopic score showed significant improvement compared with both baseline and 4 weeks after treatment. Analysis of middle nasal meatus flora revealed a significant decrease of Streptococcus pneumoniae after 12 weeks of clarithromycin treatment ( P < .05), while the richness, composition, and diversity were similar before and after treatment. Patients enrolled experienced no adverse drug reaction or allergic reaction, nor clinical significant liver function impairment observed. Conclusion: Postoperative low-dose long-term oral administration of clarithromycin in patients with RCRS can improve the clinical symptoms and facilitate the mucosal epithelialization, with good tolerance and safety. The efficacy of clarithromycin in patients with RCRS may be related to its regulatory effect on nasal cavity microbiota.

The Impact of Antibiotics and Steroids on the Nasal Microbiome in Patients with Chronic Rhinosinusitis: A Systematic Review According to PICO Criteria

“…Eighteen patients with RCRS were treated with low-dose (250 mg, once daily) clarithromycin for 12 weeks after Endoscopic Sinus Surgery (ESS). As a result, the authors found a decrease in Streptococcus pneumoniae in the microbiota, concluding that postoperative low-dose long-term oral administration of clarithromycin in patients with RCRS has a low risk of causing nasal flora imbalance and can promote mucosal epithelialization and improve clinical symptoms [22]. Siu et al collected thirty subjects undergoing ESS for CRS and randomized them to one of three groups: doxycycline (100 mg daily for seven days); roxithromycin (300 mg daily for seven days), and control (no antibiotics).…”

“…Even regarding the therapeutic role of antibiotics in CRS, the conclusions of the collected papers differ. Chen et al, detecting a decrease in Streptococcus pneumoniae, stated that long-term oral administration at low doses of clarithromycin may have a regulatory effect on the nasal microbiota, allowing for mucosal epithelialization and improvement in clinical symptoms in patients with RCRS [22]. In contrast, Siu et al found no significant changes in community or bacterial load, thus highlighting the poor sinonasal penetration of the drug as well as the unproven efficacy and possible impact of dysbiosis in sinuses and off-target sites.…”

“…In such circumstances, it is unclear if the results reported were due specifically to the antibiotics or to changes in the nasal mucosa due to previous surgery. Furthermore, the duration of antibiotic therapy in the cited studies was very varied, ranging from 1-2 weeks in the studies of Alammar et al [26], Siu et al [23], Jain et al [29], and Hauser et al [25] to 12 weeks or more in the studies by Chen et al [22] and Renteria et al [27]. Another important limitation is the inability to differentiate the effects of antibiotics and/or INC from the nasal saline irrigations.…”

Correlation analysis of TGF-β1, MMP-9, TIMP-1, IL-1, IL-4, IL-6, IL-17, and TNF-α in refractory chronic rhinosinusitis: A retrospective study

“…1 The incidence of this disease has experienced an increased trend through time, approximately 4.8% to 9.7% in China and 6.9% to 27.1% in Europe. 2,3 Currently, the glucocorticoid combined with surgery is often used to treat chronic sinusitis. However, many patients still developed a variety of symptoms such as head and face tightness, heavy feeling, nasal congestion, and mucopurulent rhinitis after receiving treatment.…”