zithromax and Rhinitis

In 1984, the effectiveness of low-dose, long-term erythromycin treatment (macrolide therapy) for diffuse panbronchiolitis (DPB) was first reported in Japan. The 5-year survival rate for DPB improved from 62.9 to 91.4% after implementation of macrolide therapy. The usefulness of this treatment has since been demonstrated in patients with other chronic airway diseases, such as chronic bronchitis, cystic fibrosis, bronchiectasis, bronchial asthma, and chronic rhinosinusitis (CRS). The new 14-membered macrolides clarithromycin and roxithromycin and the 15-membered macrolide azithromycin are also effective for treating these inflammatory diseases. The mechanism of action of the 14- and 15-membered macrolides may involve anti-inflammatory rather than anti-bacterial activities. Macrolide therapy is now widely used for the treatment of CRS in Japan; it is particularly effective for treating neutrophil-associated CRS and is useful for suppressing mucus hypersecretion. However, macrolide therapy is not effective for eosinophil-predominant CRS, which is characterized by serum and tissue eosinophilia, high serum IgE levels, multiple polyposis, and bronchial asthma. Recent reports have described the clinical efficacy of macrolides in treating other inflammatory diseases and new biological activities (e.g., anti-viral). New macrolide derivatives exhibiting anti-inflammatory but not anti-bacterial activity thus have therapeutic potential as immunomodulatory drugs. The history, current state, and future perspectives of macrolide therapy for treating CRS in Japan will be discussed in this review.

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiolitis; Chronic Disease; Clarithromycin; Erythromycin; Haemophilus Infections; History, 20th Century; History, 21st Century; Humans; Japan; Macrolides; Nasal Polyps; Rhinitis; Sinusitis

Macrolides have shown beneficial effects in the treatment of chronic rhinosinusitis (CRS). This study aimed to compare the effect of azithromycin and clarithromycin in combination with conventional therapies for the treatment of CRS.. This single-blind randomized controlled trial was conducted during 2018-2019 at the Otorhinolaryngology Clinic of Shahid Mohammadi Hospital, Bandar Abbas, Iran. Out of 102 selected patients, 90 were included in the analysis. Patients were selected through convenience sampling and randomly assigned to two equal groups. In addition to conventional therapies (nasal irrigation, betamethasone injection, oxymetazoline and fluticasone spray, guaifenesin syrup, and steam inhalation), the patients in the clarithromycin group received clarithromycin 500 mg tablets twice daily for four weeks. The other group received azithromycin 500 mg tablets daily for four weeks. Patients' symptoms were evaluated pre- and post-intervention, and the Lund-Mackay (LM) scoring system was used for the staging of CRS based on computed tomography scan findings. Data were analyzed using SPSS software, and P<0.05 was considered statistically significant.. Patients in both groups were comparable in terms of age and sex. Complete resolution of symptoms was significantly higher in the azithromycin group than the clarithromycin group (71.1% vs. 24.4%, P<0.001). Baseline LM scores did not differ significantly between the groups (P=0.120). However, post-intervention, LM scores reduced considerably in both groups, but the change was significantly higher in the azithromycin group (P<0.001).. In combination with conventional therapies for CRS in adults, a four-week course of treatment with azithromycin is more effective than clarithromycin.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Chronic Disease; Clarithromycin; Humans; Macrolides; Rhinitis; Single-Blind Method; Sinusitis; Treatment Outcome

The sinonasal microbiome is believed to play an important role in the pathophysiology of refractory chronic rhinosinusitis (CRS). We evaluated changes in the microbiome following a 4-month course of low-dose azithromycin. Assessing microbiome alterations following such a treatment may help identify underlying mechanisms of this drug.. A total of 48 adults with refractory CRS were enrolled in a double-blind, randomized, placebo-controlled trial. Patients were randomized to 250 mg of azithromycin or placebo 3 times weekly for 4 months. During this time, daily budesonide saline irrigations were continued. Sinonasal swabs were collected by endoscopically-assisted method prior to treatment initiation and at the end of it, and sent for 16S ribosomal RNA gene sequencing. High-resolution ANCHOR pipeline was used to infer and annotate putative species. The 2 patient groups were compared using DESeq2 differential abundance analysis.. From initiation to the end of azithromycin treatment, patients showed a significant difference in beta diversity analysis (p = 0.0004) along with a significant decrease in 71 different operational taxonomic units (OTUs) of Staphylococcus aureus (false discovery rate [FDR] < 0.05) obtained from the differential abundance analysis. This was not observed in placebo-treated patients. By the end of treatments, azithromycin-treated patients had a significant decrease in 29 different OTUs of S. aureus (FDR < 0.05) when compared to placebo.. A 4-month course of 250 mg of azithromycin 3 times weekly in patients with refractory CRS significantly decreases S. aureus abundance in the sinonasal microbiome. Considering the pathogenic role of S. aureus in the refractory CRS population, azithromycin may constitute an additional therapeutic option to help control this disease.

Topics: Adult; Azithromycin; Chronic Disease; Humans; Microbiota; Rhinitis; Sinusitis; Staphylococcus aureus

Refractory chronic rhinosinusitis (CRS) remains a significant burden for patients, often leaving them with few therapeutic options that provide low-morbidity, long-term, and meaningful symptomatologic and endoscopic disease improvement. Macrolides have long been thought to offer both an immunomodulatory and antimicrobial effect. Our objective was to evaluate the efficacy of low-dose, long-term azithromycin in a carefully selected high-risk population failing appropriate medical therapy of budesonide nasal irrigations (BNIs) and endoscopic sinus surgery (ESS).. A double-blind, randomized, placebo-controlled trial was completed in a single tertiary-care center assessing the addition of 250 mg azithromycin, 3 times per week for 16 weeks, in adults failing ESS and high-volume BNIs. Associated comorbidities, as well as symptomatologic, microbiologic, and serologic values, were systematically collected.. A total of 128 patients were enrolled and underwent ESS followed by BNI. At the 4-month post-ESS visit, 48 patients showed disease persistence and were randomized to azithromycin or placebo. Overall, azithromycin, when compared with placebo, did not show a statistically significant difference in disease clearance (54% vs 33%, respectively; p = 0.146), although patients with disease clearance who were on azithromycin showed significantly better 22-item Sino-Nasal Outcome Test score improvements than patients on placebo (18 vs -0.9, respectively; p = 0.046). In a subgroup analysis excluding aspirin-exacerbated respiratory disease (AERD) patients, azithromycin significantly improved disease clearance when compared with placebo (71% vs 35%, respectively; p = 0.031), with a number needed to treat of 3 (2.8).. Low-dose azithromycin is a therapeutic option with few side effects. Its use can show favorable clinical outcomes in this difficult-to-treat population, especially if patients are AERD-negative.

Topics: Adrenal Cortex Hormones; Adult; Anti-Bacterial Agents; Azithromycin; Chronic Disease; Double-Blind Method; Endoscopy; Humans; Rhinitis; Sinusitis; Treatment Outcome

Chronic eosinophilic rhinosinusitis with nasal polyps (CRSwNP eosinophilic) is characterised by the formation of benign and bilateral nasal polyps. We aimed to compare the effectiveness of azithromycin as an immunomodulator with the use of a placebo in patients presenting with CRSwNP concomitant with asthma and aspirin intolerance after 3 months of treatment and at a 1-year follow-up.. We performed a randomised, double-blind, placebo-controlled trial. Patients received 500 mg azithromycin orally three times/week for 12 weeks. Improvement was evaluated by staging, the Sino-Nasal Outcome Test (SNOT-22), and nasal polyp biopsy. Data collected at pretreatment and 3 months posttreatment were compared. Quality of life was evaluated at the 1-year follow-up.. Twenty-seven and 21 patients were treated with azithromycin and a placebo, respectively. The medication was well tolerated overall. Twenty patients (74%) in the azithromycin group and three patients (14%) in the placebo group were not refer- red for surgery at the end of the 3-month treatment. Regarding subjective improvement, there was a median decrease only in the azithromycin group, and the between-group difference was significant. SNOT-22 improvement was maintained in the azithromy- cin group at the 1-year follow-up.. Azithromycin could be considered a therapeutic option for patients presenting with CRSwNP concomitant with asthma and aspirin intolerance.

Topics: Azithromycin; Chronic Disease; Humans; Nasal Polyps; Quality of Life; Rhinitis; Treatment Outcome

In persistent chronic rhinosinusitis (CRS), conventional treatment is often insufficient. Long-term, low-dose administration of macrolides has been suggested as a treatment option. The MACS (Macrolides in chronic rhinosinusitis) study is a randomized placebo-controlled trial evaluating the efficacy of azithromycin (AZM) in CRS.. We describe a group of patients with recalcitrant CRS with and without nasal polyps unresponsive to optimal medical and (in 92% also) surgical treatment. Patients were treated with AZM or placebo. AZM was given for 3 days at 500 mg during the first week, followed by 500 mg per week for the next 11 weeks. Patients were monitored until 3 months post-therapy. The assessments included Sino-Nasal Outcome Test-22 (SNOT-22), a Patient Response Rating Scale, Visual Analogue Scale (VAS), Short Form-36 (SF-36), rigid nasal endoscopy, peak nasal inspiratory flow (PNIF), Sniffin' Sticks smell tests and endoscopically guided middle meatus cultures.. Sixty patients with a median age of 49 years were included. Fifty per cent had asthma and 58% had undergone revision sinus surgery. In the SNOT-22, Patient Response Rating Scale, VAS scores and SF-36, no significant difference between the AZM and the placebo groups was demonstrated. Nasal endoscopic findings, PNIF results, smell tests and microbiology showed no relevant significant differences between the groups either.. At the investigated dose of AZM over 3 months, no significant benefit was found over placebo. Possible reasons could be disease severity in the investigated group, under-dosage of AZM and under-powering of the study. Therefore, more research is urgently required.

Topics: Adult; Aged; Anti-Bacterial Agents; Azithromycin; Chronic Disease; Double-Blind Method; Drug Administration Schedule; Endoscopy; Female; Humans; Macrolides; Male; Middle Aged; Rhinitis; Sinusitis; Time Factors; Treatment Outcome; Young Adult

In this double-blind, parallel-group, multicenter study, 169 patients with symptoms of maxillary sinusitis but without radiographically confirmed empyema (pus) were randomly assigned to receive either 500 mg azithromycin once daily for 3 days (87 patients) or placebo daily for 3 days (82 patients). Nasal secretion, maxillary tenderness and pain, nasal obstruction, general malaise, and hyposmia were assessed at the start of the study and on days 4, 11, and 25 of treatment. After 11 days 58% of the patients in the azithromycin group were cured versus 31% in the placebo group; after 25 days the cure rate was 79% versus 67%, respectively. When both cure and improvement were considered, the corresponding figures after day 25 were 90% and 88%, respectively. Adverse events, predominantly gastrointestinal, occurred in 24 (27%) of the azithromycin-treated patients and in 15 (18%) of those treated with placebo, but the difference was not statistically significant. There was a difference in efficacy in favor of azithromycin in the treatment of rhinitis with symptoms of maxillary sinusitis but without radiological signs of empyema (pus). Antibiotics should only be used to alleviate symptoms in patients with moderate to severe symptoms, as the results after 25 days for both improvement and cure are equal. In the treatment of acute rhinitis with symptoms and signs of maxillary sinusitis but without empyema, treatment with azithromycin seems to result in a better cure rate after 10-12 days when compared with placebo.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Azithromycin; Double-Blind Method; Female; Humans; Male; Maxillary Sinusitis; Middle Aged; Rhinitis; Treatment Outcome

Previous in vitro transcriptomic profiling suggests azithromycin exerts its effects in patients with chronic rhinosinusitis (CRS) via modulation of type 1 inflammation and restoration of epithelial barrier function. We wished to verify these postulated effects using in vitro models of epithelial repair and in vivo transcriptional profiling.. Functional effects of azithromycin in CRS were verified using in vitro models of wounding. The mechanism of the effect of azithromycin was assessed in vivo using transcriptomic profiling.. Academic medical center.. Effects of azithromycin on the speed of epithelial repair were verified in a wounding model using primary nasal epithelial cells (pNEC) from CRS patients. Nasal brushings collected pre-and posttreatment during a placebo-controlled trial of azithromycin for CRS patients unresponsive to surgery underwent transcriptomic profiling to identify implicated pathways.. Administration of azithromycin improved the wound healing rates in CRS pNECs and prevented the negative effect of Staphylococcus aureus on epithelial repair. In vivo, response to azithromycin was associated with downregulation in pathways of type 1 inflammation, and upregulation of pathways implicated in the restoration of the cell cycle.. Restoration of healthy epithelial function may represent a major mode of action of azithromycin in CRS. In vitro models show enhanced epithelial repair, while in vivo transcriptomics shows downregulation of pathways type 1 inflammation accompanied by upregulation of DNA repair and cell-cycle pathways. The maximal effect in patients with high levels of type 1-enhanced inflammation suggests that azithromycin may represent a novel therapeutic option for surgery-unresponsive CRS patients.

Topics: Azithromycin; Chronic Disease; Humans; Inflammation; Nasal Mucosa; Nasal Polyps; Rhinitis; Sinusitis

Topics: Anti-Inflammatory Agents; Azithromycin; Betacoronavirus; Cells, Cultured; Chronic Disease; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Down-Regulation; Host-Pathogen Interactions; Humans; Interleukin-1beta; Male; Membrane Proteins; Nasal Mucosa; Pandemics; Pilot Projects; Pneumonia, Viral; Rhinitis; SARS-CoV-2; Serine Endopeptidases; Serine Proteases; Signal Transduction; Sinusitis

Seven-week-old 32-week premature triplets were hospitalized because of rhinorrhea, cough with color change and posttussive emesis. One infant had a positive direct fluorescent antibody test for Bordetella pertussis, so all were treated with 5 days of azithromycin. Two of the infants were subsequently diagnosed with hypertrophic pyloric stenosis and underwent surgical pyloromyotomies 6 and 7 weeks, respectively, after the initial admission.

Topics: Anti-Bacterial Agents; Azithromycin; Bordetella pertussis; Cough; Cyanosis; Female; Humans; Infant, Newborn; Infant, Premature, Diseases; Pyloric Stenosis, Hypertrophic; Rhinitis; Triplets; Vomiting; Whooping Cough

A previous study found that a single 2-g dose of azithromycin extended release (AZ-ER) was as efficacious as 10 days of levofloxacin (LFX) 500 mg QD in adults with acute bacterial rhinosinusitis (ABRS). The speed with which patients experience resolution of ABRS symptoms has not been reported.. The purpose of this study was to evaluate the resolution of ABRS symptoms after a single 2-g dose of AZ-ER compared with 10 days of LFX.. This was a retrospective analysis of data from a published international, randomized, double-blind, double-dummy clinical trial conducted between January 21, 2003, and February 20, 2004, that included 534 adult (age >or=18 years) outpatients with ABRS. All patients entering the study were required to have purulent nasal discharge, purulent drainage in the posterior pharynx, or purulent discharge from the maxillary sinus orifice and at least 1 of 3 other protocol-defined cardinal symptoms of ABRS (sinus pain, pressure, or tenderness) for >or=7 days. In addition, they were required to have at least 2 of the following 6 noncardinal symptoms at baseline: cough, fever, headache, nasal congestion, postnasal discharge, and leukocytosis. All patients who received medication were assessed for the occurrence of adverse events at study visits during and after therapy. At the ontreatment visit (between days 3 and 5), baseline symptoms were reassessed as resolved, improved, same, new, or worse. Resolution of symptoms was calculated as the proportion of patients with 3 or 4 cardinal symptoms either resolved (if present at baseline) or not new (if absent at baseline). Concomitant medications other than antibiotics were allowed as needed for symptomatic treatment.. Demographic characteristics were similar at baseline between the AZ-ER and LFX treatment arms (mean age, 38.4 and 39.5 years, respectively), although more women were randomized to receive LFX (62.9%) than AZ-ER (53.3%) (P = 0.025). More than 90% of patients in both arms had >or=3 ABRS symptoms at baseline. At the on-treatment visit, resolution of >or=3 ABRS symptoms was achieved in 88 of 270 AZ-ER patients (32.6%) and 61 of 261 LFX patients (23.4%) (P = 0.018). Resolution of individual symptoms in the AZ-ER and LFX groups at 3 to 5 days was as follows: sinus pain (92/253[36.4%] and 77/251 [30.7%]; P = NS), sinus pressure (97/243 [39.9%] and 68/244 [27.9%]; P = 0.005), sinus tenderness (83/218 [38.1%] and 73/214 [34.1%]; P = NS), and nasal discharge (57/270 [21.0%] and 49/264 [18.6%]; P = NS). Treatment-related adverse events were reported by 63 of 270 AZ-ER patients (23.3%) and 41 of 268 LFX patients (15.3%). Gastrointestinal disturbances were the most common adverse events, including nausea (4.4% and 3.4%) and abdominal pain (2.6% and 0.4%).

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; Delayed-Action Preparations; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Levofloxacin; Male; Middle Aged; Ofloxacin; Randomized Controlled Trials as Topic; Retrospective Studies; Rhinitis; Sinusitis; Treatment Outcome

Acute bacterial rhinosinusitis, which is a major health problem, is treated with antibiotics. We developed a mouse model of acute bacterial rhinosinusitis to gain a better understanding of the pathophysiology of the disease. Our goal was to investigate the response to acute rhinosinusitis when treated with either a bactericidal or a bacteriostatic antibiotic.. C57BL/6 mice were infected intranasally with Streptococcus pneumoniae. One day after inoculation, the mice were treated with either moxifloxacin (bactericidal) or azithromycin (bacteriostatic). Different groups were euthanized during the first five days post-inoculation. Bacterial counts from nasal lavage culture and the cell markers GR1, CD11b, CD3, CD4, and CD8 in sinus tissue were evaluated by flow cytometry.. Azithromycin led to rapid clearance of the bacteria and of the inflammation in contrast to placebo. Surprisingly, moxifloxacin showed a limited effect. Investigations of this limited effect of moxifloxacin suggested a high metabolic clearance, a low concentration at the site of infection, and low persistent post-antibiotic effects of moxifloxacin in mice.. Our animal model of acute sinusitis has great utility for studying the disease, but the difference between mice and man must always be considered in making extrapolations from animal experiments to the human experience.

Topics: Acute Disease; Animals; Anti-Bacterial Agents; Aza Compounds; Azithromycin; CD11b Antigen; CD4 Antigens; CD8 Antigens; Disease Models, Animal; Female; Fluoroquinolones; Male; Mice; Mice, Inbred C57BL; Moxifloxacin; Pneumococcal Infections; Quinolines; Rhinitis; Sinusitis; Streptococcus pneumoniae

Topics: Acute Disease; Azithromycin; Bacterial Infections; Chemistry, Pharmaceutical; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Maxillary Sinusitis; Microspheres; Ofloxacin; Randomized Controlled Trials as Topic; Rhinitis; Risk Assessment; Severity of Illness Index; Treatment Outcome

Traditional approaches to antimicrobial management of acute bacterial rhinosinusitis (ABRS) focus on courses of therapy of at least 10 days duration. The rationale for this length of therapy originated from studies in tonsillopharyngitis. Short-course antibiotic therapy for ABRS with 3-5 days of azithromycin has proved equally effective. Potential added benefits of short-course therapy include improved compliance, fewer adverse events as well as reduced risk of treatment failure, bacterial resistance and cost. Single-dose therapy is now possible with a novel microsphere formulation of azithromycin, which permits administration of a higher 2.0 g oral dose. This has proved as effective and well tolerated as 10 days levofioxacin 500 mg/day in patients with uncomplicated ABRS. High single-dose therapy has the potential to maximize adherence to prescribed therapy and thus to help in the battle to control rising antibiotic resistance among respiratory pathogens.

Topics: Acute Disease; Adult; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Microspheres; Middle Aged; Ofloxacin; Rhinitis; Sinusitis; Time Factors; Treatment Outcome

Azithromycin activity in vivo has been studied in a group of children with acute respiratory tract infections in order to test the efficacy and tolerability of this antibiotic. The study involved 135 children treated with a single daily 10 mg/kg dose of azithromycin for three consecutive days. Ten days after this treatment 100% of children with otitis media, tracheobronchitis, or rhinosinusitis and 95.9% of children with pharyngo-tonsillitis were cured. Recurrences were never observed. Azithromycin proved remarkably effective for treatment of acute respiratory infections and otitis media in children. Tolerability and therapeutic compliance were excellent.

Topics: Acute Disease; Azithromycin; Bacteria; Bronchitis; Child; Child, Preschool; Evaluation Studies as Topic; Female; Humans; Infant; Male; Otitis Media; Pharyngitis; Respiratory Tract Infections; Rhinitis; Sinusitis; Tonsillitis; Tracheitis