These rates of ototoxicity exceed the previously believed risks of azithromycin-induced hearing loss, which was limited to about 25 case reports, almost all of which reported reversible hearing loss. Azithromycin is weakly pro-arrhythmogenic causes abnormal heart rhythms. Azithromycin can prolong the QTc interval and in rare cases, induce the life-threatening heart arrhythmia known as torsades de pointes.
A large retrospective study we reviewed here, by Ray NEJM suggested the chance of sudden cardiac death after an outpatient prescription for a short course of azithromycin was about 1 in 12, by comparison, 1 in 30, controls--people taking other antibiotics, or no antibiotics--had sudden cardiac death during equivalent time periods. However, most of the risk was concentrated in patients with heart disease: these patients had a risk for sudden cardiac death of 1 in 4, after a single outpatient azithromycin course.
Excluding these patients, the risk was much lower, likely about 1 in 50, or 1 in , these are broad estimates. Notably, these calculated event rates were after single short antibiotic courses. The cardiovascular risks of taking daily azithromycin are not known.
As would be expected, daily azithromycin promotes the emergence of bacteria resistant to azithromycin. What this might mean clinically or epidemiologically is unknown. As an example from another study , a single course of azithromycin in COPD patients resulted in more than half of the S. Clinical Takeaway: The NEJM brand name and the reputations of these accomplished authors attached to this opinion piece will go far toward making azithromycin an accepted therapy for preventing COPD exacerbations.
Whether the exacerbations prevented will outweigh the expected downsides cardiovascular deaths, hearing loss, and antibiotic resistance , I guess we'll find out later.
They responsibly propose stringent limitations on who should receive azithromycin to prevent COPD exacerbations, such as:. Citing the observed pharmacokinetics of azithromycin , authors believe that daily azithromycin will result in unnecessarily high lung tissue levels, and that azithromycin mg three times weekly e. They suggest this may reduce the risk of adverse events, acknowledging this is not based on any outcomes data.
Needless to say, a patient with hearing loss or QTc prolongation should prompt further evaluation and likely, drug discontinuation. Wenzel RP et al. NEJM ; Get our weekly email update , and explore our library of practice updates and review articles. PulmCCM is an independent publication not affiliated with or endorsed by any organization, society or journal referenced on the website. Terms of Use Privacy Policy. Although exacerbations have a considerable clinical impact, some patients could be safely treated at home.
Roche et al developed a scoring system, based on variables at admission to hospital for COPD exacerbation age, exacerbation severity, and dyspnea , that may be useful for predicting risk of death and requirement for post-hospital support. There is evidence that COPD exacerbations cluster together, and a high-risk period for recurrence has been identified in the first 8 weeks following an initial event.
Risk factors for COPD are also risk factors for the frequency and severity of exacerbations, and as such, are potential targets for intervention. These include smoking cessation, prevention of respiratory infections, and avoiding a rapid decline in lung function. Reprinted with permission from Massachusetts Medical Society. In addition to bronchodilators, other classes of drugs have been shown to reduce exacerbation risk in specific subsets of patients with COPD.
A randomized trial of the macrolide azithromycin, taken daily for 1 year in addition to usual therapy, demonstrated a significant reduction in the risk of exacerbations in patients with COPD at increased risk of exacerbation.
There is evidence that pneumococcal and annual influenza vaccinations reduce the risk of exacerbation and hospitalization in patients with COPD, and it is recommended that these are offered to patients with COPD.
Comorbidities of COPD, such as cardiovascular disease, gastroesophageal reflux disease, depression, and osteoporosis, are associated with increased susceptibility to exacerbations and can also contribute to how COPD develops. Preventative strategies should therefore consider these comorbid conditions. Although there is sparse evidence from randomized trials demonstrating that treating comorbidities improves COPD, several treatment approaches have shown a benefit in observational studies.
Statin therapy may help to improve outcomes in patients with COPD and peripheral arterial disease 66 and other cardiovascular comorbidities. For example, in a pooled analysis of long-term studies in COPD, the oral anti-inflammatory agent roflumilast has not been associated with major cardiovascular events in long-term studies. A better understanding of the mechanisms triggering exacerbations will help to determine the optimal use of preventative strategies in future.
Exacerbations of COPD have a substantial impact on health status and cumulative effects on lung function. Many exacerbations are unreported, which not only underestimates their incidence, but may also lead to under-treatment and poorer recovery.
Distinct COPD exacerbation subtypes have been proposed, which may differ in prognosis and response to treatment. The management of COPD should involve phenotype-directed strategies, and efforts have been made to identify biomarkers that could help guide treatment. In addition, efforts to prevent exacerbations should aim to reduce risk factors and manage comorbid conditions.
Understanding the mechanisms by which COPD exacerbations occur may determine the best course of preventative strategy and lead to development of novel interventions.
All fees were contracted via his institution. National Center for Biotechnology Information , U. Published online Feb Author information Copyright and License information Disclaimer. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
This article has been cited by other articles in PMC. Keywords: COPD, exacerbation, phenotype, biomarker, bronchodilator. What are exacerbations? How do we define exacerbations? Exacerbation phenotypes There is heterogeneity in COPD clinical manifestations, outcomes, and responses to treatment. Open in a separate window. Figure 1. How do we assess exacerbations? Figure 2. Figure 3. Management of exacerbations Systemic corticosteroid therapy Current evidence-based guidelines for the management of COPD state that in the absence of contraindications, oral corticosteroids should be used in conjunction with other therapies in all patients admitted to hospital with acute exacerbations.
Home management Although exacerbations have a considerable clinical impact, some patients could be safely treated at home. Preventing exacerbations There is evidence that COPD exacerbations cluster together, and a high-risk period for recurrence has been identified in the first 8 weeks following an initial event. Risk factors as targets for intervention Risk factors for COPD are also risk factors for the frequency and severity of exacerbations, and as such, are potential targets for intervention.
Figure 4. Other approaches to reduce exacerbation risk In addition to bronchodilators, other classes of drugs have been shown to reduce exacerbation risk in specific subsets of patients with COPD. Treating comorbid conditions Comorbidities of COPD, such as cardiovascular disease, gastroesophageal reflux disease, depression, and osteoporosis, are associated with increased susceptibility to exacerbations and can also contribute to how COPD develops.
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