BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) can lead to high frequencies and rates of hospitalization and mortality. Macrolides are a class of antibiotics that possess both antimicrobial and anti-inflammatory properties. Since the occurrence of AECOPDs is associated with aggravation of airway inflammation and bacterial infections, prophylactic macrolide treatment may be an effective approach towards the prevention of AECOPDs.
METHODS: We systemically searched the PubMed, Embase and Cochrane Library databases to identify randomized controlled trials (RCTs) that evaluated the effect of prophylactic macrolide therapy on the prevention of AECOPDs. The primary outcomes were the total number of patients with one or more exacerbations as well as the rate of exacerbations per patient per year.
RESULTS: Nine RCTs comprising 1666 patients met the inclusion criteria. Pooled evidence showed macrolides could reduce the frequency of exacerbations in patients with COPD by both unweighted (RR = 0.70; 95% CI: 0.56-0.87; P < 0.01) and weighted approaches (RR = 0.58, 95% CI: 0.43-0.78, P < 0.01). Subgroup analysis showed only 6-12 months of erythromycin or azithromycin therapy could be effective. Moreover, among studies with 6-12 months of azithromycin therapy, both the daily dosing regimen and the intermittent regimen significantly reduced exacerbation rates. The overall number of hospitalizations and the all-cause rate of death were not significantly different between the treatment and control groups. A tendency for more adverse events was found in the treatment groups (OR = 1.55, 95%CI: 1.003-2.39, P = 0.049).
CONCLUSIONS: Our results suggest 6-12 months erythromycin or azithromycin therapy could effectively reduce the frequency of exacerbations in patients with COPD. However, Long-term treatment may bring increased adverse events and the emergence of macrolide-resistance. A recommendation for the prophylactic use of macrolide therapy should weigh both the advantages and disadvantages.
The purpose of this review was to evaluate the literature to assess the incidence and true clinical relevance of recent Food and Drug Administration warnings regarding QT prolongation with azithromycin, given its widespread use, with over 40 million US outpatient prescriptions written in 2011. A literature search of MEDLINE (1946 to May 2013) and International Pharmaceutical Abstracts (1970 to May 2013) was conducted using the terms azithromycin, QT prolongation, torsades de pointes, arrhythmia, and cardiovascular death. A bibliographic search was also performed. Several relevant studies and case reports were identified and reviewed. One cohort study revealed an increased risk of cardiovascular death with azithromycin compared to no antibiotic, especially in those with higher cardiovascular risk. Another cohort study comparing azithromycin, penicillin V, and no antibiotic in a younger Danish population with less cardiac risk found no increased cardiovascular death associated with azithromycin use. The majority of case reports involved ill and/or elderly patients with multiple comorbidities and concomitant medications who were already at a higher risk of cardiovascular events. Although there is evidence that azithromycin may induce QT prolongation and adverse cardiac events, the incidence is fairly limited to patients with high baseline risk, including those with preexisting cardiovascular conditions and concomitant use of other QT-prolonging drugs.
BACKGROUND: Azithromycin has been used for many years for the treatment of patients with various types of bacterial infections, as well as for the secondary prevention of coronary events. There is a growing concern, however, that azithromycin may be associated with an increased cardiovascular (CV) risk and may lead to CV-related death in high-risk patients.
OBJECTIVE: This systematic review of randomized controlled trials was conducted to analyze and describe the CV risk and safety outcomes associated with azithromycin therapy.
METHODS: A meta-analysis was conducted based on the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases from 1990 through September 2013. Specific medical search terms in the English language included "azithromycin," "macrolide," "antibiotic," "cardiovascular diseases," and "cardiovascular events" and were used to identify relevant randomized clinical trials that assessed the risk for CV events in patients receiving azithromycin therapy or placebo. The randomized clinical trials that were selected included patients who received azithromycin or placebo for the treatment of infection or for the secondary prevention of coronary events. Major health outcome measures included mortality, hospitalization, and coronary intervention. Meta-analyses were performed using a random effects model.
RESULTS: A total of 12 randomized clinical trials included 15,588 patients. Patients were divided into 2 groups, either to azithromycin therapy or to placebo. Compared with patients who had not received azithromycin, patients who had received azithromycin had an overall risk ratio (RR) of death of 0.877 (95% confidence interval [CI], 0.752-1.024; P = .097). No heterogeneity was observed (I(2) = 0%). Similarly, no differences were found in the pooled RRs for hospitalization or for clinical intervention for CV events (RR, 1.005; 95% CI, 0.922-1.094; P = .915; I(2) = 0% and RR, 0.999; 95% CI, 0.896-1.125; P = .984; I(2) = 0%, respectively).
CONCLUSION: No increased risks for mortality or for CV events associated with azithromycin therapy compared with placebo were found among patients included in the 12 randomized clinical trials reviewed in this analysis.
Long-term treatment with macrolides has recently been shown to reduce COPD exacerbations in doses lower than bactericidal doses. This article aims to critically review the international literature relating to the long-term effectiveness and safety of macrolides and to estimate the budget impact of preventing exacerbations with azithromycin in Belgium. Controlled clinical studies focusing on the prevention of COPD exacerbations with long-term macrolide treatment were identified in PubMed, EMBASE, Controlled Trials Registry of the Cochrane Library, and Social Science and Citation Index. The budget impact of preventing exacerbations with azithromycin in Belgium over a one-year period was calculated as the difference between the additional expenditure of annual treatment with azithromycin and the savings in hospital expenditure arising from fewer COPD exacerbations in patients with GOLD stages II-IV. Prevalence and resource use data were derived from the literature and unit cost data from Belgian sources. The literature review suggests that long-term treatment of COPD patients with azithromycin, erythromycin or clarithromycin is effective and safe, and reduces exacerbations and related hospitalizations. However, uncertainty remains about the specific patient population that is most likely to benefit from long-term macrolide treatment, the optimal dose and duration of macrolide treatment, and the potential impact of long-term macrolide treatment on resistance. The budget impact analysis demonstrated that annual hospital savings of €950 million resulting from fewer exacerbations outweighed additional expenditure on azithromycin of €595 million, implying that the prevention of COPD exacerbations with azithromycin is a cost saving strategy in Belgium.
OBJECTIVE: To determine if antibiotics are efficacious in stable COPD. METHODS: Pubmed, embase and cochrane database of controlled trials were searched from inception to december 2012. Quality assessment was done as per cochrane collaborations tool. The extracted data were then computed using STATA software. We converted the estimates to the common metric of a relative risk, since all studies compared two groups and reported binary outcomes. RRs were pooled and we calculated average RRs across measures within each study and used the average estimate in cross-study meta-analysis. RESULTS: Of 3912 articles searched, 8 RCTs met the inclusion criteria. The overall estimate revealed that antibiotics (azithromycin, clarithromycin, levofloxacin) have a significant role in preventing acute exacerbation (Relative Risk = 0.702, 95% confidence interval (CI) 0.632 – 0.781, P < 0.001). The test for heterogeneity was Q= 4.143 on 7 degrees of freedom (p= 0.763). CONCLUSION: There is statistical evidence of the superiority of antibiotics in reducing the frequency of acute exacerbation in stable COPD warranting identification of patient groups most likely to benefit.
BACKGROUND: Macrolide antibiotics have anti-inflammatory effects, and long-term administration may reduce chronic obstructive pulmonary disease (COPD) exacerbations. OBJECTIVE: To investigate the effects of long-term treatment of macrolide therapy for COPD. METHODS: We searched the PubMed and Embase databases to identify randomized controlled trials that evaluated the effect of macrolide therapy (of at least 2 weeks) for COPD. The primary outcome assessed was the frequency of acute exacerbations during follow-up. RESULTS: Six trials involving 1,485 COPD patients were included in the analysis. Analysis of the pooled data of all 6 trials showed that macrolide administration reduced the frequency of acute exacerbations of COPD [risk ratio (RR) = 0.62; 95% CI 0.43-0.89, p = 0.01]. Subgroup analysis showed that only erythromycin might be associated with decreased COPD exacerbations (erythromycin: p = 0.04, azithromycin: p = 0.22, clarithromycin: p = 0.18). Moreover, macrolide therapy for 3 months did not significantly reduce the number of exacerbations (p = 0.18), whereas a beneficial effect was conclusive in the 6-month (p = 0.009) and 12-month (p = 0.03) treatment subgroups. In addition, nonfatal adverse events were more frequent in the macrolide treatment groups than in the controls (RR = 1.32; 95% CI 1.06-1.64, p = 0.01). However, related clinical factors had no influence on the overall result (p = 0.19). There was no publication bias among the included trials. CONCLUSIONS: Macrolide therapy was effective and safe in decreasing the frequency of exacerbations in patients with COPD. Treatment might provide a significant benefit but only when therapy lasts more than 6 months.
INTRODUCTION: Macrolides are of unique interest in preventing COPD exacerbations because they possess a variety of antibacterial, antiviral and anti-inflammatory properties. Recent research has generated renewed interest in prophylactic macrolides to reduce the risk of COPD exacerbations. Little is known about how well these recent findings fit within the context of previous research on this subject. The purpose of this article is to evaluate, via exploratory meta-analysis, whether the overall consensus favors prophylactic macrolides for prevention of COPD exacerbations.
METHODS: EMBASE, Cochrane and Medline databases were searched for all relevant randomized controlled trials (RCTs). Six RCTs were identified. The primary endpoint was incidence of COPD exacerbations. Secondary endpoints including mortality, hospitalization rates, adverse events and likelihood of having at least one COPD exacerbation were also examined.
RESULTS: There was a 37% relative risk reduction (RR = 0.63, 95% CI: 0.45-0.87, p value = 0.005) in COPD exacerbations among patients taking macrolides compared to placebo. Furthermore, there was a 21% reduced risk of hospitalization (RR = 0.79, 95% CI: 0.69-0.90, p-value = 0.01) and 68% reduced risk of having at least one COPD exacerbation (RR = 0.34, 95% CI 0.21-0.54, p-value = 0.001) among patients taking macrolides versus placebo. There was also a trend toward decreased mortality and increased adverse events among patients taking macrolides but these were not statistically significant.
CONCLUSIONS: Prophylactic macrolides are an effective approach for reducing incident COPD exacerbations. There were several limitations to this study including a lack of consistent adverse event reporting and some degree of clinical and statistical heterogeneity between studies.
Journal»The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
BACKGROUND: Exacerbations contribute substantially to the morbidity and mortality associated with chronic obstructive pulmonary disease (COPD).
OBJECTIVES: To assess whether prophylactic antibiotic treatment reduces exacerbations in patients with COPD and/or chronic bronchitis.
METHODS: Medline, EMBASE, Cochrane Central Register of Controlled Trials, Koreamed and references from relevant publications were searched up to October 2011. Randomised controlled trials comparing the effect of any prophylactic antibiotics with placebo for at least 3 months were included. The co-primary outcomes were the frequency of exacerbations of COPD or chronic bronchitis and adverse treatment events.
RESULTS: A total of 19 trials involving 3932 subjects were included in the analysis: 5 recent trials included patients with moderate to severe COPD, whereas 14 older trials included patients with chronic bronchitis. The use of antibiotics significantly reduced the rate of COPD exacerbations (risk ratio [RR] 0.73, 95%CI 0.66-0.82), the number of chronic bronchitis exacerbations (standardised mean difference -0.23, 95%CI -0.35--0.11) and the proportion of patients with exacerbations of chronic bronchitis (RR 0.93, 95%CI 0.87-0.99).
CONCLUSION: Prophylactic antibiotic treatment has a significant effect in reducing exacerbations in patients with COPD and/or chronic bronchitis.
Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) can lead to high frequencies and rates of hospitalization and mortality. Macrolides are a class of antibiotics that possess both antimicrobial and anti-inflammatory properties. Since the occurrence of AECOPDs is associated with aggravation of airway inflammation and bacterial infections, prophylactic macrolide treatment may be an effective approach towards the prevention of AECOPDs.
METHODS:
We systemically searched the PubMed, Embase and Cochrane Library databases to identify randomized controlled trials (RCTs) that evaluated the effect of prophylactic macrolide therapy on the prevention of AECOPDs. The primary outcomes were the total number of patients with one or more exacerbations as well as the rate of exacerbations per patient per year.
RESULTS:
Nine RCTs comprising 1666 patients met the inclusion criteria. Pooled evidence showed macrolides could reduce the frequency of exacerbations in patients with COPD by both unweighted (RR = 0.70; 95% CI.: 0.56-0.87; P < 0.01) and weighted approaches (RR = 0.58, 95% CI.: 0.43-0.78, P < 0.01). Subgroup analysis showed only 6-12 months of erythromycin or azithromycin therapy could be effective. Moreover, among studies with 6-12 months of azithromycin therapy, both the daily dosing regimen and the intermittent regimen significantly reduced exacerbation rates. The overall number of hospitalizations and the all-cause rate of death were not significantly different between the treatment and control groups. A tendency for more adverse events was found in the treatment groups (OR = 1.55, 95%CI: 1.003-2.39, P = 0.049).
CONCLUSIONS:
Our results suggest 6-12 months erythromycin or azithromycin therapy could effectively reduce the frequency of exacerbations in patients with COPD. However, Long-term treatment may bring increased adverse events and the emergence of macrolide-resistance. A recommendation for the prophylactic use of macrolide therapy should weigh both the advantages and disadvantages.
