Effects of prophylactic antibiotics on patients with stable COPD: a systematic review and meta-analysis of randomized controlled trials

Wang, Yuanyuan; Zijp, Tanja R; Bahar, Muh. Akbar; Kocks, Janwillem; Wilffert, Bob

doi:10.1093/jac/dky326

Cited by 9 publications

(4 citation statements)

References 32 publications

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“…Positive effects of macrolides may extend across airways disease; meta-analytic evidence in COPD [17] and bronchiectasis [18] indicates that ⩾12 weeks of prophylactic antibiotics (majority macrolides) reduced exacerbations and improved quality of life.…”

Section: Discussionmentioning

confidence: 99%

Does maintenance azithromycin reduce asthma exacerbations? An individual participant data meta-analysis

et al. 2019

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BackgroundPreventing exacerbations is an important goal of asthma treatment. Long-term treatment with azithromycin may help achieve this. Our aim was to conduct a systematic review and individual participant data (IPD) meta-analysis to examine the efficacy of azithromycin in reducing exacerbations in asthma, and in the subphenotypes of noneosinophilic asthma, eosinophilic asthma and severe asthma.MethodWe completed a systematic search of Embase, MEDLINE, PubMed, Cochrane Library, ClinicalTrials.gov and reference lists of previous systematic reviews in February 2019. We included parallel-group, double-blind, randomised controlled trials in adults comparing at least 8 weeks of azithromycin treatment with placebo, where the outcome of exacerbations was assessed over at least 6 months. Data were extracted from published sources, Cochrane Risk of Bias Tool was applied and IPD were sought from authors. Reviews were undertaken in duplicate. We conducted an IPD meta-analysis on the primary outcome of exacerbations and a random effects meta-analysis for secondary outcomes.ResultsThree studies were identified (n=604). In the IPD meta-analysis, treatment with azithromycin was associated with a reduced rate of exacerbations (oral corticosteroid course due to worsening asthma, antibiotic use for lower respiratory tract infection, hospitalisation and/or emergency department visits) in asthma as well as in the noneosinophilic, eosinophilic and severe asthma subgroups. Examining each exacerbation type separately, patients with eosinophilic asthma reported fewer oral corticosteroid courses, and patients with noneosinophilic and severe asthma reported fewer antibiotic courses. Azithromycin was well tolerated.DiscussionMaintenance use of azithromycin reduces exacerbations in patients with eosinophilic, noneosinophilic and severe asthma.

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Section: Discussionmentioning

confidence: 99%

Does maintenance azithromycin reduce asthma exacerbations? An individual participant data meta-analysis

et al. 2019

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“…Only the 14-day regimen of RESPIRE 1 showed a benefit of inhaled ciprofloxacin with adjusted difference, and other original publications on each study did not fully discuss this point. Since improvement of quality of life is one of the important treatment goals in managing bronchiectasis, 2,24 this discrepancy needs to be evaluated in depth for each trial. Likewise, changes in pulmonary function were also not different between the two groups in the present analysis.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of inhaled ciprofloxacin agents for the treatment of bronchiectasis: a systematic review and meta-analysis of randomized controlled trials

Lim

Hong

2019

Ther Adv Respir Dis

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Background: The efficacy of inhaled ciprofloxacin agents in the treatment of patients with bronchiectasis is controversial. The objective of the study was to review systematically the efficacy of inhaled ciprofloxacin agents in patients with bronchiectasis. Methods: We searched PubMed, EMBASE, and Cochrane Library databases for randomized controlled trials (RCTs) evaluating inhaled ciprofloxacin agents among patients with bronchiectasis. Data were pooled using a meta-analysis technique. Results: Two phase II and four phase III RCTs were included with a total of 1685 patients. Treatment durations of phase III studies were 48 weeks, while those of phase II studies were shorter. Pooled analysis of overall studies exhibited a statistically significant benefit of inhaled ciprofloxacin agents in three exacerbation outcome measures, including time to first exacerbation (hazard ratio 0.74, 95% confidence interval [CI] 0.63–0.86, I2 23%), exacerbation frequency (risk ratio [RR] 0.73, 95% CI 0.61–0.86, I2 42%), and exacerbation proportion (RR 0.85, 95% CI 0.76–0.96, I2 25%) without significant heterogeneity. Outcomes evaluating pulmonary function, quality of life, and adverse events were not significantly different between the two groups. Although eradication of respiratory pathogens was more frequently observed, the emergence of ciprofloxacin resistance was also significantly higher in the ciprofloxacin group. Conclusions: A meta-analysis of RCTs of inhaled ciprofloxacin agents showed clinical benefit in terms of pulmonary exacerbations in patients with bronchiectasis. Since a significant increase of resistance was also noticed, clinical trials with a longer study period are required for a conclusive assessment. The reviews of this paper are available via the supplemental material section.

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“…Although penicillin (e.g., amoxicillin and co-amoxiclav) kills bacteria directly as a bactericidal, they cannot prevent episodes caused by viral infections, which cannot be treated by antibiotics. Of note, if antibiotics were prophylactically used among COPD patients in either continuous or intermittent way, 18% of subsequent exacerbations could be prevented effectively [35].…”

Section: Primary Findingsmentioning

confidence: 99%

Real-World Effects of Antibiotic Treatment on Acute COPD Exacerbations in Outpatients: A Cohort Study under the PharmLines Initiative

et al. 2022

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Background: Although antibiotic treatment is recommended for acute exacerbations of chronic obstructive pulmonary disease (AECOPD), its value in real-world settings is still controversial. Objectives: This study aimed to evaluate the short- and long-term effects of antibiotic treatment on AECOPD outpatients. Methods: A cohort study was conducted under the PharmLines Initiative. We included participants with a first recorded diagnosis of COPD who received systemic glucocorticoid treatment for an AECOPD episode. The exposed and reference groups were defined based on any antibiotic prescription during the AECOPD treatment. The short-term outcome was AECOPD treatment failure within 14–30 days after the index date. The long-term outcome was time to the next exacerbation. Adjustment for confounding was made using propensity scores. Results: Of the 1,105 AECOPD patients, antibiotics were prescribed to 518 patients (46.9%) while 587 patients (53.1%) received no antibiotics. The overall antibiotic use was associated with a relative risk reduction of AECOPD treatment failure by 37% compared with the reference group (adjusted odds ratio [aOR] 0.63 [95% CI: 0.40–0.99]). Protective effects were similar for doxycycline, macrolides, and co-amoxiclav, although only the effect of doxycycline was statistically significant (aOR 0.53 [95% CI: 0.28–0.99]). No protective effect was seen for amoxicillin (aOR 1.49 [95% CI: 0.78–2.84]). The risk of and time to the next exacerbation was similar for both groups. Conclusion: Overall, antibiotic treatment, notably with doxycycline, supplementing systemic glucocorticoids reduces short-term AECOPD treatment failure in real-world outpatient settings. No long-term beneficial effects of antibiotic treatment on AECOPD were found for the prevention of subsequent exacerbations.

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Effects of prophylactic antibiotics on patients with stable COPD: a systematic review and meta-analysis of randomized controlled trials

Abstract: Prophylactic antibiotics were effective in preventing COPD exacerbations and improving quality of life among stable patients with moderate to severe COPD. The choice of prophylactic antibiotics should be analysed and considered case by case, especially for long and continuous use.

Cited by 9 publications

References 32 publications

Does maintenance azithromycin reduce asthma exacerbations? An individual participant data meta-analysis

Does maintenance azithromycin reduce asthma exacerbations? An individual participant data meta-analysis

Efficacy of inhaled ciprofloxacin agents for the treatment of bronchiectasis: a systematic review and meta-analysis of randomized controlled trials

Real-World Effects of Antibiotic Treatment on Acute COPD Exacerbations in Outpatients: A Cohort Study under the PharmLines Initiative

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