Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by persistent or chronic airflow limitation. It is typically progressive in nature and associated with an enhanced chronic inflammatory response in the airways and lungs to noxious particles or gases.1 Smoking is the main risk factor for COPD, with a small proportion of cases linked to passive smoking and genetic diseases, for example, [alpha]₁ antitrypsin deficiency.

The World Health Organization has predicted that COPD will be the third leading cause of death worldwide by 2030, and the Global Burden of Disease Study estimated that more than 300 million people were affected by COPD in 2013.2 The prevalence of the disease varies by country, with rates highest in low socioeconomic countries.

The signs and symptoms of COPD include dyspnea, chronic cough, and sputum production. Exacerbations of the disease are acute in onset and involve an increase in 1 or more symptoms, for example, increased level of dyspnea, worsening of chronic cough, or increase in sputum production for a sustained period (over 48 hours). The risk of exacerbation increases with the severity of airflow limitation in a patient and is often linked to respiratory infections and exposure to environmental pollution, for example, black smoke particulate matter.3 Exacerbations of COPD can lead to increased morbidity including potential loss of lung function due to inflammation and resultant deconditioning that can lead to time off work and loss of independence.

There is a range of evidence-based approaches aimed at reducing the risk of COPD exacerbations. These include avoidance of cigarette smoke and air pollution, vaccination against influenza and pneumococcal disease, and preventive medication regimens involving inhaled drugs, for example, long-acting [beta]-agonists and corticosteroids and/or oral medicines such as phosphodiesterase 4 inhibitors. The use of prophylactic antibiotics has also been proposed as a preventive measure, with the aim of reducing the bacterial load and thus limiting progression of the disease. In addition, some antibiotics have anti-inflammatory properties that can also modify disease progression.

OBJECTIVES

The primary objective of this review4 was to determine whether regular treatment (continuous, intermittent, or pulsed) with prophylactic antibiotics reduces exacerbations or affects quality of life in patients with COPD. This review was an update of one conducted in 2013.5

INTERVENTION/METHODS

The review included randomized controlled trials, including cluster randomized controlled trials and crossover trials, that compared use of antibiotics versus a placebo. The studies included adults, older than 18 years, with a definitive diagnosis of COPD. Patients with bronchiectasis, asthma, or genetic disease, for example, cystic fibrosis, were excluded.

The interventions involved the administration of oral antibiotics, including penicillin, quinolones, macrolides, and sulfonamides, in applicable daily doses at least 3 times per month for a period of at least 3 months.

There were 2 primary outcomes considered:

1. number of exacerbations-this included the total number of patients who experienced exacerbations and the frequency of exacerbations in the study period and

2. health-related quality of life.

Secondary outcome measures included the following:

* duration and severity of exacerbations;

* days of disability;

* frequency and duration of hospital admissions;

* reduction in lung function from baseline as measured by forced expiratory volume in 1 second and forced vital capacity;

* drug resistance as measured by microbial sensitivity;

* death due to all-cause mortality, including respiratory causes; and

* adverse effects.

RESULTS

There were 16 studies included in this review, 7 from the original 2013 review5 and 9 new studies. However, 2 studies were prematurely terminated, so the authors reported on the results from only 14 studies, representing a total of 3932 participants. The studies ranged from 3 to 36 months in duration, and the antibiotics investigated included azithromycin, erythromycin, clarithromycin, doxycycline, roxithromycin, and moxifloxacin.

Three studies compared the use of continuous antibiotic therapy to placebo, and the results showed that the number of patients experiencing 1 or more exacerbations was significantly reduced with the use of prophylactic antibiotics. Further analysis showed that pulsed treatment regimens had a smaller treatment effect than continuous and intermittent regimens. The rate of exacerbations per patient per year was also reduced with continuous and intermittent antibiotic prophylaxis, in a finding that was statistically significant. A significant difference was also identified for the median length of time to first exacerbation, which was lengthened in patients who received continuous antibiotic therapy and in 1 study of intermittent antibiotic therapy compared with placebo.

Health-related quality of life was explored in 9 studies, and where an improvement in quality of life was identified, it was associated with continuous and intermittent antibiotic prophylaxis with no clear improvement found with pulsed antibiotic regimens. No significant differences were identified for the secondary outcomes: frequency of hospital admissions, change in lung function, serious adverse events, or all-cause mortality; however, for both mortality and adverse events, confidence intervals were too wide to rule out an effect.

The specific adverse events reported in some of the studies may have clinical relevance based on their severity. The adverse events varied according to the type of antibiotic used; for example, azithromycin was associated with a significant hearing loss in the treatment group. The use of moxifloxacin was linked to an increase in gastrointestinal adverse events in a finding that was statistically significant. Some adverse events were not significantly more frequent in the treatment groups; however, the seriousness of these, for example, development of long QTc or tinnitus, led to discontinuation of the antibiotics concerned. The development of antibiotic resistance was addressed in 6 studies (n = 2486 participants), with 4 studies identifying evidence of antibiotic resistance.

CONCLUSIONS

This author concluded that the prophylactic use of macrolide prophylactic antibiotics for a period of up to 12 months in patients diagnosed with COPD is likely to reduce the number of patients with exacerbations, exacerbation frequency, median time to first exacerbation, and possible health-related quality of life. These benefits were associated with continuous and intermittent macrolide regimens, with pulsed regimens found to be less effective.

The adverse events associated with these regimens were found to include serious effects such as hearing loss and the development of antibiotic resistance. Therefore, the benefits should be balanced against the potential risks before treatment is prescribed and patients routinely monitored for any adverse effects.

IMPLICATIONS FOR PRACTICE

Chronic obstructive pulmonary disease is a common respiratory disease and one that is expected to increase in prevalence, with the World Health Organization projecting that it will be the third largest cause of death worldwide by 2030. Therefore, it is likely that nurses will encounter patients with COPD in their practice across a range of clinical environments. For this reason, nurses should remain up to date with best practice for prevention of exacerbations in their COPD patients, including the benefits and risks of prophylactic treatment with antibiotics.

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