Antibiotics Not Always Necessary for Acute COPD Exacerbations

Chronic obstructive pulmonary disease (COPD) is a common chronic, progressive lung disease that includes two conditions: chronic bronchitis (in which the breathing airways become inflamed and narrowed) and emphysema (in which the lung’s air sacs are permanently damaged).[1] COPD is characterized by difficulty breathing. Other symptoms include persistent cough, increased mucus production, wheezing and chest tightness. The disease affects approximately 15 million Americans and results in more than 140,000 deaths in the U.S. each year.[2]

Stable COPD patients are managed by reducing exposure to factors that can damage the lungs, including smoking and environmental irritants (for example, air pollution), and taking long-acting bronchodilator drugs (such as formoterol [PERFOROMIST] and salmeterol [SEREVENT]), which open up the airways.[3] An important goal in the management of these patients is to reduce the occurrence of acute COPD exacerbations (flare-ups): episodes of sudden, sustained worsening of respiratory symptoms beyond normal day-to-day variations. These exacerbations are characterized by increased airway inflammation resulting in increased shortness of breath. Other symptoms may include increased sputum production, increased cough and wheezing.

COPD exacerbations often impair health status and may accelerate the decline of lung function. Therefore, they typically require additional treatments, such as taking short-acting “rescue inhaler” bronchodilators (for example, albuterol [ACCUNEB, PROAIR, PROVENTIL-HFA, VENTOLIN HFA, XOPENEX]) and a short course of corticosteroids. Additionally, severe COPD exacerbations may necessitate hospitalization.

However, there is a controversy regarding using antibiotics on a routine basis for patients with acute COPD exacerbations.[4] These exacerbations are not always caused by bacterial infections, but some doctors may prescribe antibiotics just to “be on the safe side” for all patients who experience exacerbations.[5] Such overuse of antibiotics contributes to the general problem of antibiotic resistance and exposes patients to an increased risk of a severe type of diarrhea caused by Clostridium difficile infection in the intestines. Learn what the most recent evidence and guidelines say about this important topic.

Effectiveness of antibiotics for COPD exacerbations

Approximately one-half of COPD exacerbations are triggered by bacterial infections, whereas the remaining cases are triggered by viral infections or environmental irritants.[6] However, bacterial causes of exacerbation can be hard to confirm: While purulent (colored, such as deep yellow, green or brown) sputum is usually a sign of bacterial infection, sputum culture provides information only about the presence of bacteria (colonization) in the airways, not whether the bacteria is causing a respiratory infection and a related COPD exacerbation.[7] Therefore, sputum culture is not recommended unless sputum is purulent, and this testing usually is limited to exacerbations that result in hospitalization.[8]

A systematic review by the Cochrane Collaboration (a nonprofit international organization that specializes in medical literature reviews) characterized as “low quality” and “inconclusive” the evidence from the few completed placebo-controlled clinical trials that examined the use of antibiotics in patients with mild-to-moderate COPD exacerbations who were treated at home.[9] The data did suggest that use of antibiotics reduced the chances of treatment failure (defined as no improvement in symptoms, despite treatment, within seven to 28 days) compared with placebo.

The Cochrane review also found that patients with very severe acute exacerbations who were treated with antibiotics in an intensive care unit (ICU) had lower death rates than did those who received a placebo. In contrast, patients with severe acute COPD exacerbations who were treated with antibiotics at the hospital (but not in an ICU) and those with mild-to-moderate COPD exacerbations who were treated with antibiotics at home did not have lower death rates than did those who received a placebo.

Guideline recommendations

The latest guidelines by the Global Initiative for Chronic Obstructive Lung Disease (GOLD), Inc. (an international group of COPD specialists) recommend the use of antibiotics in patients with COPD exacerbations who have purulent sputum together with increased sputum volume or increased shortness of breath and in those who require mechanical ventilation (treatment with an artificial breathing machine).[10]

The most recent guidelines by the National Institute for Health and Care Excellence (NICE) in the U.K. concur with the GOLD guidelines that changes in sputum color and increased sputum volume or thickness are important factors for determining which patients may benefit from using antibiotics for COPD exacerbations.[11] However, these guidelines recommend that the use of antibiotics should be considered on an individual patient basis and that additional factors should be taken into account. These factors include the uncertain benefit of antibiotics in many cases and the increased risk of adverse effects and antibiotic resistance with repeated antibiotic courses, balanced against the severity of the exacerbation, the need for hospitalization, exacerbation and hospitalization history, risk of COPD complications, and any previous sputum culture results.

When an antibiotic is necessary for acute COPD exacerbations, the NICE guidelines recommend taking one of three first-line oral antibiotics that generally are effective for common bacteria that trigger such exacerbations: amoxicillin (AMOXIL, LAROTID), doxycycline (ACTICLATE, DORYX, MONODOX, ORACEA, VIBRAMYCIN) and clarithromycin (generic only).[12] For individuals whose symptoms worsen after taking one of these antibiotics for at least two to three days, these guidelines recommend taking one of the other antibiotics. For individuals at a higher risk of treatment failure, the NICE guidelines recommend one of three additional antibiotics: amoxicillin and clavulanate (AUGMENTIN), levofloxacin (generic only) and sulfamethoxazole and trimethoprim (BACTRIM, SEPTRA, SULFATRIM PEDIATRIC).

If an antibiotic is deemed appropriate for acute COPD exacerbations, both the GOLD and NICE guidelines recommend a short-term course to reduce the risk of antibiotic resistance and adverse effects (such as yeast infections and diarrhea).[13],[14] Specifically, the GOLD guidelines recommend a five-to-seven-day course, and the NICE guidelines recommend a five-day course.

What You Can Do

If you have COPD, discuss the information in this article with your doctor when preparing your “action plan” for early treatment of acute exacerbations.[15] Depending on your condition, unless you have purulent sputum combined with increased sputum volume or increased shortness of breath, it may be best not to start antibiotic therapy right away if you develop an exacerbation. However, seek immediate medical help if your symptoms worsen significantly within the time that is specified by your doctor (usually two to three days) or if you feel very unwell. You may need an antibiotic in these cases.
 

References

[1] National Institutes of Health, National Heart, Lung, and Blood Institute. COPD. https://www.nhlbi.nih.gov/health-topics/copd. Accessed July 5, 2019.

[2] Centers for Disease Control and Prevention. COPD. November 27, 2018. https://www.cdc.gov/dotw/copd/. Accessed July 5, 2019.

[3] Global Initiative for Chronic Obstructive Lung Disease, Inc. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. 2019. https://goldcopd.org/wp-content/uploads/2018/11/GOLD-2019-v1.7-FINAL-14Nov2018-WMS.pdf. Accessed July 9, 2019.

[4] Puhan MA, Vollenweider D, Latshang T, et al. Exacerbations of chronic obstructive pulmonary disease: when are antibiotics indicated? A systematic review. Respir Res. 2007;8(April 4):30.

[5] Vollenweider DJ, Frei A, Steurer-Stey CA, et al. Antibiotics for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2018 (October 29);10:CD010257.

[6] Ibid.

[7] Qureshi H, Sharafkhaneh A, Hanania NA. Chronic obstructive pulmonary disease exacerbations: latest evidence and clinical implications. Ther Adv Chronic Dis. 2014;5(5):212-227.

[8] National Institute for Health and Care Excellence (NICE). Chronic obstructive pulmonary disease in over 16s: diagnosis and management. December 5, 2018. https://www.nice.org.uk/guidance/ng115/resources/chronic-obstructive-pulmonary disease-in-over-16s-diagnosis-and-management-pdf-66141600098245. Accessed July 9, 2019.

[9] Vollenweider DJ, Frei A, Steurer-Stey CA, et al. Antibiotics for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2018(October 29);10:CD010257.

[10] Global Initiative for Chronic Obstructive Lung Disease, Inc. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. 2019. https://goldcopd.org/wp-content/uploads/2018/11/GOLD-2019-v1.7-FINAL-14Nov2018-WMS.pdf. Accessed July 9, 2019.

[11] National Institute for Health and Care Excellence. Chronic obstructive pulmonary disease (acute exacerbation): antimicrobial prescribing. December 5, 2018. https://www.nice.org.uk/guidance/ng114/resources/chronic-obstructive-pulmonary-disease-acute-exacerbation-antimicrobial-prescribing-pdf-66141598418629. Accessed July 9, 2019.

[12] Ibid.

[13] Global Initiative for Chronic Obstructive Lung Disease, Inc. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. 2019. https://goldcopd.org/wp-content/uploads/2018/11/GOLD-2019-v1.7-FINAL-14Nov2018-WMS.pdf. Accessed July 9, 2019.

[14] National Institute for Health and Care Excellence. Antimicrobial prescribing for acute exacerbations of COPD. December 5, 2018. https://www.nice.org.uk/guidance/ng114/resources/chronic-obstructive-pulmonary-disease-acute-exacerbation-antimicrobial-prescribing-pdf-66141598418629. Accessed July 9, 2019.

[15] Lareau S, Moseson E, Slatore CG. Exacerbation of COPD. Am J Respir Crit Care Med. 2018;198(11):P21-P22.