Antibiotic Use in the Management of Acute Exacerbations of Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is estimated to affect around 5% of people over 45 years of age, yet accounts for over half of the disease burden due to respiratory conditions. This progressive condition is characterised by persistent airflow limitation due to small airways disease and alveolar destruction. This can be caused by abnormal inflammatory responses arising from the long-term exposure to noxious particles or gases. Cigarette smoking is the most common risk factor, although environmental factors such as dust, gas, chemical fumes, smoke or air pollution may contribute. Genetic factors may also play a role. For example, alpha-1 antitrypsin deficiency is a genetic disorder that is associated with an increased risk of emphysema.

Smoking cessation remains the most important intervention to limit lung damage in COPD. However, pharmacotherapy is also used to relieve symptoms and improve quality of life. Medications that may be used for the management of stable disease include:

• Short-acting bronchodilator therapy, e.g. a short-acting beta₂ agonist (SABA);
• Long-acting bronchodilator monotherapy, e.g. a long-acting beta₂ agonist (LABA) or long-acting muscarinic antagonist (LAMA);
• Long-acting bronchodilator dual therapy, e.g. LABA plus LAMA combination therapy; or
• Triple therapy, i.e. LABA, LAMA plus inhaled corticosteroid.

Acute exacerbations are managed with inhaled bronchodilators, although systemic corticosteroids may also be required. The use of antibiotics in this setting is not as well-defined. It is known that not all acute exacerbations have an infective cause. Non-infective causes of exacerbations include environmental pollutants as well as serious conditions such as heart failure and pulmonary embolism.

Studies suggest that infectious causes are involved in 88% of acute exacerbations of COPD. Respiratory viruses are commonly implicated. Viruses that are often identified in these patients include influenza A, rhinovirus, and respiratory syncytial virus (RSV). Features suggestive of a bacterial infection include increasing dyspnoea along with increasing sputum volume and either a change in sputum colour or purulence.

The benefits of antibiotics need to be balanced against their potential harms. Antibiotic use is associated with adverse effects such as diarrhoea and yeast infections, while also increasing the risk of Clostridioides difficile infection. Reducing the inappropriate use of antibiotics is also important to address the issue of antibiotic resistance. The most recent AURA (Antimicrobial Use and Resistance in Australia) Report indicates that COPD has some of the highest rates of inappropriate antibiotic use, with 65% of prescriptions considered non-compliant with guideline recommendations.

The Therapeutic Guidelines advise that the benefit of antibiotics for acute exacerbations is related to disease severity. A Cochrane meta-analysis demonstrated that, while antibiotics may have some benefits in the management of acute exacerbations, these effects are often small. In addition, the benefits are inconsistent for some outcomes (such as treatment failure) and absent for other outcomes (including mortality and length of hospital stay) in most patient groups. However, for patients managed in the intensive care unit, antibiotics were associated with a strong beneficial effect.

If antibiotics are considered appropriate for an acute exacerbation of COPD, amoxicillin or doxycycline are the first-line options recommended by the Therapeutic Guidelines. A recent study further supports the use of antibiotics, particularly doxycycline, in this setting.

Doxycycline is a tetracycline antibiotic. The guidelines recommend a dose of 100mg daily for five days. Oesophageal irritation and ulceration can occur if the tablet or capsule adheres to the oesophagus. To reduce this risk, it is advised to administer tablets with adequate fluid and to ensure the patient remains upright for at least half an hour after each dose.

The guidelines recommend amoxicillin to be administered at a dose of 500mg three times daily or 1g twice daily for five days. Doses may be taken without respect to food, but should be spaced as evenly as possible.

Lack of response to these antibiotics may not always require a change to broader-spectrum therapy. Attention should be given to ensuring the patient is receiving appropriate inhaled bronchodilator therapy. Oral corticosteroids may also be required. Consideration of viral and non-infective causes of the exacerbation should also be considered and managed appropriately.