Dr Tse Hoi Nam
Specialist in Respiratory Medicine
Consultant in Respiratory Medicine, Hong Kong Baptist Hospital
Clinical Associate Professor (Honorary), Department of Medicine and Therapeutics, The Chinese University of Hong Kong (CUHK)

An exacerbation of chronic obstructive pulmonary disease (COPD) is defined as an event characterised by increased dyspnea and/or cough and sputum that worsens in <14 days which may be accompanied by tachypnea and/or tachycardia and is often associated with increased local and systemic inflammation caused by infection, pollution, or other insult to the airways.¹ Acute exacerbations of COPD (AECOPD) are associated with significant morbidity, mortality, and economic burden.² Optimal treatment of exacerbations is a key focus of COPD management, with the aim to improve the quality of life of patients with this disabling and chronic condition.

Dr Tse Hoi Nam describes the treatment strategies for AECOPD, including the role of fluoroquinolones in AECOPD management.

Q1. What is the relationship between bacterial infection and AECOPD?

To begin, current definitions of COPD exacerbations are inconsistent across studies. Definitions may be based on the presence of symptoms (‘symptom‐based’ definition), the types of healthcare resources used, such as the prescription of medication by a general practitioner or whether hospital admission is required (‘healthcare-based’ definition), or a combination of both definitions.³ In general, however, AECOPD is associated with an increased level of dyspnoea, worsening of chronic cough, and/or an increase in the volume and/or purulence of the sputum produced.⁴ AECOPD is triggered predominantly by bacterial or viral pathogens in approximately up to 60% of cases.⁵ The underlying mechanisms of exacerbations caused by bacteria are still not completely understood. However, most evidence indicates that further amplification of the inflammatory process triggered by bacteria plays a key role in the development and progression of AECOPD.⁶ Bacteria primarily infect the lower airways and increase airway inflammation. This leads to increased numbers of activated neutrophils in sputum, and further increases the cytokine levels [tumour necrosis factor (TNF)-α and interleukin 8 (IL-8)] during the exacerbation.⁶

Q2. What are the bacterial pathogens most frequently responsible for AECOPD?

In Hong Kong, just like many other countries, the most common bacterial species associated with AECOPD include Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae.⁵ In some cases, AECOPD may be associated with atypical pathogens such as Mycoplasma pneumoniae.⁵ Patients with recurring episodes of AECOPD, bronchitis and/or bronchiectasis, and have recent history of hospital admissions may be at higher risk of exacerbations caused by Pseudomonas aeruginosa and other Gram-negative species.^{7, 8}

Q3. Please provide your recommended treatment strategies and pathways for the management of patients with AECOPD resulting from bacterial infections.

In general, the goals of management of AECOPD are to improve expiratory airflow, reduce lung inflammation, improve gas exchange, and provide symptom relief.⁹ To determine the intensity of the treatment required, a comprehensive assessment of exacerbation severity should be conducted in all patients presenting with AECOPD.¹⁰ Depending on the severity, the acute management of AECOPD involves use of bronchodilators, steroids, antibiotics, oxygen and noninvasive ventilation. According to the 2022 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, the severity of AECOPD can be graded according to the intensity of treatment required¹¹:

Mild: treated with short-acting bronchodilators only

Moderate: treated with short-acting bronchodilators plus antibiotics and/or oral corticosteroids

Severe: requires either hospitalisation or a visit to the emergency department and may also be associated with respiratory failure

Antibiotics are often used in the acute management of inpatients or outpatients with AECOPD, because bacteria are commonly implicated in a substantial proportion of these cases. In patients with AECOPD who meet the criteria for antibiotic therapy, antibiotics should be selected based on their coverage of the most common respiratory pathogens associated with AECOPD.¹⁰ Empiric treatment for patients with AECOPD does not usually cover atypical pathogens such as Mycoplasma pneumoniae, unless specific clinical characteristics are suggestive of such infection.

Examples of commonly prescribed antibiotics include amoxycillin (with or without clavulanic acid), a macrolide or tetracycline, or a respiratory quinolone.¹¹ Although there is no strong evidence regarding the optimal duration of antibiotic therapy for AECOPD, the GOLD guidelines recommend a short course of 5 days of antibiotics.¹¹

Q4. What are your clinical considerations when selecting antibiotics for the empirical treatment of AECOPD?

The selection of an antibiotic for empiric therapy is based upon several factors, including clinical criteria, local resistance factors and epidemiological factors. In Hong Kong, physicians follow the GOLD guidelines for the management of patients with AECOPD. The 2022 GOLD guidelines recommend initiating antibiotics in patients with AECOPD who have three cardinal symptoms: an increase in dyspnoea, sputum volume, and sputum purulence; or have two of the cardinal symptoms, if increased purulence of sputum is one of the two symptoms; or if the patient requires mechanical ventilation (invasive or noninvasive).¹⁰ In our clinical practice, augmentin is usually recommended for mild and moderate cases of AECOPD, to cover the common causative bacteria. For patients with more advanced disease or frequent exacerbations, antibiotic therapy may also need to be suitable for Pseudomonas aeruginosa infection.

Q5. Based on your clinical experience, what is the role of fluoroquinolones (e.g. levofloxacin) in the treatment of AECOPD?

Fluoroquinolones, such as levofloxacin, cover a wide range of typical and atypical pathogens, and appear to be particularly beneficial for patients with more severe AECOPD associated with Pseudomonas aeruginosa. Fluoroquinolones have many advantageous pharmacokinetic properties including high oral bioavailability, large volume of distribution, and broad-spectrum activity against relevant pathogens. Respiratory fluoroquinolones (moxifloxacin, gemifloxacin and levofloxacin) should ideally be reserved for patients with severe COPD, significant cardiac comorbidity or frequent exacerbations.¹² Furthermore, it is advisable to use fluoroquinolones for AECOPD treatment with caution in regions with a high prevalence of tuberculosis (TB) infection, such as in Hong Kong.¹³ Empirical use of fluoroquinolones in patients with AECOPD may cause delay in TB diagnosis and also contribute to fluoroquinolone resistance of Mycobacterium tuberculosis.

References

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