Dr Charoen Chuchottaworn
Senior Medical Advisor, Central Chest Institute of Thailand, Thailand
Consultant, Department of Medical Services, Ministry of Public Health, Thailand
Consultant, Tuberculosis Division, Department of Disease Control, Ministry of Public Health, Thailand

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are commonly caused by respiratory tract infections.¹ Though exacerbations may be caused by viruses and other environmental factors, bacteria are most commonly implicated in these infections; as such, empiric antibiotic therapy is often prescribed in patients with AECOPD.^{2, 3} Exacerbations of COPD are associated with significant patient morbidity and mortality⁴; for the optimal management of these patients, the antibiotic treatment selected must therefore be appropriate for respiratory bacterial infection.

Dr Charoen, based in Thailand, shares his expert opinion on the management of AECOPD, and discusses his insights on the suitability of levofloxacin for his patients.

Q1: AECOPD can be commonly caused by both bacteria and viruses.² Given the urgency of the clinical situation, what are the readily available clinical parameters or tools to discriminate between the causative pathogens when making decision of whether to initiate antibiotics in moderate or severe AECOPD?

AECOPD can be attributed to various causes, including viral or bacterial infections, as well as non-infectious factors like pollutants. In clinical practice, distinguishing between causes can be challenging.⁵ Numerous clinical criteria and simple scoring systems have been assessed and recommended for guiding the initiation of antibiotics.^{6, 7} The Anthonisen criteria are commonly utilised to determine whether antibiotics should be initiated in AECOPD patients.⁶ These criteria involve assessing three symptoms: increasing dyspnoea, increasing sputum volume, and whether purulent sputum is present. If a patient with AECOPD presents with all three symptoms, antibiotics should be promptly started. Biomarkers, such as procalcitonin levels and C-reactive protein (CRP) levels, are also useful in evaluating the need for antibiotics, particularly when the clinical criteria or scoring system yields ambiguous results.⁸ Typically, in practice, clinicians tend to prescribe antibiotics for patients with moderate or severe AECOPD to prioritise their safety.

Q2: If bacteria were found to be the causative pathogen, what would be your next steps in patient management, with regard to antibiotic selection? What disease, patient and treatment factors would you consider when making your decision?  

If the causative agent of AECOPD was identified as bacteria, and further investigation reveals the specific bacterial species and their susceptibility to drugs, selecting an appropriate antibiotic becomes relatively straightforward. However, in most cases, the specific pathogen causing AECOPD is unknown, although there is generally strong suspicion of bacterial involvement. In such situations, the selection of antibiotics should take into account several factors, including the clinical severity of AECOPD, the patient’s comorbidities, local data on commonly implicated bacterial pathogens, and the drug susceptibility patterns of these pathogens.⁹

For patients with greater clinical severity of AECOPD and underlying comorbidities, it becomes essential to consider antibiotics that can effectively target relatively severe bacterial pathogens, particularly Gram-negative pathogens. The local patterns of drug susceptibility among bacterial pathogens play a crucial role in treatment and should be used as a guide to determine the most appropriate antibiotics.⁹ This approach helps to maximise the potential benefits of treatment by ensuring that the chosen antibiotics are effective against the prevalent bacterial strain in the specific geographical region.⁹

Q3: Difficult-to-manage bacteria, such as Pseudomonas aeruginosa, are the most concerning pathogen, among patients with AECOPD who develop community-acquired pneumonia (CAP).¹⁰ What would be your treatment strategy for patients with AECOPD requiring hospitalisation owing to CAP?

Although Pseudomonas aeruginosa is known as a challenging pathogen to treat, it is not commonly found to be a causative agent of AECOPD. In cases where AECOPD is caused by CAP, the antibiotic treatment strategy should follow the treatment guidelines for CAP. In cases requiring hospitalisation, the recommended approach is to initiate treatment with beta-lactam antibiotics along with macrolides or respiratory fluoroquinolones to effectively cover both bacterial and atypical pathogens.

Concerns regarding Pseudomonas aeruginosa in community-acquired infections arise in patients with chronic structural lung diseases, a history of broad-spectrum antibiotic use, or immunocompromised conditions. The diagnosis of this difficult-to-treat bacteria requires confirmation through culture, especially in situations of community-acquired infection.¹¹

Q4: Based on your clinical experience, what are the key benefits of levofloxacin use compared with other fluoroquinolones and antibiotics used in the management of AECOPD?

Respiratory fluoroquinolones, specifically levofloxacin and moxifloxacin, are the preferred choice of antibiotics for respiratory tract infections, including AECOPD resulting from an infectious process. Although the aforementioned drugs have some pharmacokinetic differences, their pharmacodynamics are highly similar. Of the two options, levofloxacin has demonstrated a favourable clinical safety profile, particularly owing to its lower risk of cardiotoxicity.^{12, 13} Safety reports from clinical trials and post-marketing surveillance indicate that levofloxacin does not appear to be associated with the hepatotoxic and cardiotoxic effects that have been observed with the use of certain fluoroquinolones.¹⁴ Levofloxacin has also shown comparable clinical efficacy to other antibiotics in the management of AECOPD.¹⁵

Q5: Given the poor health condition of patients who develop AECOPD, what are your thoughts on the suitability – in terms of safety and tolerability – of levofloxacin treatment?

AECOPD patients with compromised general health or underlying comorbidities are at an increased risk of experiencing more frequent AECOPD episodes and are also relatively susceptible to Gram-negative bacterial infections.^{16, 17} For such cases, fluoroquinolones are considered the antibiotics of choice. Respiratory fluoroquinolones, in particular, exhibit broad-spectrum activity against both Gram-positive and Gram-negative bacteria, as well as atypical pathogens like Mycoplasma and Chlamydophila.

There have been reports of a significant proportion of respiratory infections involving Mycoplasma pneumoniae strains that are resistant to macrolides.¹⁸ Given this development, levofloxacin, with its established safety profile and lower incidence of adverse drug reactions compared with other fluoroquinolones, is deemed suitable for use in patients with poor general health.¹⁸ The decreased occurrence of adverse drug reactions contributes to improved patient adherence to the prescribed treatment.

Q6: With the emergence of antimicrobial-resistant organisms, what are your opinions on treatment with a 2-day course of levofloxacin compared to a standard 7-day course, in the treatment of patients with AECOPD?

As is commonly known, the prolonged use of antibiotics creates selective pressure on microbes, leading to the emergence of resistant organisms while suppressing susceptible microbes. However, a prospective, randomised, double-blind controlled study has demonstrated that a shorter 2-day course of levofloxacin is non-inferior to the standard 7-day course.¹⁹ This finding was supported by the absence of significant differences in the need for additional antibiotics, intensive care unit (ICU) admission, exacerbation-free interval days, and mortality between the two treatment durations.¹⁹ It is important to note that patients with AECOPD may not necessarily perceive these parameters. Although the one-year re-exacerbation rate was slightly higher in the 2-day course group, this difference did not reach statistical significance.¹⁹ However, the incidence of adverse events was lower in the 2-day course group compared to the 7-day course group.¹⁹ The relatively low incidence of adverse events with the short course was found to contribute to improved patient adherence to the treatment regimen.

References

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