1. Antimicrobial Prescribing in the Management of COPD
Dr Teck Wee Boo
Consultant Microbiologist, GUH
Senior Lecturer, Bacteriology, NUI Galway

2. Exacerbation of COPD Acute event
Worsening of patient’s respiratory symptoms beyond normal day-to-day variations
Leading to a change in medication
- GOLD guidelines 2011

3. Impact of COPD exacerbations
Quality of life – negative impact
Accelerate rate of decline in lung function
Significant mortality, esp in hospitalised patients
Socioeconomic costs

4. Clinical diagnosis of exacerbation
Acute change of symptoms beyond baseline levels:
Change in purulence of sputum
Increase in sputum volume
Increase in dyspnoea

5. Causes of exacerbation of COPD
Infective causes (~80-85%)
Bacterial causes
Viral causes
Non-infective causes (~15-20%?)
Air pollution
Other factors

6. Infective causes Bacterial (50%): Haemophilus influenzae
Streptococcus pneumoniae
Moraxella catarrhalis
Pseudomonas aeruginosa (advanced disease)
Chlamydophila pneumoniae
Mycoplasma pneumoniae
?S. aureus; ?E. coli; ?Pneumocystis

7. Infective causes Viral (20-30%): Mixed (viral-bacterial): Rhinovirus
Influenza and Parainfluenza viruses
Respiratory syncytial virus
Others
Mixed (viral-bacterial):
Potential synergistic activity

9. Pathophysiology Baseline bacterial colonisation ↓
Acute trigger (eg. new bacterial/viral strain)
Acute-on-chronic inflammation
(epithelial adhesion, chemokines, neutrophils)
Increase in respiratory symptoms (+/- systemic)
Development of immune response

10. Antimicrobial therapy in COPD exacerbation
Treatment of bacterial infection in exacerbation of COPD can reduce mortality and treatment failure
Not always easy to distinguish between bacterial vs viral causes
Severity of symptoms
Purulent sputum: increased likelihood of bacterial aetiology
Anthonisen et al (1987); Stockley et al (2000)

11. Antimicrobial therapy in COPD exacerbation
Benefit seen in moderate or severe exacerbations
Anthonisen et al.: greatest benefit from antibiotic Rx in patients with presence of all 3 symptoms (increased dyspnoea, sputum purulence & volume)
Berry et al.; Allegra et al.: benefit of Rx seen in moderate & severe cases

12. Recommendations for antimicrobial therapy
NICE (National Institute for Clinical Excellence, NHS) guideline (2004): antimicrobial Rx for COPD exacerbations associated with history of more purulent sputum
GOLD (Global initiative for chronic Obstructive Lung Disease) (2011): Rx for patients with all 3 symptoms, or 2 symptoms one of which is purulent sputum

13. Choice of antimicrobial agents
Most guidelines recommend:
Aminopenicillin (eg. amoxicillin or amoxicillin-clavulanate) Or
Macrolide (eg. clarithromycin)
Tetracycline (eg. doxycycline)

14. PO dosages Amoxicillin 500mg – 1g TDS
Amoxicillin-clavulanate 625mg TDS
Clarithromycin 500mg BD

15. Choice of antimicrobial agents
Need to be guided by local susceptibility patterns as well
Other considerations:
severity of illness,
risk factors: age ≥65; comorbidities like cardiac disease or diabetes; advanced disease; frequency of exacerbations, recent antibiotics, etc.

17. Antimicrobial susceptibility
Respiratory isolates 2008, 2009
Streptococcus pneumoniae:
Penicillin (oral): 10% high-level resistance
Erythromycin: 25-31% resistance
Tetracycline: 18-23% resistance

18. When to send sputum for culture
Severe cases of exacerbation
Hospitalised patients; mechanical ventilation
Non-response to standard treatment
Frequent Rx courses
Concern re: possibility of P. aeruginosa

19. Duration of treatment Generally: 5-10 days
Meta-analysis (El Moussaoui et al., 2008): 5-day course just as efficacious as 7-10 day course for mild-to-moderate cases
Any risk factors for poorer outcome?
Individual patient’s clinical response

20. Preventative measures
Influenza vaccination
Reduce mortality & severity of illness
Reduce late exacerbations?
Pneumococcal vaccination
No direct evidence of efficacy in reducing pneumococcal exacerbations
But may benefit from reducing incidence of pneumococcal pneumonia

21. Summary
Significant proportion of exacerbations of COPD are due to bacterial pathogens
Treatment of bacterial exacerbation can be beneficial to patient
Sputum purulence should be used to guide indication for antimicrobial therapy
Average Rx duration 5-10 days

22. Thank you!