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

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

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

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

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

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

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

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

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)

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

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

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

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

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.

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

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

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

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

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

Thank you!