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Antimicrobial Prescribing in the Management of COPD
Dr Teck Wee BooConsultant Microbiologist, GUHSenior Lecturer, Bacteriology, NUI Galway
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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
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Impact of COPD exacerbations
Quality of life – negative impact Accelerate rate of decline in lung
function Significant mortality, esp in
hospitalised patients Socioeconomic costs
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Clinical diagnosis of exacerbation
Acute change of symptoms beyond baseline levels:
Change in purulence of sputum Increase in sputum volume Increase in dyspnoea
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Causes of exacerbation of COPD
Infective causes (~80-85%) Bacterial causes Viral causes
Non-infective causes (~15-20%?) Air pollution Other factors
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Infective causes
Bacterial (50%): Haemophilus influenzae Streptococcus pneumoniae Moraxella catarrhalis Pseudomonas aeruginosa (advanced
disease)
Chlamydophila pneumoniae Mycoplasma pneumoniae ?S. aureus; ?E. coli; ?Pneumocystis
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Infective causes
Viral (20-30%): Rhinovirus Influenza and Parainfluenza viruses Respiratory syncytial virus Others
Mixed (viral-bacterial): Potential synergistic activity
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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
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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 aetiologyAnthonisen et al (1987); Stockley et al
(2000)
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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
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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
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Choice of antimicrobial agents
Most guidelines recommend: Aminopenicillin (eg. amoxicillin or
amoxicillin-clavulanate)Or Macrolide (eg. clarithromycin)Or Tetracycline (eg. doxycycline)
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PO dosages
Amoxicillin 500mg – 1g TDS
Amoxicillin-clavulanate 625mg TDS
Clarithromycin 500mg BD
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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.
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77% 78%89% 93%
82%92%
84%78%
0%
20%
40%
60%
80%
100%
amoxicillin clarithromycin tetracycline TMP-SMZ
Antimicrobial susceptibility of H. influenzae isolates, GUH
2008 2009
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Antimicrobial susceptibility
Respiratory isolates 2008, 2009 Streptococcus pneumoniae:
Penicillin (oral): 10% high-level resistance
Erythromycin: 25-31% resistance Tetracycline: 18-23% resistance
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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
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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
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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
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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
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Thank you!