antimicrobial prescribing in the management of copd dr teck wee boo consultant microbiologist, guh...

Antimicrobial Prescribing in the Management of COPD

Dr Teck Wee BooConsultant Microbiologist, GUHSenior 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%): 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 aetiologyAnthonisen 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)Or 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.

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

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!