When to Use Antibiotics in Acute Exacerbation of Chronic Obstructive
Pulmonary Disease
Stephanie Manning, Pharm.D. CandidateOUHSC College of Pharmacy
Seminar – PHAR 7970March 10, 2011
Summary of Topics
• COPD overview– Epidemiology, definition, and pathogenesis
• Current research
• Current guidelines
• Application of research data
• Future directions
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Objectives
1. Identify 3 symptoms which change acutely during a COPD exacerbation.
2. Outline the 5 components of the proposed model of pathogenesis of bacterial exacerbations.
3. Assess the need for antibiotic therapy in a patient experiencing a COPD exacerbation according to current guidelines.
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Overview of COPD
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Question
The fourth leading cause of death in the United States is:
a) Heart disease
b) Cancer
c) Chronic obstructive pulmonary disease (COPD)
d) Cerebrovascular accidents
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EpidemiologyPrevalence• 2001: 12.1 million over age 25 in the U.S.• > 40 years of age• Men > Women
Morbidity and Mortality• 8 million office/hospital outpatient visits and 1.5 million ER
visits in the U.S. in the year 2000• Men: 46.4 deaths per 100,000• Women: 34.2 deaths per 100,000
Centers for Disease Control and Prevention Chronic Obstructive Pulmonary Disease (COPD) page. CDC website: http://www.cdc.gov/copd/data.htmGlobal Strategy for the Diagnosis, Management and Prevention of COPD, 2010. Available from: http://www.goldcopd.org.Williams DM, et al. Chronic Obstructive Pulmonary Disease. In: DiPiro JT, et al, eds. Pharmacotherapy: a pathophysiologic approach. 7th ed, 2008.
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Stable COPD• Chronic disease
• Loss of lung function
• Airflow limitation and abnormal inflammatory response
• Diagnosis based on:– Symptoms– History of exposure: tobacco smoke, occupational dusts
and chemicals
Williams DM, Bourdet SV. Chronic Obstructive Pulmonary Disease. In: DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: a pathophysiologic approach. 7th ed. McGraw-Hill Companies, Inc; 2008: 495-499. 7
Exacerbation of COPD• Acute change in baseline symptoms:
– Dyspnea, cough, and/or sputum production
• Consequences:– Decreased quality of life– Accelerated lung function decline– Increased mortality– Increased resource utilization and costs
Williams DM, Bourdet SV. Chronic Obstructive Pulmonary Disease. In: DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: a pathophysiologic approach. 7th ed. McGraw-Hill Companies, Inc; 2008: 495-499.
Can Respir J 2008;15 (Suppl A):1A-8A. 8
Exacerbation: Goals of Therapy• Prevention of hospitalization or reduction in
hospital stay
• Prevention of acute respiratory failure and death
• Resolution of symptoms
• Return to baseline
Williams DM, Bourdet SV. Chronic Obstructive Pulmonary Disease. In: DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: a pathophysiologic approach. 7th ed. McGraw-Hill Companies, Inc; 2008: 495-499. 9
Pathogenesis and Infection
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Etiology of COPD Exacerbations
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Infectious Noninfectious
~20% Mucoid Sputum
~20% Mucoid Sputum
Viral
~40-50%~40-50%Atypical
~5-10%Bacterial-viral co-
infection may occur
~5-10%Bacterial-viral co-
infection may occur
Bacterial
~40-50%~40-50%
Allergies, smoking, pollution, stress;
undertreatment or nonadherence in established COPD
Allergies, smoking, pollution, stress;
undertreatment or nonadherence in established COPD
Anzueto A. Primary care management of chronic obstructive pulmonary disease to reduce exacerbations and their consequences. Am J Med Sci. 2010;340(4):309-318.
Purulent SputumPurulent Sputum
Bacteria as a Cause of Exacerbation• Common bacteria:
– Haemophilus influenzae– Streptococcus pneumoniae– Moraxella catarrhalis– Pseudomonas aeruginosa
• Indicators of bacterial infection– Bronchoscopic sampling in pooled analysis of studies– Purulent sputum
Sethi S, Murphy TF. Infection in the pathogenesis and course of chronic obstructive pulmonary disease. N Engl J Med. 2008;359:22. 12
Proposed Model of Pathogenesis
Acquire new bacterial strain
Change in airway/systemic inflammation
Change in airway/systemic inflammation
Pathogen virulenceHost lung defense
Pathogen virulenceHost lung defense
Increased respiratory symptoms
Increased respiratory symptoms
Strain-specific immune response,
+/- Antibiotics
Strain-specific immune response,
+/- Antibiotics
Elimination of infecting strainElimination of infecting strain
Sethi S, Murphy TF. Infection in the pathogenesis and course of chronic obstructive pulmonary disease. N Engl J Med. 2008;359:22. 13
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Adapted from Sethi S, Murphy TF. Infection in the pathogenesis and course of chronic obstructive pulmonary disease. N Engl J Med . 2008;359:22.
Innate Lung Defense
• Disruption of innate lung defense
• Impaired mucociliary clearance
• Impaired phagocytosis of alveolar macrophage
• Epithelial cells as physical barrier and orchestrators of host defense
Proposed Model of Pathogenesis
Acquire new bacterial strain
Acquire new bacterial strain
Change in airway/systemic inflammation
Change in airway/systemic inflammation
Pathogen virulenceHost lung defense
Pathogen virulenceHost lung defense
Increased respiratory symptoms
Increased respiratory symptoms
Strain-specific immune response,
+/- Antibiotics
Strain-specific immune response,
+/- Antibiotics
Elimination of infecting strainElimination of infecting strain
Sethi S, Murphy TF. Infection in the pathogenesis and course of chronic obstructive pulmonary disease. N Engl J Med. 2008;359:22. 15
COPD Exacerbation Treatment: Role of Antibiotics
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Exacerbation Treatment
• Oxygen therapy
• Dose/frequency of bronchodilators
• Glucocorticosteroids
• Mechanical ventilation
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• Antibiotics
Global Strategy for the Diagnosis, Management and Prevention of COPD, 2010. Available from: http://www.goldcopd.org.
Controversy Over Antibiotic Use
• Overuse can lead to resistance
• 20% of exacerbations are noninfectious
• Mixed results from studies
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Current Research
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Ofloxacin vs. Placebo
• Study design: Prospective randomized controlled trial
• Objective
• Therapy: ofloxacin vs. placebo
• Primary outcome measures
20Nouira S, et al. Once daily oral ofloxacin in chronic obstructive pulmonary disease exacerbation requiring mechanical ventilation; a randomised placebo-controlled trial. Lancet. 2001;358:2020-25.
Results
21Nouira S, et al. Once daily oral ofloxacin in chronic obstructive pulmonary disease exacerbation requiring mechanical ventilation; a randomised placebo-controlled trial. Lancet. 2001;358:2020-25.
Doxycycline vs. Placebo
• Study design: Prospective randomized controlled trial
• Objective
• Therapy: doxycycline vs. placebo
• Primary and secondary outcome measures
22Daniels, et al. Antibiotics in addition to systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2010;181:150-157.
Results
23Daniels, et al. Antibiotics in addition to systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2010;181:150-157.
Early Antibiotic Administration
• Study design: Retrospective cohort
• Objective
• Primary and secondary outcome measures
24Rothberg MB, et al. Antibiotic therapy and treatment failure in patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease. JAMA. May 2010;303(20):2035-2042.
Cohort Study Design
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Treatment Failure
No Treatment Failure
Treatment Failure
No Treatment Failure
Study design. Duke University Medical Center Library. http://www.mclibrary.duke.edu/subject/ebm/studies.html. last modified 8-26-2008. (Accessed 2-28-2011).
Results
26Rothberg MB, et al. Antibiotic therapy and treatment failure in patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease. JAMA. May 2010;303(20):2035-2042.
Treatment Failure Length of Stay & Cost
Non-Hospitalized Exacerbation Patients
• Study design: Systematic review
• Objective
• Study subjects
27Ram FSF, et al. Antibiotics for exacerbations of chronic obstructive pulmonary disease (Review). Cochrane Database Sys. Rev. (2): CD004403, 2006.
Results
28Ram FSF, et al. Antibiotics for exacerbations of chronic obstructive pulmonary disease (Review). Cochrane Database Sys. Rev. (2): CD004403, 2006.
Current Guidelines
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GOLD Guidelines
Antibiotics should be given to patients with:
• All 3 cardinal symptoms:– dyspnea– sputum volume– sputum purulence
• 2 of the cardinal symptoms if sputum purulence included
• Severe exacerbation requiring mechanical ventilation30Global Strategy for the Diagnosis, Management and Prevention of COPD, 2010. Available from: http://www.goldcopd.org.
Application of Research Data
• Continue to use antibiotics in severe exacerbations requiring mechanical ventilation
• Limit antibiotic use to those patients requiring hospitalization for their exacerbation
• Administer antibiotics early, if necessary, within first 2 days of hospital admission
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Future Directions: Serum C-Reactive Protein (CRP) Guidance
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Subgroup Analysis in Doxycycline Study
Daniels, et al. Antibiotics in addition to systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2010;181:150-157.
Future Directions:Procalcitonin Guidance
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• Randomized controlled trial
• Standard therapy group vs. procalcitonin group
• Equivalent clinical success rate (p = 0.853)
Stolz D, et al. Antibiotic treatment of exacerbations of COPD: a randomized, controlled trial comparing procalcitonin-guidance with standard therapy. Chest 2007;131:9-19.
Review of Topics
• COPD overview– Epidemiology, definition, and pathogenesis
• Current research
• Current guidelines
• Recommendations
• Future directions
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Questions?
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