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Three Part Question

In [a patient with an acute exacerbation of COPD] does [administration of a course of antibiotics] [improve outcome and hasten recovery]?

Clinical Scenario

A 78 year old man with a history of COPD attends the emergency department with a recent increase in shortness of breath, cough and wheeze. You diagnose him as suffering from an exacerbation of COPD and treat him with oxygen, nebulised salbutamol and steroids. You wonder if a course of antibiotics would also be of benefit.

Search Strategy

Medline 1966-11/03 using the Ovid interface. In addition the Cochrane Database of Systematic Reviews was searched and the National Institute of Clinical Excellence website was searched for relevant guidelines.
[{(exp chronic disease OR exp hospitals, chronic disease OR chronic.mp) AND (exp lung disease, obstructive OR obstructive.mp)} OR exp emphysema OR exp pulmonary emphysema OR emphysema.mp OR exp bronchitis OR bronchitis.mp OR exp COPD.mp OR COAD.mp OR airway obstruction.mp] AND [exp acute disease OR acute.mp OR exacerbation.mp] AND [exp antibiotics OR antibiotic$.mp] AND [exp Meta-analysis OR meta-analysis.mp OR exp review literature OR Review.mp OR systematic review.mp OR guideline$.mp OR exp clinical protocol OR protocol.mp]

Search Outcome

Altogether 200 papers were found of which 4 meta-analyses or systematic reviews provided the highest level of evidence.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Saint S et al, 1995, USA	9 randomised trials (n=1101) including inpatients and outpatients with exacerbations of COPD	Meta-analysis	Mortality benefit of antibiotics vs placebo, (effect size transformed into units of standard deviation)	0.22 (95% CI 0.10-0.34)	English language search only Variety of antibiotics combined to produce these figures
			Change in peak expiratory flow rate	Small but significant improvement 10.75 L/min (95% CI, 4.96 to 16.54l/min) (6 trials 836pts)
British Thoracic Society, 1997	Initiated by the Standards of Care Committee of the British SocietyA core group of individuals produced background papers which were collated into a single document. This was discussed over a two day period by a larger group which included respiratory physicians from both teaching and teaching and district general hospitals across the UK, geriatricians, general practitioners, nurses, and public health physicians	Systematic review and guideline	Situations in which antibiotics are proven to be of use in hospital and non hospital settings	When two of the following three are present:1. increased breathlessness2. increased sputum volume3. development of purulent sputumAny patient with pH<7.35 should also receive antibiotics	Paper search strategy may not have been systematic, search methods not fully described
			Duration of treatment	A maximum of 7 days should always be sufficient
			Antibiotic of choice	Oral treatment with common antibiotics such as amoxicillin or tetracycline should be considered 1st choice
Mcrory DC et al, 2001,	Systematic review conducted by a joint panel from the AmericanCollege of Physicians (ACP)-American Society for Internal Medicine (ASIM) and the American Collegeof Chest Physicians (ACCP)	Systematic review	Findings from 11 RCTs looking at antibiotics vs placebo (They found two additional papers to the meta-analysis of Saint et al)	3 papers found a statistical benefit, 3 papers found a non-significant benefit and the remainder showed no benefit. Benefits were larger, the more severe the exacerbation	Study effects were not summarized by meta-analysis
			Number of days of administration	Days of administration ranged from 3 to 10 days in these studies
NICE, 2003	Full NICE guideline for the management of patients with COPDNote: currently only in its 2nd draft. 270 received antibiotics, 92 did not.	Systematic review	Grade A recommendations	Antibiotics should be used to treat exacerbations of COPDassociated with a history of purulent sputumAntibiotics are more likely to be helpful in patients with more severeunderlying disease
			Grade B recommendations	Patients with exacerbations without purulent sputum do not needantibiotic therapy unless there is consolidation on a chestradiograph or clinical signs of pneumonia

Comment(s)

A large number of papers have addressed this question in hospital and community settings. A well conducted meta-analysis by Saint et al found 9 Randomised Controlled Trials in this area and found a statistically significant mortality benefit in patients receiving antibiotics. In addition they showed a significant benefit in terms of Peak expiratory flow rate. Several large groups have published guidelines. The American Colleges joint statement found an additional 2 papers to Saint et al, and concluded that antibiotics were of benefit and that the more severe the exacerbation the greater the benefit. The British Thoracic Society Guidelines state that antibiotics should be used for anyone with 2 of: increased breathlessness, increased production of sputum or purulent sputum. NICE are currently in their second draft for producing new guidelines in this area. In addition to the 11 papers used above they have found 3 more studies of interest. They recommend that all patients with purulent sputum should have antibiotics and that there is greater benefit in patients with more severe underlying disease.

Clinical Bottom Line

Antibiotics improve outcome in acute exacerbations of COPD, especially when associated with purulent sputum, more severe exacerbations or severe underlying disease.

References

1. Saint S, Bent S, Vittinghoff E et al. Antibiotics in COPD exacerbations: A Meta-analysis. JAMA 1995;273(12):957-60.
2. British Thoracic Society Nebulizer Project Group Nebulizer therapy. Guidelines. Thorax 1997;52:Suppl-24.
3. McCrory DC, Brown C, Gelfand SE, et al. Management of acute exacerbations of COPD: a summary and appraisal of published evidence. Chest 2001;119:1190-1209.
4. National Institute of Clinical Excellence. Chronic obstructive pulmonary disease: management of adults with chronic obstructive pulmonary disease in primary and secondary care. 2003 2003