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1
Anthonisen MD, Manfreda J, Warren CPW, Hershfield ES, Harding GKM, Nelson NA. Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Int Med 1987;106:196-204. RATIONALE: Describes the cardinal signs of an infective exacerbation of COPD and the evidence for commencing antibiotics. Randomised double blinded cross-over trial showed a significant benefit from using antibiotics. Success rate with antibiotic therapy 68% vs 55% with placebo.

2
Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for Diagnosis, Management, and Prevention of COPD. Management of exacerbations. Updated December 2009. Discusses the aetiology, pathophysiology and evidence based therapeutic management of COPD. Antibiotic therapy is stratified according to severity of disease. S. pneumoniae, H. influenzae, M. catarrhalis remain the predominant pathogens in mild disease.

3
Chronic obstructive pulmonary disease. Management of COPD in adults in primary and secondary care. NICE Clinical Guideline 12 February 2004. http://guidance.nice.org.uk/CG101 Accessed 23.09.14. RATIONALE: A meta-analysis of nine trials found a small but statistically significant effect favouring antibiotics over placebo in patients with exacerbations of COPD. Effect size 0.22 (95% CI, 0.1 to 0.34). Four studies assessed whether there was a relationship between severity of exacerbation and the effectiveness of antibiotic use. Three of these studies suggest that the worse the COPD severity of exacerbation (lung function impairment (FEV1, PEFR), purulence of sputum) then the greater the degree of benefit from antibiotics.

4
El Moussaoui R, Roede BM, Speelman P, Bresser P, Prins JM, Bossuyt PMM. Short-course antibiotic treatment in acute exacerbations of chronic bronchitis and COPD: a meta-analysis of double-blind studies. Thorax 2008;63:415-22. RATIONALE: In this meta-analysis they concluded that a short course of antibiotic treatment was as effective as the traditional longer treatment in patients with mild to moderate exacerbations of chronic bronchitis and COPD. The meta-analysis included 21 double-blind randomised clinical trials with 10,698 adults with exacerbation of COPD or chronic bronchitis, no antimicrobial therapy at the time of diagnosis and random assignment to antibiotic treatment for less than or equal to 5 days versus more than 5 days. At early follow-up (<25 days), the summary odds ratio (OR) for clinical cure with short treatment versus conventional treatment was 0.99 (95% CI 0.90 to 1.08). At late follow-up the summary OR was 1.0 (95% CI 0.91 to 1.10. No trials of amoxicillin or doxycycline were included in the meta-analysis; however there is no microbiological reason that a 5 day course of these agents would be inferior to a 5 day course of clarithromycin in acute exacerbations of COPD.

The POCAST project is funded by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Healthcare Associated Infections and Antimicrobial Resistance at Imperial College London and by the Imperial College Healthcare Charity (Grant Ref No:7006/P36U).