The role of antibiotics in Chronic Obstructive: Pulmonary Disease
More details
Hide details
3rd Department of Pneumonology, Athens Hospital for Chest Diseases “Sotiria”, Athens, Greece
6th Department of Pneumonology, Athens Hospital for Chest Diseases “Sotiria”, Athens, Greece
Adamantia Liapikou   

3rd Department of Pneumonology, Athens Hospital for Chest Diseases “Sotiria”, Mesogion 152, 11527 Athens, Greece
Pneumon 2013;26(1):84–94
Chronic obstructive pulmonary disease (COPD) is the fourth most common cause of death worldwide. Recurrent acute exacerbation of COPD (AE-COPD) are common attributes of its course, and are related to the progress of the disease and its high cost. In the USA, that cost is estimated at $7,757 per exacerbation, mainly due to hospitalization expenses. Patients with repeated acute exacerbations rapidly display reduced lung function and they have a prolonged recovery time and an increased likelihood of suffering from depression or stress, which may consequently lead to a poorer quality of life. Given the fact that almost half of AE-COPD episodes are the outcome of infection, the administration of antimicrobial medication is recommended for patients suffering from exacerbations or severe COPD. In order to administer antibiotics correctly, the risk factors involved in the exacerbation and the choice of the appropriate antibiotics for patients of low and high risk should be taken into consideration. In accordance with the international guidelines, the prophylactic use of antibiotics for patients with COPD is not recommended, although ongoing clinical trials are reevaluating the administration of macrolides as a means of preventing exacerbations, based on their anti-inflammatory properties.
Sobradillo-Pena V, Miravitlles M, Gabriel R, et al. Geographic variations in prevalence and underdiagnosis of COPD: results of the IBERPOC multicentre epidemiological study. Chest 2000; 118: 981–989.
Quon BS, Gan WQ, Sin DD. Contemporary management of acute exacerbations of COPD: a systematic review and metaanalysis. Chest 2008; 133(3): 756-66. Review.
Berkius J, Nolin T, Mårdh C, Karlström G, Walther SM; Swedish Intensive Care Registry. Characteristics and long-term outcome of acute exacerbations in chronic obstructive pulmonary disease: an analysis of cases in the Swedish Intensive Care Registry during 2002-2006. Acta Anaesthesiol Scand 2008; 52(6): 759-765.
Papi A, Bellettato CM, Braccioni F, et al. Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations. Am J Respir Crit Care Med 2006; 173: 1114–1121.
Falagas ME, Avgeri SG, Matthaiou D, et al. Short- verus longduration antimicrobial treatment for exacerbations of chronic bronchitis: a meta-analysis. J Antimic Chemother 2008; 62:442- 450.
Miravitlles M, Marín A, Monsó E, et al. Colour of sputum is a marker for bacterial colonization in chronic obstructive pulmonary disease. Respir Res 2010; 11:58.
Rosell A, Monsó E, Soler N, et al. Microbiologic determinants of exacerbation in chronic obstructive pulmonary disease. Arch Intern Med 2005; 165: 891-897.
Monso E, Rosell A, Bonet G, et al. Risk factors for lower airway bacterial colonization in chronic bronchitis. Eur Resp J 1999; 13: 338-342.
Wilkinson TM, Patel IS, Wilks M, Donaldson GC, Wedzicha JA. Airway bacterial load and FEV1 decline in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2003;167(8):1090-1095. Epub 2003 Jan 24.
Sethi S. Infection as a comorbidity of COPD. Eur Respir J 2010; 35: 1209-1215.
Monsó E, Ruiz J, Rosell A, et al. Bacterial infection in chronic obstructive pulmonary disease.A study of stable and exacerbated outpatients using the protected specimen brush. Am J Respir Crit Care Med 1995; 152:1316-1320.
Bandi V, Apicella MA, Mason E, et al. Nontypeable Haemophilus influenzae in the lower respiratory tract of patients with chronic bronchitis. Am J Respir Crit Care Med 2001; 164:2114-2119.
Soler N, Ewig S, Torres A, Filella X, Gonzalez J, Zaubet A. Airway inflammation and bronchial microbial patterns in patients with stable chronic obstructive pulmonary disease. Eur Respir J 1999; 14: 1015-1022.
Wenzel RP, Fowler AA 3rd, Edmond MB. Antibiotic prevention of acute exacerbations of COPD. N Engl J Med 2012; 367(4): 340-347. Review.
Soler N, Torres A, Ewig S, et al. Bronchial microbial patterns in severe exacerbations of chronic ostbructive pulmonary disease (COPD) requiring mechanical ventilation. Am J Respir Crit Care Med 1998; 157: 1498-1505.
Patel IS, Seemungal TA, Wilks M, Lloyd-Owen SJ, Donaldson GC, Wedzicha JA. Relationship between bacterial colonisation and the frequency, character, and severity of COPD exacerbations. Thorax 2002; 57(9): 759-764.
Sethi S, Maloney J, Grove L, Wrona C, Berenson CS. Airway inflammation and bronchial bacterial colonization in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2006; 173: 991-998.
18. Global Strategy for Diagnosis, Management, and Prevention of COPD. December 2011.
American Thoracic Society/European Respiratory Society Task Force. Standards for the diagnosis and management of patients with COPD. Version 1.2. New York, NY: American Thoracic Society 2004.
Eller J, Ede A, Schaberg T, Niederman MS, Mauch H, Lode H. Infective exacerbations of chronic bronchitis: relation between bacteriologic etiology and lung function. Chest 1998; 113(6): 1542-1548.
Miravitlles M, Espinosa C, Fernández-Laso E, Martos JA, Maldonado JA, Gallego M. Relationship between bacterial flora in sputum and functional impairment in patients with acute exacerbations of COPD. Study Group of Bacterial Infection in COPD. Chest 1999; 116(1): 40-46.
Sethi S, Wrona C, Grant BJ, Murphy TF. Strain-specific immune response to Haemophilus influenzae in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2004; 169: 448–453.
Berenson CS, Garlipp MA, Grove LJ, Maloney J, Sethi S. Impaired phagocytosis of nontypeable Haemophilus influenzae by human alveolar macrophages in chronic obstructive pulmonary disease. J Infect Dis 2006; 194(10):1375–1384.
Hiltke TJ, Schiffmacher AT, Dagonese AJ, Sethi S, Murphy TF. Horizontal transfer of the gene encoding outer membrane protein P2 of nontypeable Haemophilus influenzae, in a patient with chronic obstructive pulmonary disease. J Infect Dis 2003; 188(1):114–117.
Murphy TF, Kirkham C. Biofilm formation by nontypeable Haemophilus influenzae: strain variability, outer membrane antigen expression and role of pili. BMC Microbiol 2002; 2:7.
Khair OA, Davies RJ, Devalia JL. Bacterial-induced release of inflammatory mediators by bronchial epithelial cells. Eur Respir J 1996; 9(9):1913–1922.
Eldika N, Sethi S. Role of nontypeable Haemophilus influenzae in exacerbations and progression of chronic obstructive pulmonary disease. Curr Opin Pulm Med 2006;12(2):118–124.
Fahy JV, Dickey BF. Airway mucus function and dysfunction. N Engl J Med 2010;363(23):2233–2247.
Diederen BM, van der Valk PD, Κluytmans JA, et al. The role of atypical pathogens in exacerbations of chronic obstructive pulmonary disease. Eur Respir J 2007; 30 (2): 240-244.
Blasi F, Damato S, Cosentini R, et al. Chlamydia pneumoniae and chronic bronchitis: association with severity and bacterial clearance following treatment. Thorax 2002; 57: 672–676.
Lieberman D, Lieberman D, Ben-Yaakov M, et al. Serological evidence of Mycoplasma pneumoniae infection in acute exacerbation of COPD. Diagn Microbiol Infect Dis 2002; 44: 1–6.
Rohde G, Wiethege A, Borg I, et al. Respiratory viruses in exacerbations of chronic obstructive pulmonary disease requiring hospitalization: a case-control study. Thorax 2003; 58(1): 37-42.
Quint JK, Donaldson GC, Goldring JJ, et al. Serum IP-10 as a biomarker of human rhinovirus infection at exacerbation of COPD. Chest 2010; 137: 812–822.
Daniels J, Snijders D, Lutter R, et al. Procalcitonin versus Creactive protein in the management of severe acute exacerbations of COPD. Chest 2010; 138: 1108-1115.
Woodhead M, Blasi F, Ewig S, et al; Joint Taskforce of the ERS and ESCMID. Guidelines for the management of adult lower respiratory tract infections--full version. Clin Microbiol Infect. 2011; 17 Suppl 6:E1-59.
Evensen A. Management of COPD exacerbations. Am Fam Physician 2010; 81(5): 607-613.
Siddiqi A, Sethi S. Optimizing antibiotic selection in treating COPD exacerbations. International Journal of COPD 2008; 3(1): 31-44.
Dev D, Wallace E, Sankaran R, et al. Value of C-reactive protein measurements in exacerbations of chronic obstructive pulmonary disease. Respir Med 1998; 92(4):664-667.
Wedzicha JA, Seemungal TA, MacCallum PK, et al. Acute exacerbations of chronic obstructive pulmonary disease are accompanied by elevations of plasma fibrinogen and serum IL-6 levels. Thromb Haemost 2000; 84(2): 210-215.
Bafadhel M, Clark TW, Reid C, et al. Procalcitonin and C-reactive protein in hospitalized adult patients with community-acquired pneumonia or exacerbation of asthma or COPD. Chest 2011; 139: 1410-1418.
Soler N, Esperatti M, Ewig S, Huerta A, Agusti C, Torres A. Sputum purulence-guided antibiotic use in hospitalized patients with exacerbations of COPD. Eur Respir J 2012. In press.
Lindenauer PK, Pekow P, Gao S, et al. Quality of care for patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease. Ann Intern Med 2006; 144: 894–903.
Anthonisen NR, Manfreda J, Warren CP, et al. Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Intern Med 1987; 106: 196-204.
Blasi F, Ewig S, Torres A, et al. A review of guidelines for antibacterial use in acute exacerbations of chronic bronchitis. Pulm Pharmacol Ther 2006, 19: 361–9.
Wilson R. Treatment of COPD exacerbations: antibiotics. Eur Respir Rev, 2005; 14: 32–8.
Stockley RA, O’Brien C, Pye A, Hill SL. Relationship of sputum colour to nature and outpatient management of acute exacerbations of COPD. Chest 2000; 117(6): 1638-1645.
Montero M, Dominguez M, Orozco-Levi M, Salvado M, Knobel H. Mortality of COPD patients infected with multi-resistant Pseudomonas aeruginosa: a case and control study. Infection 2009; 37:16–19.
Garcia-Vidal C, Almagro P, Romaní V, et al. Pseudomonas aeruginosa in patients hospitalized for COPD exacerbation: a prospective study. Eur Respir J 2009; 34(5):1072-1078.
Ram FSF, Rodriguez-Roisin R, Granados-Navarrete A, et al. Antibiotics for exacerbations of chronic obstructive pulmonary disease (review).The Cochrane Library 2009, issue 2.
Vanhoof R, Camps K, Carpentier M, et al. 10th survey of antimicrobial resistance in noninvasive clinical isolates of Streptococcus pneumoniae collected in Belgium during winter 2007-2008. Pathol Biol (Paris). 2010 Apr; 58(2):147-51. doi: 10.1016/j.patbio.2009.07.018.Epub 2009 Nov 4.
Peterson LR. Penicillins for treatment of pneumococcal pneumonia: does in vitro resistance really matter? Clin Infect Dis 2006; 42:224-33.
Daneman N, McGeer A, Green K, Low DE; Toronto Invasive Bacterial Diseases Network. Macrolide resistance in bacteremic pneumococcal disease: implications for patient management. Clin Infect Dis. 2006 Aug 15;43(4):432-8. Epub 2006 Jul 7.
Niederman M, Luna C. Community Acquired Pneumonia Guidelines: A Global Perspective. Semin Respir Crit Care Med 2012; 33:298–310.
Bouza E, García-Garrote F, Cercenado E, et al. Pseudomonas aeruginosa: A survey of resistance in 136 hospitals in Spain. The Spanish Pseudomonas aeruginosa Study Group. Antimicrob Agents Chemother 1999; 43: 981-2.
Anzueto A, Miravitlles M. Short-course fluoroquinolone therapy in exacerbations of chronic bronchitis and COPD. Respir Med. 2010; 104(10): 1396-403. Review.
El Moussaoui R, Roede BM, Speelman P, Bresser P, Prints M, Bossuyt PMM. Short-course antibiotic treatment in acute exacerbations of chronic bronchitis and COPD: meta-analysis of doube-blind studies. Thorax 2008; 63:415-422.
Grossman RF, Ambrusz ME, Fisher AC, Khashab MM, Kahn JB. Levofloxacin 750 mg QD for five days versus amoxicillin/ clavulanate 875 mg/125 mg BID for ten days for treatment of acute bacterial exacerbation of chronic bronchitis: a post hoc analysis of data from severely ill patients. Clin Ther 2006 Aug;28(8):1175-1180.
Chodosh S, DeAbate CA, Haverstock D, Aneiro L, Church D. Short-course moxifloxacin therapy for treatment of acute bacterial exacerbations of chronic bronchitis. The Bronchitis Study Group. Respir Med 2000 Jan; 94(1):18-27.
Daniels JM, Snijders D, de Graaff CS, et al. Antibiotics in addition to systemic corticosteroids for acute exacerbations of COPD. Am J Respir Crit Care Med 2010; 181: 150–157.
Effing TW, Kerstjens AM, Monninkhof EM, et al. Definitions of exacerbations. Does it really matter in clinical trials on COPD? Chest 2009; 136: 918-992.
Miravitlles M. Do we need new antibiotics for treating exacerbations of COPD? Ther Adv Respir Dis 2007; 1(1): 61-76.
Rothberg MB, Pekow PS, Lahti M, et al. Antibiotic therapy and treatment failure in patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease. JAMA 2010; 303: 2035–2042.
Calverley PM, Anderson JA, Celli B, et al. Salmeterol and fluticasone proprionate and survival in chronic obstructive pulmonary disease. N Engl J Med 2007; 356: 775–789.
Nannini L, Cates CJ, Lasserson TJ, et al. Combined corticosteroid and long-acting b-agonist in one inhaler versus placebo for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2007; 4: CD003794.
Restrepo MI, Mortensen EM, Pugh JA, et al. COPD is associated with increased mortality in patients with community-acquired pneumonia. Eur Respir J 2006; 28: 346–351.
Garcia-Vidal C, Calbo E, Pascual V, et al. Effects of systemic steroids in patients with severe community-acquired pneumonia. Eur Respir J 2007.
Liapikou A, Polverino E, Ewig S, et al. Severity and Outcomes of hospitalised community-acquired pneumonia in COPD patients. Eur Respir J 2011 Sep 20.
Miravitlles M. Prevention of exacerbations of COPD with pharmacotherapy. Eur Repir Rev 2010; 19 (116): 119-126.
Black PN, McDonald CF. Interventions to reduce the frequency of exacerbations of chronic obstructive pulmonary disease. Postgrad Med J 2009; 85: 141-147.
Black P, Staykova T, Chacko E, et al. Prophylactic antibiotic therapy for chronic bronchitis. Cochrane Database Syst Rev 2003; 1: CD004105.
Suzuki T, Yamaya M, Sekizawa K, et al. Erythromycin inhibits rhinovirus infection in cultured human tracheal epithelial cells. Am J Respir Crit Care Med 2002; 165:1113–1118.
Jang YJ, Kwon H-J, Lee BJ. Effects of clarithromycin on rhinovirus-16 infection in A549 cells. Eur Respir J 2006; 27:12–19.
Labro MT, Abdelghaffer H. Immunomodulation by macrolide antibiotics. J Chemother 2001; 13:3–8.
Hodge S, Hodge G, Jersmann H, et al. Azithromycin improves macrophage phagocytic function and expression of mannose receptor in COPD. Am J Respir Crit Care Med 2008; 178:139–148.
Kanoh S, Rubin BK. Mechanisms of action and clinical application of macrolides as immunomodulatory medications. Clin Microbiol Rev 2010; 23(3):590-615. Review.
Banerjee D, Khair OA, Honeybourne D. The effect of oral clarithromycin on health status and sputum bacteriology in stable COPD. Respir Med 2005; 99(2): 208-215.
Seemungal TAR, Wilkinson TMA, Hurst JR, Perera WR, Sapsford RJ, Wedzicha JA. Long-term erythromycin therapy is associated with decreased chronic obstructive pulmonary disease exacerbations. Am J Respir Crit Care Med 2008; 178(11): 1139-1147. Epub 2008 Aug 21.
Lange P. Chronic obstructive pulmonary disease and risk of infection. Pneumonol Alergol Pol 2009; 77: 284-288.
Sethi S, Jones PW, Theron MS, et al. Pulsed moxifloxacin for the prevention of exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial. Respiratory research 2010; 11:10.
Albert RK, Connett J, Bailey WC, et al. Azithromycin for prevention of exacerbations of COPD. N Engl J Med 2011; 365: 689-698.