Ein neues Konzept der antimikrobiellen Therapie von Patienten mit akuter Exazerbation der chronisch-obstruktiven Lungenerkrankung (COPD)

Zusammenfassung

In der Praxis stellt die antimikrobielle Therapie einen festen Bestandteil in der Behandlung von Patienten mit akuter Exazerbation der COPD dar. Demgegenüber ist die Datenlage für eine solche Therapie sehr begrenzt. Die meisten Plazebo-kontrollierten Studien entsprechen nicht mehr den methodischen Standards, die aktuell gefordert werden müssen. Aus den verfügbaren Daten wird ein Konzept der antimikrobiellen Therapie entwickelt, das zu einer restriktiven Indikationsstellung für eine solche Therapie anleitet. Die wichtigsten Punkte dieses Konzepts umfassen dabei die Orientierung des Behandlungsortes sowie der Indikation zur antimikrobiellen Therapie am Schweregrad der akuten Exazerbation (nicht primär der COPD) sowie am Typ der Exazerbation (Typ I nach Anthonisen). Die Differenzialindikation erfolgt entsprechend einer intraindividuellen Rotation zur Begrenzung des antimikrobiellen Selektionsdrucks. Das vorgestellte Konzept kann gleichzeitig heute schon klinische Anwendung finden und einen Rahmen für die Bearbeitung offener Fragen in künftigen Studien darstellen.

Abstract

In practice, antimicrobial treatment is usually thought to be regularly indicated in the treatment of patients with acute exacerbations of COPD. However, data supporting this practice are very limited. Most placebo-controlled studies do not satisfy currently required methodological quality standards. We develop a concept of restrictive indications for antimicrobial treatment from the available data. Cornerstones of this concept include the selection of treatment setting as well as the indication for antimicrobial treatment according to the severity of the acute exacerbation (not primarily of COPD) and to the type of exacerbation (Anthonisen type I). The selection of antimicrobial agents is based on an intraindividual rotation concept in order to limit antimicrobial selection pressure. The concept presented here can at the same time be used as a clinical guide as well as a framework for future studies dealing with currently unresolved issues.

Literatur

• 1 Celli B R, MacNee W,. ATS/ERS Task Force . Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper.  Eur Respir J. 2004;  23 932-946
• 2 Guidelines for the diagnosis and treatment chronic obstructive bronchitis and pulmonary emphysema issued by Deutsche Atemwegsliga and Deutsche Gesellschaft für Pneumologie.  Pneumologie. 2002;  56 704-738
• 3 Woodhead M, Blasi F, Ewig S. et al . Guidelines for the management of adult lower respiratory tract infections.  Eur Respir J. 2005;  26 1138-1180
• 4 Höffken G, Lorenz L, Kern W. et al . S3-Leitlinie zu ambulant erworbener Pneumonie und tiefen Atemwegsinfektionen.  Pneumologie. 2005;  59 612-664
• 5 Cabello H, Torres A, Celis R. et al . Bacterial colonization of distal airways in healthy subjects and chronic lung disease: a bronchoscopic study.  Eur Respir J. 1997;  10 1137-1144
• 6 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
• 7 Riise G C, Larsson S, Larrson P. et al . The intrabronchial microbial flora in chronic bronchitis patients: a target for N-acetylcysteine therapy?.  Eur Respir J. 1994;  7 94-101
• 8 Soler N, Ewig S, Torres A. et al . Airway inflammation and bronchial microbial patterns in stable patients with chronic obstructive pulmonary disease (COPD).  Eur Respir J. 1999;  14 1015-1022
• 9 Zalacain R, Sobradillo V, Amilibia J. et al . Predisposing factors to bacterial colonization in chronic obstructive pulmonary disease.  Eur Respir J. 1999;  13 343-348
• 10 Patel I S, Seemungal T AR, Wilks M. et al . Relationship between bacterial colonization and the frequency, character, and severity of COPD exacerbations.  Thorax. 2002;  57 759-764
• 11 Seemungal T, Harper-Owen R, Bhowmik A. et al . Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 2001;  164 1618-1623
• 12 Sethi S, Evans N, Grant B JB. et al . New strains of bacteria and exacerbations of chronic obstructive pulmonary disease.  N Engl J Med. 2002;  347 465-471
• 13 Donaldson G C, Seemungal T AR, Bhowmik A. et al . Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease.  Thorax. 2002;  57 847-852
• 14 Wilkinson T MA, Patel I S, Wilks M. et al . Airway bronchial load and FEV₁ decline in patients with chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 2003;  167 1090-1095
• 15 Anzueto A, Niederman M S, Tillotson G S. Etiology, susceptibility, and treatment of acute bacterial exacerbations of complicated chronic bronchitis in the primary care setting: ciprofloxacin 750 mg b. i. d. versus clarithromycin 500 mg b. i. d. Bronchitis study group.  Clin Ther. 1998;  20 885-900
• 16 Fagon J Y, Chastre J, Trouillet J L. et al . Characterisation of distal microflora during acute exacerbations of chronic bronchitis.  Am Rev Respir Dis. 1990;  142 1004-1008
• 17 Soler N, Torres A, Ewig S. et al . Bronchial microbial patterns in severe exacerbations of chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation.  Am J Respir Crit Care Med. 1998;  157 1498-1505
• 18 Beaty C D, Grayston J T, Wang S P. et al . Chlamydia pneumoniae, strain TWAR, infection in patients with chronic obstructive pulmonary disease.  Am Rev Respir Dis. 1991;  144 1408-1410
• 19 Blasi F, Legnani D, Lombardo W M. et al . Chlamydia pneumoniae infection in acute exacerbations of chronic obstructive pulmonary disease (COPD).  Eur Respir J. 1993;  6 19-22
• 20 Mogulkoc N, Karakurt S, Isalska B. et al . Acute purulent exacerbation of chronic obstructive pulmonary disease and Chlamydia pneumoniae infection.  Am J Respir Crit Care Med. 1999;  160 349-353
• 21 McHardy V U, Inglis J M, Calder M A. A study of infective and other factors in exacerbations of chronic bronchitis.  Br J Dis Chest. 1980;  74 228-238
• 22 McNamara M J, Philipas I A, Williams O B. Viral and mycoplasma pneumoniae infections in exacerbations of chronic lung disease.  Am Rev Respir Dis. 1969;  100 19-24
• 23 Smith C B, Golden C A, Kanner R E. et al . Association of viral and mycoplasmal infections with respiratory illness in patients with chronic obstructive pulmonary diseases.  Am Rev Respir Dis. 1980;  121 225-232
• 24 Buscho R O, Saxtan D, Shultz P S. et al . Infection with viruses and Mycoplasma pneumoniae during exacerbations of chronic bronchitis.  J Infect Dis. 1978;  137 377-383
• 25 Lieberman D, Lieberman D, Shmarkov O. et al . Serological evidence of Legionella species infection in acute exacerbation of COPD.  Eur Respir J. 2002;  19 392-397
• 26 Rohde G, Wiethege A, Borg I. et al . Respiratory viruses in exacerbations of chronic obstructive pulmonary disease requiring hospitalisation: a case-control study.  Thorax. 2003;  58 37-42
• 27 Smith C B, Golden C A, Klauber M R. et al . Interactions between viruses and bacteria in patients with chronic bronchitis.  J Infect Dis. 1976;  134 552-561
• 28 Saint S, Bent S, Vittinghoff E. et al . Antibiotics in chronic obstructive pulmonary disease exacerbations: a meta-analysis.  JAMA. 1995;  273 957-960
• 29 Sachs A PE, Koeter G H, Groenier K H. et al . Changes in symptoms, peak expiratory flow, and sputum flora during treatment with antibiotics of exacerbations in patients with chronic obstructive pulmonary disease in general practice.  Thorax. 1995;  50 758-763
• 30 Nouria S, Marghli S, Belghith M. et al . Once daily oral ofloxacin in chronic obstructive pulmonary disease exacerbation requiring mechnical ventilation: a randomized placebo-controlled trial.  Lancet. 2001;  358 2020-2025
• 31 Anthonisen N, Manfreda J, Warren C PW. et al . Antibiotic therapy in excerbations of chronic obstructive pulmonary disease.  Ann Intern Med. 1987;  106 196-204
• 32 Jorgensen A F, Coolidge J, Pedersen P A. et al . Amoxicillin in treatment of acute uncomplicated exacerbations of chronic bronchitis.  Scand J Prim Health. 1992;  16 7-11
• 33 Nicotra M B, Rivera M, Awe R J. Antibiotic therapy of acute exacerbations of chronic bronchitis.  Ann Intern Med. 1982;  97 18-21
• 34 Stockley R A, O'Brien C, Pye A. et al . Relationship of sputum colour to nature and outpatient management of acute exacerbations of COPD.  Chest. 2000;  117 1638-1645
• 35 Ball P, Harris J M, Lowson D. et al . Acute infective exacerbations of chronic bronchitis.  Quart J Med. 1995;  88 61-68
• 36 Dewan N A, Rafique S, Kanwar B. et al . Acute exacerbation of COPD. Factors associated with poor treatment outcome.  Chest. 2000;  117 662-671
• 37 Adams S, Melo J, Luther M. et al . Antibiotics are associated with lower relapse rates in outpatients with acute exacerbations of COPD.  Chest. 2000;  117 1345-1352
• 38 Wilson R, Allegra L, Huchon G. et al . Short-term and long-term outcomes of moxifloxacin compared to standard antibiotic treatment in acute exacerbations of chronic bronchitis.  Chest. 2004;  125 953-964
• 39 Seneff M G, Wagner D P, Wagner R P. et al . Hospital and 1-year survival of patients admitted to intensive care units with acute exacerbation of chronic obstructive pulmonary disease.  JAMA. 1995;  274 1852-1857
• 40 Gunen H, Hacievliyagil S S, Kosar F. et al . Factors affecting survival of hospitalised patients with COPD.  Eur Respir J. 2005;  26 234-241
• 41 European Study on Community-acquired pneumonia (ESOCAP) Commitee . Guidelines for management of adult community-acquired lower respiratory tract infections.  Eur Respir J. 1998;  11 986-991
• 42 Eller J, Ede A, Schaberg T. et al . Infective exacerbations of chronic obstructive pulmonary disease. Relation between bacteriologic etiology and lung function.  Chest. 1998;  113 1542-1548
• 43 Miravitlles M, Espinosa C, Fernandez-Laso E. et al . Relationship between bacterial flora in sputum and functional impairment in patients with acute exacerbations of COPD.  Chest. 1999;  116 40-46
• 44 Brauers J, Bagel S, Kresken M. Ambulant erworbene Atemwegsinfektionen. Resistenzen bakterieller Erreger gegenüber Antibiotika in Deutschland.  Med Welt. 2004;  10 327-331
• 45 Miravittles M, Torres A. No more equivalence trials for antibiotics in exacerbations of COPD, please.  Chest. 2004;  125 811-813
• 46 Chodosh S, Schreurs A, Siami G. et al . Efficacy of oral ciprofloxacin vs. clarithromycin for treatment of acute bacterial exacerbations of chronic bronchitis. The Bronchitis Study Group.  Clin Infect Dis. 1998;  27 730-738
• 47 Wilson R, Schentag J J, Ball P. et al . A comparison of gemifloxacin and clarithromycin in acute exacerbations of chronic bronchitis and long-term clinical outcomes.  Clin Ther. 2002;  24 639-652
• 48 Lode H, Eller J, Linnhoff A. et al . Levofloxacin versus clarithromycin in COPD exacerbation: focus on exacerbation-free interval.  Eur Respir J. 2004;  24 947-953
• 49 Ruhe J J, Hasbun R. Streptococcus pneumoniae bacteremia: duration of previous antibiotic use and association with penicillin resistance.  Clin Infect Dis. 2003;  36 1132-1138
• 50 Paul M, Benuri-Silbiger I, Soares-Weiser K. et al . Beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and meta-analysis of randomised trials.  BMJ. 2004;  328 668-673
• 51 Safdar N, Handelsman J, Maki D G. Does combination antimicrobial therapy reduce mortality in Gram-negative bacteraemia? A meta-analysis.  Lancet Infect Dis. 2004;  4 519-527