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MICROBIOLOGY OF BRONCHIECTASIS AND ANTIBIOTIC TREATMENT

MICROBIOLOGY OF BRONCHIECTASIS AND ANTIBIOTIC TREATMENT. Prof. Dr. Abdullah Sayıner, Ege UMS Dept. of Chest Diseases. Conflict of interest. Pfizer Novartis Bayer Abdi İbrahim. Vicious circle hypothesis. Damage şn the bronchial wall and epithelium. Dysfunction in mucociliary clearance.

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MICROBIOLOGY OF BRONCHIECTASIS AND ANTIBIOTIC TREATMENT

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  1. MICROBIOLOGY OF BRONCHIECTASIS AND ANTIBIOTIC TREATMENT Prof. Dr. Abdullah Sayıner, Ege UMS Dept. of Chest Diseases

  2. Conflict of interest • Pfizer • Novartis • Bayer • Abdi İbrahim

  3. Vicious circle hypothesis Damage şn the bronchial wall and epithelium Dysfunction in mucociliary clearance Chronic and exacerbating inflammation Colonization of lower respiratory tract and frequent exacerbations Cole PJ. Clin Ther 1991; 13: 194-8

  4. Aims of antibiotic treatment • In stable period, eradication of colonizing bacteria • In exacerbations, treatment of acute infection In exacerbations, colonizing bacteria increase in number or a new strain develops. Monso E, Am J Respir Crit Care Med 1995; 152: 1316-20 Sethi S, New Eng J Med 2002; 347: 465

  5. Hemophilus influenzae • Colonizes 15-50% of the patients • Can adhere to the respiratory mucus and epithelial cells using adhesion molecules and pyli, resulting in colonization. • Through genetic mutations or horizontal gene transfer, can change its phenotype or surface antigens, thus can avoid immune response and oxidative stress. • Can form a biofilm (amorphous matrix) in the respiratory tract, which surrounds the colonies. It can decrease its metabolism and growth rate in this environment. Foweraker JE. Eur Respir Mon 2011; 52: 68-96 Gilsdorf JR. Infect Immun 2004; 72: 2457-61 Starner TD. Am J Respir Crit Care Med 2006; 174: 213-220

  6. Pseudomonas aeruginosa • Colonizes 10-40% of the patients • More frequently isolated in patients in whom the disease is diagnosed before 14 years of age, FEV1 level is low, sputum volume is high and there is saccular bronchiectasis. • More frequent exacerbations and hospitalizations, worse quality of life, faster decline in pulmonary function Ho PL. Chest 1998; 114: 1594-98 Kömüs N. Tuberk Toraks 2006; 54: 355-62

  7. Survival of Pseudomonasin the respiratory tract • Biofilm formation • Bacteria with different phenotypes – alginate production, lowered metabolic rate, frequent mutations etc – can coexist within the same patient. → Easy adaptation to changes in the environment • Natural resistance to several antibiotics + acquired resistance to several others through chromosomal mutations or gene transfer • Difficulties in bacteriologic diagnosis because of the existence of multiple phenotypes in the chronic infection environment. Gillham MI. J Antimicrob Chemother 2009; 63: 728-32

  8. Biofilm • Biofilm formation: Alginate and proteins + DNA fragments from host cells + various metabolites → protection against phagocytosis by neutrophils and macrophages → Anaerobic environment under the biofilm surface → Effectiveness of aminoglycosides  → Metabolic activity  → Effectiveness of beta-lactams ve quinolones  Yang L. J Bacteriol 2008; 190: 2767-76 Walters MC. Antimicrob Agents Chemother 2003; 47: 317-23

  9. Other microorganisms • Streptococcus pneumoniae: Particularly, in patients with Ig or complement deficiencies • Moraxella catarrhalis • Staphylococcus aureus • Viruses • Mycobacteria other than tuberculosis

  10. Sputum culture Possibility of isolated bacteria not being the phenotype causing the infection Determination of the causative agent and its susceptibility to drugs

  11. Sputum culture • Sputum sample must be obtained prior to the initiation of antibiotic treatment. • Useful if the empiric treatment is not successful or if there is a possibility of deescalation (narrowing of antibiotic spectrum).

  12. Antibiotic treatment • Some patients with bronchiectasis may produce large amounts of and purulent sputum in stable period. Therefore, when deciding on antibiotic treatment, symptoms during stable period and additional evidence of infection should carefully be questioned. • There is no randomized, controlled study evaluating effectiveness of antibiotic treatment in exacerbations of bronchiectasis.

  13. IV ceftazidime (n=18) vs oral levofloxacin (n=17) for 10 days in exacerbations of bronchiectasis • Evaluation of clinical parameters before and after treatment Tsang KW ve ark. Eur Respir J 1999;14:1206

  14. Addition of ciprofloxacin to inhaled tobramycin Patients with Pseudomonas infection Multicenter, randomized, placebo controlled study Treatment for 14 days No difference in clinical findings Bilton D. Chest 2006;130:1503

  15. Turkish Thoracic Society recommendations

  16. Risk factors for Pseudomonas infection • Hospitalization within the preceding month • Antibiotic use for four times or more during the preceding year or once during the preceding month • Severe (resulting in respiratory failure) exacerbation • Isolation of P. aeruginosa in previous exacerbation or in stable period

  17. Turkish Thoracic Society recommendations

  18. Macrolides – anti-inflamatory effects • Decrease in mucus secretion in airways • Inhibition of production of proinflammatory cytokines (IL-8) and adhesion molecules, resulting in decreased neutrohil chemotaxis • Disrution of biofilm which is formed by and which protects P.aeruginosa and prevention of its reformation • There is not enough clinical evidence supporting these positive effects. BUT • Potential for development of resistance • Adverse effects on cardiac signal transmission Amsden GW. JAC 2005;55:10 Crosbie PAJ. Eur Respir J 2009;33:171

  19. Macrolides: Clinical studies in bronchiectasis Crosbie PAJ. Eur Respir J 2009;33:171

  20. Inhaled tobramycin • Inhalation using a nebulizer (300mg bid) • 28-day treatment cycles followed by 28-day off-drug periods • Outcomes in patients with cystic fibrosis colonized with P. aeruginosa to whom this treatment is administered: placebo-controlled study (3 cycles)  10% increase in FEV1 levels (vs 2% decrease in plcb group)  1 log decrease in concentration of colonizing Pseudomonas  23% decrease in hospitalizations  Increase in prevalence of drug-resistant strains (25%32%) Ramsey BW. N Engl J Med 1999;340:23

  21. 74 patients colonised with P. aeruginosa • Randomized, placebo-controlled trial • Inhaled tobramycin (IT) / placebo for four weeks • Eradication in 13/37 IT patients Barker AF ve ark. AJRCCM 2000;162:481

  22. Barker AF ve ark. AJRCCM 2000;162:481

  23. Barker AF ve ark. AJRCCM 2000;162:481

  24. Inhaled tobramycin: Adverse events (%) Barker AF ve ark. AJRCCM 2000;162:481

  25. Summary • Bronchial colonization / infection have an adverse effect on the course and prognosis of bronchiectasis. • H. influenzae and P. aeruginosa more frequently colonizes patients with worse pulmonary function and saccular bronchiectasis. • In spite of some theoretic problems, bacteriologic examination of the sputum should be done. • There is weak evidence that the use of antibiotics during exacerbations is associated with limited benefits. • Long-term macrolide treatment can be considered in patients with frequent exacerbations. Inhaled tobramycin does not seem to be very effective in patients with non-cystic fibrosis bronchiectasis.

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