1. COPD SPUTUM PRODUCERS AND THE INFLUENCE ON ANTIBIOTIC RESISTANCE Sarah Thurston PhD student

2. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) Characterised by airflow limitation that is not fully reversible Caused by noxious particles or gases (smoking) Damage caused by inflammatory response Loss of surface area for gaseous exchange Creagh & Krausz, Oxford Textbook of Pathology 1992

3. Changes to surface target expression e.g. Penicillin binding proteins Changes to cell permeability e.g. porin expression Active removal of toxic components e.g. efflux pumps Production of enzymes that destroy the antibiotic e.g. Β- lactamases Adapted from Kyd, J, et al, 2011 Curr Drug Tar 12: 521-530 MECHANISMS OF ANTIBIOTIC RESISTANCE

4. AIMS OF STUDY To establish antibiotic resistance prevalence and patterns in COPD patients by using routine culture methods To identify sub- populations of COPD patients who are more at risk of developing antibiotic resistance

5. METHODS 293 patients from the London COPD cohort 2948 sputum sample results 5 years Predicted FEV 1 measured when sample taken Semi- quantitative drug sensitivity tests (DSTs) Resistant isolates reported

6. The spontaneous production of sputum for at least 3 months per year over the previous 2 years Medical Research Council, 1965 CHRONIC BRONCHITIS DEFINITION

7. PATIENT CHARACTERISTICS OF THE LONDON COPD COHORT Age, years (SD)69.9 (8.9) Male, %58 Average Length in Study, months (SD)28.4 (19.9) FEV 1 Predicted, % (SD)47.8 (16.5) FEV 1 / FVC (SD)0.46 (0.13) Sputum Producers, %77.5 Exacerbation Samples, %68.26 Current Smokers, %31.72 FEV 1, forced expiratory volume in 1 second, FVC, forced vital capacity

8. RESULTS 293 patients Bacteria +ve 92 patients (31.4%) Bacteria -ve 201 patients (68.6%) DSTs 87 patients (94.6%) No DSTs 5 patients (5.4%) Resistance 69 patients (79.3%) 69/293 patients (23.5%) Non- resistance 18 patients (20.7%) Frequently Resistant 30 patients (43.5%) 30/293 patients (10.2%) Infrequently Resistant 39 patients (56.5%)

9. Resistant (p = 0.577) LUNG FUNCTION AND ANTIBIOTIC RESISTANCE

10. Average resistance % SPUTUM PRODUCTION AND ANTIBIOTIC RESISTANCE

11. ANTIBIOTIC EXPOSURE Average AB days per yearn (SD) Total16.2 (10.3) Non- Sputum Producers16.2 (31.3) Sputum Producers16.4 (11.0) Non- resistant15.6 (11.9) Resistant17.8 (17.2)

12. 31.4% patients with bacteria culture positive 79.3% of these patients with resistance observed 10.2% patients with frequently resistant samples 23.5% COPD patients will develop resistance within 28.4 months RESULTS SUMMARY

13. *Community Acquired RTI % Resistant Isolates COPD COHORT % Resistant Isolates AMP15.4 20.19 H. InfluenzaeCLARI0.9 17.65 ERYTHRO6 33.33 AMP90.3 87.8 M. catarrhalisCLARI0 0 ERYTHRO0.2 3.7 Results summary *Morrissey, I, et al, 2008. J Antimicrob Chemother 62: 97-103

14. Conclusion There is an increased risk of antibiotic resistance in sputum producers There is no evidence that disease severity has any impact on resistance prevalence Further resistance studies will reveal the changing trends in local isolates.

15. Prof. Wisia A Wedzicha Academic Unit of Respiratory Medicine Dr Tim D McHugh Clinical Centre for Microbiology Dr Gavin C Donaldson Academic Unit of Respiratory Medicine Acknowledgements