Thank you for viewing this presentation. We would like to remind you that this material is the property of the author. It is provided to you by the ERS for your personal use only, as submitted by the author. 2008 by the author 1Unitof Pulmonary Rehabilitation, IRCCS San Raffaele, Velletri, Rome, Italy 2Unit of Respiratory Medicine, Department of Internal Medicine, University of Rome “Tor Vergata”, Rome, Italy Prulifloxacin in the treatment of acute exacerbations of COPD in cigarette smokers Gianluca Biscione1, Girolmina Crigna1, Franco Pasqua1, Mario Cazzola2 Bacterial isolates and cigarette smoking in patients with COPD: results from an Italian multicentre survey No H. S. S. aureus M. No Smoking patients influenzae pneumoniae catarrhalis isolates index* South 193 36,6% 22,3% 7,3% 6,7% 17,1% 648,9 North 83 15,7% 15,7% 25,3% 6,0% 12,0% 653,6 Totals 276 30,4% 20,3% 12,7% 6,5% 15,6% 650,4 Smoking 827,1 599,1 691,2 541,9% 445,6% index >800 48.8% 26,8% 40,0% 11,2% 20,9% <400 21.4% 46,4% 20,0% 55,6% 51,1% Pulmonary function FEV1 56.6% 65,7% 55,1% 69,1% 70,1% FVC 68.8% 74,8% 63,0% 80,5% 77,8% *Number of cigarettes smoked daily x years of smoking Cazzola et al, Clin Ther 1990;12:105-17 Cigarette smoking and Haemophilus influenzae There is an association between heavy cigarette smoking and LRTI. Heavy smokers are particularly susceptible to LRTI caused by H. influenzae. The effect on respiratory function of both cigarette smoking and H. influenzae infection appeared to be cumulative. Cazzola et al, Clin Ther 1990;12:105-17 Tobacco or pure nicotine stimulate the growth of H. influenzae in vitro in nutritionally poor bacteriological media tobacco nicotine Roberts e Cole, J Clin Pathol 1979;32:728-31 Germs isolated in sputum during exacerbations of COPD according to impairment in FEV1 Miravitlles et al, Chest 1999;116:40-6 Factors independently associated with isolation of the most common potentially pathogenic microorganisms Miravitlles et al, Chest 1999;116:40-6 Degree of functional impairment, smoking habit and empiric treatments Low FEV1 and active tobacco smoking are data that should be considered when establishing an empiric antibiotic treatment for exacerbated COPD. The influence that new empiric treatments, which are used according to the degree of functional impairment and the smoking habit, may have on improving the condition of the patient is a subject worthy of further investigation. Cazzola et al, J Chemother 1991;3:245-9 Miravitlles et al, Chest 1999;116:40-6 Prulifloxacin CH3 O N O S O N N CH3 F COOH O 6-fluoro-1-methyl-7-[4-[(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl]-1-piperazinyl]-4-oxo- 1H,4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid Prulifloxacin is the prodrug of ulifloxacin A comparison of the MICs of ulifloxacin and other fluoroquinolones for respiratory pathogens isolated in 1998 to 2000 in Italy Organism Ulifloxacin Ciprofloxacin Levofloxacin (prulifloxacin) H. influenzae ≤0,015 0,03 0,06 M. catarrhalis 0,06 0,12 0,12 K. pneumoniae 0,12 0,25 1 S. pneumoniae 1 1 1 P. aeruginosa 1 1 2 S. aureus 0,5 0,5 0,25 Montanari et al. AA&C 2001;45:3616-22 Prats et al. Eur J Clin Microbiol Infect Dis 2002;21:328-334 Penetration of prulifloxacin (600 mg) into lung tissue after oral administration to subjects undergoing lobectomy or pneumonectomy Concentrazione tempo Concia et al. Clin Pharmacokinet 2005;44:1287-94 The efficacy of an antibiotic to treat lower respiratory tract infections can depend on the levels reached by the drug and the retention times in the different pulmonary sites of infection Cazzola et al, Am J Respir Med 2002 Aim of the study These features suggest that prulifloxacin should be considered an appropriate antibiotic for the treatment of AECOPD in smokers. In order to confirm this hypothesis, we treated a group of smokers that came to our observation because of an AECOPD with this fluoroquinolone. Patients Sixty-one eligible adult smokers suffering from COPD, hospitalized or outpatients, of both sexes, with symptoms and signs compatible with the usual diagnosis criteria for acute exacerbation (e.g., increased cough, dyspnea, increased sputum volume, and increased sputum purulence) and a positive culture of a pre-therapy sputum specimen with a respiratory pathogen. Methods Clinical evaluation and bacteriological examination of sputum before therapy and at 3–5 (post therapy) and 10–14 (late post therapy) days after the completion of treatment. Oral prulifloxacin 600mg once daily for 10 days and a short course of oral prednisolone 25 mg/die. Clinical (symptomatic) response assessment cure: an elimination of signs and symptoms and no recurrence at the follow-up visits; improvement: a significant, but incomplete, resolution of signs or symptoms; relapse: worsening of signs and symptoms following an initial improvement; failure: no improvement. Patients were designated as unappreciable if they could not be assigned to a category and were disqualified for efficacy analysis. Bacteriological response assessment At post- therapy visit • eradication: pathogen eliminated; • persistence: culture positive for original pathogen; • colonization: culture positive for a new pathogen without the signs of infection; • superinfection: culture positive for a new pathogen during therapy (required symptomatic response) At late post therapy visit • eradication: pathogen eliminated; • relapse: recurrence of the same pathogen with or without the development of resistance (required a positive follow-up culture preceded by at least one negative culture); • colonization: culture positive for a new pathogen without the signs of infection; • eradication with reinfection: culture positive for a new pathogen after treatment (required symptomatic response of failure or relapse). No follow-up sputum specimen produced for culture • presumed microbiological persistence: no follow-up culture obtained with asymptomatic response of relapse or failure; • presumptive eradication: implied absence of appropriate material for culture, or culture not clinically indicated (required symptomatic response of cure or improvement); • indeterminate: could not be evaluated (bacteriological response could not be defined or categorized), or new antibiotic started for a condition other than the study indication before appropriate material for culture was obtained, or no pathogen isolated from the pre-therapy culture. Most common bacterial species isolated in sputum of 61 smokers suffering from AECOPD Clinical response rates Bacteriological responses by organism Conclusion The results of our study show that 10 day treatment with 600mg prulifloxacin od was effective and well tolerated in the treatment of AECOPD in adult smokers. Prulifloxacin was extremely active against the main pathogen of clinical relevance in smokers, H. influenzae, and it was also active against S. pneumoniae, S. aureus, and M. catarrhalis. Thus, prulifloxacin 600mg od can be considered a first choice treatment for AECOPD in smokers.
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