pulmoПульмонологияPULMONOLOGIYA0869-01892541-9617Scientific and Practical Journal “PULMONOLOGIYA” LLC10.18093/0869-0189-2007-0-6-67-72pulmo-2006Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL STUDIESОткрытое несравнительное исследование эффективности и безопасности левофлоксацина при обострении ХОБЛAn open non-comparative trial of efficacy and safety of levofloxacin in acute exacerbation of COPDЧучалинА. Г.ChuchalinA. G.

Москва

АвдеевС. Н.AvdeevS. N.

Москва

БаймакановаГ. Е.BaymakanovaG. E.

Москва

НуралиеваГ. С.NuralievaG. S.

Москва

ФГУ НИИ пульмонологии РосздраваRussian Federation200728122007066772Copyright © Чучалин А.Г., Авдеев С.Н., Баймаканова Г.Е., Нуралиева Г.С., 20072007Чучалин А.Г., Авдеев С.Н., Баймаканова Г.Е., Нуралиева Г.С.Chuchalin A.G., Avdeev S.N., Baymakanova G.E., Nuralieva G.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.pulmonology.ru/pulm/article/view/2006

Цель исследования — оценить клиническую и микробиологическую эффективность, безопасность и переносимость левофлоксацина у больных с обострением ХОБЛ средней и тяжелой степени. В открытое нерандомизированное проспективное исследование включено 20 больных с обострением ХОБЛ — 16 мужчин, 4 женщины (средний возраст 63,1 ± 8,6 года) со стажем курения 36,2 ± 14,3 пачек / лет. Препарат назначали в дозе 500 мг в сутки в течение 7 дней (18 пациентов), больным, из мокроты которых выделены штаммы P. aerugi2 nosa, — 1 000 мг в сутки 14 дней (2 пациента). Оценка переносимости и клинической и микробиологической эффективности терапии проводилась через 3, 7 и 14 дней от ее начала. Клиническое улучшение к 3-му дню терапии отмечено у 15 больных (75 %), к 7-му дню у 19 больных (95 %). Достоверные положительные изменения у больных наблюдались в показателях ФВД (повышение ОФВ1 с 40,5 ± 14,7 до 52,0 ± 18,6 %; р = 0,0001; повышение ФЖЕЛ с 68,3 ± 21,3 до 77,6 ± 15,0 %; р = 0,005). На фоне проводимой терапии отмечалось снижение уровня гемоглобина (р = 0,013) и лейкоцитов крови (р = 0,001). Эрадикация и предполагаемая эрадикация возбудителя наблюдались в 81,8 % случаев. Переносимость препарата была признана отличной у 85 % больных, хорошей — у 15 %. Побочные реакции были редкими, легкими и транзиторными и не требовали отмены препарата. Левофлоксацин является эффективным антибиотиком для терапии обострений ХОБЛ среднетяжелого и тяжелого течения: его клиническая эффективность по окончании терапии составила 95 %, микробиологическая — 82 %. Препарат хорошо переносится больными, отмечен удобный режим дозирования.

The trial was aimed to evaluation of clinical and microbiological efficacy, safety and tolerability of levofloxacin in patients with moderate to severe acute exacerbation of COPD. There was an open, non-randomised prospective study involving 20 patients with acute exacerbation of COPD (16 males, 4 females, the average age, 63.1 ± 8.6 yrs; smoking history, 36.2 ± 14.3 pack/yrs). The drug was administered in the daily dose of 500 mg during 7 days (in 18 patients) or 1 000 mg during 14 days (in 2 patients with P.aeruginosa isolated from sputum). Clinical and microbiological efficacy and tolerability were evaluated in 3, 7 and 14 days of the antimicrobial therapy. Clinical improvement in 3 days of the therapy was noted in 15 patients (75 %) and in 7 days in 19 patients (95 %). Significant improvement was found in lung function parameters (FEV1 , from 40.5 ± 14.7 % pred. to 52.0 ± 18.6 %pred.; р = 0.0001; FVC, from 68.3 ± 21.3 %pred. to 77.6 ± 15.0%pred .; р = 0.005). During the therapy, blood hemoglobin level (р = 0.013) and leukocytes count (р = 0.001) have decreased. Eradication and supposed eradication of pathogens were obtained in 81.8 % of the cases. The drug tolerability was considered as excellent in 85 % of the patients and good in 15 % of the patients. Adverse events were rare, mold and transitional and did not require withdrawal of the drug. Therefore, levofloxacin is an effective antimicrobial drug for treatment of moderate to severe acute exacerbation of COPD; clinical efficacy was 95 % and microbiological efficacy was 82 %.The drug is well tolerated and has a convenient dosing regimen.

ReferencesGlobal Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO workshop report. The 2006 report is available on www.goldcopd.comGlobal Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO workshop report. The 2006 report is available on www.goldcopd.comBurge S., Wedzicha J.A. COPD exacerbations: definitions and classifications. Eur. Respir. J. 2003; 21 (suppl. 41): 46s–53s.Burge S., Wedzicha J.A. COPD exacerbations: definitions and classifications. Eur. Respir. J. 2003; 21 (suppl. 41): 46s–53s.Seemungal T.A.R., Donaldson G.C., Paul E.A. et al. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 1998; 151: 1418–1422.Seemungal T.A.R., Donaldson G.C., Paul E.A. et al. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 1998; 151: 1418–1422.Donaldson G.C., Seemungal T.A.R., Bhowmik A., Wedzicha J.A. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax 2002; 57: 847–852.Donaldson G.C., Seemungal T.A.R., Bhowmik A., Wedzicha J.A. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax 2002; 57: 847–852.Zielinski J., MacNee W., Wedzicha J. et al. Causes of death in patients with COPD and chronic respiratory failure. Monaldi Arch. Chest Dis. 1997; 52: 43–47.Zielinski J., MacNee W., Wedzicha J. et al. Causes of death in patients with COPD and chronic respiratory failure. Monaldi Arch. Chest Dis. 1997; 52: 43–47.Ball P. Epidemiology and treatment of chronic bronchitis and its exacerbations. Chest 1995; 108 (suppl. 3): 43s–52s.Ball P. Epidemiology and treatment of chronic bronchitis and its exacerbations. Chest 1995; 108 (suppl. 3): 43s–52s.Ewig S., Rodriguez2Roisin R., Torres A. Indications for and choice of antibiotics in COPD. In: Similowski T., Whitelaw W.A., Derenne J.-P. (eds.). Clinical management of chronic obstructive pulmonary disease. New York: Marcel Dekker Inc., 2002. 427–449.Ewig S., Rodriguez2Roisin R., Torres A. Indications for and choice of antibiotics in COPD. In: Similowski T., Whitelaw W.A., Derenne J.-P. (eds.). Clinical management of chronic obstructive pulmonary disease. New York: Marcel Dekker Inc., 2002. 427–449.Fagon J.2Y., Chastre J., Trouillet J.2L. et al. Characterization of distal bronchial microflora during acute exacerbation of chronic bronchitis. Am. Rev. Respir. Dis. 1990; 142: 1004–1008.Fagon J.2Y., Chastre J., Trouillet J.2L. et al. Characterization of distal bronchial microflora during acute exacerbation of chronic bronchitis. Am. Rev. Respir. Dis. 1990; 142: 1004–1008.Soler N., Torres A., Ewig S. et al. Bronchial microbial patterns in severe exacerbations of chronic obstructive pulmonary disease requiring mechanical ventilation. Am. J. Respir. Crit. Care Med. 1998; 157: 1498–1505.Soler N., Torres A., Ewig S. et al. Bronchial microbial patterns in severe exacerbations of chronic obstructive pulmonary disease requiring mechanical ventilation. Am. J. Respir. Crit. Care Med. 1998; 157: 1498–1505.Авдеев С.Н., Шанина А.Г., Чучалин А.Г. Бактериальная инфекция у больных ХОБЛ с острой дыхательной недостаточностью. Клин. микробиол. и антимикроб. Химиотер. 2005; 7 (3): 245–254.Авдеев С.Н., Шанина А.Г., Чучалин А.Г. Бактериальная инфекция у больных ХОБЛ с острой дыхательной недостаточностью. Клин. микробиол. и антимикроб. Химиотер. 2005; 7 (3): 245–254.Nouira S., Marghli S., Belghith M. et al. Once daily oral ofloxacin in in chronic obstructive pulmonary disease exacerbation requiring mechanical ventilation: a randomised placebo-controlled trail. Lancet 2001; 358: 2020–2025.Nouira S., Marghli S., Belghith M. et al. Once daily oral ofloxacin in in chronic obstructive pulmonary disease exacerbation requiring mechanical ventilation: a randomised placebo-controlled trail. Lancet 2001; 358: 2020–2025.O'Donnell J.A., Gelone S.P. The newer fluoroquinolones. Infect. Dis. Clin. N. Am. 2004; 18: 691–716.O'Donnell J.A., Gelone S.P. The newer fluoroquinolones. Infect. Dis. Clin. N. Am. 2004; 18: 691–716.Greenberg R.N. Overview of patient compliance with medication dosing: a literature review. Clin. Ther. 1994; 6: 592–599.Greenberg R.N. Overview of patient compliance with medication dosing: a literature review. Clin. Ther. 1994; 6: 592–599.De Abate C.A., Russel M., McElvaine P. et al. Safety and efficacy of oral levofloxacin versus cefuroxime axetil in acute bacterial exacerbations of chronic bronchitis. Respir. Care 1997; 42: 206–213.De Abate C.A., Russel M., McElvaine P. et al. Safety and efficacy of oral levofloxacin versus cefuroxime axetil in acute bacterial exacerbations of chronic bronchitis. Respir. Care 1997; 42: 206–213.Habib M.P., Russell M., De Abate C.A., et al. Multicenter, randomized study comparing efficacy and safety of oral levofloxacin and cefaclor in the treatment of acute exacerbations of chronic bronchitis. Infect. Dis. Clin. Practice 1998; 7: 1–9.Habib M.P., Russell M., De Abate C.A., et al. Multicenter, randomized study comparing efficacy and safety of oral levofloxacin and cefaclor in the treatment of acute exacerbations of chronic bronchitis. Infect. Dis. Clin. Practice 1998; 7: 1–9.Davies B.I., Maesen F.P. Clinical effectiveness of levofloxacin in patients with acute purulent exacerbations of chronic bronchitis: the relationship with in-vitro activity. J. Antimicrob. Chemother. 1999; 43: 83–90.Davies B.I., Maesen F.P. Clinical effectiveness of levofloxacin in patients with acute purulent exacerbations of chronic bronchitis: the relationship with in-vitro activity. J. Antimicrob. Chemother. 1999; 43: 83–90.Shah P.M., Maesen F.P., Dolmann A. et al. Levofloxacin versus cefuroxime axetil in the treatment of acute exacerbations of chronic bronchitis: results of a randomized, double-blind study. J. Antimicrob. Chemother. 1999; 43: 529–539.Shah P.M., Maesen F.P., Dolmann A. et al. Levofloxacin versus cefuroxime axetil in the treatment of acute exacerbations of chronic bronchitis: results of a randomized, double-blind study. J. Antimicrob. Chemother. 1999; 43: 529–539.Weiss LR. Open-label, randomized comparison of the efficacy and tolerability of clarithromycin, levofloxacin, and cefuroxime axetil in the treatment of adults with acute bacterial exacerbations of chronic bronchitis. Clin. Ther. 2002; 24: 1414–1425.Weiss LR. Open-label, randomized comparison of the efficacy and tolerability of clarithromycin, levofloxacin, and cefuroxime axetil in the treatment of adults with acute bacterial exacerbations of chronic bronchitis. Clin. Ther. 2002; 24: 1414–1425.Amsden G.W., Baird I.M., Simon S., Treadway G. Efficacy and Safety of Azithromycin vs Levofloxacin in the Outpatient Treatment of Acute Bacterial Exacerbations of Chronic Bronchitis. Chest 2003; 123: 772–777.Amsden G.W., Baird I.M., Simon S., Treadway G. Efficacy and Safety of Azithromycin vs Levofloxacin in the Outpatient Treatment of Acute Bacterial Exacerbations of Chronic Bronchitis. Chest 2003; 123: 772–777.Sethi S, Fogarty C, Fulambarker A. A randomized, doubleblind study comparing 5 days oral gemifloxacin with 7 days oral levofloxacin in patients with acute exacerbation of chronic bronchitis. Respir Med 2004; 98: 697–707Sethi S, Fogarty C, Fulambarker A. A randomized, doubleblind study comparing 5 days oral gemifloxacin with 7 days oral levofloxacin in patients with acute exacerbation of chronic bronchitis. Respir Med 2004; 98: 697–707Lode H., Eller J., Linnhoff A., Ioanas M. The evaluation of therapy-free interval in COPD patients study group. Levofloxacin versus clarithromycin in COPD exacerbation: focus on exacerbation-free interval. Eur. Respir. J. 2004; 24: 947–953.Lode H., Eller J., Linnhoff A., Ioanas M. The evaluation of therapy-free interval in COPD patients study group. Levofloxacin versus clarithromycin in COPD exacerbation: focus on exacerbation-free interval. Eur. Respir. J. 2004; 24: 947–953.Urueta2Robledo J., Ariza H., Jardim J.R. et al. Moxifloxacin versus levofloxacin against acute exacerbations of chronic bronchitis: The Latin American Cohort. Respir Med 2006; 100: 1504–1511.Urueta2Robledo J., Ariza H., Jardim J.R. et al. Moxifloxacin versus levofloxacin against acute exacerbations of chronic bronchitis: The Latin American Cohort. Respir Med 2006; 100: 1504–1511.Anthonisen N.R., Manfreda J., Warren C.P.W. et al. Antibiotic therapy in acute exacerbations of chronic obstructive pulmonary disease. Ann. Intern. Med. 1987; 106: 196–204.Anthonisen N.R., Manfreda J., Warren C.P.W. et al. Antibiotic therapy in acute exacerbations of chronic obstructive pulmonary disease. Ann. Intern. Med. 1987; 106: 196–204.Beam T.R., Gilbert D.N., Kunin C.M. (eds.) with modifications by a European Working Party. Guidelines for the clinical evaluation of anti-infective drugs. Published for: The European Society of Clinical Microbiology and Infectious Disease; 1993.Beam T.R., Gilbert D.N., Kunin C.M. (eds.) with modifications by a European Working Party. Guidelines for the clinical evaluation of anti-infective drugs. Published for: The European Society of Clinical Microbiology and Infectious Disease; 1993.Quanjer Ph. H., Tammeling G.J., Cotes J.E. et al. Lung volumes and forced ventilatory flows. Eur. Respir. J. 1993; 6 (suppl. 16): 5–40.Quanjer Ph. H., Tammeling G.J., Cotes J.E. et al. Lung volumes and forced ventilatory flows. Eur. Respir. J. 1993; 6 (suppl. 16): 5–40.Murray P.R., Washington J.A. Microscopic and bacteriologic analysis of expectorated sputum. Mayo Clin. Proc. 1975; 50: 339–344.Murray P.R., Washington J.A. Microscopic and bacteriologic analysis of expectorated sputum. Mayo Clin. Proc. 1975; 50: 339–344.National Committee for Clinical Laboratory Standards. Performance standards for antimicrobial susceptibility testing (vol. 17). Philadelphia, PA: NCCLS; 1997; 1: M57–M100.National Committee for Clinical Laboratory Standards. Performance standards for antimicrobial susceptibility testing (vol. 17). Philadelphia, PA: NCCLS; 1997; 1: M57–M100.Blasi F., Tarsia P., Aliberti S. et al. Highlights on the appropriate use of fluoroquinolones in respiratory tract infections. Pulm. Pharmacol. Ther. 2006; 19 (suppl. 1): 11–19.Blasi F., Tarsia P., Aliberti S. et al. Highlights on the appropriate use of fluoroquinolones in respiratory tract infections. Pulm. Pharmacol. Ther. 2006; 19 (suppl. 1): 11–19.O'Donnell J.A., Gelone S.P. The newer fluoroquinolones. Infect. Dis. Clin. N. Am. 2004; 18: 691–716.O'Donnell J.A., Gelone S.P. The newer fluoroquinolones. Infect. Dis. Clin. N. Am. 2004; 18: 691–716.Siempos I.I., Dimopoulos G., Korbila I.P. et al. Macrolides, quinolones, and amoxicillin/clavulanate for chronic bronchitis: a meta-analysis. Eur. Respir. J. 2007; 29: 1127–1137.Siempos I.I., Dimopoulos G., Korbila I.P. et al. Macrolides, quinolones, and amoxicillin/clavulanate for chronic bronchitis: a meta-analysis. Eur. Respir. J. 2007; 29: 1127–1137.Чучалин А.Г., Синопальников А.И., Фесенко О.В. Результаты открытого нерандомизированного несравнительного исследования эффективности и безопасности левофлоксацина при внебольничной пневмонии и обострении хронического бронхита. Пульмонология 2002; 4: 71–78.Чучалин А.Г., Синопальников А.И., Фесенко О.В. Результаты открытого нерандомизированного несравнительного исследования эффективности и безопасности левофлоксацина при внебольничной пневмонии и обострении хронического бронхита. Пульмонология 2002; 4: 71–78.Ruiz2Gonzalez A., Gimenez A., Gomez2Arbones X. et al. Open-label, randomized comparison trial of long-term outcomes of levofloxacin versus standard antibiotic therapy in acute exacerbations of chronic obstructive pulmonary disease. Respirology 2007; 12: 117–121.Ruiz2Gonzalez A., Gimenez A., Gomez2Arbones X. et al. Open-label, randomized comparison trial of long-term outcomes of levofloxacin versus standard antibiotic therapy in acute exacerbations of chronic obstructive pulmonary disease. Respirology 2007; 12: 117–121.Антибиотикорезистентность в России: Возбудители внебольничных инфекций. Available on http://www.antibiotic.ru.Антибиотикорезистентность в России: Возбудители внебольничных инфекций. Available on http://www.antibiotic.ru.Козлов Р.С., Сивая О.В., Шпынев К.В. и др. Антибиотикорезистентность Streptococcus pneumoniae в России в 1999–2005 гг.: результаты многоцентровых проспективных исследований ПеГАС-I и ПеГАС-II. Клин. микробиол. и антимикроб. Химиотер. 2006; 8 (1): 33–47.Козлов Р.С., Сивая О.В., Шпынев К.В. и др. Антибиотикорезистентность Streptococcus pneumoniae в России в 1999–2005 гг.: результаты многоцентровых проспективных исследований ПеГАС-I и ПеГАС-II. Клин. микробиол. и антимикроб. Химиотер. 2006; 8 (1): 33–47.Martinez F.J., Grossman R.F., Zadeikis N. et al. Patient stratification in the management of acute bacterial exacerbation of chronic bronchitis: the role of levofloxacin 750 mg. Eur. Respir. J. 2005; 25: 1001–1010.Martinez F.J., Grossman R.F., Zadeikis N. et al. Patient stratification in the management of acute bacterial exacerbation of chronic bronchitis: the role of levofloxacin 750 mg. Eur. Respir. J. 2005; 25: 1001–1010.Bonfiglio G. Is levofloxacin as active as ciprofloxacin against Pseudomonas aeruginosa? Chemotherapy 2001; 47: 239–242.Bonfiglio G. Is levofloxacin as active as ciprofloxacin against Pseudomonas aeruginosa? Chemotherapy 2001; 47: 239–242.Owens R.C. Risk assessment for antimicrobial agentinduced QTc interval prolongation and torsades de pointes. Pharmacotherapy 2001; 21: 301–319.Owens R.C. Risk assessment for antimicrobial agentinduced QTc interval prolongation and torsades de pointes. Pharmacotherapy 2001; 21: 301–319.

The authors declare that there are no conflicts of interest present.