Keywords
antibiotic resistance; general practice; bacterial lysates; adults
Abstract
Background
Chronic Obstructive Pulmonary Disease (COPD) is one of the most frequent pathologies in which antibiotics are used because 50% of the exacerbations are attributable to a bacterial infection.
The aims of our study were: i)to perform a meta-analysis on the efficacy of the bacterial lysate OM-85 BV in preventing acute exacerbations in patients with COPD; ii) to evaluate whether this preventive treatment can lead to significant savings for the National Health Service (NHS).
Methods
A systematic research was conducted in the electronic database MEDLINE (PubMed) in June 2017-July 2020, collecting evidences without time restrictions. Only randomized controlled trials (RCTs) were included. The keywords used were "OM 85 BV AND chronic bronchitis" and "OM 85 BV AND COPD".
We realized the cost-effectiveness analysis (CEA) considering the costs for a treatment with OM-8BV, the costs for the treatment of an acute exacerbation and the number of prevented exacerbations.
Results
59 publications were found, but the meta-analysis was conducted on 13 studies conducted between 1981 and 2015.OM-85 BV is responsible of a statistically significant reduction in the mean number of COPD exacerbations (p <0.01; WMD -0.86;CI 95% -1.38, -0.34) and in the days of antibiotic therapy (p <0.01; WMD -9.49;CI 95% -11.93, -7.05).
The cost-effectiveness ratio with a negative value is in favor to treatment.
Conclusions
OM-85 BV is effective in reducing exacerbations, and could lead to significant savings for the NHS. Moreover, reducing the number of exacerbations it avoids an over-use of antibiotics and the consequent antibiotic resistance.
References
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Agabiti N. (2013) Epidemiologia delle Malattie Respiratorie Croniche in Italia.
Alessia Stilo GT, Lucia Melcarne , Maria Eufemia Gioffrè , Nicola Nante ,Gabriele Messina , Pasqualina Laganà. (2016) Hand washing in operating room: a procedural comparison. Epidemiology Biostatistics and Public Health 13: e11734-11731/11737.
Anthonisen NR, Manfreda J, Warren CP, et al. (1987) Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Intern Med 106: 196-204.
Beaton DE, Bombardier C, Katz JN, et al. (2001) Looking for important change/differences in studies of responsiveness. OMERACT MCID Working Group. Outcome Measures in Rheumatology. Minimal Clinically Important Difference. J Rheumatol 28: 400-405.
Bergemann R, Brandt A, Zoellner U, et al. (1994) Preventive treatment of chronic bronchitis: a meta-analysis of clinical trials with a bacterial extract (OM-85 BV) and a cost-effectiveness analysis. Monaldi Arch Chest Dis 49: 302-307.
Cazzola M, Rogliani P and Curradi G. (2008) Bacterial extracts for the prevention of acute exacerbations in chronic obstructive pulmonary disease: a point of view. Respir Med 102: 321-327.
Cimen P, Unlu M, Kirakli C, et al. (2015) Should Patients With COPD Be Vaccinated? Respir Care 60: 239-243.
Collet JP, Shapiro P, Ernst P, et al. (1997) Effects of an immunostimulating agent on acute exacerbations and hospitalizations in patients with chronic obstructive pulmonary disease. The PARI-IS Study Steering Committee and Research Group. Prevention of Acute Respiratory Infection by an Immunostimulant. Am J Respir Crit Care Med 156: 1719-1724.
Cvoriscec B, Ustar M, Pardon R, et al. (1989) Oral immunotherapy of chronic bronchitis: a double-blind placebo-controlled multicentre study. Respiration 55: 129-135.
Debbas N and Derenne JP. (1990) Preventive effects of an immunostimulating product on recurrent infections of chronic bronchitis in the elderly. Lung 168 Suppl: 737-740.
Emmerich B, Emslander HP, Pachmann K, et al. (1990) Local immunity in patients with chronic bronchitis and the effects of a bacterial extract, Broncho-Vaxom, on T lymphocytes, macrophages, gamma-interferon and secretory immunoglobulin A in bronchoalveolar lavage fluid and other variables. Respiration 57: 90-99.
Emmerich B, Pachmann K, Milatovic D, et al. (1992) Influence of OM-85 BV on different humoral and cellular immune defense mechanisms of the respiratory tract. Respiration 59 Suppl 3: 19-23.
Epicentro. (2012) Resistenze agli antibiotici. Available at: http://www.epicentro.iss.it/focus/resistenza_antibiotici/resistenza.asp.
G Troiano IM, N Nante, M Lancia, M Bacci. (2018) Candida autovaccination: a new strategy to prevent antifungal resistance? Journal of Infection Prevention 9: 202-202.
Hutas I. B-NG, Kraszko P. (1993) Statistical analysis of a double blind randomized clinical study of Broncho-Vaxom vs placebo in patients suffering from bronchitis. Statistical Report, Biometrix SA, Stand 412: 1-22.
L Righi RA-G, MQ Picat, H Benmansour, R Flicoteaux, H Jacquier, B Bercot, N Nante, S Chevret, L Raskine. (2016) Changing epidemiology and impact of resistant bacteria in 2010-2015 in a French Teaching Hospital. European Journal of Public Health 26.
Li J, Zheng JP, Yuan JP, et al. (2004) Protective effect of a bacterial extract against acute exacerbation in patients with chronic bronchitis accompanied by chronic obstructive pulmonary disease. Chin Med J (Engl) 117: 828-834.
Lucioni C. DC, De Benedetto F. . (2005) I costi della broncopneumopatia cronica ostruttiva: la fase prospettica dello Studio ICE (Italian Costs for Exacerbations in COPD). . Pharmacoeconomics-Italian Research Articles 7: 119-134.
Magyar P. MG, Nagy IA., Tarjan E., Zsiray M., Lantos A. (1985) The therapeutic and preventive effects of Broncho-Vaxom, a lyophilized bacterial lysate, in chorinc bronchitis: a double-blinc placebo-controlled study. Proceedings 4th congress of the European Society of Pneumology (SEP) - Milano/Stresa.
Mauel J, Van Pham T, Kreis B, et al. (1989) Stimulation by a bacterial extract (Broncho-Vaxom) of the metabolic and functional activities of murine macrophages. Int J Immunopharmacol 11: 637-645.
Messerli C, Michetti F, Sauser-Hall P, et al. (1981) [Effect of a bacterial lysate (Broncho-Vaxom) in the therapy of chronic bronchitis: multi-center double-blind clinical trial]. Rev Med Suisse Romande 101: 143-146.
Mestecky J, McGhee JR, Arnold RR, et al. (1978) Selective induction of an immune response in human external secretions by ingestion of bacterial antigen. J Clin Invest 61: 731-737.
Orcel B, Delclaux B, Baud M, et al. (1994) Oral immunization with bacterial extracts for protection against acute bronchitis in elderly institutionalized patients with chronic bronchitis. Eur Respir J 7: 446-452.
Orlandi O. BV, Donner CF., Fumagalli G., Rimoldi R., Grassi C. (1985) Immunological treatment using lysate in the prevention of recurrent bronchitis: a multicentre Italian study. Proceedings 4th congress of the European Society of Pneumology (SEP) - Milano/Stresa.
Pan L, Jiang XG, Guo J, et al. (2015) Effects of OM-85 BV in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis. J Clin Pharmacol 55: 1086-1092.
Rabe KF, Hurd S, Anzueto A, et al. (2007) Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 176: 532-555.
Rajagopalan P, Dournon E, Vilde JL, et al. (1987) Direct activation of human monocyte-derived macrophages by a bacterial glycoprotein extract inhibits the intracellular multiplication of virulent Legionella pneumophila serogroup 1. Infect Immun 55: 2234-2239.
Ravasio R. (2015) Cost-effectiveness analysis of long-acting bronchodilators for the treatment of COPD (moderate to very severe). GRHTA 2: 143-151.
Rossi A. (2005) Antibiotici nel trattamento della broncopneumopatia cronica ostruttiva riacutizzata. Available at: https://www.progettoasco.it/riviste/rivista_simg/2005/02_2005/3.pdf.
S. Xinogalos DD, D. Varonos. (1993) Clinical effectiveness of Broncho-Vaxom (BV) in patients with chronic obstructive pulmonary disease. Int J Immunotherapy IX: 135-142.
Sethi S. (2000) Infectious etiology of acute exacerbations of chronic bronchitis. Chest 117: 380S-385S.
Siddiqi A and Sethi S. (2008) Optimizing antibiotic selection in treating COPD exacerbations. Int J Chron Obstruct Pulmon Dis 3: 31-44.
Soler M, Mutterlein R and Cozma G. (2007) Double-blind study of OM-85 in patients with chronic bronchitis or mild chronic obstructive pulmonary disease. Respiration 74: 26-32.
Tang H, Fang Z, Saborio GP, et al. (2015) Efficacy and Safety of OM-85 in Patients with Chronic Bronchitis and/or Chronic Obstructive Pulmonary Disease. Lung 193: 513-519.
Tang H. FZ, Xiu Q. (2011) Efficacy and safety of bacterial lysates in patients with chronic obstructive pulmonary diseases and exacerbation. Eur Respir J 38: 3358.
Villa E, Garelli V, Braido F, et al. (2010) May we strengthen the human natural defenses with bacterial lysates? World Allergy Organ J 3: S17-23.
WHO. (2015) Antibiotic resistance: multi-country public awareness survey. Geneva.
Wilkinson TM, Donaldson GC, Hurst JR, et al. (2004) Early therapy improves outcomes of exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 169: 1298-1303.
Agabiti N. (2013) Epidemiologia delle Malattie Respiratorie Croniche in Italia.
Alessia Stilo GT, Lucia Melcarne , Maria Eufemia Gioffrè , Nicola Nante ,Gabriele Messina , Pasqualina Laganà. (2016) Hand washing in operating room: a procedural comparison. Epidemiology Biostatistics and Public Health 13: e11734-11731/11737.
Anthonisen NR, Manfreda J, Warren CP, et al. (1987) Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Intern Med 106: 196-204.
Beaton DE, Bombardier C, Katz JN, et al. (2001) Looking for important change/differences in studies of responsiveness. OMERACT MCID Working Group. Outcome Measures in Rheumatology. Minimal Clinically Important Difference. J Rheumatol 28: 400-405.
Bergemann R, Brandt A, Zoellner U, et al. (1994) Preventive treatment of chronic bronchitis: a meta-analysis of clinical trials with a bacterial extract (OM-85 BV) and a cost-effectiveness analysis. Monaldi Arch Chest Dis 49: 302-307.
Cazzola M, Rogliani P and Curradi G. (2008) Bacterial extracts for the prevention of acute exacerbations in chronic obstructive pulmonary disease: a point of view. Respir Med 102: 321-327.
Cimen P, Unlu M, Kirakli C, et al. (2015) Should Patients With COPD Be Vaccinated? Respir Care 60: 239-243.
Collet JP, Shapiro P, Ernst P, et al. (1997) Effects of an immunostimulating agent on acute exacerbations and hospitalizations in patients with chronic obstructive pulmonary disease. The PARI-IS Study Steering Committee and Research Group. Prevention of Acute Respiratory Infection by an Immunostimulant. Am J Respir Crit Care Med 156: 1719-1724.
Cvoriscec B, Ustar M, Pardon R, et al. (1989) Oral immunotherapy of chronic bronchitis: a double-blind placebo-controlled multicentre study. Respiration 55: 129-135.
Debbas N and Derenne JP. (1990) Preventive effects of an immunostimulating product on recurrent infections of chronic bronchitis in the elderly. Lung 168 Suppl: 737-740.
Emmerich B, Emslander HP, Pachmann K, et al. (1990) Local immunity in patients with chronic bronchitis and the effects of a bacterial extract, Broncho-Vaxom, on T lymphocytes, macrophages, gamma-interferon and secretory immunoglobulin A in bronchoalveolar lavage fluid and other variables. Respiration 57: 90-99.
Emmerich B, Pachmann K, Milatovic D, et al. (1992) Influence of OM-85 BV on different humoral and cellular immune defense mechanisms of the respiratory tract. Respiration 59 Suppl 3: 19-23.
Epicentro. (2012) Resistenze agli antibiotici. Available at: http://www.epicentro.iss.it/focus/resistenza_antibiotici/resistenza.asp.
G Troiano IM, N Nante, M Lancia, M Bacci. (2018) Candida autovaccination: a new strategy to prevent antifungal resistance? Journal of Infection Prevention 9: 202-202.
Hutas I. B-NG, Kraszko P. (1993) Statistical analysis of a double blind randomized clinical study of Broncho-Vaxom vs placebo in patients suffering from bronchitis. Statistical Report, Biometrix SA, Stand 412: 1-22.
L Righi RA-G, MQ Picat, H Benmansour, R Flicoteaux, H Jacquier, B Bercot, N Nante, S Chevret, L Raskine. (2016) Changing epidemiology and impact of resistant bacteria in 2010-2015 in a French Teaching Hospital. European Journal of Public Health 26.
Li J, Zheng JP, Yuan JP, et al. (2004) Protective effect of a bacterial extract against acute exacerbation in patients with chronic bronchitis accompanied by chronic obstructive pulmonary disease. Chin Med J (Engl) 117: 828-834.
Lucioni C. DC, De Benedetto F. . (2005) I costi della broncopneumopatia cronica ostruttiva: la fase prospettica dello Studio ICE (Italian Costs for Exacerbations in COPD). . Pharmacoeconomics-Italian Research Articles 7: 119-134.
Magyar P. MG, Nagy IA., Tarjan E., Zsiray M., Lantos A. (1985) The therapeutic and preventive effects of Broncho-Vaxom, a lyophilized bacterial lysate, in chorinc bronchitis: a double-blinc placebo-controlled study. Proceedings 4th congress of the European Society of Pneumology (SEP) - Milano/Stresa.
Mauel J, Van Pham T, Kreis B, et al. (1989) Stimulation by a bacterial extract (Broncho-Vaxom) of the metabolic and functional activities of murine macrophages. Int J Immunopharmacol 11: 637-645.
Messerli C, Michetti F, Sauser-Hall P, et al. (1981) [Effect of a bacterial lysate (Broncho-Vaxom) in the therapy of chronic bronchitis: multi-center double-blind clinical trial]. Rev Med Suisse Romande 101: 143-146.
Mestecky J, McGhee JR, Arnold RR, et al. (1978) Selective induction of an immune response in human external secretions by ingestion of bacterial antigen. J Clin Invest 61: 731-737.
Orcel B, Delclaux B, Baud M, et al. (1994) Oral immunization with bacterial extracts for protection against acute bronchitis in elderly institutionalized patients with chronic bronchitis. Eur Respir J 7: 446-452.
Orlandi O. BV, Donner CF., Fumagalli G., Rimoldi R., Grassi C. (1985) Immunological treatment using lysate in the prevention of recurrent bronchitis: a multicentre Italian study. Proceedings 4th congress of the European Society of Pneumology (SEP) - Milano/Stresa.
Pan L, Jiang XG, Guo J, et al. (2015) Effects of OM-85 BV in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis. J Clin Pharmacol 55: 1086-1092.
Rabe KF, Hurd S, Anzueto A, et al. (2007) Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 176: 532-555.
Rajagopalan P, Dournon E, Vilde JL, et al. (1987) Direct activation of human monocyte-derived macrophages by a bacterial glycoprotein extract inhibits the intracellular multiplication of virulent Legionella pneumophila serogroup 1. Infect Immun 55: 2234-2239.
Ravasio R. (2015) Cost-effectiveness analysis of long-acting bronchodilators for the treatment of COPD (moderate to very severe). GRHTA 2: 143-151.
Rossi A. (2005) Antibiotici nel trattamento della broncopneumopatia cronica ostruttiva riacutizzata. Available at: https://www.progettoasco.it/riviste/rivista_simg/2005/02_2005/3.pdf.
S. Xinogalos DD, D. Varonos. (1993) Clinical effectiveness of Broncho-Vaxom (BV) in patients with chronic obstructive pulmonary disease. Int J Immunotherapy IX: 135-142.
Sethi S. (2000) Infectious etiology of acute exacerbations of chronic bronchitis. Chest 117: 380S-385S.
Siddiqi A and Sethi S. (2008) Optimizing antibiotic selection in treating COPD exacerbations. Int J Chron Obstruct Pulmon Dis 3: 31-44.
Soler M, Mutterlein R and Cozma G. (2007) Double-blind study of OM-85 in patients with chronic bronchitis or mild chronic obstructive pulmonary disease. Respiration 74: 26-32.
Tang H, Fang Z, Saborio GP, et al. (2015) Efficacy and Safety of OM-85 in Patients with Chronic Bronchitis and/or Chronic Obstructive Pulmonary Disease. Lung 193: 513-519.
Tang H. FZ, Xiu Q. (2011) Efficacy and safety of bacterial lysates in patients with chronic obstructive pulmonary diseases and exacerbation. Eur Respir J 38: 3358.
Villa E, Garelli V, Braido F, et al. (2010) May we strengthen the human natural defenses with bacterial lysates? World Allergy Organ J 3: S17-23.
WHO. (2015) Antibiotic resistance: multi-country public awareness survey. Geneva.
Wilkinson TM, Donaldson GC, Hurst JR, et al. (2004) Early therapy improves outcomes of exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 169: 1298-1303.