How Does Erdosteine Perform in Combination with Antibiotics?
Erdosteine is an oral mucoactive drug that reduces mucus viscosity by degrading disulfide bonds in the mucin polymer. It achieves this effect through a free thiol group in its main active metabolite, N-thiodiglycolyl-homocysteine. In addition to its mucolytic action, erdosteine exhibits antioxidant and anti-inflammatory effects and reduces bacterial adhesion, thereby enhancing the effectiveness of certain antibiotics. We provide a summary of study results demonstrating its effect on enhancing the efficacy of drugs administered in the treatment of respiratory diseases.
Combination with Antibiotics
Earlier works demonstrated the impact of erdosteine on increasing the concentration of amoxicillin in the sputum of patients with acute exacerbation of chronic bronchitis1 and subsequently the synergistic effect of erdosteine with amoxicillin in the treatment of patients with chronic bronchitis during infectious exacerbation of the disease, without increasing the incidence of adverse effects.2 They also provided evidence that erdosteine enhances the anti-adhesive action of clarithromycin on Staphylococcus aureus3 and that its addition to ciprofloxacin enhances the inhibition of bacterial adhesion to mucous membranes.4
Combination with Drugs Administered to COPD Patients
Subsequent studies revealed in vitro synergistic effects of erdosteine with budesonide and salbutamol5, 6 and demonstrated that erdosteine enhances airway response to salbutamol in patients with mild to moderate chronic obstructive pulmonary disease (COPD).7
Erdosteine is a prodrug, and the active free thiol group (RSH) only forms after its metabolism into the active metabolite in the liver. Therefore, it does not cause unwanted interactions in the digestive tract or reduce the efficacy of other drugs, especially antibiotics, when co-administered.
Enhanced Efficacy of Antibiotics in Children with LRTI
In 2007, results were published from a multicenter randomized double-blind placebo-controlled study comparing the addition of erdosteine or placebo to amoxicillin in children with lower respiratory tract infection (LRTI). It included 158 patients who were treated for 7 ± 2 days. The primary endpoint was cough, with other evaluation criteria including auscultatory findings and body temperature at the start of therapy, after 3 days, and at the end. Safety was closely monitored.
The results showed a 47% reduction in cough by the 3rd day in the erdosteine group, which indicated a significantly greater effect compared to the placebo (33% reduction; p < 0.0001). This benefit of erdosteine sustained statistical significance even at the end of the treatment. A significant impact of erdosteine addition on the reduction of rales was also observed after 3 days of treatment. The safety of the treatment was confirmed.8
Reduction in the Occurrence and Duration of COPD Exacerbations
In 2017, the RESTORE study was completed, which evaluated the impact of adding erdosteine to maintenance therapy for COPD (short-acting beta agonists, anticholinergics, adrenergics in combination with corticosteroids, xanthines, glucocorticoids) on the occurrence and duration of exacerbations. The study was a prospective randomized double-blind placebo-controlled trial involving 445 patients aged 40–80 years with stage II/III COPD.
Adding erdosteine at a dose of 300 mg twice daily led to a 19% reduction in the occurrence of exacerbations over 12 months compared to placebo (0.91 vs. 1.13 exacerbations per patient per year; p = 0.01), which was due to a reduction in the occurrence of mild exacerbations, and a 25% reduction in the duration of exacerbations regardless of their severity (9.55 vs. 12.63 days; p = 0.023). The proportion of patients experiencing adverse events was similar in both therapeutic groups.9
Increased Penetration of Antibiotics into Biofilm
Last year, a study was published on combinations of erdosteine with various antibiotics, demonstrating that its addition increases the antibiotic effect against strains of Staphylococcus aureus sensitive and resistant to methicillin (MSSA, MRSA) forming resistant biofilms. This suggests that erdosteine enhances antibiotic penetration into biofilms, likely by disrupting the polymer substances in the intercellular matrix, warranting further confirmation in future studies.10
(zza)
Sources:
1. Ricevuti G., Mazzone A., Uccelli E. et al. Influence of erdosteine, a mucolytic agent, on amoxycillin penetration into sputum in patients with an infective exacerbation of chronic bronchitis. Thorax 1988; 43 (8): 585–590, doi: 10.1136/thx.43.8.585.
2. Marchioni C. F. , Polu J. M., Taytard A. et al. Evaluation of efficacy and safety of erdosteine in patients affected by chronic bronchitis during an infective exacerbation phase and receiving amoxycillin as basic treatment (ECOBES, European Chronic Obstructive Bronchitis Erdosteine Study). Int J Clin Pharmacol Ther 1995; 33 (11): 612–618.
3. Braga P. C., Zuccotti T., Dal Sasso M. Bacterial adhesiveness: effects of the SH metabolite of erdosteine (mucoactive drug) plus clarithromycin versus clarithromycin alone. Chemotherapy 2001; 47 (3): 208–214, doi: 10.1159/000063223.
4. Dal Sasso M., Bovio C., Culici M., Braga P. C. The combination of the SH metabolite of erdosteine (a mucoactive drug) and ciprofloxacin increases the inhibition of bacterial adhesiveness achieved by ciprofloxacin alone. Drugs Exp Clin Res 2002; 28 (2–3): 75–82.
5. Dal Sasso M., Bovio C., Culici M. et al. The SH-metabolite I of erdosteine, a mucolytic drug, enhances the inhibitory effect of salbutamol on the respiratory burst of neutrophils. Drugs Exp Clin Res 2002; 28 (4): 147–154.
6. Dal Sasso M., Culici M., Guffanti E. E. et al. A combination of budesonide and the SH-metabolite I of erdosteine acts synergistically in reducing chemiluminescence during human neutrophil respiratory burst. Pharmacology 2005; 74 (3): 127–134, doi: 10.1159/000084295.
7. Dal Negro R., Visconti M., Trevisan F. et al. Erdosteine enhances airway response to salbutamol in patients with mild-to-moderate COPD. Ther Adv Respir Dis 2008; 2 (5): 271–277, doi: 10.1177/1753465808096109.
8. Balli F., Bergamini B., Calistru P. et al. Clinical effects of erdosteine in the treatment of acute respiratory tract diseases in children. Int J Clin Pharmacol Ther 2007; 45 (1): 16–22, doi: 10.5414/cpp45016.
9. Dal Negro R. W., Wedzicha J. A., Iversen M. et al.; RESTORE group. Effect of erdosteine on the rate and duration of COPD exacerbations: the RESTORE study. Eur Respir J 2017; 50 (4): 1700711, doi: 10.1183/13993003.00711-2017.
10. Pani A., Lucini V., Dugnani S., Scaglione F. Erdosteine enhances antibiotic activity against bacteria within biofilm. Int J Antimicrob Agents 2022 Mar; 59 (3): 106529, doi: 10.1016/j.ijantimicag.2022.106529.
Did you like this article? Would you like to comment on it? Write to us. We are interested in your opinion. We will not publish it, but we will gladly answer you.
