813. Combination of N-Acetyl-Cysteine With Clarithromycin Against Mycobacterium avium Infection

Abstract

Background N-Acetyl-cysteine (NAC) is widely used in patients with chronic pulmonary diseases. In previous studies, its antimicrobacterial and antimycobacterial effects have been reported. Among its effect in Mycobacteria, it has been mainly studied in Mycobacterium tuberculosis. Here, we examined whether NAC has antibiotic activity against M. avium.MethodsThe antimycobacterial effect of NAC was assessed in JCM 15430 M. avium strain infected A-549 (human lung epithelial cells) and MH-S (mouse alveolar macrophages). These cells were infected with M. avium at multiplicity of infection of 10 for 1 hours, washed and then cultivated for 5 days. Bacterial uptake was evaluated at 0 days and 5 days of cultivation. For the NAC treatment group, 5% FBS medium with 10 mM NAC was used as culture medium. We also tested its effect in combination with clarithromycin in vivo. BALB/c mice were infected intranasally with M. avium, and were given NAC (400 mg/kg) or clarithromycin (100 mg/kg) or both by gavage daily for 6 days. On day 7 of infection, lungs were harvested and CFU, cytokines and antimicrobial peptides were measured.ResultsNAC treatment of M. avium-infected A-549 and MH-S resulted in a significant reduction of mycobacterial loads (P = 0.014 and P = 0.014). In vivo, NAC treatment resulted in a significant reduction of mycobacterial loads in the lungs of M. avium-infected mice (P = 0.007). When in combination with clarithromycin, we also had an additional reduction (vs. clarithromycin monotherapy; P = 0.001). Several antimicrobial peptides significantly increased when treated with NAC and clarithromycin combination therapy.ConclusionNAC exhibits potent anti-mycobacterial effects and may limit M. avium infection. In addition with clarithromycin, it showed an additive effect in reduction of mycobacterial loads. Interestingly, in our study, several antimicrobial peptides increased significantly which may be one of the possibility on how NAC is involved in antimycobacterial effects. These results indicate that NAC may be an additional option in treating M. avium-infected patients in future, along with its classical drug regimens containing clarithromycin.Disclosures All authors: No reported disclosures.