Antimycobacterial activity of nonantibiotics associated with the polypharmacy of cystic fibrosis (CF) against mycobacterium abscessus

Abstract

Background: Antimicrobial resistance (AMR) has rendered certain species of Mycobacterium difficult to treat clinically, particularly the nontuberculous Mycobacterium, Mycobacterium abscessus, in patients with cystic fibrosis (CF). Such patients are treated with several nonantibiotic medicines, which may have antimicrobial properties. Given the growing burden of AMR in M. abscessus, it is importtant to investigate the antimicrobial activity of all medicines used in the treatment of such patients. It was, therefore, the aim of this study to examine the antimicrobial activity of 10 nonantibiotic medicines used commonly in the treatment of CF. Methods: Antibiotic susceptibility studies were performed on human clinical isolates of M. abscessus (n = 16) including 11 smooth isolates, four rough isolates and one Reference isolate (NCTC 13031), against the following 10 nonantibiotic medicines:-aspirin (850 ug/ml), chlorphenamine (400 ug/ml), Creon (4000 international units/ml), cyclizine (50 mg/ml), DNase (1 μg/ml), hypertonic saline (NaCl) 7% (w/v), ibuprofen (44.4 mg/ml), lansoprazole (300 ug/ml), paracetamol (10 mg/ml), and prednisolone (500 ug/ml). Results: Of the 10 nonantibiotic drugs investigated, inhibition of M. abscessus was noted with chlorphenamine (400 ug/ml), cyclizine (50 mg/ml), ibuprofen (44.4 mg/ml) and lansoprazole (300 ug/ml), with no activity associated with aspirin (850 ug/ml), Creon (4000 international units/ml), DNase (1 μg/ml), hypertonic saline (NaCl) 7% (w/v), paracetamol (10 mg/ml), and prednisolone (500 ug/ml). The minimum inhibitory concentration (MIC) of cyclizine to M. abscessus (n = 6) ranged from 8.0 to 12.5 ug/ml, with a mean MIC, MIC50, and MIC90of 10.6, 10.0 and 12.5 ug/ml, respectively. Conclusion: This study identified that chlorphenamine, cyclizine, ibuprofen, and lansoprazole have in vitro antimycobacterial activity against clinical M. abscessus, isolated from patients with CF. Further studies should now examine potential antimicrobial synergy between these compounds and common conventional antimycobacterial antibiotics, including the macrolides and fluoroquinolones, to decide how best to exploit such positive interactions to reduce AMR burden and improve treatment regimens.

Keywords

• Antibiotic resistance
• cystic fibrosis
• drug discovery
• Mycobacterium abscessus
• treatment