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

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.

Antimicrobial effect of dimethyl sulfoxide and N, N-Dimethylformamide on Mycobacterium abscessus: Implications for antimicrobial susceptibility testing.

Background: The emergence of antimicrobial resistance globally has initiated the discovery of novel antibiotics and other antimicrobial substances. Many of these novel compounds may be found in phytochemicals, where these novel compounds are extremely difficult to redissolve for antimicrobial susceptibility testing, following extraction. The aim of this study was to examine the potential antimicrobial effects of the common solvents, dimethyl sulfoxide (DMSO) and N, N-dimethylformamide (DMF), which are commonly employed as solvents of novel antimicrobial substances, with the nontuberculous Mycobacterium and Mycobacterium abscessus. Methods: : M. abscessus clinical isolates (n = 17 isolates) were examined for the antimicrobial effects of DMSO and DMF. McFarland 0.5 standards of each isolate were prepared individually on Columbia Blood agar onto which DMSO and DMF were added (10 µl) in the range neat (undiluted) - 10,000-fold (10-4) dilution and incubated. Zones of inhibition were recorded in mm. Results: : DMSO and DMF had an inhibitory effect on M. abscessus (n = 17 clinical isolates). This inhibitory effect was avoided by diluting DMSO 10-fold and DMF 10,000-fold. Conclusion: : Such data are important when employing these common solvents with molecules which are difficult to dissolve into solution, including conventional antibiotics, as well as novel antimicrobial agents, particularly in antimicrobial susceptibility studies. Investigators should therefore be aware of this inhibition and avoid working with these solvents at high concentration to avoid bacterial growth inhibition. The use of appropriate experimental controls is highly recommended in such circumstances to avoid the reporting of false-positive antimicrobial effects.