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Cracking the resistance of non-tuberculosis mycobacterium against existing antibiotics

Mycobacterium avium (M. avium) is quickly becoming the most prevalent Mycobacterium infection in western countries. M. avium is an opportunistic pulmonary pathogen, infecting patients who often are vulnerable due to existing medical conditions. Antibiotic therapy of M. avium is long (generally 18 months) and often unsuccessful at eliminating the infection, promoting resistance to commonly used antibiotics, such as clarithromycin. M. avium exists as a biofilm in lung infections, adding to the difficulty in eradicating the infection. My research investigated potential M. avium biofilm dispersing agents, as well as antibiotic synergy for improved M. avium eradication. Our findings show that ten clinically isolated M. avium samples were all highly resistant (>16μg/mL) to antibiotics commonly used in the treatment of M. avium infections, both in planktonic and biofilm phenotypes. Some isolates were found to have MICs of >128μg/mL. M. avium isolates differed in biofilm phenotype, and correspondingly, their susceptibility to antibiotics and potential biofilm dispersing agents. No antibiotics tested during this research had significant bactericidal or bacteriostatic action on any M. avium isolates, in planktonic or biofilm phenotype. The addition of 3.6mg/mL aspirin (acetylsalicylic acid) or 3.6mg/mL ibuprofen to planktonic and biofilm cells showed significant increase in M. avium cell death. Previously identified biofilm dispersing agents, such as mannitol, N-acetyl-L-cysteine, active manuka honey, methylglyoxal, Lipitor®, 2,4-dinitrophenol and EDTA, had no significant effect on dispersing M. avium biofilms or increasing their susceptibility to antibiotics. A concentrations of 4mg/mL aspirin combined with 8mg/mL of EDTA had significant effects, sterilizing and completely eradicating in vitro three week old mature M. avium biofilms. Future work should be conducted into the specific pathways aspirin and ibuprofen effect. Furthermore, development of effective agonists/antagonists of those pathways to disperse M. avium biofilms should be researched. Research into improved and novel Mycobacterial antibiotics are needed to develop drugs capable of successfully treating M. avium infections.
Type of thesis
Hodson, C. J. (2015). Cracking the resistance of non-tuberculosis mycobacterium against existing antibiotics (Thesis, Master of Science (Research) (MSc(Research))). University of Waikato, Hamilton, New Zealand. Retrieved from https://hdl.handle.net/10289/9504
University of Waikato
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