CF patients are highly susceptible to infections with non-tuberculous mycobacteria. Mycobacterium abscessus complex (MABSC) is a complex of three closely related “species” of rapidly growing mycobacterium. Significant differences exist between M. abscessus isolates; Abscessus ssp (Abscessus sensu stricto) is the most virulent compared to M. abscessus ssp bolletii and Mycobacterium massiliense. The difference depends on the ERM (Erythromycin Ribosome Methyltransferase) gene and can be detected by PCR.
MABSC is one of the most antibiotic-resistant RGMs (Rapidly growing Mycobacterium): very few drugs are potentially active, and of these, only few can be administered orally. M. abscessus, in common with other mycobacterial species, has high levels of natural resistance to most classes of antibiotics, due to the presence of an impermeable cell wall, antibiotic-modifying/inactivating enzymes, efflux pumps and genetic polymorphisms in target genes. Additionally, M. abscessus is resistant to classical antituberculous drugs such as rifampicin and ethambutol. Therefore, with current antibiotic options, M. Abscessus is a chronic incurable infection for most CF patients.
Treatment guidelines issued by the American Thoracic Society in 2007 recommended a multi-drug regimen that included a macrolide (clarithromycin) for the treatment of pulmonary M. abscessus disease. More recent guidelines for the management of M. abscessus infection in CF patients recommended treatment with a macrolide (azithromycin), an aminoglycoside (amikacin) and at least one other drug of a different class.
Thus, there is a significant unmet medical need for safe and effective antimicrobial treatment of MABSC lung infections in CF patients. FDA has identified NTM as a Disease Areas to be the focus of FDA for 2016-2017.
We have conducted a compassionate treatment for two patients with CF who suffer from NTM (Non-Tuberculosis Mycobacterium) infections. The NO treatment regime as well as the device for this treatment were supplied by AIT ltd.
For preliminary results of this study see the following slides: