Abstract
Mycobacteriosis is mainly caused by two groups of species: Mycobacterium tuberculosis and non-tuberculosis mycobacteria (NTM). The pathogens cause not only respiratory infections, but also general diseases. The common problem in these pathogens as of today is drug resistance. Tuberculosis (TB) is a major public health concern. A major challenge in the treatment of TB is anti-mycobacterial drug resistance (AMR), including multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. Recently, the success rate of the treatment of drug-resistant tuberculosis (DR-TB) has improved significantly with the introduction of new and repurposed drugs, especially in industrialized countries such as Japan. However, long-term treatment and the adverse events associated with the treatment of DR-TB are still problematic. To solve these problems, optimal treatment regimens designed/tailor-made for each patient are necessary, regardless of the location in the world. In contrast to TB, NTM infections are environmentally oriented. Mycobacterium avium-intracellulare complex (MAC) and Mycobacterium abscessus species (MABS) are the major causes of NTM infections in Japan. These bacteria are naturally resistant to a wide variation of antimicrobial agents. Macrolides, represented by clarithromycin (CLR) and amikacin (AMK), show relatively good correlation with treatment success. However, the efficacies of potential drugs for the treatment of macrolide-resistant MAC and MABS are currently under evaluation. Thus, it is particularly difficult to construct an effective treatment regimen for macrolide-resistant MAC and MABS. AMR in NTM infections are rather serious in Japan, even when compared with challenges associated with DR-TB. Given the AMR problems in TB and NTM, the appropriate use of drugs based on accurate drug susceptibility testing and the development of new compounds/regimens that are strongly bactericidal in a short-time course will be highly expected.
Highlights
anti-mycobacterial drug resistance (AMR) in non-tuberculosis mycobacteria (NTM) infections are rather serious in Japan, even when compared with challenges associated with drug-resistant tuberculosis (DR-TB)
Reported that 31% of cases in Asia were caused by RGM including Mycobacterium abscessus species (MABS), which is epidemiological studies of NTM diseases are still few, the reported statistics ind the highest proportion amongst the regions investigated [7]
In the new ATS/ERS/ESCMID/IDSA guidelines, AZM is recommended as the first choice of macrolide compared to CLR
Summary
The standard short-course regimen is utilized for the initial treatment of TB in Japan. The 2020 revision of the guidelines recommend switching from injections to BDQ in short-term regimens [11] In response to these changes, the definitions of pre-extensively drug resistance- and extensively drug resistance (XDR)-TB were changed in 2021 (Table 2) [14]. Shortening the duration of treatment is appealing [10], the patient must have been treated with a second-line drug for less than one month and be susceptible to fluoroquinolones to be eligible for the WHO shorter regimen [10]. Shortening the duration of treatment for TB has been a longstanding issue, Dorman et al recently reported in an open-label, randomized, controlled phase 3 trial that a short-term (four months) regimen for the treatment of newly diagnosed TB, in which RIF was replaced with rifapentine and moxifloxacin (MFLX), showed non-inferior results to a standard six-month regimen [15]
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