To separate Mycobacterium abscessus subsp. bolletii from Mycobacterium abscessus subsp. abscessus using species identification, and to investigate the in vitro activity of amikacin, cefoxitin, imipenem, levofloxacin, moxifloxacin, clarithromycin, azithromycin, and linezolid against Mycobacterium abscessus. Seventy M. abscessus isolates, previously identified by 16S rRNA sequencing, were further identified by comparative sequence analysis of rpoB and hsp65. Drug susceptibility testing was conducted using the microplate Alamar Blue assay in accordance with Clinical and Laboratory Standards Institute (CLSI) guidelines and interpreted using CLSI breakpoints. Of the 70 strains, 45 (64%) were M. abscessus subsp. abscessus and 25 (36%) were M. abscessus subsp. bolletii. The majority of M. abscessus isolates were susceptible to azithromycin, amikacin, linezolid, and imipenem (M. abscessus subsp. abscessus: 93%, 98%, 93%, and 73%, respectively; M. abscessus subsp. bolletii: 96%, 96%, 80%, and 68%, respectively). Approximately half of the M. abscessus isolates were moderately susceptible to cefoxitin and moxifloxacin (M. abscessus subsp. abscessus 53% and 49%; M. abscessus subsp. bolletii 72% and 68%). Nearly all the M. abscessus isolates were resistant to levofloxacin (M. abscessus subsp. abscessus 96%, M. abscessus subsp. bolletii 100%). Inducible clarithromycin resistance was found in M. abscessus. After 14 days of incubation, 83% M. abscessus subsp. abscessus and 36% M. abscessus subsp. bolletii were resistant to clarithromycin. Using rpoB and hsp65, M. abscessus subsp. bolletii could be distinguished from M. abscessus subsp. abscessus. Amikacin and azithromycin showed excellent activity against M. abscessus in vitro. Imipenem, linezolid, cefoxitin, and moxifloxacin also showed good activity. Levofloxacin was inactive against M. abscessus. Although clarithromycin showed excellent activity against M. abscessus on day 3, inducible resistance occurred, and after 14 days clarithromycin showed little activity against M. abscessus subsp. abscessus, but still had good activity against M. abscessus subsp. bolletii.

Current TB treatment regimens are hindered by drug resistance, numerous adverse effects, and long treatment durations, highlighting the need for ‘me-better’ treatment regimens. Host-directed therapy (HDT) has gained recognition as a promising approach in TB treatment. It allows the repurposing of existing drugs approved for other conditions and aims to enhance the effectiveness of existing anti-TB therapies, minimize drug resistance, decrease treatment duration, and adverse effects. By modulating the host immune response, HDT ameliorates immunopathological damage and improves overall outcomes by promoting autophagy, antimicrobial peptide production, and other mechanisms. It holds promise for addressing the challenges posed by multiple and extensively drug-resistant Mycobacterium tuberculosis strains, which are increasingly difficult to treat using conventional therapies. This article reviews various HDT candidates, including repurposed drugs, explores their underlying mechanisms such as autophagy promotion and inflammation reduction, while emphasizing their potential to improve TB treatment outcomes and outlining future research directions.

The blood concentration of isoniazid (INH) is evidently affected by polymorphisms in N -acetyltransferase 2 (NAT2), an enzyme that is primarily responsible for the trimodal (i.e., fast, intermediate, and slow) INH elimination. The pharmacokinetic (PK) variability, driven largely by NAT2 activity, creates a challenge for the deployment of a uniform INH dosage in tuberculosis (TB) patients.

Background: To determine the diagnostic accuracy of a nanopore sequencing assay of PCR products from a M. tuberculosis complex-specific region for testing of bronchoalveolar lavage fluid (BALF) samples or sputum samples from suspected pulmonary tuberculosis (PTB) patients and compare the results to results obtained for MGIT and Xpert assays. Methods: Cases with suspected PTB (n = 55) were diagnosed from January 2019 to December 2021 based on results of nanopore sequencing, MGIT culture, and Xpert MTB/RIF testing of BALF and sputum samples collected during hospitalization. Diagnostic accuracies of assays were compared. Results: Ultimately, data from 29 PTB patients and 26 non-PTB cases were analyzed. PTB diagnostic sensitivities of MGIT, Xpert MTB/RIF, and nanopore sequencing assays were 48.28%, 41.38%, and 75.86%, respectively, thus demonstrating that nanopore sequencing provided greater sensitivity than was provided by MGIT culture and Xpert assays (P < 0.05). PTB diagnostic specificities of the respective assays were 65.38%, 100%, and 80.77%, which corresponded with kappa coefficient (κ) values of 0.14, 0.40, and 0.56, respectively. These results indicate that nanopore sequencing provided superior overall performance as compared to Xpert and MGIT culture assays and provided significantly greater PTB diagnostic accuracy than Xpert and sensitivity comparable to that of the MGIT culture assay. Conclusion: Our findings suggest that improved detection of PTB in suspected cases was achieved using nanopore sequencing-based testing of BALF or sputum samples than was achieved using Xpert and MGIT culture-based assays, and nanopore sequencing results alone cannot be used to rule out PTB.