Tuberculosis (TB) remains a significant global health concern, particularly with the emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). Traditional methods for diagnosing drug resistance in TB are time-consuming and often lack accuracy, leading to delays in appropriate treatment initiation and exacerbating the spread of drug-resistant strains. In recent years, artificial intelligence (AI) techniques have shown promise in revolutionizing TB diagnosis, offering rapid and accurate identification of drug-resistant strains. This comprehensive review explores the latest advancements in AI applications for the diagnosis of MDR-TB and XDR-TB. We discuss the various AI algorithms and methodologies employed, including machine learning, deep learning, and ensemble techniques, and their comparative performances in TB diagnosis. Furthermore, we examine the integration of AI with novel diagnostic modalities such as whole-genome sequencing, molecular assays, and radiological imaging, enhancing the accuracy and efficiency of TB diagnosis. Challenges and limitations surrounding the implementation of AI in TB diagnosis, such as data availability, algorithm interpretability, and regulatory considerations, are also addressed. Finally, we highlight future directions and opportunities for the integration of AI into routine clinical practice for combating drug-resistant TB, ultimately contributing to improved patient outcomes and enhanced global TB control efforts.

Bedaquiline is currently a key drug for treating multidrug-resistant or rifampin-resistant tuberculosis. We report and discuss the unusual development of resistance to bedaquiline in a teenager in Namibia, despite an optimal background regimen and adherence. The report highlights the risk for bedaquiline resistance development and the need for rapid drug-resistance testing.

Tubercular pyomyositis is a rare but distinct clinical entity which is difficult to diagnose especially in a patient with underlying autoimmune disease. The treatment is even more challenging if it is a multi-drug resistant strain. Here we report a patient with primary Sjögren\'s syndrome who presented with persistent inflammation of his right arm which was later diagnosed as multi-drug resistant tubercular pyomyositis. This case highlights the need for a high index of suspicion for tuberculosis in all cases of pyomyositis.

UNASSIGNED: Drug-resistant tuberculosis (DR-TB) is a threat to tuberculosis (TB) control. Extra-pulmonary forms of DR-TB (DR-epTB) are not well characterized. This review summarizes the clinical features, resistance patterns and treatment outcomes of DR-epTB.
UNASSIGNED: We searched EMBASE to identify studies that reported drug-resistance among extra-pulmonary TB sites. All age groups were included in this review. Studies which did not describe drug-resistance patterns at extra-pulmonary TB sites were excluded. We summarized the proportion of resistance to individual anti-TB drugs as well as multi-drug resistant (MDR), pre-extensively drug resistant (pre-XDR) and extensively drug-resistant (XDR) TB.
UNASSIGNED: Eighteen studies with a total of 10,222 patients with extra-pulmonary TB of whom 1,236 (12.0%) had DR-epTB, were included in this review. DR-epTB was mostly reported in young people aged 28 to 46 years. While TB meningitis is the most commonly studied form, adenitis is the commonest form of DR-epTB reported in 21% to 47%. Central nervous system TB (3.8% to 51.6%), pleural TB (11.3% to 25.9%), skeletal TB (9.4% to 18.1%), abdominal TB (4.3% to 6.5%), and disseminated TB (3.8%) are also encountered. The HIV co-infection rate is reported to be 5.0% to 81.3% while 2.6% to 25.4 % have diabetes mellitus. Clinical symptoms of DR-epTB are consistent with morbidity in the affected body system. Among patients with DR-epTB, the proportion of MDR TB was 5% to 53% while that for pre-XDR TB and XDR TB was 3% to 40% and 4% to 33%, respectively. Treatment success is achieved in 26% to 83% of patients with DR-epTB while death, treatment loss-to-follow up, and treatment failure occur in 2% to 76%, 7% to 15%, and 0% to 4% respectively. Patients with DR-epTB were reported to have poorer outcomes than those with pulmonary DR-TB and extra-pulmonary drug-susceptible TB.
UNASSIGNED: Clinical features of DR-epTB are similar to those observed among people with drug-susceptible EPTB but patients with DR-epTB post worse treatment outcomes.

Definitions of resistance in multidrug-resistant tuberculosis (MDR TB) and extensively drug-resistant tuberculosis (XDR TB) have been updated. Pre-XDR TB, defined as MDR TB with additional resistance to fluoroquinolones, and XDR TB, with additional resistance to bedaquiline or linezolid, are frequently associated with treatment failure and toxicity. We retrospectively determined the effects of pre-XDR/XDR TB resistance on outcomes and safety of MDR TB treatment in France. The study included 298 patients treated for MDR TB at 3 reference centers during 2006-2019. Of those, 205 (68.8%) cases were fluoroquinolone-susceptible MDR TB and 93 (31.2%) were pre-XDR/XDR TB. Compared with fluoroquinolone-susceptible MDR TB, pre-XDR/XDR TB was associated with more cavitary lung lesions and bilateral disease and required longer treatment. Overall, 202 patients (67.8%) had favorable treatment outcomes, with no significant difference between pre-XDR/XDR TB (67.7%) and fluoroquinolone-susceptible MDR TB (67.8%; p = 0.99). Pre-XDR/XDR TB was not associated with higher risk for serious adverse events.

In 2020, European Network for Health Technology Assessment (EUnetHTA) published a relative effectiveness analysis (REA) of Pretomanid in combination with Bedaquiline and Linezolid for the treatment of extensively drug-resistant (XDR) or treatment-intolerant or nonresponsive multidrug-resistant (MDR) tuberculosis (TB) (REA PTJA14). This REA may have a significant value for low- and middle-income countries (LMICs) outside Europe, particularly those with a high burden of drug-resistant TB. This commentary focuses on whether the REA PTJA14 can be transferred and to what extent a REA can be translated to LMICs context outside Europe. We found that the assessments on the clinical effectiveness and risks of bias reported in REA PTJA14 are useful for LMICs outside Europe. The highly standardized management of TB will support the applicability of the REA to LMICs outside of Europe. Transferring this REA can reduce workload and efficiently use limited resources to conduct health technology assessment (HTA). However, the transfer should consider several critical issues, including variations in health system delivery and clinical practice and setting-specific constraints. In the TB context, the differences in the current standard treatment for XDR or nonresponsive MDR TB, resources availability for drug-resistant TB management, and how healthcare is delivered in the countries can complicate the applicability of the REA PTJA14. Given that LMICs have limitations in doing HTA, it is now critical to develop standard guidelines for transferring REA or other HTA results from high-income countries or other LMICs to maximize the benefits of the REA for LMICs outside Europe.

We report the emergence of an atpE mutation in a clinical Mycobacterium tuberculosis strain. Genotypic and phenotypic bedaquiline susceptibility testing displayed variable results over time and ultimately were not predictive of treatment outcome. This observation highlights the limits of current genotypic and phenotypic methods for detection of bedaquiline resistance.

Tuberculosis (TB) is a leading cause of death from a single infectious agent, Mycobacterium tuberculosis (Mtb). Although progress has been made in TB control, still about 10 million people worldwide develop TB annually and 1.5 million die of the disease. The rapid emergence of aggressive, drug-resistant strains and latent infections have caused TB to remain a global health challenge. TB treatments are lengthy and their side effects lead to poor patient compliance, which in turn has contributed to the drug resistance and exacerbated the TB epidemic. The relatively low output of newly approved antibiotics has spurred research interest toward alternative antibacterial molecules such as silver nanoparticles (AgNPs). In the present study, we use the natural biopolymer alginate to serve as a stabilizer and/or reductant to green synthesize AgNPs, which improves their biocompatibility and avoids the use of toxic chemicals. The average size of the alginate-capped AgNPs (ALG-AgNPs) was characterized as nanoscale, and the particles were round in shape. Drug susceptibility tests showed that these ALG-AgNPs are effective against both drug-resistant Mtb strains and dormant Mtb. A bacterial cell-wall permeability assay showed that the anti-mycobacterial action of ALG-AgNPs is mediated through an increase in cell-wall permeability. Notably, the anti-mycobacterial potential of ALG-AgNPs was effective in both zebrafish and mouse TB animal models in vivo. These results suggest that ALG-AgNPs could provide a new therapeutic option to overcome the difficulties of current TB treatments.

UNASSIGNED: Undernutrition is associated with unfavourable treatment outcomes among people with drug-resistant tuberculosis (DRTB). Factors influencing the treatment outcomes among undernourished people with DRTB are not well characterised. The aim of this study was to determine factors associated with treatment success among undernourished people with DRTB in Uganda.
UNASSIGNED: We analysed data from a retrospective cohort of people with DRTB from 16 treatment sites in Uganda. We included participants with a pre-treatment body mass index (BMI) of <18.5 kilograms/meters2 (kg/m2). Participants were categorised as having mild (BMI of 18.5-17 kg/m2), moderate (BMI of 16.9-16.0 kg/m2) or severe (BMI of <16.0 kg/m2) undernutrition. We performed logistic regression analysis to determine factors associated with treatment success.
UNASSIGNED: Among 473 people with DRTB, 276 (58.4%) were undernourished (BMI < 18.5 Kg/m2) and were included in the study. Of these, 92 (33.3%) had mild, 69 (25.0%) had moderate and 115 (41.7%) had severe undernutrition. The overall treatment success rate (TSR) for the undernourished was 71.4% (n = 197). Although the TSR was similar among participants with mild (71.7%), moderate (78.3%) and severe (67.0%) undernutrition (p = 0.258), all treatment failure cases (n =6) were among participants with severe undernutrition (p = 0.010). Cigarette smoking (odds ratio (OR) = 0.19, 95% CI 0.07-0.47, p < 0.001), urban residence (OR = 0.31, 95% CI 0.14-0.70, p = 0.005) and moderate (OR = 0.14, 95% CI 0.06-0.35, p < 0.001) and severe anaemia (OR = 0.06, 95% CI 0.01-0.29, p = 0.001) were associated with lower odds of treatment success.
UNASSIGNED: Most undernourished people with DRTB have severe undernutrition. Smoking and anaemia are modifiable factors which upon appropriate intervention could improve treatment success. The effect of urban residence on the TSR needs to be evaluated further.

BACKGROUND: Patients with drug resistant tuberculosis (DR-TB) with comorbidities and drug toxicities are difficult to treat. Guidelines recommend such patients to be managed in consultation with a multidisciplinary team of experts (the \"TB consilium\") to optimise treatment regimens. We describe characteristics and treatment outcomes of DR-TB cases presented to the national DR-TB consilium in Uganda between 2013 and 2019.
METHODS: We performed a secondary analysis of data from a nation-wide retrospective cohort of DR-TB patients with poor prognostic indicators in Uganda. Patients had a treatment outcome documented between 2013 and 2019. Characteristics and treatment outcomes were compared between cases reviewed by the consilium with those that were not reviewed.
RESULTS: Of 1,122 DR-TB cases, 189 (16.8%) cases from 16 treatment sites were reviewed by the consilium, of whom 86 (45.5%) were reviewed more than once. The most frequent inquiries (N = 308) from DR-TB treatment sites were construction of a treatment regimen (38.6%) and management of side effects (24.0%) while the most frequent consilium recommendations (N = 408) were a DR-TB regimen (21.7%) and \"observation while on current regimen\" (16.6%). Among the cases reviewed, 152 (80.4%) were from facilities other than the national referral hospital, 113 (61.1%) were aged ≥ 35 years, 72 (40.9%) were unemployed, and 26 (31.0%) had defaulted antiretroviral therapy. Additionally, 141 (90.4%) had hepatic injury, 55 (91.7%) had bilateral hearing loss, 20 (4.8%) had psychiatric symptoms and 14 (17.7%) had abnormal baseline systolic blood pressure. Resistance to second-line drugs (SLDs) was observed among 9 (4.8%) cases while 13 (6.9%) cases had previous exposure to SLDs. Bedaquiline (13.2%, n = 25), clofazimine (28.6%, n = 54), high-dose isoniazid (22.8%, n = 43) and linezolid (6.7%, n = 13) were more frequently prescribed among cases reviewed by the consilium than those not reviewed. Treatment success was observed among 126 (66.7%) cases reviewed.
CONCLUSIONS: Cases reviewed by the consilium had several comorbidities, drug toxicities and a low treatment success rate. Consilia are important \"gatekeepers\" for new and repurposed drugs. There is need to build capacity of lower health facilities to construct DR-TB regimens and manage adverse effects.