The TB Portals program is an international consortium of physicians, radiologists, and microbiologists from countries with a heavy burden of drug-resistant tuberculosis working with data scientists and information technology professionals. Together, we have built the TB Portals, a repository of socioeconomic/geographic, clinical, laboratory, radiological, and genomic data from patient cases of drug-resistant tuberculosis backed by shareable, physical samples. Currently, there are 1,299 total cases from five country sites (Azerbaijan, Belarus, Moldova, Georgia, and Romania), 976 (75.1%) of which are multidrug or extensively drug resistant and 38.2%, 51.9%, and 36.3% of which contain X-ray, computed tomography (CT) scan, and genomic data, respectively. The top Mycobacterium tuberculosis lineages represented among collected samples are Beijing, T1, and H3, and single nucleotide polymorphisms (SNPs) that confer resistance to isoniazid, rifampin, ofloxacin, and moxifloxacin occur the most frequently. These data and samples have promoted drug discovery efforts and research into genomics and quantitative image analysis to improve diagnostics while also serving as a valuable resource for researchers and clinical providers. The TB Portals database and associated projects are continually growing, and we invite new partners and collaborations to our initiative. The TB Portals data and their associated analytical and statistical tools are freely available at https://tbportals.niaid.nih.gov/.KEYWORDS tuberculosis, digital health, interactive portals, MDR-TB, Mycobacterium tuberculosis, query, XDR-TB, drug-resistant TB T uberculosis (TB) continues to represent a major health problem worldwide. An estimated one-third of the world's population is living with latent TB (1). In 2015, there were an estimated 10.4 million new (incident) TB cases worldwide, of which 5.9 million (56%) were among men, 3.5 million (34%) were among women, and 1.0 million (10%) were among children. People living with HIV accounted for 1.2 million (11%) of

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Bedaquiline is recommended by the World Health Organization for the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB). We pooled data from 5 cohorts of patients treated with bedaquiline in France, Georgia, Armenia, and South Africa and in a multicountry study. The rate of culture conversion to negative at 6 months (by the end of 6 months of treatment) was 78% (95% CI 73.5%–81.9%), and the treatment success rate was 65.8% (95% CI 59.9%–71.3%). Death rate was 11.7% (95% CI 7.0%–19.1%). Up to 91.1% (95% CI 82.2%–95.8%) of the patients experienced > 1 adverse event, and 11.2% (95% CI 5.0%–23.2%) experienced a serious adverse event. Lung cavitations were consistently associated with unfavorable outcomes. The use of bedaquiline in MDR and XDR TB treatment regimens appears to be effective and safe across different settings, although the certainty of evidence was assessed as very low.

Background Bedaquiline and delamanid are newly available drugs for treating multidrug-resistant tuberculosis (MDR TB); however, there is limited data guiding their use and no comparison studies. Methods We conducted a prospective observational study among patients with MDR TB in Georgia receiving a bedaquiline or delamanid-based treatment regimen. Monthly sputum cultures, minimal inhibitory concentration testing, and adverse event monitoring were performed. Primary outcomes were culture conversion rates and clinical outcomes. Targeted maximum likelihood estimation (TMLE) and superlearning were utilized to produce a covariate-adjusted proportion of outcomes for each regimen. Results Among 156 patients with MDR TB, 100 were enrolled and 95 were receiving a bedaquiline (n=64) or delamanid (n=31) based regimen. Most were male (82%) and the median age was 38 years. Rates of previous treatment (56%) and cavitary disease (61%) were high. The most common companion drugs included linezolid, clofazimine, cycloserine and a fluoroquinolone. Median effective drugs received among patients on bedaquiline (4, IQR 4-4) and delamanid (4, IQR 3.5-5) based regimens were similar. Rates of acquired drug resistance were significantly higher among patients receiving delamanid versus bedaquiline (36% vs. 10%, p <0.01). Adjusted rates of sputum culture conversion at two months (67 vs. 47%, p=0.10) and six months (95 vs. 74%, p<0.01) and favorable clinical outcomes (96 vs. 72%, p<0.01) were higher among patients receiving bedaquiline versus delamanid. Conclusions Among patients with MDR TB, bedaquiline-based regimens were associated with higher rates of sputum culture conversion and favorable outcomes and a lower rate of acquired drug resistance versus delamanid-based regimens.

Improved knowledge regarding the tissue penetration of antituberculosis drugs may help optimize drug management. Patients with drug-resistant pulmonary tuberculosis undergoing adjunctive surgery were enrolled. Serial serum samples were collected, and microdialysis was performed using ex vivo lung tissue to measure pyrazinamide concentrations. Among 10 patients, the median pyrazinamide dose was 24.7 mg/kg of body weight. Imaging revealed predominant lung lesions as cavitary (n ϭ 6 patients), mass-like (n ϭ 3 patients), or consolidative (n ϭ 1 patient). On histopathology examination, all tissue samples had necrosis; eight had a pH of Յ5.5. Tissue samples from two patients were positive for Mycobacterium tuberculosis by culture (pH 5.5 and 7.2). All 10 patients had maximal serum pyrazinamide concentrations within the recommended range of 20 to 60 g/ml. The median lung tissue free pyrazinamide concentration was 20.96 g/ml. The median tissue-to-serum pyrazinamide concentration ratio was 0.77 (range, 0.54 to 0.93). There was a significant inverse correlation between tissue pyrazinamide concentrations and the amounts of necrosis (R ϭ Ϫ0.66, P ϭ 0.04) and acid-fast bacilli (R ϭ Ϫ0.75, P ϭ 0.01) identified by histopathology. We found good penetration of pyrazinamide into lung tissue among patients with pulmonary tuberculosis with a variety of radiological lesion types. Our tissue pH results revealed that most lesions had a pH conducive to pyrazinamide activity. The tissue penetration of pyrazinamide highlights its importance in both drug-susceptible and drug-resistant antituberculosis treatment regimens.