Clofazimine for treatment of multidrug-resistant non-tuberculous mycobacteria.

BACKGROUND: /QUESTION: Nontuberculous mycobacteria (NTM) infections are increasingly detected but difficult to cure given complex drug-resistance patterns. Select U.S. centers have incorporated clofazimine in the treatment of NTM but experience is limited as procurement restrictions hamper widespread use. METHODS: A prospective cohort study was performed in patients diagnosed with pulmonary or extrapulmonary NTM infection and treated with clofazimine between February 2015 and April 2019 at a tertiary referral hospital. Treatment success was defined by a combined outcome of clinical stabilization, microbiologic cure and radiologic improvement. Secondary outcomes included all-cause mortality and time to sputum culture conversion. Uni/multi-variate regression were used to define associations between pre-determined predictor variables and overall treatment outcome. RESULTS: Of 44 patients enrolled, 39 (89 %) received clofazimine along with a median of 3 concomitant antibiotics. Thirty-one (80 %) of patients had pulmonary NTM infection, with Mycobacterium abscessus group and Mycobacterium avium complex being the most common species groups identified. Of 36 people with evaluable outcomes, 35 (97 %) survived and 22 (58 %) had treatment success, including 12 of 19 (63 %) with Mycobacterium abscessus group. In multivariate analysis, patients with Mycobacterium abscessus group were more likely to experience treatment success (OR 18.22, 95%CI 0.972-341.43, p = 0.052), while macrolide resistance predicted a lack of treatment success (OR 0.053, 95%CI 0.003-0.841, p = 0.037). Clofazimine was well-tolerated. CONCLUSION: Adding clofazimine to multi-class antibiotic regimens for drug-resistant NTM infection led to treatment success in the majority treated. Randomized controlled studies are needed to determine the individual impact of clofazimine within an otherwise optimized drug regimen.

A Geospatial Bibliometric Review of the HIV/AIDS Epidemic in the Russian Federation.

Background: Increasing rates of HIV/AIDS in Eastern Europe and Central Asia contrast global trends, but the scope of HIV/AIDS research originating from Russian Federation and countries of the former Soviet Union has not been quantified. Methods: We searched six major scientific databases in Russian and English languages with medical subject heading terms "HIV" or "AIDS" and "Russia" or "Soviet Union" from 1991 to 2016. Each abstract indexed was reviewed and tagged for 25 HIV/AIDS research themes, location of research focus and first author. Results and Discussion: A total of 2,868 articles were included; 2,156 (75.1%) and 712 (24.8%) described research in the Russian Federation and countries of the former Soviet Union, respectively. There were 15 publications per million population in Russian Federation. Federal districts of the Russian Federation with the highest rates of HIV had the most limited publications. An interactive web-map with time-lapse features and links to primary literature was created using ArcGIS® technology [http://arcg.is/2FUIJ5v]. Conclusion: We found a lower than expected publication rate in the Russian Federation relative to rising HIV prevalence. The greatest deficits were in the most HIV burdened regions in the Russian Federation. Our findings highlight opportunities for new research strategies and public health efforts among key populations and subnational regions.

Sensitive and specific detection of ligands using engineered riboswitches.

Riboswitches are RNA elements found in non-coding regions of messenger RNAs that regulate gene expression through a ligand-triggered conformational change. Riboswitches typically bind tightly and specifically to their ligands, so they have the potential to serve as highly effective sensors in vitro. In B. subtilis and other gram-positive bacteria, purine nucleotide synthesis is regulated by riboswitches that bind to guanine. We modified the xpt-pbuX guanine riboswitch for use in a fluorescence quenching assay that allowed us to specifically detect and quantify guanine in vitro. Using this assay, we reproducibly detected as little as 5 nM guanine. We then produced sensors for 2'-deoxyguanosine and cyclic diguanylate (c-diGMP) by appending the P1 stem of the guanine riboswitch to the ligand-binding domains of a 2'-deoxyguanosine riboswitch and a c-diGMP riboswitch. These hybrid sensors could detect 15 nM 2'-deoxyguanosine and 3 nM c-diGMP, respectively. Each sensor retained the ligand specificity of its corresponding natural riboswitch. In order to extend the utility of our approach, we developed a strategy for the in vitro selection of sensors with novel ligand specificity. Here we report a proof-of-principle experiment that demonstrated the feasibility of our selection strategy.