Browsing by Subject "Antibiotics, Antitubercular"
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Item Open Access Improved tuberculosis outcomes with daily vs. intermittent rifabutin in HIV-TB coinfected patients in India.(The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 2016-09) Jenks, JD; Kumarasamy, N; Ezhilarasi, C; Poongulali, S; Ambrose, P; Yepthomi, T; Devaraj, C; Benson, CASetting
Y R Gaitonde Centre for AIDS Research and Education, Chennai, India.Objective
To compare anti-tuberculosis treatment outcomes in individuals with human immunodeficiency virus (HIV) and tuberculosis (TB) co-infection on atazanavir/ritonavir (ATV/r) antiretroviral therapy (ART) plus daily rifabutin (RBT) 150 mg with those on ATV/r plus thrice-weekly RBT 150 mg.Design
A retrospective study was conducted of two HIV-TB co-infected cohorts between 2003 and 2014. Basic demographic and TB outcome data were obtained from an electronic database and patient records. The χ(2) and Fisher's exact test were used to compare daily and intermittent RBT treatment groups.Results
Of 292 individuals on an ATV/r-based ART regimen plus RBT, 118 (40.4%) received thrice-weekly RBT and 174 (59.6%) daily RBT. Patients in the two RBT treatment groups were similar in sex, age, previous history of TB, site of TB and acid-fast bacilli smear status. More individuals in the daily vs. the intermittent RBT group achieved clinical cure (73.0% vs. 44.1%, P < 0.001), with no significant differences in relapse/recurrence or all-cause mortality between groups.Conclusion
There were higher rates of clinical TB cure in individuals on a boosted protease inhibitor-based ART regimen with daily RBT compared to intermittently dosed RBT. Optimal RBT dosing in this setting requires further investigation.Item Open Access Interception of host angiogenic signalling limits mycobacterial growth.(Nature, 2015-01-29) Oehlers, Stefan H; Cronan, Mark R; Scott, Ninecia R; Thomas, Monica I; Okuda, Kazuhide S; Walton, Eric M; Beerman, Rebecca W; Crosier, Philip S; Tobin, David MPathogenic mycobacteria induce the formation of complex cellular aggregates called granulomas that are the hallmark of tuberculosis. Here we examine the development and consequences of vascularization of the tuberculous granuloma in the zebrafish-Mycobacterium marinum infection model, which is characterized by organized granulomas with necrotic cores that bear striking resemblance to those of human tuberculosis. Using intravital microscopy in the transparent larval zebrafish, we show that granuloma formation is intimately associated with angiogenesis. The initiation of angiogenesis in turn coincides with the generation of local hypoxia and transcriptional induction of the canonical pro-angiogenic molecule Vegfaa. Pharmacological inhibition of the Vegf pathway suppresses granuloma-associated angiogenesis, reduces infection burden and limits dissemination. Moreover, anti-angiogenic therapies synergize with the first-line anti-tubercular antibiotic rifampicin, as well as with the antibiotic metronidazole, which targets hypoxic bacterial populations. Our data indicate that mycobacteria induce granuloma-associated angiogenesis, which promotes mycobacterial growth and increases spread of infection to new tissue sites. We propose the use of anti-angiogenic agents, now being used in cancer regimens, as a host-targeting tuberculosis therapy, particularly in extensively drug-resistant disease for which current antibiotic regimens are largely ineffective.