Background: Drug-resistant (DR) tuberculosis (TB) is typically characterized by resistance to a single or combination of first- and/or second-line anti-TB agents and commonly includes rifampicin-resistant (RR)-TB, multidrug-resistant (MDR)-TB, pre-extensively drug-resistant (pre-XDR)-TB and XDR-TB. Historically, all variations of DR-TB required treatment with second-line drugs which are less effective and more toxic than first-line options, have a longer treatment duration and are more expensive to both patients and providers. The World Health Organization (WHO) now recommends a new second-line 3-drug 6-month all-oral regimen consisting of bedaquiline, pretomanid, and linezolid referred to as BPaL.
View Article and Find Full Text PDFBackground: The bedaquiline-pretomanid-linezolid regimen has been reported to have 90% efficacy against highly drug-resistant tuberculosis, but the incidence of adverse events with 1200 mg of linezolid daily has been high. The appropriate dose of linezolid and duration of treatment with this agent to minimize toxic effects while maintaining efficacy against highly drug-resistant tuberculosis are unclear.
Methods: We enrolled participants with extensively drug-resistant (XDR) tuberculosis (i.
Children affected by rifampicin-resistant tuberculosis (RR-TB; TB resistant to at least rifampicin) are a neglected group. Each year an estimated 25,000-30,000 children develop RR-TB disease globally. Improving case detection and treatment initiation is a priority since RR-TB disease is underdiagnosed and undertreated.
View Article and Find Full Text PDFDrug-resistant tuberculosis (DR-TB) continues to pose a threat to the global eradication of TB. Regimens for extensively drug-resistant (XDR) TB are lengthy and poorly tolerated, often with unsuccessful outcomes. The TB Alliance Nix-TB trial investigated the safety and efficacy of a 26-week regimen of bedaquiline, pretomanid and linezolid (BPaL) in participants with XDR-TB, multidrug-resistant (MDR) TB treatment failure or intolerance.
View Article and Find Full Text PDFBackground: Patients with highly drug-resistant forms of tuberculosis have limited treatment options and historically have had poor outcomes.
Methods: In an open-label, single-group study in which follow-up is ongoing at three South African sites, we investigated treatment with three oral drugs - bedaquiline, pretomanid, and linezolid - that have bactericidal activity against tuberculosis and to which there is little preexisting resistance. We evaluated the safety and efficacy of the drug combination for 26 weeks in patients with extensively drug-resistant tuberculosis and patients with multidrug-resistant tuberculosis that was not responsive to treatment or for which a second-line regimen had been discontinued because of side effects.
Objective: In resource-limited settings, where genotypic drug resistance testing is rarely performed and poor adherence is the most common reason for treatment failure, programmatic approaches to handling treatment failure are essential. This study was performed to describe one such approach to adherence optimisation.
Methods: This was a single-arm study of patients on second-line protease inhibitor (PI)-based antiretroviral therapy (ART) with a HIV-1 RNA ≥400 copies/ml in Johannesburg, South Africa, between 1 March 2012 and 1 December 2013.
This guideline is an update of the post-exposure prophylaxis (PEP) guideline published by the Southern African HIV Clinicians Society in 2008. It updates the recommendations on the use of antiretroviral medications to prevent individuals who have been exposed to a potential HIV source, via either occupational or non-occupational exposure, from becoming infected with HIV. No distinction is made between occupational or non-occupational exposure, and the guideline promotes the provision of PEP with three antiretroviral drugs if the exposure confers a significant transmission risk.
View Article and Find Full Text PDFIn HIV infection, progression of immunodeficiency is associated with increased risk of paucibacillary and disseminated forms of tuberculosis (TB). As a result, the clinical presentation may be atypical and the conventional diagnostic assays often unreliable, resulting in significant treatment delays. Here, we report a case of HIV-associated immune reconstitution inflammatory syndrome and TB meningitis.
View Article and Find Full Text PDFExtrapulmonary tuberculosis (EPTB) is common in HIV-infected patients, especially at lower CD4 cell counts, yet is often difficult to diagnose with certainty. A 35-year-old man presented with dyspnoea and constitutional symptoms of tuberculosis (TB). Laboratory investigations included a positive HIV test and a CD4 cell count of 138 cells/μL.
View Article and Find Full Text PDF