Population Pharmacokinetic Analysis of Bedaquiline-Clarithromycin for Dose Selection Against Pulmonary Nontuberculous Mycobacteria Based on a Phase 1, Randomized, Pharmacokinetic Study.

Based on the in vitro profile of bedaquiline against mycobacterial species, it is being investigated for clinical efficacy against pulmonary nontuberculous mycobacteria (PNTM). Being a cytochrome P450 3A substrate, pharmacokinetic interactions of bedaquiline are anticipated with clarithromycin (a cytochrome P450 3A inhibitor), which is routinely used in pulmonary nontuberculous mycobacteria treatment. This phase 1, randomized, crossover study assessed the impact of steady-state clarithromycin (500 mg every 12 hours for 14 days) on the pharmacokinetics of bedaquiline and its metabolite (M2) after single-dose bedaquiline (100 mg; n  =  16).

The cost-effectiveness of a bedaquiline-containing short-course regimen for the treatment of multidrug-resistant tuberculosis in South Africa.

: Bedaquiline-containing regimens have demonstrated improved outcomes over injectable-containing regimens in the long-term treatment of multidrug-resistant tuberculosis (MDR-TB). Recently, the World Health Organization (WHO) recommended replacing injectables in the standard short-course regimen (SCR) with a bedaquiline-containing regimen. The South African national TB program similarly recommends a bedaquiline-containing regimen.

Long-term impact of the adoption of bedaquiline-containing regimens on the burden of drug-resistant tuberculosis in China.

Background: Currently available injectable agents are inadequate to address the high drug-resistant tuberculosis (DR-TB) burden in China. Regimens including the oral agent bedaquiline have been shown to be efficacious and safe, leading to its incorporation into multiple national TB treatment programs. This analysis evaluated the impact of increased adoption of bedaquiline-containing regimens on the DR-TB burden in China.

Bedaquiline- versus injectable-containing drug-resistant tuberculosis regimens: a cost-effectiveness analysis.

Background: Drug-resistant tuberculosis (DR-TB) continues to be a major public health challenge with suboptimal treatment outcomes including well-documented treatment-related toxicities. We compared the cost-effectiveness of bedaquiline (BDQ) containing regimens with injectable containing regimens (short-course regimen [SCR] and long-course regiman [LCR]) in India, Russia, and South Africa.

Methods: The analysis evaluated the direct costs of DR-TB treatment which included drugs, hospitalization, injectable-related adverse event costs, and other costs.

Evaluation of six months sputum culture conversion as a surrogate endpoint in a multidrug resistant-tuberculosis trial.

The emergence of multidrug resistant-tuberculosis (MDR-TB), defined as Mycobacterium tuberculosis strains with in vitro resistance to at least isoniazid and rifampicin, has necessitated evaluation and validation of appropriate surrogate endpoints for treatment response in drug trials for MDR-TB. The trial that has demonstrated efficacy of bedaquiline, a diarylquinoline that inhibits mycobacterial ATP synthase, possesses the requisite features to conduct this evaluation. Approval of bedaquiline for use in MDR-TB was based primarily on the results of the controlled C208 Stage II study (ClinicalTrials.

Health outcomes of bedaquiline in the treatment of multidrug-resistant tuberculosis in selected high burden countries.

Background: Less than one-third of patients who are estimated to be infected with multidrug-resistant tuberculosis (MDR-TB) receive MDR-TB treatment regimens, and only 48% of those who received treatment have successful outcomes. Despite current regimens, newer, more effective and cost-effective approaches to treatment are needed. The aim of the study was to project health outcomes and impact on healthcare resources of adding bedaquiline to the treatment regimen of MDR-TB in selected high burden countries: Estonia, Russia, South Africa, Peru, China, the Philippines, and India.

Cost-effectiveness of adding bedaquiline to drug regimens for the treatment of multidrug-resistant tuberculosis in the UK.

Objective: To evaluate the cost-effectiveness of adding bedaquiline to a background regimen (BR) of drugs for multidrug-resistant tuberculosis (MDR-TB) in the United Kingdom (UK).

Methods: A cohort-based Markov model was developed to estimate the incremental cost-effectiveness ratio of bedaquiline plus BR (BBR) versus BR alone (BR) in the treatment of MDR-TB, over a 10-year time horizon. A National Health Service (NHS) and personal social services perspective was considered.

Rifapentine for the treatment of pulmonary tuberculosis.

Rifapentine is a recently approved antituberculosis drug that has not yet been widely used in clinical settings. Clinical data support intermittent use of rifapentine with isoniazid during the continuation phase of tuberculosis treatment. Patients with culture-positive, noncavitary, pulmonary tuberculosis whose sputum smear is negative for acid-fast bacilli at the end of the 2-month intensive treatment phase are eligible for rifapentine therapy.

Malaria: 30 years of experience at a New York City teaching hospital.

Two previous reviews summarized the New York Hospital experience with 110 cases of malaria from 1968 to 1990. We have extended these studies to include 59 cases of malaria seen from 1991 to 1999 and analyze trends over the past 30 years. Plasmodium falciparum remains the most common species, 38 (64%) of the 59 cases, with the majority of them, 34 (89%) of 38 cases, being acquired in Africa.