Bedaquiline-pretomanid-moxifloxacin-pyrazinamide for drug-sensitive and drug-resistant pulmonary tuberculosis treatment: a phase 2c, open-label, multicentre, partially randomised controlled trial.

Background: The current tuberculosis (TB) drug development pipeline is being re-populated with candidates, including nitroimidazoles such as pretomanid, that exhibit a potential to shorten TB therapy by exerting a bactericidal effect on non-replicating bacilli. Based on results from preclinical and early clinical studies, a four-drug combination of bedaquiline, pretomanid, moxifloxacin, and pyrazinamide (BPaMZ) regimen was identified with treatment-shortening potential for both drug-susceptible (DS) and drug-resistant (DR) TB. This trial aimed to determine the safety and efficacy of BPaMZ.

An international observational study to assess the impact of the Omicron variant emergence on the clinical epidemiology of COVID-19 in hospitalised patients.

Background: Whilst timely clinical characterisation of infections caused by novel SARS-CoV-2 variants is necessary for evidence-based policy response, individual-level data on infecting variants are typically only available for a minority of patients and settings.

Methods: Here, we propose an innovative approach to study changes in COVID-19 hospital presentation and outcomes after the Omicron variant emergence using publicly available population-level data on variant relative frequency to infer SARS-CoV-2 variants likely responsible for clinical cases. We apply this method to data collected by a large international clinical consortium before and after the emergence of the Omicron variant in different countries.

Delamanid Central Nervous System Pharmacokinetics in Tuberculous Meningitis in Rabbits and Humans.

Central nervous system tuberculosis (TB) is devastating and affects vulnerable populations. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculous meningitis (TBM) specifically are nearly uniformly fatal, with little information being available to guide the treatment of these patients. Delamanid (DLM), a nitro-dihydro-imidazooxazole, is a new, well-tolerated anti-TB drug with a low MIC (1 to 12 ng/ml) against It is used for the treatment of pulmonary MDR-TB, but pharmacokinetic (PK) data for DLM in the central nervous system (CNS) of patients with TBM are not available.

Efficacy and safety of delamanid in combination with an optimised background regimen for treatment of multidrug-resistant tuberculosis: a multicentre, randomised, double-blind, placebo-controlled, parallel group phase 3 trial.

Background: Delamanid is one of two recently approved drugs for the treatment of multidrug-resistant tuberculosis. We aimed to evaluate the safety and efficacy of delamanid in the first 6 months of treatment.

Methods: This randomised, double-blind, placebo-controlled, phase 3 trial was done at 17 sites in seven countries (Estonia, Latvia, Lithuania, Moldova, Peru, the Philippines, and South Africa).

Estimating the future burden of multidrug-resistant and extensively drug-resistant tuberculosis in India, the Philippines, Russia, and South Africa: a mathematical modelling study.

Background: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are emerging worldwide. The Green Light Committee initiative supported programmatic management of drug-resistant tuberculosis in 90 countries. We used estimates from the Preserving Effective TB Treatment Study to predict MDR and XDR tuberculosis trends in four countries with a high burden of MDR tuberculosis: India, the Philippines, Russia, and South Africa.

Association between Regimen Composition and Treatment Response in Patients with Multidrug-Resistant Tuberculosis: A Prospective Cohort Study.

Background: For treating multidrug-resistant tuberculosis (MDR TB), the World Health Organization (WHO) recommends a regimen of at least four second-line drugs that are likely to be effective as well as pyrazinamide. WHO guidelines indicate only marginal benefit for regimens based directly on drug susceptibility testing (DST) results. Recent evidence from isolated cohorts suggests that regimens containing more drugs may be beneficial, and that DST results are predictive of regimen effectiveness.

Multidrug-Resistant Tuberculosis Treatment Outcomes in Relation to Treatment and Initial Versus Acquired Second-Line Drug Resistance.

Background: Resistance to second-line drugs develops during treatment of multidrug-resistant (MDR) tuberculosis, but the impact on treatment outcome has not been determined.

Methods: Patients with MDR tuberculosis starting second-line drug treatment were enrolled in a prospective cohort study. Sputum cultures were analyzed at a central reference laboratory.

Additional drug resistance of multidrug-resistant tuberculosis in patients in 9 countries.

Data from a large multicenter observational study of patients with multidrug-resistant tuberculosis (MDR TB) were analyzed to simulate the possible use of 2 new approaches to treatment of MDR TB: a short (9-month) regimen and a bedaquiline-containing regimen. Of 1,254 patients, 952 (75.9%) had no resistance to fluoroquinolones and second-line injectable drugs and thus would qualify as candidates for the 9-month regimen; 302 (24.

Sputum culture conversion as a prognostic marker for end-of-treatment outcome in patients with multidrug-resistant tuberculosis: a secondary analysis of data from two observational cohort studies.

Background: Sputum culture conversion is often used as an early microbiological endpoint in phase 2 clinical trials of tuberculosis treatment on the basis of its assumed predictive value for end-of-treatment outcome, particularly in patients with drug-susceptible tuberculosis. We aimed to assess the validity of sputum culture conversion on solid media at varying timepoints, and the time to conversion, as prognostic markers for end-of-treatment outcome in patients with multidrug-resistant (MDR) tuberculosis.

Methods: We analysed data from two large cohort studies of patients with MDR tuberculosis.

Extensive drug resistance acquired during treatment of multidrug-resistant tuberculosis.

Background: Increasing access to drugs for the treatment of multidrug-resistant (MDR) tuberculosis is crucial but could lead to increasing resistance to these same drugs. In 2000, the international Green Light Committee (GLC) initiative began to increase access while attempting to prevent acquired resistance.

Methods: To assess the GLC's impact, we followed adults with pulmonary MDR tuberculosis from the start to the end of treatment with monthly sputum cultures, drug susceptibility testing, and genotyping.

Weight gain and response to treatment for multidrug-resistant tuberculosis.

Alternatives to culture are needed in high burden countries to assess whether response to treatment of multidrug-resistant-tuberculosis (MDR-TB) is satisfactory. The objective was to assess the association of weight gain and treatment outcome. The methods included analysis of clinical, bacteriologic, and weight from 439 MDR-TB patients in the Philippines.

Design and implementation of an HIV/AIDS electronic medical record system (HIV/AIDS EMR) in the Philippines.

An electronic medical record system can help scale up the HIV/AIDS treatment program of a country. The authors illustrate how an HIV/AIDS electronic medical record system (HIV/AIDS EMR) was designed and implemented among treatment facilities across the Philippines.

Evaluation of the TB-Biochip oligonucleotide microarray system for rapid detection of rifampin resistance in Mycobacterium tuberculosis.

The TB-Biochip oligonucleotide microarray system is a rapid system to detect mutations associated with rifampin (RIF) resistance in mycobacteria. After optimizing the system with 29 laboratory-generated rifampin-resistant mutants of Mycobacterium tuberculosis, we evaluated the performance of this test using 75 clinical isolates of Mycobacterium tuberculosis. With this small sample set, the TB-Biochip system displayed a sensitivity of 80% and a specificity of 100% relative to conventional drug susceptibility testing results for RIF resistance.