pretomanid (PA-824) / Global Alliance for TB Drug Development - LARVOL DELTA

A Pilot Study on the Utility of Whole Genome Sequencing for Detecting Drug Resistance in Mycobacterium tuberculosis in the Current Scenario. (PubMed, Indian J Med Microbiol) - "Resistance detected by WGS was as follows: Isoniazid 23(39.6%), Rifampicin 21(36.2%), FQs 21(36.2%), Ethambutol 18(31%), Linezolid 12(20.6%), Streptomycin 8(13.8%), Kanamycin 6(10.3%), Amikacin and Capreomycin 5(8.6%), Para-amino salicylic acid 1(1.7%) and Ethionamide 1(1.7%). No resistance was detected to Pyrazinamide, Bedaquiline, Clofazimine, Delamanid and Pretomanid...Intermediate Resistance (IR) and potential novel mutations were observed in a few cases, Overall accuracy for first-line drugs between pDST vs WGS was >98% &pDST vs LPA >95%, while for second-line drugs accuracy was >96% and >90% respectively. IR and potential novel mutations should be followed up closely to understand their clinical significance."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Real-world treatment outcomes and adverse events during BPaLM therapy for rifampicin-resistant TB. (PubMed, IJTLD Open) - "BPaLM/BPaL achieved excellent early effectiveness but required frequent regimen modifications. Successful implementation of short-course RR/MDR-TB regimens requires anticipatory toxicity monitoring, flexible regimen management, and robust treatment support systems."

Adverse events • HEOR • Journal • Real-world evidence • Hematological Disorders • Infectious Disease • Pain • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Efficacy of quabodepistat alone and in combination with delamanid and bedaquiline against Mycobacterium tuberculosis in an NHP model evaluated by [18F] FDG PET/CT and bacterial burden. (PubMed, Antimicrob Agents Chemother) - "Bedaquiline (B), delamanid (D), and pretomanid (P) are used in combination regimens with other anti-TB drugs for MDR-TB; however, agents with novel mechanisms of action are needed...Additionally, the activities of D and P monotherapies were similar in this model. The evaluation of these agents in the marmoset TB model supports further investigation of Q as a component of shorter TB regimens."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Linezolid in the era of bedaquiline-pretomanid-linezolid-based regimens: an indispensable challenge. (PubMed, Respir Res Clin Pract) - No abstract available

Journal

Mechanism of the M. tuberculosis DprE1-DprE2 epimerase complex and inhibition by anti-tubercular drugs. (PubMed, Nat Chem Biol) - "Pretomanid and delamanid are prodrugs, whose active derivatives have been reported to target decaprenylphosphoribose-2'-reductase, DprE2, while quabodepistat is a noncovalent inhibitor of decaprenylphosphoribose-2'-oxidase, DprE1. Quabodepistat binds to DprE1 with a unique mode. Our data reveal the mode of action of these drugs, allowing rational design of new derivatives for improved tuberculosis treatments."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Treatment of multidrug-resistant tuberculosis with bedaquiline, pretomanid, linezolid, and moxifloxacin following near-total gastrectomy. (PubMed, ASM Case Rep) - "Phenotypic drug susceptibility testing could not be performed due to poor growth; however, a line probe assay performed on the isolate identified resistance to rifampin and isoniazid...This case demonstrates successful use of the all-oral BPaLM regimen in a patient with prior gastrectomy when supported by therapeutic drug monitoring. Evaluating drug exposure may help optimize treatment outcomes in patients at risk for drug malabsorption."

Journal • Gastric Adenocarcinoma • Gastric Cancer • Infectious Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Tuberculosis

Multidrug-Resistant Tuberculosis Presenting With Severe Intestinal Involvement and Cecal Volvulus (ACG 2026) - "She was started on BPaLM therapy (bedaquiline, pretomanid, linezolid, and moxifloxacin). Figure: Figure 2. CT abdomen/pelvis showing marked cecal dilation with findings consistent with cecal volvulus."

Cough • Gastrointestinal Disorder • Infectious Disease • Inflammation • Respiratory Diseases • Tuberculosis

Black hairy tongue: an early adverse effect of linezolid in treatment of multidrug resistant tuberculosis. (PubMed, BMJ Case Rep) - "A man in his 20s with microbiologically confirmed multidrug-resistant pulmonary tuberculosis was initiated on a regimen comprising bedaquiline, pretomanid, linezolid and moxifloxacin...The patient was advised on oral hygiene measures with which complete resolution occurred within 8-10 days, with no recurrence on follow-up and he was transitioned to an individualised longer regimen.This case highlights that black hairy tongue is a rare, early and reversible adverse effect of linezolid. Prompt recognition and appropriate management can prevent unnecessary discontinuation of effective multidrug-resistant tuberculosis therapy and improve treatment adherence."

Adverse events • Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Implications of edge cases for antimicrobial susceptibility predictions for rifampin, delamanid, and pretomanid with the WHO Mycobacterium tuberculosis mutation catalog. (PubMed, Microbiol Spectr) - "However, we demonstrate that false-resistant results occur even using the WHO mutation catalog for rifampin, delamanid, and pretomanid. Similar exceptions linked to the additional grading rules of the catalog are possible for other drugs, underlining the importance of monitoring the performance of the catalog continuously."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Data-driven reaction optimization and mechanism classification for Tuberculosis drugs on the high-throughput experimentation platform | Poster Board #D17 (ACS-Fall 2026) - "First, we targeted reaction optimization of the debromination step in pretomanid synthesis, one of the latest drugs for tuberculosis (TB) treatment, using the large language model (LLM)-assisted high-throughput experiment (HTE) platform...Up to 8 parallel reaction kinetics data were acquired on the nano scale using automated liquid handling robots on the 1536 wellplates, and reaction mechanisms were derived based on the high-throughput kinetics data via a machine learning classification model. Together, this platform will evolve into a universal engine for drug synthesis, offering a general solution for optimizing various complex reactions, determining reaction mechanisms, and advancing toward fully autonomous experimentation."

Infectious Disease • Respiratory Diseases • Tuberculosis

Comparative whole genome analysis of Mycobacterium tuberculosis isolated from BPaLM and individualized regimen treated patients at Dr. Soetomo Hospital, Indonesia. (PubMed, Mol Biol Rep) - "Beijing lineage strains predominated and were associated with increased drug resistance. Variants in efflux regulatory genes may contribute to the emergence of multidrug-resistant strains. The Mann-Whitney U test revealed no statistically significant difference between the two groups, with a p-value of 0.4136 (p > 0.05). Furthermore, genomic analysis revealed that the BPALM group exhibited a lower burden of single nucleotide polymorphisms (SNPs) and fewer unique cumulative genetic variants than the Individualized treatment group."

Clinical • Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

SYNERGY: Study of Combinations of Novel Promising Drugs for Pulmonary Tuberculosis (clinicaltrials.gov) - P2 | N=135 | Not yet recruiting | Sponsor: TASK Applied Science

New P2 trial • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Bactericidal Activity and Safety of Nicotinamide in Combination With Bedaquiline, Pretomanid, and Linezolid in Drug-susceptible Pulmonary Tuberculosis (clinicaltrials.gov) - P2 | N=165 | Suspended | Sponsor: Gates Medical Research Institute | Recruiting ➔ Suspended

Trial suspension • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Catalysing tuberculosis elimination in Indonesia: Health economic and policy insights from the BPaL regimen. (PubMed, PLoS One) - "BPaL is effective, affordable, and ready to scale. Integrating it into Indonesia's Jaminan Kesehatan Nasional (JKN) framework and expanding decentralised diagnostics could accelerate progress towards WHO End TB 2030 targets. Our findings offer a replicable model for other low- and middle-income settings."

HEOR • Journal • Retrospective data • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

What is new in Tuberculosis? (PubMed, Clin Med (Lond)) - "In parallel, treatment strategies are evolving, with shorter and more effective regimens available for latent TB, active disease, and multidrug-resistant TB. This review provides an overview of the epidemiology, clinical presentation, diagnosis, and management of TB, with a focus on recent advances relevant to clinical practice in the UK."

Journal • Review • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Enhancing renal tuberculosis treatment: lysozyme-mediated targeted drug delivery approaches. (PubMed, In Silico Pharmacol) - "Our study showed that ethambutol, pretomanid, and terizidone demonstrated the most stable interactions with HEWL. Additionally, in vitro and in vivo validation will be essential for advancing these findings toward clinical application. The online version contains supplementary material available at 10.1007/s40203-026-00691-8."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Diagnosis, Management, and Outcome of Antituberculous Drug-Induced Liver Injury in a Low-Resource Setting: A Case Report. (PubMed, Case Rep Infect Dis) - "The patient failed rechallenge and was transitioned to an all-oral second-line antituberculous regimen consisting of bedaquiline, pretomanid, linezolid, and moxifloxacin, alongside direct-acting antiviral therapy for chronic hepatitis C. This resulted in the resolution of liver injury and the successful completion of tuberculosis treatment without complications. This case highlights the diagnostic and management challenges of AT-DILI in low-resource settings, particularly where baseline liver function testing, serial monitoring, and access to single-drug formulations for rechallenge are limited."

Journal • Anorexia • Fibrosis • Gastroenterology • Hepatitis C • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Cirrhosis • Liver Failure • Pain • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Cerebrospinal Fluid Concentrations of Bedaquiline, Pretomanid, and Linezolid During Curative Treatment of Fluoroquinolone-Resistant Pre-Extensively Drug-Resistant Tuberculous Meningitis. (PubMed, Open Forum Infect Dis) - "A patient with fluoroquinolone-resistant pre-extensively drug-resistant (pre-XDR) TBM was cured with a 10-month regimen based on BPaL with clofazimine and cycloserine. BPaL achieved therapeutic concentrations in CSF for most TB strains. Further research is required into optimal treatment and dosing of drug-resistant TBM."

Journal • CNS Disorders • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Emergence of dual bedaquiline and linezolid resistance during treatment of pre-extensively drug-resistant tuberculosis: A case report from Zambia. (PubMed, IDCases) - "A 28-year-old HIV-positive Zambian man, virologically suppressed on tenofovir-lamivudine-dolutegravir, was initially treated for drug-sensitive pulmonary tuberculosis. Following relapse and treatment failure, rifampicin resistance was confirmed, and he was initiated on a second-line regimen...A six-month regimen of bedaquiline, pretomanid, and linezolid was commenced...A salvage regimen comprising delamanid, ethambutol, cycloserine, clofazimine, and meropenem was initiated, and the patient remains on treatment under close clinical and laboratory monitoring...The simultaneous acquisition of resistance to bedaquiline and linezolid significantly limits treatment options. Strengthening adherence support, improving laboratory turnaround times, and enhancing pharmacovigilance systems are essential to preserve the effectiveness of novel regimens in Zambia and similar settings."

Journal • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Mitigating intellectual property barriers to HIV and comorbidities treatment in Eurasian Patent Organization countries: programme results and policy implications (AIDS 2026) - "The drugs included tenofovir/emtricitabine (Armenia, Russia), rilpivirine (Russia), long-acting rilpivirine, islatravir, lenacapavir (EAPO); sofosbuvir (Russia); molnupiravir (EAPO, Russia), nirmatrelvir (EAPO); pretomanid in bedaquiline/pretomanid/linezolid regimen, pretomanid granulate, pretomanid amorphous form (EAPO), bedaquiline (Belarus, Kazakhstan, Kyrgyzstan). EECA communities developed expertise on patent challenges, successfully opposed patents, and revealed and addressed systemic barriers to CSO engagement in access-related IP work. The programme has potential for expansion, as demonstrated by a CBO opposition in Uzbekistan in December 2025 (delamanid). Results from the structural barrier analysis call for legal reform to enhance community involvement in mitigating IP barriers and improving access to medicines."

Hepatitis C • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • Tuberculosis

Synergism in drug combination of new tuberculosis antibiotics for drug-resistant Mycobacterium tuberculosis in vitro. (PubMed, Microbiol Spectr) - "Novel antituberculosis drugs such as bedaquiline (BDQ), pretomanid (Pa824), and delamanid (DLM) offer a promising treatment for DR-TB...In this research, we evaluated the synergistic effects of two dual-drug combinations (BDQ-Pa824 and BDQ-DLM) and four triple-drug combinations (BDQ-DLM-clofazimine [CFZ], BDQ-DLM-linezolid [LZD], BDQ-Pa824-CFZ, and BDQ-Pa824-LZD) against 30 Mycobacterium tuberculosis (MTB) strains isolated from TB patients...In this research, we evaluated the synergistic antimycobacterial efficacy of the new optimized antituberculosis regimen (BDQ-DLM-LZD or BDQ-DLM-CFZ) and the standard regimen (BDQ-Pa824-LZD or BDQ-Pa824-CFZ) for TB strains. This highlights the therapeutic substitutability of BDQ-DLM or BDQ-Pa824-based triple-drug regimens for TB strains."

Journal • Preclinical • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

No phenotypic resistance observed for most group-3 and -4 variants in Mycobacterium tuberculosis genes related to bedaquiline, clofazimine, delamanid, and pretomanid in a Central and West African context. (PubMed, Microbiol Spectr) - "Notably, mmpR5 variants associated with elevated bedaquiline/clofazimine MICs were identified in eight isolates, suggesting that some patients in this cohort may have harbored pre-existing resistance-associated variants yet remained potentially eligible for bedaquiline-containing regimens. These findings contribute to improving the interpretation of genomic resistance data and strengthening surveillance of resistance to bedaquiline, clofazimine, delamanid, and pretomanid."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Cost-effectiveness of BPaL-based and 9-month modified all-oral short treatment regimens for rifampicin-resistant tuberculosis in Belarus. (PubMed, PLOS Glob Public Health) - "We evaluated the cost-effectiveness of BPaL-based regimens containing bedaquiline, pretomanid, and linezolid with either moxifloxacin or clofazimine (BPaL(M/C)); mSTR composed of bedaquiline, levofloxacin, linezolid, clofazimine, cycloserine, or delamanid; and standard of care (SOC; ≥ 18-month regimens) for MDR/RR-TB and pre-XDR-TB in Belarus over a 20-year horizon using a cohort-based Markov model. The scale-up analysis showed that expanding use of shorter regimens in Belarus could generate annual TB programme budget savings exceeding USD 9.8 million. BPaL(M/C) and mSTR are cost-effective alternatives to SOC in Belarus, offering substantial economic benefits at both patient and programmatic levels."

HEOR • Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

In vitro characterization of GSK2556286 in combination with bedaquiline and pretomanid against Mycobacterium tuberculosis. (PubMed, Antimicrob Agents Chemother) - "These findings suggest that GSK286 may be a promising companion to B, with or without Pa, particularly under conditions with a sub-optimal B dose, where the GSK286 + B interaction was more clearly observed. These studies offer new insights into this drug combination to guide future research toward better tuberculosis treatments."

Journal • Preclinical • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Sorfequiline-based Regimens in Adults With Newly Diagnosed Drug-sensitive Pulmonary TB (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: Global Alliance for TB Drug Development | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis