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

Pretomanid: The life-saving drug to combat Pakistan's TB crisis. (PubMed, J Pak Med Assoc) - No abstract available

Journal

Laboratory strengthening strategies to advance drug susceptibility testing for BPaL regimens in TB treatment. (PubMed, Public Health Action) - "Our study highlights the need for continued investment in training and infrastructure to integrate DST into routine diagnostics and to support scale-up of BPaL regimens in high TB-burden settings."

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

QUANTUM: A Study of Quabodepistat-containing Regimens for the Treatment of Drug-resistant Pulmonary Tuberculosis (clinicaltrials.gov) - P3 | N=532 | Recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Not yet recruiting ➔ Recruiting

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

Whole-Genome and Targeted Sequencing of 75 Drug-Resistant Mycobacterium tuberculosis Clinical Isolates in South Korea. (PubMed, Ann Lab Med) - "Specifically, we analyzed mutations associated with resistance against isoniazid (INH), rifampicin (RIF), moxifloxacin (MFX), pyrazinamide (PZA), pretomanid (PMD), delamanid (DLM), linezolid (LZD), and bedaquiline (BDQ) and compared them with those in the 2023 WHO mutation catalog. However, PZA results were discrepant for 16 isolates. Our findings highlight the potential of WGS and targeted sequencing as powerful tools for diagnosing TB drug resistance and emphasize the need for further validation before their routine implementation in clinical settings."

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

Real-world safety profile of novel anti-multidrug-resistant tuberculosis drugs: a disproportionality analysis based on the FAERS database. (PubMed, BMJ Open) - "Our study highlights the differences in common ADEs of BDQ, DLM and Pa, as well as the differences in these ADEs among genders and age groups, providing valuable insights for clinical application."

Journal • Real-world evidence • Retrospective data • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Disorders • Hepatology • Infectious Disease • Inflammation • Liver Failure • Pain • Pancreatitis • Pulmonary Disease • Respiratory Diseases • Tuberculosis • ROR1

Direct targeted next-generation sequencing for diagnosis of drug-resistant tuberculosis from clinical samples - An update. (PubMed, Indian J Tuberc) - "For respiratory samples with rifampicin resistance, tNGS could be used for the rapid detection of additional drug resistance including newer and repurposed drugs like Bedaquiline, Delamanid, Pretomanid, Linezolid and Clofazimine for which no rapid molecular tests are currently available. tNGS could be performed using different platforms like Illumina, Oxford Nanopore Technology and/or Ion torrent and diverse bio-informatic pipeline options. Positioning of a tNGS with portability system in the current TB diagnostic algorithm and its use in the clinical management of patients' needs further evaluation and efforts."

Biomarker • Journal • Next-generation sequencing • Review • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Whole genome sequencing-based detection of extensively drug-resistant tuberculosis from Ethiopia. (PubMed, Commun Med (Lond)) - "Whole-genome sequencing identifies dominant mutations in genes such as gyrA, atpE, and Rv067 that are associated with resistance to second-line anti-tuberculosis drugs. Significant cross-resistance is observed between key second-line drugs, bedaquiline and clofazimine, as well as delamanid and pretomanid. This finding highlights the need for routine genomic surveillance to detect drug resistance early, improve treatment outcomes, and prevent transmission."

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

Exploring the anti-tuberculosis activity mechanism of OTB-658: Multi-omics analysis. (PubMed, J Pharm Biomed Anal) - "OTB-658, a novel oxazolidinone for tuberculosis, is designed to provide improved efficacy and safety compared to linezolid (LZD) in combination with bedaquiline and pretomanid (BPaL). Through an integrative approach combining whole genome, proteomics, transcriptomics, the results suggest that OTB-658 exerts its antimicrobial effects by targeting the 50S ribosomal subunit, thereby disrupting bacterial protein synthesis. This study is significant for advancing the drug's clinical trial research process and the application of OTB-658 in the treatment."

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

A PAN-USR TB Multi-Center Trial (clinicaltrials.gov) - P3 | N=610 | Recruiting | Sponsor: Shenzhen Third People's Hospital | Not yet recruiting ➔ Recruiting

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

A 6 to 9-month oral regimen for rifampicin-resistant tuberculosis: a randomised open-label non-inferiority trial in China. (PubMed, Clin Microbiol Infect) - "The all-oral regimen was non-inferior to the 9-month injectable-containing regimen, offering an alternative for patients lacking access to bedaquiline, delamanid or pretomanid. However, its efficacy against the latest WHO-recommended bedaquiline-containing regimens requires further validation."

Head-to-Head • Journal • Hepatology • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

WITHDRAWN Evaluating lineage specific response to tuberculosis treatment regimens using clinical Mycobacterium tuberculosis Complex Isolates (ASTMH 2025) - "The IC50 of first line drugs like rifampicin varied up to 4fold between Mtb lineage 4 and Maf lineage 6...Trial1 (bedaquiline, linezolid, rifapentine) and Trial2 (bedaquiline, clofazimine, moxifloxacin) were most effective against Mtb lineage 2, while SimpliciTB (bedaquiline, pretomanid, moxifloxacin, pyrazinamide) and Trial1 showed superior activity against Mtb lineage 4...MTBC lineage diversity significantly impacts regimen efficacy. Trial1 and End TB showed enhanced activity against specific lineages, underscoring the potential of lineage-tailored treatments to shorten therapy and improve TB control."

Clinical • Infectious Disease • Respiratory Diseases • Tuberculosis

Pretomanid for the treatment of drug resistant pulmonary tuberculosis: a comprehensive review. (PubMed, Arch Microbiol) - "Pretomanid, a novel nitroimidazoles or nitroimidazooxazines, was recently approved as part of BPaL (Bedaquiline, Pretomanid, and Linezolid) regimen for treating extensively drug-resistant (XDR) and treatment-intolerant/ nonresponsive multidrug-resistant (MDR) cases of pulmonary tuberculosis (TB). The better understanding of resistance patterns and molecular mechanisms underpinning pretomanid resistance is crucial for the establishment of uniform phenotypic DST methods and the development of molecular tools for rapid identification/ surveillance of pretomanid resistance. The present review explores the role of pretomanid in treating MDR and XDR-TB cases and provides an updated overview of the pharmacological properties, mechanisms of action, clinical efficacy, and the impact of resistance on the long-term effectiveness of pretomanid in TB treatment regimens."

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

Managing Drug-Resistant Tuberculosis: A Case Report on BPaLM Regimen and Linezolid-Induced Neuropathy (APSR 2025) - "The LIFT-TB initiative introduced the BPaLM regimen (bedaquiline, pretomanid, linezolid, and moxifloxacin) in 2020, offering a more effective and convenient treatment...Diagnostic tests confirmed multidrug-resistant TB (MDR-TB), with rifampicin and high-level isoniazid resistance...This case underscores the importance of frequent monitoring to manage side effects and ensure adherence, as adverse reactions often lead to treatment failure. Novel regimens enhance DR-TB management in the Philippines, but patient safety remains a priority."

Case report • Clinical • Chronic Cough • Cough • Infectious Disease • Pain • Respiratory Diseases • Tuberculosis

Tracking the evolution of an extensively drug-resistant cross-border Mycobacterium tuberculosis cluster, Europe, January 2016 up to August 2025: implications for European surveillance. (PubMed, Euro Surveill) - "First reported in 2020 across Romania, Italy and the United Kingdom, this cluster progressed from multidrug-resistant (MDR) and pre-extensively drug-resistant (pre-XDR) to XDR, including resistance to pretomanid. Evidence of ongoing local transmission is available for Italy, where 10 cases were reported from 2021 to 2025. Strengthened whole genome sequencing-based surveillance is needed to inform timely, coordinated public health responses."

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

RAD-TB: Trial of Novel Regimens for the Treatment of Pulmonary Tuberculosis (clinicaltrials.gov) - P2 | N=315 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Mar 2027 ➔ Aug 2027 | Trial primary completion date: Mar 2026 ➔ Nov 2026

Trial completion date • Trial primary completion date • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Discrepancies between Genotypic Resistance Based on WGS and Phenotypic Resistance to Bedaquiline, Delamanid, Pretomanid, and Linezolid in Drug-Resistant M. tuberculosis Isolates from South Korea (AMP 2025) - "These findings indicate the existence of resistance mechanisms not yet included in the current WHO mutation catalogue. The mismatch between pDST and whole-genome sequencing results highlights the need to combine phenotypic and genetic methods, and to continuously improve resistance mutation classification for more accurate prediction of drug resistance."

Infectious Disease • Respiratory Diseases • Tuberculosis

Treatment of Drug-Resistant Tuberculosis (DR-TB) in Germany, Austria and Switzerland - Updated Recommendations Based on the WHO Guidelines 2025 (PubMed, Pneumologie) - "DR-TB includes resistant forms of Mycobacterium tuberculosis, including isoniazid monoresistance, multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB), pre-extensively drug-resistant TB (pre-XDR-TB) and extensively drug-resistant TB (XDR-TB). For MDR/RR-TB and pre-XDR-TB without additional resistance to bedaquiline and/or linezolid, two 6-month, purely oral short-term regimens are recommended (BPaLM or BDLLfx for MDR/RR-TB and BPaL or BDLC for pre-XDR-TB [*B = bedaquiline, C = clofazimine, D = delamanid, L = linezolid, Lfx = levofloxacin; M = moxifloxacin; Pa = pretomanid])...Due to the low number of cases, treatment in specialized centers or in cooperation with them is recommended. The aim is to provide effective, tolerable therapy that is adapted to the resistance situation in order to ensure therapeutic success and prevent further development of drug-resistance."

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

Mycobacterium tuberculosis genomic surveillance in Mexico. Characterization of variants in drug resistance and efflux pump genes. (PubMed, Front Microbiol) - "In this study, we performed WGS analysis on 49 pulmonary tuberculosis isolates from Mexican patients to identify mutations conferring resistance to 11 key antimicrobial agents: four first-line drugs (isoniazid, rifampicin, ethambutol, and pyrazinamide) and 7 second line drugs (fluoroquinolones, ethionamide/prothionamide, amikacin, kanamycin, capreomycin, streptomycin, and bedaquiline). The identification of new resistance-associated variants (RAV) from clinical isolates underrepresented in global databases, contributes to develop improved diagnostic tools, optimize treatment regimens, and probably to elucidate antibiotic resistance mechanisms. Specifically, the identification of RAVs for new drugs like bedaquiline, pretomanid, delamanid, and linezolid, which are central to the most recent schemes of treatment (BPaLM, BPaL, BDLLfxC, BLMZ), is key to the improvement of patient outcomes and preventing the emergence of resistance to these critical therapeutic options."

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

MDR TUBERCULOSIS RETREATMENT AFTER FAILED INITIAL BPAL-M COURSE (CHEST 2025) - "HE was initially started on bridging regimen of meropenem. Amoxicillin-clavulanate, ethambutol, linezolid and moxifloxacin...His diabetes was controlled on insulin, Januvia and metformin...In 2019, after two ground breaking research studies – TBPRACTECAL 1 and Ze-Nix-TB - a novel all-oral 4-drug combination regimen was approved for the treatment of rifampin multi-drug resistant Tuberculosis in the form of bedaquiline (B), pretomanid (Pa), linezolid and moxifloxacin, more commonly known as BPaL-M... Treatment of drug resistance Tuberculosis has changed with the introduction of BPaL-M regimen to a shorter duration with higher efficacy. Access to the drugs, control of co-morbid conditions such as diabetes and adequate drug level monitoring remain crucial to ensure that treatment failures are left to a minimum."

Cardiovascular • Congestive Heart Failure • Cough • Diabetes • Heart Failure • Infectious Disease • Metabolic Disorders • Respiratory Diseases • Tuberculosis

Effectiveness and safety of the BPaL regimen in the Philippines. (PubMed, J Clin Tuberc Other Mycobact Dis) - "Treatment success among multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB) patients in the Philippines increased with the introduction of a 9-month all-oral treatment regimen; however, this remained sub-optimal, and patients continued to endure the burdensome and toxic effects of component medicines. In 2022, the World Health Organization recommended a 6-month MDR-TB regimen (bedaquiline, pretomanid, and linezolid or BPaL given for 26 weeks)...Linezolid dose modifications, and BPaL regimen interruption occurred in 66 % and 18 %, respectively. The BPaL regimen had a remarkably high treatment success, rapid culture conversion, and a manageable safety profile among MDR/RR-TB patients in this study despite fluoroquinolone resistance and comorbidities."

Journal • Diabetes • Human Immunodeficiency Virus • Infectious Disease • Metabolic Disorders

Impact of fluoroquinolone resistance on the cost-effectiveness of empiric treatment for multidrug- or rifampicin-resistant tuberculosis. (PubMed, PLOS Glob Public Health) - "The WHO recommends the bedaquiline, pretomanid, and linezolid (BPaL) regimen with the additional fluoroquinolone antibiotic moxifloxacin (BPaLM) for initial treatment of multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB). In the absence of fluoroquinolone DST, empirical use of BPaLM resulted in $58 (interquartile range: $49-$73), $32 (IQR: $23-$53), $35 (IQR: $28 - $51), $174 (IQR: $161 - $209) per DALY averted in Georgia, India, the Philippines, and South Africa respectively. Our findings support the empirical use of BPaLM as a potential replacement for BPaL for the treatment of MDR/RR-TB in the absence of fluoroquinolone DST, even if fluoroquinolone resistance prevalence were to increase, reinforcing recent WHO recommendations."

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

Treatment outcomes among patients with drug-resistant tuberculosis managed with BPaL/BPaLM regimen in the Southeast Zone of Nigeria. (PubMed, Pan Afr Med J) - "The recent World Health Organization (WHO) recommendation of the BPaLM regimen, consisting of bedaquiline, pretomanid, linezolid, and moxifloxacin for treatment of pre-extensively drug-resistant tuberculosis (Pre-XDR) and rifampicin-resistant tuberculosis (MDR-TB/RR), has been shown to have favorable treatment outcomes. Over 86% of the patients treated had no documentation for adverse events, while 54% of the MDR-TB/RR cases were new cases. using the BPaLM regimen for DR-TB treatment results in favorable patient outcomes."

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

Hemoptysis in a patient with MDR-tuberculosis: successful diagnosis with photon counting CT and embolization of a Rasmussen aneurysm. (PubMed, Infection) - "This case highlights the importance of considering Rasmussen aneurysms as a potential cause of hemoptysis in patients with cavitary MDR-TB, even several months after starting antibiotic therapy. Prompt imaging-based diagnosis and endovascular intervention are critical to avoid life-threatening complications."

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

QUANTUM: A Study of Quabodepistat-containing Regimen for the Treatment of Drug-resistant Pulmonary Tuberculosis (clinicaltrials.gov) - P3 | N=532 | Not yet recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

New P3 trial • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

PanACEA - STEP2C -01 (clinicaltrials.gov) - P2 | N=390 | Recruiting | Sponsor: Michael Hoelscher | N=270 ➔ 390 | Trial completion date: Feb 2025 ➔ Dec 2027 | Trial primary completion date: Feb 2025 ➔ Oct 2027

Enrollment change • Trial completion date • Trial primary completion date • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis