Page 8-9 10 11 11-13 11 11 11-13 13 13 Topic 1: Treatment of isoniazid-susceptible, rifampin-susceptible TB in adults

The gap

Evidence profile

Sourced from the recommendations and future work of the source papers, classified as general, drawn from work published between 2024 and 2026, spanning 3 journals. Those papers have been cited 267 times in total.

Supporting evidence — 4 representative gaps

• Updates on the Treatment of Drug-Susceptible and Drug-Resistant Tuberculosis: An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline (2024) · American Journal of Respiratory and Critical Care Medicine · cited 122× · doi

  Page 8-9 10 11 11-13 11 11 11-13 13 13 Topic 1: Treatment of isoniazid-susceptible, rifampin-susceptible TB in adults with a 4-month rifapentine-moxifloxacin vs. 6-month regimen 13-15 Topic 2: Treatment of non-severe presumed isoniazid-susceptible, rifampin-susceptible TB in children with 4-months vs. 6-months of standard therapy 15-17 Topic 3: Treatment of rifampin-resistant, fluoroquinolone resistant TB 17- 21 with a 6-month BPaL regimen vs. 15-month or longer regimens Topic 4: Treatment of rifampin-resistant, fluoroquinolone sensitive TB 21-26 with a 6-month BPaLM regimen vs. 15-month or longer regimens

  generalrecommendations
  Keywords: month topic treatment susceptible rifampin regimen resistant isoniazid months fluoroquinolone longer regimens page adults rifapentine
• Updates on the Treatment of Drug-Susceptible and Drug-Resistant Tuberculosis: An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline (2024) · American Journal of Respiratory and Critical Care Medicine · cited 122× · doi

  Drug-Sensitive TB PICO Question 1: In adolescents and adults with drug-susceptible pulmonary TB, is a four month regimen composed of two months of isoniazid, rifapentine, pyrazinamide, moxifloxacin followed by two months of isoniazid, rifapentine, moxifloxacin (2HPZM/2HPM) as efficacious and safe as the standard six month drug-susceptible TB regimen of two months of isoniazid, rifampin, pyrazinamide, ethambutol (2HRZE) followed by four months of isoniazid, rifampin (4HR) endorsed by the ATS/CDC/ERS/IDSA guidelines? 1. Topic/Overview/Background Standard treatment for culture-positive DS-TB has required ≥6 months of antibiotics (6). Shorter, effective regimens enable patients to be cured faster and can potentially reduce treatment costs, 13 improve patient quality of life, and increase completion of therapy. The Joint Panel reviewed evidence from Study 31/A5349, a randomized, open-label, phase 3 trial comparing two 4-month rifapentine- containing regimens to the standard 6-month control regimen (11). Participants aged 12 years and older with newly diagnosed pulmonary TB were enrolled at 34 trial sites worldwide (Table 5). 2. Summary of evidence for benefits and harms For the 4-month rifapentine and moxifloxacin (RPT-MOX) based regimen compared to the standard 6- month regimen (consisting of 2 months of isoniazid, rifampin, pyrazinamide, and ethambutol followed by 4-months of isoniazid and rifampin, 2HRZE/4HR), the Joint Panel assessed equivalent outcomes of TB disease-free survival at 12 months post-randomization (cure/favorable outcome); treatment retention; acquired drug resistance; adverse events (grade 3 or higher); and, all-cause mortality within 14 days after the last dose of study medication (Table 5,Table S1). The microbiologically eligible population for analysis had 791 participants in the 4-month RPT-MOX arm and 768 participants in the 6-month control arm, all with culture-confirmed susceptibility to isoniazid, rifampin, and fluoroquinolones. RPT-MOX was non-inferior to control (84.6% vs. 85.4% cure, respectively). No significant differences in outcomes were identified for RPT-MOX and 6-month standard regimens based on smear grade, cavitation, radiologic extent, age, diabetes, body weight, or HIV status. However, the number of participants living with HIV infection, diabetes, or extreme weight or age was small (e.g., around 9% of trial participants were people living with HIV infection with CD4 count ≥100 cells/μL, and most participants were aged under 35 years (11, 12) (Table S1). As part of the ADOLOPMENT process, we adapted the WHO guideline question, evidence table, EtD framework and recommendation to the scope and audience of this guideline. We performed a literature search to update the evidence base. The literature search revealed no other clinical trials to include in this question, and only one study and corresponding analysis from the WHO guideline was utilized. While other clinical trials included shorter regimens for the treatment of DS-TB, they did not address the specific PICO question regarding a rifapentine-moxifloxacin regimen.

  generalrecommendations
  Keywords: month months isoniazid regimen participants rifapentine standard rifampin drug question moxifloxacin treatment regimens evidence pyrazinamide
• Molecular mechanisms of resistance and treatment efficacy of clofazimine and bedaquiline against Mycobacterium tuberculosis (2024) · Frontiers in Medicine · cited 23× · doi

  Our current review provides information on the efficacy of BDQ and CFZ alone and their combination use in the treatment of DR-/ MDR-TB patients. The addition of BDQ and CFZ to the therapeutic TB regimens significantly improves results for MDR-TB patients. The use of BDQ and/or CFZ-containing regimens demonstrated low mortality with high culture conversion rates. Along with this, our review also supports and provides information regarding drug resistance as well as DST to BDQ and CFZ in in vitro and clinical Mtb strains. The second-line anti-TB drugs without DST lead to the potential for known and unknown drug resistance to the BDQ and

  generalfuture work
  Keywords: review provides information patients regimens drug resistance current efficacy alone combination treatment addition therapeutic improves
• Efficacy and safety of oxiracetam for cognitive and functional outcomes after acute traumatic brain injury in Chinese populations: a systematic review and meta-analysis of randomized controlled trials (2026) · Frontiers in Pharmacology · doi

  rationale in for provides these the Most randomized evidence on oxiracetam after TBI comes from small trials conducted in China. These trials address three distinct questions: whether oxiracetam adds benefit to usual care, whether it is more effective than piracetam, and whether it adds benefit to a nimodipine-based regimen. Comparability is further limited by differences in formulation, route, dose, treatment duration, time from injury to treatment, outcome assessment, injury severity, and background care. Consequently, estimates from short-course intravenous racemic oxiracetam, oral regimens, and 90-day evaluations of L-oxiracetam may not reflect the same clinical effect. Accordingly, we systematically reviewed randomized trials conducted in China that evaluated oxiracetam in adults with acute TBI. We estimated efficacy and safety separately by comparator and outcome domain, verified treatment regimens and numerical data against the source reports, and summarized the contemporary phase 3 LOCATE trial narratively because its intervention and follow-up differed from those of the earlier trials.

  generalrecommendations
  Keywords: oxiracetam trials whether treatment randomized conducted china adds benefit care injury outcome regimens rationale provides

Questions about this gap