Pretomanid 200mg tablets

Concerns regarding the rise of drug-resistant tuberculosis (DR-TB) infections and the need for new drugs with shorter treatment time and fewer side effects have been voiced by the World Health Organization (WHO). The WHO revised its guideline to treat multi-drug resistant tuberculosis (MDR-TB) with a 6-month course of BPaLM (bedaquiline, pretomanid, linezolid and moxifloxacin) in 2022. However, a thorough study and meta-analysis of available evidence is required due to the limited confidence of the evidence confirming the effectiveness of pretomanid-containing regiments. The aim of this systematic review and meta-analysis was to evaluate the effectiveness of pretomanid-containing regiments in treating DR-TB patients. Data from six search engines were searched using inclusion criteria based on the PICOS framework. The keywords of pretomanid and tuberculosis or their alternatives were used. Using RoB2 Cochrane risk-of-bias tool for randomized clinical trials, data were independently extracted and the quality of the data was evaluated. Odds ratio (OR) and heterogeneity tests were used and the findings were presented in ORs and forest plots. A total of four studies with 237 patients was included in the final analysis and 204 (86%) patients had favorable outcome (cured) and 33 (14%) was not cured. Pretomanid-containing regimen (OR: 46.73; 95%CI: 11.76–185.7) and BPaLM/BPaL (OR: 41.67; 95%CI: 8.86–196.73) regimens were associated with favorable outcome (cured). This meta-analysis indicates that the pretomanid-containing regimen and the BPaLM/BPaL regimen could increase the chance to have favorable outcome in DR-TB patients.

Abstract licence: CC BY-NC 4.0

Novel anti-tuberculosis (TB) drugs have been shown to effectively treat drug-resistant TB (DR-TB). However, there is a risk of hepatotoxicity. We aimed to evaluate the incidence of hepatotoxicity in TB patients receiving bedaquiline (BDQ), delamanid (DLM), and/or pretomanid (Pa). This meta-analysis (PROSPERO: CRD42024564922) systematically explored electronic databases (i.e., Clinicaltrials.gov, Cochrane CENTRAL, Embase, PROQUEST, PubMed, ScienceDirect, and SinoMed) for clinical trials reporting the incidence of hepatotoxicity upon administering BDQ, DLM, and/or Pa. Primary endpoints were the overall incidence of elevated liver enzymes, particularly alanine transferase (ALT), aspartate transferase (AST), and gamma-glutamyl transferase (GGT). Proportion meta-analysis was performed for each outcome of interest. Sixteen trials with pooled 4086 participants. The combination of BDQ + Pa was associated with increased ALT (10.6%) and AST (10.4%). Among the individual drugs, Pa-containing regimens had the highest incidence of elevated liver enzymes (ALT [18.9%], AST [20.3%], and GGT [12.8%]). DLM-containing regimens had the lowest incidence (ALT [0.2%], AST [0.7%], and GGT [1%]). For BDQ-containing regimens, the incidence of elevated liver enzymes was similar to the standard of care (SOC): ALT (5.5%) vs. (6.9%) and AST (7.5%) vs. (10.8%), respectively. GGT elevation was more common among the groups receiving BDQ compared to SOC (10% vs. 3.1%). Overall, all the included trials were of high or fair quality. Among all the studied drugs, DLM alone demonstrated the highest hepatic safety, while regimens containing BDQ, Pa, or their combination showed higher hepatotoxic risks compared to SOC. We recommend regular liver function monitoring for DR-TB patients receiving these novel anti-TB drugs.

Abstract licence: CC BY-NC-ND 4.0

INTRODUCTION Certain anti-tuberculosis drugs, i.

Abstract licence: CC BY-NC 4.0

Background: The success of modern drug-resistant tuberculosis (DR-TB) regimens increasingly depends on linezolid (LZD) and pretomanid (Pa), yet the emergence of resistance to these critical agents threatens to reverse recent treatment advances, with limited consolidated evidence available from high-burden settings such as South Africa. Objectives: To systematically review and meta-analyse South African data on LZD and Pa resistance, minimum inhibitory concentrations (MICs), resistance-associated mutations, and treatment outcomes. Eligibility Criteria: We included clinical trials, cohort studies, surveillance studies, and molecular investigations conducted in South Africa from 2013 onward that reported resistance prevalence, MIC data, genotypic mutations, or treatment outcomes related to LZD and/or Pa. Information Sources: PubMed, PubMed, Embase, Web of Science, and grey literature sources were searched from January 2013 to 31 December 2025 in accordance with PRISMA 2020 guidelines. Risk of Bias: Study quality was assessed using the Joanna Briggs Institute (JBI) cohort appraisal checklist. Included Studies: Seventeen studies representing provincial and national cohorts were included. Synthesis of Results: Random-effects meta-analysis was used to estimate pooled baseline resistance. Subgroup, sensitivity, and meta-regression analyses were performed. Results: Random-effects meta-analysis demonstrated a pooled baseline LZD resistance prevalence of 0.53% (95% CI: 0.01–1.83; I2 = 81.1%) in routine South African cohorts, while substantially higher resistance (33%) was observed in treatment-failure populations. Baseline LZD MICs were typically 0.125–1.0 µg/mL, while elevated MICs (up to 8.0 µg/mL) were associated with rplC and rrl mutations, particularly rplC Cys154Arg. No confirmed phenotypic Pa resistance was identified across included South African cohorts, despite the detection of resistance-associated mutations in genomic surveillance studies. MIC values remained within the range of 0.016–1.0 µg/mL. Mutations in ddn, fbiA, fbiC, and fgd1 were reported in genomic studies. Treatment success rates ranged from 63.6% to 99% for LZD-containing regimens and approached 90% for Pa-based regimens. Limitations: Limited study numbers, heterogeneity in laboratory methods, and overrepresentation of certain provinces may affect generalizability. Conclusions: Baseline resistance to LZD and Pa in South Africa remains low, supporting continued programmatic use. Ongoing molecular surveillance is essential to detect resistance amplification and preserve regimen efficacy.

Abstract licence: CC BY 4.0

Abstract The availability of safety data, particularly concerning adverse events (AEs) associated with the new shorter regimen for drug‐resistant tuberculosis (TB) containing a bedaquiline–pretomanid‐based regimen, is still limited. This systematic review aims to provide a comprehensive and updated analysis of AEs related to this new regimen by combining safety data from clinical trials, implementation and pharmacovigilance studies. We conducted a search using PubMed, Medline and Web of Science to identify studies that reported AE data for bedaquiline–pretomanid‐based regimens. In total, 14 studies from various countries were included in the analysis, comprising seven clinical trials, six implementation studies and one pharmacovigilance study. AE detection methods differed between clinical trials and implementation studies. Clinical trials utilised structured and standardised detection methods, whereas implementation and pharmacovigilance studies relied on spontaneous reporting with a higher prevalence of AEs reported in clinical trials (62.2–100%) compared to implementation studies (41.8–72.8%). Serious AEs developed in 2.2–30.2% of patients. Among those with serious AEs, 7.7–54.3% required interruption of TB drugs, while 3.5–13% required withdrawal of TB drugs. AE outcomes showed full recovery in 79.2%. However, 23–32% of patients reported AEs even after completing their treatment. Understanding AEs is crucial for healthcare professionals to enhance patient care, as early detection and appropriate management of AEs is essential in TB treatment to increase tolerability, minimise complications and optimise clinical outcomes. Further research is necessary to implement active monitoring for this new TB regimen in real‐world settings.

Abstract licence: CC BY-NC-ND 4.0