terizidone / Generic mfg. - LARVOL DELTA

Cerebrospinal fluid penetration of cycloserine/terizidone and clofazimine in patients with pulmonary TB. (PubMed, Antimicrob Agents Chemother) - "Cycloserine and clofazimine concentrations in CSF approximated their estimated unbound (active) concentration in plasma, thus suggesting good penetration of the unbound drug into the CSF, supporting their potential use in TBM regimens. This study demonstrates a feasible and reproducible method for effective assessment of CSF drug penetration for CNS infections."

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

Treatment outcomes of bedaquiline-resistant tuberculosis: a retrospective and matched cohort study. (PubMed, Lancet Infect Dis) - "Current treatment options for bedaquiline-resistant tuberculosis result in prolonged therapy, delayed microbiological responses, and poor clinical outcomes. Implementation of more rapid resistance testing, including targeted next-generation sequencing, and access to novel treatment options within randomised controlled trials for bedaquiline-resistant tuberculosis, are priorities for tuberculosis programmes."

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

A Case of Pre-Extensively Drug-Resistant Tuberculosis in KwaZulu-Natal, South Africa (ASTMH 2024) - "His prior left neck abscess aspirate culture (on initial presentation), later demonstrated growth of M. tuberculosis : Resistant - INH, Rifampin, Fluoroquinolones, Second-line injectables. For the management of at minimum pre-extensively drug-resistant TB, he was to restart/continue linezolid for 1 year; start delamanid for 0.5-1 year; continue bedaquiline for 1 year; stop ethambutol, pyrazinamide, and high-dose isoniazid. Levofloxacin was continued given patient’s overall clinical improvement with monitoring. Also, the plan was to add clofazimine and terizidone for 18 months. This is a challenging case of diagnosed pre-XDR TB, which has a nuanced and complex management that providers should recognize and understand."

Clinical • Cough • Human Immunodeficiency Virus • Infectious Disease • Respiratory Diseases • Tuberculosis • CD4

Assessing potential drug-drug interactions between clofazimine and other frequently used agents to treat drug-resistant tuberculosis. (PubMed, Antimicrob Agents Chemother) - "Clofazimine is included in drug regimens to treat rifampicin/drug-resistant tuberculosis (DR-TB), but there is little information about its interaction with other drugs in DR-TB regimens. We evaluated the pharmacokinetic interaction between clofazimine and isoniazid, linezolid, levofloxacin, and cycloserine, dosed as terizidone...A posteriori power size calculations predicted that our sample sizes had 97%, 90%, and 87% power at P < 0.05 to detect a 30% change in clearance of isoniazid, linezolid, and cycloserine, respectively. Although clofazimine increased the area under the curve of levofloxacin by 19%, this is unlikely to be of great clinical significance, and the lack of interaction with other drugs tested is reassuring."

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

Pharmacokinetics and Safety of Group A and B Anti-Tuberculosis Drugs Used in Treatment of Rifampicin-Resistant Tuberculosis during Pregnancy and Post-Partum: A Narrative Review. (PubMed, Pathogens) - "Existing data suggest that fluoroquinolones, bedaquiline, clofazimine and terizidone may be used safely in pregnancy. While plenty of questions remain regarding the exposure to Group A and B antituberculosis drugs through breastmilk, existing literature suggests minimal harm to the breastfed infant. Pregnant patients and their infants should be included in therapeutic trials and pharmacokinetic studies of effective antituberculosis drugs."

Journal • PK/PD data • Review • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

A Single-Run HPLC-MS Multiplex Assay for Therapeutic Drug Monitoring of Relevant First- and Second-Line Antibiotics in the Treatment of Drug-Resistant Tuberculosis. (PubMed, Pharmaceutics) - "The assay was sufficiently sensitive to monitor drug concentrations over five half-lives for rifampicin, rifabutin, levofloxacin, moxifloxacin, bedaquiline, linezolid, clofazimine, terizidone/cycloserine, ethambutol, delamanid, pyrazinamide, meropenem, prothionamide, and para-amino salicylic acid (PAS). All relevant antibiotics from their regimens could be quantified and high-dose therapy was initiated, followed by microbiological conversion. In conclusion, we developed a multiplex assay that enables TDM of the relevant first- and second-line anti-tuberculosis medicines in a single run and was able to show its applicability in TDM of two drug-resistant tuberculosis patients."

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

Optimizing dosing of the cycloserine pro-drug terizidone in children with rifampicin-resistant tuberculosis. (PubMed, Antimicrob Agents Chemother) - "With current terizidone dosing, pediatric cycloserine exposures are lower than adult values for several weight groups. New optimized dosing is suggested for prospective evaluation."

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

InDEX: The Individualized M(X) Drug-resistant TB Treatment Strategy Study (clinicaltrials.gov) - P4 | N=205 | Terminated | Sponsor: Centre for the AIDS Programme of Research in South Africa | N=448 ➔ 205 | Recruiting ➔ Terminated; WHO 2022 guidelines for DR-TB treatment are set to change. These guidelines recommend the use of an all-oral short course BPAL regimen.Therefore ongoing implementation of the study is considered futile.

Enrollment change • Trial termination • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • CD4

Infant Exposure to Antituberculosis Drugs via Breast Milk and Assessment of Potential Adverse Effects in Breastfed Infants: Critical Review of Data. (PubMed, Pharmaceutics) - "We performed a systematic search in PubMed for bedaquiline, clofazimine, cycloserine/terizidone, levofloxacin, linezolid, pretomanid/pa824, pyrazinamide, streptomycin, ethambutol, rifampicin and isoniazid, supplemented with update references found in LactMed. Concerns for potential adverse effects in breastfed infants could be ruled out for bedaquiline, cycloserine/terizidone, linezolid and pyrazinamide. Adequate studies should be performed covering the scenario in treated mothers, breast milk and infants."

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

Variation in missed doses and reasons for discontinuation of anti-tuberculosis drugs during hospital treatment for drug-resistant tuberculosis in South Africa. (PubMed, PLoS One) - "We found that incomplete treatment for second-line injectables and PAS during hospitalization was higher than for other anti-TB drugs. To maximize treatment success, interventions to improve person-centered care and mitigate adverse events may be necessary in cases when PAS or amikacin (2020 WHO recommended Group C drugs) are needed."

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

InDEX: The Individualized M(X) Drug-resistant TB Treatment Strategy Study (clinicaltrials.gov) - P4 | N=448 | Recruiting | Sponsor: Centre for the AIDS Programme of Research in South Africa | Trial completion date: Jul 2022 ➔ Mar 2023 | Trial primary completion date: Dec 2021 ➔ Dec 2022

Trial completion date • Trial primary completion date • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • CD4

Pharmacokinetics of standard versus high-dose isoniazid for treatment of multidrug-resistant tuberculosis. (PubMed, J Antimicrob Chemother) - "Markedly lower isoniazid exposures were observed in participants on combination MDR-TB treatment compared with monotherapy. Isoniazid displays saturable kinetics at doses >10 mg/kg. The safety implications of these phenomena remain unclear."

Journal • PK/PD data • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • NAT2

Treatment outcomes 24 months after initiating short, all-oral bedaquiline-containing or injectable-containing rifampicin-resistant tuberculosis treatment regimens in South Africa: a retrospective cohort study. (PubMed, Lancet Infect Dis) - "Patients in the bedaquiline group experienced significantly higher rates of treatment success at 24 months. This finding supports the use of short bedaquiline-containing regimens in eligible patients."

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

Linezolid-Associated Posterior Reversible Leuco-encephalopathy Syndrome in a Patient with Disseminated Tuberculosis. (PubMed, Trop Doct) - "She was then put on modified ATT (moxifloxacin, terizidone, and linezolid). Brain imaging was suggestive of PRES. Linezolid was withdrawn, following which she showed an excellent clinical and radiological recovery."

Clinical • Journal • CNS Disorders • Hepatology • Infectious Disease • Inflammation • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Pharmacokinetics and Drug-Drug Interactions of Abacavir and Lamuvudine Co-administered With Antituberculosis Drugs in HIV-Positive Children Treated for Multidrug-Resistant Tuberculosis. (PubMed, Front Pharmacol) - "Population pharmacokinetic models were developed for lamivudine (n = 54) and abacavir (n = 50) in 54 HIV-positive children established on NRTIs; 27 with MDR-TB (combinations of high-dose isoniazid, pyrazinamide, ethambutol, ethionamide, terizidone, fluoroquinolones, and amikacin), and 27 controls without TB. Clearance was predicted to reach half its mature value 2 (lamivudine) and 3 (abacavir) months after birth, with completion of maturation for both drugs at 2 years. No significant difference was found in key pharmacokinetic parameters of lamivudine and abacavir when co-administered with routine drugs used for MDR-TB in HIV-positive children."

Clinical • Journal • PK/PD data • Human Immunodeficiency Virus • Infectious Disease • Pediatrics • Pulmonary Disease • Respiratory Diseases • Tuberculosis

An Open-label RCT to Evaluate a New Treatment Regimen for Patients With Multi-drug Resistant Tuberculosis (clinicaltrials.gov) - P2/3; N=154; Completed; Sponsor: University of Cape Town; Active, not recruiting ➔ Completed

Clinical • Trial completion • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

[VIRTUAL] Late Breaking Abstract - Therapeutic drug monitoring in a patient with very advanced XDR-TB (ERS 2021) - "Phenotypic drug susceptibility testing revealed drug-resistance to all 1st- and 2nd-line anti-tuberculosis drugs apart from terizidone, delamanid, and pretomanid. Under treatment with 800 mg moxifloxacin and standard doses of bedaquiline, terizidone, delamanid, and meropenem/amoxiclav, no sustainable culture conversion could be achieved over five months...In summary, TDM-guided therapy can help to overcome low-intermediate level resistance in M/XDR-TB. However, extended treatment duration might be needed to achieve cure."

Clinical • Late-breaking abstract • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

[VIRTUAL] Efficacy of linezolide-free chemotherapy schemes in patients with highly drug-resistant tuberculosis (ERS 2021) - "The combination of fluoroquinolones (Fq), bedaquiline (Bdq) and linezolid (Lzd) is the basis for the treatment of tuberculosis with extensively and pre-extensively drug-resistant M. tuberculosis (XDR/pre-XDR-TB)...The frequency of use of chemotherapy drugs: Bdq – 100%; Fq – 100%; cycloserine/terizidone – 82.4%; prothionamide – 79.4%; pyrazinamide – 76.5%; capreomycin – 47.1%; ethambutol – 35.6%; PAS – 20.6%; amikacin – 14.7%...Conclusion. The chemotherapy regimen based on Bdq and Fq, but without Lzd, in XDR/pre-XDR-TB patients with previous unsuccessful courses of treatment, is effective in terms of mycobacteria elimination and is better than this figure among MDR-TB patients in Russia/"

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