<sec><title>BACKGROUND</title>TB preventive treatment (TPT) prevents the development of TB disease in individuals at risk progression from infection to disease. However, implementation TPT for children is poor most high-burden settings. The long duration and pill burden 6-month once-daily isoniazid regimen (6H) pose significant barriers completion. We aimed understand children’s, caregivers’, healthcare providers’ experiences 12-week once-weekly rifapentine (3HP) using a...

Linezolid is increasingly important for multidrug-resistant tuberculosis (MDR-TB) treatment. However, among children with MDR-TB, there are no linezolid pharmacokinetic data, and its adverse effects have not yet been prospectively described. We characterised the pharmacokinetics, safety, optimal dose of in treated MDR-TB.

Rifampicin doses of 40 mg/kg in adults are safe and well tolerated, may shorten anti-TB treatment improve outcomes, but have not been evaluated children.To characterize the pharmacokinetics safety high rifampicin children with drug-susceptible TB.The Opti-Rif trial enrolled dosing cohorts 20 aged 0-12 years, incremental dose escalation each subsequent cohort, until achievement target exposures or concerns. Cohort 1 opened a 15 for 14 days, single higher (35 mg/kg) on day 15. Pharmacokinetic...

ABSTRACT Levofloxacin is increasingly used in the treatment of multidrug-resistant tuberculosis (MDR-TB). There are limited pediatric pharmacokinetic data to inform dose selection for children. Children routinely receiving levofloxacin (250-mg adult tablets) MDR-TB prophylaxis or disease Cape Town, South Africa, underwent sampling following receipt a 15 20 mg/kg body weight given as whole crushed tablet(s) orally via nasogastric tube. Pharmacokinetic parameters were estimated using nonlinear...

Safety concerns persist for long-term pediatric fluoroquinolone use. Seventy children (median age, 2.1 years) treated with levofloxacin 10–20 mg/kg once daily multidrug-resistant tuberculosis observation time, 11.8 months) had few musculoskeletal events, no levofloxacin-attributed serious adverse and Fridericia-corrected QT interval >450 ms. Long-term was safe well tolerated.

In 2010, the World Health Organization (WHO) revised dosing guidelines for treatment of childhood tuberculosis. Our aim was to investigate first-line antituberculosis drug exposures under these guidelines, explore dose optimization using current dispersible fixed-dose combination (FDC) tablet rifampicin/isoniazid/pyrazinamide; 75/50/150 mg, and suggest a new FDC with weight bands.Children drug-susceptible tuberculosis in Malawi South Africa underwent pharmacokinetic sampling while receiving...

Moxifloxacin is a recommended drug for rifampin-resistant tuberculosis (RR-TB) treatment, but there limited pediatric pharmacokinetic and safety data, especially in young children. We characterize moxifloxacin population pharmacokinetics QT interval prolongation evaluate optimal dosing children with RR-TB.Pharmacokinetic data were pooled from 2 observational studies South African RR-TB routinely treated oral once daily. The Fridericia-corrected (QTcF)-interval characterized NONMEM....

Lopinavir-ritonavir forms the backbone of current first-line antiretroviral regimens in young HIV-infected children. As multidrug-resistant (MDR) tuberculosis (TB) frequently occurs children high-burden TB settings, it is important to identify potential interactions between MDR-TB treatment and lopinavir-ritonavir. We describe pharmacokinetics drug-drug lopinavir-ritonavir drugs routinely used for A combined population pharmacokinetic model was developed jointly lopinavir ritonavir 32 (16...

Abstract Background Pharmacokinetic data for bedaquiline in children are limited. We described the pharmacokinetics and safety of South African adolescents receiving treatment multidrug/rifampicin-resistant tuberculosis (MDR/RR-TB) routine care. Methods In this observational cohort study, aged 6–17 years at recommended doses as part MDR/RR-TB underwent semi-intensive pharmacokinetic sampling. Bedaquiline M2 metabolite plasma concentrations were quantified, nonlinear mixed-effects modeling...

Rifampicin-resistant tuberculosis (RR-TB) involves treatment with many drugs that can prolong the QT interval; this risk may increase when multiple QT-prolonging are used together. We assessed interval prolongation in children RR-TB receiving one or more drugs. Data were obtained from two prospective observational studies Cape Town, South Africa. Electrocardiograms performed before and after drug administration of clofazimine (CFZ), levofloxacin (LFX), moxifloxacin (MFX), bedaquiline (BDQ),...

BACKGROUND: The treatment of rifampicin-resistant TB (RR-TB) in children is evolving rapidly. As newer regimens are introduced into routine care, it vital to compare their outcome and safety with well-characterised clinical cohorts treated historical regimens.METHODS: Study sample comprised a prospective observational cohort on RR-TB treatment, enrolled from 2011 2015 Cape Town, South Africa. Children were followed for safety, response outcome.RESULTS: Of 136 included, 27 (19.9%) living HIV...

Abstract Pharmacological interactions limit treatment options for children living with human immunodeficiency virus (HIV) and tuberculosis (TB). We found that 12 mg/kg twice daily raltegravir chewable tablets (administered after crushing) safely achieved pharmacokinetic targets in HIV aged 4 weeks to <2 years receiving concurrent rifampin treat TB. Clinical Trials Registration NCT01751568.

ABSTRACT Clofazimine is recommended for the treatment of rifampicin-resistant tuberculosis (RR-TB), but there currently no verified dosing guideline its use in children. There only limited safety and pharmacokinetic (PK) data available We aimed to characterize clofazimine PK relationship with QT-interval prolongation An observational cohort study South African children <18 years old routinely treated RR-TB a clofazimine-containing regimen was analyzed. 100 mg gelatin capsules were given...

To evaluate the proportion of children with lopinavir Cmin ≥1 mg/L when receiving a novel 8-hourly lopinavir/ritonavir dosing strategy during rifampicin co-treatment.

BACKGROUND: High-dose isoniazid (INH H ) (15–20 mg/kg/day) could be administered to overcome low-level INH resistance, but pharmacokinetic data are sparse. METHODS: This observational study included South African children (<15 years) receiving as preventive therapy, or treatment for multidrug-resistant TB (MDR-TB) exposure disease. Pharmacokinetic sampling was performed after an dose of 20 mg/kg. Non-compartmental analysis and multivariable regression models were used evaluate...

BACKGROUND: Multidrug-resistant TB (MDR-TB) treatment for children frequently includes unpalatable drugs with low overall acceptability. This can negatively impact and their caregivers´ experiences is an important contributor to poor adherence, potentially, outcomes. Children preferences MDR-TB are not well documented. We describe priorities inform future regimens.METHODS: conducted a cross-sectional qualitative study at hospital in South Africa using semi-structured interviews participatory...

There are no pharmacokinetic data in children on terizidone, a pro-drug of cycloserine and World Health Organization (WHO)-recommended group B drug for rifampicin-resistant tuberculosis (RR-TB) treatment. We collected <15 years routinely receiving 15-20 mg/kg daily terizidone RR-TB developed population model assuming 2-to-1 molecular ratio between cycloserine. included 107 with median (interquartile range) age weight 3.33 (1.55, 5.07) 13.0 (10.1, 17.0) kg, respectively. The pharmacokinetics...

Given the high prevalence of multidrug-resistant (MDR)-TB in HIV burden settings, it is important to identify potential drug-drug interactions between MDR-TB treatment and widely used nucleoside reverse transcriptase inhibitors (NRTIs) HIV-positive children. Population pharmacokinetic models were developed for lamivudine (n = 54) abacavir 50) 54 children established on NRTIs; 27 with (combinations high-dose isoniazid, pyrazinamide, ethambutol, ethionamide, terizidone, fluoroquinolones,...

Hepatocellular injury has been reported commonly in adults on rifampicin-resistant and multidrug-resistant tuberculosis (RR/MDR-TB) treatment. However, there are limited data children.Two pharmacokinetic studies of children (0-17 years) routinely treated for RR/MDR-TB were conducted Cape Town, South Africa between October 2011 February 2020. adverse events (AEs; defined as elevated alanine aminotransferase [ALT]) documented serially. Data analyzed to determine the incidence, etiology, risk...

Treatment options for children with Rifampicin-resistant tuberculosis (RR-TB) remain limited, and para-aminosalicylic acid (PAS) is still a relevant component of treatment regimens. Prevention resistance to companion drugs by PAS dose related, at higher concentrations, may exhibit significant bactericidal activity in addition its bacteriostatic properties. The optimal dosing uncertain, specifically delayed-release granule preparations, which are the most used. A population pharmacokinetic...