Introduction: Erector spinae plane blocks have become popular for thoracic surgery. Despite a theoretically favorable safety profile, intercostal spread occurs and systemic toxicity is possible. Pharmacokinetic data are needed to guide safe dosing.
View Article and Find Full Text PDFAlthough tuberculosis (TB) is preventable and curable, the lengthy treatment (generally 6 months), poor patient adherence, high inter-individual variability in pharmacokinetics (PK), emergence of drug resistance, presence of comorbidities, and adverse drug reactions complicate TB therapy and drive the need for new drugs and/or regimens. Hence, new compounds are being developed, available drugs are repurposed, and the dosing of existing drugs is optimized, resulting in the largest drug development portfolio in TB history. This review highlights a selection of clinically available drug candidates that could be part of future TB regimens, including bedaquiline, delamanid, pretomanid, linezolid, clofazimine, optimized (high dose) rifampicin, rifapentine, and para-aminosalicylic acid.
View Article and Find Full Text PDFCarbapenems are recommended for treatment of drug-resistant tuberculosis. Optimal dosing remains uncertain. To evaluate the 14-day bactericidal activity of meropenem, at different doses, with or without rifampin.
View Article and Find Full Text PDFMeropenem is being investigated for repurposing as an anti-tuberculosis drug. This study aimed to develop a meropenem population pharmacokinetics model in patients with pulmonary and identify covariates explaining inter-individual variability. Patients were randomized to one of four treatment groups: meropenem 2 g three times daily plus oral rifampicin 20 mg/kg once daily, meropenem 2 g three times daily, meropenem 1 g three times daily, and meropenem 3 g once daily.
View Article and Find Full Text PDFBackground: Intravenous phenobarbital remains the first-line therapy in the management of neonatal seizures. Shortages of intravenous phenobarbital in South Africa necessitated the addition of oral levetiracetam as part of management of neonatal seizures.
Objective: We evaluated the pharmacokinetics of crushed immediate-release levetiracetam tablets administered to neonates to terminate seizures.
Background: South Africa has one of the highest tuberculosis incidence rates. Biologic disease-modifying anti-rheumatic drugs are associated with an increased risk of tuberculosis. The objective of this study was to describe the tuberculosis disease incidence rate among public sector patients receiving biologic therapies in the Western Cape Province.
View Article and Find Full Text PDFPurpose: Para-aminosalicylic acid (PAS) is currently one of the add-on group C medicines recommended by the World Health Organization for multidrug-resistant tuberculosis treatment. At the recommended doses (8-12 g per day in two to three divided doses) of the widely available slow-release PAS formulation, studies suggest PAS exposures are lower than those reached with older PAS salt formulations and do not generate bactericidal activity. Understanding the PASER dose-exposure-response relationship is crucial for dose optimization.
View Article and Find Full Text PDFFollowing its introduction as an antituberculosis agent close to 75 years ago, the use of para-aminosalicylic acid (PAS) has been limited by gastrointestinal intolerance and multiple formulations were produced in attempts to reduce its occurrence. More recently, an enteric-coated, granular, slow-release PAS formulation (PASER) was introduced and is now in wide-spread use for the treatment of drug-resistant tuberculosis. The current PASER dosing regimen is based on recommendations derived from older studies using a variety of different PAS formulations and relegate PAS to a role as an exclusively bacteriostatic agent.
View Article and Find Full Text PDFPara-aminosalicylic acid (PAS), often the last drug remaining for treatment of drug-resistant tuberculosis, is notorious for causing gastrointestinal intolerance; however, the cause of PAS intolerance is uncertain. The objective of this study was to assess relationships between peak concentrations of PAS administered as a granular slow-release enteric coated formulation, and its metabolites acetyl-PAS and glycine-PAS, and intolerance. PAS and its metabolites were measured in 29 adult patients with drug-resistant tuberculosis at Brooklyn Hospital, Cape Town, randomized to receive granular slow-release enteric-coated PAS 4 g twice daily or 8 g once daily for 1 week, followed by the alternative regimen.
View Article and Find Full Text PDFThe introduction of rifampicin (rifampin) into tuberculosis (TB) treatment five decades ago was critical for shortening the treatment duration for patients with pulmonary TB to 6 months when combined with pyrazinamide in the first 2 months. Resistance or hypersensitivity to rifampicin effectively condemns a patient to prolonged, less effective, more toxic, and expensive regimens. Because of cost and fears of toxicity, rifampicin was introduced at an oral daily dose of 600 mg (8-12 mg/kg body weight).
View Article and Find Full Text PDFThe glycopeptide antibiotic vancomycin is used for treatment of methicillin-resistant Gram-positive cocci. Adequate vancomycin plasma concentrations are related to bacterial cure. However, inter- and intrapatient variability make it difficult to achieve therapeutic vancomycin concentrations.
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