pharmacokinetics
PharmacologyMeropenem-Tobramycin Combination Regimens Combat Carbapenem-Resistant Pseudomonas aeruginosa in the Hollow-Fiber Infection Model Simulating Augmented Renal Clearance in Critically Ill PatientsAugmented renal clearance (ARC) is common in critically ill patients and is associated with subtherapeutic concentrations of renally eliminated antibiotics. We investigated the impact of ARC on bacterial killing and resistance amplification for meropenem and tobramycin regimens in monotherapy and combination. Two carbapenem-resistant Pseudomonas aeruginosa isolates...
Clinical TherapeuticsTarget-Controlled Infusion of Cefepime in Critically Ill PatientsAttainment of appropriate pharmacokinetic-pharmacodynamic (PK-PD) targets for antimicrobial treatment is challenging in critically ill patients, particularly for cefepime, which exhibits a relative narrow therapeutic-toxic window compared to other beta-lactam antibiotics. Target-controlled infusion (TCI) systems, which deliver drugs to achieve specific target drug concentrations, have successfully been implemented for improved dosing of...
PharmacologyPharmacokinetics of Telavancin in Adult Patients with Cystic Fibrosis during Acute Pulmonary ExacerbationAdults with cystic fibrosis (CF) frequently harbor Staphylococcus aureus, which is increasingly antibiotic resistant. Telavancin is a once-daily rapidly bactericidal antibiotic active against methicillin-, linezolid-, and ceftaroline-resistant S. aureus. Because CF patients experience alterations in...
PharmacologyA Population Pharmacokinetic Model-Guided Evaluation of Ceftolozane-Tazobactam Dosing in Critically Ill Patients Undergoing Continuous Venovenous HemodiafiltrationThe aim of this work was to describe optimized dosing regimens of ceftolozane-tazobactam for critically ill patients receiving continuous venovenous hemodiafiltration (CVVHDF). We conducted a prospective observational pharmacokinetic study in adult critically ill patients with clinical indications for ceftolozane-tazobactam and CVVHDF. Unbound drug concentrations were measured from serial prefilter blood, postfilter blood, and...
Clinical TherapeuticsIntracellular Pharmacodynamic Modeling Is Predictive of the Clinical Activity of Fluoroquinolones against TuberculosisClinical studies of new antitubercular drugs are costly and time-consuming. Owing to the extensive tuberculosis (TB) treatment periods, the ability to identify drug candidates based on their predicted clinical efficacy is vital to accelerate the pipeline of new therapies. Recent failures of preclinical models in predicting the activity of fluoroquinolones underline the importance of developing new and more robust predictive tools that...
PharmacologyModeling and Simulation of Pretomanid Pharmacodynamics in Pulmonary Tuberculosis PatientsPretomanid (PA-824) is a nitroimidazole in clinical testing for the treatment of tuberculosis. A population pharmacodynamic model for pretomanid was developed using a Bayesian analysis of efficacy data from two early bactericidal activity (EBA) studies, PA-824-CL-007 and PA-824-CL-010, conducted in Cape Town, South Africa.
PharmacologyPopulation Pharmacokinetics of Doxycycline in ChildrenDoxycycline is a tetracycline-class antimicrobial labeled by the U.S. Food and Drug Administration for children >8 years of age for many common childhood infections. Doxycycline is not labeled for children ≤8 years of age, due to the association between tetracycline-class antibiotics and tooth staining, although doxycycline may be used off-label under severe conditions.
Clinical TherapeuticsPharmacokinetics and Dialytic Clearance of Isavuconazole during In Vitro and In Vivo Continuous Renal Replacement TherapyThe pharmacokinetics (PK) and dialytic clearance of isavuconazole in vitro and in 7 solid-organ transplant patients undergoing continuous renal replacement therapy (CRRT) were evaluated.
PharmacologyObservational, Prospective Single-Center Study of Antibiotic Prophylaxis with High-Dose Cefoxitin in Bariatric SurgeryThe optimal dose of cefoxitin for antibiotic prophylaxis in obese patients remains uncertain. We evaluated the adequacy of a 4-g dosing regimen of cefoxitin against the most common pathogens that infect patients undergoing bariatric surgery. This observational prospective study included obese patients who required bariatric surgery and a 4-g dose of cefoxitin as an antibiotic prophylaxis. Serum concentrations were measured during...
