pharmacodynamics
Experimental TherapeuticsIn Vivo Pharmacodynamic Evaluation of Omadacycline against Staphylococcus aureus in the Neutropenic Mouse Pneumonia ModelOmadacycline is an effective therapy for community-acquired bacterial pneumonia (CABP). Given its potent activity against methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA), we sought to determine the pharmacodynamic activity and target pharmacokinetic/...
PharmacologyEx Vivo Urinary Bactericidal Activity and Urinary Pharmacodynamics of Fosfomycin after Two Repeated Dosing Regimens of Oral Fosfomycin Tromethamine in Healthy Adult SubjectsThe ex vivo bactericidal activity and pharmacodynamics of fosfomycin in urine were evaluated in 18 healthy subjects. Subjects received 3 g every other day (QOD) for 3 doses and then every day (QD) for 7 doses or vice versa. Serial urine samples were collected before and up to 24 h after dosing on days 1 and 5. Eight bacterial strains with various genotypic and phenotypic susceptibilities to fosfomycin were used for all...
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...
Experimental TherapeuticsWCK 5222 (Cefepime-Zidebactam) Pharmacodynamic Target Analysis against Metallo-β-Lactamase-Producing Enterobacteriaceae in the Neutropenic Mouse Pneumonia ModelWCK 5222 is a combination of cefepime and the novel β-lactam enhancer (BLE) zidebactam. Zidebactam has a dual mechanism of action involving high-affinity penicillin binding protein 2 (PBP2) binding as well as inhibition of Ambler class A and C enzymes.
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.
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...
Experimental TherapeuticsDetermination of Pharmacodynamic Target Exposures for Rezafungin against Candida tropicalis and Candida dubliniensis in the Neutropenic Mouse Disseminated Candidiasis ModelRezafungin (CD101) is a novel echinocandin under development for once-weekly intravenous (i.v.) dosing. We evaluated the pharmacodynamics (PD) of rezafungin against 4 Candida tropicalis and 4 Candida dubliniensis strains, using the neutropenic mouse invasive candidiasis model. The area under the...
PharmacologyAmikacin Initial Dose in Critically Ill Patients: a Nonparametric Approach To Optimize A Priori Pharmacokinetic/Pharmacodynamic Target Attainments in Individual PatientsAmikacin is commonly used for probabilistic antimicrobial therapy in critically ill patients with sepsis. Its narrow therapeutic margin makes it challenging to determine the right individual dose that ensures the highest efficacy target attainment rate (TAR) in this setting. This study aims to develop a new initial dosing approach for amikacin by optimizing the a priori TAR in this population.
Clinical TherapeuticsEpithelial Lining Fluid and Plasma Concentrations of Dalbavancin in Healthy Adults after a Single 1,500-Milligram InfusionDalbavancin is a lipoglycopeptide antibiotic with a prolonged half-life. A phase 1 study assessed dalbavancin levels in epithelial lining fluid (ELF) in 35 healthy adults using ELF bronchial microsampling up to 168 h after administration of 1,500 mg dalbavancin. The penetration of dalbavancin into ELF was 36%. ELF levels of dalbavancin exceeded the MIC90s of ...
PharmacologyKinetic Driver of Antibacterial Drugs against Plasmodium falciparum and Implications for Clinical DosingAntibacterial drugs are an important component of malaria therapy. We studied the interactions of clindamycin, tetracycline, chloramphenicol, and ciprofloxacin against Plasmodium falciparum under static and dynamic conditions. In microtiter plate assays (static conditions), and as expected, parasites displayed the delayed death response characteristic for apicoplast-...