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Defining the Active Fraction of Daptomycin against Methicillin-Resistant Staphylococcus aureus (MRSA) Using a Pharmacokinetic and Pharmacodynamic Approach

Our objective was to study the pharmacodynamics of daptomycin in the presence of varying concentrations of human serum (HS) in vitro to quantify the fraction of daptomycin that is ‘active’. Time kill experiments were performed with daptomycin (0 to 256 mg/L) against two MRSA strains at log-phase growth, in the presence of HS (0%, 10%, 30%, 50%, 70%) combined with Mueller-Hinton ...

Oseltamivir Population Pharmacokinetics in the Ferret: Model Application for Pharmacokinetic/Pharmacodynamic Study Design

The ferret is a suitable small animal model for preclinical evaluation of efficacy of antiviral drugs against various influenza strains, including highly pathogenic H5N1 viruses. Rigorous pharmacokinetics/pharmacodynamics (PK/PD) assessment of ferret data has not been conducted, perhaps due to insufficient information on oseltamivir PK. Here, based on PK data from several studies ...

Multiple Nuclear Gene Phylogenetic Analysis of the Evolution of Dioecy and Sex Chromosomes in the Genus Silene

In the plant genus Silene, separate sexes and sex chromosomes are believed to have evolved twice. Silene species that are wholly or largely hermaphroditic are assumed to represent the ancestral state from which dioecy evolved. This assumption is important for choice of outgroup species for inferring the genetic and chromosomal changes involved in the evolution of dioecy, but is ...

Population Pharmacokinetics of Intravenous Polymyxin B in Critically Ill Patients: Implications for Selection of Dosage Regimens

Background. Polymyxin B is a last-line therapy for multidrug-resistant gram-negative bacteria. There is a dearth of pharmacokinetic data to guide dosing in critically ill patients. Methods. Twenty-four critically ill patients were enrolled and blood/urine samples were collected over a dosing interval at steady state. Polymyxin B concentrations were measured by liquid ...

Nucleotide diversity in Silene latifolia autosomal and sex-linked genes

Suo Qiu Roberta Bergero Alan Forrest Vera B. Kaiser Deborah Charlesworth () 0 State Key Laboratory of Biocontrol and Key Laboratory of Gene Engineering of the Ministry of Education, Sun Yat-Sen

Application of Pharmacokinetic-Pharmacodynamic Modeling and the Justification of a Novel Fusidic Acid Dosing Regimen: Raising Lazarus From the Dead

Perhaps the most crucial step in the clinical development of an antimicrobial agent is the selection of a dosing regimen. Such decisions impact not only the success of a program but also the well being of individual patients, the emergence of resistance, and society as a whole. For fusidic acid, the selection of a dosing regimen for the treatment of patients with acute bacterial ...

Factors Influencing Time to Vancomycin-Induced Clearance of Nonendocarditis Methicillin-Resistant Staphylococcus aureus Bacteremia: Role of Platelet Microbicidal Protein Killing and agr Genotypes

Background. Vancomycin susceptibility, the accessory gene global regulator (agr) genotype and function, staphylococcal cassette chromosome (SCC) mec type, and susceptibility to cationic thrombin-induced platelet microbicidal protein 1 (tPMP-1) have been individually predictive of duration of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. This investigation evaluated ...

SPLINDID: a semi-parametric, model-based method for obtaining transcription rates and gene regulation parameters from genomic and proteomic expression profiles

Purpose: To evaluate a semi-parametric, model-based approach for obtaining transcription rates from mRNA and protein expression. Methods: The transcription profile input was modeled using an exponential function of a cubic spline and the dynamics of translation; mRNA and protein degradation were modeled using the Hargrove–Schmidt model. The transcription rate profile and the ...

Pharmacokinetics-Pharmacodynamics of Antimicrobial Therapy: It's Not Just for Mice Anymore

Forrest 1 George L. Drusano 0 0 Emerging Infections and Fungal Pharmacodynamics Laboratory, Ordway Research Institute , Albany , New York 1 Institute for Clinical Pharmacodynamics Since the advent of the

Relationships between Patient- and Institution-Specific Variables and Decreased Antimicrobial Susceptibility of Gram-Negative Pathogens

The identification of patients infected with antibiotic-resistant strains of bacteria for inclusion in clinical trials remains a serious challenge for the future development of agents for use against such infections. To identify patient- and institution-specific factors predictive of reduced susceptibility of Enterobacter species, Pseudomonas aeruginosa, and Klebsiella pneumoniae ...

Accessory Gene Regulator Group II Polymorphism in Methicillin-Resistant Staphylococcus aureus Is Predictive of Failure of Vancomycin Therapy

We studied methicillin-resistant Staphylococcus aureus (MRSA) isolates to determine if the group II polymorphism at the accessory gene regulator (agr) locus demonstrated any relationship with the clinical efficacy of vancomycin. One hundred twenty-two MRSA isolates from 87 patients treated with vancomycin were evaluated. Forty-five of 87 patients had no clinical or bacteriological ...

Pharmacodynamic Interactions of Antibiotics Alone and in Combination

Clinical trials show that the area under the inhibitory curve (AUIC) is predictive of antibacterial killing rates in patients with nosocomial pneumonia and is useful for predicting clinical or microbiological outcomes and making dosage adjustments with β-lactams, quinolones, aminoglycosides, and vancomycin. The AUIC values of two antibiotics are additive, and since antibiotics are ...