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Your search keyword '"Knippenberg, B."' showing total 2 results
Start Over Author "Knippenberg, B." Publisher american society for microbiology
2 results on '"Knippenberg, B."'

1. Validation and application of a dried blood spot assay for biofilm-active antibiotics commonly used for treatment of prosthetic implant infections

Author

Knippenberg, B., Page-Sharp, Madhu, Salman, S., Clark, B., Dyer, J., Batty, Kevin, Davis, T., Manning, L., Knippenberg, B., Page-Sharp, Madhu, Salman, S., Clark, B., Dyer, J., Batty, Kevin, Davis, T., and Manning, L.

Abstract

Dried blood spot (DBS) antibiotic assays can facilitate pharmacokinetic (PK)/pharmacodynamic (PD) studies in situations where venous blood sampling is logistically difficult. We sought to develop, validate, and apply a DBS assay for rifampin (RIF), fusidic acid (FUS), and ciprofloxacin (CIP). These antibiotics are considered active against organisms in biofilms and are therefore commonly used for the treatment of infections associated with prosthetic implants. A liquid chromatography-mass spectroscopy DBS assay was developed and validated, including red cell partitioning and thermal stability for each drug and the rifampin metabolite desacetyl rifampin (Des-RIF). Plasma and DBS concentrations in 10 healthy adults were compared, and the concentration-time profiles were incorporated into population PK models. The limits of quantification for RIF, Des-RIF, CIP, and FUS in DBS were 15 µg/liter, 14 µg/liter, 25 µg/liter, and 153 µg/liter, respectively. Adjusting for hematocrit, red cell partitioning, and relative recovery, DBS-predicted plasma concentrations were comparable to measured plasma concentrations for each antibiotic (r > 0.95; P < 0.0001), and Bland-Altman plots showed no significant bias. The final population PK estimates of clearance, volume of distribution, and time above threshold MICs for measured and DBS-predicted plasma concentrations were comparable. These drugs were stable in DBSs for at least 10 days at room temperature and 1 month at 4°C. The present DBS antibiotic assays are robust and can be used as surrogates for plasma concentrations to provide valid PK and PK/PD data in a variety of clinical situations, including therapeutic drug monitoring or studies of implant infections.

Published
2016

2. Validation and Application of a Dried Blood Spot Assay for Biofilm-Active Antibiotics Commonly Used for Treatment of Prosthetic Implant Infections.

Author

Knippenberg B, Page-Sharp M, Salman S, Clark B, Dyer J, Batty KT, Davis TM, and Manning L

Subjects
Adult, Chromatography, Liquid methods, Ciprofloxacin therapeutic use, Drug Monitoring methods, Female, Fusidic Acid therapeutic use, Hematocrit methods, Humans, Male, Middle Aged, Reproducibility of Results, Rifampin therapeutic use, Tandem Mass Spectrometry methods, Anti-Bacterial Agents therapeutic use, Biofilms drug effects, Biological Assay methods, Dried Blood Spot Testing methods, Prostheses and Implants microbiology, Prosthesis-Related Infections drug therapy, Prosthesis-Related Infections microbiology
Abstract

Dried blood spot (DBS) antibiotic assays can facilitate pharmacokinetic (PK)/pharmacodynamic (PD) studies in situations where venous blood sampling is logistically difficult. We sought to develop, validate, and apply a DBS assay for rifampin (RIF), fusidic acid (FUS), and ciprofloxacin (CIP). These antibiotics are considered active against organisms in biofilms and are therefore commonly used for the treatment of infections associated with prosthetic implants. A liquid chromatography-mass spectroscopy DBS assay was developed and validated, including red cell partitioning and thermal stability for each drug and the rifampin metabolite desacetyl rifampin (Des-RIF). Plasma and DBS concentrations in 10 healthy adults were compared, and the concentration-time profiles were incorporated into population PK models. The limits of quantification for RIF, Des-RIF, CIP, and FUS in DBS were 15 μg/liter, 14 μg/liter, 25 μg/liter, and 153 μg/liter, respectively. Adjusting for hematocrit, red cell partitioning, and relative recovery, DBS-predicted plasma concentrations were comparable to measured plasma concentrations for each antibiotic (r > 0.95; P < 0.0001), and Bland-Altman plots showed no significant bias. The final population PK estimates of clearance, volume of distribution, and time above threshold MICs for measured and DBS-predicted plasma concentrations were comparable. These drugs were stable in DBSs for at least 10 days at room temperature and 1 month at 4°C. The present DBS antibiotic assays are robust and can be used as surrogates for plasma concentrations to provide valid PK and PK/PD data in a variety of clinical situations, including therapeutic drug monitoring or studies of implant infections., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Published
2016
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