Validation and application of a dried blood spot assay for biofilm-active antibiotics commonly used for treatment of prosthetic implant infections
MetadataShow full item record
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.
Showing items related by title, author, creator and subject.
Page-Sharp, M.; Nunn, T.; Salman, S.; Moore, B.; Batty, Kevin; Davis, T.; Manning, L. (2015)Dried blood spot (DBS) antibiotic assays can facilitate pharmacokinetic/pharmacodynamic (PK/PD) studies in situations where venous blood sampling is logistically and/or ethically problematic. In this study, we aimed to ...
Penicillin dried blood spot assay for use in patients receiving intramuscular benzathine penicillin G and other penicillin preparations to prevent rheumatic feverPage-Sharp, Madhu; Coward, J.; Moore, Brioni; Salman, S.; Marshall, L.; Davis, T.; Batty, Kevin; Manning, L. (2017)© 2017 American Society for Microbiology. All Rights Reserved. Rheumatic heart disease (RHD) remains an important global health challenge. Administration of benzathine penicillin (BPG) every 3 to 4 weeks is recommended ...
Artemisinin-Naphthoquine Combination Therapy for Uncomplicated Pediatric Malaria: a Pharmacokinetic StudyBatty, Kevin; Salman, Sam; Moore, Brioni; Benjamin, John; Lee, Sook Ting; Page-Sharp, Madhu; Pitus, Nolene; Ilett, Kenneth; Mueller, Ivo; Hombhanje, Francis; Siba, Peter; Davis, Timothy (2012)Artemisinin-naphthoquine (ART-NQ) is a coformulated antimalarial therapy marketed as a single-dose treatment in Papua New Guinea and other tropical countries. To build on limited knowledge of the pharmacokinetic properties ...