AFFINERGY, LLC — Department of Health and Human Services SBIR Phase II: 300

Description

DESCRIPTION provided by applicant Severe Gram positive infections are difficult to treat and associated with high mortality in hospital settings Daptomycin is a broad spectrum antibiotic that has been successfully used to treat persisting Gram positive infections including skin and soft tissue infections right sided endocarditis and bacteremia Daptomycin is also highly effective against drug resistant strains such as methicillin resistant S aureus MRSA and vancomycin resistant enterococci VRE Current daptomycin dosing guidelines are derived from limited studies in healthy individuals where pharmacokinetics are highly predictable Unfortunately daptomycin pharmacokinetics are highly variable in the critically ill patients that typically receive the drug This leads to sub therapeutic dosing increased rates of treatment failure and in recent years the emergence of daptomycin resistant strains Therapeutic monitoring of daptomycin concentrations would thus enable clinicians to adjust doses in order to maintain an effective circulating concentration ultimately improving outcomes and preventing adverse effects Unfortunately there is no FDA approved test to measure daptomycin concentrations in a clinical setting Multiple clinical studies have concluded that current daptomycin dosing guidelines for critically ill and septic patients need to be reevaluated and adjusted and regular measurement of daptomycin levels in these patients are needed to ensure effective treatment To address this critical need Affinergy is developing a novel assay format using daptomycin binding phage to measure daptomycin concentrations in plasma At the conclusion of this Phase II project we will file a regulatory submission for FDA clearance of our assay PUBLIC HEALTH RELEVANCE Daptomycin is successfully used to treat severe Gram positive infections including methicillin resistant S aureus MRSA and vancomycin resistant enterococci VRE Current daptomycin dosing guidelines are derived from healthy patients However daptomycin pharmacokinetics are highly variable in critically ill patients and there are no FDA approved assays that can be used to therapeutically monitor daptomycin concentrations in the clinic In this application we propose to develop a novel phage based assay to facilitate measurement of daptomycin concentration in biological fluids