Sepsis represents one of the fastest growing health-care problems today, and is responsible for more than 250,000 deaths every year. Annually, over 2.5 million patients are admitted to intensive care units due to severe sepsis and healthcare costs associated with sepsis exceeds $17 billion in the US alone. Despite the advancements in the sepsis treatment, management of the illness is complicated and patient outcomes are compromised due to lack of proper diagnostic tools. The development of new and effective therapies for sepsis suffers from the inability to select patients who will most likely respond to specific treatments, and to precisely titrate dosing and duration. Although pharmacogenomics has been used to try to predict drug response in sepsis patients, there has been limited success with this approach. Thus there is a growing need for biomarkers that can indicate both the likely utility of a drug and titration of the dosage.
Novel predictive and pharmacodynamic serum biomarkers for treatment with L-carnitine in patients with sepsis
Using metabolomics researchers at the University of Michigan differentiated patients as either “carnitine responders” or “carnitine non-responders” thereby personalizing and targeting L-carnitine therapy to a unique group of septic patients, who are most likely to be responsive to treatment. The blood (serum) metabolite (small molecules) used in this approach include but are not limited to ketone bodies, acetylcarnitine (AC), carnitine © and AC:C ratio. Clinical data shows traditional phenotyping (e.g., sequential organ failure score (SOFA)) alone is not sufficient to identify carnitine responsive sepsis patients and metabolic data can be leveraged for early clinical therapeutic intervention. Additionally metabolites of L-carnitine drug response that change over time were identified, and could possibly be used to monitor the drug’s effectiveness and the occurrence of potential adverse drug reactions.
- To identify sepsis patients who are most likely to be responsive to treatment with L-carnitine
- To predict drug response and adverse drug reactions for treatment with L-carnitine in patients with sepsis
- Point-of-care diagnostics for treatment with L-carnitine in patients with sepsis
- First “pharmacometabolomics” strategy for personalized (precision) medicine in sepsis
- Ability to identify potential responders to L-carnitine therapy for sepsis, enabling clinical therapeutic decision-making early in the course of the disease
- Minimally invasive approach for sample collection. Blood serum-based tests are well accepted by patients and are widely used in clinical settings. Hence the tests can be prescribed routinely and frequently as a precautious measure to monitor high-risk patient population
- Highly sensitive and quantitative approach to predict drug response in sepsis