Methods and devices for bone infection treatment selection
Inventors
Aronow, Bruce J. • Harley, John B. • Hostetter, Margaret • Kaufman, Kenneth
Assignees
United States Government As Represented By Us Department Of Veterans Affairs • Cincinnati Childrens Hospital Medical Center • Government of the United States of America
Publication Number
US-10583148-B2
Publication Date
2020-03-10
Expiration Date
2035-04-08
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Abstract
Disclosed are methods for identifying patients at increased risk of developing disseminated staphylococcal infection, which includes the steps of determining that the patient has a mutation in one or more genes selected from a MPDZ network gene, a CGNL1 network gene, a PRKRIR network gene, a MED26 network gene, a tight junction protein gene, or an immune modulator gene; and treating the patient for disseminated staphylococcal infection. Also disclosed are solid substrates and/or assays useful for carrying out the disclosed methods.
Core Innovation
The invention provides methods for identifying patients at increased risk of developing disseminated staphylococcal infection by determining the presence of mutations in one or more genes selected from a MPDZ network gene, a CGNL1 network gene, a PRKRIR network gene, a MED26 network gene, tight junction protein genes, or immune modulator genes, and subsequently treating the patient for disseminated staphylococcal infection. Also disclosed are solid substrates and assays useful for carrying out these identification methods.
The problem addressed is the poor understanding of host susceptibility to Staphylococcus aureus, a pathogen responsible for invasive infections including osteomyelitis, which is a common childhood infection requiring hospitalization. Current treatments do not adequately stratify patients by genetic susceptibility to disseminated infection, leading to potential delays or inadequacies in administering the most effective therapeutic protocols.
The invention specifically enables stratification of patients with bone infection, such as osteomyelitis, by detecting mutations acting as biomarkers predictive of risk for disseminated staphylococcal infection. This risk stratification guides treatment decisions including surgical intervention and use of bactericidal antibiotics, allowing rapid and tailored therapy for individuals who have an underlying genetic susceptibility to severe infection.
Claims Coverage
The patent contains independent claims focused on methods for detecting specific mutations in patients diagnosed with bone infections using mutation-specific probes, and methods for treatment based on detection.
Mutation detection using mutation-specific probes
A method of detecting a mutation in a human diagnosed with a bone infection by obtaining a biological sample and detecting whether a specific mutation (such as Leu739Ile in CGNL1) is present using a probe specific for that mutation and detecting binding between the probe and mutation.
Treatment administration upon mutation detection
Following detection of the mutation, administering an antibiotic selected from teicoplanin, vancomycin, gentamicin, or combinations thereof to the patient diagnosed with a bone infection.
Detection of additional specific mutations using nucleic acid probes
Methods further comprising detection of other mutations such as Leu602Phe in PRKRIR, Leu35Pro in MPDZ, and Ala464Thr in MED26 using nucleic acid probes comprising detectable labels specific to the respective mutations.
The independent claims cover methods of detecting specific mutations in bone infection patients using mutation-specific probes and subsequent treatment with specified antibiotics, highlighting detection of particular mutations in CGNL1, PRKRIR, MPDZ, and MED26 genes and treatment protocols responsive to such detection.
Stated Advantages
Identification of patients at increased risk of disseminated staphylococcal infection enables targeted and timely treatment.
Allows the use of appropriate surgical intervention and bactericidal antibiotics tailored to genetic susceptibility.
Provides a risk-stratification tool for predicting genetic susceptibility to disseminated infection after osteomyelitis, improving therapeutic outcomes.
Documented Applications
Stratification of patients with bone infections, including osteomyelitis, to identify those needing surgical intervention and/or bactericidal antibiotic treatment.
Use of solid substrates and assays such as microarrays and RT-PCR to detect mutations in genes linked to susceptibility to disseminated staphylococcal infection.
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