Nucleic Acid Probes for Vancomycin Resistance Gene Detection

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Solution Overview

Problem

Current diagnostic methods for vancomycin-resistant Enterococcus (VRE) infections are slow, prone to false negatives, and lack sensitivity and specificity, necessitating the development of rapid and accurate tests for effective treatment and infection control.

Innovation Solution

Nucleic acid probes and primers are developed for detecting and isolating vancomycin resistance genes from Enterococcus and other genera, enabling rapid and specific identification of VRE, allowing for efficient patient and personnel screening, and environmental surface testing.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If culture-based diagnostic methods are used for VRE determination, then definitive diagnosis can be achieved, but the process takes 48 hours or longer and has high false negative rate

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidturn-around time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The diagnostic process is segmented into two distinct phases: (1) a rapid NAT screening phase that provides preliminary results in 2-5 hours to quickly identify potential VRE cases, and (2) a confirmatory culture phase that provides definitive diagnosis. This segmentation allows the system to deliver fast initial results while maintaining diagnostic reliability through subsequent confirmation.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The NAT test performs preliminary detection of vancomycin resistance genes before the culture process is complete. By conducting the nucleic acid amplification test in parallel with or before the culture confirmation, the system provides advance warning of potential VRE infections, enabling earlier clinical intervention while the culture confirmation is pending.

Inventive Principle:
Principle #10Preliminary action

2Loss of time

If NAT tests are adopted for VRE detection, then turn-around time is reduced to 2-5 hours, but sensitivity and specificity are insufficient

Engineering Contradiction:
Improveturn-around timeVSAvoidsensitivity and specificity
Core Design Contradiction:
Loss of timeVSReliability

Solution Approach 1:

The invention merges the rapid NAT testing approach with the reliable culture-based confirmation method into a unified diagnostic algorithm. The NAT test provides fast preliminary results using vanA and vanB gene detection, while the culture method provides definitive confirmation. By combining these two methods in sequence, the system achieves both rapid response (2-5 hours) and high diagnostic reliability.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The NAT test acts as an intermediary screening tool that triages patients into high-risk and low-risk categories. Positive NAT results trigger immediate confirmatory culture testing and alert clinicians to potential VRE cases, while negative NAT results allow for continued standard care. This intermediary role enables the system to leverage the speed of NAT while maintaining the reliability of culture methods.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Productivity

If culture-based methods with BEAV plates are used, then VRE can be presumed based on colonial morphology, but additional culture steps are required for confirmation

Engineering Contradiction:
Improvescreening efficiencyVSAvoidconfirmation time
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The NAT test performs preliminary identification of vancomycin resistance genes before culture confirmation is needed. By detecting the presence of vanA or vanB genes in the initial 2-5 hour window, the system preliminarily identifies VRE cases, allowing clinicians to initiate appropriate precautions and treatments while the confirmatory culture steps are being completed.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The diagnostic workflow is segmented so that NAT testing handles the initial screening and identification function, separating this time-sensitive task from the slower culture confirmation process. This segmentation allows the screening phase to operate independently and rapidly, while the confirmation phase proceeds in parallel without delaying the initial diagnostic response.

Inventive Principle:
Principle #1Segmentation

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The described assays provide a high degree of sensitivity and specificity for detecting vancomycin resistance genes, enabling rapid diagnosis and effective treatment regimens, significantly reducing VRE transmission in clinical settings.

Implementation Method 1

nucleic acid probes and primers for detecting, isolating and sequencing all known, characterized variants of the vanA, vanB, vanC1, vanC2/3, vanD, vanE, and vanG vancomycin resistance genes

Methodology Applied
Scientific EffectHybridization:

Implementation Method 2

Adoption of nucleic acid-based tests (NAT) (such as polymerase chase reaction (PCR)) has led to diagnostic tests with significantly better turn-around time

Methodology Applied
Scientific EffectPCR amplification:

Data Source

PatentEP2473630B1Optimized probes and primers and methods of using same for the detection, screening, isolation and sequencing of vancomycin resistance genes and vancomycin resistant enterococci
Publication Date: 2017.11.08 QIAGEN GMBH
  • EP2473630B1 patent drawingFigure 1
  • EP2473630B1 patent drawingFigure 2
  • EP2473630B1 patent drawingFigure 3

AI summary

Described herein are primers and probes useful for detecting, screening, isolating, and sequencing of the vancomycin resistance genes and vancomycin resistant Enterococci and methods of using the described primers and pr.