Antimicrobial Susceptibility Testing Using Surfactant Charge Adjustment

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Solution Overview

Problem

Current antimicrobial susceptibility testing (AST) methods are time-consuming, often requiring eight hours, leading to delayed antimicrobial treatment and increased antimicrobial resistance, and are limited in their ability to handle variations in microbial surface charge due to resistance acquisition.

Innovation Solution

A rapid AST system and method that involves inoculating microorganisms into a test panel with varying concentrations of cationic antimicrobials, determining growth ratios, and using surfactants to adjust cell membrane charge for improved binding of cationic signaling agents, allowing for faster and more accurate susceptibility testing.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of time

If current AST methods are used, then accuracy of susceptibility testing is maintained, but time required for AST determination increases to eight hours or more

Engineering Contradiction:
Improvetime required for AST determinationVSAvoidaccuracy of susceptibility testing
Core Design Contradiction:
Loss of timeVSReliability

Solution Approach 1:

The method performs preliminary actions by inoculating microorganisms into the test panel and incubating for a short period (e.g., 2-4 hours) to allow initial growth and expression of susceptibility phenotypes. This preliminary incubation enables rapid detection methods to work effectively, reducing total testing time while maintaining accuracy.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent uses intermediaries such as fluorescent probes, dyes, or signaling agents that bind to microbial surfaces or metabolic products. These intermediaries amplify the detection signal, allowing accurate susceptibility determination in reduced time by making subtle phenotypic differences more detectable.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If cationic signaling agents are used for rapid AST, then testing speed increases, but variations in microbial surface charge due to resistance acquisition reduce measurement accuracy

Engineering Contradiction:
Improvetesting speedVSAvoidaccuracy of surface charge measurement
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The method changes parameters by adjusting pH, ionic strength, or adding specific ions (e.g., Mg2+, Ca2+) to standardize the microbial surface charge environment. This normalization allows cationic signaling agents to bind consistently across different microbial strains and resistance states, maintaining measurement precision while enabling rapid testing.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a standardized reference state by using control wells with known microbial suspensions. These controls serve as references to compare against test samples, compensating for variations in surface charge and ensuring accurate interpretation of rapid AST results even when microbial characteristics vary.

Inventive Principle:
Principle #26Copying

3Object-affected harmful factors

If broad-spectrum antimicrobials are administered during waiting period, then patient safety is maintained, but antimicrobial resistance increases and patient health deteriorates

Engineering Contradiction:
Improvepatient safetyVSAvoidantimicrobial resistance and patient health deterioration
Core Design Contradiction:
Object-affected harmful factorsVSObject-generated harmful factors

Solution Approach 1:

The rapid AST method provides early feedback (within 2-4 hours) on microbial susceptibility to specific antimicrobials. This feedback enables clinicians to adjust therapy from broad-spectrum to targeted narrow-spectrum antimicrobials, preventing the development of resistance while maintaining patient safety by ensuring effective treatment.

Inventive Principle:
Principle #23Feedback

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

This approach significantly reduces the time required for AST determinations, enhances the accuracy of antimicrobial susceptibility testing by accounting for variations in microbial surface charge, and facilitates more effective antimicrobial stewardship.

Implementation Method 1

measuring an association of a cationic signaling agent with the cell wall of the microorganism

Methodology Applied
Scientific EffectElectrostatic interaction: Electrostatics

Implementation Method 2

using surfactants to adjust cell membrane charge for improved binding of cationic signaling agents

Methodology Applied
Scientific EffectSurfactant action: Surfactant

Data Source

PatentUS11649477B2Assays and reagents for antimicrobial susceptibility testing
Publication Date: 2023.05.16 SELUX DIAGNOSTICS
  • US11649477B2 patent drawing
  • US11649477B2 patent drawing
  • US11649477B2 patent drawing

AI summary

Systems and methods for antimicrobial susceptibility testing (AST) are provided in which variances in anionic charge of microbes are taken into account. Cationic surfactants may be used to sensitize otherwise resistant microorganisms to polycationic antibiotics, such as polymyxins. Since microorganisms gain polycationic antibiotic resistance through mutations that decrease surface anionic charge, the susceptibility of a microorganism to a polycationic antibiotic may be indicative of its surface charge. In order to enable electrostatic interactions with the microorganism surface, a cationic surfactant may be applied to increase the anionic charge of the microorganism.