Potentiating Agents for Resistant Microbial Infections
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Solution Overview
Problem
The decline in the effectiveness of antimicrobials due to microbial adaptation leads to increased resistance, and there is a scarcity of new antimicrobial molecules entering the market, making it difficult to treat microbial infections effectively.
Innovation Solution
Compounds of formula (I) are used at low doses where they are inactive, potentiating the effect of antimicrobials by enhancing their activity against bacterial and fungal infections without exhibiting antimicrobial properties themselves, thus overcoming resistance mechanisms and toxicity constraints.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If compounds of formula (I) are used at high doses to exhibit antimicrobial properties, then antimicrobial activity is improved, but toxicity increases to unacceptable levels
Solution Approach 1:
The patent applies parameter changes by utilizing the same compound (I) at two different concentration parameters: high concentrations (≥1000 mg/L) for direct antimicrobial activity and low concentrations (0.01-100 mg/L) for potentiating activity. This dual-parameter approach allows the system to achieve different functional outcomes from the same substance, resolving the contradiction between antimicrobial efficacy and toxicity.
Solution Approach 2:
The patent employs compound (I) as an intermediary substance that mediates between the host and the pathogen. At low doses, it acts as a potentiator that enhances the effectiveness of antimicrobial agents without directly killing microbes, thereby reducing the need for high-dose antimicrobial administration and associated toxicity. This intermediary role allows the system to achieve therapeutic effects while minimizing harmful side effects.
2Reliability
If new antimicrobial molecules are discovered to combat resistance, then effectiveness against resistant microbes is improved, but the scarcity of new molecules worsens treatment options
Solution Approach 1:
The patent applies universality by demonstrating that compound (I) can potentiate multiple different classes of antimicrobial agents (beta-lactams, aminoglycosides, fluoroquinolones, macrolides, tetracyclines, and antifungals) against various resistant microbial strains. This multi-functional capability allows a single potentiator to work across diverse treatment scenarios, effectively expanding the utility of existing antimicrobial arsenal without requiring constant development of new molecules.
Solution Approach 2:
The patent utilizes parameter changes by altering the concentration parameter of compound (I) to achieve potentiation effects across different antimicrobial agents and resistant strains. The low dose range (0.01-100 mg/L) serves as a universal potentiating concentration that can enhance the activity of various antimicrobial classes, providing a versatile solution to resistance problems without depleting the limited pool of new antimicrobial molecules.
3Reliability
If compounds of formula (I) are used at doses close to their MIC to potentiate antimicrobials, then potentiation effect is improved, but toxicity becomes unacceptable for medical use
Solution Approach 1:
The patent resolves this contradiction through parameter changes by identifying and utilizing a specific low concentration parameter range (0.01-100 mg/L) for compound (I) that provides potentiation effects while maintaining acceptable toxicity profiles for medical use. This optimized parameter range is distinct from both the high concentrations needed for direct antimicrobial activity and the intermediate concentrations near MIC, creating a safe therapeutic window for potentiating applications.
Solution Approach 2:
The patent applies partial action by using sub-MIC concentrations of compound (I) that are insufficient for direct antimicrobial killing but sufficient to modulate microbial susceptibility to other antimicrobial agents. This partial action approach allows the system to achieve the desired potentiation effect without reaching the toxic thresholds associated with higher concentrations, effectively decoupling potentiation activity from toxic side effects.
Data Source
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AI summary
The invention relates to a potentiated antimicrobial agent for use in the treatment of a microbial infection, characterised in that said antimicrobial agent is used in association with a compound of formula I, (I) the mass ratio of compound of formula (I) : antimicrobial agent varying between 8 : 1 and 1 : 10, and in that the microbial infection is induced in particular by a pathogen of strain A and, on said strain A, the concentration of compound (I) corresponds to the following equation: [C] < [CMI] / x, wherein: [C] is the concentration according to the invention of compound (I) to be used on strain A; [CMI] is the CMI measured for compound (I), alone, on strain A; and x is greater than or equal to 100, advantageously greater than 1,000, more advantageously x is between 2,000 and 10,000, or even greater than 50,000.