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Antibiotic Dereplication Using the Antibiotic Resistance Platform
Published on: October 17, 2019
Pre-Target Interception Defines Carbapenem Failure in Carbapenem-Resistant Enterobacterales: A Mechanistic Framework
Eman Marzouk1, Ayman Elbehiry1
1Department of Public Health, College of Applied Medical Sciences, Qassim University, P.O. Box 6666, Buraydah 51452, Saudi Arabia.
Pharmaceutics
|June 26, 2026
Summary
Carbapenem-resistant Enterobacterales (CRE) infections pose treatment challenges. A new model, PTIM, highlights antibiotic loss at infection sites, guiding nanomedicine development for better CRE treatment outcomes.
Area of Science:
- Infectious Diseases
- Pharmacology
- Biotechnology
Background:
- Carbapenem-resistant Enterobacterales (CRE) infections present significant therapeutic challenges due to limited treatment options and high mortality rates.
- Despite advancements in resistance-targeted therapies and pharmacokinetic (PK) optimization, treatment failures in CRE infections remain common.
- Understanding the interplay between bacterial resistance mechanisms and antibiotic exposure at the infection site is crucial for improving therapeutic outcomes.
Purpose of the Study:
- To review and synthesize evidence on carbapenem pharmacokinetics, bacterial resistance, and nanoparticle (NP)-based delivery systems in CRE infections.
- To propose the Pre-Target Interception Model (PTIM) to explain treatment failure as the loss of active antibiotic before reaching its target.
- To assess nanocarrier systems within the PTIM framework for their potential to overcome barriers to effective antibiotic delivery in CRE infections.
Main Methods:
- Mechanistic synthesis of existing evidence on carbapenem PKs, bacterial resistance, and NP delivery systems.
- Development of the Pre-Target Interception Model (PTIM) to conceptualize antibiotic exposure and loss.
- Evaluation of nanocarrier systems based on their ability to protect antibiotics, enhance tissue penetration, and improve retention against resistance mechanisms.
Main Results:
- The Pre-Target Interception Model (PTIM) framework identifies factors limiting effective antibiotic exposure within infected tissues as key to treatment failure.
- Nanocarrier systems show potential for protecting antibiotics and enhancing delivery, but face challenges in clinical translation.
- Current limitations include manufacturing complexities, variable NP performance, and lack of validation in CRE-specific models.
Conclusions:
- PTIM offers a novel perspective on CRE treatment failure, focusing on antibiotic loss prior to target engagement.
- Nanomedicines hold promise for improving antibiotic delivery in CRE infections, but require further development and validation.
- Future progress necessitates quantitative assessment of antibiotic exposure at infection sites and standardized evaluation of nanocarrier performance in clinically relevant models.
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