Correcting a Fundamental Flaw in the Paradigm for Antimicrobial Susceptibility Testing

Area of Science:

• Microbiology
• Infectious Diseases
• Pharmacology

Background:

• Antibiotic resistance is a growing global health crisis.
• Current in vitro antimicrobial susceptibility testing (AST) methods do not accurately reflect in vivo conditions.
• This limitation leads to the misidentification of effective and ineffective antibiotic therapies.

Purpose of the Study:

• To evaluate the efficacy of standard AST versus a modified AST that mimics host environments.
• To identify key factors in host environments that influence antibiotic efficacy.
• To improve the predictive accuracy of AST for clinical antibiotic selection.

Main Methods:

• Standard AST was performed using conventional media.
• A modified AST was conducted using media supplemented with sodium bicarbonate to mimic host environments.
• Antibiotic efficacy was validated in mouse models of infection and sepsis.

Main Results:

• Standard AST incorrectly identified several antibiotics as ineffective or effective.
• Modified AST accurately predicted antibiotic efficacy in vivo, identifying drugs effective for bacterial clearance and host survival.
• Sodium bicarbonate supplementation was crucial for improving the predictive value of AST.

Conclusions:

• Standard AST is unreliable for predicting in vivo antibiotic efficacy.
• Host-mimicking AST, particularly with sodium bicarbonate, enhances the accuracy of antibiotic selection.
• This improved testing has the potential to optimize antibiotic development, testing, and prescription practices.