Rethinking Reference Methods for Antibacterial Susceptibility Testing Beyond Broth Microdilution
For five decades broth microdilution has served as the AST reference method, but it poorly mimics in vivo conditions, requires multiple days, and cannot evaluate agents targeting virulence rather than growth. This review outlines key considerations for developing novel standardised reference methods that must correlate with clinical efficacy and gain international regulatory recognition.
The original study
Contemporary Considerations for Establishing Reference Methods for Antibacterial Susceptibility Testing.
- Authors
- Humphries RM, Miller L, Zimmer B, Matuschek E, Hindler JA
- Journal
- Journal of clinical microbiology
- Type
- Journal Article, Review
- PMID
- 36971571
Original abstract
Antibacterial susceptibility testing (AST) is performed to guide therapy, perform resistance surveillance studies, and support development of new antibacterial agents. For 5 decades, broth microdilution (BMD) has served as the reference method to assess in vitro activity of antibacterial agents against which both novel agents and diagnostic tests have been measured. BMD relies on in vitro inhibition or killing of bacteria. It is associated with several limitations: it is a poor mimic of the in vivo milieu of bacterial infections, requires multiple days to perform, and is associated with subtle, difficult to control variability. In addition, new reference methods will soon be needed for novel agents whose activity cannot be evaluated by BMD (e.g., those that target virulence). Any new reference methods must be standardized, correlated with clinical efficacy and be recognized internationally by researchers, industry, and regulators. Herein, we describe current reference methods for in vitro assessment of antibacterial activity and highlight key considerations for the generation of novel reference methods.