The new document provides framework for drug developers on appropriate use and modification of reference AST methods during antimicrobial development.
The Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) have jointly published new guidance on modifications to antimicrobial susceptibility testing (AST) methods, aimed at supporting drug developers while maintaining testing standards.
The document, titled “Modification of Antimicrobial Susceptibility Testing Methods,” addresses the growing need for clear protocols as pharmaceutical companies develop new antimicrobial agents to combat rising drug resistance. The guidance emphasizes that while modifications to standard AST methods may sometimes be necessary, such changes must be scientifically justified and clinically meaningful.
“While there are certainly instances where modifications of the reference method are necessary, this decision should not be made lightly and should never be made solely to report a lower MIC,” says Dr James S Lewis II, Oregon Health and Science University Departments of Pharmacy and Infectious Diseases and co-chair for the CLSI subcommittee on AST, in a release.
Maintaining Gold Standard Methods
The document reinforces broth microdilution in cation-adjusted Mueller-Hinton broth, as defined by CLSI M07 and ISO 20776-1, as the gold standard reference method for AST. The guidance warns against attempts to artificially lower minimum inhibitory concentration values, calling such practices scientifically unsound and potentially misleading.
Lewis notes that previous modifications to reference methods have often led to delays in clinical utilization of novel agents or curtailed their clinical use due to complexity introduced by changes to standard methods.
“The development of accurate and practical antimicrobial susceptibility testing methods is critical to ensuring new agents can be reliably implemented in clinical laboratories,” says Amy Mathers, MD, University of Virginia Medical School Department of Pathology and co-chair of the CLSI subcommittee for AST, in a release.
Industry Impact and Implementation
The guidance comes as antimicrobial resistance continues to pose global public health threats, making timely development and reliable testing of new antimicrobial agents crucial. The document was developed by the joint CLSI and EUCAST New Drug Alternative Methods Ad Hoc Working Group to provide a clear framework for the industry.
Both organizations recommend adherence to the reference BMD method and close consultation with AST experts to ensure any modifications are warranted, effective, and feasible for implementation in routine laboratory settings.
“In working closely with EUCAST, we hope the coming guidance will help prevent unnecessary investment in methods that may not be feasible for routine lab use and will ultimately support the broader goal of getting effective therapies to patients efficiently and reliably,” says Mathers in a release.
CLSI and EUCAST are actively developing additional joint guidance to further support harmonized AST method development and modification. The full document is now available through both organizations’ websites.
