Editor’s Note: If antimicrobial drugs are the “express train” to cure, then antimicrobial susceptibility testing information is the “map” for accurate navigation. For a long time, China’s antimicrobial “map” has still referred to European and American standards, urgently needing to establish breakpoint standards suitable for Chinese patients. At the recent Fourth National Congress of the Chinese Medical Association on Bacterial and Fungal Infections (BISC 2024), Professor Qiwen Yang, Vice Chairman of the National Antimicrobial Susceptibility Testing Committee and from Peking Union Medical College Hospital of the Chinese Academy of Medical Sciences, brought a fascinating report on the “Progress in China’s Antimicrobial Susceptibility Testing System.” The report is summarized below.
Antimicrobial susceptibility breakpoint standards are crucial for accurately reporting susceptibility results in the laboratory and for clinicians’ proper use of antimicrobial drugs. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the Clinical and Laboratory Standards Institute (CLSI) are internationally renowned academic organizations for setting antimicrobial susceptibility breakpoints, each establishing its own system. Due to historical reasons and limitations in talent and research conditions in the corresponding fields, China has long used European and American breakpoint standards. However, European and American breakpoint standards are based on pharmacokinetic parameters of foreign populations and the minimum inhibitory concentration (MIC) distribution characteristics of foreign strains, which differ from those of Chinese populations and strains, leading to potential misinterpretation of susceptibility results when using European and American breakpoints in China. In addition, there are differences in breakpoint systems between EUCAST and CLSI. Even for the same drug and same organism, there are often different breakpoints, causing great confusion for clinical laboratories in China. Therefore, establishing China’s own antimicrobial drug susceptibility breakpoints is crucial for guiding clinical infection treatment and laboratory susceptibility testing, filling the gap in our country’s industry.
Establishment of the National Antimicrobial Susceptibility Testing Committee (ChinaCAST) Marks the First Step Towards “Chinese Breakpoints”
In 2022, the “National Action Plan to Combat Microbial Resistance (2022-2025)” issued by 13 departments, including the National Health Commission, clearly stated the need to “preliminarily establish a clinical microbial drug susceptibility breakpoint standard system suitable for China’s actual conditions.” The National Health Commission organized the establishment of the National Antimicrobial Susceptibility Testing Committee in 2022, whose full name in Chinese is the “Expert Committee of the National Health Commission on Antimicrobial Susceptibility Testing and Standard Research,” and in English is “ChinaCAST.”
The establishment of ChinaCAST aims to implement relevant national requirements, organize experts from various fields such as clinical microbiology, clinical pharmacology, and clinical infectious diseases to jointly promote research and standard formulation related to antimicrobial drug susceptibility breakpoints, thereby establishing a standard system for clinical antimicrobial drug susceptibility testing in China.
The work of ChinaCAST mainly includes:
Formulating work plans and organizing implementation: Clearly define the key drugs, research methods, research division of labor, and completion deadlines for a certain period, and organize various research medical institutions to conduct related research according to the work plan.
Formulating antimicrobial drug breakpoint standards and publishing them: Organize the formulation of breakpoint standards for important antimicrobial drugs based on the research results of various medical institutions and submit them to the National Health Commission for publication.
Evaluation after the implementation of standards: Regularly evaluate the clinical application of important antimicrobial drug breakpoint standards published, and improve or revise the drug breakpoint standards based on the evaluation results.
Organizing the establishment of a standard system for antimicrobial susceptibility testing: Including but not limited to methodological standardization, detection of special resistance mechanisms, and performance evaluation of susceptibility testing methods.
Organizing the assessment of research institution capabilities: Assess the capabilities of research medical institutions in the fields of epidemiological cutoff values, pharmacokinetic/pharmacodynamic (PK/PD) cutoff values, and clinical cutoff values.
Professional technical capacity training: Training on antimicrobial susceptibility testing and breakpoint-related topics.
Regularly organizing communication with relevant departments of the National Medical Products Administration, including but not limited to the setting of antimicrobial breakpoints, clinical application and effectiveness evaluation of drug breakpoints, safety evaluation, and updates to drug instructions.
Steady Progress: ChinaCAST Achieves a Good Start in Its Work
With the support of relevant departments and the efforts of the expert committee and various levels of medical institutions, ChinaCAST has made steady progress since its establishment, achieving a good start. The main progress in several aspects is as follows:
Establishment of the National Antimicrobial Susceptibility Testing Committee
Thirty clinical microbiology committee members, eleven clinical pharmacology committee members, and fourteen clinical infectious diseases committee members were selected as the first members of the National Antimicrobial Susceptibility Testing Committee. At the same time, twenty-nine epidemiological cutoff value research institutions, fourteen PK/PD cutoff value research institutions, and twenty-three clinical cutoff value research institutions have been identified.
Publication and interpretation of “Antimicrobial Drug Susceptibility Testing System-EUCAST Application Tools and Standard Operating Procedures”
This book translates content from EUCAST on bacterial and fungal drug breakpoints, drug dosages, quality control ranges, and expert rules, serving as a convenient reference tool for clinical physicians and clinical microbiologists. It has been presented and distributed at major academic conferences, and four interpretation documents have been uploaded to the ChinaCAST official website, reaching an audience of nearly ten thousand.
Publication of explanatory documents (application forms) for establishing clinical breakpoints for antimicrobial drugs
Detailed explanations of the basis for establishing clinical breakpoints, providing clear templates for establishing clinical breakpoint applications for antimicrobial drugs.
Establishment of epidemiological cutoff values (ECOFFs) for daptomycin against Staphylococcus aureus
This is the first epidemiological breakpoint study of antimicrobial drugs in China completed independently by multiple domestic centers according to international standards, and has been published in the international journal “Journal of Antimicrobial Chemotherapy.”
Establishment of ECOFFs for ciprofloxacin
Ciprofloxacin belongs to a new generation of quinolone drugs. ChinaCAST has established its clinical breakpoints for Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Pseudomonas aeruginosa, Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, and Streptococcus pneumoniae.
Establishment of clinical breakpoints for ertapenem
Ertapenem is a fourth-generation cephalosporin. ChinaCAST has established its clinical breakpoints for Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Scientific papers related to this work have been published in the “Journal of Antimicrobial Chemotherapy.”
Establishment of clinical breakpoints for eravacycline
Eravacycline is a novel, fully synthetic broad-spectrum antibacterial drug and the world’s first fluorocycline antibacterial drug. Currently, ChinaCAST has established its clinical breakpoints for Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Streptococcus pneumoniae, Moraxella catarrhalis, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. This is the first set of clinical breakpoints for antimicrobial drugs with independent intellectual property rights in China.
Establishment of the ChinaCAST Antimicrobial Susceptibility Testing Review Process
ChinaCAST includes three working groups: the Clinical Microbiology Working Group, the Clinical Pharmacology Working Group, and the Clinical Infectious Diseases Working Group, chaired by Professor Qiwen Yang, Professor Zhang Jing, and Professor Zheng Bo, respectively. The three working groups have clear division of labor and collaborate to complete the review of antimicrobial susceptibility breakpoints. The group leaders formulate work plans for their terms and are required to provide annual work summaries.
Working Together to Establish China’s Antimicrobial Susceptibility Testing System
In recent years, multidrug-resistant bacteria such as carbapenem-resistant Gram-negative bacteria (CRO) continue to be highly prevalent in China, and the availability of antimicrobial treatment drugs is limited. Without scientifically reasonable clinical breakpoints, the difficulty of clinical antimicrobial treatment will be further increased. In addition to establishing clinical breakpoints for eravacycline, ChinaCAST is also committed to improving the clinical breakpoints for other drugs used to treat CRO infections.
Guiding clinical practice to use antimicrobial drugs more reasonably through the determination of antimicrobial drug susceptibility breakpoints is key to winning the battle against bacterial resistance. It is hoped that under the leadership of ChinaCAST, China will establish an antimicrobial susceptibility breakpoint system at an early date, providing clinicians with more accurate treatment “navigation.”
Researcher, Doctoral Supervisor
National “Ten Thousand Talents Program” Leading Talent in Scientific and Technological Innovation
Associate Director, Department of Laboratory Medicine, Peking Union Medical College Hospital
Chairman, Chinese Antimicrobial Susceptibility Testing Committee of the European Society of Clinical Microbiology and Infectious Diseases (ChiCAST)
Vice Chairman, Expert Committee of the National Health Commission on Antimicrobial Susceptibility Testing and Standard Research
Secretary-General and Deputy Director, Clinical Microbiology Laboratory Professional Committee of the Chinese Hospital Association
Principal Investigator of more than 70 research projects, including the National Natural Science Foundation of China and the National Key Research and Development Program
Published over 180 papers in domestic and international journals, with over 70 papers as first or corresponding author, including publications in journals such as Lancet Microbe, Clin Infect Dis, EMERG MICROBES INFEC, and Clinical Chemistry in the fields of infection and microbiology
Granted 25 invention patents as the first inventor, with the resulting products widely used in clinical frontline medical care both domestically and internationally
Recipient of numerous awards, including one Second Prize for Higher Education Science and Technology Progress Award, one Second Prize of the Chinese Preventive Medicine Association Science and Technology Award, one Second Prize of the Beijing Science and Technology Award, two Third Prizes of the Chinese Medical Association Science and Technology Award, one Third Prize of the Huaxia Medical Science and Technology Award, and seven Sub-specialty Awards of the Chinese Medical Association; awarded an Outstanding Prize in the Beijing Youth Academic Speech Contest; named one of the “Top 100 Most Influential Academic Papers in China” in 2011, and recipient of the Top Academic Paper Award for Chinese High-quality Scientific and Technological Journals (Pioneer 5000) in 2013.
