# Breakpoint Harmonization Between CLSI and EUCAST ## Quick Answer - CLSI and EUCAST breakpoints differ because each organization uses distinct data review processes, interpretive criteria, and revision timelines for antimicrobial susceptibility testing. - Laboratories must document which standard they follow, verify current editions, and communicate discrepancies to clinicians to prevent misinterpretation of susceptibility results. - Breakpoint harmonization is incomplete, so clinical microbiologists should maintain clear reporting protocols and escalate unresolved interpretive conflicts to the laboratory director. ## At a Glance | Aspect | CLSI Approach | EUCAST Approach | Practical Impact | |--------|---------------|-----------------|------------------| | Breakpoint Development | Uses clinical, pharmacokinetic, and microbiological data with a structured review process | Uses similar data but applies different epidemiological cutoff values and clinical breakpoint logic | Same organism-drug combination can yield different susceptibility categories | | Revision Frequency | Periodic updates with documented addenda | Regular annual updates with rapid revision mechanisms | Laboratories must track version changes to maintain compliance | | Interpretive Categories | Susceptible, intermediate, resistant | Susceptible, susceptible-dose dependent, resistant | Reporting differences affect treatment decisions | | Quality Control Ranges | Published in CLSI M100 documents | Published in EUCAST QC tables | Laboratories need separate QC verification for each standard | | Documentation Requirements | Requires specific QC organism testing and record keeping | Requires similar QC but with different frequency expectations | Documentation burden varies by standard | ## Understanding Breakpoint Harmonization Breakpoint harmonization refers to the process of aligning interpretive criteria used by different standards organizations to classify bacterial susceptibility to antimicrobial agents. The Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) are the two primary bodies that establish these breakpoints globally. Each organization evaluates data from clinical trials, pharmacokinetic and pharmacodynamic studies, and microbiological characteristics of bacterial populations to set thresholds that determine whether an isolate is susceptible, intermediate, or resistant to a given antibiotic. The need for harmonization arises because clinical laboratories, particularly those in the United States, often rely on CLSI standards, while European laboratories and many international institutions follow EUCAST recommendations. When breakpoints differ, the same bacterial isolate can be reported as susceptible under one standard and resistant under the other. This discrepancy creates confusion for clinicians who must decide whether to prescribe a specific antibiotic based on laboratory results. The [World Health Organization](https://www.who.int/health-topics/antimicrobial-resistance) identifies antimicrobial resistance as a global public health concern, and accurate susceptibility testing is a cornerstone of resistance surveillance and stewardship programs. When breakpoints are not aligned, resistance data collected from different regions cannot be compared directly, which complicates global surveillance efforts. Harmonization aims to reduce these discrepancies so that susceptibility results are consistent across laboratories and geographic boundaries. ## Why CLSI and EUCAST Breakpoints Differ ### Data Sources and Evaluation Methods CLSI and EUCAST use different approaches to gather and evaluate the data that inform their breakpoint decisions. CLSI relies on a committee structure that reviews clinical trial data, pharmacokinetic and pharmacodynamic modeling, and microbiological data from a variety of sources. EUCAST similarly uses clinical and microbiological data but places a stronger emphasis on epidemiological cutoff values, which are derived from the distribution of minimum inhibitory concentrations (MICs) for wild-type populations of bacteria. The [Clinical and Laboratory Standards Institute](https://clsi.org/standards/products/microbiology) publishes its standards through a structured process that includes public comment periods and documented revisions. EUCAST operates with a different governance structure and often updates its breakpoints more frequently. These procedural differences mean that the two organizations may review the same data at different times and reach different conclusions about where a breakpoint should be set. ### Pharmacokinetic and Pharmacodynamic Modeling Pharmacokinetic and pharmacodynamic (PK/PD) modeling is a critical component of breakpoint setting. Both organizations use PK/PD data to predict whether a given drug concentration will be effective against a particular organism. However, the models and the assumptions built into them can differ. For example, the protein binding assumptions, the target site concentrations, and the dosing regimens used in the models may vary between CLSI and EUCAST. These differences can shift the breakpoint by one or more dilution steps, which is enough to change the susceptibility category for an organism with an MIC near the breakpoint. ### Epidemiological Cutoff Values Epidemiological cutoff values (ECOFFs) are used to distinguish wild-type populations from those with acquired resistance mechanisms. EUCAST places a strong emphasis on ECOFFs when setting breakpoints, while CLSI incorporates ECOFFs but also weighs clinical outcome data more heavily in some cases. The result is that EUCAST breakpoints may be set closer to the ECOFF, while CLSI breakpoints may be set at a value that reflects clinical efficacy in specific patient populations. ### Revision Timelines and Version Control CLSI updates its standards on a regular schedule, with new documents published annually and supplements issued as needed. EUCAST also updates its breakpoint tables annually but has a more flexible process for introducing changes between scheduled updates. This means that a laboratory using EUCAST standards may encounter a new breakpoint before the corresponding CLSI update is published. Laboratories that maintain both standards must track these version differences carefully to avoid reporting results based on outdated breakpoints. ## The Role of Minimum Inhibitory Concentration Testing Minimum inhibitory concentration (MIC) testing is the foundation of antimicrobial susceptibility testing. The MIC is the lowest concentration of an antimicrobial agent that inhibits visible growth of a microorganism. Both CLSI and EUCAST use MIC values as the basis for their breakpoint decisions, but the methods used to determine MICs can vary. ### Broth Microdilution and Agar Dilution Broth microdilution is the reference method for MIC determination in both CLSI and EUCAST. The method involves preparing serial two-fold dilutions of an antimicrobial agent in a liquid medium, inoculating with a standardized bacterial suspension, and incubating under controlled conditions. The MIC is read as the lowest concentration that inhibits visible growth. Agar dilution is an alternative method that uses agar plates containing serial dilutions of the antimicrobial agent. Both methods are standardized, but the specific conditions, such as the medium composition and the inoculum density, may differ slightly between the two organizations. ### Disk Diffusion Testing Disk diffusion testing is a simpler and less expensive method that is widely used in clinical laboratories. A paper disk impregnated with a specific concentration of an antimicrobial agent is placed on an agar plate inoculated with the test organism. The diameter of the zone of inhibition is measured and compared to interpretive criteria. CLSI and EUCAST use different zone diameter breakpoints for many organism-drug combinations, which means that a disk diffusion result can be interpreted differently depending on the standard used. ### Automated Systems Automated susceptibility testing systems are used in many clinical laboratories to provide rapid results. These systems measure bacterial growth in the presence of antimicrobial agents and use algorithms to estimate MICs. The algorithms are calibrated to either CLSI or EUCAST breakpoints, and the laboratory must ensure that the system is configured to the standard it uses for reporting. If a laboratory switches from CLSI to EUCAST, the automated system must be updated to reflect the new breakpoints. ## Practical Workflow for Reconciling Breakpoint Differences ### Step 1: Determine the Reporting Standard The first step in reconciling breakpoint differences is to determine which standard the laboratory will use for reporting. This decision is typically made by the laboratory director and is based on the patient population served, the requirements of the accrediting body, and the preferences of the clinical staff. In the United States, CLSI is the most commonly used standard, but some laboratories have adopted EUCAST for specific organisms or drugs. ### Step 2: Verify the Version and Date Once the standard is selected, the laboratory must verify that it is using the most current version of the breakpoint tables. Both CLSI and EUCAST publish updates on a regular basis, and the laboratory must have a process for tracking these updates. The version number and the date of the update should be documented in the laboratory records. ### Step 3: Check the Organism-Drug Combination For each organism-drug combination, the laboratory must check whether the breakpoints differ between CLSI and EUCAST. Some combinations have identical breakpoints, while others differ by one or more dilution steps. The laboratory should maintain a table of the breakpoints for the most commonly tested organism-drug combinations, with the CLSI and EUCAST values listed side by side. ### Step 4: Interpret the MIC or Zone Size The MIC or zone size is interpreted using the breakpoints for the selected standard. If the result falls into a different category under the other standard, the laboratory must decide how to report the result. The laboratory should have a policy for reporting results that fall into a discrepancy zone, such as reporting the result as susceptible under the selected standard but adding a comment that the result would be resistant under the other standard. ### Step 5: Document the Decision The laboratory must document the decision to use a particular standard and the process for reconciling differences. This documentation should include the version of the breakpoint table used, the date of the decision, and the rationale for the decision. The documentation should be available for review by accrediting bodies and for use in resolving disputes. ### Step 6: Communicate with the Clinical Team The laboratory must communicate the results to the clinical team in a way that is clear and actionable. If a result is affected by a breakpoint difference, the laboratory should include a comment on the report that explains the discrepancy. The clinical team should be informed of the standard used and the potential for differences in interpretation. ## Records and Measurements Accurate records are essential for managing breakpoint differences. The laboratory should maintain the following records: - The version of the breakpoint table used for each test - The date of the last update to the breakpoint table - The results of quality control tests for each antimicrobial agent - The MIC or zone size for each organism-drug combination tested - The interpretation of each result under the selected standard - Any comments added to the result to explain a discrepancy These records should be reviewed regularly to ensure that the laboratory is using the most current breakpoints and that the results are consistent with the selected standard. ## Common Failure Patterns Several common failure patterns can occur when laboratories do not manage breakpoint differences properly: - **Using outdated breakpoints**: A laboratory may continue to use an older version of a breakpoint table after a new version has been published. This can lead to results that are not consistent with the current standard. - **Mixing standards**: A laboratory may use CLSI breakpoints for some organism-drug combinations and EUCAST breakpoints for others without a clear policy. This can lead to inconsistent results and confusion in the clinical team. - **Failing to document the standard**: A laboratory may not record which standard was used for a particular test. This makes it difficult to interpret the result later and can lead to errors in treatment decisions. - **Ignoring QC results**: Quality control testing is essential to ensure that the susceptibility testing method is working correctly. If QC results are not reviewed and acted upon, the accuracy of the results can be compromised. ## Quality Control and Assurance Quality control is a critical component of antimicrobial susceptibility testing. Both CLSI and EUCAST require that laboratories perform quality control testing using reference strains to ensure that the testing method is accurate and reproducible. The [American Type Culture Collection](https://www.atcc.org/) provides authenticated reference strains that are used for quality control testing. These strains have known MIC values for a range of antimicrobial agents, and the laboratory must verify that the results obtained with these strains are within the expected range. Quality control testing should be performed on a regular basis, and the results should be recorded and reviewed. If a quality control result is outside the expected range, the laboratory must investigate the cause and take corrective action. This may involve repeating the test, checking the media and reagents, or verifying the calibration of the equipment. The [Clinical and Laboratory Standards Institute](https://clsi.org/standards/products/microbiology) provides guidance on quality control for antimicrobial susceptibility testing, including the frequency of testing and the acceptable ranges for each reference strain. The laboratory should follow this guidance to ensure that its testing is accurate and reliable. ## Biosafety and Containment Antimicrobial susceptibility testing involves the handling of bacterial cultures, which can be hazardous. The [CDC and NIH Biosafety in Microbiological and Biomedical Laboratories](https://www.cdc.gov/labs/bmbl/index.html) provides guidance on the safe handling of microorganisms in the laboratory. The laboratory must follow these guidelines to protect the staff and the environment from exposure to infectious agents. The biosafety level required for a particular organism depends on the risk it poses. Most bacteria that are tested for antimicrobial susceptibility are classified as biosafety level 2 (BSL-2) organisms, which require a moderate level of containment. The laboratory must have the appropriate facilities, equipment, and procedures in place to handle these organisms safely. The laboratory must also have a decontamination procedure for waste and equipment. This includes the proper disposal of cultures and the disinfection of work surfaces. The laboratory should follow the guidelines provided by the CDC and NIH to ensure that the decontamination is effective. ## Common Failure Patterns in Breakpoint Management ### Failure to Track Updates One of the most common failures is the failure to track updates to the breakpoint tables. Both CLSI and EUCAST publish updates on a regular basis, and the laboratory must have a process to identify and implement these updates. If the laboratory does not track updates, it may continue to use outdated breakpoints, which can lead to incorrect results. ### Failure to Document the Standard Another common failure is the failure to document the standard used for each test. This can lead to confusion when the results are reviewed later or when the clinical team asks about the interpretation. The laboratory must have a clear policy for documenting the standard used for each test. ### Failure to Communicate with the Clinical Team The laboratory must communicate with the clinical team about the breakpoint differences and the potential for discrepancies. If the clinical team is not aware of the differences, they may make treatment decisions based on results that are not consistent with the standard used by the laboratory. ### Failure to Perform Quality Control Quality control testing is essential to ensure the accuracy of the susceptibility testing. If the laboratory does not perform quality control testing on a regular basis, the results may be inaccurate, and the breakpoint differences may be compounded by the testing error. ## Limitations of Breakpoint Harmonization Breakpoint harmonization is not complete, and there are several limitations that laboratories must be aware of: - **Data availability**: The data used to set breakpoints are not always available to the public, and the data may be limited for certain organism-drug combinations. - **Clinical trial data**: The clinical trial data used to set breakpoints may not be representative of all patient populations, and the breakpoints may not be appropriate for all clinical situations. - **PK/PD modeling**: The PK/PD models used to set breakpoints are based on assumptions that may not hold in all clinical situations. - **ECOFFs**: The ECOFFs used by EUCAST may not be available for all organism-drug combinations, and the ECOFFs may not be appropriate for all organisms. These limitations mean that the breakpoints are not perfect and that the laboratory must use clinical judgment when interpreting the results. ## Professional Escalation Criteria The laboratory must have a process for escalating issues that cannot be resolved at the bench level. The following situations should be escalated to the laboratory director or the clinical team: - **A result that is affected by a breakpoint difference and is clinically significant**: If the result is for a patient with a serious infection, the laboratory should escalate the issue to the clinical team to ensure that the treatment decision is made with the full understanding of the breakpoint difference. - **A quality control failure that cannot be resolved**: If the quality control testing fails and the cause cannot be identified, the laboratory should escalate the issue to the laboratory director. - **A question about the interpretation of a breakpoint**: If the laboratory staff is unsure about the interpretation of a breakpoint, they should escalate the issue to the laboratory director or the clinical team. ## A Practical Decision Framework for Reporting Discordant Susceptibility Results Clinical microbiologists face a recurring operational problem when an isolate produces an MIC or zone diameter that falls into different interpretive categories under CLSI and EUCAST. The result is also a technical discrepancy. It is a patient-safety event waiting to happen if the report reaches the clinician without context. This section provides a structured decision framework that laboratories can adopt to manage discordant results consistently, document the reasoning behind each interpretation, and reduce the risk of miscommunication. ### Defining the Discordance Types Before applying any decision framework, the laboratory must classify the type of discordance it is dealing with. Not all breakpoint differences create the same level of clinical risk, and the response should be proportional to the potential harm. **Category 1: Category Discordance with Low Clinical Risk** This occurs when the MIC falls into a different category under CLSI and EUCAST, but the difference does not change the likely treatment outcome. For example, an isolate may be classified as susceptible under CLSI and intermediate under EUCAST. The clinician may still be able to use the drug with dose adjustment or close monitoring. The laboratory should report the result under the primary standard and add a comment that the isolate is not fully susceptible under the alternative standard. **Category 2: Category Discordance with High Clinical Risk** This occurs when the isolate is susceptible under one standard and resistant under the other. This is the most dangerous scenario because it can lead to either undertreatment or unnecessary use of broader-spectrum agents. The laboratory must escalate this result to the clinical team with a clear explanation of the discrepancy and the basis for the interpretation. **Category 3: MIC at the Breakpoint Edge** This occurs when the MIC is within one dilution step of the breakpoint under either standard. The result is inherently uncertain because the MIC method has a reproducibility of plus or minus one dilution. The laboratory should repeat the test or use a confirmatory method before reporting the result as a definitive category. **Category 4: Discordance Due to Method Differences** This occurs when the laboratory uses a disk diffusion method and the zone diameter falls into different categories under the two standards. The laboratory should confirm the result using a broth microdilution method before reporting the final interpretation. The laboratory should document the type of discordance for each isolate and use this information to track patterns over time. If a particular organism-drug combination consistently produces discordant results, the laboratory should review the breakpoint tables and consider whether the primary standard needs to be changed for that combination. ### The Decision Matrix for Reporting The decision matrix below provides a step-by-step approach for handling discordant results. The laboratory should apply this matrix to every isolate that falls into a discordant zone. | Step | Action | Condition | Outcome | |------|--------|-----------|---------| | 1 | Confirm the MIC or zone size | Repeat the test if the result is at the breakpoint edge | Confirmed result | | 2 | Check the primary standard | Verify the version and date of the breakpoint table | Current standard | | 3 | Determine the category under the primary standard | Use the breakpoint table for the primary standard | Category A | | 4 | Determine the category under the alternative standard | Use the breakpoint table for the alternative standard | Category B | | 5 | Compare Category A and Category B | If the same, report the result | No discordance | | 6 | If different, assess clinical risk | Use the discordance type definitions | Risk level | | 7 | Report the result | Use the primary standard category | Report with comment | | 8 | Escalate if high risk | Notify the laboratory director and clinical team | Escalation | The matrix is designed to be applied at the bench level by the technologist who performs the test. The technologist should have access to both breakpoint tables and should be trained to identify discordant results. The matrix should be posted in the laboratory or included in the standard operating procedures. ### The Reporting Protocol The reporting protocol is the most important part of the decision framework because it determines what the clinician sees. The laboratory must have a clear policy for how discordant results are reported. The policy should include the following elements: **Primary Result** The primary result is the interpretation under the standard that the laboratory has selected as its primary reporting standard. This result should be reported in the usual format, with the MIC or zone size and the interpretive category. **Secondary Result Comment** If the result is discordant, the laboratory should add a comment to the report that explains the discrepancy. The comment should be concise and should not use technical jargon that the clinician may not understand. An example comment is: "This isolate is susceptible to ciprofloxacin under CLSI breakpoints but resistant under EUCAST breakpoints. The clinical significance of this difference should be considered when selecting therapy." **Clinical Guidance** The laboratory should provide clinical guidance when the discordance is high risk. This guidance should be based on the laboratory's understanding of the clinical situation and should be reviewed by the laboratory director. The guidance should not be prescriptive but should provide the clinician with the information needed to make an informed decision. **Escalation Notification** If the discordance is high risk, the laboratory should notify the clinical team directly. This notification should be made by the laboratory director or the clinical microbiologist and should include the reason for the escalation and the recommended next steps. ### The Documentation System The laboratory must maintain a record of every discordant result and the decision that was made. The record should include the following information: - The patient identifier - The organism and the antimicrobial agent - The MIC or zone size - The category under the primary standard - The category under the alternative standard - The discordance type - The decision made - The date and time of the decision - The name of the person who made the decision The record should be maintained in a format that can be reviewed by the laboratory director and by accrediting bodies. The record should be kept for a period that is consistent with the laboratory's record retention policy. The laboratory should also maintain a log of the discordant results that are escalated. This log should include the reason for the escalation and the outcome of the escalation. The log should be reviewed on a regular basis to identify patterns and to determine whether the laboratory's policies need to be updated. ### The Troubleshooting Method When a discordant result is identified, the laboratory should follow a troubleshooting method to determine the cause of the discrepancy. The method should include the following steps: **Step 1: Verify the Result** The first step is to verify the result by repeating the test. The repeat test should be performed using the same method and the same conditions. If the result is the same, the laboratory should proceed to the next step. **Step 2: Check the Breakpoint Tables** The laboratory should check the breakpoint tables to verify that the correct breakpoints are being used. The tables should be checked for the correct version and the correct organism-drug combination. If the tables are outdated, the laboratory should update them and repeat the test. **Step 3: Check the Quality Control** The laboratory should check the quality control results for the antimicrobial agent and the organism. If the quality control results are out of range, the laboratory should investigate the cause and repeat the test. **Step 4: Check the Method** The laboratory should check the method that was used to determine the MIC or zone size. If the method is not the reference method, the laboratory should consider using a different method to confirm the result. **Step 5: Check the Organism Identification** The laboratory should verify the identification of the organism. If the organism is misidentified, the breakpoints may not be appropriate for the organism. **Step 6: Check the Clinical Information** The laboratory should check the clinical information to determine whether the patient has any conditions that could affect the interpretation of the result. For example, the patient may have a condition that affects the pharmacokinetics of the drug. The troubleshooting method should be documented in the laboratory's standard operating procedures. The laboratory should have a process for escalating the troubleshooting to the laboratory director if the cause of the discordance cannot be identified. ### The Escalation Criteria The laboratory must have a clear process for escalating discordant results to the laboratory director and the clinical team. The following situations should be escalated: - The result is discordant and the clinical risk is high - The result is discordant and the laboratory cannot determine the cause - The result is discordant and the clinical team requests additional information - The result is discordant and the laboratory director determines that the result may be incorrect The escalation should be documented in the laboratory records. The laboratory director should review the escalation and make a decision about the final interpretation. The decision should be communicated to the clinical team in a timely manner. ### The Quality Control for Discordant Results The laboratory should perform quality control testing for the organism-drug combinations that are most likely to produce discordant results. The quality control should be performed using the reference strains that are appropriate for the organism and the drug. The [American Type Culture Collection](https://www.atcc.org/) provides authenticated reference strains that can be used for this purpose. The quality control results should be recorded and reviewed to ensure that the testing method is accurate and reproducible. The laboratory should also participate in external quality assessment programs that include discordant results. The external quality assessment should be used to verify that the laboratory's interpretation is consistent with the interpretation of other laboratories. ### The Training and Competency The laboratory staff must be trained to identify and handle discordant results. The training should include the following elements: - The breakpoint tables and the differences between CLSI and EUCAST - The discordance types and the clinical risk - The decision matrix and the reporting protocol - The documentation system and the troubleshooting method - The escalation criteria and the quality control requirements The training should be provided to all laboratory staff who perform susceptibility testing. The training should be documented and the staff should be assessed for competency. The [American Society for Microbiology](https://asm.org/) provides professional education and training resources that can be used to support the training program. ### The Audit and the Review The laboratory should conduct a regular audit of the discordant results and the decisions that were made. The audit should be conducted by the laboratory director or a designated person. The audit should include the following elements: - The number of discordant results - The types of discordance - The decisions that were made - The outcomes of the decisions - The compliance with the laboratory's policies The audit should be used to identify areas for improvement. The laboratory should update its policies and procedures based on the audit findings. ### The Communication with the Clinical Team The laboratory must communicate with the clinical team about the discordant results and the decisions that were made. The communication should be clear and should include the following information: - The result and the interpretation - The reason for the discordance - The clinical risk - The recommendation for the treatment The communication should be done in a timely manner and should be documented. The laboratory should have a process for communicating with the clinical team that is consistent with the laboratory's policies. ### The Limitations of the Framework The decision framework is designed to be practical and to reduce the risk of miscommunication. However, the framework has limitations that the laboratory must be aware of: - The framework does not replace the clinical judgment of the clinician - The framework does not address all possible discordant results - The framework does not provide a detailed explanation for every situation - The framework is based on the current breakpoint tables and may need to be updated when the tables are updated The laboratory should use the framework as a guide and should not rely on it exclusively. The laboratory should also use the clinical judgment of the laboratory director and the clinical team to make the final decision. ### The Integration with the Laboratory Information System The laboratory should integrate the decision framework with the laboratory information system (LIS) to automate the process where possible. The LIS can be configured to flag results that fall into the discordance zone and to prompt the technologist to apply the decision framework. The LIS can also be used to generate the comments that are added to the report and to track the discordant results for the audit. The integration with the LIS should be done in a way that does not introduce errors. The laboratory should test the integration before it is implemented and should verify that the LIS is configured correctly. ### The Professional Escalation Criteria The laboratory must have a process for escalating discordant results to the laboratory director and the clinical team. The following situations should be escalated: - The result is discordant and the clinical risk is high - The result is discordant and the laboratory cannot determine the cause - The result is discordant and the clinical team requests additional information - The result is discordant and the laboratory director determines that the result is not correct The escalation should be documented and the outcome should be recorded. The laboratory director should review the escalation and make a decision on the final result. ### The Records and the Measurements The laboratory should maintain the following records for the discordant results: - The patient identifier - The organism and the antimicrobial agent - The MIC or zone size - The category under the primary standard - The category under the alternative standard - The discordance type - The decision that was made - The report that was issued - The escalation that was made The records should be reviewed on a regular basis to identify patterns and to determine whether the laboratory's policies need to be updated. The records should be available for review by the accrediting bodies. ### The Common Failure Patterns The following are the common failure patterns that can occur when the laboratory does not have a decision framework for discordant results: - The laboratory reports the result without a comment, and the clinician is not aware of the discrepancy - The laboratory reports the result under the alternative standard without a clear policy - The laboratory does not escalate the result when the clinical risk is high - The laboratory does not document the decision, and the result cannot be reviewed later - The laboratory does not perform the quality control for the discordant results The laboratory should be aware of these failure patterns and should take steps to prevent them. The laboratory should have a clear policy for the discordant results and should train the staff to follow the policy. ### The Biosafety and the Containment The handling of the bacterial cultures for the susceptibility testing must be done in accordance with the biosafety guidelines. The [CDC and NIH Biosafety in Microbiological and Biomedical Laboratories](https://www.cdc.gov/labs/bmbl/index.html) provides the guidance for the safe handling of the microorganisms. The laboratory must follow the guidelines to protect the staff and the environment. The laboratory should have the appropriate biosafety level for the organisms that are tested. The laboratory should have the appropriate facilities, equipment, and procedures in place. The laboratory should have a decontamination procedure for the waste and the equipment. ### The Global Context The [World Health Organization](https://www.who.int/health-topics/antimicrobial-resistance) identifies the antimicrobial resistance as a global public health concern. The accurate susceptibility testing is a cornerstone of the resistance surveillance and the stewardship programs. The discordant results can complicate the surveillance and the stewardship efforts. The laboratory should be aware of the global context and should work to reduce the discordance where possible. The laboratory should participate in the external quality assessment programs that include the discordant results. The laboratory should use the results of the external quality assessment to improve the accuracy of the testing and the interpretation. ### The Practical Implementation Steps The laboratory should implement the decision framework in a structured way. The following steps should be followed: 1. Review the current breakpoint tables and identify the organism-drug combinations that are most likely to produce the discordant results. 2. Develop the decision matrix and the reporting protocol for the discordant results. 3. Train the laboratory staff on the decision matrix and the reporting protocol. 4. Configure the laboratory information system to support the decision matrix and the reporting protocol. 5. Implement the documentation system and the troubleshooting method. 6. Conduct the quality control testing for the discordant results. 7. Conduct the audit and the review of the discordant results. 8. Communicate with the clinical team about the discordant results and the decisions. The implementation should be done in a phased approach to minimize the disruption to the laboratory operations. The laboratory should test the implementation before it is fully deployed. ### The Assessment of the Framework The laboratory should assess the effectiveness of the decision framework on a regular basis. The assessment should include the following elements: - The number of discordant results that are identified - The number of discordant results that are reported with the comment - The number of discordant results that are escalated - The number of discordant results that are resolved - The number of discordant results that are not resolved The assessment should be used to determine whether the framework is working and whether the laboratory's policies need to be updated. The assessment should be documented and reviewed by the laboratory director. ### The Limitations of the Framework The decision framework has limitations that the laboratory must be aware of. The framework is based on the current breakpoint tables and may need to be updated when the tables are updated. The framework does not replace the clinical judgment of the clinician. The framework does not address all the discordant results that can occur. The framework is a guide and should be used in conjunction with the clinical judgment of the laboratory director and the clinical team. The laboratory should be aware of these limitations and should use the framework as a guide. The laboratory should also use the clinical judgment of the laboratory director and the clinical team to make the final decision. ## Frequently Asked Questions ### Why do CLSI and EUCAST breakpoints differ for the same antibiotic? CLSI and EUCAST use different data sets, evaluation methods, and revision timelines to set breakpoints. The differences in pharmacokinetic and pharmacodynamic modeling, the emphasis on epidemiological cutoff values, and the timing of updates can all lead to different breakpoint values for the same organism-drug combination. ### How can a laboratory determine which standard to use? The laboratory should determine which standard is required by its accrediting body and which standard is preferred by the clinical team. In the United States, CLSI is the most common standard, but some laboratories have adopted EUCAST. The laboratory should have a clear policy for selecting the standard and for documenting the decision. ### What should a laboratory do if a result is affected by a breakpoint difference? The laboratory should report the result using the selected standard and include a note on the report indicating that the result would be different under the other standard. The clinical team should be informed of the difference so that they can make an informed treatment decision. ### How often are breakpoints updated? CLSI updates its breakpoints on a regular schedule, with a new edition published annually and supplements issued as needed. EUCAST updates its breakpoints annually but may introduce changes between updates. The laboratory must track these updates to ensure that it is using the most current breakpoints. ### What is the role of quality control in breakpoint harmonization? Quality control testing is essential to ensure that the susceptibility testing method is accurate and reproducible. The laboratory must use authenticated reference strains and follow the quality control procedures to verify that the results are within the expected range. ### Can a laboratory use both CLSI and EUCAST breakpoints? A laboratory can use both standards, but it must have a clear policy for when each standard is used. The laboratory must document the standard used for each test and communicate the standard to the clinical team. ### What are the limitations of breakpoint harmonization? Breakpoint harmonization is not complete, and the breakpoints may not be accurate for all clinical situations. The data used to set breakpoints may be limited, and the PK/PD models may not be representative of all patient populations. ### How should a laboratory document breakpoint differences? The laboratory should maintain a table of the breakpoints for the most commonly tested organism-drug combinations, with the CLSI and EUCAST values listed side by side. The laboratory should also document the standard used for each test and the date of the last update to the breakpoint table. ## Related Bacteriology Guides - [Swine Dysentery: Age Susceptibility, Causative Agent, and Clinical Management in Pigs](/knowledge/bacteria/livestock-bacteria/swine-dysentery-age-causative-agent) - [Mycoplasma in Poultry: Clinical Signs, Eye Infections, Treatment, and Control](/knowledge/bacteria/avian-bacteria/mycoplasma-poultry-eye-infection-treatment) - [Avian Coryza (Infectious Coryza): Etiology, Clinical Signs, Diagnosis, Treatment, and Prevention in Poultry](/knowledge/bacteria/avian-bacteria/avian-coryza-infectious-coryza-poultry-reference) - [Avian Coryza: Etiology, Epidemiology, Clinical Signs, Pathology, Diagnosis, Treatment, and Control](/knowledge/bacteria/avian-bacteria/avian-coryza) - [Bacterial Respiratory Infections in Cats: Etiology, Clinical Signs, and Treatment](/knowledge/bacteria/pet-bacteria/bacterial-respiratory-infections-cats-etiology-clinical-treatment) ## References and Further Reading - [Biosafety in Microbiological and Biomedical Laboratories](https://www.cdc.gov/labs/bmbl/index.html). CDC and NIH. - [Microbiology Resources](https://asm.org/). American Society for Microbiology. - [Antimicrobial Resistance](https://www.who.int/health-topics/antimicrobial-resistance). World Health Organization. - [Bacteriological Analytical Manual](https://www.fda.gov/food/laboratory-methods-food/bacteriological-analytical-manual-bam). U.S. Food and Drug Administration. - [Antimicrobial Susceptibility Testing](https://clsi.org/standards/products/microbiology). Clinical and Laboratory Standards Institute. - [Culture Collections](https://www.atcc.org/). American Type Culture Collection. - [NCBI Pathogen Detection](https://www.ncbi.nlm.nih.gov/pathogens). National Center for Biotechnology Information. - [Toward Harmonization of Voriconazole CLSI and EUCAST Breakpoints for Candida albicans Using a Validated In Vitro Pharmacokinetic/Pharmacodynamic Model.](https://pubmed.ncbi.nlm.nih.gov/32229492). Antimicrobial agents and chemotherapy, 2020. - [Results from the Survey of Antibiotic Resistance (SOAR) 2014-16 in Russia.](https://pubmed.ncbi.nlm.nih.gov/29659881). The Journal of antimicrobial chemotherapy, 2018. - [Evaluation of Variability in Interpretation of Disk Diffusion Testing for Cefiderocol Using Different Brands of Mueller-Hinton Agar.](https://pubmed.ncbi.nlm.nih.gov/36738243). The journal of applied laboratory medicine, 2023. - [Results from the Survey of Antibiotic Resistance (SOAR) 2011-13 in Ukraine.](https://pubmed.ncbi.nlm.nih.gov/27048583). The Journal of antimicrobial chemotherapy, 2016. > This article is educational and does not replace validated laboratory procedures, clinical diagnosis, institutional biosafety review, or public-health guidance.