3.5 Antimicrobial susceptibilities

The drug susceptibility tests are grouped together in the LOINC database under the Class ABXBACT. Various agencies, including the FDA and CLSI in the U.S. and EUCAST in Europe, publish guidelines for determining susceptibility of different organisms to different antimicrobials.

In LOINC, antimicrobial susceptibility tests are named according to the generic name of the drug tested and the methodology used in testing, with Property of susceptibility (Susc), and with Scale of quantitative (Qn), semi-quantitative (SemiQn), ordinal (Ord), and quantitative or ordinal (OrdQn). Thus, appropriate names would be:

Ticarcillin+Clavulanate:Susc:Pt:Isolate:Qn:MLC
Ampicillin:Susc:Pt:Isolate:OrdQn:MIC
Ampicillin:Susc:Pt:Isolate:OrdQn:Agar diffusion

The following table lists Methods in drug-susceptibility tests.

Methodless codes also exist for each antimicrobial agent.

3.5.1 Susceptibility thresholds based on type of infection (“Breakpoints”)

In most cases, susceptibility thresholds are the same for a given organism+antibiotic combination regardless of infection site or route of antibiotic administration. However, for some antibiotic+organism combinations, the threshold (“breakpoint”) varies based on route of administration and/or type of infection, including meningitis, pneumonia, and urinary tract infection. These are two independent parameters: there are cases where one antibiotic could have multiple different breakpoints depending on the combination of route and type of infection, and others where one antibiotic will have a single breakpoint regardless of route and type of infection. For example, depending on whether or not the patient has suspected meningitis there are two different breakpoints for parenteral penicillin. But, there is a single breakpoint for vancomycin. The susceptibility test itself is carried out exactly the same way regardless of the breakpoint. It is only for the final step of assigning a susceptibility result that the specific breakpoint becomes important. These data are published by the same agencies (FDA, CLSI, EUCAST) that publish the common susceptibility thresholds.

Prior to the 2.58 LOINC release, we specified that the susceptibility threshold was based on a meningitis breakpoint in the Component, e.g., Cefepime.meningitis. However, the concept really identifies an antimicrobial susceptibility result for a patient with suspected meningitis rather than a susceptibility result for a meningitis form of the antibiotic. Therefore, as of LOINC 2.58, we moved “meningitis” from the Component to the System: Isolate.meningitis. In upcoming releases, we will also be adding codes with the Systems Isolate.pneumonia and Isolate.UTI.

Note that Isolate.meningitis (or “.pneumonia”, “.UTI”) indicates that the particular susceptibility result being reported is for an antibiotic that has a meningitis breakpoint and that the patient is suspected to have meningitis. This does not necessarily mean that a particular patient has meningitis. For the same patient with suspected meningitis, the result for an antibiotic that does not have a published meningitis breakpoint will be reported using a code with Isolate as the System.

3.5.2 Genotypic resistance testing and predicted susceptibility

Genotypic resistance testing is done to look for genes or gene mutations that confer resistance to a drug or class of drugs. The subtle difference between phenotypic susceptibility and genotypic resistance testing is that susceptibility testing is used to determine whether or not a particular organism’s growth is actually inhibited in the presence of an antimicrobial, while testing for resistance mechanisms or genes is used to determine whether or not such genes or mutations are present and to predict whether the organism will be inhibited in the presence of a particular antimicrobial.

Various Methods are available to test for the genetic information (e.g., specific resistance genes or nucleotide alterations in native genes) that encodes resistance mechanisms, including Probe.amp.tar, Non-probe.amp.tar, and Sequencing. Until 2018, LOINC bacterial genotypic susceptibility testing terms used the specific Methods named above; however, as approved by the Laboratory LOINC Committee in June 2018, moving forward we are recommending using the Molgen Method for all bacterial molecular resistance testing to obviate the need to create different terms for different molecular Methods (Probe.amp.tar, Sequencing, etc.). New terms will be created with the Method Molgen, and terms that were previously created with a Method other than Molgen will be reviewed and either updated to Molgen if not duplicative or the Status will be changed to Discouraged.

Historically, susceptibility testing was always phenotypic; it was always performed on an Isolate, which is a microorganism from a patient specimen that is grown and isolated on culture media. However, with new molecular techniques, genotypic testing can be performed directly on patient specimens without the pre-step of isolating the organism. Rather than create separate terms for every possible patient specimen that can be tested, the Laboratory LOINC Committee approved an approach in June 2018 to create single terms for each resistance gene or resistance-conferring mutation with the System Isolate/Specimen. These terms will represent assays that can be done using a traditional isolated colony or on a direct specimen. This approach does NOT imply that every manufacturer’s genotypic assay is approved for testing on an isolate or any type of specimen.

Existing terms with Isolate or other specific specimens as the System will be reviewed and either updated to the same model if not duplicative or the Status will be changed to Discouraged.

LOINC terms that represent the predicted susceptibility of an organism to a particular antimicrobial based on the presence or absence of resistance genes or resistance-conferring mutations in native genes will contain the drug name or class in the Component, Isolate/Specimen as the System, and Genotyping as the Method. This model was also approved by the Laboratory LOINC Committee in June 2018.