Establishing standardized operating procedures for pathogen identification and in vitro antimicrobial susceptibility testing is one of the fundamental requirements for strengthening the capacity of microbiology laboratories. This practice is of significant practical importance for optimizing clinical drug selection, enhancing the diagnosis and treatment of infectious diseases, and addressing the emergence of drug‑resistant pathogens. The antimicrobial susceptibility testing standards developed by the Clinical and Laboratory Standards Institute (CLSI) serve as a guiding document that Chinese laboratories are expected to follow; the most recent version, released in 2014, introduced guidelines for susceptibility testing of Enterobacteriaceae. “Dose-Dependent Sensitivity (SDD)” This information plays an important role in improving antimicrobial susceptibility reporting, preventing clinicians from overinterpreting “intermediate” results as “resistant,” and ensuring the rational use of antimicrobial agents.

1.  Definition of “SDD” “SDD” stands for susceptible‑dose dependent, referring to strain susceptibility that depends on the dose administered to the patient. When a strain’s antimicrobial susceptibility result (MIC or disk diffusion) falls within the SDD range, clinicians should optimize the dosing regimen—such as increasing the dose and/or frequency—to achieve clinical efficacy. Because higher doses are most likely to cover SDD‑defined strains, clinicians should consider using the maximum allowable dose.

2. The Relationship Between “SDD” and “Intermediary” : In bacterial susceptibility testing, the “intermediate” category already encompasses the concept of “SDD”; however, clinicians and microbiologists often fail to understand or overlook intermediate results. The CLSI recommends using “SDD” instead of “intermediate” when reporting cefepime susceptibility for Enterobacteriaceae. Cefepime is approved in multiple dosage regimens; when a strain exhibits a cefepime MIC of 4 or 8 mg/L (or an inhibition zone diameter of 19–24 mm), “SDD” underscores the use of a high‑dose regimen to treat the infection.

However, not all “intermediate” results will be replaced by “SDD.” The SDD approach may be used only when sufficient evidence demonstrates that the alternative approved dosing regimen is appropriate for microorganisms whose MIC (or zone diameter) falls between “susceptible” and “resistant.” At present, for antimicrobial agents with multiple dosing options—such as other extended‑spectrum cephalosporins—CLSI also evaluates whether the SDD criteria can be applied.

3.  Set the dosing regimen for “SDD” : As the pharmacokinetics and pharmacodynamics of antimicrobial agents continue to evolve, their role in establishing MIC breakpoints has become increasingly important. For adult patients with normal renal function, appropriate use of these breakpoints requires clinicians to administer systemic doses that meet or exceed the expected levels at the site of infection in order to achieve clinical efficacy. The CLSI has therefore established dosage regimens corresponding to “susceptible” or “SDD” breakpoints.

4. How to Implement and Use “SDD” in Clinical Practice The laboratory communicates the CLSI “SDD” criteria to relevant clinicians through various channels and collaborates with hospital information system staff to establish an appropriate implementation plan, ensuring that cefepime MICs of 4 or 8 mg/L for Enterobacteriaceae are reflected on clinical report forms. As the U.S. Food and Drug Administration (FDA) has not yet updated the breakpoints for cefepime, manufacturers are currently unable to adopt the new CLSI breakpoints. In such cases, the laboratory may manually adjust the breakpoints and conduct breakpoint‑confirmation studies.

If the laboratory needs to annotate “SDD,” CLSI recommends: “The susceptible breakpoint is based on a 1 g/12 h dosing regimen; the SDD breakpoint is based on higher cefepime dosing regimens (e.g., higher doses and/or more frequent administration), but not exceeding the maximum approved dose.”

For situations where the new cefepime breakpoints can be applied but “SDD” cannot be reported, laboratory personnel, infection control staff, the pharmacy department, and the infectious diseases department must jointly determine whether “intermediate” can be used in place of “SDD.” Furthermore, reporting either the MIC or the inhibition zone diameter alone carries a certain risk of misinterpretation. If the laboratory is unable to report “SDD,” when reporting both the MIC and the inhibition zone diameter—never solely the inhibition zone diameter—additional interpretation of the results should be provided.

Although “SDD” is applicable to all patients and any specimen type, clinicians must take into account the clinical and physiological characteristics of individual patients when interpreting SDD results. SDD does not require special quality control; standard QC procedures are sufficient. For strains positive for extended-spectrum β-lactamases (ESBLs), there is no need to reclassify “susceptible” or “SDD” results as “resistant.” In 2010, CLSI discontinued routine ESBL testing. When using the new breakpoints for cefepime, routine ESBL testing is also not required in patient reports; however, ESBL testing may be performed for infection control or epidemiological studies.

References:

Chinese Journal of Laboratory Medicine, 2014 Volume 37, Issue 4, April