Susceptible, Intermediate, or Resistant: What the Categories Actually Mean (and Why "Intermediate" Isn't a Maybe)

Antimicrobial susceptibility testing is most often used for guidance in the therapy of bacterial infections. When the result of antimicrobial susceptibility testing is reported to the clinician, pathogenic microorganisms are classified into one of the three categories; “resistant”, “intermediate” or “susceptible”. Other less used categories are “susceptible-dose dependent” and “non-susceptible”. These interpretive criteria are based on MIC or zone diameter values.

Figure: Antimicrobial susceptibility testing

There's No Universal "Resistant" Number

A common misconception: that an 18 mm zone of inhibition, or an MIC of 4 μg/mL, means the same thing every time. It doesn't. Every breakpoint is specific to one organism-drug combination, set by CLSI (or EUCAST, the European equivalent) using three things together: how the MIC distribution of that drug looks across known-susceptible and known-resistant populations of that organism, what concentration the drug actually achieves in serum or tissue at standard dosing, and which resistance mechanisms are known to operate in that species.

That's why the same zone diameter can be "Susceptible" for one drug-organism pair and "Resistant" for another; the cutoff itself moves. A lab report's S/I/R call is only meaningful when read against the correct breakpoint table for that specific isolate and that specific drug — never as a flat ruler reading.

Each clinician and laboratory worker must understand the exact definition and clinical significance of these categories.

1. Susceptible:  This category indicates that the antimicrobial agent in question may be an appropriate choice for treating the infection caused by the bacterial isolate tested.  i.e. the organism is likely to respond to treatment with this drug, at the recommended dosage. Bacterial resistance is absent or at a clinically insignificant level.
2. Intermediate: Not "kind of susceptible"; a real pharmacokinetic category. An isolate falls here when the drug concentration needed to inhibit it sits close to, but above, what's normally achievable in serum at standard dosing. That doesn't always mean the drug fails. It can still work in two specific situations: when the drug naturally concentrates far above serum levels at the infection site (e.g., fluoroquinolones and β-lactams in urine), or when a higher-than-standard dose is safe to give because the drug has a wide safety margin (e.g., many β-lactams). Outside those situations, response rates for Intermediate isolates are genuinely lower than for Susceptible ones — it's a real, narrower therapeutic window, not just a number close to the cutoff.
3. Resistant. If an isolate is resistant to a particular antibiotic; it won’t be inhibited by the usually achievable concentrations of the agent with normal dosage schedules. This isolate is expected not to respond to a given drug, irrespective of the dosage and of the location of the infection. Antimicrobials of this category are not the appropriate choice for treating the infection caused by the bacterial isolate tested. That bacterial isolate is not inhibited by serum-achievable levels of the drug.

Note: For testing the response of staphylococci to benzylpenicillin, only the categories “susceptible” and “resistant” (corresponding to the production of β-lactamase) are recognized.

Other categories

1. Susceptible-Dose Dependent (SDD):“susceptible-dose dependent” is a new category for antibacterial susceptibility testing. If a particular isolate falls under this category, we have to remember that the susceptibility of that isolate depends on the dosing regimen used. Higher doses or more frequent doses or both are used to achieve a concentration level that is likely to be clinically effective against the isolate. While prescribing that antibiotics clinicians should give proper consideration to the maximum approved dosage regimen.
2. Non-susceptible (NS): The “non-susceptible” category is used for isolates for which only a susceptible interpretive criterion has been designated because of the absence or rare occurrence of resistant strains. Isolates for which the antimicrobial agent MICs are above or zone diameters below the value indicated for the susceptible breakpoint should be reported as non-susceptible.

Why This Distinction Actually Changes Treatment

The Intermediate UTI: A patient's urine culture grows E. coli, reported as "Intermediate" to ampicillin. Read in isolation, that looks like a drug to avoid. But ampicillin concentrates dramatically higher in urine than it does in serum — often well above what the Intermediate breakpoint assumes. For a straightforward lower UTI, that same "Intermediate" isolate can be treated successfully with ampicillin, even though the identical report would be a poor choice for, say, ampicillin-treated bacteremia from the same organism. The category isn't a verdict on the bacterium — it's a prediction tied to where the infection actually is.

All Five Categories at a Glance

Learning & Remembering

Quick hook (optional): S-I-R as a decision, not just a label — Send it (use it), Increase dose or pick your site (Intermediate), Reject it (Resistant).

Clinical story: The Intermediate UTI (above) — why the same lab report can mean "good choice" for one infection and "wrong choice" for another, depending only on where the infection is.

One sentence that captures it: S/I/R isn't a property of the bacterium alone — it's a prediction about whether the achievable drug concentration at the actual site of infection will beat that specific organism, which is exactly why the same report can mean different things for a UTI versus bacteremia.

Exam facts

References and further reading

• CLSI. M100—Performance Standards for Antimicrobial Susceptibility Testing. Clinical and Laboratory Standards Institute; current annual edition.

• EUCAST. Breakpoint tables for interpretation of MICs and zone diameters. European Committee on Antimicrobial Susceptibility Testing; current version.

• Image source: created with BioRender.com