What do sensitive, intermediate, and resistant mean in terms of antibiotic (antibacterial) susceptibility?

Understanding Antibiotic Susceptibility Categories: Sensitive, Intermediate, and Resistant

Antibiotic susceptibility categories directly predict clinical outcomes, with sensitive bacteria likely to respond to standard treatment, intermediate requiring special considerations, and resistant bacteria unlikely to respond even to maximum antibiotic doses.

Definitions of Susceptibility Categories

Susceptible (Sensitive)

• Indicates that an infection caused by the tested bacterial strain is likely to respond to treatment with the antibiotic at recommended dosages 1
• Bacteria classified as susceptible lack resistance mechanisms or have low-level resistance mechanisms that don't significantly affect clinical outcomes 1
• Treatment with standard doses of the antibiotic is expected to be effective 1

Intermediate

• Represents bacterial strains that fall between clinically susceptible and clinically resistant categories 1
• Infections caused by these strains have variable or indeterminate responses to standard antibiotic therapy 1
• May still be effectively treated if:
  • The antibiotic can be concentrated at the infection site (e.g., urinary tract infections) 1
  • Higher dosages of the antibiotic can be safely administered 1
• Serves as a technical buffer zone to minimize classification errors for organisms with MICs close to breakpoints 1

Resistant

• Indicates that infection is highly unlikely to respond even to maximum doses of the given antibiotic 1
• Bacteria possess specific resistance mechanisms that can be demonstrated either phenotypically or genotypically 1
• May be further qualified as having "low-level" or "high-level" resistance depending on the degree of resistance 1
• Clinical failure is expected even with increased dosing 1

Clinical Implications and Decision Making

• These categories are determined based on:
  • The antibiotic's in vitro properties 1
  • Pharmacokinetics of the drug 1
  • Achievable concentrations at infection sites 1
  • Correlation with clinical outcomes 2
• Breakpoints (specific MIC values) are used to assign bacteria to these categories 1
• The classification directly guides antibiotic selection in clinical practice 2

Technical Aspects of Susceptibility Testing

• Minimum Inhibitory Concentration (MIC) is the lowest concentration of an antibiotic that inhibits bacterial growth 2
• Various methods determine susceptibility:
  • Broth dilution, agar dilution, and gradient diffusion (E-test) measure MIC directly 2
  • Disk diffusion method measures zones of inhibition around antibiotic disks 2
• Results must follow standardized methods (e.g., those developed by EUCAST or CLSI) to ensure reproducibility 1, 2

Important Considerations and Pitfalls

• Susceptibility testing in laboratories may not always reflect the actual response in vivo 3
• Phenotypic resistance can occur without genetic changes in certain conditions:
  • Bacterial growth in biofilms 3
  • Stationary growth phase 3
  • Persistence states 3
• These situations are not typically considered in standard susceptibility tests 3
• Recent harmonization efforts (ISO standard 20776 and EUCAST) aim to make susceptibility categorization more consistent across Europe and globally 4
• Susceptibility patterns change over time due to emerging resistance, requiring ongoing surveillance 5

Practical Application

• When selecting antibiotics, always prioritize "susceptible" options when available 2
• For "intermediate" results, consider:
  • Using higher doses if safe 1
  • Using antibiotics that concentrate at the infection site 1
  • Combining with other antibiotics if appropriate 5
• For "resistant" results, avoid using the antibiotic as it will likely fail and may promote further resistance 6
• Consider that even very low antibiotic concentrations (below MIC) can select for resistant bacteria 6