What is antibiotic sensitivity and susceptibility?

Antibiotic Sensitivity and Susceptibility

Antibiotic sensitivity and susceptibility testing determines whether bacteria will respond to specific antibiotics, with results categorized as susceptible, intermediate, or resistant based on standardized breakpoints that predict clinical response to treatment.

Definition and Classification

Antibiotic sensitivity testing measures how effectively antibiotics inhibit bacterial growth. According to the European Society of Clinical Microbiology and Infectious Diseases (EUCAST), bacteria are classified into three categories 1:

• Susceptible (S): Infection is likely to respond to standard dosing of the antibiotic
• Intermediate (I): Infection may respond if the antibiotic concentrates at the infection site or if dosage is increased
• Resistant (R): Infection is highly unlikely to respond even to maximum doses

This classification has both microbiological and clinical implications:

• Microbiological perspective: Measures the presence of resistance mechanisms
• Clinical perspective: Predicts treatment response in patients

Testing Methods

The primary methods for determining antibiotic sensitivity include:

1. Minimum Inhibitory Concentration (MIC): The lowest concentration of an antibiotic that prevents visible bacterial growth under defined conditions 1

   • Measured in mg/L
   • Can be determined through:
     • Broth dilution
     • Agar dilution
     • Gradient diffusion (E-test)

2. Disk Diffusion Method: Measures zones of inhibition around antibiotic-containing disks

   • Results are correlated with MICs through statistical methods 1

3. Minimum Bactericidal Concentration (MBC): The lowest concentration that reduces bacterial count by 99.9% (3 logarithms) 1

Interpreting Results

Interpretation of sensitivity testing relies on breakpoints - specific MIC or zone diameter values that categorize bacteria 1, 2:

• Breakpoints are established based on:
  • Antibiotic pharmacokinetics
  • Distribution of MICs among bacterial populations
  • Clinical outcome data
  • Achievable drug concentrations at infection sites

When interpreting culture results 2:

• S (Susceptible): First choice for therapy
• I (Intermediate): Consider only in specific situations
• R (Resistant): Avoid use as infection is unlikely to respond

Clinical Application

The primary purpose of sensitivity testing is to guide antibiotic selection:

1. First priority: Use antibiotics reported as "Susceptible" 2
2. Second priority: Consider intermediate sensitivity antibiotics when no susceptible options exist 2
3. Third priority: Resort to resistant antibiotics only after infectious disease consultation 2

FDA drug labels emphasize that antibiotics should be used only for infections proven or strongly suspected to be caused by susceptible bacteria 3, 4. When culture results are available, they should guide therapy selection or modification.

Antibiogram and Resistance Profiles

• Antibiogram: Documents a bacterium's pattern of susceptibility to multiple antibiotics 1
• Resistance profile: Alternative way to describe susceptibility patterns (e.g., RRRS for resistance to multiple antibiotics) 1

Clinical Implications and Pitfalls

Important Considerations

• Intermediate sensitivity antibiotics may still be effective when:

  • The antibiotic concentrates at the infection site
  • Higher dosages can be safely administered
  • Limited treatment options are available 2

• Treatment success with intermediate antibiotics varies by infection site:

  • More likely in urinary tract infections
  • Less likely in bloodstream infections 2

Common Pitfalls

1. Ignoring local resistance patterns: Local epidemiology should inform empiric therapy when culture results are unavailable 3, 4

2. Overlooking concentration-dependent effects: Some antibiotics may be effective against "intermediate" bacteria when they achieve high concentrations at infection sites 2

3. Failing to monitor treatment response: Patients treated with intermediate sensitivity antibiotics require careful monitoring for treatment failure 2

4. Selection of resistant bacteria: Even very low antibiotic concentrations can select for resistant bacteria, highlighting the importance of appropriate antibiotic use 5

Resistance Mechanisms

Bacteria can develop resistance through various mechanisms:

• Microbiological resistance: Possession of any resistance mechanism demonstrated phenotypically or genotypically 1
• Clinical resistance: Infection unlikely to respond to even maximum antibiotic doses 1
• Cross-resistance: Insusceptibility to multiple antibiotics within the same chemical class 1
• Associated resistance: Resistance affecting multiple chemical classes due to mechanisms like impermeability or efflux 1

Regular surveillance of antibiotic susceptibility patterns is essential for guiding empiric therapy and tracking resistance trends 6.