T2i: Steps to eradicate bacteria

  1. Bind to target site on bacteria

a. Penetrate the organism

b. Avoid being pumped back out

c. Remain intact (avoid b-lactam hydrolysis)

2. Occupy an adequate number of binging sites (concentration dependant)

3. Remain at the binding site for long enough

2 major determinants of bacterial killing → TIME it remains at binding site


Time Dependant

  • B lactams
  • Clindamicyn
  • Macrolides
  • Linezolid

All these a/b spend an extensive amount of time bound to the microorganism

Concentration Dependant

  • Aminoglycosides
  • Quinolones
  • Metronidazole

High concentrations at binding site eradicates organism


There are 3 major patterns of antimicrobial kill characteristics

  • “concentration-dependent killing” (determined by Cmax)
  • “time dependent killing” (determined by time above MIC)
  • area under the concentration-time curve (determined by AUC above MIC)


  • Cmax = maximal or peak concentration
  • “concentration-dependent killing”
  • some antimicrobials depend on Cmax/MIC ratio as an important predictor of antimicrobial efficacy
  • higher the concentration, greater the rate and extent of microbial killing
  • aminoglycosides should ideally have Cmax/MIC ratio of at least 8-10 to prevent resistance

Time Above MIC

  • Time above MIC is duration that the antibiotic levels are above the MIC
  • “time dependent killing”
  • The ideal dosing regimen for certain antimicrobials is to maximise the duration pathogens are exposed to them
  • g. beta-lactams, clindamycin, erythromycin, linezolid
  • for beta-lactams and erythromycin, maximum killing is seen when the time above MIC is 70% of dosing interval


  • AUC above MIC is the area under the concentration-time curve that is above the MIC
  • some antimicrobials are dependent on this for maximal killing effect
  • 24h AUC/MIC is a predictor of efficacy
  • eg. fluoroquinolones
    — for gram negative bacteria, optimal 24h AUC/MIC ~ 125
    — for gram positives bacteria, optimal 24h AUC/MIC ~ 40