microbial susceptibility testing and antibiogram

• minimum inhibitory concentration (MIC)

  • serial dilutions of antibiotic are made in liquid microbial growth medium
  • each tube is inoculated w/ same number of microorganisms for a specified amount of time
  • lowest concentration of antibiotic preventing growth (appearance of turbidity) is considered to be the MIC
  • MIC represents the concentration of the antimicrobial agent that inhibits the visible growth of the organism in vitro
  • nowadays, the process of determining MIC is largely automated
• manual antimicrobial susceptibility testing methods

  • broth macrodilution
  • broth microdilution (most common)
  • Kirby Bauer Disk Diffusion
  • measures diameter to determine if microorganism is susceptible or not susceptible
  • E test (epsilometer test)
• MIC interpretation/breakpoints

  • the pt's MIC is compared to a predetermined standardized breakpoint and subsequently categorized
  • in US, Clinical Laboratory Standards Institute (CLSI) determines what the clinical breakpoint for a specific antibiotic would be to a specific organism
  • to determine breakpoints, CLSI uses data such as PK/PD properties of the drug in question, resistance mechanisms, and other clincal data (dose, indication, etc.)
• MIC interpretation per CLSI

  • susceptible
  • isolates w/ an MIC at or below the susceptible breakpoint are inhibited by the usually achievable concentrations of antimicrobial agent when the dosage recommended to treat the site of infections is used, resulting is likely clinical efficacy
  • can be treated w/ drug
  • intermediate
  • isolates w/ MICs that approach usually attainable blood and tissue levels and for which response rates may be lower than for susceptible isolates
  • may be treatable w/ drug, but require adjusted dose
• MIC interpretation per CLSI (cont.)

  • resistant
  • isolates w/ an MIC at or above the resistant breakpoint are not inhibited by the usually achievable concentrations of the agent w/ normal dosage schedule
• patient's MIC vs clinical breakpoint

  • clinical breakpoints are standardized for specific organism and each antibiotic tested for that organism, not for an individual pt
  • on the other hand, the MIC is at the pt level
• one more MIC interpretation - susceptible dose dependent (SDD)

  • susceptibility of an isolate depends on the dosing regimen that is used in the pt
  • use a dosing regimen (for ex, high doses, more frequent doses or both) that results in higher drug exposure than that achieved w/ the dose that was used to establish the susceptible breakpoint (depending on the dose, it will be susceptible)
  • currently recommended for only a few microorganisms and drugs (instead of the intermediate), more often seen w/ fungal MICs
• major points

  • MIC values vary from one drug to another and from one bacterium to another, and thus the MIC values are NOT comparable btwn antibiotics or btwn organisms
  • do not be tempted to select an antibiotic solely because the MIC is lower than other options
  • however, you can make comparisons as long as BOTH microorganism and drug are same
• antibiotic resistance

  • innate resistance - inherently present in bacteria
  • acquired resistance - not inherently present but acquired via horizontal gene transfer
  • inducible resistance - resistance induced by an antimicrobial agent
• basic terminology on antibiotic use

  • empiric therapy - cause of infection is unknown, so it is treated broadly
  • definitive therapy - cause of infection is known, so it is treated w/ specific antibiotic
  • primary prophylaxis - given to pt who is at risk but has not develop an infection yet
  • example: surgical prophylaxis, travel medicine (malaria)
  • secondary prophylaxis - given to pt who have the infection
  • goal is to prevent it from re-occurring
  • example: done w/ herpes virus
  • de-escalation - process from going from empiric therapy (more broad) to definitive therapy (specific)
• what is an antibiogram?

  • report of antimicrobial susceptibilities of local bacterial isolates submitted to the hospital's clinical microbiology laboratory
  • used by clinicians to
  • assess local susceptibility rates
  • aid in selecting empiric antibiotic therapy
  • monitor resistance trends over time w/in an institution
  • each hospital has its own antibiogram
  • usually organized by location
  • inpatient/floor
  • outpatient/ER
  • intensive care units (ICU)
  • some separate urinary vs. non-urinary samples
  • completed annually
• is there a minimum acceptable susceptibility?

  • severe disease: > (or equal to) 90 - 95 %
  • moderate disease: > (or equal to) 85%
  • mild disease: > (or equal to) 80%