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Antimicrobial susceptibility testing (AST) determines the minimum inhibitory concentration or MIC of antimicrobial agents. The MIC is a measurement of the activity of an antimicrobial agent against an organism. It is defined as the lowest concentration of an antimicrobial agent that inhibits growth of the microorganism. Clinical breakpoints are derived from a number of data including a) the pharmacokinetics/pharmacodynamics of an antimicrobial agent, b) the MIC distribution of a large number of isolates, and c) clinical outcome data for a patient population treated with the antimicrobial of interest.
AST should be performed on pure culture isolates of pathogenic bacteria (or those potentially pathogenic in special situations) grown from specimens that have been appropriately collected so as not to confuse clinically significant isolates with normal or contaminating flora. Susceptibility testing is indicated for any organism that contributes to an infectious process warranting antimicrobial chemotherapy if its susceptibility cannot be reliably predicted from the organism’s identity.
The MIC obtained during AST is helpful in indicating the concentration of antimicrobial agent required at the site of infection necessary to inhibit the infecting organism. The MIC are accompanied by interpretive categories (ie, susceptible, susceptible-dose dependent, intermediate, nonsusceptible, or resistant) when applicable.
Determining the in vitro susceptibility of aerobic bacteria involved in human infections
Refer to the "Reference Values" section for interpretation of various categories.
In vitro susceptibility does not guarantee clinical response. Therefore, the decision to treat with a particular agent should not be based solely on the antimicrobial susceptibility testing result.
Results are reported as minimum inhibitory concentration (MIC) in mcg/mL and as susceptible, susceptible-dose dependent, intermediate, resistant, or nonsusceptible according to the Clinical and Laboratory Standards Institute (CLSI) guidelines.
In some instances an interpretive category cannot be provided based on available data and the following comment will be included: "There are no established interpretive guidelines for agents reported without interpretations."
The "susceptible" category implies that isolates are inhibited by the usually achievable concentrations of antimicrobial agent when the dosage recommended to treat the site of infection is used, resulting in likely clinical efficacy.
Susceptible-Dose Dependent (D):
The "susceptible-dose dependent" category implies that susceptibility of an isolate is dependent on the dosing regimen that is used in the patient. In order to achieve levels that are likely to be clinically effective against isolates for which the susceptibility testing results are in the D category, it is necessary to use a dosing regimen (ie, higher doses, more frequent doses, or both) that results in higher drug exposure than the dose that was used to establish the susceptible breakpoint. Consideration should be given to the maximum approved dosage regimen, because higher exposure gives the highest probability of adequate coverage of a D isolate. The drug label should be consulted for recommended doses and adjustment for organ function.
The "intermediate" category includes isolates with antimicrobial agent minimum inhibitory concentrations (MICs) that approach usually attainable blood and tissue levels, and for which response rates may be lower than for susceptible isolates.
Note: The intermediate category implies clinical efficacy in body sites where the drugs are physiologically concentrated or when a higher than normal dosage of a drug can be used. This category also includes a buffer zone, which should prevent small, uncontrolled, technical factors from causing major discrepancies in interpretations, especially for drugs with narrow pharmacotoxicity margins.
The "resistant" category implies that the isolates are not inhibited by the usually achievable concentrations of the agent with normal dosage schedules and/or that demonstrate MIC that fall in the range where specific microbial resistance mechanisms are likely, and clinical efficacy of the agent against the isolate has not been reliably shown in treatment studies.
The "nonsusceptible" category is used for isolates for which only a susceptible interpretive category has been designated because of the absence or rare occurrence of resistant strains. Isolates for which the antimicrobial agent MICs are above the value indicated for the susceptible breakpoint are reported as nonsusceptible.
Note: An isolate that is interpreted as nonsusceptible does not necessarily mean that the isolate has a resistance mechanism. It is possible that isolates with MIC above the susceptible breakpoint that lack resistance mechanisms may be encountered within the wild-type distribution subsequent to the time the susceptible-only breakpoint was set.
(Clinical and Laboratory Standards Institute: Performance Standards for Antimicrobial Susceptibility Testing. 26th Informational Supplement. CLSI document M100S. Wayne, PA, 2016)
1. Jorgensen JH, Ferraro MJ: Antimicrobial susceptibility testing: a review of general principles and contemporary practices. Clin Infect Dis 2009 Dec 1;49(11):1749-1755
2. Clinical and Laboratory Standards Institute: Performance Standards for Antimicrobial Susceptibility Testing. 26th Informational Supplement. CLSI document M100S. Wayne, PA, 2016
3. Jenkins SG, Schuetz AN: Current concepts in laboratory testing to guide antimicrobial therapy. Mayo Clin Proc 2012 Mar;87(3):290-308