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Determining the in vitro susceptibility of aerobic bacteria involved in human infections
When this test is ordered, the reflex tests may be performed and charged separately. All aerobically growing bacteria submitted will automatically have susceptibility testing performed and billed as appropriate. Antimicrobial agent appropriate to the organism and specimen source will be chosen from the panels listed below.
Note: Mayo Medical Laboratories will not perform susceptibility testing on select agents (eg, Bacillus anthracis, Brucella species, Burkholderia mallei, Burkholderia pseudomallei, Francisella tularensis, and Yersinia pestis). Please consult with your state health department or the CDC regarding antimicrobial susceptibility testing of such isolates.
Gram-negative bacillus: amikacin, ampicillin, ampicillin/sulbactam, aztreonam, cefazolin, cefdinir, cefepime, ceftazidime, ceftriaxone, ciprofloxacin, ertapenem, fosfomycin, gentamicin, levofloxacin, meropenem, nitrofurantoin, piperacillin/tazobactam, tobramycin, and trimethoprim/sulfamethoxazole (TMP/SMX). The 2011 Clinical and Laboratory Standards Institute (CLSI) breakpoints for cephalosporins and carbapenems have been implemented. Confirmation testing for extended spectrum beta-lactamases is performed on Escherichia coli, Klebsiella species, and Proteus mirabilis isolates by request. Klebsiella pneumoniae carbapenemase (KPC)/New Dehli-metallo-beta-lactamase (NDM) molecular testing, modified Hodge testing, and/or Carbapenemase-Carba NP Test are available for individual order.
Staphylococcus species: ceftaroline (methicillin-resistant Staphylococcus aureus: MRSA only), clindamycin, levofloxacin, linezolid, minocycline, mupirocin, nitrofurantoin, oxacillin, rifampin, TMP/SMX, and vancomycin. D-test is performed on all isolates for detection of clindamycin resistance.
Enterococcus species: gentamicin synergy, levofloxacin, linezolid, nitrofurantoin, penicillin, and vancomycin
Streptococcus species: cefepime, ceftriaxone, erythromycin, levofloxacin, meropenem, penicillin, tetracycline, TMP/SMX, and vancomycin
Haemophilus species: ampicillin if beta-lactamase negative
Neisseria gonorrhoeae: cefixime, ceftriaxone ciprofloxacin, tetracycline
Helicobacter pylori: amoxicillin, ciprofloxacin, clarithromycin, metronidazole, tetracycline
See Helicobacter pylori Diagnostic Algorithm in Special Instructions.
For antimicrobial agents not part of above panels: testing is available upon special request at an additional charge per antimicrobial (eg, ceftolozane/tazobactam, colistin, daptomycin, tigecycline).
Antimicrobial susceptibility testing (AST) determines the minimum inhibitory concentration (MIC) (of a series of increasing concentrations) of antimicrobial incorporated in agar plates, which inhibits the growth of bacteria inoculated on the surface of the agar.
Prior studies have determined a â€œbreakpointâ€œ or MIC value for each antimicrobial, above which the bacterium being tested is considered resistant to that agent. The most important factor contributing to the determination of the â€œbreakpointâ€œ is probably the expected serum concentration of antimicrobial achieved after giving the usual dosage. The â€œcategoryâ€œ result (â€œsusceptibleâ€œ or â€œresistantâ€œ) provided along with the MIC is determined by comparing the MIC result with the â€œbreakpoint.â€œ
AST should be performed on pure culture isolates of pathogenic (or potentially pathogenic in special situations) bacteria grown from specimens that have been appropriately collected so as not to confuse clinically significant isolates with normal flora.
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.
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.
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 D category may be assigned when doses well above those used to calculate the susceptible breakpoint are approved and used clinically.
The "intermediate" category includes isolates with antimicrobial agent minimum inhibitory concentrations (MIC) that approach usually attainable blood and tissue levels, and for which response rates may be lower than for susceptible isolates. 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 MICs 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 criterion 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 is 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 MICs 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.
(CLSI. Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth Informational Supplement. CLSI document M100-S25. Wayne, PA, Clinical and Laboratory Standards Institute, 2015)
A â€œsusceptibleâ€œ category result and a low minimum inhibitory concentration value indicate in vitro susceptibility of the organism to the antimicrobial tested.
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.
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. CLSI. Performance Standards for Antimicrobial Susceptibility Testing; 25th Informational Supplement. CLSI document M100-S25. Wayne, PA, Clinical and Laboratory Standards Institute, 2015