Download Use of Antimicrobial Susceptibility Data to Guide Therapy

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Use of Antimicrobial Susceptibility Data to Guide Therapy
Note: This is a brief description of some important concepts in the use of susceptibility data to guide
therapy. This information is in no way intended to supersede clinical judgment, information provided in
package inserts or textbooks, nor to replace a thorough review of the many fine books and information
sources on antimicrobial use. For further information and eloquent descriptions of this topic, it is
suggested that you consult the following source: Small Animal Clinical Pharmacology and Therapeutics
by Dawne Merton Boothe published by W.B. Saunders Co in 2001.
The efficacy of a particular antimicrobial drug in treating an infection depends on a variety of factors
including those associated with the host, the drug, and the bacterium. The two factors that we will
consider here are those associated with the drug and the "bug". Each antimicrobial drug has
characteristics that should be considered as part of the drug selection process. These include: toxicity,
mode of action (bacteriostatic vs. bacteriocidal), tissue distribution, plasma half-life, achievable plasma
concentrations, spectrum, and cost among others. Much of this information is available on the package
insert for the drug or a PDR.
The bacteria involved in the infectious process have individual characteristics of sensitivity/resistance to
certain drugs, rapidity with which the bacteria acquire resistance to various classes of drugs, and site of
persistence and growth (e.g. intracellular vs extracellular). DCPAH provides information regarding the
susceptibility/resistance of individual bacterial isolates to various drugs and drug classes by providing
either quantitative (MIC) and/or qualitative (S, I, R) antimicrobial susceptibility results.
The MIC is particularly valuable because this value can be used to compare the relative efficacy of
different drugs and to calculate doses that may need to be customized in particularly challenging
infections. Simply defined, the MIC is the minimum concentration of the drug that will inhibit the in vitro
growth of the organism and is specific to the organism isolated and the drug. This means that the drug
concentration at the site of infection should be at least equal to the MIC value. Package inserts and
PDR's and various textbooks (citations below) contain information about achievable drug
concentrations in various tissues with various dosing regimens. For some drugs these values have
been established in various animal species but in many cases, the data must be extrapolated from
human testing.
Another important variable in using MIC data is the so called "Resistant Breakpoint MIC" and this is the
approximate drug concentration that can be reasonably achieved safely in the plasma using the normal
dose and route of administration of the drug. Thus the Breakpoint MIC takes into account the clinical
pharmacology of the drug and is specific for the host, dose, and drug but is not usually organism
specific. Resistant Breakpoint MICs are determined by testing organizations and are available in
various references and, for some drugs, in a table provided by DCPAH (Resistance Breakpoints for
Antimicrobials used in Animals) on the DCPAH CD or website.
Armed with the organism MIC measured at DCPAH and the Resistant Breakpoint MIC, you can begin
to compare the relative efficacy of various antimicrobials to treat a given infection. We are frequently
asked if the way to use MIC data to choose a drug is to use the drug with the "lowest number". The
answer is an unequivocal NO! The MICs for various drugs must be compared as they relate to the
Resistance Breakpoint MIC for that drug. The Resistant Breakpoint MIC is divided by the measured
MIC provided by DCPAH to derive an efficacy ratio—or a measure of how far the measured MIC is from
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Diagnostic Center for Population & Animal Health | 4125 Beaumont Road, Lansing, MI 48910-8104 | PH: 517.353.1683 FX: 517.353.5096 | www.animalhealth.msu.edu
the Resistant Breakpoint for that drug. A drug with a high efficacy ratio should be more effective that a
drug with a lower efficacy ratio would be.
Confused yet? An example might be helpful. Suppose the measured MIC for an E. coli isolate from a
dog was 1 ug/ml for enrofloxacin and 1 ug/ml for gentamicin. Using the chart provided, the Resistant
Breakpoint MIC's for these drugs are determined to be >4 ug/ml for enrofloxacin (at the 5mg/kg dose)
and >8 ug/ml for gentamicin. Therefore, the efficacy ratio for enrofloxacin in this particular infection
would be 4 (4 divided by 1) and that for gentamicin would be 8 (8 divided by 1). The drug with the
higher efficacy ratio, in this case gentamicin, would be predicted to be more effective in this infection.
This type of calculation can be repeated to compare a whole series of drugs and this information can be
factored in with the many other considerations in choosing an antimicrobial.
Another example: Here is an example (shaded green) of a typical report issued by DCPAH on a skin
culture from a dog:
Moderate numbers of Staphylococcus pseudintermedius
Resistant
Breakpoint
MIC for PO Efficacy
MIC
Interp
Therapy
Ratio
Amikacin
<= 4
S
16
4
Amoxicillin/Clav
<=0.25/0.12
S
1
4
Ampicillin
R
Cefoxitin
<= 2
S
Cephalothin
<= 2
S
8
4
Clindamycin
<= 0.25
S
4
16
Enrofloxacin
<= 0.5
S
4
8
Erythromycin*
<= 0.5
S
8*
16
Gentamicin*
<= 1
S
8*
8
Orbifloxacin
<= 1
S
8
8
Oxacillin
<= 2
S
4
2
Penicillin
R
Trimethoprim/Sulfa*
<= 0.5/9.5
S
4
8
Tetracycline
>8
R
*No species-specific interpretive criteria available; based on human interpretive criteria.
In this case, the data from DCPAH is shaded in light green and the analysis by the veterinarian in light
blue. Assume you want to use a drug that is good for skin infections and is available for PO use which
narrows your choices somewhat. Next, to compare the relative efficacy of the drug choices, you look
up the Resistant Breakpoint MIC (Resistance Breakpoints for Antimicrobials used in Animals) and
calculate the Efficacy ratio as described above. In this example, there are several reasonable choices
but it appears that both clindamycin and erythromycin would be a great choice as it has the highest
efficacy ratio.
WEBCD.BACT.REF.013.02
IssueDate 10/09/2015
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Diagnostic Center for Population & Animal Health | 4125 Beaumont Road, Lansing, MI 48910-8104 | PH: 517.353.1683 FX: 517.353.5096 | www.animalhealth.msu.edu
References and other sources of information:
Small Animal Clinical Pharmacology and Therapeutics by Dawne Merton Boothe, W.B. Saunders Co.,
2001.
Antimicrobial Therapy in Veterinary Medicine, Third Edition, J.F. Prescott, J.D. Baggot, and R.D.
Walker, Eds., Iowa State University Press, 2000.
CLSI. Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria
Isolated From Animals. 3rd ed. CLSI supplement VET01S. Wayne, PA: Clinical and Laboratory
Standards Institute; 2015.
CLSI. Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth International
Supplement. CLSI document M100-S25. Wayne, PA: Clinical and Laboratory Standards Institute; 2015.
Physicians Drug Reference
Package inserts from antimicrobials
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