To improve the predictability and clinical utility of antimicrobial treatment for urine tract infections, Antech Diagnostics is introducing a new urine minimum inhibitory concentration (MIC) antibiotic sensitivity test methodology using an automated microdilutional technique. MIC testing guides antibiotic selection by determining whether the tested bacteria are likely to be sensitive or resistant to any given antibiotic. Most antibiotics are tested over 3–5 doubling dilutions that represent a range of concentrations (in µg/mL) at which susceptible bacteria are either inhibited or killed and can be achieved in serum following a standard dose.

The "susceptibility breakpoint" is an important concept in interpreting MIC results. If one were to evaluate an antibiotic against numerous strains of a bacterium (e.g., E. Coli) using doubling dilutions, the antimicrobial activity pattern would be similar to that shown in the figure below. Many strains of bacteria will be killed by low concentrations of the antibiotic; these are sensitive strains of bacteria. Bacteria with intrinsic or acquired resistance mechanisms typically require much higher concentrations of antibiotic to be killed. The concentration of antibiotic slightly greater than that required to kill sensitive strains of bacteria is the susceptibility breakpoint (in the example shown, at 1 µg/ml). The concentrations of antibiotics tested include the breakpoint concentration and 2 to 4 doubling dilutions from the breakpoint (e.g, 1 µg/mL, 0.5 µg/mL, 0.25 µg/mL, 0.125 µg/mL).

In interpreting MIC test results, the further that the MIC for a particular antibiotic is below its susceptibility breakpoint, the more effective that antibiotic is likely to be against that particular bacterium.

Sometimes, despite an MIC prediction of resistance, an antibiotic will be successful because very large concentrations can be obtained at the site of infection (e.g., urine). However, because the MIC test is not linear over an infinite concentration range, it is best to assume that the probability of successful treatment decreases as the MIC of the antibiotic increases.

Antech’s new urine MIC testing utilizes an automated microdilutional methodology to determine both the MIC of antimicrobials commonly used to treat lower urinary tract infections as well as a prediction of susceptibility or resistance based upon achievable urinary concentrations. The higher breakpoints used in interpreting a urine MIC are 1 to 2 dilutions higher than those of systemic MIC breakpoints, depending upon the particular antibiotic and its ability to accumulate in urine. The predictability of successful treatment is based upon the infection being in the lower urinary tract and uncomplicated. As glomerular filtration rate, renal blood flow and urine concentrating ability all affect antimicrobial concentrations, less than predicted outcomes may result in patients with complicated or upper urinary tract infections.

Key points in using the urine MIC panel to choose an antibiotic and dose:

• All other things being equal (cost, safety, ease of use, compliance), use the antibiotic with the lower MIC in its testing range.
• The higher the MIC in the testing range, the higher the dose needed and vice versa.

Urine Cultures

Antech Diagnostics routinely performs quantitative urine cultures (urine colony counts) when liquid urine, as opposed to a Copan swab, is submitted. The preferred method of urine collection for culture is by cystocentesis. Urine should be placed in a sterile red top tube (not a serum separator tube) and labeled "Urine for Culture". Only a small volume of urine (~ 0.5 mL) is needed; a separate container of urine should be submitted for routine urinalysis.

Results are reported as the number or range of colony forming units (cfu) per mL of urine, along with identification of the organism and its antimicrobial sensitivity (Table).

Animals should be off antibiotics for at least 48-72 hours prior to urine culture. Routine transport time to the lab does not influence urine culture results.

Copan swabs of urine or urine submitted in broth are not preferred for urine culture, and enable reporting only of semiquantitative culture results.

Reference: Modified from Osborne. Compendium 17: 1233-1249, 1995.

March 2001 Antech News

• The subheading for Avian, Exotics & Small Mammal Testing was inadvertently left out of the final copy (right column, page 1 above "Hematology" to top of page 2). This has been corrected on the web site (see address below).
• The spun green top tube (GRT) is the preferred sample for chemistry profiles of these avian and exotic species, but is NOT recommended for routine use in small and large animal testing.