dardized procedure1,3. Standardized procedures are based on a dilution method (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of penicillin or ampicillin. The susceptibility of Group A streptococcus to penicillin or amoxicillin should be interpreted according to the criteria in TABLE 2.
Diffusion Technique
Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure2 requires the use of a standardized inoculum concentration. This procedure uses paper disks impregnated with 10 units penicillin or 10 mcg ampicillin to test the susceptibility of S. pyogenes to penicillin or amoxicillin. Reports from the laboratory providing results of the standard single-disk susceptibility test should be interpreted according to the criteria in TABLE 2
Table 2. Susceptibility Test Results Interpretive Criteria for Beta-Hemolytic Streptococci including Streptococcus pyogenes
Antimicrobial Minimum Inhibitory
Concentration (mcg/mL) Disk Diffusion
(zone diameter in mm)
Penicillin ≤0.12 = Susceptible ≥24 = Susceptible
Ampicillin ≤0.25 = Susceptible ≥24 = Susceptible
The current absence of data on resistant isolates precludes defining any categories other than “Susceptible”. Isolates yielding results suggestive of a “nonsusceptible” category should be retested, and if the result is confirmed, the isolate should be submitted to a reference laboratory for further testing.
Quality Control
Standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of the supplies and reagents used in the assay, and the techniques of the individuals performing the test. Standard penicillin or ampicillin powders should provide the MIC ranges provided in TABLE 3. For the disk diffusion technique using the 10 unit penicillin disk or 10 μg ampicillin disk the criteria in TABLE 3 should be achieved.
3. Acceptable Quality Control Ranges for Susceptibility Testing
ATCC = American Type Culture Collection
QC Organism Antimicrobial Minimum Inhibitory
Concentration (mcg/mL) Disk Diffusion
(zone diameter in mm)
Streptococcus pneumoniae Penicillin 0.25 – 1 24 – 30
ATCC 49619 Ampicillin 0.06 – 0.25 30 - 36
13. NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies in animals have not been performed to eva luate carcinogenic potential. Studies to detect mutagenic potential of amoxicillin alone have not been conducted; however, the following information is available from tests on a 4:1 mixture of amoxicillin and potassium clavulanate (Augmentin). Augmentin was non-mutagenic in the Ames bacterial mutation assay, and the yeast gene conversion assay. Augmentin was weakly positive in the mouse lymphoma assay, but the trend toward increased mutation frequencies in this assay occurred at doses that were also associated with decreased cell survival. Augmentin was negative in the mouse micronucleus test, and in the dominant lethal assay in mice. Potassium clavulanate alone was tested in the Ames bacterial mutation assay and in the mouse micronucleus test |
