Amoxicillin is similar to penicillin in its bactericidal action against susceptible bacteria during the stage of active multiplication. It acts through the inhibition of cell wall biosynthesis that leads to the death of the bacteria. Resistance to amoxicillin is mediated primarily through enzymes called beta-lactamases that cleave the beta-lactam ring of amoxicillin, rendering it inactive. Amoxicillin has been shown to be active against most isolates of the bacteria listed below, both and in clinical infections as described in the section.
Mechanism of Action
Method of Resistance
in vitroINDICATIONS AND USAGE
Gram-Positive Bacteria
| Gram-Negative Bacteria
|
spp. Alpha and β-hemolytic streptococci.
Enterococcus faecalis
Staphylococcus
Streptococcus pneumoniae
| Escherichia coli
Haemophilus influenzae
Neisseria gonorrhoeae
Proteus mirabilis
Helicobacter pylori
|
(susceptibility to amoxicillin can be determined using ampicillin powder and a 10 mcg ampicillin disk) When available, clinical microbiology should provide the results of susceptibility test results for antimicrobial drugs used in resident hospitals to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting an antimicrobial drug product for treatment. Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure. Standardized procedures are based on dilution methods (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of ampicillin powder. The MIC values should be interpreted according to the criteria in Table 4.
Susceptibility Test Methods:
in vitroDilution Techniques:
2,3
Diffusion Techniques:
Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 10 mcg ampicillin to test the susceptibility of bacteria to ampicillin. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for amoxicillin. Reports from the laboratory providing results of the standard single-disk susceptibility test with a 10 mcg ampicillin disk should be interpreted according to the criteria listed in Table 4.
3
Table 4. Susceptibility Test Interpretive Criteria for Amoxicillin | Minimum Inhibitory Concentration (mcg/mL)
| Disk Diffusion (zone diameter in mm)
|
|---|
| Susceptible | Intermediate | Resistant | Susceptible | Intermediate | Resistant |
|---|
* should be tested using a 1 mcg oxacillin disk. Isolates with oxacillin zone sizes of ≥ 20 mm are susceptible to amoxicillin. An amoxicillin MIC should be determined on isolates of with oxacillin zone sizes of ≤ 19 mm. **A positive beta lactamase test indicates resistance to amoxicillin. Isolates that are resistant to penicillin by MIC testing are also expected to be resistant to amoxicillin.
S. pneumoniaeS. pneumoniae
|
spp.
Enterococcus
| ≤ 8
| -
| ≥ 16
| ≥ 17
| -
| ≤ 16
|
spp.
Staphylococcus
| ≤ 0.25
|
| ≥ 0.5
| ≥ 29
|
| ≤ 28
|
Streptococci, viridians group (alpha-hemolytic streptococci)
| ≤ 0.25
| 0.5 to 4
| ≥ 8
| -
| -
| -
|
β-hemolytic streptococci
| ≤ 0.25
| -
| -
| ≥ 24
| -
| -
|
(non-meningitis isolates)*
Streptococcus pneumoniae
| ≤ 2
| 4
| ≥ 8
| -
| -
| -
|
Enterobacteriaceae
| ≤ 8
| 16
| ≥ 32
| ≥ 17
| 14 to 16
| ≤ 13
|
Haemophilus influenzae
| ≤ 1
| 2
| ≥ 4
| ≥ 22
| 19 to 21
| ≤ 18
|
Neisseria gonorrhoeae**
| -
| -
| -
| -
| -
| -
|
A report of “Susceptible” indicates the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches concentrations that are usually achievable. A report of “Intermediate” indicates that result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. The intermediate category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. The intermediate category also provides a buffer zone, which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches concentrations that are usually achievable and other therapy(ies) are likely to be preferred. Susceptibility techniques require use of laboratory control microorganisms to control the technical aspects of the laboratory standardized procedures. Standard ampicillin powder should provide the MIC values described below. For the diffusion technique using the 10 mcg ampicillin disk, the criteria are provided in Table 5.
Quality Control
2,3,4
Table 5. Acceptable Quality Control Ranges for Amoxicillin| Bacteria | ATCC# | MIC Range (mcg/mL)
| Disk Diffusion Zone Range (mm)
|
|---|
ATCC = American Type Culture Collection
#
|
Escherichia coli
| 25922
| 2 to 8
| 16 to 22
|
Enterococcus faecalis
| 29212
| 0.5 to 2
|
|
Haemophilus influenzae
| 49247
| 2 to 8
| 13 to 21
|
Staphylococcus aureus
| 29213
| 0.5 to 2
|
|
25923
|
| 27 to 35
|
Streptococcus pneumoniae
| 49619
| 0.06 to 0.25
|
|
Amoxicillin susceptibility testing methods for determining minimum inhibitory concentrations (MICs) and zone sizes have not been standardized, validated, or approved for testing . Specimens for and clarithromycin susceptibility test results should be obtained on isolates from patients who fail triple therapy. If clarithromycin resistance is found, a non-clarithromycin-containing regimen should be used.
Susceptibility Testing for :
Helicobacter pyloriin vitroH. pyloriH. pylori
