Amoxicillin (Page 5 of 7)

12.4 Microbiology

Mechanism of Action

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.

Mechanism of Resistance

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 in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.

Gram-Positive Bacteria

Enterococcus faecalis

Staphylococcus spp.

Streptococcus pneumoniae

Streptococcus spp. (alpha and beta-hemolytic)

Gram-Negative Bacteria

Escherichia coli

Haemophilus influenzae

Helicobacter pylori

Proteus mirabilis

Susceptibility Test Methods

When available, the clinical microbiology laboratory should provide cumulative in vitro susceptibility test results for antimicrobial drugs used in local hospitals and practice areas 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 the most effective antimicrobial.

Dilution Techniques: 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 test method (broth or agar) 2,4. The MIC values should be interpreted according to the criteria in Table 4.

Diffusion Techniques: Quantitative methods that require measurement of zone diameters can also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds 3,4. The zone size should be determined using a standardized test method 3.

Susceptibility to amoxicillin of Enterococcus spp., Enterobacteriaceae, and H. influenzae , may be inferred by testing ampicillin 4. Susceptibility to amoxicillin of Staphylococcus spp., and beta-hemolytic Streptococcus spp., may be inferred by testing penicillin 4. The majority of isolates of Enterococcus spp. that are resistant to ampicillin or amoxicillin produce a TEM-type beta-lactamase. A beta-lactamase test can provide a rapid means of determining resistance to ampicillin and amoxicillin 4.

Susceptibility to amoxicillin of Streptococcus pneumoniae (non-meningitis isolates) may be inferred by testing penicillin or oxacillin 4. The interpretive criteria for S. pneumoniae to amoxicillin are provided in Table 4 4.

Table 4. Susceptibility Interpretive Criteria for Amoxicillin
*
S. pneumoniae 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 S. pneumoniae with oxacillin zone sizes of ≤ 19 mm 4.

Minimum Inhibitory Concentration

(mcg/mL)

Disk Diffusion (Zone Diameter in mm)

Susceptible

Intermediate

Resistant

Susceptible

Intermediate

Resistant

Streptococcus pneumoniae

(non-meningitis isolates) *

≤ 2

4

≥ 8

-

-

-

A report of “Susceptible” indicates the antimicrobial is likely to inhibit growth of the pathogen if the antimicrobial compound reaches a concentration at the infection site necessary to inhibit growth of the pathogen. A report of “Intermediate” indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated. This category also provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates the antimicrobial is not likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentration usually achievable at the infection site; other therapy should be selected.

Susceptibility Testing for Helicobacter pylori

Amoxicillin in vitro susceptibility testing methods for determining minimum inhibitory concentrations (MICs) and zone sizes have not been standardized, validated, or approved for testing H. pylori. Specimens for H. pylori 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.

Quality Control

Standardized susceptibility test procedures 2,3,4 require 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 control. Standard amoxicillin powder should provide the following range of MIC values provided in Table 5 4. For the diffusion technique the criteria provided in Table 5 should be achieved.

Table 5. Acceptable Quality Control Ranges for Amoxicillin *
*
QC limits for testing E. coli 35218 when tested on Haemophilus Test Medium (HTM) are ≥ 256 mcg/mL for amoxicillin; testing amoxicillin may help to determine if the isolate has maintained its ability to produce beta-lactamase 4.
ATCC = American Type Culture Collection

Quality Control Microorganism

Minimum Inhibitory Concentrations (mcg/mL)

Disc Diffusion Zone Diameter

(mm)

Streptococcus pneumoniae ATCC 49619

0.03 to 0.12

—-

Klebsiella pneumoniae ATCC 700603

>128

—-

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