AUGMENTIN ES-600 (Page 2 of 7)

Aerobic Gram-Positive Microorganisms:

Streptococcus pneumoniae (including isolates with penicillin MICs ≤ 2 mcg/mL)

Aerobic Gram-Negative Microorganisms:

Haemophilus influenzae (including β-lactamase–producing isolates)

Moraxella catarrhalis (including β-lactamase–producing isolates)

The following in vitro data are available, but their clinical significance is unknown.

At least 90% of the following microorganisms exhibit in vitro minimum inhibitory concentrations (MICs) less than or equal to the susceptible breakpoint for amoxicillin/clavulanic acid. However, the safety and efficacy of amoxicillin/clavulanic acid in treating infections due to these microorganisms have not been established in adequate and well-controlled trials.

Aerobic Gram-Positive Microorganisms:

Staphylococcus aureus (including β-lactamase–producing isolates)

NOTE: Staphylococci which are resistant to methicillin/oxacillin must be considered resistant to amoxicillin/clavulanic acid.

Streptococcus pyogenes

NOTE: S. pyogenes do not produce β-lactamase, and therefore, are susceptible to amoxicillin alone. Adequate and well-controlled clinical trials have established the effectiveness of amoxicillin alone in treating certain clinical infections due to S. pyogenes.

Susceptibility Test Methods:

When available, the clinical microbiology laboratory should provide cumulative results of 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 Technique:

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.^1,2 Standardized procedures are based on dilution methods (broth for S. pneumoniae and H. influenzae) or equivalent with standardized inoculum concentration and standardized concentrations of amoxicillin/clavulanate potassium powder.

The recommended dilution pattern utilizes a constant amoxicillin/clavulanate potassium ratio of 2 to 1 in all tubes with varying amounts of amoxicillin. MICs are expressed in terms of the amoxicillin concentration in the presence of clavulanic acid at a constant 2 parts amoxicillin to 1 part clavulanic acid. The MIC values should be interpreted according to criteria provided in Table 3.

Diffusion Technique:

Quantitative methods that require measurement of zone diameters also provides reproducible estimates of the susceptibility of bacteria to antimicrobials. One such standardized technique requires the use of a standardized inoculum concentration.^2,3 This procedure uses paper disks impregnated with 30 mcg amoxicillin/clavulanate potassium (20 mcg amoxicillin plus 10 mcg clavulanate potassium) to test susceptibility of microorganisms to amoxicillin/clavulanate potassium. Disk diffusion zone sizes should be interpreted according to criteria provided in Table 3.

Table 3. Susceptibility Test Result Interpretive Criteria for Amoxicillin/Clavulanate Potassium

Pathogen	Minimum Inhibitory Concentration (mcg/mL)			Disk Diffusion (Zone Diameter in mm)
Pathogen	S	I	R	S	I	R
Streptococcus pneumoniae (non-meningitis isolates)	≤ 2/1	4/2	≥ 8/4	Not Applicable (NA)
Haemophilus influenzae	≤ 4/2	NA	≥ 8/4	≥ 20	NA	≤ 19

NOTE: Susceptibility of S. pneumoniae should be determined using a 1-mcg oxacillin disk. Isolates with oxacillin zone sizes of ≥ 20 mm are susceptible to amoxicillin/clavulanic acid. An amoxicillin/clavulanic acid MIC should be determined on isolates of S. pneumoniae with oxacillin zone sizes of ≤ 19 mm.

NOTE: β-lactamase–negative, ampicillin-resistant H. influenzae isolates must be considered resistant to amoxicillin/clavulanic acid.

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

Standardized susceptibility test procedures require the use of quality control microorganisms to determine the performance of the test procedures.^1-3 Standard amoxicillin/clavulanate potassium powder should provide the MIC ranges for the quality control organisms in Table 4. For the disk diffusion technique, the 30 mcg-amoxicillin/clavulanate potassium disk should provide the zone diameter ranges for the quality control organisms in Table 4.

Table 4. Acceptable Quality Control Ranges for Amoxicillin/Clavulanate Potassium

Quality Control Organism	Minimum Inhibitory Concentration Range(mcg/mL)	Disk Diffusion(Zone DiameterRange in mm)
* ATCC is a trademark of the American Type Culture Collection. † When using Haemophilus Test Medium (HTM).
Escherichia coli ATCC® * 35218 †(H. influenzae quality control)	4/2 to 16/8	17 to 22
Haemophilus influenzae ATCC 49247	2/1 to 16/8	15 to 23
Streptococcus pneumoniae ATCC 49619	0.03/0.016 to 0.12/0.06	NA