CLINICAL PHARMACOLOGY
DURICEF is rapidly absorbed after oral administration. Following single doses of 500 mg and 1000 mg, average peak serum concentrations were approximately 16 and 28 μg/mL, respectively. Measurable levels were present 12 hours after administration. Over 90% of the drug is excreted unchanged in the urine within 24 hours. Peak urine concentrations are approximately 1800 μg/mL during the period following a single 500 mg oral dose. Increases in dosage generally produce a proportionate increase in DURICEF (cefadroxil monohydrate, USP) urinary concentration. The urine antibiotic concentration, following a 1 g dose, was maintained well above the MIC of susceptible urinary pathogens for 20 to 22 hours.
Microbiology
In vitro tests demonstrate that the cephalosporins are bactericidal because of their inhibition of cell-wall synthesis. Cefadroxil has been shown to be active against the following organisms both in vitro and in clinical infections (see INDICATIONS AND USAGE ):
Beta-hemolytic streptococci
Staphylococci, including penicillinase-producing strains
Streptococcus (Diplococcus) pneumoniae
Escherichia coli
Proteus mirabilis
Klebsiella species
Moraxella (Branhamella) catarrhalis
Note: Most strains of Enterococcus faecalis (formerly Streptococcus faecalis) and Enterococcus faecium (formerly Streptococcus faecium) are resistant to DURICEF. It is not active against most strains of Enterobacter species, Morganella morganii (formerly Proteus morganii), and P. vulgaris. It has no activity against Pseudomonas species and Acinetobacter calcoaceticus (formerly Mima and Herellea species).
Susceptibility tests: Diffusion techniques
The use of antibiotic disk susceptibility test methods which measure zone diameter give an accurate estimation of antibiotic susceptibility. One such standard procedure1 which has been recommended for use with disks to test susceptibility of organisms to cefadroxil uses the cephalosporin class (cephalothin) disk. Interpretation involves the correlation of the diameters obtained in the disk test with the minimum inhibitory concentration (MIC) for cefadroxil.
Reports from the laboratory giving results of the standard single-disk susceptibility test with a 30 μg cephalothin disk should be interpreted according to the following criteria:
| Zone diameter (mm) | Interpretation |
| ≥ 18 | (S) Susceptible |
| 15–17 | (I) Intermediate |
| ≤ 14 | (R) Resistant |
A report of “Susceptible” indicates that the pathogen is likely to be inhibited by generally achievable blood levels. A report of “intermediate susceptibility” suggests that the organism would be susceptible if high dosage is used or if the infection is confined to tissue and fluids (e.g., urine) in which high antibiotic levels are attained. A report of “Resistant’’ indicates that achievable concentrations of the antibiotic are unlikely to be inhibitory and other therapy should be selected.
Standardized procedures require the use of laboratory control organisms. The 30 μg cephalothin disk should give the following zone diameters:
| Organism | Zone Diameter (mm) |
| Staphylococcus aureus ATCC 25923 | 29–37 |
| Escherichia coli ATCC 25922 | 17–22 |
Dilution Techniques
When using the NCCLS agar dilution or broth dilution (including microdilution) method2 or equivalent, a bacterial isolate may be considered susceptible if the MIC (minimum inhibitory concentration) value for cephalothin is 8 μg/mL or less. Organisms are considered resistant if the MIC is 32 μg/mL or greater. Organisms with an MIC value of less than 32 μg/mL but greater than 8 μg/mL are intermediate.
As with standard diffusion methods, dilution procedures require the use of laboratory control organisms. Standard cephalothin powder should give MIC values in the range of 0.12 μg/mL and 0.5 μg/mL for Staphylococcus aureus ATCC 29213. For Escherichia coli ATCC 25922, the MIC range should be between 4.0 μg/mL and 16.0 μg/mL. For Streptococcus faecalis ATCC 29212, the MIC range should be between 8.0 and 32.0 μg/mL.
|
