CLINICAL PHARMACOLOGY
Cefadroxil (cefadroxil (cefadroxil hemihydrate) hemihydrate) is rapidly absorbed after oral administration. Following single
doses of 500 and 1000 mg, average peak serum concentrations were approximately
16 and 28 mcg/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 mcg/mL during the
period following a single 500 mg oral dose. Increases in dosage generally produce
a proportionate increase in cefadroxil (cefadroxil (cefadroxil hemihydrate) hemihydrate) 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 (cefadroxil (cefadroxil hemihydrate) hemihydrate) 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 cefadroxil (cefadroxil (cefadroxil hemihydrate) hemihydrate) . 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 MimaandHerella
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 (cefadroxil (cefadroxil hemihydrate) hemihydrate) 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 (cefadroxil (cefadroxil hemihydrate) hemihydrate) .
Reports from the laboratory giving results of the standard single-disk susceptibility
test with a 30 mcg cephalothin disk should be interpreted according to the following
criteria:
Zone Diameter Interpretation
(mm) |
≥18 |
(S) Susceptible |
15 to 17 |
(I) Intermediate |
≤14 (R) Resistant |
(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 mcg cephalothin disk should give the following zone diameters:
Organism |
Zone Diameter
(mm) |
Staphylococcus aureus ATCC 25923 |
29 to 37 |
Escherichia coli ATCC 25922 |
17 to 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 mcg/mL or less. Organisms are considered resistant if the MIC is 32 mcg/mL
or greater. Organisms with an MIC value of less than 32 mcg/mL but greater than
8 mcg/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 mcg/mL and 0.5 mcg/mL for Staphylococcus aureus
ATCC 29213. For Escherichia coli ATCC 25922, the MIC range should be
between 4 mcg/mL and 16 mcg/mL. For Streptococcus faecalis ATCC 29212,
the MIC range should be between 8 and 32 mcg/mL.
REFERENCES
1. National Committee for Clinical Laboratory Standards,
Approved Standard, Performance Standards for Antimicrobial Disk Susceptibility
Test, 4th Edition, Vol. 10(7): M2-A4, Villanova, PA, April, 1990.
2. National Committee for Clinical Laboratory Standards,
Approved Standard: Methods for Dilution Antimicrobial Susceptibility Tests
for Bacteria that Grow Aerobically, 2nd Edition, Vol. 10(8): M7-A2, Villanova,
PA, April, 1990.