A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Ceclor Pharmacology, Pharmacokinetics, Studies, Metabolism - Cefaclor
Ceclor Pharmacology, Pharmacokinetics, Studies, Metabolism - Cefaclor
CLINICAL PHARMACOLOGY
Cefaclor is well absorbed after oral administration to fasting subjects. Total absorption is the same whether the drug is given with or without food; however, when it is taken with food, the peak concentration achieved is 50% to 75% of that observed when the drug is administered to fasting subjects and generally appears from three fourths to 1 hour later. Following administration of 250-mg, 500-mg, and 1-g doses to fasting subjects, average peak serum levels of approximately 7, 13, and 23 µg/mL respectively were obtained within 30 to 60 minutes. Approximately 60% to 85% of the drug is excreted unchanged in the urine within 8 hours, the greater portion being excreted within the first 2 hours. During this 8-hour period, peak urine concentrations following the 250-mg, 500-mg, and 1-g doses were approximately 600, 900, and 1900 µg/mL, respectively. The serum half-life in normal subjects is 0.6 to 0.9 hour. In patients with reduced renal function, the serum half-life of cefaclor is slightly prolonged. In those with complete absence of renal function, the plasma half-life of the intact molecule is 2.3 to 2.8 hours. Excretion pathways in patients with markedly impaired renal function have not been determined. Hemodialysis shortens the half-life by 25% to 30%.
Microbiology
In vitro tests demonstrate that the bactericidal
action of the cephalosporins
results from inhibition
of cell-wall synthesis. Cefaclor has been shown to be active against most
strains of the following microorganisms, both in vitro and in clinical
infections as described in the INDICATIONS
AND USAGE section.
Aerobes: Gram-positive
- Staphylococci, including coagulase-positive, coagulase-negative, and
penicillinase-producing strains
- Streptococcus pneumoniae
- Streptococcus pyogenes (group A ß-hemolytic streptococci)
Aerobes: Gram-negative
- Escherichia coli
- Haemophilus influenzae, including ß-lactamase-producing
ampicillin-resistant strains
- Klebsiella sp
- Proteus mirabilis
The following in vitro data are available, but their clinical
significance is unknown.
Cefaclor exhibits in vitro minimal
inhibitory concentrations
(MICs) of 8 mcg/ mL or less against most (90%) strains of the following
microorganisms; however, the safety and effectiveness
of cefaclor in treating clinical infections due to these microorganisms
have not been established in adequate and well-controlled clinical
trials.
Aerobes: Gram-negative
- Citrobacter diversus
- Moraxella (Branhamella) catarrhalis
- Neisseria gonorrhoeae
Anaerobes: Gram-positive
- Bacteroides sp (excluding
Bacteroides fragilis)
- Peptococci
- Peptostreptococci
- Propionibacterium acnes
Note: Pseudomonas spp., Acinetobacter calcoaceticus and most strains of enterococci ( Enterococcus faecalis , group D streptococci), Enterobacter spp., indole-positive Proteus, Morganella morganii (formerly Proteus morganii ), Providencia rettgeri (formerly Proteus rettgeri ), and Serratia spp. are resistant to cefaclor. When tested by in vitro methods, staphylococci exhibit cross-resistance between cefaclor and methicillin-type antibiotics.
Disk Susceptibility Tests
Dilution Techniques Quantitative methods that are used to determine minimum inhibitory concentrations (MIC) provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure that has been recommended for use with cefaclor powder uses a standardized dilution method 1 (broth, agar, or microdilution). The MIC values obtained should be interpreted according to the following criteria:
|
MIC (µg/mL)
|
Interpretation *
|
|
≤8
|
Susceptible (S)
|
|
16
|
Intermediate (I)
|
|
≥32
|
Resistant (R)
|
|
*When testing
H. influenzae
spp. these interpretive standards are applicable only to broth microdilution method using Haemophilus Test Medium (HTM)
1
|
Note: ß-lactamase-negative, ampicilin-resistant strains of H. influenzae should be considered resistant to cefaclor despite apparent in vitro susceptibility to this agent. Interpretation should be as stated above for results using dilution techniques.
Standardized susceptibility test procedures require the use of laboratory control microorganisms. Standard cefaclor powder should provide the following MIC values:
|
Microorganism
|
|
MIC (µg/mL)
|
|
E. coli
|
ATCC 25922
|
1-4
|
|
E. faecalis
|
ATCC 29212
|
>32
|
|
S. aureus
|
ATCC 29213
|
1-4
|
|
When testing
H. influenzae
* |
|
Microorganism
|
|
MIC (µg/mL)
|
|
H. influenzae
|
ATCC 49766
|
1-4
|
|
*Broth microdilution test performed using Haemophilus Test Medium (HTM)
1
|
Diffusion Techniques: Quantitative methods that require
measurement of zone diameters
provide reproducible estimates of the susceptibility of bacteria
to antimicrobial compounds.
One such standardized procedure that has been recommended for use with
disks to test the, susceptibility
of microorganisms to cefaclor uses the 30-mcg cefaclor disk. Interpretation
involves correlation of
the diameter obtained in
the disk test
with the MIC for cefaclor. Reports from the laboratory
providing results of the standard single-disk susceptibility
test with a 30-mcg cefaclor disk
should be interpreted according to the following criteria:
|
Zone diameter
(mm)
|
Interpretation
|
|
³ 18
|
Susceptible (S)
|
|
15 - 17
|
Intermediate (I)
|
|
£ 14
|
Resistant (R)
|
When Testing H. Influenzae*
|
Zone diameter
(mm)
|
Interpretation
|
|
³ 20
|
Susceptible (S)
|
|
17 - 19
|
Intermediate (I)
|
|
£ 16
|
Resistant (R)
|
- * Disk susceptibility
tests performed using Haemophilus Test Medium (HTM)1
Standardized susceptibility
test procedures require the use
of laboratory control microorganisms. The 30-mcg cefaclor disk
should provide the following zone diameters in these laboratory
test quality
control strains:
| Microorganisms |
Zone Diameter (mm)
|
| E.coli A.C.
25922 |
23 - 27
|
| S.aureus A.C.
25923 |
27 - 31
|
When Testing H. Influenzae*
|
Microorganisms
|
Zone Diameter (mm)
|
| H.influenzae A.C.
49766 |
25 - 31
|
Dilution Techniques: Quantitative methods that are used
to determine minimum inhibitory
concentrations provide reproducible estimates of the susceptibility
of bacteria to antimicrobial
compounds. One such standardized procedure
uses a standardized dilution
method2 (broth, agar, or microdilution) or equivalent
with cefaclor powder. The MIC values obtained should be interpreted according
to the following criteria:
|
MIC (mcg/ mL)
|
Interpretation
|
|
8
|
Susceptible (S)
|
|
16
|
Intermediate (I)
|
|
32
|
Resistant (R)
|
Interpretation should be as stated above for results using diffusion
techniques. As with standard
diffusion techniques, dilution
methods require the use of laboratory
control microorganisms. Standard
cefaclor powder should provide the following MIC
values:
| Microorganism |
MIC (mcg/ mL)
|
| E.Coli A.C.
25922 |
1 - 4
|
| E.faecalis A.C.
29212 |
> 32
|
| S.aureus A.C.
29213 |
1 - 4
|
When Testing H. Influenzae*
| Microorganism |
MIC (mcg/ mL)
|
| H.influenzae A.C.
49247 |
.12 - .5
|
REFERENCES:
1. National Committee for Clinical Laboratory Standards,
Performance standards for antimicrobial
disk susceptibility
tests - 5th ed., Approved Standard NCCLS Document M2-A5, Vol 13, No
24, NCCLS, Villanova, PA, 1993.
2. National Committee for Clinical Laboratory Standards,
Methods for dilution antimicrobial
susceptibility tests
for bacteria that grow aerobically
- 3rd ed., Approved Standard NCCLS Document M7-A3, Vol 13, No
25, NCCLS, Villanova, PA, 1993.
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