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
Cefizox Pharmacology, Pharmacokinetics, Studies, Metabolism - Ceftizoxime
Cefizox Pharmacology, Pharmacokinetics, Studies, Metabolism - Ceftizoxime
CLINICAL PHARMACOLOGY
The table below demonstrates
the serum levels and duration
of Cefizox (ceftizoxime for injection,
USP) following IM administration
of 500 mg and 1 gram doses,
respectively, to normal
volunteers.
|
Serum Concentrations After Intramuscular
Administration Serum Concentration (mcg/mL)
|
|
Dose
|
1/ 2hr
|
1 hr
|
2hr
|
4hr
|
6hr
|
8hr
|
|
500mg
|
13.3
|
13.7
|
9.2
|
4.8
|
1.9
|
0.7
|
|
1 gm
|
36.0
|
39.0
|
31.0
|
15.0
|
6.0
|
3.0
|
Following IV administration
of 1,2, and 3 gram doses
of Cefizox to normal volunteers, the following serum
levels were obtained.
|
Serum Concentrations After Intra Serum
Concentration venous Adm (mcg/mL) inistration
|
| Dose |
5 min
|
10 min
|
30 min
|
1 hr
|
2 hr
|
4 hr
|
8 hr
|
| 1 gram |
ND
|
ND
|
60.5
|
38.9
|
21.5
|
8.4
|
1.4
|
| 2grams |
131.8
|
110.9
|
77.5
|
53.6
|
33.1
|
12.1
|
2.0
|
| 3grams |
221.1
|
174.0
|
112.7
|
83.9
|
47.4
|
26.2
|
4.8
|
| ND=Not Done |
A serum half-life
of approximately 1.7 hours was observed after IV
or IM administration.
Cefizox is 30% protein
bound.
Cefizox is not metabolized, and is excreted virtually unchanged
by the kidneys in 24 hours. This provides a high urinary
concentration.
Concentrations greater than 6000 mcg/mL have been achieved in the
urine by 2 hours after a 1 gram
dose of Cefizox intravenously.
Probenecid slows tubular secretion
and produces even higher serum
levels, increasing the duration of measurable serum
concentrations. Cefizox achieves therapeutic levels in various bodyfluids,
e.g., cerebrospinal
fluid (in patients with
inflamed meninges), bile, surgical
wound fluid,
pleural fluid,
aqueous humor, ascitic fluid,
peritoneal fluid,
prostatic fluid
and saliva, and in the
following bodytissues: heart,
gallbladder, bone, biliary,
peritoneal, prostatic, and uterine.
In clinical experience
to date, no disulfiram-like
reactions have been reported with Cefizox.
Microbiology
The bactericidal
action of Cefizox (ceftizoxime
for injection, USP)
results from inhibition
of cell-wall synthesis. Cefizox is highly resistant to a broad spectrum
of beta-lactamases (penicillinase and cephalosporinase), including
Richmond types I, II, III, TEM, and IV, produced by both aerobic
and anaerobic gram-positive
and gram-negative
organisms. Cefizox is active against a wide range
of gram-positive
and gram-negative
organisms, and is usually active against the following organisms
in vitro and in clinical situations (see NDICATIONS
AND USAGE).
Gram-Positive Aerobes
- Staphylococcus aureus (including penicillinase- and nonpenicillinase-producing
strains) NOTE: Methicillin-resistant staphylococci
are resistant to cephalosporins, including ceftizoxi me.
- Staphylococcus epidermidis (including penicillinase-
and nonpenicillinase-producing strains)
- Streptococcus agalactiae
- Streptococcus pneumoniae
- Streptococcus pyogenes
NOTE: Ceftizoxime is usually inactive against most strains
of Enterococcus faecalis (formerly S. faecalis).
Gram-Negative Aerobes
- Acinetobacter spp.
- Enterobacter spp.
- Escherichia coli
- Haemophilus influenzae (including ampicillin-resistant
strains)
- Klebsiella pneumoniae
- Morganella morganii (formerly Proteus
morganii)
- Neisseria gonorrhoeae
- Proteus mirabilis
- Proteus vulgaris
- Providencia rettgeri (formerly Proteus
rettgeri)
- Pseudomonas aeruginosa
- Serratia marcescens
Anaerobes
- Bacteroides spp.
- Peptococcus spp.
- Peptostreptococcus spp.
Ceftizoxime is usually active against the following organisms in
vitro, but the clinical
significance of these data is unknown.
Gram-Positive Aerobes
Gram-Negative Aerobes
- Aeromonas hydrophila
- Citrobacter spp.
- Moraxella spp.
- Neisseria meningitidis
- Pasteurella multocida
- Providencia stuartii
- Salmonella spp.
- Shigella spp.
- Yersinia enterocolitica
Anaerobes
- Actinomyces spp.
- Bifidobacterium spp.
- Clostridium spp.
- NOTE: Most strains of Clostridium difficile are
resistant.
- Eubacterium spp.
- Fusobacterium spp.
- Propionibacterium spp.
- Veillonella spp.
Susceptibility Testing
Diffusion Techniques: Quantitative methods that require
measurement of zone diameters
give the most precise estimate of the susceptibility of bacteria
to antimicrobial
agents. One such standard
procedure1 has been recommended for use with disks to test
susceptibility
of organisms to ceftizoxime. Interpretation involves the correlation
of the diameters obtained in the disk test
with the minimum inhibitory
concentration
(MIC) for ceftizoxime.
Organisms should be tested with the ceftizoxime disk, since ceftizoxime
has been shown by in vitro tests to be active against certain
strains found resistant when other beta-lactam disks are used.
Reports from the laboratory
giving results of the standard
single-disk susceptibility test
with a 30 mcg ceftizoxime
disk should be interpreted
according to the following criteria (with the exception of Pseudomonas
aeruginosa).
|
Zone Diameter (mm)
|
Interpretation
|
|
20
|
(S) Susceptible
|
|
15-19
|
(MS) Moderately Susceptible
|
|
14
|
(R) Resistant
|
A report of “Susceptible”
indicates that the pathogen
is likely to be inhibited by generally achievable blood
levels. A report of “Moderately
Susceptible” 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 ceftizoxime disk
should give the following zone
diameters.
|
Organism
|
ATCC Zone
|
Diameter (mm)
|
| Escherichia coli |
25922
|
30-36
|
| Pseudomonas aeruginosa |
27853
|
12-17
|
| Staphylococcus aureus |
25923
|
27-35
|
Susceptibility Testing for Pseudomonas
in Urinary Tract Infections: Most strains of Pseudomonasaeruginosa
are moderately susceptible
to ceftizoxime. Ceftizoxime achieves high levels in the urine
(greater than 6000 mcg/mL at 2 hours with 1 gram
IV) and therefore, the
following zone sizes should
be used when testing ceftizoxime for treatment
of urinary tract
infections caused by Pseudomonas aeruginosa.
Susceptible organisms produce zones of 20 mm
or greater, indicating that the test
organism is likely
to respond to therapy.
Organisms that producezones of 11 to 19 mm
are expected to be susceptible when the infection
is confined to the urinary
tract (in which high antibiotic
levels are attained).
Resistant organisms produce zones of 10 mm
or less, indicating that other therapy
should be selected.
Dilution Techniques: When using the NCCLS agar
dilution or broth dilution
(including microdilution) method
2 or equivalent, the following MIC
data should be used for interpretation.
|
MIC (mcg/mL)
|
Interpretation
|
|
8
|
(S) Susceptible
|
|
16-32
|
(MS) Moderately Susceptible
|
|
64
|
(R) Resistant
|
As with standard disk
diffusion methods,
dilution procedures
require the use of laboratory
control organisms. Standard
ceftizoxime powder should
give MIC values in the following
ranges.
|
Organism
|
ATCC
|
MIC (mcg/mL)
|
| Escherichia coli |
25922
|
0.03-0.12
|
| Pseudomonas aeruginosa |
27853
|
16-64
|
| Staphylococcus aureus |
25923
|
2-8
|
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