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Studies have shown that following intravenous administration of cefazolin to normal volunteers, mean serum concentrations peaked at approximately 185 mcg/mL and were approximately 4 mcg/mL at 8 hours for a 1 gram dose.
The serum half-life for cefazolin is approximately 1.8 hours following IV administration.
In a study (using normal volunteers) of constant intravenous infusion with dosages of 3.5 mg/kg for 1 hour (approximately 250 mg) and 1.5 mg/kg the next 2 hours (approximately 100 mg), cefazolin produced a steady serum level at the third hour of approximately 28 mcg/mL.
Studies in patients hospitalized with infections indicate that cefazolin produces mean peak serum levels approximately equivalent to those seen in normal volunteers.
Bile levels in patients without obstructive biliary disease can reach or exceed serum levels by up to five times; however, in patients with obstructive biliary disease, bile levels of cefazolin are considerably lower than serum levels ( < 1.0 mcg/mL).
In synovial fluid, the cefazolin level becomes comparable to that reached in serum at about 4 hours after drug administration.
Studies of cord blood show prompt transfer of cefazolin across the placenta.
Cefazolin is present in very low levels in the milk of nursing mothers.
Cefazolin is excreted unchanged in the urine. In the first 6 hours approximately 60% of the drug is excreted in the urine and this increases to 70% to 80% within 24 hours.
Controlled studies on adult normal volunteers, receiving 1 gram 4 times a day for 10 days, monitoring CBC, SGOT, SGPT, bilirubin, alkaline phosphatase, BUN, creatinine, and urinalysis, indicated no clinically significant changes attributed to cefazolin.
In vitro tests demonstrate that the bactericidal action of cephalosporins results from inhibition of cell wall synthesis. Cefazolin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in INDICATIONS.
Staphylococcus aureus (including beta-lactamase-producing strains)
Streptococcus pyogenes, Streptococcus agalactiae, and other strains of streptococci Streptococcus pneumoniae
Methicillin-resistant staphylococci are uniformly resistant to cefazolin, and many strains of enterococci are resistant.
Most strains of indole positive Proteus (Proteus vulgaris), Enterobacter spp., Morganella morganii, Providencia rettgeri, Serratia spp., and Pseudomonas spp. are resistant to cefazolin.
Quantitative methods that require measurement of zone diameters provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure1 that has been recommended for use with disks to test the susceptibility of microorganisms to cefazolin uses the 30-mcg cefazolin disk. Results of the standardized single-disk susceptibility test1 with a 30-mcg cefazolin disk should be interpreted according to the following criteria:
RECOMMENDED RANGES FOR CEFAZOLIN SUSCEPTIBILITY TESTING
|Zone Diameter (mm)||Interpretation|
|≥ 18||Susceptible (S)|
|≤ 14||Resistant (R)|
Standardized single-disk susceptibility test should be performed ONLY with a 30-mcg cefazolin disk.
A report of “Susceptible” indicates that the pathogen is likely to be inhibited by usually achievable concentrations of the antimicrobial compound in the blood. A report of “Intermediate” indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, 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 dosage of drug 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 “Resistant” indicates that usually achievable concentrations of the antimicrobial compound in the blood are unlikely to be inhibitory and that other therapy should be selected.
Standardized susceptibility test procedures require the use of laboratory control microorganisms. The 30-mcg cefazolin disk should provide the following zone diameters in these laboratory test quality control strains:
|Microorganism||Zone Diameter (mm)|
|E. coli ATCC® 25922||21-27|
|S. aureus ATCC® 25923||29-35|
The cefazolin disk should not be used for testing susceptibility to other cephalosporins.
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 cefazolin powder. The MIC values obtained should be interpreted according to the following criteria:
|≤ 16||Susceptible (S)|
|≥ 64||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 cefazolin powder should provide the following MIC values:
|S. aureus ATCC® 25923||0.25-1.0|
|E. coli ATCC® 25922||1.0-4.0|
1. National Committee for Clinical Laboratory Standards (NCCLS). January 2003. Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard-Eighth Edition. NCCLS Document M2-A8 and Disk Diffusion Supplemental Tables M100-S13. NCCLS, Wayne, PA, USA.
2. National Committee for Clinical Laboratory Standards (NCCLS). January 2003. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard-Sixth Edition. NCCLS Document M7-A6 and MIC Testing Supplemental Tables, M100-S13. NCCLS, Wayne, PA, USA.
Last reviewed on RxList: 2/9/2009
This monograph has been modified to include the generic and brand name in many instances.
Additional Cefazolin Injection Information
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