CLINICAL PHARMACOLOGY
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 concentration at the third hour of approximately 28 mcg/mL.
Studies in patients hospitalized with infections indicate that cefazolin produces mean peak serum concentrations approximately equivalent to those seen in normal volunteers.
Bile concentrations in patients without obstructive biliary disease can reach or exceed serum concentrations by up to five times; however, in patients with obstructive biliary disease, bile concentrations of cefazolin are considerably lower than serum concentrations (< 1 mcg/mL).
In synovial fluid, the cefazolin concentration 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 concentrations 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.
In patients undergoing peritoneal dialysis (2 l/hr, Cefazolin produced mean serum levels of approximately 10 and 30 mcg/mL after 24 hours' instillation of a dialyzing solution containing 50 mgi/l and 150 mg/l, respectively. Mean peak levels were 29 mcg/mL (range 13-44 mcg/ml) with 50 mg/l (three patients), and 72 mcg/mL (range 26 -142 mcg/mL) with 150 mg/I (six patients). Intraperitoneal administration of Cefazolin is usually well tolerated.
Controlled studies on adult normal volunteers, receiving 1 gram 4 times a day for 10 days, monitoring CBC, AST (SGOT), ALT (SGPT), bilirubin, alkaline phosphatase, BUN, creatinine and urinalysis, indicated no clinically significant changes attributed to cefazolin.
Microbiology
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 the INDICATIONS AND USAGE section:
Aerobic Gram-positive microorganisms:
Staphylococcus aureus (including penicillinase-producing strains)
Staphylococcus epidermidis
Streptococcus pneumoniae
Streptococcus pyogenes and other strains of Streptococci
NOTE: Methicillin-resistant staphylococci are uniformly resistant to cefazolin. Many Enterococcus strains are resistant to cefazolin.
Aerobic Gram-negative microorganisms:
Escherichia coli
Haemophilus influenzae
Klebsiella species
Proteus mirabilis
NOTE: Most strains of indole positive Proteus (Proteus vulgaris) , Enterobacter cloacae, Morganella morganii and Providencia rettgeri are resistant. Serratia, Pseudomonas, Mima and Herellea species are almost uniformly resistant to cefazolin.
Susceptibility Testing:
Dilution Techniques:
Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MiCs). These MlCs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MlCs should be determined using a standardized procedure. Standardized procedures are based on a dilution method1 (broth) or equivalent with standardized inoculum concentrations and standardized concentrations of cefazolin powder. The MlC values should be interpreted according to the following criteria:
For Enterobacteriaceae and Staphylococcus spp.
| MIC (mcg/mL) | lnterpretation |
| < 8 | Susceptible (S) |
| 16 | Intermediate (I) |
| > 32 | Resistant (R) |
A report of "Susceptible" indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. 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 which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of "Resistant" indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.
Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard cefazolin powder should provide the following MIC values:
| Microorganism | MIC (mcg/mL |
| S. aurecus ATCC 29213 | 0.25 to 1 |
| E. coli ATCC 25922 | 1 to 4 |
Diffusion Techniques:
Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure2 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 30-mcg cefazolin to test the susceptibility of microorganisms to cefazolin.
Reports from the laboratory providing results of the standard single-disk susceptibility lest with a 30-mcg cefazolin disk should be interpreted according to the following criteria:
For Enterobacteriaceae using the 30-mcg cefazolin disk
| Zone diameter (mm) | Interpretation |
| > 18 | Susceptible (S) |
| 15 to 17 | Intermediate (I) |
| < 14 | Resistant (R) |
For Staphylococcus spp. using the 30-mcg cefazolin or the 30-mcg cephalothin disks
| Zone diameter (mm) | Interpretation |
| > 18 | Susceptible (S) |
| 15 to 17 | Intermediate (I) |
| < 14 | Resistant (R) |
Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for cefazolin.
As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 30-mcg cefazolin disk should provide the following zone diameters in this laboratory test quality control strain:
| Microorganism | Zone diameter (mm) |
| S. aureus ATCC 25923 | 29 to 35 |
| E. coli ATCC 25922 | 23 to 29 |
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