Drug Information for CEFAZOLIN FOR INJECTION USP (Hospira, Inc.): CLINICAL PHARMACOLOGY

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  • After intramuscular administration of cefazolin to normal volunteers, the mean serum concentrations were 37 mcg/mL at 1 hour and 3 mcg/mL at 8 hours following a 500 mg dose, and 64 mcg/mL at 1 hour and 7 mcg/mL at 8 hours following a 1 gram dose.

    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 and approximately 2 hours following IM 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 for injection 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 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. Cefazolin achieves peak urine concentrations of approximately 2,400 mcg/mL and 4,000 mcg/mL respectively following 500 mg and 1 gram intramuscular doses.

    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 mg/L and 150 mg/L, respectively. Mean peak levels were 29 mcg/mL (range 13 to 44 mcg/mL) with 50 mg/L (3 patients), and 72 mcg/mL (range 26 to 142 mcg/mL) with 150 mg/L (6 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, SGOT, 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:

  • Gram-Positive Aerobes:

  • Staphylococcus aureus (including beta-lactamase-producing strains)

    Staphylococcus epidermidis

    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.

  • Gram-Negative Aerobes:

  • Escherichia coli

    Proteus mirabilis

    Most strains of indole positive Proteus (Proteus vulgaris), Enterobacter spp., Morganella morganii, Providencia rettgeri, Serratia spp., and Pseudomonas spp. are resistant to cefazolin.

  • Diffusion Techniques

  • 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)
    15 to 17 Intermediate (I)
    = 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:

    MicroorganismZone diameter (mm)
    E. coliATCC 25922 21 to 27
    S. aureusATCC 25923 29 to 35

    The cefazolin disk should not be used for testing susceptibility to other cephalosporins.

  • 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 cefazolin powder. The MIC values obtained should be interpreted according to the following criteria:

    MIC (mcg/mL) Interpretation
    = 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:

    MicroorganismMIC (mcg/mL)
    S. aureusATCC 259230.25 to 1
    E. coliATCC 25922 1 to 4
  • Drug Information Provided by National Library of Medicine (NLM).
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