Cefazolin Mechanism of Action and Administration Route
Cefazolin is only available as a parenteral (intravenous or intramuscular) formulation and has no oral dosage form available for clinical use. 1
Mechanism of Action
Cefazolin is a first-generation cephalosporin antibiotic that works by:
- Inhibiting bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs)
- Disrupting the final transpeptidation step of peptidoglycan synthesis
- Causing bacterial cell lysis through activation of autolytic enzymes
Antimicrobial Spectrum
Cefazolin demonstrates excellent activity against:
- Gram-positive organisms: Streptococcus pneumoniae, Staphylococcus aureus (methicillin-susceptible), and group A streptococci 2, 3
- Some gram-negative organisms: Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis 2, 3
However, cefazolin has limited activity against:
- Enterobacter species
- Indole-positive Proteus
- Pseudomonas aeruginosa
- Enterococci 2
Parenteral Administration
Since cefazolin is only available in parenteral form, the standard dosing includes:
- Intravenous (IV): 1-2g every 8 hours for most infections 1
- Intramuscular (IM): 1g provides mean peak serum concentrations of 38.8 μg/ml at 1 hour post-injection 4
- Subcutaneous (SC): An alternative route with 74.8% bioavailability compared to IV administration 5
Clinical Applications
Cefazolin is primarily used for:
- Surgical prophylaxis: Single dose of 1-2g IV (with reinjection if surgery exceeds 4 hours) 1
- Infective endocarditis prophylaxis: Alternative for penicillin-allergic patients who cannot take oral medication - 1g IV/IM for adults, 50 mg/kg for children 1
- Treatment of skin and soft tissue infections: Particularly those caused by methicillin-susceptible S. aureus 1
Pharmacokinetics
- Half-life: Approximately 2-2.7 hours in patients with normal renal function 6, 4
- Protein binding: High (81%), which affects its antibacterial activity in serum 4
- Elimination: Primarily renal, with dosage adjustments needed in patients with impaired kidney function 6
Important Clinical Considerations
- Cefazolin has minimal pain upon intramuscular injection, making it preferable to some other parenteral antibiotics 2, 3
- For patients requiring oral therapy, appropriate alternatives include:
- Cephalexin (first-generation oral cephalosporin)
- Cefuroxime or cefprozil (second-generation oral cephalosporins)
- Cefpodoxime or cefdinir (third-generation oral cephalosporins) 7
Cautions and Contraindications
- Cross-reactivity with penicillin allergy: Cephalosporins should not be administered to patients with history of anaphylaxis, angioedema, or urticaria after penicillin treatment 1
- Elderly patients (>60 years) may have prolonged excretion time, potentially requiring dosage adjustment 6
Remember that when oral antibiotic therapy is needed, an appropriate oral cephalosporin or alternative antibiotic class must be selected based on the infection type and suspected pathogens, as cefazolin itself is not available in oral form.