Cefazolin
Cefazolin is a parenteral **first-generation cephalosporin** antibiotic widely used in veterinary medicine. Although not FDA-approved for veterinary species, it is a clinical workhorse for **surgical prophylaxis** (especially orthopedic and soft tissue procedures) and the treatment of systemic infections, including sepsis. **Clinical Pearls:** * **Spectrum of Activity:** Exhibits excellent coverage against most Gram-positive pathogens (e.g., *Staphylococcus intermedius*, *S. aureus*, *Streptococcus* spp.) and variable to poor coverage against Gram-negative pathogens. It is highly effective against most anaerobes, with the notable exception of *Bacteroides fragilis*. * **Pharmacodynamics:** It is a **time-dependent** bactericidal antibiotic. Efficacy relies on keeping the drug concentration at the site of infection above the Minimum Inhibitory Concentration (MIC) for the majority of the dosing interval. Constant rate intravenous infusion (CRI) protocols are increasingly utilized to optimize this parameter. * **Administration:** Must be given parenterally (IV, IM, SC, IO) as it is not appreciably absorbed orally. IV injections should be administered slowly over 3-5 minutes to minimize adverse reactions.
Mecanismo: Cefazolin is a **bactericidal beta-lactam antibiotic**. **Mechanism of Action:** * **Target:** Binds to specific **Penicillin-Binding Proteins (PBPs)** located inside the bacterial cell wall. * **Pathway:** Beta-lactam ring binds PBPs → Inhibition of the transpeptidation enzyme → Prevention of peptidoglycan cross-linking → Weakening of the bacterial cell wall. * **Result:** The defective cell wall makes the bacteria highly susceptible to osmotic pressure, leading to **cell lysis** and death. As a time-dependent antibiotic, its bacterial killing is maximized by optimizing the duration of time that free drug concentrations remain above the MIC (T > MIC).
Dosificación por especie
- Gram-positive infections · 10 mg/kg or 10-30 mg/kg · IV, IM · q8h · 10 mg/kg IV or IM q8h; OR 10-30 mg/kg IV q8h
- Gram-negative infections · 30 mg/kg or 10-30 mg/kg · IM, SC, IV · q8h · 30 mg/kg IM or SC; OR 10-30 mg/kg IV q8h
- Surgical prophylaxis (Orthopedic procedures) · 20 mg/kg at induction followed by 20 mg/kg every 90 minutes until wound closure · IV · q90m · Perioperative
- Surgical prophylaxis (Soft tissue surgery) · 20 mg/kg at time of surgery followed by a second dose of 20 mg/kg 6 hours later · IV/SC · Once then 6 hours later · Perioperative · First dose IV, second dose SC
- Sepsis · 20-25 mg/kg · IV · q4-8h
- Systemic infections · 33 mg/kg · IV, IM · q8-12h · As long as necessary
- Susceptible infections · 20-25 mg/kg · IM, IV · q8h
- Infections in neonates · 10-30 mg/kg · IV, IO · q8h
- Susceptible infections · 25 mg/kg · IV, IM · q6h
- Susceptible infections · 25 mg/kg · IV, IM · q6-8h
- Susceptible infections (Foals) · 20 mg/kg · IV · q8-12h
Vías de administración
Contraindicaciones
- Patients with a known history of hypersensitivity to cephalosporins
Efectos adversos
- Hypersensitivity reactions (rashes, fever, eosinophilia, anaphylaxis)
- Pain at the IM injection site
- Sterile abscesses or local tissue reactions (rare)
- Thrombophlebitis (following IV administration)
- Nephrotoxicity (minimal risk at clinical doses)
- Neurotoxicity or seizures (associated with very high IV doses)
- GI flora disruption (in nursing neonates)
Interacciones farmacológicas
- Aminoglycosides · Potential for additive nephrotoxicity; use concurrently with caution.
- Amphotericin B · Potential for additive nephrotoxicity; use concurrently with caution.
- Probenecid · Competitively blocks the renal tubular secretion of cefazolin, thereby increasing serum levels and prolonging the elimination half-life.
Monitorización
- Clinical efficacy (resolution of clinical signs, normalization of WBC count, fever reduction)
- Renal function (BUN, creatinine, urinalysis) in patients with pre-existing renal impairment
- Signs of hypersensitivity or injection site reactions
Sobredosis
Cephalosporin overdoses are unlikely to cause significant problems. However, **very high doses given rapidly IV could potentially cause seizures** or neurotoxicity. Treatment for overdose should be supportive and symptomatic.
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