Cefazolin

Usage

Cefazolin, a first-generation cephalosporin antibiotic, is primarily used for the treatment and prophylaxis of bacterial infections caused by susceptible gram-positive organisms, such as Streptococcus pneumoniae, Staphylococcus aureus (MSSA), and group A beta-hemolytic streptococci, and some gram-negative bacteria like Escherichia coli, Proteus mirabilis, Klebsiella spp., and Haemophilus influenza. It is commonly prescribed for respiratory tract infections, urinary tract infections, skin and soft tissue infections, biliary tract infections, bone and joint infections, septicemia, and endocarditis. It is also frequently used as a prophylactic agent in surgical procedures to prevent surgical site infections.

Pharmacological Classification: Antibiotic (Beta-lactam, Cephalosporin, First-generation)

Mechanism of Action: Cefazolin inhibits bacterial cell wall synthesis by binding to and inactivating penicillin-binding proteins (PBPs), which are essential for cross-linking peptidoglycans in the bacterial cell wall. This disruption leads to cell wall instability and bacterial lysis.

Alternate Names

Cefazolin Sodium

Brand Names: Ancef, Kefzol, Cefazolin Sandoz, Cefazolin-AFT

How It Works

Pharmacodynamics: Cefazolin exerts its bactericidal effect by disrupting bacterial cell wall synthesis, leading to cell death. Its activity is primarily against gram-positive bacteria.

Pharmacokinetics:

• Absorption: Cefazolin is poorly absorbed orally and is therefore administered intravenously (IV) or intramuscularly (IM). It achieves therapeutic concentrations in various tissues and fluids, including bone, joints, bile, and synovial fluid. It also crosses the placental barrier and is present in low concentrations in breast milk.
• Metabolism: Cefazolin is not extensively metabolized.
• Elimination: Cefazolin is primarily eliminated unchanged by renal excretion, with a half-life of approximately 1.5-2 hours in patients with normal renal function.

Mode of Action: Cefazolin binds to specific PBPs within the bacterial cell wall, inhibiting the transpeptidation reaction, a crucial step in peptidoglycan synthesis. This leads to weakened cell walls, ultimately resulting in bacterial cell lysis and death.

Elimination Pathways: Primarily renal excretion.

Dosage

Standard Dosage

Adults:

• Mild to Moderate Infections: 250-500 mg IV or IM every 8 hours.
• Moderate to Severe Infections: 500 mg - 1 g IV or IM every 6-8 hours.
• Severe, Life-Threatening Infections: 1-1.5 g IV every 6 hours (maximum 12 g/day).

Children (≥ 1 month):

• Mild to Moderate Infections: 25-50 mg/kg/day IV or IM divided every 6-8 hours (maximum 3 g/day).
• Severe Infections: 100-150 mg/kg/day IV or IM divided every 6-8 hours (maximum 6 g/day).
• Neonates (<28 days): Please refer to specialized neonatal dosing guidelines.

Special Cases:

• Elderly Patients: Dose adjustments may be necessary based on renal function. Monitor renal function closely.
• Patients with Renal Impairment: Dosage adjustments are required based on creatinine clearance (CrCl).
• Patients with Hepatic Dysfunction: No specific dosage adjustment is typically required, but caution is advised.
• Patients with Comorbid Conditions: Individualized dosing may be required depending on specific conditions.

Clinical Use Cases:

• Surgical Prophylaxis: 1-2 g IV/IM 30-60 minutes before the procedure. For prolonged procedures (>2 hours), an intraoperative dose of 0.5-1 g IV may be given. Postoperatively, 0.5-1 g IV every 6-8 hours for 24 hours. Specific surgical procedures may have different recommendations.
• Intubation/Mechanical Ventilation/ICU Use: Dosing depends on the underlying infection being treated.
• Emergency Situations: Dose depends on the specific situation and infection being treated.

Dosage Adjustments:

• Renal Impairment: Dosage adjustments are required based on CrCl. See resources for specific guidelines.

Side Effects

Common Side Effects:

• Pain, redness, swelling at injection site
• Nausea, vomiting, diarrhea
• Genital itching, rash

Rare but Serious Side Effects:

• Severe allergic reactions (anaphylaxis, angioedema)
• Clostridium difficile-associated diarrhea (pseudomembranous colitis)
• Seizures (especially with high doses and renal impairment)
• Stevens-Johnson syndrome

Long-Term Effects:

• Potential for superinfection with prolonged use
• Vitamin K deficiency

Contraindications

• Hypersensitivity to cefazolin or other cephalosporins
• Severe or immediate hypersensitivity to penicillins or carbapenems

Drug Interactions

• Probenecid: Reduces renal excretion of cefazolin, increasing serum levels. Co-administration is generally not recommended.
• Anticoagulants (e.g., warfarin): May enhance anticoagulant effects. Monitor INR closely.
• Other nephrotoxic drugs (e.g., aminoglycosides): May increase the risk of nephrotoxicity.

Pregnancy and Breastfeeding

• Pregnancy: Cefazolin is generally considered safe to use during pregnancy (Pregnancy Category B). However, it should be used only if clearly needed.
• Breastfeeding: Cefazolin is excreted in breast milk in low concentrations. Monitor the infant for potential side effects such as diarrhea or thrush.

Drug Profile Summary

• Mechanism of Action: Inhibits bacterial cell wall synthesis.
• Side Effects: See above.
• Contraindications: See above.
• Drug Interactions: See above.
• Pregnancy & Breastfeeding: Generally safe, use with caution.
• Dosage: See above.
• Monitoring Parameters: Renal function, signs of infection, signs of bleeding (if on anticoagulants).

Popular Combinations:

Cefazolin is often used in combination with metronidazole for surgical prophylaxis in colorectal procedures.

Precautions

• Careful inquiry about penicillin allergy before administration. Cross-reactivity can occur.
• Monitor for signs of superinfection, especially with prolonged use.
• Closely monitor renal function, especially in elderly patients and those with renal impairment.
• Monitor for signs and symptoms of Clostridium difficile infection.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Cefazolin?

A: See above for detailed dosing guidelines for adults, children, and special populations.

Q2: How is Cefazolin administered?

A: Cefazolin is administered intravenously (IV) or intramuscularly (IM).

Q3: What are the most common side effects of Cefazolin?

A: Common side effects include pain, redness, and swelling at the injection site, as well as nausea, vomiting, and diarrhea.

Q4: Is Cefazolin safe to use during pregnancy?

A: Cefazolin is generally considered safe to use during pregnancy (Pregnancy Category B); however, it should be used only if clearly needed. Consult with a specialist for guidance.

Q5: Can Cefazolin be used in patients with renal impairment?

A: Yes, but dosage adjustments are required based on creatinine clearance. Consult specific dosing guidelines for renal impairment.

Q6: What are the signs of a serious allergic reaction to Cefazolin?

A: Signs of a serious allergic reaction include hives, difficulty breathing or swallowing, and swelling of the face, lips, tongue, or throat. Seek immediate medical attention if these occur.

Q7: What should I do if a patient develops diarrhea while taking Cefazolin?

A: Diarrhea can be a sign of Clostridium difficile infection. Monitor the patient and inform the treating physician, who may order stool cultures.

Q8: What is the mechanism of action of Cefazolin?

A: Cefazolin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), which are essential for cross-linking peptidoglycans.

Q9: Can Cefazolin be used to treat MRSA infections?

A: Cefazolin is not effective against methicillin-resistant Staphylococcus aureus (MRSA).

Q10: How long should Cefazolin be administered for surgical prophylaxis?

A: Surgical prophylaxis typically involves a single dose given 30-60 minutes preoperatively, sometimes with an additional intraoperative dose during lengthy procedures. Postoperative dosing for up to 24 hours may be necessary. Specific guidelines vary by procedure. Consult surgical and infectious disease specialists for specific recommendations.

This information is current as of February 16, 2025, and is subject to change with updates in medical knowledge and practice. Always consult the latest medical references and guidelines.