Cefazolin
1. Drug Name
Generic Name: Cefazolin
Brand Names: Ancef, Kefzol, and others.
2. Drug Classification
Class: Antibiotic, Cephalosporin
Subclass: First-Generation Cephalosporin
3. Mechanism of Action
Primary Action: Cefazolin is a first-generation cephalosporin antibiotic that works by inhibiting bacterial cell wall synthesis. It binds to and inactivates penicillin-binding proteins (PBPs), which are essential for the synthesis and maintenance of the bacterial cell wall. This causes a weakening of the cell wall and eventually leads to bacterial lysis and cell death, particularly in actively dividing bacteria.
Spectrum of Activity: Cefazolin is primarily effective against gram-positive bacteria such as Staphylococcus aureus (including methicillin-susceptible strains) and Streptococcus pneumoniae, as well as some gram-negative bacteria like Escherichia coli and Klebsiella pneumoniae. It is generally not effective against more resistant gram-negative organisms or enterococci.
Resistance: Some resistance may occur due to beta-lactamase production, but cefazolin is relatively resistant to some beta-lactamases compared to other cephalosporins. However, it is ineffective against MRSA (methicillin-resistant Staphylococcus aureus) and other multi-drug resistant organisms.
4. Pharmacokinetics
Absorption: Cefazolin is not absorbed orally and must be administered parenterally (usually IV or IM).
Distribution: It is widely distributed in body fluids and tissues, including the lungs, liver, kidneys, and bones. It also penetrates the cerebrospinal fluid (CSF) to a lesser degree, especially if the meninges are inflamed.
Metabolism: Cefazolin is minimally metabolized in the liver and is excreted largely unchanged in the urine.
Excretion: The drug is primarily excreted via the kidneys. Its half-life is approximately 1.8–2.5 hours in patients with normal renal function, allowing for dosing every 8–12 hours.
Special Considerations: Dose adjustments are required in patients with renal dysfunction to avoid drug accumulation, as renal clearance is the primary route of elimination.
5. Indications
Primary Indications:
Surgical Prophylaxis: Cefazolin is commonly used for prophylaxis in surgeries to prevent infection, especially in clean and clean-contaminated procedures.
Infections due to Gram-Positive Organisms:
Skin and soft tissue infections (e.g., cellulitis, wound infections).
Osteomyelitis.
Respiratory tract infections (e.g., pneumonia).
Urinary tract infections (e.g., cystitis, pyelonephritis).
Endocarditis: It may be used for prophylaxis and treatment in certain cases.
Off-label Uses:
Biliary Tract Infections: Used in combination with other agents for complicated infections.
Empiric Therapy for Sepsis: Particularly in patients with suspected gram-positive infections.
Specific Populations: Cefazolin is frequently used in both pediatric and adult patients for skin and soft tissue infections and surgical prophylaxis.
6. Dosage and Administration
Adult Dosing:
Infections: The typical adult dose for infections is 1–2 grams IV/IM every 8 hours. Severe infections may require doses up to 12 grams per day, divided every 6–8 hours.
Surgical Prophylaxis: 1–2 grams IV given 30–60 minutes before the start of surgery.
Pediatric Dosing:
Infections: 25–50 mg/kg IV/IM every 8 hours, with a maximum daily dose of 12 grams.
Surgical Prophylaxis: 20 mg/kg IV given 30–60 minutes before surgery.
Renal/Hepatic Adjustments: In patients with renal insufficiency (CrCl < 30 mL/min), the dosing interval should be extended to every 12 hours or longer, depending on the degree of impairment.
Route of Administration: Cefazolin is administered via IV or IM injection. The IM injection should be administered into a large muscle mass to minimize pain and irritation at the injection site.
7. Contraindications
Absolute Contraindications:
Known hypersensitivity to cefazolin, cephalosporins, or any of the excipients.
Severe allergic reactions to penicillins or other beta-lactam antibiotics, as there may be cross-sensitivity.
Relative Contraindications:
Renal Impairment: Care should be taken in patients with renal dysfunction, as dose adjustments are necessary to avoid accumulation of the drug.
Pregnancy: Cefazolin is generally considered safe during pregnancy (Category B), but it should only be used when the benefits outweigh the risks.
8. Warnings and Precautions
Hypersensitivity Reactions: Severe allergic reactions, including anaphylaxis, can occur. Patients with a history of penicillin allergy should be monitored closely, as cross-reactivity with cephalosporins can occur (although the risk is lower than with other cephalosporins).
Clostridium difficile-associated Diarrhea (CDAD): As with other antibiotics, cefazolin may disrupt normal gut flora, increasing the risk of CDAD. Serious cases can lead to colitis.
Renal Dysfunction: Cefazolin is primarily eliminated via the kidneys. In patients with renal impairment, dose adjustments and monitoring of renal function are necessary.
Biliary Sludging: Cefazolin may cause biliary sludge in some patients, which is reversible upon discontinuation of therapy.
9. Adverse Effects
Common Adverse Effects (≥10%):
Pain at the injection site (for IM/IV administration).
Diarrhea.
Rash.
Nausea and vomiting.
Less Common but Clinically Significant:
Allergic Reactions: Urticaria, anaphylaxis, and other hypersensitivity reactions.
Hematologic: Thrombocytopenia, eosinophilia, leukopenia.
Gastrointestinal: Pseudomembranous colitis, abdominal pain.
Renal: Elevated serum creatinine, interstitial nephritis (rare).
Serious Adverse Reactions:
Severe allergic reactions such as anaphylaxis or Stevens-Johnson syndrome.
Hemolytic anemia.
Seizures (rare, with high doses or renal failure).
10. Drug Interactions
Major Drug Interactions:
Probenecid: Probenecid may decrease the renal clearance of cefazolin, leading to increased serum levels and potential toxicity.
Anticoagulants (e.g., Warfarin): Cefazolin may enhance the anticoagulant effect of warfarin, increasing the risk of bleeding. Monitoring of INR is recommended when used together.
Aminoglycosides (e.g., Gentamicin): When combined with aminoglycosides, cefazolin can cause an additive effect against gram-negative infections, but there is also an increased risk of nephrotoxicity.
Food-Drug Interactions: No significant food-drug interactions are known with cefazolin, though it should be given parenterally for optimal absorption.
Lab Test Interference: Cefazolin may cause false-positive results in tests for urine glucose (non-reducing sugar method) and the Coombs test.
11. Clinical Pharmacology
Pharmacodynamics: Cefazolin is bactericidal due to its inhibition of bacterial cell wall synthesis. Its activity is concentration-dependent, meaning higher serum concentrations are more effective at killing bacteria.
Additional Effects: Although primarily effective against gram-positive organisms, cefazolin’s broad spectrum includes some important gram-negative pathogens, making it useful in treating a range of community-acquired infections.
12. Special Populations
Pregnancy: Category B – Cefazolin has not shown evidence of harm to the fetus in animal studies and is considered safe during pregnancy for treating infections when clinically indicated.
Lactation: Cefazolin is excreted into breast milk in low amounts. It is generally considered safe for use during breastfeeding, but close monitoring of the infant is recommended.
Pediatrics: Cefazolin is commonly used in pediatric patients, especially for infections like skin infections and surgical prophylaxis. It is safe but should be dosed according to weight.
Renal/Hepatic Dysfunction: Dosage adjustments are required in patients with renal failure (CrCl <30 mL/min). Hepatic adjustments are generally not necessary unless severe hepatic dysfunction is present.
13. Therapeutic Uses
First-Line Indications:
Surgical prophylaxis, especially in procedures involving skin and soft tissue infections.
Infections caused by gram-positive cocci (e.g., skin infections, urinary tract infections, pneumonia).
Combination Therapy: May be used in combination with other antibiotics for polymicrobial infections (e.g., with metronidazole for intra-abdominal infections).
14. Monitoring and Follow-Up
Lab Tests: Serum creatinine and blood urea nitrogen (BUN) should be monitored in patients with renal dysfunction. Liver function tests may also be monitored in long-term therapy.
Symptom Monitoring: Observe for any allergic reactions, gastrointestinal symptoms, or signs of nephrotoxicity.
Toxicity Monitoring: Monitor for any signs of bleeding or hematologic abnormalities if used with anticoagulants.
15. Overdose Management
Symptoms of Overdose: Overdose can lead to confusion, seizures, or gastrointestinal distress (nausea, vomiting).
Treatment Protocols: No specific antidote exists for cefazolin overdose. Symptomatic treatment is recommended, including gastric lavage and activated charcoal if the overdose is recent.
Supportive Measures: In cases of overdose, renal function should be monitored, and hydration should be maintained.
16. Patient Counseling Information
Key Points to Discuss with Patients:
Complete the full course of therapy, even if you feel better before finishing the medication.
Inform your doctor if you have a history of allergies, especially to cephalosporins or penicillin.
Notify your healthcare provider if you experience any severe side effects, such as rash, difficulty breathing, or swelling.
Signs/Symptoms to Watch For:
Seek medical attention if you experience symptoms of a severe allergic reaction or gastrointestinal distress, such as diarrhea with blood or persistent abdominal pain.