What is the coverage and dosing regimen for Ancef (Cefazolin)?

Ancef (Cefazolin) Coverage and Dosing

Ancef (cefazolin) is a first-generation cephalosporin that provides excellent coverage against methicillin-susceptible Staphylococcus aureus (MSSA), streptococci including Streptococcus pneumoniae, and many gram-negative organisms including Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, but lacks activity against MRSA, enterococci, and most anaerobes. 1, 2

Antimicrobial Spectrum

Gram-Positive Coverage

• Highly effective against MSSA - this is a primary indication for cefazolin 1, 3
• Excellent activity against Streptococcus pneumoniae and Group A/B streptococci 1, 2
• Does NOT cover MRSA - alternative agents like vancomycin or linezolid must be used if MRSA is suspected 3
• Does NOT cover enterococci 2

Gram-Negative Coverage

• Good activity against E. coli and Klebsiella species (4-8 fold more active than other first-generation cephalosporins) 4, 5
• Covers Proteus mirabilis effectively 5, 6
• Limited activity against indole-positive Proteus species 5
• Does NOT cover Pseudomonas aeruginosa or other non-fermenting gram-negatives 2

Anaerobic Coverage

• Minimal to no anaerobic coverage - not appropriate for infections requiring anaerobic coverage 2

Standard Dosing Regimens

Adult Dosing for Infections

For MSSA skin and soft tissue infections: 1 gram IV every 8 hours 1, 3

For moderate to severe infections: 500 mg to 1 gram IV every 6-8 hours 2

For severe, life-threatening infections (endocarditis, septicemia): 1-1.5 grams IV every 6 hours 2

For mastitis: 1 gram IV every 8 hours for 7-10 days (increase to 2 grams every 8 hours for severe infections) 3

For mild infections from susceptible gram-positive cocci: 250-500 mg IV every 8 hours 2

For uncomplicated UTI: 1 gram IV every 12 hours 2

For pneumococcal pneumonia: 500 mg IV every 12 hours 2

Surgical Prophylaxis Dosing

Standard surgical prophylaxis: 2 grams IV administered 30-60 minutes prior to incision, with redosing of 1 gram if procedure duration exceeds 4 hours 7

For cardiac surgery: 2 grams IV plus 1 gram in cardiopulmonary bypass priming solution, with redosing of 1 gram at the 4th hour intraoperatively 7

For neurosurgery/spine surgery with implants: 2 grams IV as single dose, with redosing of 1 gram if duration exceeds 4 hours 7

For urologic procedures: 1 gram IV every 8 hours 7

Postoperative prophylaxis: 500 mg to 1 gram IV every 6-8 hours for 24 hours postoperatively (may extend to 3-5 days for high-risk procedures like open-heart surgery or prosthetic arthroplasty) 2

Pediatric Dosing

For mild to moderate infections: 25-50 mg/kg/day divided every 8 hours (or every 6 hours) 2

For severe infections: Up to 100 mg/kg/day divided every 8 hours 2

For staphylococcal infections: 33 mg/kg/dose IV every 8 hours (or 150 mg/kg/day divided every 8 hours) 1, 7, 3

For infective endocarditis: 100 mg/kg/day IV divided every 8 hours (maximum 12 grams daily) 1, 7

For CNS infections: 100 mg/kg/day divided every 8 hours to ensure adequate CNS penetration 7

For GBS prophylaxis in neonates (maternal dosing): 2 grams IV initial dose, then 1 gram IV every 8 hours until delivery 1

Safety note: Not recommended for premature infants and neonates due to lack of established safety data 2

Renal Dose Adjustments

Critical consideration: Failure to adjust dosing in renal impairment can lead to drug accumulation, neurotoxicity, and seizures 8

CrCl ≥55 mL/min or SCr ≤1.5 mg/dL: Full dose with no adjustment 2

CrCl 35-54 mL/min or SCr 1.6-3.0 mg/dL: Full dose but extend interval to at least every 8 hours 2

CrCl 11-34 mL/min or SCr 3.1-4.5 mg/dL: Give 1/2 usual dose every 12 hours (after loading dose) 2

CrCl ≤10 mL/min or SCr ≥4.6 mg/dL: Give 1/2 usual dose every 18-24 hours (after loading dose) 2

Pharmacokinetic Advantages

• Prolonged half-life: 2 hours (versus 1.4 hours for cephaloridine), allowing for less frequent dosing 4
• High serum levels: Achieves peak concentrations of 38.8 mcg/mL after 1 gram IM, with detectable levels at 8 hours 4, 6
• Good tissue penetration: Effective penetration into breast tissue and other soft tissues 3, 6
• High protein binding: 81% protein-bound, which may reduce free drug activity in serum but contributes to sustained levels 4
• Painless IM administration: Unlike other cephalosporins, cefazolin causes minimal pain with intramuscular injection 5, 6

Critical Pitfalls and Caveats

Dosing Errors

• Never confuse cefazolin with ertapenem - ertapenem is dosed once daily, while cefazolin requires every 6-8 hour dosing for most infections 1
• Do not use once-daily dosing except in specific surgical prophylaxis contexts - this leads to subtherapeutic trough levels 1
• Always adjust for renal dysfunction - a case report documented fatal seizures from excessive dosing (2 grams every 4 hours instead of every 12 hours) in a patient with renal impairment 8

Coverage Limitations

• Failure to cover MRSA will result in treatment failure - if MRSA is suspected or confirmed, switch to vancomycin or linezolid 3
• Inadequate for abscess without drainage - antibiotics alone will fail if surgical drainage is not performed 3
• Not effective for anaerobic infections - add metronidazole or use alternative agents for polymicrobial infections 2

Monitoring Requirements

• Clinical response should occur within 48-72 hours - if no improvement, obtain cultures, broaden coverage, or evaluate for complications like abscess formation 3
• Monitor renal function especially in elderly patients, those with pre-existing CNS conditions, or baseline renal impairment, as these factors potentiate neurotoxicity risk 8

Penicillin Allergy Considerations

• Cefazolin can be safely used in most patients with penicillin allergy, though cross-reactivity concerns have historically led to use of less effective alternatives 9
• For severe beta-lactam allergy, use vancomycin (30 mg/kg/day in 2 divided doses) or clindamycin (600-900 mg IV every 8 hours) as alternatives 3