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 it does NOT cover MRSA, atypical bacteria, or most anaerobes. 1, 2, 3

Antimicrobial Spectrum

Gram-Positive Coverage

• Excellent activity against MSSA and methicillin-susceptible coagulase-negative staphylococci 1, 2
• Excellent activity against Streptococcus pneumoniae and Group A/B streptococci 1, 3
• No activity against MRSA—alternative agents like vancomycin or linezolid must be used if MRSA is suspected or confirmed 2

Gram-Negative Coverage

• Good activity against E. coli and Klebsiella species (4-8 fold more active than other first-generation cephalosporins) 4, 5
• Good activity against Proteus mirabilis 3, 5
• Moderate activity against other indole-positive Proteus species (only 60% susceptibility) 5
• No reliable coverage for Pseudomonas aeruginosa, Enterobacter, or other resistant gram-negatives 3

Standard Adult Dosing Regimens

Treatment Dosing (Every 8 Hours is Standard)

• Mild infections (susceptible gram-positive cocci): 250-500 mg IV every 8 hours 3
• Moderate to severe infections (including MSSA skin/soft tissue infections): 1 g IV every 8 hours 1, 3
• Severe, life-threatening infections (endocarditis, septicemia): 1-1.5 g IV every 6 hours 3
• Mastitis: 1 g IV every 8 hours for 7-10 days 2
• Uncomplicated UTI: 1 g IV every 12 hours 3
• Pneumococcal pneumonia: 500 mg IV every 12 hours 3

Surgical Prophylaxis Dosing

• Standard prophylaxis: 2 g IV administered 30-60 minutes prior to incision 6
• Redosing during surgery: 1 g IV if procedure duration exceeds 4 hours 6
• Cardiac surgery: 2 g IV plus 1 g in cardiopulmonary bypass priming solution, with 1 g redosing at 4 hours intraoperatively 6
• Neurosurgery/spine with implants: 2 g IV as single dose, with 1 g redosing if duration exceeds 4 hours 6
• Postoperative: 500 mg-1 g IV every 6-8 hours for 24 hours (may extend to 3-5 days for high-risk procedures like open-heart surgery or prosthetic arthroplasty) 3
• GBS prophylaxis in labor: 2 g IV initial dose, then 1 g IV every 8 hours until delivery 1

Pediatric Dosing

• Mild to moderate infections: 25-50 mg/kg/day divided every 8 hours (or every 6 hours for more frequent dosing) 3
• Severe infections: Up to 100 mg/kg/day divided every 8 hours 3
• Staphylococcal infections: 33 mg/kg/dose every 8 hours OR 150 mg/kg/day divided every 8 hours 1, 6
• Infective endocarditis: 100 mg/kg/day divided every 8 hours (maximum 12 g daily) 1, 6
• CNS infections: 100 mg/kg/day divided every 8 hours for adequate CNS penetration 6
• Not recommended in premature infants and neonates due to lack of safety data 3

Renal Dose Adjustments

Critical pitfall: Failure to adjust dosing in renal impairment can lead to neurotoxicity and seizures, particularly in elderly patients with pre-existing CNS conditions. 7

• CrCl ≥55 mL/min or SCr ≤1.5 mg/dL: Full dose, no adjustment needed 3
• CrCl 35-54 mL/min or SCr 1.6-3.0 mg/dL: Full dose but extend interval to at least every 8 hours 3
• CrCl 11-34 mL/min or SCr 3.1-4.5 mg/dL: Give 50% of usual dose every 12 hours (after loading dose) 3
• CrCl ≤10 mL/min or SCr ≥4.6 mg/dL: Give 50% of usual dose every 18-24 hours (after loading dose) 3
• Always give an appropriate loading dose based on infection severity before implementing reduced dosing 3

Pharmacokinetic Advantages

• Prolonged half-life of 2 hours (versus 1.4 hours for cephaloridine), allowing for less frequent dosing 4
• High serum protein binding (81%), which may reduce free drug activity in serum but provides sustained blood levels 4
• Excellent tissue penetration into breast tissue and other soft tissues 2
• Painless intramuscular injection compared to other cephalosporins 5
• Peak serum levels after 1 g IM: approximately 38.8 mcg/mL at 1 hour, with detectable levels at 8 hours 4

Critical Pitfalls and Caveats

Dosing Errors

• Do not confuse with ertapenem, which is dosed once daily—cefazolin requires every 8-hour dosing for most infections to maintain therapeutic levels 1
• Avoid once-daily dosing except in specific surgical prophylaxis contexts; this is not standard practice for treatment 1

Treatment Failures

• MRSA coverage: Cefazolin has zero activity against MRSA; use vancomycin (30 mg/kg/day in 2 divided doses) or linezolid (600 mg every 12 hours) instead 2
• Abscess drainage: Failure to drain abscesses will result in treatment failure regardless of appropriate antibiotic therapy 2
• Inadequate duration: Insufficient treatment duration may lead to recurrence, particularly in complicated infections 2

Neurotoxicity Risk

• High-dose cefazolin in renal dysfunction can cause encephalopathy and seizures due to drug accumulation and effects on neurotransmitter balance 7
• Risk factors: Older age, pre-existing CNS conditions (stroke, dementia), and renal failure significantly increase neurotoxicity risk 7
• Monitoring: Consider therapeutic drug monitoring in high-risk patients to prevent toxicity 7

Penicillin Allergy

• Cross-reactivity concerns exist but are often overstated; cefazolin can be safely used in many patients with penicillin allergy, though alternative agents (clindamycin 600-900 mg IV every 8 hours) should be considered for severe beta-lactam allergies 2, 8