What is the recommended dose and timing when transitioning from Rocephin (Ceftriaxone) to Ancef (Cefazolin)?

Transitioning from Rocephin to Ancef: Dose and Timing

When transitioning from ceftriaxone (Rocephin) to cefazolin (Ancef), administer cefazolin at standard dosing (1-2 grams IV every 8 hours for most infections) starting 12-24 hours after the last ceftriaxone dose, accounting for ceftriaxone's prolonged half-life of 5.8-8.7 hours. 1, 2

Understanding the Pharmacokinetic Rationale

The key to this transition lies in understanding ceftriaxone's unique pharmacokinetics:

• Ceftriaxone has an exceptionally long elimination half-life of 5.8-8.7 hours, which is substantially longer than most cephalosporins 2
• This extended half-life allows once-daily dosing and means therapeutic concentrations persist well beyond the dosing interval 1, 3
• Cefazolin, in contrast, requires dosing every 8 hours due to its shorter half-life 4

Recommended Transition Protocol

Timing the Switch

• Wait 12-24 hours after the last ceftriaxone dose before initiating cefazolin to avoid unnecessary overlap while ensuring continuous antimicrobial coverage 1, 2
• For patients receiving ceftriaxone once daily, the transition is straightforward: give the first cefazolin dose at the time the next ceftriaxone dose would have been due 3
• For patients receiving ceftriaxone twice daily (e.g., for meningitis at 2 grams every 12 hours), initiate cefazolin 12 hours after the last ceftriaxone dose 5

Cefazolin Dosing by Indication

For methicillin-susceptible staphylococcal endocarditis (native valve):

• Cefazolin 6 grams/day IV in 3 divided doses (2 grams every 8 hours) for 4-6 weeks 4
• This is explicitly recommended as an alternative for penicillin-allergic patients with non-anaphylactic reactions 4

For methicillin-susceptible staphylococcal infections (general):

• Cefazolin 100 mg/kg/day IV divided every 8 hours (maximum 12 grams daily) 4
• For adults, this typically translates to 1-2 grams every 8 hours depending on infection severity 4

For pediatric endocarditis:

• Cefazolin 100 mg/kg/day IV divided every 8 hours (maximum 12 grams daily) 4

Critical Considerations When Transitioning

Spectrum of Activity Differences

• Ceftriaxone has broader Gram-negative coverage than cefazolin, particularly against resistant Enterobacteriaceae 3
• Cefazolin has superior activity against methicillin-susceptible staphylococci compared to ceftriaxone 4
• Ensure the pathogen is susceptible to cefazolin before making the switch—this transition is most appropriate for confirmed methicillin-susceptible staphylococcal infections 4

When This Transition is Appropriate

This switch is most commonly made in the following scenarios:

• Confirmed methicillin-susceptible Staphylococcus aureus endocarditis where cefazolin is preferred for definitive therapy 4
• De-escalation from empiric broad-spectrum therapy (ceftriaxone) to targeted therapy (cefazolin) once susceptibilities are known 4
• Cost considerations when cefazolin's narrower spectrum is adequate for the identified pathogen 6

Common Pitfalls to Avoid

• Do not use cefazolin for CNS infections: Unlike ceftriaxone, which achieves excellent CSF penetration, cefazolin does not adequately penetrate the blood-brain barrier 5, 2
• Do not use cefazolin for Gram-negative infections: Cefazolin lacks the Gram-negative coverage of ceftriaxone and should not be used for Enterobacteriaceae or other Gram-negative pathogens 3
• Avoid in patients with anaphylactic penicillin allergy: While cefazolin is recommended for non-anaphylactic penicillin allergies, patients with true anaphylaxis should receive vancomycin instead 4
• Monitor for treatment failure: If switching empirically before culture results, ensure clinical improvement continues after the transition 6

Monitoring After Transition

• Assess clinical response within 48-72 hours of the switch to ensure continued improvement 6
• Monitor renal function as cefazolin requires dose adjustment in renal impairment (unlike ceftriaxone, which does not require adjustment until severe renal dysfunction) 1, 2
• For endocarditis, continue the full duration of therapy (4-6 weeks for native valve, ≥6 weeks for prosthetic valve) regardless of when the switch occurs 4