From the Guidelines
Cefazolin can be used as an alternative to ceftriaxone for treating uncomplicated cellulitis, as it has excellent coverage against the most common causative organisms, including Streptococcus and Staphylococcus species 1. For uncomplicated cellulitis, cefazolin is typically given as 1-2 g IV every 8 hours. The duration of treatment is usually 5 days, but may be extended if the infection has not improved within this time period, as recommended by the Infectious Diseases Society of America 1. Cefazolin is often preferred for cellulitis because:
- It has a narrower spectrum than ceftriaxone, which helps reduce the risk of antibiotic resistance.
- It's generally less expensive than ceftriaxone. However, ceftriaxone may be preferred in certain situations:
- If there's suspicion of more resistant organisms
- In cases of severe infection or sepsis
- When once-daily dosing is needed (ceftriaxone is given once daily, while cefazolin requires multiple daily doses) Always consider local antibiotic resistance patterns and patient-specific factors when choosing an antibiotic. If methicillin-resistant Staphylococcus aureus (MRSA) is suspected, additional or alternative antibiotics, such as vancomycin, may be necessary, as recommended by the Infectious Diseases Society of America 1.
From the Research
Comparison of Cefazolin and Ceftriaxone for Treating Cellulitis
- Cefazolin can be used as an alternative to ceftriaxone for treating cellulitis, as shown in a study published in 2002, which found that a once-daily regimen of cefazolin plus probenecid was equivalent to a once-daily regimen of ceftriaxone plus oral placebo for the treatment of moderate-to-severe cellulitis in adults 2.
- Another study published in 1996 also found that a single daily administration of cefazolin with probenecid was equivalent in efficacy to a single daily administration of ceftriaxone for the outpatient treatment of skin and soft tissue infections, including cellulitis 3.
- A review of pharmacokinetic and clinical evidence published in 2004 found that once-daily cefazolin and probenecid was an effective regimen for the treatment of skin and soft tissue infections, including cellulitis 4.
- The efficacy of cefazolin compared to ceftriaxone was also evaluated in a study published in 1984, which found that clinical cure with or without surgery was achieved in 77% of patients treated with cefazolin and 81% of patients treated with ceftriaxone 5.
Pharmacokinetics and Tolerability
- A study published in 2025 found that subcutaneous administration of cefazolin was well tolerated and had a bioavailability of 74.8% compared to intravenous administration 6.
- The study also found that simulated subcutaneous doses of 3g twice daily had similar pharmacokinetic profiles to standard intravenous dosing of 2g three times daily 6.