Cefazolin Dosing for MSSA Bacteremia
For MSSA bacteremia, cefazolin should be dosed at 2 grams IV every 8 hours, which is the standard regimen supported by both FDA labeling and clinical guidelines for serious staphylococcal infections. 1
Standard Dosing Regimen
The recommended dose is cefazolin 2 grams IV every 8 hours (6 grams total daily dose) for bacteremia and other severe MSSA infections. 1
- The FDA label specifically lists "severe, life-threatening infections (e.g., endocarditis, septicemia)" as requiring 1 to 1.5 grams every 6 hours, though contemporary practice commonly uses 2 grams every 8 hours for bacteremia 1
- IDSA guidelines list cefazolin 1 gram every 8 hours as an alternative to nafcillin/oxacillin for MSSA skin and soft tissue infections, but bacteremia represents a more severe infection requiring higher dosing 2
- For severe infections in pediatric patients, total daily dosage may be increased to 100 mg/kg of body weight 1
Why Cefazolin is Preferred Over Antistaphylococcal Penicillins
Cefazolin demonstrates superior clinical outcomes compared to nafcillin/oxacillin for MSSA bacteremia, with lower mortality and fewer adverse effects. 3
- Meta-analysis shows cefazolin reduces mortality (OR 0.69,95% CI 0.58-0.82) and clinical failure (OR 0.56,95% CI 0.37-0.85) compared to antistaphylococcal penicillins 3
- Cefazolin has significantly lower rates of nephrotoxicity (OR 0.36) and hepatotoxicity (OR 0.12) compared to nafcillin/oxacillin 3
- Discontinuation due to adverse effects is substantially lower with cefazolin (OR 0.24,95% CI 0.12-0.48) 3
- Recent expert consensus supports using cefazolin for most patients with MSSA bacteremia given its favorable safety profile and large-scale observational data supporting efficacy 2
Renal Dose Adjustments
Dose reduction is required for patients with impaired renal function, applied after an initial loading dose. 1
- CrCl ≥55 mL/min: Full dose (2 grams every 8 hours) 1
- CrCl 35-54 mL/min: Full dose but extend interval to at least every 8 hours 1
- CrCl 11-34 mL/min: Half the usual dose (1 gram) every 12 hours 1
- CrCl ≤10 mL/min: Half the usual dose (1 gram) every 18-24 hours 1
- Hemodialysis patients: High-dose cefazolin (2-3 grams) administered only during each hemodialysis session has been shown effective and safe, with shorter length of stay and lower costs 4
Duration of Therapy
Treatment duration depends on the source and complications of bacteremia:
- Uncomplicated bacteremia (no endocarditis, no metastatic foci): minimum 14 days of IV therapy 2
- Complicated bacteremia with metastatic infection: 4-6 weeks typically required 2
- Once clinically improved with cleared bacteremia and no endocarditis/metastatic abscess, transition to oral therapy may be appropriate after 2-3 weeks 2
Important Clinical Considerations
The cefazolin inoculum effect (CzIE) remains controversial but should not preclude cefazolin use in most patients. 2
- Some MSSA isolates demonstrate increased MICs (≥16 mcg/mL) with higher inocula in vitro, but clinical significance remains uncertain 2
- Large observational studies support cefazolin efficacy despite theoretical CzIE concerns 2
- The superior safety profile of cefazolin compared to antistaphylococcal penicillins justifies its use as first-line therapy 2
For patients with reported penicillin allergy, allergy evaluation should be pursued to enable cefazolin use rather than defaulting to vancomycin. 5
- Vancomycin results in lower cure rates (67.3% vs 83.4% for cefazolin) and higher recurrence rates (14.8% vs 9.3%) 5
- Most patients with reported penicillin allergy are not truly allergic and can safely receive cefazolin after appropriate evaluation 5
- Skin testing when appropriate allows safe cefazolin administration with superior outcomes 5
Avoid ceftriaxone as an alternative to cefazolin for MSSA bacteremia. 6