From the Guidelines
Cefazolin IV once daily plus probenecid is not recommended as standard therapy for Staphylococcus aureus bacteremia. The preferred treatment for methicillin-sensitive S. aureus bacteremia is cefazolin or nafcillin/oxacillin administered multiple times daily (typically every 8 hours), not once daily with probenecid, as suggested by the 2015 ESC guidelines for the management of infective endocarditis 1. While probenecid can prolong the half-life of beta-lactam antibiotics by reducing renal clearance, this approach lacks robust clinical evidence for treating serious bloodstream infections.
Key Considerations
- S. aureus bacteremia requires consistent antibiotic levels above the minimum inhibitory concentration to effectively clear the infection and prevent complications like endocarditis or metastatic foci.
- Standard treatment typically involves 2 weeks of therapy for uncomplicated bacteremia and 4-6 weeks for complicated cases (endocarditis, osteomyelitis, etc.), as outlined in the guidelines 1.
- Source control through removal of infected devices or drainage of abscesses is essential.
- Blood cultures should be repeated to confirm clearance of bacteremia.
- For methicillin-resistant S. aureus, vancomycin or daptomycin would be appropriate instead, with vancomycin dosing adjusted to achieve a trough level of ≥20 mg/L and an AUC/MIC ≥400 for MRSA infections 1.
Treatment Recommendations
- For methicillin-susceptible staphylococci, cefazolin 6 g/day or cefotaxime 6 g/day IV in 3 doses is recommended for penicillin-allergic patients with non-anaphylactic reactions 1.
- Vancomycin 30–60 mg/kg/day IV in 2–3 doses is recommended for penicillin-allergic patients or methicillin-resistant staphylococci, with monitoring of serum trough vancomycin levels 1.
- Daptomycin 10 mg/kg/day IV once daily is an alternative therapy for MRSA bacteremia, with monitoring of plasma CPK levels at least once a week 1.
Given the high mortality associated with S. aureus bacteremia (15-50%), treatment should follow established guidelines rather than alternative dosing strategies without strong supporting evidence 1.
From the Research
Efficacy of IV Cefazolin with Probenecid for Staphylococcus aureus Bacteremia
- The combination of intravenous (IV) cefazolin with probenecid for the treatment of Staphylococcus aureus bacteremia has been considered due to its potential benefits in improving outcomes 2, 3.
- Studies have shown that cefazolin offers several pharmacologic advantages over antistaphylococcal penicillins, including more convenient dosing regimens, which can lead to better compliance and reduced healthcare utilization 2.
- A systematic review and meta-analysis found that cefazolin was associated with a significant reduction in mortality and clinical failure compared to antistaphylococcal penicillins for the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia 3.
Once-Daily Treatment Options
- Once-daily treatment options for MSSA bacteremia have been explored, but current evidence does not support their use as the primary treatment option 4.
- However, some studies suggest that certain once-daily antibiotics, such as ceftriaxone and daptomycin, may be effective in specific cases, such as osteomyelitis or in patients who cannot tolerate first-line therapy 4, 5.
Combination Therapy
- Combination therapy with cefazolin and other antibiotics, such as probenecid, may enhance the efficacy of treatment for Staphylococcus aureus bacteremia 5.
- The use of cefazolin in combination with other antibiotics, such as daptomycin, has been shown to have synergistic effects and improve outcomes in refractory staphylococcal bacteremia 5.
Partial Oral Antibiotic Treatment
- Partial oral antibiotic treatment has been explored as an alternative to traditional intravenous antibiotic therapy for complicated Staphylococcus aureus bacteremia, particularly in people who inject drugs 6.
- Studies have found that transition to oral antibiotics after at least 10 days of effective intravenous antibiotic therapy can be a viable option for patients who have received initial intravenous therapy and have cleared their bacteremia 6.