Is Ceftriaxone (Ceftriaxone) effective for Methicillin-Sensitive Staphylococcus aureus (MSSA) bacteremia?

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Last updated: April 22, 2025View editorial policy

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From the Guidelines

Ceftriaxone is not the preferred treatment for methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia. The first-line treatment for MSSA bacteremia is an anti-staphylococcal penicillin such as nafcillin or oxacillin, or cefazolin if the patient has a non-anaphylactic penicillin allergy, as recommended by evidence-based and guideline-supported practices 1.

Key Points to Consider

  • Use of cefazolin or an anti-staphylococcal penicillin (ASP) for MSSA is the recommended approach 1
  • Ceftriaxone has higher MICs (minimum inhibitory concentrations) and poorer clinical outcomes compared to the recommended first-line agents
  • The pharmacokinetic properties of ceftriaxone, including protein binding and elimination half-life, make it less effective at maintaining concentrations above the MIC for MSSA throughout the dosing interval
  • If first-line agents cannot be used due to severe allergies or other contraindications, vancomycin or daptomycin would be more appropriate alternatives than ceftriaxone

Treatment Duration

The treatment duration for MSSA bacteremia should be 4–6 weeks for bacteremia with high-risk features, as suggested by the guidelines 1.

Clinical Decision Making

In clinical practice, the choice of antibiotic should be guided by the susceptibility pattern of the isolate, the severity of the infection, and the patient's underlying health status. The use of ceftriaxone for MSSA bacteremia is not supported by the most recent and highest quality evidence 1.

From the FDA Drug Label

Ceftriaxone for Injection is indicated for the treatment of the following infections when caused by susceptible organisms: ... BACTERIAL SEPTICEMIA Caused by Staphylococcus aureus, ...

Ceftriaxone can be used for the treatment of MSSA bacteremia as it is indicated for the treatment of bacterial septicemia caused by Staphylococcus aureus, which includes MSSA (Methicillin-Susceptible Staphylococcus aureus) 2.

From the Research

Ceftriaxone for MSSA Bacteremia

  • Ceftriaxone has been studied as a potential treatment for methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, with some studies suggesting it may be an effective alternative to traditional therapies 3, 4, 5.
  • A case series published in 2017 found that ceftriaxone was effective in treating MSSA bacteremia, with clinical cure observed in 7 out of 15 patients and microbiological cure observed in all patients 3.
  • A retrospective study published in 2022 compared ceftriaxone to cefazolin for the treatment of MSSA bacteremia and found no difference in clinical cure rates between the two groups 4.
  • Another retrospective study published in 2014 found that ceftriaxone was associated with similar clinical and microbiological outcomes compared to standard of care therapy for MSSA bacteremia 5.
  • However, a more recent study published in 2023 found that definitive treatment with ceftriaxone was associated with a higher risk of treatment failure within 90 days compared to cefazolin or antistaphylococcal penicillins 6.
  • The use of ceftriaxone for MSSA bacteremia is still a topic of debate, with some studies suggesting it may be a viable alternative to traditional therapies, while others raise concerns about its efficacy 7, 6.

Key Findings

  • Ceftriaxone may be an effective alternative to traditional therapies for MSSA bacteremia, but more research is needed to confirm its efficacy 3, 4, 5.
  • Ceftriaxone has been associated with similar clinical and microbiological outcomes compared to standard of care therapy for MSSA bacteremia 5.
  • However, ceftriaxone may be associated with a higher risk of treatment failure within 90 days compared to cefazolin or antistaphylococcal penicillins 6.
  • The use of ceftriaxone for MSSA bacteremia should be approached with caution, taking into account the potential risks and benefits, as well as the individual patient's clinical situation 7, 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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