What is the treatment for Methicillin-Susceptible Staphylococcus aureus (MSSA) bacteremia with high-dose cefazolin (Ancef) 3 grams every 8 hours?

From the Guidelines

High-dose cefazolin at 3g every 8 hours is an appropriate and effective treatment option for MSSA bacteremia. This dosing regimen provides adequate coverage against MSSA and achieves sufficient drug concentrations in the bloodstream to effectively clear the infection. Cefazolin is preferred over nafcillin or oxacillin for MSSA infections because it has similar efficacy with less toxicity, fewer dosing requirements, and lower cost, as supported by the guidelines from the Infectious Diseases Society of America 1. The high-dose regimen (3g every 8 hours) is particularly important for serious infections like bacteremia to ensure adequate drug concentrations at the infection site and prevent treatment failure.

Key considerations for treatment include:

• Treatment duration for uncomplicated MSSA bacteremia is typically 2 weeks from the first negative blood culture, but may be extended to 4-6 weeks if there are complications such as endocarditis, osteomyelitis, or metastatic infections, as recommended by the European Society of Cardiology 1.
• Regular monitoring of blood cultures until clearance, along with clinical improvement assessment, is essential.
• Renal dose adjustment may be necessary for patients with kidney impairment, and monitoring for adverse effects such as rash, diarrhea, or Clostridioides difficile infection is recommended.
• The American Heart Association suggests that IE caused by staphylococci that are penicillin susceptible should be treated with antistaphylococcal β-lactam antibiotics rather than aqueous crystalline penicillin G because clinical laboratories are not able to detect penicillin susceptibility 1.

Overall, the choice of antibiotic and treatment duration should be individualized based on the patient's specific condition, the severity of the infection, and the presence of any complications or underlying health conditions.

From the FDA Drug Label

CLINICAL PHARMACOLOGY After intramuscular administration of cefazolin to normal volunteers, the mean serum concentrations were 37 mcg/mL at 1 hour and 3 mcg/mL at 8 hours following a 500 mg dose, and 64 mcg/mL at 1 hour and 7 mcg/mL at 8 hours following a 1 gram dose Studies have shown that following intravenous administration of cefazolin to normal volunteers, mean serum concentrations peaked at approximately 185 mcg/mL and were approximately 4 mcg/mL at 8 hours for a 1 gram dose. In vitro tests demonstrate that the bactericidal action of cephalosporins results from inhibition of cell wall synthesis Cefazolin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in INDICATIONS AND USAGE Gram-Positive Aerobes Staphylococcus aureus (including beta-lactamase-producing strains)

The dose of 3g every 8 hrs for MSSA bacteremia is not directly addressed in the provided drug label. However, based on the information provided, cefazolin has been shown to be active against Staphylococcus aureus, including beta-lactamase-producing strains.

• The serum concentrations of cefazolin after a 1 gram dose are approximately 185 mcg/mL at peak and 4 mcg/mL at 8 hours.
• The drug label does not provide specific dosing recommendations for MSSA bacteremia at a dose of 3g every 8 hrs. Given the lack of direct information, it is uncertain whether this dosing regimen would be effective for MSSA bacteremia 2.

From the Research

Treatment of MSSA Bacteremia

• The use of high-dose cefazolin (3g every 8 hours) for the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia is not directly addressed in the provided studies.
• However, studies have compared the effectiveness of cefazolin with other antibiotics, such as nafcillin or oxacillin, for the treatment of MSSA infections complicated by bacteremia 3.
• Cefazolin has been shown to have similar clinical efficacy and better tolerability compared to antistaphylococcal penicillins (ASPs) for the treatment of MSSA bacteremia 4.
• Aggressive cefazolin dosing may mitigate the role of cefazolin inoculum effect and improve clinical outcomes 4.

Dosage and Administration

• The optimal dosage and administration of cefazolin for MSSA bacteremia is not specified in the provided studies.
• However, it is mentioned that cefazolin offers more convenient dosing regimens compared to ASPs 4.
• Once-daily treatment options for MSSA bacteremia have been reviewed, but current evidence does not support their use 5.

Clinical Outcomes

• Studies have shown that cefazolin is associated with improved clinical outcomes, including reduced mortality and similar odds of recurrence, compared to nafcillin or oxacillin for MSSA infections complicated by bacteremia 3.
• The association between oxacillin MIC and acute treatment outcomes with cefazolin and ASPs has been evaluated, and no differences were found in the rate of primary outcome occurrence between patients with an oxacillin MIC ≥ 1 μg/mL and an MIC < 1 μg/mL 6.
• Patients with MSSA bacteremia and a reported penicillin allergy should have the allergy addressed for optimal treatment, and full allergy evaluation with skin testing seems to be preferred 7.