In this episode, I’ll discuss recommendations on the dose of cefazolin for a CNS infection.
When a CNS infection such as meningitis, ventriculitis, or a brain abscess is due to methicillin susceptible staph aureus, an antistaphylococcal penicillin such as nafcillin has been considered the first-line therapy. With the long duration of therapy needed for CNS infections, adverse events like elevated serum transaminases, neutropenia, and interstitial nephritis can frequently complicate therapy. In addition, nafcillin requires administration every 4 hours which adds to the burden of care.
Cefazolin is thought of as second-line for MSSA CNS infections, even though it does not need q4h dosing and has a more favorable adverse event profile when compared to nafcillin. A group of authors recently published a narrative review in the journal Pharmacotherapy that evaluated available clinical and pharmacokinetic/pharmacodynamic data for cefazolin use in CNS infections. Additionally, the authors produced a recommendation for cefazolin use.
Some of the key points made by the authors are:
Despite lower proportional blood-to-CSF penetration (ie., “percent penetration”), emerging data in humans has shown that cefazolin achieves therapeutic concentrations within the CSF.
… longstanding dogma that cefazolin does not reach the CNS in sufficient concentrations has limited research efforts.
One potential barrier to the widespread adoption of cefazolin for treatment of CNS infections is concern regarding the cefazolin inoculum effect (CIE) for MSSA… However, data suggests that cefazolin is an effective treatment option for infective endocarditis, further suggesting that the inoculum effect is solely an in vitro phenomenon.
When evaluating the rate of adverse effects for nafcillin vs cefazolin, the authors highlight an article of patients with MSSA bacteremia that found significantly less rates of nephrotoxicity and allergic reaction with cefazolin and a trend towards lower rates of hepatotoxicity.
The authors finish by saying that cefazolin is likely a safe and effective alternative to nafcillin for a variety of CNS infections due to MSSA. They recommend that if cefazolin is used for a CNS infection, doses higher than 2 grams IV every 8 hours need to be used to ensure adequate concentrations in the CSF. They suggest either 2 grams IV every 6 hours or a continuous infusion of 8 to 10 grams daily. These dosing recommendations assume normal renal function, and no recommendations are made for patients with altered renal function other than the consideration of therapeutic monitoring of cefazolin levels. Unfortunately the ability to do so without using a send-out laboratory is not widespread among hospitals.
The conclusion of the article is:
Although more research is needed to directly compare cefazolin to antistaphylococcal penicillins for CNS infections, current data support that dose-optimized cefazolin may be a reasonable and potentially superior alternative therapy.
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