Do you choose an antibiotic with CSF penetration, such as nafcillin over cefazolin, in the setting of MSSA endocarditis with septic emboli to the brain (assuming no concomitant meningitis or brain abscess)?

The prevailing theory that cefazolin has poor CNS penetration is really based on 3-4 studies performed in the 1980s (Nolan & Ulmer, PMID 7365282) where they were extrapolating data from studies looking at cephalothin concentration in CSF. Another study looking specifically at cefazolin concentration in the body (Thys et al., PMID 984782) only looked at 4 patients who had no demonstratable cefazolin concentrating in the CSF space, although the same study could not find demonstratable cefazolin in...

I have started using cefazolin in such instances, guided by existing data indicating reasonable CNS penetration. I will administer a higher dosage of 2 gm IV every 6 hours. I have observed a case where septic emboli progressed to an MSSA brain abscess despite treatment with cefazolin 2 gm IV every 8 hours. Consequently, I remain cautious about using cefazolin for more severe CNS infections.

Yes. Ancef is better tolerated than nafcillin.