Efficient Penetration of Terbinafine into Brain Abscesses in a Lung Transplant Recipient with Scedosporiosis: A Short Communication.

BACKGROUND

Scedosporium spp. typically infect the lungs and can disseminate to various tissues, including the central nervous system (CNS). Voriconazole and terbinafine are both used to treat scedosporiosis. While voriconazole has been reported to have good CNS permeability, the permeability of terbinafine in humans remains unclear.

METHODS

The authors describe a case of Scedosporium apiospermum infection with brain abscesses in a lung transplant recipient treated with voriconazole and terbinafine. Drug concentrations were measured in the biopsied brain abscess, the surrounding normal cerebrum, serum, and cerebrospinal fluid (CSF). Brain-to-serum and CSF-to-serum partition coefficients for each drug were calculated based on serum concentrations estimated at the time of abscess biopsy and lumbar puncture using population pharmacokinetic models.

RESULTS

Trough serum concentrations of voriconazole and terbinafine were 6.28 mcg/mL and 0.41 mcg/mL, respectively. Seven hours after administration, the concentrations in cerebrum were 5.65 mcg/mL and 0.85 mcg/mL, respectively, and those in brain abscess were 4.05 mcg/mL and 1.06 mcg/mL, respectively. The estimated brain-to-serum partition coefficients were 0.730 for voriconazole and 0.553 for terbinafine, indicating substantial penetration of both drugs into the infected tissue. The brain abscess size decreased in this case, suggesting a therapeutic antifungal effect of these agents. However, the measured CSF concentrations at 5 hours postdose were 2.69 mcg/mL for voriconazole and <0.002 mcg/mL for terbinafine. The CSF-to-serum partition coefficients were 0.365 for voriconazole and <5.64 × 10 -4 for terbinafine, indicating poor CSF permeability of terbinafine.

CONCLUSIONS

These findings suggest that terbinafine has the potential to treat fungal infections within the brain, but may be less effective for CSF infections. Further studies are warranted to clarify incorporation of these agents into CNS infection treatment strategies.