Relationship between intracranial hypertension and antifungal agent levels in the CSF of patients with cryptococcal meningitis

Background. Intracranial hypertension in cryptococcal meningoencephalitis may affect efficacy of antifungal agents. The aim of this study is to correlate the intracranial pressure (IP) with the concentrations of antifungal agents in the cerebrospinal fluid (CSF) of patients with cryptococcal meningitis admitted at Hospital de Clínicas de Porto Alegre (HCPA), a tertiary-care hospital in Brazil. Methods. A prospective cohort study was done from June 2014 to June 2015. CSF samples from patients with cryptococcal meningitis were collected at least 3 times during their follow-up: the first was taken on the first day of admission (D1), the second was taken on day 7 (D7) and the third was taken on day 14 (D14) after admission at HCPA. The intracranial pressure was measured by a spinal manometry during the lumbar punctures; CSF samples were sent to assess the antifungal agents levels of amphotericin B and fluconazole, which were the antifungal agents routinely used in the treatment of cryptococcal meningitis in our institution. Considering 5-flucytosine is not available in our institution, we could not assess the CSF levels for this specific antifungal agent. CSF levels were measured by high performance liquid chromatography as previously described. Results. A total of 15 patients with cryptococcal meningitis were included in the study. Among them, 2 patients (13,3%) had C. gattii and 13 patients (86,7%) had C. neoformans isolated from the CSF. The major underlying condition was HIV (66,6%), followed by solid organ transplant (26,6%) and no underlying condition (6,8%). The table contains the average concentrations of fluconazole (FCZ), amphotericin B (AMB) and intracranial pressure (IP). Average concentrations of drugs and intracranial pressure and the Standard Deviation (SD) of patients with cryptococcal meningitis on each day of follow-up Conclusion. Our study suggests that the levels of fluconazole seem to decrease with elevated intracranial pressure. Levels of Amphotericin B did not change significantly with elevated intracranial pressure. Further studies are necessary to evaluate the role of intracranial hypertension on the therapeutic efficacy of these agents. Disclosures. L. Goldani, GSK: Investigator, Research support