Title : Lack of association between YEASTONE antifungal susceptibility of cryptococcus meningitis cerebrospinal fluid isolates and risk factors for poor prognosis
Background: Cryptococcal meningitis (CM) is associated with high mortality. The relation between antifungal susceptibility and treatment outcomes is not well characterized. There is paucity of surveillance data of cerebrospinal fluid (CSF) isolates of cryptococcus investigated with YEASTONE colorimetric broth microdilution susceptibility testing.
Methods: This was a retrospective study of laboratory-confirmed CM patients at a single-center between 2010 and 2016. Antifungal susceptibility of CSF isolates was determined by YEASTONE colorimetric broth microdilution. Clinical parameters, CSF laboratory indices, and antifungal susceptibility results were analyzed to identify risk factors for mortality.
Results: There were 53 isolates. High rates of resistance to fluconazole and flucytosine were observed in this cohort. Voriconazole showed the lowest MIC (0.06 µg/mL) and lowest rate of resistance (3.8%). There was no significant correlation between antifungal susceptibility and mortality. On univariate analysis, hematological malignancy, concurrent cryptococcemia, high Sequential Organ Failure Assessment (SOFA) score, low Glasgow coma scale (GCS) score, low CSF glucose level, high CSF cryptococcal antigen titer, and high serum cryptococcal antigen burden were associated with mortality. On multivariate analysis, meningitis with concurrent cryptococcemia, GCS score, and high CSF cryptococcus burden, were independent predictors of poor prognosis.
Conclusion: Concomitant cryptococcemia, low CSF glucose level, high CSF and serum cryptococcus antigen burden were risk factors for mortality. CM patients with fluconazole MIC ≥64 µg/mL showed extremely high mortality. However, both early and late mortality rates were not significantly different between CM wild type and non-wild type species.
Audience take away:
It is an emerging critical issue about “Cryptococcus meningits”, which is a high mortality disease happened on not only immunocompromised but also immunocompetent hosts. Second, Cryptococcus fungemia is a difficult-to-treat issue because of high morbidity and mortality. Very few reports discussed about the using Thermo Scientific Sensititre YeastONE susceptibility testing to correlate with the treatment outcome of cryptococcus. Our study revealed the in vitro antifungal susceptibility test did not correlate treatment outcome very well. concomitant cryptococcemia, low CSF glucose level, high CSF and serum cryptococcus antigen burden were predictors for mortality. We think it is an important information for not only clinicians but also clinical microbiologist.