Lack of Association between YEASTONE Antifungal Susceptibility Tests and Clinical Outcomes of Cryptococcus Meningitis

Abstract

The relation between antifungal susceptibility and treatment outcomes is not well-characterized. There is paucity of surveillance data for cerebrospinal fluid (CSF) isolates of cryptococcus investigated with YEASTONE colorimetric broth microdilution susceptibility testing. A retrospective study of laboratory-confirmed cryptococcus meningitis (CM) patients was conducted. The antifungal susceptibility of CSF isolates was determined using YEASTONE colorimetric broth microdilution. Clinical parameters, CSF laboratory indices, and antifungal susceptibility results were analyzed to identify risk factors for mortality. High rates of resistance to fluconazole and flucytosine were observed in this cohort. Voriconazole had the lowest MIC (0.06 µg/mL) and lowest rate of resistance (3.8%). In a 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. In a multivariate analysis, meningitis with concurrent cryptococcemia, GCS score, and high CSF cryptococcus burden, were independent predictors of poor prognosis. Both early and late mortality rates were not significantly different between CM wild type and non-wild type species.

Temporal trends in antifungal susceptibility of Cryptococcus neoformans isolates from a reference laboratory in the United States, 2011–2021

“…Similar to our results, a study conducted in patients with cryptococcal meningitis reported a higher mortality in patients with AMB non‐WT (40%) compared with patients with AMB WT (22.8%) isolates receiving AMB‐containing regimens 40 . Another study in patients with cryptococcal meningitis demonstrated higher mortality in patients with cryptococcal isolates with elevated MICs for AMB and FLC, especially when patients had an isolate with FLC MIC of greater than 64 mg/L 41 . In contrast, other studies have shown no difference in outcomes.…”

“…40 Another study in patients with cryptococcal meningitis demonstrated higher mortality in patients with cryptococcal isolates with elevated MICs for AMB and FLC, especially when patients had an isolate with FLC MIC of greater than 64 mg/L. 41 In the treatment of severe forms of cryptococcosis, the relevance of an elevated MIC to a single antifungal agent may be diminished by the frequent utilisation of combination antifungal therapy.…”

Antifungal Resistance in Cryptococcal Infections

“…Mortality due to cryptococcosis among patients co-infected with HIV and treated with amphotericin B and fluconazole was not associated with MIC data, indicating low resistance rates from 0% to 5.8% for C. neoformans and C. gattii , respectively [ 60 , 101 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 ]. Therefore, in general, we need a better way to evaluate the in vitro correlation with clinical response to therapy [ 62 , 121 , 129 ].…”