Analytical validation: Comparison of two laboratory-based methods for CSF quantitative cryptococcal cultures

Quantitative cryptococcal culture of the cerebrospinal fluid (CSF) is commonly used in cryptococcal meningitis research. We assessed the 'marble method' to evenly spread CSF onto two Sabouraud dextrose agar plates compared with the 'droplet method' using drops of CSF evenly placed around two halves of one agar plate. We found high concordance between the two methods. The Bland-Altman plot showed that the droplet method differed from the marble method by an average of -0.044 log10 CFU/ml CSF, with 95% limits of agreement from -0.324 to 0.235, indicating a small bias in favor of the marble method (P < 0.001). The droplet method of quantitative cryptococcal culture had no clinical difference compared to the marble method.