Reproducibility of CSF quantitative culture methods for estimating rate of clearance in XXXX .

@entity1 @entity1330 @entity791 @entity693
Quantitative cerebrospinal fluid (CSF) cultures provide a measure of disease severity in @entity1330 . The fungal clearance rate by quantitative cultures has become a primary endpoint for phase II clinical trials. This study determined the inter-assay accuracy of three different quantitative culture methodologies. Among 91 @entity1 with @entity693 in Kampala, Uganda, during August-November 2013, 305 CSF samples were prospectively collected from @entity1 at multiple time points during treatment. Samples were simultaneously cultured by three methods: (1) St. George's 100   mcl input volume of CSF with five 1:10 serial dilutions, (2) @entity791 Clinical Trials Group (ACTG) method using 1000, 100, 10   mcl input volumes, and two 1:100 dilutions with 100 and 10   mcl input volume per dilution on seven agar plates; and (3) 10   mcl calibrated loop of undiluted and 1:100 diluted CSF (loop). Quantitative culture values did not statistically differ between St. George-ACTG methods (P= .09) but did for St. George-10   mcl loop (P< .001). Repeated measures pairwise correlation between any of the methods was high (r>= 0.88). For detecting sterility, the ACTG-method had the highest negative predictive value of 97% (91%  St. George, 60% loop), but the ACTG-method had occasional (   10%) difficulties in quantification due to colony clumping. For CSF clearance rate, St. George-ACTG methods did not differ overall (mean -0.05      0.07 log10CFU/ml/day;P= .14) on a group level; however, individual-level clearance varied. The St. George and ACTG quantitative CSF culture methods produced comparable but not identical results. Quantitative cultures can inform treatment management strategies.
