Serum D-arabinitol measured by automated quantitative enzymatic assay for detection and therapeutic monitoring of experimental disseminated candidiasis: correlation with tissue concentrations of Candida albicans

Abstract

In order to further understand serum D-arabinitol (DA) as a marker for the diagnosis of disseminated candidiasis and for monitoring response to antifungal therapy, we studied the serum levels of this Candida carbohydrate metabolite by rapid automated enzymatic assay in rabbits with experimental disseminated candidiasis. The enzymatic reaction steps were performed on a standard automated clinical chemistry analyser. As a correction for renal impairment, data were expressed as serum D-arabinitol/creatinine ratio (DA/Cr). Serum creatinine concentrations were determined from the same sample with the same instrument, thereby allowing rapid determination of the DA/Cr within one laboratory. The DA/Cr was determined in 321 samples from 132 rabbits. The mean serum DA/Cr in 31 normal non-infected rabbits was 1·51 ± 0·2 µm mg⁻¹ dl⁻¹. Among 84 rabbits with disseminated candidiasis and pre-terminal samples, there was a direct correlation between DA/Cr and tissue concentration of Candida albicans (r=0·80; P<0·001). A threshold of elevated DA/Cr (≥ 3·0 µm mg⁻¹ dl⁻¹) was evident in rabbits with a tissue concentration of C. albicans ≥ 3 × 10⁴ colony forming units (CFU) g⁻¹. Elevated DA/Cr was detected in 48 (89%) of 54 rabbits at a C. albicans tissue concentration of ≥ 3 × 10⁴ CFU g⁻¹ vs. one (3%) of 30 rabbits with <3 × 10⁴ CFU g⁻¹ (P<0·0001). Among all 101 rabbits with disseminated candidiasis, an elevated DA/Cr was detected at any point during infection in 60 (92%) of 65 rabbits having a C. albicans tissue concentration ≥ 3 × 10⁴ CFU g⁻¹ vs. 13 (36%) of 36 rabbits with <3 × 10⁴ CFU g⁻¹ (P<0·0001). The relationship between the tissue response to antifungal therapy and change in DA/Cr was then further analysed. Ten (91%) of 11 rabbits with a tissue-proven response to antifungal therapy (defined as ≥ 10²-fold reduction of CFU g⁻¹ in comparison to untreated controls) had a >50% reduction in elevated DA/Cr levels. By comparison, 10 (83%) of 12 treated rabbits with no response to therapy had persistently elevated DA/Cr levels (P<0·001). These findings provide an experimental basis for understanding the patterns of expression of serum DA in disseminated candidiasis and further indicate that serial DA/Cr measurements may be useful for diagnosis and therapeutic monitoring of disseminated candidiasis.