D-arabinitol in the diagnosis of invasive candidiasis

University dissertation from Department of Clinical Science and Department of Laboratory Medicine, Medical Faculty, Lund University, Lund, Sweden

Abstract: Invasive candidiasis (IC) is a serious condition and timely diagnosis with early initiation of antifungal therapy is imerative for improving outcomes. Arabinitol is a sugar alcohol with two stereoisomers, D-arabinitol (DA) and L-arabintiol (LA). Several pathogenic Candida species produce DA in vitro and high DA levels have been detected in serum and urine in patients with IC. Renal dysfunction affects serum DA levels, serum and urine DA/LA or serum DA/creatinine are therefore measured to correct for kidney dysfunction. DA/LA ratio in urine was examined in neonatal infants in Lund, in patients with hematologic malignancies in Brisbane, Australia, and in HIV patients. Urine samples were collected on filter paper, which was found easy to apply and facilitated shipment of samples. DA/LA ratio is a reliable diagnostic method of IC in neonatal infants, all six infants with IC had elevated DA/LA ratios. Additionally five of eight infants receiving empirical antifungal treatment had elevated DA/LA ratios. The DA/LA ratio had lower sensitivity in hematology patients in Australia probably reflecting local changes in the epidemiology of candidemia with increased proportion of fungemias caused by C. krusei. HIV patients had normal DA/LA ratios and elevated ratios were not detected in five patients with Candida esophagitis. Clinical usage of DA/LA ratio in urine was studied iat the pediatric oncology unit (POU) and at the neonatal intensive care unit (NICU) in Lund. Screening of neutropenic children with cancer at the POU was found to decrease the number of IC but at the NICU the number of IC remained unchanged where the DA/LA ration was obtained only when IC was suspected. In vitro studies on DA production showed DA production in C. dubliniensis and C. krusei although C. krusei was found to produce low levels of DA. Neither in vitro nor in vivo DA production was detected in C. glabrata. DA production rate was highest in C. albicans and both intra and inter species variation of in vitro DA production was observed, which warrants further studies on the DA production rate and the sensitivity of DA/LA ratio in clinical use.