Diagnosis and therapeutic monitoring of invasive candidiasis by rapid enzymatic detection of serum D-arabinitol.
BACKGROUND
Using a rapid automated enzymatic assay, we prospectively investigated serum D-arabinitol (DA), a biochemical marker of invasive candidiasis, in a large population of high-risk patients to determine its potential diagnostic, therapeutic, and prognostic significance in invasive candidiasis.


METHODS
A total of 3,223 serum samples were collected from 274 patients with cancer. Serum DA concentrations were determined in coded serum samples analyzed by rapid enzymatic assay. Creatinine also was analyzed in the same system to determine a serum DA and creatinine ratio (DA/Cr). The sensitivity, specificity, correlation with therapeutic response, and prognostic significance were analyzed for all patient study groups.


RESULTS
A DA/Cr of > or = 4.0 mumol/L per mg/dL was detected in 31 (74%) of all 42 cases of fungemia and 25 (83%) of the 30 cases of the subset of persistent fungemia. Elevated DA/Cr was detected in 4 (40%) of 10 patients with tissue-proven, deeply invasive candidiasis and negative blood cultures (eg, hepatosplenic candidiasis or localized abscess) and 7 (44%) of 16 cases of deep mucosal candidiasis (eg, esophageal candidiasis). Elevated serial DA/Cr levels also were detected in persistently febrile and granulocytopenic patients requiring empirical amphotericin B. Among 26 assessable cases of fungemia, abnormally elevated DA/Cr values were detected in 14 (54%) before, 10 (38%) after, and 2 (8%) simultaneously with the first microbiologic report of fungemia. The trends of serial DA/Cr values correlated with therapeutic response in 29 (85%) of 34 patients with assessable cases of fungemia, decreasing in 8 (89%) of 9 patients with clearance of fungemia and increasing in 21 (84%) of 25 patients with persistence of fungemia. Among the 34 assessable patients with fungemia, mortality was directly related to the trend of serial DA/Cr determinations over time: 71% among fungemic patients who had persistently elevated or increasing DA/Cr, and 18% among the fungemic patients who had resolving DA/Cr or never had elevated DA/Cr (P < 0.01).


CONCLUSIONS
Rapid enzymatic detection of DA in serially collected serum samples from high-risk cancer patients permitted detection of invasive candidiasis, early recognition of fungemia, and therapeutic monitoring in DA-positive cases. Serially collected serum DA determinations complement blood cultures for improving detection and monitoring therapeutic response in patients at risk for invasive candidiasis.
Walsh
T J
TJ
Infectious Diseases Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Merz
W G
WG
Lee
J W
JW
Schaufele
R
R
Sein
T
T
Whitcomb
P O
PO
Ruddel
M
M
Burns
W
W
Wingard
J R
JR
Switchenko
A C
AC
D002177:Candidiasis / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000628:therapy; D016022:Case-Control Studies; D004796:Clinical Enzyme Tests; D003404:Creatinine / Q000097:blood; D006801:Humans; D009369:Neoplasms / Q000150:complications; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D016037:Single-Blind Method; D013402:Sugar Alcohols / Q000097:blood*; D013997:Time Factors; D016896:Treatment Outcome
D013402:Sugar Alcohols; D003404:Creatinine; C014999:arabitol