Measurement of the D-arabinitol/L-arabinitol ratio in urine of neutropenic patients treated empirically with amphotericin B.

The aim of the present study was to evaluate the diagnostic significance of the D-arabinitol/L-arabinitol ratio in urine of neutropenic patients with suspected fungal infection. D-arabinitol/L-arabinitol ratios were determined in 373 serial urine samples of 104 patients with haematological malignancies receiving empirical amphotericin B treatment for suspected invasive fungal infection. Twenty-eight (8%) urine samples obtained from 17 (16%) patients were positive (ratio > or =4). Eight (47%) patients had positive urine samples at the initiation of empirical amphotericin B treatment and the rest from 7 to 30 days after empirical therapy was started. Several urine samples were positive in six patients. Only one of the five patients with candidemia had elevated D-arabinitol/L-arabinitol ratios (persistent Candida krusei fungaemia). Four patients with transient candidemia and seven patients with invasive mould infections were negative. Patients who died during the study period had significantly higher D-arabinitol/L-arabinitol ratios than patients who survived (P=0.0002). Pneumonia was the most common manifestation of infection (53% of patients with elevated D-arabinitol/L-arabinitol ratios) and was associated with an especially high mortality (67%). The present study shows that elevated urine D-arabinitol/L-arabinitol ratios are common in febrile, neutropenic patients. However, the urine arabinitol test did not detect transient candidemia at elevated levels during the course of infection. Furthermore, D-arabinitol/L-arabinitol ratios were often elevated in the late phase of infection only. This contests the use of this test in guiding the initiation of antifungal therapy. The detection of elevated arabinitol levels in neutropenic patients during empirical amphotericin B treatment is associated with poor prognosis.

Immune response in patients with persistent candiduria and occult candidemia.

PURPOSE: We evaluated the immunological response in patients with persistent candiduria with or without occult candidemia. MATERIALS AND METHODS: Levels of Thl (pro-inflammatory interleukin [IL]-1, IL-2 and tumor necrosis factor-alpha) and Th2 (anti-inflammatory IL-4 and IL-10) cytokines were measured in the sera of patients with persistent candiduria. Polymerase chain reaction assessment of the 158 base pair candidal actin gene was used to detect Candida albicans in blood to identify occult candidemia. RESULTS: During a 14-month period 66 hospitalized patients with a mean age of 63 years (range 44 to 80) with persistent candiduria were evaluated. Occult candidemia developed in 27 patients (41%) as evidenced by detection of candidal actin gene in the sera by polymerase chain reaction. Risk factors included antibiotics in 27 patients (100%), central venous catheter in 22 (81%), urinary catheter in 21 (78%), total parenteral nutrition in 18 (66%), diabetes mellitus in 16 (59%) and abdominal surgery in 14 (52%). A total of 17 age matched patients with a mean age of 59 years hospitalized for elective general or vascular surgical procedures with no clinical or laboratory evidence of urinary or hematogenous fungal or bacterial infection served as controls. Serum levels of Th2 cytokines were elevated in 18 of 39 patients with persistent candiduria alone, and in 22 of 27 patients with candiduria and occult candidemia compared to controls (p<0.002). Th1 cytokines were within normal limits or slightly decreased in all patients with persistent candiduria with or without candidemia. CONCLUSIONS: These observations indicate that an abnormal immune response develops in patients with persistent candiduria with or without candidemia.

Candiduria as an early marker of disseminated infection in critically ill surgical patients: the role of fluconazole therapy.

The significance of candiduria in critically ill patients remains unclear. It may represent harmless colonization or a potentially life-threatening infection. We analyzed 47 patients in the surgical intensive care unit (SICU) (trauma: 20, general surgery: 15, neurosurgery: 12) who had candiduria, defined by a colony count greater than 100,000/mL. Twenty-seven of these patients were studied retrospectively. Twenty were evaluated prospectively. All patients were receiving broad-spectrum antibiotics for bacterial infections. Retrospective group: ten patients (group A) did not develop disseminated candidiasis, whereas 17 patients (group B) did. Group B had higher APACHE II scores on admission (13.4 +/- 7.8) and at the time of candiduria (13.7 +/- 4.4) when compared with group A [admission: 5.0 +/- 4.6; candiduria: 6.7 +/- 3.6 (p < 0.02)]. In group B, disseminated candidiasis was not diagnosed and treated until 9.9 +/- 4.4 days after development of candiduria. Prospective group: twenty patients with candiduria were treated with systemic fluconazole (group C) at the time of candiduria. The APACHE II scores of group C on admission (12.8 +/- 3.9) and at the time of candiduria (10.5 +/- 4.0) were comparable with those of group B. No patient in Group C developed disseminated candidiasis. The septic mortality rates of groups A, B, and C were 0%, 53%, and 5%, respectively (p < 0.05-0.0001). In patients exhibiting ongoing sepsis and organ failure (high APACHE scores), candiduria may be an early indicator of systemic infection. Diagnosis of disseminated infection and its treatment may be delayed if conventional criteria for candidiasis (positive blood cultures, multiple site isolation) are awaited.(ABSTRACT TRUNCATED AT 250 WORDS)