Background/Aims: Fungal infection, particulary with Candida spp., has been identified as an important cause of morbidity and mortality in patients with acute liver failure. Fungal colonisation of superficial mucosal sites usually precedes invasive infection. We investigated colonisation patterns in patients with acute liver disease receiving fluconazole therapy in order to investigate the possibility of emergence of fluconazole-resistant C. albicans or other species. Methods: During a 6-month study period, we studied all patients referred to our unit with acute liver disease by twice-weekly sampling and mycological analysis of specimens from superficial mucosal and other sites as appropriate. Patients were treated with prophylactic antimicrobials including 100 mg fluconazole daily in accordance with our usual protocol. Results: Twenty-two patients with acute liver disease were studied, eight of whom underwent transplantation. Eighteen patients were colonised by fungi at presentation, and six developed secondary colonisation during fluconazole therapy. Four of these patients (all transplanted) became colonised by resistant species; one of these was Aspergillus fumigatus, which led to death. There were no other invasive fungal infections identified during the study period, and no fluconazole-resistant C. albicans were identified. Conclusions: Resistance to fluconazole is unlikely to develop in C. albicans during short-term fluconazole prophylaxis in acute liver disease, and in this study we did not find evidence of invasive disease from other Candida spp. during fluconazole therapy. However, in patients at particularly high risk, other strategies are required to prevent infection with Aspergillus spp.
During the first month after bone marrow transplantation, approximately 15% of patients develop acute renal failure (ARF). This usually occurs in the setting of hepatic veno-occlusive disease (VOD). Prior clinical data have suggested that this form of ARF has a hemodynamic basis, analogous to the hepatorenal syndrome (HRS). If so, then proximal tubular injury would not be expected. To directly test this hypothesis, enzymuria (N-acetyl-beta-D-glucosaminidase [NAG]) was quantitated in the following groups of patients within the first 35 days after BMT: (1) VOD+ARF (serum creatinine level > 1.5 mg/dL; N = 10); (2) VOD with relatively normal renal function (serum creatinine level < 1.5 mg/dL; N = 11); and (3) patients without hepatic or renal complications (BMT controls; N = 12). For comparison, NAG was also quantitated in the following groups of non-BMT patients: (1) toxic/ischemic acute tubular necrosis (ATN) (N = 10); (2) jaundice without azotemia (N = 5); and (3) HRS (N = 6). Urine samples from eight healthy subjects established normal NAG concentrations (2.5 +/- 0.5 microU/mg urinary creatinine; mean +/- SE). All non-BMT patients with ATN had markedly elevated NAG levels (61 +/- 12; P < 0.001), validating the test as a marker of tubular damage. NAG concentrations were significantly elevated in all of the control BMT patients (24 +/- 3; P < 0.01), and the presence of VOD was associated with further striking increments (approximately 50 times normal). However, the degree of enzymuria was virtually identical for VOD patients with (125 +/- 27) and without (122 +/- 17) ARF. Jaundice in a non-BMT setting was associated with only mild NAG elevations (11 +/- 2). However, striking enzymuria was noted in all HRS patients (61 +/- 20), equaling the levels seen with ATN. The following conclusions were derived: (1) subclinical tubular injury, as defined by enzymuria, appears to be ubiquitous after BMT; (2) VOD dramatically increases the extent of enzymuria; (3) the degree of enzymuria in VOD patients is not correlated with renal dysfunction, implying that the associated ARF has a large hemodynamic component; and (4) HRS and ATN manifest comparable degrees of enzymuria, suggesting that substantial tubular damage exists in both of these forms of ARF.
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