Impact of intravenous administration of voriconazole in critically ill patients with impaired renal function

The administration of voriconazole by the intravenous (i.v.) route in patients with moderate or severe renal failure is limited because of potential toxic effects of the accumulation of the solvent vehicle sulphobutylether beta cyclodextrin sodium. This study aimed to assess the impact of intravenous voriconazole administration on renal and liver function in critically ill patients with impaired renal function treated with this antifungal drug. The study population consisted of a retrospective cohort of patients admitted to medical-surgical intensive care units (ICUs) who were treated with i.v. voriconazole for more than 3 days. Patients with impaired renal function were those with serum creatinine concentration >1.5 mg/dL, creatinine clearance <50 mL/min, or under any extrarenal depuration procedure. Renal damage was defined as an increase of at least = 2 times initial serum creatinine level or starting of an extrarenal depuration procedure during voriconazole therapy. Liver damage was defined as an increase of = 4 times the initial serum concentration of liver enzymes, or = 2 times in patients with previous impaired liver function. A total of 69 patients was included in the study of which 26 (37.7%) had impaired renal function at the beginning of voriconazole treatment (serum creatinine >2.5 mg/dL in 10 patients). Mean (SD) duration of voriconazole treatment was 13.0 (9.5) days in patients with normal renal function and 11.2 (6.3) days in those with altered renal function. Renal damage during voriconazole therapy occurred in 13 (30.2%) patients with initial normal renal function and in 4 (15.4%) in patients with impaired renal function (P = 0.257). Liver damage during treatment with voriconazole was observed in 12 (27.9%) patients with normal initial renal function and in 3 (11.5%) patients with impaired renal function (P = 0.281). Renal failure developing during voriconazole treatment was associated with a significantly higher mortality rate (82.4% vs. 44.%, P = 0.01), except in the subgroup of patients with altered renal function before starting i.v. voriconazole (60% size=1>vs. 75%, P = 0.385). The use of i.v. voriconazole in ICU patients with pretreatment impaired renal function was not associated with renal or liver damage nor with an increase in ICU mortality.     

Risk factors for candidaemia in critically ill patients: a prospective surveillance study

Candidaemia is frequently a life-threatening complication in patients admitted to the intensive care unit (ICU). To assess the risk factors for candidaemia in critically ill patients with prolonged ICU stay, a total of 1765 adult patients admitted for at least 7 days to 73 medical-surgical ICUs of 70 tertiary care hospitals in Spain participated in a prospective cohort study. Candidaemia was defined as recovery of Candida spp. from blood culture. Sixty-eight episodes of candidaemia occurred in 63 patients, representing 35.7 episodes per 1000 ICU patients admitted, with an incidence rate of 1.5 episodes per 1000 days of ICU stay. Causative fungi were C. albicans in 57.1% of cases and non-albicans Candida spp. in 42.9%. In the multivariate analysis, independent factors significantly associated with candidaemia were Candida colonisation (OR = 4.12, 95% CI: 1.82-9.33), total parenteral nutrition (OR = 3.89, 95% CI: 1.73-8.78), elective surgery (OR = 2.75, 95% CI: 1.17-6.45) and haemofiltration procedures (OR = 1.96, 95% CI: 1.06-3.62). In the ICU setting in Spain and in patients who have stayed in units for >7 days, more than half of cases of candidaemia were caused by C. albicans. Risk factors for candidaemia identified included Candida colonisation, elective surgery, total parenteral nutrition and haemodialysis.