High-dose fluconazole therapy in Intensive Care Unit

Fungal infections have become one of the emerging complications in intensive care patients and the morbidity and mortality linked to these infections underlines the importance of managing these pathologies.

The clinical and laboratory difficulties of diagnosing candidiasis prompted us to identify patients at risk and to intervene as soon as possible, where there was the "suspicion" of active infection, using adequate, so-called "empiric" treatment. The major risk factors include the use of invasive devices (central venous catheters), the administration of multiple antibiotic treatment and parenteral nutrition. In our Intensive Care ward (multi-purpose), we examined 1933 patients who had undergoing 1211 urine cultures (following consolidated clinical criteria). "Empiric treatment" was used in 378 high-risk patients with unstable clinical symptoms and positive urinary fungal colonisations using high-dose fluconazole (800 mg/die) according to the guidelines set down by BSAC. The mean duration of treatment was 12+2 days and urine cultures became negative in all patients after 1 or 2 weeks of treatment.

We observed that fluconazole was generally well tolerated: only 10% of patients presented augmented hepatic transaminase. This phenomenon was always transient. Renal function remained unchanged (creatinine clearance). A severe infection with hematogenous dissemination was reported in 6 cases: "empiric treatment" was used in 5 cases with 800 mg/die of fluconazole and 1 case received amphotericin B 1 mg/kg/die (because no clinical improvement was observed after 48-72 hours of fluconazole treatment). Three of these 6 cases died, 2 of which were not directly linked to fungal infection, and 3 patient were discharged from the ward.

We found that fluconazole offers a treatment option that is less toxic, less expensive and equally effective for these infections, provided that it is used at an adequate dose and that high-risk patients are identified for "empiric treatment". No significant increases in resistance were noted, as is demonstrated by the fact that only 1 case of candidemia required conversion to amphotericin B.