Longitudinal evaluation of intensive care unit-related fluconazole use in Spain and Germany

Objective

To evaluate utilization patterns and outcomes associated with i.v. fluconazole therapy within ICUs in Spain and Germany.

Methods

A prospective longitudinal observational study was conducted within 14 hospital ICUs in Spain and five in Germany. Patients on i.v. fluconazole therapy were included and were followed over one hospitalization period (admission until discharge). Data were collected during 2004, using electronic case report forms. Data included patient disease characteristics, patient risk status (APACHE scores), type of fluconazole therapy, drug-related adverse events, length of fluconazole therapy, and length of hospital stay. Switches in fluconazole therapy, dosing changes, additional concomitant antifungal therapy, overall mortality, and clinical outcomes were also evaluated. Logistic regression models determined univariate and multivariate associations with mortality.

Results

A total of 303 patients were enrolled. Fluconazole was used initially as prophylaxis in 29 (9.6%) patients, preemptive therapy in 85 (28.1%) patients, empiric therapy in 140 (46.2%) patients and as definitive therapy in 49 (16.2%) patients. Thirty-six patients switched from fluconazole to a broader spectrum anti-fungal agent, and seven received a second concomitant antifungal drug. Reasons for switching therapies included lack of response due to suspected resistance, documented resistance or clinical reasons other than resistance. Thirty-two patients (10.6%) experienced fluconazole-related adverse events. The overall study mortality rate was 41.9% (127/303 patients). Mortality was significantly associated with switching i.v. treatment (odds ratio 5.0; 95% CI 2.3–11.1) and the presence of adverse events (odds ratio 4.1; 95% CI 1.8–9.2).

Conclusion

The observational nature of this study precludes the establishment of any causality. This research merely documents the experiences of ICU patients who have been prescribed i.v. fluconazole therapy. Our results showed high mortality rates in the enrolled ICU patients. Patients developing adverse events and complications requiring a switch in fluconazole experienced worse outcomes