Fluconazole blood concentrations after enteral administration in critically-ill surgical patients exceed most candida minimal inhibitory concentrations in a double-blind, placebo-controlled trial in which fluconazole prevented candidal infections

Introduction. Enteral routes of drug administration are infrequently used in critically-ill surgical patients for fear of poor gut absorption. This may result in unnecessarily increased medication and nursing costs. We analyzed fluconazole blood concentrations following its enteral administration in a 260 patient RCT of fluconazole prophylaxis which demonstrated a 2-fold reduction of Candidal infections in the SICU. Methods. Fluconazole was administered enterally with an 800 mg loading dose followed by 400 mg QD. Semi-weekly trough fluconazole blood concentrations are available for 118 subjects. Results. The fluconazole concentrations achieved during the study are displayed (Table) as a percent of patients exceeding given concentrations. The upper 75th %ile MIC for infecting Candidal species in our trial was: Candida albicans, 0.5 μ g/ml; parapsilosis, 1.0 p, g/ml; tropicalis, 2 μ g/ml; glabrata, 16 μ g/ml. No statistically significant associations were found between fluconazole levels and Candida infection, abdominal surgery, ileus, NG tube output, or APACHE III scores (p>0.05). Conclusion. In nearly all patients, enterally-administered fluconazole (400 mg) achieved trough blood concentrations exceeding the 75th %ile MIC of all Candida, but not C. glabrata, causing infection in our study, independent of severity of illness, abdominal surgery, ileus, or nasogastric output. MIC Cut-off After Loading Mean Minimum Maximum >2 μg/ml 93% 96% 89% 97% >4 μg/ml 73% 90% 70% 92% >8 μg/ml 53% 65% 45% 81% >16 μg/ml 10% 22% 8% 33%.