Effects of fluconazole administration in critically ill patients - Analysis of bacterial and fungal resistance

Hypothesis: The administration of fluconazole in intensive care unit (ICU) patients leads to the emergence of bacterial and fungal resistance. Designs: Retrospective analysis of 2 patient cohorts: (1) critically ill pa tients treated in surgical, trauma, and medical ICUs between June 1997 and January 1999 who did and did not receive fluconazole; and (2) ICU patients with fungal infections and sensitivity testing results from June 1994 to De cember 1998. Setting: University-affiliated tertiary care hospital. Patients: The first cohort included 99 ICU patients with documented microor ganism culture(s) who were treated with (n = 50) or without (n = 49) flucon azole; the second cohort included 38 patients with Candida species infectio n, identification, and antifungal susceptibility testing. Results: Mortality (40% vs 20%; P = .03) and hospital length of stay (33.8 vs 25.6 days, P = .04) were higher in the patients treated with fluconazole compared with patients not treated with fluconazole. The ICU length of sta y was also higher in patients treated with fluconazole (23.7 vs 15.1 days; P = .009). An increase in bacterial resistance occurred in patients after f luconazole treatment as opposed to bacterial resistance of patients who wer e treated for bacterial microorganism(s) without fluconazole (16% vs 4%: P = .049). Comparison of patient populations with Candida species identificat ion before and after December 1997 showed an increase in Candida species re sistance to fluconazole (11% vs 36%; P = .16), respectively. Fungal strains were dominated by a combination of Candida albicans and Candida glabrata i n both populations (60% [before 1998] vs 82% [after 1998]), with an emergen ce of Candida non-albicans species tolerant to fluconazole. The amount of f luconazole administered and the number of patients receiving fluconazole tr eatment in the ICUs has also increased when comparing both periods. Conclusions: Comparison of critically ill patient populations with and with out fluconazole treatment found increased mortality and longer hospital and ICU lengths of stay in the fluconazole-treated group. This group also had higher bacterial pathogen resistant to antibiotics after fluconazole admini stration compared with bacterial resistance of patients without fluconazole treatment. Our results warrant concern regarding worsening bacterial infec tions, increased mortality, and an increase in Candida resistance to flucon azole: hom increased use in ICU patients, with a shift in yeast infection t hat is more difficult to treat.