SUSCEPTIBILITY PROFILES AND CLINICAL EFFICACY OF ANTIFUNGALS AGAINST CANDIDA BLOODSTREAM ISOLATES FROM CRITICALLY ILL PATIENTS: FOCUS ON INTRAVENOUS ITRACONAZOLE

Abstract In order to evaluate the susceptibility profile of itraconazole in light of the new cut-off points, we analyzed in vitro and clinical data. The in vitro activity of itraconazole was compared with that of eight comparators against 119 Candida bloodstream isolates of the period 2015-2018. Minimum inhibitory concentrations (MICs) were measured by the colorimetric MICRONAUT-S assay. The content of wells without any color change was sub-cultured to measure killing efficacy. No major differences were found against Candida albicans . Itraconazole, posaconazole and amphotericin B were the most active agents against Candida parapsilosis . Of the 32 isolates of C.parapsilosis that were resistant to fluconazole 96.9%, 78.1% and 93.8% were susceptible to itraconazole, voriconazole and posaconazole respectively. The ratio of the minimum fungicidal concentration to the MIC of itraconazole was lower than the other azoles against C.parapsilosis and C.glabrata . Itraconazole achieved greater inhibition over-time of the growth of C.parapsilosis than fluconazole. Seventy-three critically ill patients who were unresponsive to antibiotics received intravenous empirical treatment with itraconazole (n=28) or comparators (n=45). Case-control matching was done for severity, comorbidities, risk factors for candidemia, administered antibiotics and days of antifungal treatment. Breakthrough candidemia was found in 3.6% of patients treated with itraconazole and in 32.1% of comparators (p: 0.020); breakthrough candidemia by C.parapsilosis was found in 3.6% and 28.6% respectively. Results indicate that itraconazole retains a valuable susceptibility profile against Candida isolates, in particular C.parapsilosis . This superior profile may explain the clinical efficacy in the occurrence of breakthrough candidemia and warrants further clinical investigation.