Fluconazole resistance is not a predictor of poor outcome in patients with cryptococcosis.

BACKGROUND: Cryptococcus isolates with high MICs to fluconazole are increasingly reported, and a potential clinical impact has been advocated. However, there are different methods to evaluate fluconazole MICs and comparative analysis among such techniques and their comprehensive correlation with clinical outcome are not available. METHODS: Over a 13-year period (2000-2013), fluconazole MICs were determined for 62 cryptococcal isolates recovered from 22 patients with cryptococcosis using CLSI M27-A3, EUCAST, E test and Sensititre YeastOne, simultaneously. The relationship between the fluconazole MICs and the clinical outcome at week 10 was assessed in patients who received fluconazole as induction or maintenance therapy (n = 16). RESULTS: The percentage of cryptococcal strains with MIC values ≥16 µg/mL according to different methods was CLSI 1.6%, EUCAST 16.1%, E test 31.6% and Sensititre YeastOne 53.2%. Among the 16 patients treated with fluconazole, no correlation between clinical outcome and any MIC value obtained with either method was observed. The only variable independently associated with a poor outcome was having a disseminated disease. CONCLUSIONS: There is a weak correlation between fluconazole MICs against Cryptococcus spp. as determined by CLSI, EUCAST, E test and Sensititre YeastOne. Neither procedure could predict the clinical outcome of patients with cryptococcosis receiving fluconazole-based therapy. With present methods, fluconazole resistance in Cryptococcus may be clinically misleading.

Comparison of the Safety and Tolerance Profile of Micafungin with that of Other Echinocandins and Azoles in Patients with Pre-existing Child-Pugh B or C Liver Disease: A Case-Control Retrospective Study.

INTRODUCTION: To assess the association between exposure to micafungin, other echinocandins, or azoles and the development of short-term liver injury (STLI) or long-term liver injury (LTLI) in patients with Child-Pugh B or C liver disease. METHODS: Multicenter case-control study of patients with Child-Pugh B or C liver disease who received antifungals (AF) for ≥ 72 h (May 2009-May 2015) in six Spanish and Italian hospitals. All micafungin patients were randomly matched with one patient who received another echinocandin and with one patient who received azole treatment. Primary outcome was development of STLI or LTLI (development of any type of liver tumor during the follow-up period). RESULTS: Of 2335 patients with chronic liver disease admitted to the six centers, 20 (0.85%) were found to have Child-Pugh B or C liver disease and received micafungin for ≥ 72 h. During AF treatment, the frequency of STLI was 10% in each group. Most cases of STLI were asymptomatic, and AFs had to be switched to another class of AF in only two patients (one micafungin and one azole). No patients developed acute liver insufficiency, were admitted to the ICU, or had to undergo transplantation. Follow-up data (median of 1.3 years) were available for 30 patients. LTLI was observed in only one patient, who had previously received treatment with azoles. CONCLUSIONS: Our study suggests that the administration of micafungin to patients with end-stage liver disease does not imply a higher risk of developing STLI or LTLI.