Do high MICs predict the outcome in invasive fusariosis?

Abstract

Background Invasive fusariosis (IF) affects mostly severely immunocompromised hosts and is associated with poor outcome. Since Fusarium species exhibit high MICs for most antifungal agents, this could explain the poor prognosis. However, a clear-cut correlation between MIC and outcome has not been established. Objective To evaluate the correlation between MIC and outcome (6 week death rate) in patients with IF. Methods We performed a multicentre retrospective study of patients with IF who received treatment and had MIC levels determined by EUCAST or CLSI for the drug(s) used during treatment. We compared the MIC50 and MIC distribution among survivors and patients who died within 6 weeks from the diagnosis of IF. Results Among 88 patients with IF, 74 had haematological diseases. Primary treatment was monotherapy in 52 patients (voriconazole in 27) and combination therapy in 36 patients (liposomal amphotericin B + voriconazole in 23). The MIC50 and range for the five most frequent agents tested were: voriconazole 8 mg/L (range 0.5–64), amphotericin B 2 mg/L (range 0.25–64), posaconazole 16 mg/L (range 0.5–64), itraconazole 32 mg/L (range 4–64), and isavuconazole 32 mg/L (range 8–64). There was no difference in MIC50 and MIC distribution among survivors and patients who died. By contrast, persistent neutropenia and receipt of corticosteroids were strong predictors of 6 week mortality. Conclusions Our study did not show any correlation between MIC and mortality at 6 weeks in patients with IF.

Invasive Fusariosis in Patients with Hematologic Diseases

“…Among 22 patients treated with voriconazole monotherapy, the MIC 50 among patients who survived and died were 4 µg/mL and 8 µg/mL, respectively (p = 0.68). Likewise, no correlation between MIC and clinical outcome was observed among 21 patients treated with amphotericin B alone or in combination with voriconazole (29 patients) [67]. The lack of correlation between MIC and outcomes is in agreement with a study that showed similar response rates with voriconazole and amphotericin B, despite the higher MICs for voriconazole observed in antifungal susceptibility tests [23].…”

Malignant Keratitis Caused by a Highly-Resistant Strain of Fusarium Tonkinense from the Fusarium Solani Complex

“…Voriconazole is actually the most important antifungal, which in addition to locally applied drugs, can be given intravenously. This therapy should be taken into consideration irrespective of the in vitro susceptibility, since good clinical response in hematologic patients could be observed even when administered in cases with resistant pathogens and vice versa [49]. Another option could be terbinafine, although the final clinical value of this drug in clinical cases of fungal keratitis caused by the Fusarium spp.…”

EQUAL Fusariosis score 2021: An European Confederation of Medical Mycology score derived from current guidelines to measure QUALity of the clinical management of invasive fusariosis

“…However, since these methods are not widely available and because species identification adds little to treatment decisions, we gave 1 point for these procedures. The same is true for antifungal susceptibility tests, since there is no correlation between MIC and the outcome 8 . There are no randomised studies evaluating different treatment regimens for the treatment of invasive fusariosis.…”

“…The same is true for antifungal susceptibility tests, since there is no correlation between MIC and the outcome. 8 There are no randomised studies evaluating different treatment regimens for the treatment of invasive fusariosis. Furthermore, although recovery of immunity is the main prognostic factors, the role of adjunctive therapies such as G-or GM-CSF and granulocyte transfusions in the treatment is not clear.…”

“…Fusarium species usually exhibit high minimum inhibitory concentrations (MICs) to most antifungal agents including voriconazole, posaconazole, isavuconazole and amphotericin B 7 . However, a clear‐cut correlation between MIC and outcome has not been established, 8 as illustrated by the good clinical response to voriconazole despite the high MICs exhibited in the susceptibility test studies 9,10 . Treatment options for invasive fusariosis include a lipid formulation of amphotericin B and voriconazole 10 .…”