Abstract

Rhizopus is fungus of the order Mucorales, responsible for invasive diseases called mucormycosis. The correct identification of these fungi is one of the main questions raised in the literature since the diagnosis is not simple, being the necessary detection in biopsies of infected tissues and isolation of the microorganism for identification by morphological and molecular methods. In vitro susceptibility testing results are not fully clear since there are reports showing that in vitro resistance does not always mean therapeutic failure. This paper describes a case of rhino-orbito-cerebral mucormycosis in a patient with alcoholic chronic pancreatitis and secondary mellitus diabetes involving microbiological diagnostic, antifungal susceptibility tests for conidia and hypha and clinical correlation. The causative agent was identified by morphological characteristics and DNA sequencing. Minimal Inhibitory Concentration (MIC) for amphotericin B (AMB), itraconazole (ITZ) and terbinafine (TERB) was determined by broth microdilution method. Standardization of the dynamic growth evaluation patterns using the automated system BCT (BioCell-Tracer®) was obtained allowing to determining hyphae growth control and evaluating the effect of different concentrations of amphotericin B, itraconazole and terbinafine directly on growing hyphae. The fractional inhibitory concentration (FIC) for the combination of the two antifungals that the patient received at the same time, terbinafine and itraconazole, was also determined trying to correlate with clinical outcome. Strains isolated of retro-orbital abscess were identified as Rhizopus oryzae. MIC results (MIC) testing conidia showed high sensibility to amphotericin B and itraconazole in comparison to the obtained for terbinafine. The tests in the automated system BCT using hyphae showed sensibility to all tested antifungal agents and the FIC results for combination in vitro between terbinafine and itraconazole showed synergism consistent with the therapeutic success obtained for the patient who received initial treatment with amphotericin B followed for maintenance treatment with the combination itraconazole and terbinafine

Highlights

  • Mucormycosis is an invasive and difficult to treat opportunistic infection, caused by fungi of the order Mucorales, with poor prognosis in imunocompromissed patients

  • This paper describes a case of rhino-orbito-cerebral mucormycosis in a patient with alcoholic chronic pancreatitis and secondary mellitus diabetes involving microbiological diagnostic, antifungal susceptibility tests for conidia and hypha and clinical correlation

  • This article describes a case of rhino-orbito-cerebral mucoralomycoses due to Rhizopus oryzae in a patient presenting alcoholic chronic pancreatitis and secondary mellitus diabetes, diagnosed by morphological and molecular methods, antifungal susceptibility testing with conidia and hyphae, interaction obtained by the combination of antifungal agents and clinical correlation of laboratory results and clinical outcome

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Summary

Introduction

Mucormycosis is an invasive and difficult to treat opportunistic infection, caused by fungi of the order Mucorales, with poor prognosis in imunocompromissed patients. The determination of MIC (Minimal Inhibitory Concentrations) for moulds could be more reliable with utilization of a method capable to quantify the inhibition of hyphal growth in vitro in real time. This quantification permits to mimic a growth situation similar to what happens in the human body [7]-[12]. This article describes a case of rhino-orbito-cerebral mucoralomycoses due to Rhizopus oryzae in a patient presenting alcoholic chronic pancreatitis and secondary mellitus diabetes, diagnosed by morphological and molecular methods, antifungal susceptibility testing with conidia and hyphae, interaction obtained by the combination of antifungal agents and clinical correlation of laboratory results and clinical outcome

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