Abstract
Mucoromycoses (infections caused by members of the order Mucorales, phylum Mucoromycota [ex-Zygomycota]) are highly destructive, rapidly progressive infections, with dire prognoses especially when they occur in immunocompromised hosts. Current treatment guidelines recommend liposomal formulations of amphotericin B with adjunctive surgery as first line therapy, with the newer triazoles posaconazole or isavuconazole as alternative treatments, or as salvage therapy. Among the many organisms belonging to this order, a limited number of species in the genera Rhizopus, Mucor, Lichtheimia and Rhizomucor are responsible for most cases of human infection. Here, we present the minimum inhibitory concentration data (MICs) for amphotericin B, posaconazole, isavuconazole, itraconazole and voriconazole with a panel of over 300 isolates of the five most common agents of human infection (Lichtheimia corymbifera, Rhizopus arrhizus, R. microsporus, Rhizomucor pusillus and Mucor spp.) determined using the CLSI broth microdilution method. In agreement with previous studies, the most active antifungal drug for all Mucorales was amphotericin B, with MICs within the range that would predict susceptibility with Aspergillus fumigatus. Conversely, MICs for voriconazole against all species tested were high, and above the range associated with clinical efficacy with A. fumigatus. Interestingly, whilst isavuconazole and posaconazole MIC distributions indicated in vitro activity against some members of the Mucorales, activity was species-dependent for both agents. These data underscore the importance of accurate identification of the causative agents of mucoromycosis, coupled with antifungal susceptibility testing of individual isolates, in determining the optimal treatment of infections caused by these aggressive opportunistic human fungal pathogens.
Highlights
Mucoromycosis is a relatively rare, but life-threatening infection that predominantly affects immunocompromised patients, or those suffering from severe burns or physical traumas [1,2,3,4], and is caused by members of the order Mucorales, phylum Mucoromycota [5]
MIC distributions were ascertained for a total of 365 clinical isolates of members of the Mucorales submitted to the UK National Mycology Reference Laboratory (MRL) for identification and susceptibility testing during the periods 2006–2016 and 2017–2020
The results of in vitro susceptibility testing of clinical isolates of Mucorales submitted to the MRL are shown as MIC distributions for amphotericin B, itraconazole, posacoanzole, voriconazole and isavuconazole in Tables 1–5, respectively, and MIC ranges, MIC50 and
Summary
Mucoromycosis (ex-zygomycosis) is a relatively rare, but life-threatening infection that predominantly affects immunocompromised patients (patients with neutropenia, diabetic ketoacidosis or iron overload), or those suffering from severe burns or physical traumas [1,2,3,4], and is caused by members of the order Mucorales, phylum Mucoromycota [5] These fungi, which were previously classified in the now-obsolete polyphyletic phylum Zygomycota, are characterized by their pauci-septate, broad, ribbon-like hyphae and extremely rapid growth in vitro and in vivo, with extensive angioinvasion, tissue necrosis and infarction and contiguous spread the characteristic presentations of infection [6].
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