Reduced Multidrug Susceptibility Profile Is a Common Feature of Opportunistic Fusarium Species: Fusarium Multi-Drug Resistant Pattern

Abstract

The resistance among various opportunistic Fusarium species to different antifungal agents has emerged as a cause of public health problems worldwide. Considering the significance of multi-drug resistant (MDR), this paper emphasizes the problems associated with MDR and the need to understand its clinical significance to combat microbial infections. The search platform PubMed/MEDLINE and a review of 32 cases revealed a common multidrug-resistant profile exists, and clinically relevant members of Fusarium are intrinsically resistant to most currently used antifungals. Dissemination occurs in patients with prolonged neutropenia, immune deficiency, and especially hematological malignancies. Amphotericin B displayed the lowest minimum inhibitory concentrarions (MICs) followed by voriconazole, and posaconazole. Itraconazole and fluconazole showed high MIC values, displaying in vitro resistance. Echinocandins showed the highest MIC values. Seven out of ten (70%) patients with neutropenia died, including those with fungemia that progressed to skin lesions. Clinical Fusarium isolates displayed a common MDR profile and high MIC values for the most available antifungal agents with species- and strain-specific differences in antifungal susceptibility. Species identification of Fusarium infections is important. While the use of natamycin resulted in a favorable outcome in keratitis, AmB and VRC are the most used agents for the treatment of fusariosis in clinical settings.

Human fusariosis: An emerging infection that is difficult to treat

“…Although fusariosis is associated with specific climatic conditions, environmental and clinical isolates have been reported to cause infections outside previously established borders 14 . This fungus has efficient mechanisms of dispersion, and its conidia reach considerable distances 9 . Moreover, genetic similarities between clinical isolates and environmental isolates of the same species may be related to infections in patients by Fusarium spp.…”

“…Invasive infections can be widespread involving the skin, brain, bloodstream, lungs, eyes, and bones 14,17,18 . Patients with severe and prolonged neutropenia, especially those with hematological malignancies, are most susceptible to prevalent infections 9,18 .…”

“…Keratitis is one of the most common infections caused by Fusarium spp. and primarily develops from trauma to the eye, contact lens wear, and use of corticosteroids 9,19,22 . Trauma is the key predisposing factor and occurs in 40-60 % of patients 19 .…”

“…However, infections are difficult to treat because of the lack of consensus regarding treatment protocols for fusariosis in humans caused by multi-drug resistant isolates 2,8,9 . In addition, it is possible that environmental isolates from Fusarium spp.…”

In Vitro Susceptibility of Fusarium to Isavuconazole

“…This may be due in part to the poor susceptibility of Fusarium to most of the antifungal drugs currently available. Indeed, all Fusarium species are naturally resistant to echinocandins and flucytosine (11). Amphotericin B often offers the lowest MIC, but MIC 90 s of Ͼ2 mg/liter are commonly reported (8,12).…”