Successsful Voriconazole Treatment of Disseminated Fusarium Infection in an Immunocompromised Patient

Consigny, Sophie; Dhédin, Nathalie; Datry, A.; Choquet, Sylvain; Leblond, Véronique; Chosidow, Olivier

doi:10.1086/375842

Cited by 71 publications

(55 citation statements)

References 16 publications

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“…However, in our study, the VRC MICs were always higher than 2 g/ml, which agrees with the results of other studies (12,26). This drug was effective in a few clinical cases of fusariosis (2,4), although in none of them was the species involved referred to as F. solani. This is probably linked to the fact that in animal studies F. solani was clearly more virulent and more difficult to treat than F. oxysporum and F. verticillioides, the two other common species of the genus (13,18).…”

supporting

confidence: 92%

Universal In Vitro Antifungal Resistance of Genetic Clades of the Fusarium solani Species Complex

Azor

Gené

Cano

et al. 2007

Antimicrob Agents Chemother

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Eleven antifungal drugs were tested against representative isolates of the four phylogenetic clades of the Fusarium solani species complex obtained in a multilocus sequence analysis. They all showed very poor activity, with no differences among the clades. Amphotericin B was the most active drug.Fusarium solani is a fungus that is widely distributed in nature and is able to produce many plant diseases with important economic impacts and, also, severe, usually fatal, human infections (7,9,15,23). These infections can be characterized by their resistance to practically all available antifungal drugs (3,21,24). Primary therapy with voriconazole (VRC) or a lipid formulation of amphotericin B (AMB) is currently recommended (22). Although the response of Fusarium spp. to AMB is poor in general, it depends on the species involved, with F. solani being the most resistant species, at least in vitro (24). Recently, Zhang et al. (29) used a multilocus sequence analysis approach to demonstrate that under the generic name F. solani, at least 45 phylogenetically distinct species exist, most of which have not been described formally. It is unknown if antifungal susceptibility varies among these phylogenetic species. If such differences exist, knowing them could be useful for guiding clinical treatments. Due to the difficulties of testing representative strains of all the phylogenetic species, we tested isolates belonging to the four major clades, inferred from a combined phylogenetic analysis of fragments of three genes, i.e., the translation elongation factor 1␣ (EF-1␣) and ␤-tubulin genes and the internal transcribed spacer (ITS) of the nuclear rRNA gene, against traditional and new antifungal drugs.Fifty isolates from clinical or environmental sources, morphologically identified as F. solani (6), were included in the study (Table 1). Isolates were stored by lyophilization and submerged in slant cultures in mineral oil at room temperature. The procedures for DNA extraction, amplification, and sequencing of the different regions analyzed were described by Gilgado et al. (8). The annealing temperature was 55°C, and the primers used were EF-1H and EF-2T (16) for EF-1␣, TUB-F (5) and T22 (17) for ␤-tubulin, and ITS5 and ITS4 (28) for the ITS. The phylogenetic analysis was performed using PAUP*, version 4.0b10 (27). Maximum parsimony trees were obtained after 100 heuristic searches with random sequence addition and tree bisection-reconnection branch-swapping algorithms, collapsing zero-length branches, and saving of all minimal-length trees (MulTrees). The results of the partition homogeneity test showed that the three locus sequence data sets were congruent (P ϭ 0.2) and could therefore be combined. Sequences of the three genes were analyzed phylogenetically as separate (data not shown) and combined data sets.We evaluated the in vitro activities of 11 antifungal drugs against 27 representative strains (22 clinical and 5 environmental) randomly chosen from the main clades obtained in the phylogenetic analysis. The isolates were g...

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supporting

confidence: 92%

Universal In Vitro Antifungal Resistance of Genetic Clades of the Fusarium solani Species Complex

Azor

Gené

Cano

et al. 2007

Antimicrob Agents Chemother

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“…2,7 Existem evidências de que a resolução da neutropenia seja o principal fator associado à melhora do prognóstico na fusariose disseminada. 8 As estratégias do tratamento da fusariose em hospedeiro imunocomprometido ainda não estão totalmente estabelecidas. A anfotericina B e sua formulação lipossomal são as drogas sistêmicas mais eficientes e consideradas referência no tratamento da fusariose, apesar de inúmeras falhas terapêuticas.…”

Section: Discussionunclassified

“…De fato, no hospedeiro neutropênico com fusariose, a resposta a doses convencionais ou superiores de anfotericina B é geralmente pífia, e por isso um aumento no nível dos neutrófilos é considerado essencial para a cura da infecção. 8 Um dos autores (PRC) testemunhou doente portador de leucemia linfocítica crônica para desfecho fatal durante intercorrência de fusariose, na época em que o voriconazol não estava disponível no Brasil e o tratamento com anfotericina B foi ineficaz.…”

Section: Discussionunclassified

Fusariose em paciente imunocomprometido: sucesso terapêutico com voriconazol

Pincelli

Brandt

Motta

et al. 2008

An. Bras. Dermatol.

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Resumo: A infecção por Fusarium solani é afecção fúngica potencialmente grave em pacientes imunocomprometidos, sobretudo naqueles portadores de neoplasias hematológicas. A mortalidade é alta, sendo limitadas as opções terapêuticas devido às condições da imunidade do doente e à relativa resistência do fungo aos antifúngicos utilizados de rotina. O voriconazol tem-se mostrado boa alternativa terapêutica em pacientes neutropênicos que apresentam fusariose refratária ou pouco responsiva à anfotericina B. Neste artigo relata-se caso de fusariose em doente imunocomprometido tratado com sucesso com voriconazol.

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“…106 In the treatment of disseminated Fusarium infection and Trichosporon fungemia, successful management with voriconazole was rarely reported. [107][108][109] The effi cacy of posaconazole in IFIs has been evaluated in several clinical trials. In an open-label, multicenter, phase III study, posaconazole also showed activities against various IFIs in patients who were refractory to, or intolerant of, other antifungal treatment.…”

Section: Extended-spectrum Triazolesmentioning

confidence: 99%