The Zygomycetes

Dannaoui, Éric; García-Hermoso, Dea

doi:10.1007/978-1-4020-6397-8_7

Cited by 9 publications

(7 citation statements)

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“…Currently, posaconazole is used as a second-line therapy in patients with infection by mucoralean fungi that are refractory or intolerant to polyenes (11,17). So far, there is no clinical evidence on the role of posaconazole in infections caused by M. circinelloides, and few experimental data have been reported on the efficacy of posaconazole in such infections (17).…”

Section: Discussionmentioning

confidence: 99%

“…The management of infections by mucoralean fungi requires the rapid diagnosis and early initiation of appropriate antifungal therapy, surgical debridement, and removal of predisposing factors, if possible (23,26). At present, amphotericin B is the first choice in the treatment of such infections (7), but the mortality rate remains high (11). Posaconazole is a broad-spectrum antifungal drug that has shown good activity in vitro against mucoralean fungi (2).…”

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In Vitro and In Vivo Activities of Posaconazole and Amphotericin B in a Murine Invasive Infection by Mucor circinelloides: Poor Efficacy of Posaconazole

Salas

Pastor

Calvo

et al. 2012

Antimicrob Agents Chemother

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The in vitro susceptibility of 17 strains of Mucor circinelloides to amphotericin B and posaconazole was ascertained by using broth microdilution and disk diffusion methods and by determining the minimal fungicidal concentration (MFC). We evaluated the efficacy of posaconazole at 40 mg/kg of body weight/day and amphotericin B at 0.8 mg/kg/day in a neutropenic murine model of disseminated infection by M. circinelloides by using 6 different strains tested previously in vitro. In general, most of the posaconazole MICs were within the range of susceptibility or intermediate susceptibility, while the small inhibition zone diameters (IZDs) were indicative of nonsusceptibility for all isolates tested. The MFCs were >3 dilutions higher than the corresponding MICs. In contrast, amphotericin B showed good activity against all of the strains tested regardless of the method used M ucoramycoses, infections by species of Mucorales, are characterized by a rapid clinical progression and high mortality rates. Currently these infections are the third most common invasive mycoses after candidiasis and aspergillosis. Mucor circinelloides seems to be the most common species of Mucor involved in clinical cases (3). The management of infections by mucoralean fungi requires the rapid diagnosis and early initiation of appropriate antifungal therapy, surgical debridement, and removal of predisposing factors, if possible (23, 26). At present, amphotericin B is the first choice in the treatment of such infections (7), but the mortality rate remains high (11). Posaconazole is a broad-spectrum antifungal drug that has shown good activity in vitro against mucoralean fungi (2). Although several in vitro studies have shown that this drug is less active against M. circinelloides than against other species belonging to the order Mucorales, such as Rhizopus spp., Aphysomyces spp., and Saksenaea spp. (1, 2, 18, 28), there is little experimental and clinical data on the use of posaconazole against Mucor infections (17,29). In this study, we have evaluated the in vitro activity of posaconazole and amphotericin B using different methods against a relatively high number of clinical isolates of M. circinelloides and their efficacy in a neutropenic murine model of disseminated infection by clinical isolates with different posaconazole MICs. MATERIALS AND METHODSSeventeen strains molecularly identified as Mucor circinelloides (4) were tested in vitro (Table 1). Their susceptibility to posaconazole (PSC) and amphotericin B (AMB) was evaluated using a broth microdilution method, which was carried out according to the CLSI guidelines for filamentous fungi (8), and a disk diffusion method that uses nonsupplemented Mueller-Hinton agar and 6-mm-diameter paper discs containing 5 g of posaconazole or 10 g of amphotericin B (9, 10). The MICs (g/ml) and inhibition zone diameters (IZDs; mm) were read at 24 h. Although the clinical breakpoints for molds have not been developed yet, the strains were classified by following the suggested epidemiological cutoff values (...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

In Vitro and In Vivo Activities of Posaconazole and Amphotericin B in a Murine Invasive Infection by Mucor circinelloides: Poor Efficacy of Posaconazole

Salas

Pastor

Calvo

et al. 2012

Antimicrob Agents Chemother

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“…The classification of the Zygomycota is in a state of flux, and the reader is referred to recent reviews of the phylogeny of the phylum based on nuclear ribosomal sequence data [2,3], and to a recent summary by Dannaoui and Garcia‐Hermoso [4]. The phylum Zygomycota is an ecologically heterogeneous assemblage of non‐zoosporic fungi composed of two classes, the Zygomycetes and the Trichomycetes.…”

Section: Introductionmentioning

confidence: 99%

The ecology of the Zygomycetes and its impact on environmental exposure

Richardson

2009

Clinical Microbiology and Infection

241

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Zygomycetes are unique among filamentous fungi in their great ability to infect a broader, more heterogeneous population of human hosts than other opportunistic moulds. Various members of the Zygomycetes have been implicated in zygomycosis, although those belonging to the family Mucoraceae are isolated more frequently than those of any other family. The environmental microbiology literature provides limited insights into how common zygomycetes are in the environment, and provides a few clues about which ecological niches these fungi are found in. Mucorales are thermotolerant moulds that are supposedly ubiquitous in nature and widely found on organic substrates, including bread, decaying fruits, vegetable matter, crop debris, soil between growing seasons, compost piles, and animal excreta. The scientific and medical literature does not support this generalization. Sporangiospores released by mucorales range from 3 to 11 microm in diameter, are easily aerosolized, and are readily dispersed throughout the environment. This is the major mode of transmission. However, there are very few data concerning the levels of zygomycete sporangiospores in outdoor and indoor air, especially in geographical areas where zygomycosis is particularly prevalent. Airborne fungal spores are almost ubiquitous and can be found on all human surfaces in contact with air, especially on the upper and lower airway mucosa. Inhalation of sporangiospores must be a daily occurrence. Surprisingly, members of the Mucorales are very rarely found in nasal mucus, suggesting that spores in the mucus of airway mucosa are cleared by mucociliary transport or that there is a low level of airborne contamination. Zygomycetes are found occasionally in water-damaged buildings, as demonstrated by air-sampling, and analysis of settled dust by quantitative PCR. Moreover, inhalation of sporangiospores in dust has been linked to outbreaks of rhinocerebral or pulmonary zygomycosis due to excavation, construction, or contaminated air-conditioning filters. Whereas most zygomycete infections are community-acquired, nosocomial acquisition due to percutaneous routes of exposure is very important. Sporadic cases, and pseudo-outbreaks, have been linked to contaminated bandages and adhesive dressings, needles, and tongue depressors used to construct splints for intravenous and arterial cannulation sites in preterm infants. Insect bites or stings have been implicated in disease transmission in cases of cutaneous and subcutaneous zygomycosis, e.g. diseases caused by the Entomophthorales. Traumatic implantation of spores in dirt or in contaminated water, e.g. as occurred during the Asian tsunami, has led to infection in multiple patients.

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“…The filamentous fungi responsible for these infections belong to the Mucorales order. About 20 different species have been shown to be pathogenic for humans (4). According to a recent review (19), the species that were the most frequent encountered were Rhizopus spp., Mucor spp., and Cunninghamella spp., while Apophysomyces elegans and Absidia spp.…”

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Molecular and Phenotypic Evaluation of Lichtheimia corymbifera (Formerly Absidia corymbifera ) Complex Isolates Associated with Human Mucormycosis: Rehabilitation of L. ramosa

et al. 2009

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Thirty-eight isolates (including 28 isolates from patients) morphologically identified as Lichtheimia corymbifera (formerly Absidia corymbifera) were studied by sequence analysis (analysis of the internal transcribed spacer [ITS] region of the ribosomal DNA, the D1-D2 region of 28S, and a portion of the elongation factor 1␣ [EF-1␣] gene). Phenotypic characteristics, including morphology, antifungal susceptibility, and carbohydrate assimilation, were also determined. Analysis of the three loci uncovered two well-delimited clades. The maximum sequence similarity values between isolates from both clades were 66, 95, and 93% for the ITS, 28S, and EF-1␣ loci, respectively, with differences in the lengths of the ITS sequences being detected (763 to 770 bp for isolates of clade 1 versus 841 to 865 bp for isolates of clade 2). Morphologically, the shapes and the sizes of the sporangiospores were significantly different among the isolates from both clades. On the basis of the molecular and morphological data, we considered isolates of clade 2 to belong to a different species named Lichtheimia ramosa because reference strains CBS 269.65 and CBS 270.65 (which initially belonged to Absidia ramosa) clustered within this clade. As neotype A. corymbifera strain CBS 429.75 belongs to clade 1, the name L. corymbifera was conserved for clade 1 isolates. Of note, the amphotericin B MICs were significantly lower for L. ramosa than for L. corymbifera (P < 0.005) but were always <0.5 g/ml for both species. Among the isolates tested, the assimilation of melezitose was positive for 67% of the L. ramosa isolates and negative for all L. corymbifera isolates. In conclusion, this study reveals that two Lichtheimia species are commonly associated with mucormycosis in humans.Mucormycosis is a life-threatening infection that occurs in immunocompromised patients, diabetic patients with ketoacidosis, and immunocompetent patients after trauma exposure to contaminated soil (7, 18). The filamentous fungi responsible for these infections belong to the Mucorales order. About 20 different species have been shown to be pathogenic for humans (4). According to a recent review (19), the species that were the most frequent encountered were Rhizopus spp., Mucor spp., and Cunninghamella spp., while Apophysomyces elegans and Absidia spp. accounted for 6% and 5% of the cases, respectively. The true frequency is, however, difficult to assess because surveys are rare and determination of the species of the Zygomycetes class by standard mycological methods remains difficult. Indeed, all the genera and species within the family Mucoraceae (the Absidia, Rhizopus, Mucor, Rhizomucor, and Apophysomyces genera) shared similar morphological characteristics (6). The precise identification to the species level often requires the specific expertise usually available only at reference laboratories. The availability of molecular tools for taxonomic and identification purposes has changed the picture. Sequencing of various DNA targets has facilitated the recognition of phylo...

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The Zygomycetes

Cited by 9 publications

References 95 publications

In Vitro and In Vivo Activities of Posaconazole and Amphotericin B in a Murine Invasive Infection by Mucor circinelloides: Poor Efficacy of Posaconazole

In Vitro and In Vivo Activities of Posaconazole and Amphotericin B in a Murine Invasive Infection by Mucor circinelloides: Poor Efficacy of Posaconazole

The ecology of the Zygomycetes and its impact on environmental exposure

Molecular and Phenotypic Evaluation of Lichtheimia corymbifera (Formerly Absidia corymbifera ) Complex Isolates Associated with Human Mucormycosis: Rehabilitation of L. ramosa

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