Activity of Posaconazole and Other Antifungal Agents against
            <i>Mucorales</i>
            Strains Identified by Sequencing of Internal Transcribed Spacers

Alastruey‐Izquierdo, Ana; Castelli, María Victoria; Cuesta, Isabel; Monzón, Araceli; Cuenca‐Estrella, Manuel; Rodríguez-Tudela, Juan Luis

doi:10.1128/aac.01467-08

Cited by 78 publications

(83 citation statements)

References 29 publications

(28 reference statements)

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“…Most cases had previously been managed in a manner similar to that employed with our patient, with amphotericin B and surgical debridement treatment. Recent reports have shown that posaconazole has a good in vitro response (MIC, 0.1 g/liter) (16,17,18) as well as in vivo response (3,16,18), although in the reported cases of mucormycosis due to Apophysomyces trapeziformis, as with the Joplin tornado, only 6 of 13 patients responded to treatment with that compound (6,19).…”

Section: Figmentioning

confidence: 93%

Primary Cutaneous Mucormycosis Produced by the New Species Apophysomyces mexicanus

et al. 2014

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A case of fungal necrotizing fasciitis that appeared in an immunocompetent Mexican woman after a car accident is described. The patient did not respond to antifungal treatment and died 4 days later. The fungus was molecularly identified as a new species of Apophysomyces, namely, Apophysomyces mexicanus. CASE REPORTA 46-year-old woman was admitted to an emergency department 6 days after she suffered a rollover car accident, which occurred on a highway in a semiarid region with 75% relative humidity; the patient was ejected 10 meters from the car during the rollover, with consequent T12 vertebral fracture, Frankel grade B spinal cord injury, and superficial abrasions and lacerations over the neck. The patient was immobilized with a Philadelphia collar immediately after the accident, and her medical history showed type 2 diabetes mellitus, controlled with metformin-glibenclamide, and an allergy to nonsteroidal anti-inflammatory drugs. She received initial treatment in a regional hospital and was transferred to the emergency department of the Lic. Adolfo López Mateos Hospital 6 days later. After the collar was removed, a 3-cm-diameter fixed, irregular, red, swollen area was observed with a central necrosis of about 1 cm in length over the right posterior cervical triangle (Fig. 1A), along with multiple abrasions of the neck. Initial laboratory test results showed leukocytosis of 17 ϫ 10 9 /liter, glucose at 10.77 mmol/liter, hemoglobin at 121 g/liter, hematocrit at 0.352 liter/liter, urea nitrogen at 3.92 mmol/ liter, urea at 3.92 mmol/liter, and creatinine at 53.04 mmol/liter. A computed tomography (CT) scan of the neck after administration of contrast material revealed isodense homogeneous soft tissue bulking posterior to the sternocleidomastoid muscle, with no evidence of foreign bodies. An escharectomy was carried out, and ceftriaxone (2 g/day) and clindamycin (1.2 g/day) were administered. On the second day, the cellulitis and necrosis areas expanded to 10 cm in length (Fig. 1B), affecting the posterior, muscular, and submandibular cervical triangles. The patient underwent surgical exploration of the neck and debridement, which showed necrotic tissue that extended as far as the muscle. Material was collected and sent to the laboratory for histopathological examination and microbial culture. Direct mountings on KOH (10% [wt/vol]) showed dichotomously branched, broad coenocytic hyphae (Fig. 1C), similar to those observed on hematoxylin-eosin histopathology preparations (Fig. 1D). Culturing on Sabouraud dextrose agar (Difco/Becton Dickinson, Mexico) produced white, cottony fungal colonies made of pauciseptated hyphae evocative of a fungus belonging to Mucorales. Consequently, primary cutaneous mucormycosis (PCM) was diagnosed; therefore, amphotericin B deoxycholate (0.5 mg/kg of body weight/ day) and fluconazole (400 mg/day) were administered. A second debridement removed all necrotic tissue, reaching the free edges of the lesion and leaving a surgical mark (10 by 15 cm) (Fig. 1E). Despite antifungal treatment, th...

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Section: Figmentioning

confidence: 93%

Primary Cutaneous Mucormycosis Produced by the New Species Apophysomyces mexicanus

et al. 2014

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“…Practical reasons for this are the difficulties of cultivating these fungi from biopsy samples (22,34) and of differentiating zygomycete species by classical mycological techniques in clinical microbiology laboratories. Previous com-prehensive studies on susceptibility profiles against antifungal drugs in the Mucorales revealed considerable variation among and within genera and species, as defined either by applying classical parameters (5,16,35,39,40) or more recently by using molecular taxonomic methods (1,12). A recent review of in vitro activity of antifungals against zygomycetes was provided by AlastrueyIzquierdo et al (2).…”

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confidence: 99%

“…For this reason, and because of the difficulty of morphological species identification, studies on the taxon specificity of susceptibility profiles in this group of fungi need to be preceded by molecular identification of the strains under study (1). Otherwise, in clinical practice, when the only intention is to determine the most appropriate antifungal as quickly as possible, susceptibility tests could also be performed directly.…”

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confidence: 99%

Antifungal Susceptibility and Phylogeny of Opportunistic Members of the Order Mucorales

et al. 2012

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The in vitro susceptibilities of 66 molecularly identified strains of the Mucorales to eight antifungals (amphotericin B, terbinafine, itraconazole, posaconazole, voriconazole, caspofungin, micafungin, and 5-fluorocytosine) were tested. Molecular phylogeny was reconstructed based on the nuclear ribosomal large subunit to reveal taxon-specific susceptibility profiles. The impressive phylogenetic diversity of the Mucorales was reflected in susceptibilities differing at family, genus, and species levels. Amphotericin B was the most active drug, though somewhat less against Rhizopus and Cunninghamella species. Posaconazole was the second most effective antifungal agent but showed reduced activity in Mucor and Cunninghamella strains, while voriconazole lacked in vitro activity for most strains. Genera attributed to the Mucoraceae exhibited a wide range of MICs for posaconazole, itraconazole, and terbinafine and included resistant strains. Cunninghamella also comprised strains resistant to all azoles tested but was fully susceptible to terbinafine. In contrast, the Lichtheimiaceae completely lacked strains with reduced susceptibility for these antifungals. Syncephalastrum species exhibited susceptibility profiles similar to those of the Lichtheimiaceae. Mucor species were more resistant to azoles than Rhizopus species. Species-specific responses were obtained for terbinafine where only Rhizopus arrhizus and Mucor circinelloides were resistant. Complete or vast resistance was observed for 5-fluorocytosine, caspofungin, and micafungin. Intraspecific variability of in vitro susceptibility was found in all genera tested but was especially high in Mucor and Rhizopus for azoles and terbinafine. Accurate molecular identification of etiologic agents is compulsory to predict therapy outcome. For species of critical genera such as Mucor and Rhizopus, exhibiting high intraspecific variation, susceptibility testing before the onset of therapy is recommended.

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“…Identification of the species may be important to gain better knowledge of the epidemiology of zygomycosis and because the different species of Zygomycetes exhibited various antifungal susceptibilities (1,6,7). Species identification may thus be important to guide the choice of antifungal therapy.…”

Section: Discussionmentioning

confidence: 99%

Molecular Detection and Identification of Zygomycetes Species from Paraffin-Embedded Tissues in a Murine Model of Disseminated Zygomycosis: a Collaborative European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Fungal Infection Study Group (EFISG) Evaluation

et al. 2010

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The present study was performed to assess the interlaboratory reproducibility of the molecular detection and identification of species of Zygomycetes from formalin-fixed paraffin-embedded kidney and brain tissues obtained from experimentally infected mice. Animals were infected with one of five species (Rhizopus oryzae, Rhizopus microsporus, Lichtheimia corymbifera, Rhizomucor pusillus, and Mucor circinelloides). Samples with 1, 10, or 30 slide cuts of the tissues were prepared from each paraffin block, the sample identities were blinded for analysis, and the samples were mailed to each of seven laboratories for the assessment of sensitivity. A protocol describing the extraction method and the PCR amplification procedure was provided. The internal transcribed spacer 1 (ITS1) region was amplified by PCR with the fungal universal primers ITS1 and ITS2 and sequenced. As negative results were obtained for 93% of the tissue specimens infected by M. circinelloides, the data for this species were excluded from the analysis. Positive PCR results were obtained for 93% (52/56), 89% (50/56), and 27% (15/56) of the samples with 30, 10, and 1 slide cuts, respectively. There were minor differences, depending on the organ tissue, fungal species, and laboratory. Correct species identification was possible for 100% (30 cuts), 98% (10 cuts), and 93% (1 cut) of the cases. With the protocol used in the present study, the interlaboratory reproducibility of ITS sequencing for the identification of major Zygomycetes species from formalin-fixed paraffin-embedded tissues can reach 100%, when enough material is available.

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Activity of Posaconazole and Other Antifungal Agents against Mucorales Strains Identified by Sequencing of Internal Transcribed Spacers

Cited by 78 publications

References 29 publications

Primary Cutaneous Mucormycosis Produced by the New Species Apophysomyces mexicanus

Primary Cutaneous Mucormycosis Produced by the New Species Apophysomyces mexicanus

Antifungal Susceptibility and Phylogeny of Opportunistic Members of the Order Mucorales

Molecular Detection and Identification of Zygomycetes Species from Paraffin-Embedded Tissues in a Murine Model of Disseminated Zygomycosis: a Collaborative European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Fungal Infection Study Group (EFISG) Evaluation

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