Molecular Identification and<i>In Vitro</i>Response to Antifungal Drugs of Clinical Isolates of Exserohilum

Cunha, Keith Cássia da; Sutton, Deanna A.; Gené, Josepa; Capilla, Javier; Cano, Josep; Guarro, Josep

doi:10.1128/aac.00488-12

Cited by 44 publications

(37 citation statements)

References 24 publications

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“…than those recently reported for E. rostratum (28), but these drugs were still considered to demonstrate good activity by clinical experts (30). The itraconazole and posaconazole range reported by da Cunha and colleagues (28) was Ͻ0.03 to 0.125 g/ml, while for voriconazole it was slightly higher at Ͻ0.03 to 1 g/ml.…”

Section: Discussionmentioning

confidence: 61%

“…All of the E. rostratum isolates grew well at 37°C and produced conidia within 8 to 12 days on V8 juice agar and within 2 weeks on Pablum agar. Conidia had 6 to 12 distosepta, with an average of 10, and displayed a prominent hilum, making these isolates most similar morphologically to Exserohilum longirostratum, a species that has recently been placed into conspecificity with E. rostratum (28).…”

Section: By 14mentioning

confidence: 99%

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Preliminary Laboratory Report of Fungal Infections Associated with Contaminated Methylprednisolone Injections

et al. 2013

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In September 2012, the Centers for Disease Control and Prevention (CDC) initiated an outbreak investigation of fungal infections linked to injection of contaminated methylprednisolone acetate (MPA). Between 2 October 2012 and 14 February 2013, the CDC laboratory received 799 fungal isolates or human specimens, including cerebrospinal fluid (CSF), synovial fluid, and abscess tissue, from 469 case patients in 19 states. A novel broad-range PCR assay and DNA sequencing were used to evaluate these specimens. Although Aspergillus fumigatus was recovered from the index case, Exserohilum rostratum was the primary pathogen in this outbreak and was also confirmed from unopened MPA vials. Exserohilum rostratum was detected or confirmed in 191 specimens or isolates from 150 case patients, primarily from Michigan (n ‫؍‬ 67 patients), Tennessee (n ‫؍‬ 26), Virginia (n ‫؍‬ 20), and Indiana (n ‫؍‬ 16). Positive specimens from Michigan were primarily abscess tissues, while positive specimens from Tennessee, Virginia, and Indiana were primarily CSF. E. rostratum antifungal susceptibility MIC 50 and MIC 90 values were determined for voriconazole (1 and 2 g/ml, respectively), itraconazole (0.5 and 1 g/ml), posaconazole (0.5 and 1 g/ml), isavuconazole (4 and 4 g/ml), and amphotericin B (0.25 and 0.5 g/ml). Thirteen other mold species were identified among case patients, and four other fungal genera were isolated from the implicated MPA vials. The clinical significance of these other fungal species remains under investigation. The laboratory response provided significant support to case confirmation, enabled linkage between clinical isolates and injected vials of MPA, and described significant features of the fungal agents involved in this large multistate outbreak.

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Section: Discussionmentioning

confidence: 61%

Section: By 14mentioning

confidence: 99%

Preliminary Laboratory Report of Fungal Infections Associated with Contaminated Methylprednisolone Injections

et al. 2013

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“…Similar to other azoles, there is an extensive list of medications that are contraindicated or should be given with caution when coadministered with voriconazole (11). Compared to voriconazole, the potential advantage of posaconazole and itraconazole is based largely on marginally better in vitro activity of these two agents (12,13). This potential advantage over voriconazole could be negated by several factors, including much poorer oral absorption, unpredictable pharmacokinetics, and the unavailability of an intravenous formulation.…”

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confidence: 99%

Real-Time Treatment Guidelines: Considerations during the Exserohilum rostratum Outbreak in the United States

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et al. 2013

Antimicrob Agents Chemother

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“…Although Clinical and Laboratory Standards Institute interpretive breakpoints have not been established for Exserohilum spp., da Cunha et al 9 have recently tested 34 clinical isolates of E. rostratum. In comparison with their results for amphotericin B (MIC range o0.03-0.125 mg/ml), itraconazole (o0.03-0.125 mg/ml), voriconazole (o0.03-1 mg/ml), micafungin (0.03 to 416 mg/ml), the MICs for amphotericin B (0.06 mg/ml) and micafungin (0.03 mg/ml) of our isolate are similar.…”

Section: Discussionmentioning

confidence: 99%

Iatrogenic Exserohilum infection of the central nervous system: mycological identification and histopathological findings

et al. 2013

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An outbreak of fungal infections has been identified in patients who received epidural injections of methylprednisolone acetate that was contaminated with environmental molds. In this report, we present the mycological and histopathological findings in an index case of Exserohilum meningitis and vasculitis in an immunocompetent patient, who received a cervical spine epidural steroid injection for chronic neck pain 1 week before the onset of fulminant meningitis with subsequent multiple brain and spinal cord infarcts. The fungus was recovered from two separate cerebrospinal fluid specimens collected before initiation of antifungal therapy and at autopsy on standard bacterial and fungal culture media. The mold was identified phenotypically as Exserohilum species. DNA sequencing targeting the internal transcribed spacer region and D1/D2 region of 28S ribosomal DNA enabled further speciation as E. rostratum. Gross examination at autopsy revealed moderate brain edema with bilateral uncal herniation and a ventriculostomy tract to the third ventricle. The brainstem, cerebellum, and right orbitofrontal cortex were soft and friable, along with hemorrhages in the cerebellar vermis and thalamus. Microscopic examination demonstrated numerous fungi with septate hyphae invading blood vessel walls and inducing acute necrotizing inflammation. The leptomeninges were diffusely infiltrated by mixed inflammatory cells along with scattered foci of fungal elements. This is the first report of iatrogenic E. rostratum meningitis in humans. This report describes the microbiological procedures and histopathological features for the identification of E. rostratum (a pigmented vascularly invasive fungi), the cause of a current nationwide outbreak of fatal fungal meningitis.

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Molecular Identification andIn VitroResponse to Antifungal Drugs of Clinical Isolates of Exserohilum

Cited by 44 publications

References 24 publications

Preliminary Laboratory Report of Fungal Infections Associated with Contaminated Methylprednisolone Injections

Preliminary Laboratory Report of Fungal Infections Associated with Contaminated Methylprednisolone Injections

Real-Time Treatment Guidelines: Considerations during the Exserohilum rostratum Outbreak in the United States

Iatrogenic Exserohilum infection of the central nervous system: mycological identification and histopathological findings

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