Fungal Infections Associated with Contaminated Steroid Injections
- Authors: Carol A. Kauffman1, Anurag N. Malani2
- Editors: W. Michael Scheld3, James M. Hughes4, Richard J. Whitley5
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VIEW AFFILIATIONS HIDE AFFILIATIONSAffiliations: 1: Division of Infectious Diseases, Department of Internal Medicine, Veterans Affairs Ann Arbor Healthcare System, University of Michigan Medical School, Ann Arbor, MI 48105; 2: Division of Infectious Diseases, Department of Internal Medicine, St. Joseph Mercy Hospital, University of Michigan Medical School, Ann Arbor, MI 48105; 3: Department of Infectious Diseases, University of Virginia Health System, Charlottesville, VA; 4: Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA; 5: Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL
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Received 08 September 2015 Accepted 28 September 2015 Published 22 April 2016
- Correspondence: Carol A. Kauffman, [email protected]

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Abstract:
In mid-September 2012, the largest healthcare-associated outbreak in U.S. history began. Before it was over, 751 patients were reported with fungal meningitis, stroke, spinal or paraspinal infection, or peripheral osteoarticular infection, and 64 (8.5%) died. Most patients had undergone epidural injection, and a few osteoarticular injection, of methylprednisolone acetate that had been manufactured at the New England Compounding Center (NECC). The offending pathogen in most cases was Exserohilum rostratum, a brown-black soil organism that previously was a rare cause of human infection. Three lots of methylprednisolone were contaminated with mold at NECC; the mold from unopened bottles of methylprednisolone was identical by whole-genome sequencing to the mold that was isolated from ill patients. Early cases manifested as meningitis, some patients suffered posterior circulation strokes, and later cases were more likely to present with localized infection at the injection site, including epidural abscess or phlegmon, vertebral diskitis or osteomyelitis, and arachnoiditis with intradural involvement of nerve roots. Many patients with spinal or paraspinal infection required surgical intervention. Recommendations for treatment evolved over the first few weeks of the outbreak. Initially, combination therapy with liposomal amphotericin B and voriconazole was recommended for all patients; later, combination therapy was recommended only for those who were most ill, and voriconazole monotherapy was recommended for most patients. Among those patients who continued antifungal therapy for at least 6 months, outcomes for most appeared to be successful, although a few patients remain on therapy.
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Citation: Kauffman C, Malani A. 2016. Fungal Infections Associated with Contaminated Steroid Injections. Microbiol Spectrum 4(2):EI10-0005-2015. doi:10.1128/microbiolspec.EI10-0005-2015.




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Abstract:
In mid-September 2012, the largest healthcare-associated outbreak in U.S. history began. Before it was over, 751 patients were reported with fungal meningitis, stroke, spinal or paraspinal infection, or peripheral osteoarticular infection, and 64 (8.5%) died. Most patients had undergone epidural injection, and a few osteoarticular injection, of methylprednisolone acetate that had been manufactured at the New England Compounding Center (NECC). The offending pathogen in most cases was Exserohilum rostratum, a brown-black soil organism that previously was a rare cause of human infection. Three lots of methylprednisolone were contaminated with mold at NECC; the mold from unopened bottles of methylprednisolone was identical by whole-genome sequencing to the mold that was isolated from ill patients. Early cases manifested as meningitis, some patients suffered posterior circulation strokes, and later cases were more likely to present with localized infection at the injection site, including epidural abscess or phlegmon, vertebral diskitis or osteomyelitis, and arachnoiditis with intradural involvement of nerve roots. Many patients with spinal or paraspinal infection required surgical intervention. Recommendations for treatment evolved over the first few weeks of the outbreak. Initially, combination therapy with liposomal amphotericin B and voriconazole was recommended for all patients; later, combination therapy was recommended only for those who were most ill, and voriconazole monotherapy was recommended for most patients. Among those patients who continued antifungal therapy for at least 6 months, outcomes for most appeared to be successful, although a few patients remain on therapy.

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Figures
Epidemiological curve of fungal infections associated with injection of contaminated methylprednisolone acetate manufactured by the NECC. Reproduced from reference 5 with permission.

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FIGURE 1
Epidemiological curve of fungal infections associated with injection of contaminated methylprednisolone acetate manufactured by the NECC. Reproduced from reference 5 with permission.
(A) Sagittal T1 fat-saturated, postcontrast image of the lumbar spine shows dorsal intradural enhancement (arrow). (B) Axial T1 postcontrast image shows intradural enhancement and clumping (arrow) in the thecal sac, consistent with arachnoiditis. (C) Operative pathology from the intradural abscess shows fungal hyphae by Gomori methenamine silver staining.

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FIGURE 2
(A) Sagittal T1 fat-saturated, postcontrast image of the lumbar spine shows dorsal intradural enhancement (arrow). (B) Axial T1 postcontrast image shows intradural enhancement and clumping (arrow) in the thecal sac, consistent with arachnoiditis. (C) Operative pathology from the intradural abscess shows fungal hyphae by Gomori methenamine silver staining.
(A) Sagittal T2-weighted image of the cervical spine shows a dorsal epidural fluid collection consistent with a phlegmon or abscess. Tissue obtained at surgery showed fungal hyphae. (B) Linear endplate enhancement consistent with diskitis or osteomyelitis of the lumbar spine. (C) Coronal T1 fat-saturated, postcontrast image shows edema and enhancement in the left femoral head and acetabulum consistent with septic arthritis or osteomyelitis.

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FIGURE 3
(A) Sagittal T2-weighted image of the cervical spine shows a dorsal epidural fluid collection consistent with a phlegmon or abscess. Tissue obtained at surgery showed fungal hyphae. (B) Linear endplate enhancement consistent with diskitis or osteomyelitis of the lumbar spine. (C) Coronal T1 fat-saturated, postcontrast image shows edema and enhancement in the left femoral head and acetabulum consistent with septic arthritis or osteomyelitis.
Whole-body bone scan of a woman who had been on voriconazole for 4 months for meningitis and arachnoiditis shows uptake in the left and right ribs posteriorly consistent with periostitis.

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FIGURE 4
Whole-body bone scan of a woman who had been on voriconazole for 4 months for meningitis and arachnoiditis shows uptake in the left and right ribs posteriorly consistent with periostitis.
Tables
CDC case definitions of probable and confirmed fungal infections associated with contaminated methylprednisolone injection a

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TABLE 1
CDC case definitions of probable and confirmed fungal infections associated with contaminated methylprednisolone injection a
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