Fungal Infections Associated with Contaminated Steroid Injections

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.