Epidemiologic Highlight

Starting in September 2012 there was a multi-state U.S. outbreak of fungal meningitis and other infections in patients receiving epidural, paraspinal, or joint injections of preservative-free methylprednisolone acetate from a compounding pharmacy in New England, USA eventually involving 749 cases, with 31% presenting with meningitis (Chiller et al., 2013, Smith et al., 2013). Exam of unopened vials revealed fungus with Exserohilum rostratum as the major outbreak pathogen. Cases were reported to the CDC from 6 states with the most cases (Florida, Indiana, Michigan, New Jersey, Tennessee, Virginia). PCR and immunohistochemistry tests of clinical specimens found at least 2 fungi causative agents, E. rostratum (major pathogen) and A. fumigatus (minor pathogen). Other fungi, mostly common environmental molds, were identified in specimens from case patients, and in the product, but were of unclear clinical significance. 

More than 13,000 persons were exposed but disease occurred in a relatively small proportion. State-specific attack rates varied widely, from 0 to 18 cases per 100 exposed persons. Of 328 case patients 265 (81%) had central nervous system (CNS) infection and 63 (19%) had non-CNS infections only. E. rostratum was found in 96 of 268 patients (36%) for whom samples were available. Among those with CNS infections, strokes were associated with increasingly severe abnormalities in CSF. Non-CNS infections were more frequent later in the outbreak (median interval from last injection to diagnosis, 39 d for epidural abscess and 21 d for stroke), and such infections developed in patients with or without meningitis. The clinical course for case patients is uncertain, although many completed antifungal therapy and are stable or improved, but relapses are possible.
 

An outbreak subset of 544 patients received epidural injections from contaminated methylprednisolone at a pain clinic in SE Michigan between August and October 2012 (Moudgal et al., 2014). 153 (28%) were diagnosed with probable or confirmed spinal or paraspinal mycosis at the injection site. Forty-one patients had both meningitis and spinal or paraspinal infection, and 112 had only spinal or paraspinal infection.  Fungal infection was confirmed in 78 patients (51%) by finding hyphae in tissues, positive PCR, or culture. One hundred sixteen (76%) underwent operative debridement plus antifungal therapy.  Initial therapy was voriconazole + liposomal amphotericin B in 115 patients (75%) and voriconazole alone in 38 patients (25%). The median duration of liposomal amphotericin B therapy for the 115 patients who completed treatment with this agent was 13 d. This agent was stopped in most patients because CDC suggested voriconazole was likely adequate therapy for Exserohilum. Over half of patients had multiple hospital admissions for complications of the infection, the antifungal therapy, or for surgery. Seventy-three were admitted ≥ 3 times and 12 had ≥ 6 admissions. As of January, 2014, 20 of these patients remained on an azole agent. Five patients died of infection.