The Centers for Disease Control and Prevention (CDC) has issued an update on outcomes from 2012 to 2014 of the unprecedented multistate outbreak of fungal meningitis and other infections associated with contaminated methylprednisolone acetate (MPA) injection solution. The Mycoses Study Group Education and Research Consortium is conducting a long-term follow-up study and warns clinicians that infections may recur.
The consortium published their current findings, including data on relapses in some patients, in the October 30 issue of the Morbidity and Mortality Weekly Report.
“Among patients who received contaminated MPA injections, it is not known whether resuming additional steroid injections increases the risk for developing either a de novo fungal infection or a relapse of infection,” write Orion Z. McCotter, MPH, from the Mycotic Diseases Branch, Division of Foodborne, Waterborne, and Environmental Diseases, National Center for Emerging and Zoonotic Infectious Diseases, CDC, and colleagues.
“Clinicians and patients should remain watchful for symptoms of infection in patients exposed to contaminated MPA, because fungal infections can develop slowly and are difficult to eradicate,” they caution.
The CDC, state and local health departments, and the US Food and Drug Administration began investigating the outbreak in September 2012. Most cases were localized spinal or paraspinal infections, such as epidural abscess, phlegmon, discitis, vertebral osteomyelitis, arachnoiditis, or other complications at or near the injection site.
By October 23, 2013, there were 751 reported cases: 31% with meningitis only, 20% with meningitis and parameningeal infections, 43% with parameningeal infections only, and 4% with peripheral joint infections.
Two additional cases include one patient who developed clinical meningitis (cerebrospinal fluid [CSF] white blood cell count >500/μL) in November 2014, 26 months after receiving a contaminated MPA injection. CSF cultures were negative, and CSF polymerase chain reaction for Exserohilum DNA (the predominant pathogen linked to the outbreak) was negative.
However, CSF 1,3-β-D-glucan was elevated (>600 pg/mL and decreased (to 57 pg/mL) after antifungal treatment. Testing CSF in other patients also suggested that 1,3-β-D-glucan might be a sensitive and specific fungal meningitis marker reflecting clinical response.
“It is unclear whether this late onset case of meningitis is directly attributable to the contaminated steroid injection or arose from an unrelated etiology,” the authors write.
Most patients received antifungal treatment for at least 6 months after diagnosis, and by 12 months, 192 (42%) of 455 patients followed were considered cured, 41% were no longer receiving antifungals but were not cured, 7% were still receiving antifungals, 8% had died (24 of 35 deaths resulted from outbreak-associated infections), and 2% had incomplete data.
There have been eight reports of fungal infection relapse after antifungal treatment (1% of 753), with median time to relapse of 90 days (range, 20 – 662 days).
“However, a recently identified relapse that occurred 21 months after cessation of therapy highlights the need for continued vigilance by providers and patients involved in this outbreak,” the authors say.
The CDC recommends that patients with new or worsening symptoms at or near the injection site should undergo magnetic resonance imaging with contrast of the symptomatic area or areas, with a low threshold for repeat scan in patients who continue to have symptoms after a normal study.
Some patients being treated for fungal meningitis who had no previous evidence of localized infection at the injection site subsequently had evidence of localized infection on imaging studies. Even in the absence of new or worsening symptoms at or near the injection site in patients being treated for meningitis, clinicians should strongly consider obtaining a magnetic resonance imaging scan of the injection site approximately 2 to 3 weeks after diagnosis of meningitis. Early identification of new disease may allow early drainage or other specific interventions.