Real-world Experience in the Midst of an Exserohilum Meningitis Outbreak

Abstract

THE OUTBREAK OF INVASIVE FUNGAL INFECTIONS AMONG patients who received injections of contaminated methylprednisolone acetate from the New England Compounding Center continues. New cases have been reported to the Centers for Disease Control and Prevention weekly and more than 740 patients in 20 states have been diagnosed with meningitis, spinal or paraspinal infections, or joint infections (ie, epidural abscess, phlegmon, diskitis, vertebral osteomyelitis, arachnoiditis, or other complications at or near the injection site). Spinal or paraspinal infections can present weeks to months after the initial injection. Current recommendations from the Centers for Disease Control and Prevention call for patients with new or worsening symptoms at or near the injection site to undergo magnetic resonance imaging (MRI) with contrast of the symptomatic areas. In this issue of JAMA, Malani et al provide important information detailing the possibility of paraspinal or spinal infections in those without a change from their baseline pain or neuropathic symptoms. These findings suggest that current screening recommendations may need reconsideration. Patients exposed to contaminated steroids can no longer be reassured that the lack of new or progressive symptoms equates to a lack of infection. In the report by Malani et al, 36 of 172 patients (21%) screened for evidence of paraspinal or spinal infection exhibited MRI abnormalities suggestive of infection. Although a review of symptoms was not available for all screened patients, among the 115 patients surveyed, 80 (70%) had no change in their symptoms. Of these 80 patients, 13 (16%) had an abnormal MRI. A total of 35 of 115 patients experienced an increase in their baseline pain or neuropathic symptoms, yet had not received an MRI (although one may have already been ordered). After diagnostic imaging was obtained, 22 of these 35 patients (63%) had imaging findings consistent with focal infection. These results suggest either reassurance at a prior clinical visit may have been offered, or patients were not aware of the need to seek care for worsening symptoms. Virtually all patients with abnormal MRI findings met criteria from the Centers for Disease Control and Prevention for probable or proven disease. Twenty-four of these 35 patients required operative intervention as a diagnostic or therapeutic maneuver, and all 35 received antifungal therapy. In light of these findings, it may seem reasonable to mandate MRI screening for all exposed patients. However, this recommendation may not be applicable to the entire exposed population. The lot (No. 06292012@26) of contaminated steroid responsible for cases in Michigan and the majority of those in Tennessee was associated with a higher attack rate than other steroid lots (Nos. 05212012@68 and 08102012@51) causally implicated in this outbreak. The reasons for differing attack rates by region and lot number remain obscure. However, storage conditions, age of the product, extent of exposure (ie, multiple exposures), and host factors, including immunogenetic differences in susceptibility, likely each play a large role. Other institution-related or region-specific factors may contribute to patient risk for fungal infection. For example, translaminar injection was an independent risk factor for fungal infection but transforminal injection was not. Geographicor region-specific practices for injection have not been reported. Furthermore, physician preference for procedure type may play a role in the variation of attack rates between locations and should be considered in the development of diagnostic and treatment recommendations. The report by Malani et al also raises the question of how infection develops in patients without worsening underlying back pain or neuropathic symptoms. Patients with preexisting chronic pain may pay less attention to the development of slightly more pain, or increases in pain frequency. It is not clear if a validated symptom questionnaire was used in the study by Malani et al to assess subtle changes from