Thomas M. Kerkering, MD; Marissa L. Grifasi, PharmD; Anthony W. Baffoe-Bonnie, MD; Ekta Bansal, MD; Dorothy C. Garner, MD; Jean A. Smith, MD; Deborah D. Demicco, MD; Charles J. Schleupner, MD; Rabia A. Aldoghaither, MD; Vipul A. Savaliya, MD
Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M12-2734.
Reproducible Research Statement: Study protocol, statistical code, and data set: De-identified data, protocol, and statistical analysis are available on request.
Requests for Single Reprints: Thomas M. Kerkering, MD, Virginia Tech Carilion School of Medicine, 1906 Belleview Avenue, Roanoke, VA 24014.
Current Author Addresses: Drs. Kerkering, Grifasi, Baffoe-Bonnie, Bansal, Garner, Smith, Demicco, Schleupner, Aldoghaither, and Savaliya: Virginia Tech Carilion School of Medicine, 1906 Belleview Avenue, Roanoke, VA 24014.
Author Contributions: Conception and design: M.L. Grifasi, A.W. Baffoe-Bonnie, E. Bansal, D.C. Garner, J.A. Smith, D.D. Demicco, V.A. Savaliya.
Analysis and interpretation of the data: T.M. Kerkering, M.L. Grifasi, A.W. Baffoe-Bonnie, E. Bansal, D.C. Garner, J.A. Smith, D.D. Demicco, C.J. Schleupner, V.A. Savaliya.
Drafting of the article: T.M. Kerkering, M.L. Grifasi, A.W. Baffoe-Bonnie, E. Bansal, D.C. Garner, D.D. Demicco, V.A. Savaliya.
Critical revision of the article for important intellectual content: T.M. Kerkering, M.L. Grifasi, A.W. Baffoe-Bonnie, E. Bansal, D.C. Garner, J.A. Smith, D.D. Demicco, C.J. Schleupner, V.A. Savaliya.
Final approval of the article: T.M. Kerkering, M.L. Grifasi, E. Bansal, D.C. Garner, J.A. Smith, D.D. Demicco, V.A. Savaliya.
Provision of study materials or patients: M.L. Grifasi, C.J. Schleupner, V.A. Savaliya.
Statistical expertise: T.M. Kerkering.
Administrative, technical, or logistic support: T.M. Kerkering, A.W. Baffoe-Bonnie, E. Bansal, D.C. Garner, J.A. Smith, D.D. Demicco, C.J. Schleupner, R.A. Aldoghaither, V.A. Savaliya.
Collection and assembly of data: T.M. Kerkering, M.L. Grifasi, A.W. Baffoe-Bonnie, E. Bansal, D.C. Garner, J.A. Smith, D.D. Demicco, R.A. Aldoghaither, V.A. Savaliya.
This article has been corrected. The original version (PDF) is appended to this article as a supplement.
Administration of epidural steroid injections (ESIs) with contaminated methylprednisolone resulted in an outbreak of fungal meningitis in many locations in the United States.
To characterize early clinical findings and initial response to treatment.
Case series with standardized observation studied from 4 October to 31 October 2012.
An 800-bed hospital in Virginia.
172 patients who presented to the hospital with exposure to contaminated ESI.
Standardized approach to screening, case definition, treatment, and data collection.
Clinical findings, cerebrospinal fluid (CSF) values, magnetic resonance imaging (MRI), serum and CSF voriconazole concentrations, and clinician assessment of response to therapy.
Of 172 patients presenting to the hospital who had had ESI, 131 had lumbar puncture because of symptoms or signs consistent with central nervous system disease. Twenty-five (19%) had neutrophilic meningitis. All were started on voriconazole therapy alone. Three patients developed stroke during treatment. Ten patients had arachnoiditis, another had an epidural abscess, and 9 had urine retention. Fifteen continued to receive voriconazole, and 10 were switched to amphotericin B. Cerebrospinal fluid leukocyte counts began to decrease by day 13 of treatment. Findings on MRI included ventriculitis, leptomeningeal enhancement, infarction, hemorrhage, and arachnoiditis. Serum voriconazole levels varied, and CSF concentrations of voriconazole were approximately 50% those of serum. Exserohilum rostratum and Cladosporium species have been cultured.
This is an observational study of an evolving outbreak. Not all exposed patients presented for evaluation. Follow-up is too short to determine final outcomes.
Meningitis after receipt of contaminated ESI has been diagnosed in many exposed patients presenting to 1 hospital. Most patients have improved on receipt of empirical voriconazole therapy. The full natural history and long-term sequelae of this infection are currently unknown.
In the autumn of 2012, an outbreak of fungal meningitis caused by contaminated epidural steroid injections occurred in the United States.
Staff at a hospital in Virginia rapidly set up a telephone screening program for patients presenting with a history of possible exposure to the contaminated product. They developed uniform protocols for diagnosis, treatment, and follow-up in real time, based on evolving information. Here, they report early observations on patients found to have meningitis.
Patients continue to be followed, and long-term outcomes, including optimum treatment duration, are unknown.
A successful response to a 2012 fungal meningitis outbreak was achieved by rapid mobilization at the hospital level.
Appendix Table 1. Studies Ordered on CSF
Patients seen in the emergency department with symptoms or signs related to an epidural steroid injection.
Not all hospitalized patients had meningitis. This also represents the epidemic curve for the local outbreak. One hundred seventy-two patients were screened, of whom 131 had lumbar puncture and 42 were hospitalized. Twenty-five of the 42 hospitalized patients had meningitis. Other reasons for hospitalization were comorbid conditions, further evaluation of presenting illness, observation, or pain control.
Table 1. Comparison of Initial Cerebrospinal Fluid Values in Exposed Patients, With and Without Meningitis
Table 2. Presenting Signs and Symptoms and Baseline Laboratory Results at Time of Initial Positive Cerebrospinal Fluid Result for Meningitis
Representative magnetic resonance images of the brain.
A. Abnormal left pontine meningeal enhancement, with probable left fifth or sixth nerve enhancement (axial T1 postcontrast). B. Axial T1 post: abnormal meningeal enhancement along right prepontine and ambient cisterns on right. C. Left pontine infarction, nonhemorrhagic (axial T2-weighted image). D. Diffusion restriction indicating acute infarction (axial diffusion-weighted image). Correlates with panel C. E. Axial diffusion-weighted image: acute infarction, left pons.
Representative magnetic resonance images of the spine.
A. Sagittal T1 postgadolinium; dural/leptomeningeal enhancement at L5/S1. B. Sagittal postgadolinium: dural and leptomeningeal contrast enhancement. C and D. Axial postgadolinium T1 images that correlate with A and B, respectively, and show dural and nerve root enhancement (postcontrast).
Voriconazole serum concentrations.
Table 3. Adverse Events Associated With Intravenous Voriconazole
Appendix Table 2. Summary of 10 Patients Switched From Intravenous Voriconazole to Intravenous Amphotericin B Product
Change in CSF leukocyte count over time in individual patients.
Patient numbers correspond with those in Appendix Table 2. CSF = cerebrospinal fluid; LP1 = lumbar puncture at time of hospitalization; LP2 = second lumbar puncture, a mean of 6 d into treatment (range, 4 to 8 d) for 24 patients; LP3 = third lumbar puncture, a mean of 13.5 d into treatment (range, 11 to 17 d).
* Patient 6 declined a second lumbar puncture until day 18, at which time his CSF leukocyte count was 2 cells/mL.
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Kerkering TM, Grifasi ML, Baffoe-Bonnie AW, Bansal E, Garner DC, Smith JA, et al. Early Clinical Observations in Prospectively Followed Patients With Fungal Meningitis Related to Contaminated Epidural Steroid Injections. Ann Intern Med. 2013;158:154–161. doi: 10.7326/0003-4819-158-3-201302050-00568
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Published: Ann Intern Med. 2013;158(3):154-161.
CNS Infections, Hospital Medicine, Hospital-Acquired Infections, Infectious Disease, Neurology.
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