Health Advisory: Fungal Meningitis Outbreak – Change in Clinical Guidance

Health Advisory
Health Advisory
July 25, 2023

Summary:

This is an update to the Texas Department of State Health Services Health Alert issued on May 23, 2023.

The Texas Department of State Health Services (DSHS), the Centers for Disease Control and Prevention (CDC), and local public health departments are continuing to investigate an outbreak of fungal meningitis among patients hospitalized in Texas after undergoing surgical procedures under epidural anesthesia in Matamoros, Mexico. The causative organism Fusarium solani was recently isolated from one patient’s tissue culture specimen and was determined to be highly resistant to most antifungals.

DSHS is issuing this Health Advisory to alert Texas healthcare providers of recent changes in the treatment guidance for patients with this highly resistant strain of Fusarium solani. Key changes include increased dosing recommendations for amphotericin B and voriconazole along with the addition of fosmanogepix, an experimental drug in Phase II clinical trials, to the recommended treatment regimen (see the “Updated Treatment Recommendations” in this document for summary of the changes to the Interim Recommendations).

Background:

Public health officials are responding to a multistate outbreak of fungal meningitis among patients who received procedures under epidural anesthesia at River Side Surgical Center or Clinica K-3 in Matamoros, Mexico, from January 1 to May 13, 2023. These clinics were closed on May 13, 2023. The CDC recommends anyone who had surgery, including liposuction, with an epidural in Matamoros in 2023 should seek medical care to be evaluated for a possible fungal infection.

As of July 24, 2023, the outbreak includes 23 cases among Texas residents. Twenty-one patients were hospitalized, and eight have died. Cases range in age from late 20s to early 50s and include 21 females and 2 males.

Recommendations for Healthcare Providers:

This notice is for healthcare providers caring for patients who underwent a procedure under epidural anesthesia in the city of Matamoros, state of Tamaulipas, Mexico from January 1 to May 13, 2023, and therefore may be at risk of developing healthcare-associated fungal meningitis. These recommendations are based on the clinical experience of clinicians caring for patients during the current outbreak or during previous outbreaks of healthcare-associated fungal meningitis in Durango, Mexico, and the United States. 

Updated Treatment Recommendations:

Summary of important changes to guidance based on antifungal susceptibility testing results: 

  • Because of the high case-fatality rate seen during previous outbreaks of fungal meningitis involving Fusarium and the highly resistant profile of Fusarium solani isolated from a patient during the current outbreak, antifungal therapy should be started as soon as possible after collection of cerebrospinal fluid (CSF).
  • In addition to the combination of antifungal treatment with liposomal amphotericin B (Ambisome) and voriconazole, fosmanogepix is recommended.
  • Fosmanogepix is an experimental antifungal drug in phase II clinical trials, and is now recommended in addition to liposomal amphotericin B and voriconazole.
    • Obtaining fosmanogepix requires a two-step approval process:
      • Contact Pfizer at FMGXExpandedaccess@pfizer.com and ask for compassionate use of fosmanogepix; include in this email that fosmanogepix will be used for a patient in the ongoing fungal meningitis outbreak. Please copy HAIOutbreak@dshs.texas.gov in your correspondence with Pfizer.
        • Pfizer will respond with the next steps, which include a case report form and IRB approval. 
      • After Pfizer grants approval, contact the FDA at: (301) 796-3400 M-F: 8 – 4:30 EST and press * to request emergency IND (investigational new drug application).
    • Consider involving your hospital pharmacist or infectious disease pharmacist in the process for obtaining fosmanogepix.
    • The dose of fosmanogepix should be as high as Pfizer allows in their compassionate use protocol.
  • When initiating liposomal amphotericin B, 10 mg/kg dose is now recommended, instead of 5 mg/kg.
  • Voriconazole is still recommended, but clinicians should aim for a minimum trough level range of 4 to 5 micrograms per milliliter (mcg/ml) or a higher trough level if the patient can tolerate it.
  • Recommendations note that intrathecal amphotericin B has been used for certain refractory cases in the ongoing outbreak.

Healthcare providers should immediately consult with their local health department if they suspect their patient has fungal meningitis (Texas Local Public Health Contacts). If unable to make contact with your local health department, please email HAIOutbreak@dshs.texas.gov.

Diagnostic testing of all exposed patients:

For providers who suspect that they have a patient, the testing guidelines remain the same. 

Exposed patients include those who underwent a procedure under epidural anesthesia at River Side Surgical Center and Clinica K-3 in Matamoros, Mexico, from January 1 to May 13, 2023.

For both symptomatic and asymptomatic patients, the following tests are recommended:

  • Diagnostic lumbar puncture (LP), unless contraindicated
  • The following CSF tests should be performed/sent for all patients:
    • Opening pressure
    • Other routine CSF testing (e.g., color, cell counts [WBC with differential, RBC], protein, lactate, glucose)
    • Bacterial, mycobacterial, and fungal stains and cultures
  • The following CSF tests should be performed for patients with abnormal LP results:
    • Beta-d-glucan (Fungitell)
    • CSF for pan-fungal PCR testing or metagenomic testing
  • Serum Beta-d-glucan (Fungitell) and Aspergillus galactomannan
  • Brain imaging, ideally an MRI with and without contrast, is recommended in patients with symptoms to assess for meningeal enhancement, vasculitis, stenosis, hemorrhage, or ischemia, but this should not delay obtaining the LP.
  • An MRI with and without contrast is recommended for all patients with abnormal LP results (see the “Treatment and imaging recommendations for patients who present with CSF WBC >5” section of the Interim Recommendations).

DSHS recommends consultation with an infectious disease specialist while caring for a patient with suspected fungal meningitis. Providers who do not have access to infectious disease consultation or require additional expertise in management of fungal meningitis can email HAIOutbreak@dshs.texas.gov, and DSHS will help identify a provider specializing in treatment of fungal infections to provide consultation.

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