Health

Alert

UPDATE: MULTISTATE OUTBREAK OF FUNGAL MENINGITIS AND JOINT INFECTIONS ASSOCIATED WITH CONTAMINATED

STEROID MEDICATIONS

The Delaware Division of Public Health (DPH) is issuing this health alert posted by the Centers for Disease Control and Prevention (CDC).

For additional information, refer to http://emergency.cdc.gov/HAN/han00329.asp.

Below is the CDC Health Alert:

ISSUE: In addition to the injectable steroid linked to fungal meningitis from the New England Compounding Center (NECC),

all NECC products are being recalled and the FDA recommends medical professionals follow up with any patients who received an injectable

product from that compounding pharmacy.

Summary

The Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA) continue to work closely with state

public health departments on a multistate investigation of fungal meningitis and joint infections among patients who received

methylprednisolone acetate injections prepared by the New England Compounding Center (NECC) in Framingham, MA. Some of these patients who

received epidural injections also suffered strokes that may have resulted from their infection. This Health advisory notice (HAN)

provides updated information on the following:

• Status of the investigation.
• FDA issuance of a MedWatch Safety Alert on October 15 advisingclinicians to follow-up with patients who received injectable NECC products, including any ophthalmic drug that is injectable or used in

  conjunction with eye surgery, and a cardioplegic solution purchased from or produced by NECC after May 21, 2012.

• Recommendations for clinicians.
• Case definition.

Background

CDC, in collaboration with FDA, state public health departments, and state boards of pharmacy, has been investigating an ongoing outbreak

of fungal infections associated with a contaminated steroid medication, preservative-free methylprednisolone acetate (80mg/ml) prepared

by the New England Compounding Center, in Framingham, Mass. CDC and state public health departments are actively coordinating outreach to

patients who have been exposed to this contaminated medication.

As of October 16, 2012, a total of 233 cases, which includes 2 peripheral joint infections and15 deaths, have been reported in 15 states

(see CDC’s website for up-to-date information about case count

and distribution by state). The fungus Exserohilum rostratum has been recovered from clinical specimens from multiple patients

with fungal meningitis and with other spinal infections (e.g., epidural abscess). CDC and FDA continue to investigate the possibility of

contamination with additional organisms. At this time, one clinical specimen has tested positive for the fungus Aspergillus

fumigatus, and another has tested positive for the fungus Cladosporium. Fungal meningitis is not transmitted from person to

person.

The clinical presentation of infected patients with fungal meningitis remains consistent with that described in previous reports: onset

of symptoms is typically between 1 to 4 weeks following injection with a variety of symptoms, including fever, new or worsening headache,

nausea, and new neurological deficit (consistent with deep brain stroke). However, fungal infections can be slow to develop, and there

are reports of longer periods between injection and onset of symptoms; and, therefore, patients and their doctors need to watch closely

for symptoms for at least several months following the injection. Some of these patients’ symptoms were very mild in nature.

Cerebrospinal fluid (CSF) obtained from these patients has typically had an elevated white cell count (usually with a predominance of

neutrophils), and in many cases low glucose and elevated protein. As of October 16, two peripheral joint infections have been

reported.  CDC expects that through ongoing patient notification efforts, additional patients with infections of the joints may come

forward.

On September 26, 2012, NECC voluntarily recalled the following lots of methylprednisolone acetate (PF) 80mg/ml:

• Methylprednisolone Acetate (PF) 80 mg/ml Injection, Lot #05212012@68, BUD 11/17/2012
• Methylprednisolone Acetate (PF) 80 mg/ml Injection, Lot #06292012@26, BUD 12/26/2012
• Methylprednisolone Acetate (PF) 80 mg/ml Injection, Lot #08102012@51, BUD 2/6/2013

On October 6, NECC expanded its previous recalls to include all products currently in circulation that were compounded at and distributed

from its facility in Framingham, Mass. More information about this recall is available at the FDA website.

All cases reported as of October 16 have occurred after injections with methylprednisolone acetate products from one of the three lots

recalled on September 26.

FDA MedWatch: Additional NECC Products of Potential Concern

On October 15, FDA released a MedWatch Safety Alert announcing that, as a

result of the ongoing investigation of NECC, a patient with possible fungal meningitis who had received an epidural injection of

triamcinolone acetonide produced by NECC has been identified through active surveillance efforts by CDC and state health departments and

reported to FDA. Triamcinolone acetate is a type of steroid injectable product made by NECC. As of October 17, there is no laboratory

evidence of fungal infection in this patient. As noted above, all cases of fungal meningitis identified to date have been associated with

methylprednisolone acetate, another similar steroid injectable product distributed by NECC.

In addition, FDA received a report of one cardiac transplant patient with Aspergillus fumigatus infection who was administered

NECC cardioplegic solution, which is used to prevent injury to the heart during surgery. Investigation of this patient is ongoing; there

may be other explanations for this patient’s Aspergillus infection.

This is preliminary information and CDC does not have firm evidence that infections have been caused by exposure to NECC products beyond

the three previously listed lots of methylprednisolone acetate. Out of an abundance of caution, FDA has advised clinicians to follow up

with patients to whom they have administered an injectable product, including an ophthalmic drug that is injectable or used in

conjunction with eye surgery, and a cardioplegic solution purchased from or produced by NECC after May 21, 2012.

Clinicians should perform a thorough diagnostic evaluation to exclude infection in those patients who report signs and symptoms of

infection following high-risk exposure to one of these NECC products (e.g., exposure of product to sterile body site). If the evaluation

of these patients is suggestive of fungal infection, please consult existing CDC treatment guidance http://www.cdc.gov/hai/outbreaks/clinicians/index.html. Consultation with an

infectious disease specialist is strongly encouraged to help make treatment decisions in these cases.

Products from NECC can be identified by markings that indicate New England Compounding Center by name or by its acronym (NECC), and/or

the company logo. Additional information about the MedWatch Safety Alert

notice is available on the FDA website.

Recommendations for Clinicians

CDC and FDA have three recommendations for clinicians.

1. Clinicians should contact (by phone or in person) any patient who had an injection (e.g., spinal, joint) after May 21, 2012, usingany of the following three recalled lots of preservative-free methylprednisolone acetate (80mg/ml) produced by NECC,to determine if they

   are having symptoms:

   • Methylprednisolone Acetate (PF) 80mg/ml Injection, Lot# 05212012@68, BUD 11/17/2012
   • Methylprednisolone Acetate (PF) 80mg/ml Injection, Lot#06292012@26, BUD 12/26/2012
   • Methylprednisolone Acetate (PF) 80mg/ml Injection, Lot# 08102012@51, BUD 2/6/2013

   Symptoms that should prompt diagnostic evaluation include fever, new or worsening headache, neck stiffness, sensitivity to light, new

   weakness or numbness, increasing pain, redness or swelling at injection site. Some of the symptoms of patients who have ultimately been

   diagnosed with fungal meningitis have been mild and not classic for meningitis (e.g., new or worsening headache without fever or neck

   stiffness).

2. Healthcare professionals should cease use of any product produced by NECC, all of which have been recalled.
   • Through its investigation of the NECC facility, FDA cannot confirm the sterility of any of the NECC products. Clinicians are alsorequested to report any suspected adverse events following use of these products to FDA’s MedWatch program at

     1-800-332-1088 or www.fda.gov/medwatch

   As in the past, CDC continues to recommend that clinicians remain vigilant for any possible adverse events related to the use of any

   NECC product. Clinicians are encouraged to report such events to their state public health department.

3. CDC will continue to update clinical guidance as more information becomes available. As of October 16, CDC has updated clinicianguidance addressing:
   • Interim Treatment Guidance for Central Nervous System (CNS)

     and/or Parameningeal Infections Associated with Injection of Potentially Contaminated Steroid Products

   • Interim Treatment Guidance

     for Septic Arthritis Associated with Injection of Potentially Contaminated Steroid Products

   • Interim Guidance for Management of

     Asymptomatic Persons Exposed to Potentially Contaminated Steroid Products

   • Diagnostic Testing for Septic

     Arthritis and Specimen Submission to CDC – Outbreak Associated with Injection of Potentially Contaminated Steroid

     Products

   • Instructions for Clinicians Regarding

     Diagnostic Testing and Specimen Shipping for Central Nervous System and/or Parameningeal Infections

   • Role of Antifungal Prophylaxis in

     Asymptomatic Patients

These are available on the CDC website (see “additional information” below)

CDC Case Definitions

The current investigation is a rapidly evolving situation and information about cases continues to be updated. For the most recent

information about case definitions, please see CDC’s clinical guidance web page at http://www.cdc.gov/hai/outbreaks/clinicians/casedef_multistate_outbreak.html.

Additional Information

• Multistate Fungal Meningitis Outbreak Investigation (http://www.cdc.gov/hai/outbreaks/meningitis.html)
• MMWR Early Release:  Multistate Outbreak of

  Fungal Infection Associated with Injection of Methylprednisolone Acetate Solution from a Single Compounding Pharmacy — United

  States, 2012. (http://www.cdc.gov/mmwr/preview/mmwrhtml/mm61e1012a1.htm?s_cid=mm61e1012a1_w)

• CDC HAN Advisory: Meningitis and Stroke Associated with Potentially Contaminated

  Product (http://www.bt.cdc.gov/HAN/han00327.asp)

• CDC HAN Advisory:  Update:  Multistate Outbreak of Meningitis and Stroke

  Associated with Potentially Contaminated Steroid Medication (http://www.bt.cdc.gov/HAN/han00328.asp)

• CDC Website on Fungal Diseases (http://www.cdc.gov/fungal/)
• FDA Statement on Fungal Meningitis Outbreak (http://www.fda.gov/Drugs/DrugSafety/ucm322734.htm)
• Delaware Division of Public Health, Bureau of Epidemiology (24/7): 1-888-295-5156
• Delaware Division of Public Health Webpage on meningitis: http://dhss.delaware.gov/dph/files/meningocfaq.pdf

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