Clinicians should consider performing lumbar puncture in asymptomatic patients who received epidural or paraspinal injections with contaminated steroid products linked to the ongoing and widening fungal meningitis outbreak, officials with the Centers for Disease Control and Prevention (CDC) said today during a Clinician Outreach and Community Action (COCA) call.
As of today, there are 328 cases of fungal infection and 24 deaths in 18 states linked to injectable methylprednisolone acetate produced by the New England Compounding Center (NECC) in Framingham, Massachusetts. This includes 5 peripheral joint infections.
Since early in the outbreak, the CDC has recommended against antifungal prophylactic or presumptive treatment of exposed asymptomatic patients in the absence of diagnostic testing with results indicating meningitis. This recommendation "remains unchanged," Tom Chiller, MD, MPH, medical epidemiologist in the Division of Foodborne, Waterborne & Environmental Diseases, National Center for Emerging and Zoonotic Infectious Diseases at CDC said during the call.
On the basis of ongoing investigation, the CDC has determined that patients who received epidural or paraspinal injections with contaminated steroid product within the last 6 weeks (42 days) may be at greatest risk of developing meningitis and therefore additional monitoring should be considered. The agency says clinicians have 2 options:
Option 1:
- Continue to closely monitor for development of symptoms, with a low threshold for performing lumbar puncture should the patient become symptomatic. When diagnostic lumbar punctures are performed, they should be done through a site other than the site used for epidural injection when possible.
Option 2: (This option, the CDC says, is estimated to reduce the maximal risk for stroke or death from approximately 0.4% to 0.3% in comparison to option 1).
- Perform lumbar puncture, through a site other than the site used for epidural injection when possible.
- If the cerebrospinal fluid (CSF) examination shows less than or equal to 5 white blood cells (WBCs), the patient should continue to be followed very closely for onset of symptoms. If the patient remains asymptomatic, clinicians can consider repeating weekly lumbar punctures until 6 weeks (42 days) have passed since the last epidural or paraspinal injection with contaminated steroid product, at which time the patient can be monitored closely for the development of symptoms, with a low threshold for performing lumbar puncture should the patient become symptomatic.
- Patients with more than 5 WBCs in CSF should be treated for fungal meningitis according to current treatment guidance.
- In making a management decision, clinicians should also consider the risk associated with lumbar puncture (eg, post–lumbar puncture headache, CSF leak, the theoretical risk that fungi could be transferred from the epidural space into the subarachnoid space of a patient who has received epidural or paraspinal injections with contaminated steroid products).
The CDC also advises that patients who received their last epidural or paraspinal injection with contaminated steroid product more than 6 weeks (42 days) ago should continue to be closely monitored as previously recommended for development of symptoms, with a low threshold for performing lumbar puncture should the patient become symptomatic. When diagnostic lumbar punctures are performed, they should be done through a site other than the site used for epidural injection when possible, the CDC says.
During the call, Dr. Chiller emphasized that, "with our clinical expert team we are reviewing these guidelines on a daily basis and modifying them based on information we receive from treating clinicians as well as case reports of patients with these infections."
Risk Estimates Over Time
The CDC notes that as of October 22, 2012, at least 26 days should have passed since any patient received an injection with medication from these lots given that the medication was recalled on September 26, 2012.
They say the estimated remaining risk of developing meningitis is "likely to be no greater than 5% on the 26th day following their last epidural or paraspinal injection, and then decreases to a risk of no greater than 1% by 6 weeks (42 days) following injection."
The majority of these patients will have risks for meningitis much lower than this, the agency notes, "and their risk will continue to decrease as more time elapses since their last injection."
In addition, the CDC says the estimated remaining risk of stroke or death is likely to be no greater than 0.4% on the 26th day following their last epidural or paraspinal injection, and then decreases to a risk of no greater than 0.08% by 6 weeks (42 days) following injection. Again, most of these patients will have risks of stroke or death much lower than this, "and their risk will continue to decrease as more time elapses since their last injection," the CDC says.
For the most recent information about this and other clinical guidance, as well as case definitions being used in the current investigation, visit CDC's Clinician Guidance Web page.
"Serious" Problems at NECC
Meanwhile, in a report released Tuesday the Massachusetts Department of Health said a preliminary investigation of NECC revealed "serious deficiencies and significant violations of pharmacy law and regulations that clearly placed the public's health and safety at risk."
The report says the company distributed 2 of the recalled lots of methylprednisolone acetate before receiving results of sterility testing. It also says final sterilization of product did not follow proper standards for autoclaving (sterilization through high-pressure steam) as is required. The preliminary investigation also found "visible black particulate matter" in several recalled sealed vials of the drug.
Further, that early investigation showed evidence that NECC distributed large batches of compounded sterile products directly to facilities apparently for general use rather than requiring a prescription for an individual patient.
Customer Lists Available
On Wednesday, the US Food and Drug Administration (FDA) made available 2 lists of customers who received potentially contaminated products that were shipped on or after May 21, 2012, from NECC.
The first list includes customer names and addresses, organized by state.
The second list contains the same basic information as the first list but is organized alphabetically by customer name and also includes the specific products shipped, the quantities of product shipped, and the shipping date.
During today's COCA call, Janet Woodcock, MD, director of the Center for Drug Evaluation and Research at FDA, emphasized that these lists were prepared according to information provided by NECC, and the agency "cannot vouch" for the completeness or accuracy of the lists.
A notice on the FDA Web site adds: "Products shipped by NECC may be missing from the lists and facility information may be incomplete. Nevertheless, this is the best information we have available, at this time, to help inform facilities and health care providers of NECC products shipped to their facilities since May 21, 2012."
FDA is currently advising that doctors follow up with patients when the following 3 conditions are met:
- The medication was an injectable product purchased from or produced by NECC, including an ophthalmic drug that is injectable or used in conjunction with eye surgery, or a cardioplegic solution;
- The medication was shipped by NECC on or after May 21, 2012; and
- The medication was administered to patients on or after May 21, 2012.
"Since the May 21, 2012 date is the date the first of three lots of methylprednisolone acetate implicated in the current outbreak was produced, products produced and shipped by NECC on or after May 21, 2012 are believed at this time to be of greatest risk of contamination," the FDA said.
"Now that we have shipping information available, we are updating FDA's recommendation to health care providers so that they can focus their attention on following up with the patients who are believed to be at greatest risk of receiving a contaminated product."
The FDA has provided clinicians with a template for a Patient Notification Letter. This template is for healthcare professionals notifying patients administered a drug produced by NECC that has been recalled.
Find the latest MedWatch safety alert on the outbreak here:
Unsung Public Health Heroes
In an FDA Voice blog post, FDA Commissioner Margaret A. Hamburg, MD, acknowledged efforts of many individuals over the last few weeks.
"When there is a multi-state outbreak of illnesses, what federal agencies are doing in response is often the focus of attention," she said. "All too often, the dedicated efforts of countless other public servants at the state, county, and local levels aren't acknowledged as much."
"As we all strive to resolve the tragic outbreak of fungal meningitis tied to contaminated steroid injections, I want to recognize the invaluable role of our colleagues across the country. These front line public health officials at all levels of government work alongside the FDA and CDC every day, and even more closely in times of crises."
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