CDC Warns of Recurring Fungal Meningitis

By Walter F. Roche Jr.

Two new victims of the 2012 fungal meningitis outbreak have been identified by federal health officials and in one of those cases the victim was not diagnosed with the disease until 26 months after bring injected with a fungus tainted steroid.
The two new cases, both in Virginia, were included in a study released this week by the U.S. Centers for Disease Control and Prevention. The study warned health care providers to be on the lookout for symptoms even though the outbreak became public in 2012.
"It is unclear whether this late onset case of meningitis is directly attributable to the contaminated steroid injection or arose from an unrelated etiology," the study state.
The victim, whose diagnosis came 26 months after injection, did not have a prior bout with fungal meningitis.
The new cases boosted the official CDC victim count to 753, but the study contains no explanation for an even higher victim case count from federal prosecutors.
In a pending criminal case stemming from the outbreak, federal agents stated that there were 778 victims and 76 of them died. According to the CDC count there were only 64 deaths.
Kate Fowlie, a CDC spokeswoman, said the CDC tally includes those cases which met the agency's specific criteria for inclusion in the outbreak.
"We do not have information about the court case filings or those numbers," Fowlie said in an email response to questions.
The study also focused on relapses and in one case a relapse was reported some 21 months after the victim had stopped anti-fungal treatment. According to the study eight relapse cases have been reported.
One know relapse cases was Joan Peay of Nashville, Tenn. who was hospitalized in 2013 when fungal meningitis struck her for the second time.
CDC officials said that the newly reported case demonstrates the need for physicians to continuously monitor the health of known victims. 
The study could not determine whether those victims who resumed steroid injections are more likely to suffer a recurrence.
"Among patients who received contaminated MPA injections, it is not known whether resuming additional steroid injections increases the risk for developing either a de novo fungal infection or a relapse of infection," the study states.
The study is an interim report on a federally funded study based at the University of Alabama Birmingham and headed by Dr. Peter Pappas. Under the study, researchers are following the health history of outbreak victims and detailing their recoveries.
Fowlie said the study is expected to be completed in late 2016.
The 2012 outbreak, according to state and federal regulators, was the result of fungus tainted methylprednisolone acetate being injected into the spines and joints of unsuspecting patients.
Fourteen owners and former employees of the New England Compounding Center are under indictment for charges ranging from second degree murder to mail fraud as a result of a grand jury probe of the outbreak.
The firm filed for bankruptcy in late 2012 and a court approved liquidation plan includes $200 million to pay victims and creditors.

Notes from the Field: Update on Multistate Outbreak of Fungal Infections Associated with Contaminated Methylprednisolone Injections, 2012–2014

Weekly

October 30, 2015 / 64(42);1200-1

Orion Z. McCotter, MPH1; Rachel M. Smith, MD1; Mathew Westercamp, PhD1; Thomas M. Kerkering, MD2; Anurag N. Malani, MD3; Robert Latham, MD4; Sheree L. Peglow, MD5; Rajal K. Mody, MD1; Peter G. Pappas, MD6; Tom M. Chiller, MD1

During September 2012, CDC, in collaboration with state and local health departments and the Food and Drug Administration (FDA), investigated a multistate outbreak of fungal meningitis and other infections caused by injections of contaminated methylprednisolone acetate solution (MPA) (1). After this unprecedented outbreak, scientists in the CDC Mycotic Diseases Branch, along with infectious diseases specialists who cared for patients from the outbreak, clinical experts, and public health officials from affected states, have continued to monitor the recovery of affected patients. A long-term follow-up study involving these patients was initiated and is being conducted by the Mycoses Study Group Education and Research Consortium (MSGERC). This update summarizes subsequent information about the current state of the outbreak.
By October 23, 2013, the date of the final update to the outbreak website,* 751 patients had been reported. Among all outbreak-related cases, 31% of patients had meningitis only, 20% had meningitis and parameningeal infections, 43% had parameningeal infections only, and 4% had peripheral joint infections. Two additional cases have subsequently been identified, bringing the total to 753 cases. The first of these two cases occurred in 2013, but was only identified retrospectively. The final reported patient developed clinical meningitis (cerebrospinal fluid [CSF] white blood cell count >500/µL) in November 2014, 26 months after receiving a contaminated MPA injection, thereby meeting the CDC probable case definition. The patient's CSF was negative when cultured for various bacteria, viruses, and fungi. Additionally, CSF specimens were negative when tested for Exserohilum DNA (the predominant pathogen identified during the outbreak) by polymerase chain reaction. However, the level of 1,3-β-D-glucan (BDG), a fungal marker, was elevated (>600 pg/ml), and decreased (to 57 pg/ml) after antifungal treatment. Testing the CSF of patients affected by this outbreak indicated that BDG might be a sensitive and specific marker for fungal meningitis associated with this outbreak and that BDG levels might correlate with clinical response (2,3). It is unclear whether this late onset case of meningitis is directly attributable to the contaminated steroid injection or arose from an unrelated etiology.
As part of the MSGERC long-term follow-up study, clinical data for patients involved in the outbreak are being collected by the infectious disease physicians who cared for them. Preliminary data indicate that most patients received antifungal treatment for at least 6 months after diagnosis. By 12 months after the initial diagnosis, 192 (42%) of 455 patients followed by the study were considered cured (defined as no radiologic or laboratory evidence of fungal infection, resolved or improved signs and symptoms, and not having received antifungal treatment for at least 3 months), 185 (41%) were no longer receiving antifungals but did not yet meet the definition of cured, 32 (7%) were still receiving antifungal treatment, 35 (8%) had died (24 deaths were attributable to outbreak-associated infections), and 11 (2%) had incomplete follow-up data.
To date, CDC has received eight reports of relapse of fungal infection after antifungal treatment, accounting for 1% of these 753 patients. Among six relapsed patients for whom the interval from initial cessation of antifungal therapy to relapse date was known, the median time to relapse was 90 days (range = 20–662 days); however, a recently identified relapse that occurred 21 months after cessation of therapy highlights the need for continued vigilance by providers and patients involved in this outbreak.
Among patients who received contaminated MPA injections, it is not known whether resuming additional steroid injections increases the risk for developing either a de novo fungal infection or a relapse of infection. Some patients have had surgical procedures to correct underlying musculoskeletal problems, and a limited number of patients had surgical placement of orthopedic hardware, with no reports of complications attributable to the infection.
Clinicians and patients should remain watchful for symptoms of infection† in patients exposed to contaminated MPA, because fungal infections can develop slowly and are difficult to eradicate. A detailed review of patient care and outcomes is underway as part of the MSGERC long-term follow-up study.

Acknowledgments

Official Seeks to Disallow NECC Claims Worth $2 Billion +

By Walter F. Roche Jr.

A key official in the bankruptcy of the company blamed for a fatal 2012 fungal meningitis outbreak is asking a judge to disallow dozens of claims totaling well over $2 billion.
In a motion filed this week in U.S. Bankruptcy Court in Massachusetts, Paul D. Moore, the former trustee in the bankruptcy of the New England Compounding Center, said that some of those claims were duplicates, while others were superseded or amended by subsequent claims.
Still others were filed after a court deadline and some lacked the necessary documentation. Some have already been satisfied. Overall his motion calls for some 80 claims to be formally denied.
Moore, whose current title is post confirmation officer, wrote that if the claims were not denied, some of the claimants would get double payments.
The outbreak was caused by fungus tainted steroids shipped by NECC to health clinics, physicians and hospitals around the country. Seventy-six patients died, most from fungal meningitis. More than 750 were sickened
Many of the claims which Moore's motion would deny were made by health care providers, seeking to recoup expected claims from their patients sickened by the preservative free methylprednisolone acetate.
The largest single claim listed in the motion was for $1.17 billion submitted by the Saint Thomas Outpatient Neurosurgical Center in Nashville, Tenn. That claim was listed in the category of satisfied or released claims.
 On the same list was the Specialty Surgery Center of Crossville, Tenn. which had submitted a claim of $240 million.
Only one, a claim filed by the Toledo Clinic, was listed in the duplicate claim category.
The Tennessee Health Department and the Tennesssee Pharmacy Board submitted claims of $10 million apiece to cover the cost of the investigation of the outbreak. By agreement the claims were reduced to $5 million, but state officials concede it is unlikely the money will ever be recovered.
Some $200 million has been amassed in the bankruptcy and the vast majority of that money is expected to be paid to victims of the outbreak or to the survivors of those who died.
Contact:wfrochejr999@gmail.com

Cases Severed in Meningitis Criminal Cases

By Walter F. Roche Jr.

The cases of two of the defendants in the criminal investigation of the New England Compounding Center have been split off from the remaining 12 and they will be tried separately.
U.S. District Judge Richard G. Stearns Wednesday granted the motion filed by the attorney for Carla and Douglas Conigliaro for the two to be tried separately.
A third defendant, Kathy Chin, also has filed a motion for a separate trial but that motion has yet to be acted on.
The three were among 14 owners and former employees of NECC indicted late last year on charges ranging from mail fraud to second degree murder as a result of the grand jury probe of the deadly 2012 fungal meningitis outbreak that killed some 76 patients across the country.
At a recent hearing in Boston, Mass. Stearns also indicated that he may split off two other cases. Those are the charges against Barry Cadden, an owner of NECC, and Glenn Chin, NECC's chief pharmacist and Kathy Chin's husband. The two are facing 25 counts of second degree murder, among other lesser charges.
David Meier, the lawyer for Douglas and Carla Conigliaro, said his clients' cases are now "formally and legally separated from the other 12 NECC defendants." 

The two are charged with making a series of illegal withdrawals from bank accounts that were frozen under a court order.
NECC shipped fungus tainted spinal steroids to health care providers across the country who then injected the drugs into the spines and joints of unsuspecting patients.

TX Firm Voluntarily Recalling Sterile Compounded Drugs

By Walter F. Roche Jr.

A Texas firm that compounds drugs for sterile use has announced a voluntary recall of its sterile drugs, according to the U.S. Food and Drug Administration.
Downing Labs, LLC of Farmers Branch, Tex. issued the recall notice this week, stating that it was doing so out of an excess of caution. The company also stated that no adverse effects had been reported from the use of its products.
The statement did not provide the names of the drugs being recalled or the states to which they were distributed. It did say the drugs were distributed between April 20, 2015 and Sept. 15, 2015 throughout the United States and the United Kingdom.
Here is the announcement:

For Immediate Release

October 20, 2015

Contact

Consumers

Name
  pharmacist@downinglabs.com
 800-914-7435

Media

David Ball, Ball Consulting Group, LLC
  david@ballcg.com
 617-243-9950

Firm Press Release

FOR IMMEDIATE RELEASE – October 20, 2015 – Farmers Branch, TX – Downing Labs, LLC ("Downing Labs") is voluntarily recalling all lots of sterile products compounded and packaged by Downing Labs and that remain within expiry due to concerns over sterility assurance. The products were distributed nationwide and in the UK to patients and providers between April 20, 2015 and September 15, 2015. The recall does not pertain to any non-sterile compounded medications prepared by Downing Labs.
If there is a contamination in products intended to be sterile, patients are at risk of serious infections which may be life threatening. There have been no consumer complaints or reports of any issues with the recalled products to date. Downing Labs takes this measure voluntarily and solely out of an abundance of caution because Downing Labs takes the utmost care to ensure patient safety. Thus, Downing Labs is asking all patients and providers that received sterile compounded products from Downing Labs between April 20, 2015 and September 15, 2015 that remain within expiry to take the following actions:

1. Discontinue use of the products;
2. Set aside any unused product until further instructions are received on how to return the product; and
3. Contact Downing Labs at 800-914-7435 from the hours of 8:30AM-5:00PM central time Monday-Friday, or e-mail at pharmacist@downinglabs.com to discuss the return of any unused sterile compounded products. Customers should contact their physician or healthcare provider if they have experienced any problems that may be related to taking or using this drug product. Providers who have dispensed any sterile product distributed by Downing Labs to a patient(s) for use outside of the provider's office should contact the patient(s) to whom product was dispensed and advise the patient(s) of this recall.
   Adverse reactions or quality problems experienced with the use of these products may be reported to the FDA's MedWatch Adverse Event Reporting program either online, by regular mail or by fax.
   
   • Complete and submit the report Online: www.fda.gov/medwatch/report.htm
   • Regular Mail or Fax: Download form www.fda.gov/MedWatch/getforms.htm or call 1-800-332- 1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178
   This recall is being conducted with the knowledge of the FDA.
   Again, no consumer complaints have been received. Downing Labs’ primary concern is your safety and thus Downing Labs is taking this action out of an abundance of caution. Thank you for your continued support.

###

Attorneys Withdraw $2.1 million NECC Claim

By Walter F. Roche Jr.

A $2.1 million claim in the bankruptcy case of the New England Compounding Center has been withdrawn and a hearing scheduled for next month is expected to be canceled.
In a filing today in U.S. Bankruptcy Court in Massachusetts, attorneys for creditors in the NECC withdrew their claim for attorneys fees and expenses but left the door open to pursue the claims at a later date.
The creditors' attorneys had originally filed a request for $3.05 million, but later reduced the request to $2.1 million when Florida attorney Melvin Wright slashed his request from $1.35 million to $411,780.59.
In the filing today, the attorneys cited the potential cost of the Nov. 10 hearing.
"After conferring with other parties-in-interest and considering the potential costs associated with further pursuit of the omnibus application, the parties have determined that withdrawal of the omnibus application is in the best interest of the parties and the estate," the filing states.
The motion notes that the withdawal is "without prejudice to the collective and individual rights of the parties to pursue their claims in an alternative forum, including but not limited to" related civil cases now pending before U.S. District Judge Rya Zobel.
Bankruptcy Judge Henry J. Boroff, meanwhile, is still considering a trimmed down $3.75 million request from Paul D. Moore, the attorney who served as trustee in the bankruptcy. Moore initially requested $5.75 million.
Attorneys for plaintiffs have asked Boroff to further reduce Moore's fee request.
NECC is the company blamed for a 2012 fungal meningitis outbreak which sickened 778 patients across the country, killing 76 of them.
NECC filed for bankruptcy on Dec. 21, 2012. Some $200 million is expected to be available for creditors and victims of NECC.

Nashville Meningitis Cases Argued

By Walter F. Roche Jr.

Two Nashville attorneys sparred briefly over Tennessee's product liability law Wednesday in a Boston hearing on hundreds of cases stemming from the 2012 fatal fungal meningitis outbreak.
George Nolan, who represents several Tennessee victims, spoke in defense of a motion he filed to have the Judge Rya Zobel declare that the Saint Thomas Outpatient Neurosurgical Center meets the definition of a seller under Tennessee's unique product liability law.
Noting that the motion has not yet been fully briefed, Nolan said he had filed the motion prior to a related recent ruling by Zobel.
Attorneys for Tennessee victims contend that under Tennessee law health care firms like Saint Thomas can be held liable when the original seller of a defective product has been declared bankrupt. The Saint Thomas clinic purchased the steroid blamed for the outbreak from the New England Compounding Center, which filed for bankruptcy nearly three years ago.
Nolan's position was immediately challenged by Chris Tardio, the clinic's attorney.
Tardio, noted that the same issue could land before the Tennessee Supreme Court due to other legal proceedings.
In any case Tardio said he would need an extension beyond the normal 30 days to respond to Nolan's submission. He cited "mounds of discovery" that are still needed.
Clinic attorneys have vigorously disputed the claim that their clients can be held liable under the products liability law.
Zobel also heard arguments on cases in Maryland, New Hampshire and Virginia, including the case of a Virginia man who died on July 14, 2014, some two years after the outbreak became public.
Kristen Johnson, also a plaintiffs' attorney, told Zobel that plans were finally proceeding to vacate the former office of NECC in Framingham, Mass. She said that furniture and equipment would be auctioned off.
Zobel said she would consider proposals to further fill out the schedule for so-called bellweather cases which are set to get underway next Spring.
Zobel also was informed that a settlement had been reached with one of the insurance companies involved in the case. The details were not disclosed.
Meanwhile in the related bankruptcy case arguments are continuing over the $3.75 million fee request for Paul D. Moore, who served as trustee for NECC.
Lawyers for Moore filed a brief contending that a recent ruling by Zobel regarding the bellweather cases bolstered the contention that Moore's fee request was justified.
Her decision "demonstrates that the personal injury plaintiffs continue to benefit from the Chapter 11 case. The plaintiffs will benefit from speedy trials which will take place next spring," the brief states.
In a responding brief by plaintiff's attorney Thomas Sobel argued that Moore "played no role whatsoever" in  establishing the bellweather case process.
"Much of the work most critical to resolving these cases has always depended on the litigation efforts of parties other than Mr. Moore," Sobel wrote, adding that "in light of the limited amount available to tort victims, Paul Moore should not be requesting" an enhanced fee.
Contact: wfrochejr999@gmail.com

Little Agreement on First Meningitis Trials

By Walter F. Roche Jr.

With a firm trial schedule now in place, Tennessee plaintiffs and defendants in the suits stemming from the 2012 fungal meningitis outbreak remain far apart on which cases should be tried first.
Latest filings in U.S. District Court in Boston, show only one case is on both proposed lists submitted by attorneys for victims and the Saint Thomas Outpatient Neurosurgical Center.
U.S. District Court Judge Rya Zobel recently issued a ruling setting the timetable for the first Tennessee cases to be heard in her courtroom beginning next Spring.
The suits stem from the outbreak triggered by fungus tainted methylprednisolone acetate injected into the spines and joints of unsuspecting patients. The outbreak killed 76 patients across the country including 16 from Tennessee.
Zobel has asked the opposing lawyers to try to reach agreement on so-called bellwether cases (See Below) that will, hopefully, serve as templates for the hundreds of other cases stemming from the outbreak.
The opposing attorneys filed the cases under similar categories established in a related bankruptcy case. The categories are based on the severity of the victims' illness.
Victim Fredia Berry's name is the only one to appear on both lists, records show. She was injected with the the steroid at the Saint Thomas outpatient center on Aug. 24 and Sept. 7 of 2012. According the filings she subsequently underwent three lumbar punctures to determine whether she had contracted fungal meningitis.
The list submitted by Saint Thomas lawyers include Reba Temple, who was the ninth known victim of the outbreak. The former Hickman County Health Department official died three years ago.
Others on the defense list include Denis Brock, who suffered fungal meningitis and an additional infection, and Reba Skelton, who also suffered fungal meningitis.
The plaintiffs' list includes Diane Reed of Nashville, whose death left her severely handicapped husband without a caretaker and Thomas Rybinski of Smyrna, an autoworker, who died Sept. 29, 2012.
Also on the plaintiff list is Major Adam Ziegler who was injected on Sept. 11, 2012 and suffered a spinal or paraspinal infection.

 DEFENSE LIST

Reba Temple (Death)
Denis Brock (Meningitis plus infection)
Phillip and Maria Tyree (Meningitis plus infection)
Mae Parman (Meningitis only)
Reba Skelton (Meningitis only)
Fredia Berry (Local infection only)
Ashley Kinsey (No disease)
Donna Branham (No disease)

PLAINTIFF LIST

Diane Reed (Death)
Thomas Rybinski (Death)
Adam Ziegler (Local infection)
Lewis Sharer (Meningitis plus infection)
Jane Wray (Meningitis)
Anna Sullivan (Meningitis plus infection)
Fredia Berry (Lumbar punctures)
Basil McElwee (Meningitis)

A “bellwether” is a sheep that leads a flock, around whose neck a bell is hung. In a bellwether trial procedure, a random sample of cases large enough to yield reliable results is tried to a jury. A judge, jury, or participating lawyers use the resulting verdicts as a basis for resolving the remaining cases.
Bellwether Trials, Alexander D. Lahav, George Washington Law Review, April 2008, Vol. 76, No. 3 at 576, 577.