FDA finds fungus in steroid shots, meningitis toll rises
David Cohen, M.D.·Published 20 October 2012·9 min read
Key points
U.S. health officials made their first confirmation of the presence of a deadly fungus in one of three lots of steroids tied to a national meningitis outbreak as the death toll rose to 20 on Thursday.
NECC is under investigation by federal authorities over how it supplied hospitals, clinics and other healthcare providers with large orders of drugs, including whether it violated state laws regulating pharmacies.
Food and Drug Administration said it was still testing two additional lots of methylprednisolone acetate, the steroid used to treat back pain, for the presence of the rare Exserohilum fungus.
"Now we can definitively say that the injections are linked to the infection," Dr.
U.S. health officials made their first confirmation of the presence of a deadly fungus in one of three lots of steroids tied to a national meningitis outbreak as the death toll rose to 20 on Thursday.
The U.S. Food and Drug Administration said it was still testing two additional lots of methylprednisolone acetate, the steroid used to treat back pain, for the presence of the rare Exserohilum fungus. It is also testing other injectable drugs that were supplied by the New England Compounding Center, or NECC, in Massachusetts.
"Now we can definitively say that the injections are linked to the infection," Dr. Tom Chiller, an epidemiologist with the U.S. Centers for Disease Control and Prevention, told Reuters in an interview. "To date, CDC has no firm evidence of infection in any patients beyond those exposed to the contaminated lots."
THE CDC said the death toll climbed by one to 20, while nine new cases brought the national total to 254, including the first in New York - the 16th state with confirmed infections.
Michigan reported its fourth fungal meningitis death and new cases were also reported in Indiana, New Hampshire, New Jersey, Ohio and Tennessee. There are also three cases of peripheral infections in joints, the CDC said.
"There were a lot more spinal injections performed versus joint injections, but the infection rate may also reflect the fact that joint infections might be slower or the incubation period could be longer ... we just don't know," Chiller said.
"The signs and symptoms of meningitis include fever, headache, stiff neck, nausea and vomiting, photophobia (sensitivity to light) and altered mental status," the Food and Drug Administration said in a statement. "Symptoms for other possible infections may include fever; swelling, increasing pain, redness, warmth at injection site; visual changes, pain, redness or discharge from the eye; chest pain, or drainage from the surgical site (infection within the chest). Patients should contact their healthcare provider if they have any of these signs or symptoms."
FDA enforcers raided NECC’s Framingham, Mass., facility on Tuesday night. Earlier in the day, FDA officials said inspections of the facility made them worry about the sterility of any of the pharmacy's products.
Members of Congress said they wanted answers, although as of Wednesday they had not scheduled promised hearings. Massachusetts Rep. Ed Markey, a Democrat, noted that NECC distributed controlled substances including morphine and fentanyl without a proper license.
“The list of recalled NECC drug products appears to include nearly 1,000 formulations that contain controlled substances that fall under the jurisdiction of the Drug Enforcement Agency (DEA),” Markey said in a statement. NECC shipped more than 17,000 vials from the three suspect lots of steroid to clinics in 24 states. The pharmacy makes hundreds of more products.
Written and revised by
David Cohen, M.D.
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About 14,000 patients are believed to have been exposed to the potentially tainted NECC steroid and some 97 percent of them have been contacted so far, the FDA and CDC said.
NECC issued a statement saying it was "earnestly focused on determining, along with these agencies, the cause of contamination in vials of this product - and to rapidly and professionally carry out a recall to remove all NECC products from circulation."
Most of those sickened so far were injected with steroids from three particular lots made by NECC, and the sickest patients developed meningitis, an inflammation of the protective membranes, or meninges, covering the brain and spinal cord. The swelling is usually caused by bacteria or viruses, but meningitis can also be caused by a fungus. Most of those who died suffered strokes.
"As a result of the ongoing investigation of NECC, a patient with possible meningitis potentially associated with epidural injection of an additional NECC product, triamcinolone acetonide, has been identified through active surveillance and reported to FDA. Triamcinolone acetonide is a type of steroid injectable product made by NECC," the FDA said in a statement.
In addition, two patients who got steroids made by NECC injected into their ankles have developed infections. CDC doctors say they're still checking to see if the infections are fungal in nature. The two patients are not in danger of meningitis, CDC says.
At least one hospital system, Maryland-based Medstar, says it has begun compounding its own products when possible now to ensure their sterility. Bonnie Levin, who heads pharmacy services at Medstar, told NBC News the hospitals have rooms that are as sterile as operating rooms to do this.
So-called compounding pharmacies are frequently at the center of controversy. Under the FDA’s definition, compounding pharmacists are supposed to mix drugs to order only on an individual basis in response to a prescription from a doctor. FDA can step in if it suspects pharmacies are exceeding this authority, and if contamination is suspected.
U.S. doctors in Baltimore said early diagnosis and treatment of patients at risk of fungal meningitis was vital, based on the case of an otherwise healthy woman who declined rapidly after receiving steroid injections for neck pain.
Writing in the Annals of Internal Medicine, researchers at the Johns Hopkins School of Medicine described the deterioration of an unidentified 51-year-old who sought care in an emergency room for a severe headache a week after receiving an injection with tainted medication on August 31.
The CDC has said it learned about the fungal meningitis outbreak on September 21 and that it contacted patients injected as far back as May.
Patients found to be infected are treated with a fairly high dose of voriconazole, sold by Pfizer Inc under the brand name Vfend, which can cause side effects including "visual disturbances," fever and headache.
"We are finding a fair amount of toxicity," Dr. Carol Kauffman, infectious diseases chief at the University of Michigan Health System, said during an infectious disease and epidemiology conference in San Diego. "We don't want to have 80-year-olds hallucinating. That's indeed what is happening."
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CONTRACTS UNDER SCRUTINY
NECC is under investigation by federal authorities over how it supplied hospitals, clinics and other healthcare providers with large orders of drugs, including whether it violated state laws regulating pharmacies.
U.S. Senator Richard Blumenthal Of Connecticut, who previously called for a criminal investigation of NECC, raised new questions on Thursday about a government contract for medications from NECC's sister company, Ameridose.
In a letter to the U.S. Department of Defense, he cited a July purchase agreement for specialized medicines between the U.S. Army Medical Command and Ameridose. They were intended for use in the neonatal intensive care unit at the Army's Tripler Medical Center in Honolulu.
Most of the meningitis cases have been linked to Exserohilum, a fungus associated with grass and rotting wood that appears to be especially aggressive in attacking tissues in the spine and brain stem.
The CDC has said it first learned about the fungal meningitis outbreak on September 21 and health officials have linked it to tainted vials of injectable steroid methylprednisolone acetate made by the New England Compounding Center (NECC) in Framingham, Massachusetts.
U.S. Senator Richard Blumenthal of Connecticut sent a letter on Thursday to the Department of Defense seeking information about a July purchase agreement for specialized medicines between the U.S. Army Medical Command and a company called Ameridose that has the same owners as NECC.
The drugs were purchased for use in the neonatal intensive care unit at the Army's Tripler Medical Center in Honolulu.
"I am deeply concerned that this contract exposed numerous military families to a drug produced by a compounding center that was unregistered with the FDA and uninspected for safety and effectiveness," Blumenthal's letter said.
Blumenthal, who previously called for a criminal investigation of NECC, asked the DoD for information on the reasons for the sole source contract with Ameridose.
Most of the meningitis cases have been linked to Exserohilum, a fungus associated with grass and rotting wood that appears to be especially aggressive in attacking tissues in the spine and brain stem.
Fungal infections typically only attack people with severely compromised immune systems, such as patients who have had bone marrow or organ transplants. Fungal spores can enter the lungs of these patients and make their way into the blood stream, and eventually into the central nervous system.
In the case described by the team at Johns Hopkins, the injection was the woman's first and she had no medical history of having a compromised immune system, nor was she taking any long-term medications.
Doctors found nothing and sent her home, but the woman returned the next day with more severe symptoms and was admitted to the hospital, where doctors tried a series of antibiotics and other drugs as the woman continued to decline.
Tests for a host of infections, including herpes simplex virus, varicella zoster virus - which causes chicken pox and shingles - Epstein-Barr virus, cytomegalovirus and West Nile virus, were all negative, as were tests for cryptococcal fungi, a known cause of fungal meningitis.
The woman died 10 days after being admitted to hospital, the same day the team found evidence of Exserohilum in her spinal fluid. An autopsy showed massive tissue death in the brain stem, inflammation in the blood vessels and evidence of a stroke.
Based on the case, the researchers urged doctors to be aware of the signs and symptoms of fungal meningitis and to seek rapid diagnosis and treatment to prevent "serious complications and deaths."
The CDC advises patients who feel ill and are concerned they were injected with one of the recalled products to contact their physician.
On a call with healthcare providers earlier this week, the CDC said the typical incubation period was one to four weeks after injection, but that it could be up to two months or longer.
"We want you to remain vigilant for several months after injection," Dr. Tom Chiller of the CDC told physicians.
Symptoms of fungal meningitis include new or worsening headache, fever, sensitivity to light, stiff neck, weakness or numbness in any part of your body, slurred speech, increased pain, redness or swelling at the injection site.
Fungal infections typically only attack people with severely compromised immune systems, such as patients who have had bone marrow or organ transplants.
In the case described by the team at Johns Hopkins, the injection was the woman's first and she had no medical history of having a compromised immune system, nor was she taking any long-term medications.
Doctors found nothing and sent her home, but the woman returned the next day with more severe symptoms and was admitted to the hospital, where she was treated with a series of antibiotics and other drugs.
Tests for a host of infections were all negative. The woman died 10 days after being admitted to the hospital, the same day the team found evidence of Exserohilum in her spinal fluid. An autopsy showed massive tissue death in the brain stem, inflammation in the blood vessels and evidence of a stroke.
Based on the case, the researchers urged doctors to be aware of the symptoms of fungal meningitis and to seek rapid diagnosis and treatment to prevent "serious complications and deaths."
The CDC advises patients who feel ill and are concerned they were injected with one of the recalled products to contact their physicians.
On a call with healthcare providers earlier this week, the CDC said the typical incubation period was one to four weeks after injection, but that it could be two months or longer.
"We want you to remain vigilant for several months after injection," Chiller told physicians.
Symptoms of fungal meningitis include new or worsening headache, fever, sensitivity to light, stiff neck, weakness or numbness in any part of the body, slurred speech, increased pain, redness or swelling at the injection site.
