Steroid That Led to Meningitis Outbreak Difficult to Sterilize

Dr. Michael Omidi examines the difficulty in properly manufacturing the drug methylprednisolone acetate, an injectible steroid that is very vulnerable to contamination. As Dr. Michael Omidi explains, this drug was the catalyst for the recent outbreak of meningitis.  

Methylprednisolone acetate, the injectible steroid that was the catalyst for the recent outbreak of fungal meningitis, is an extremely difficult drug to manufacture properly due to the fact that it cannot be sterilized through traditional means. It cannot be heated – which would kill any microbial contaminants but seriously degrade the drug itself – and it cannot be filtered, since the drug contains crystalline particles that would also be removed.[1]

Contamination of methylprednisolone acetate has particularly devastating after-effects, since this drug remains in the system for months, and also causes the suppression of the immune-defense system.  If bacteria or fungal matter is incorporated into the mix, both the drug and the spinal fluid (if it is used in an epidural application) tend to actually fertilize the microbes, allowing them to flourish and spread throughout the body and potentially into the brain.

The recent fungal meningitis outbreaks were not the first examples of fatalities that resulted from tainted injectible steroids.  In 2001, three people in Northern California died after having received an injection of contaminated betamethasone from a compounding pharmacy.  A South Carolina compounding pharmacy issued contaminated injectible steroids which resulted in infecting seven people and killing two in 2002.  More recently, a Florida compounding pharmacy distributed contaminated steroids that caused severe vision damage to 13 patients in March of 2012.

The fact that compounding pharmacies receive their methylprednisolone from suppliers overseas (China and India) that do not have to adhere to the standards of U.S. drug companies is a cause for concern.  Active Pharmaceutical Ingredients come from suppliers grossly contaminated.  Nonetheless, it is the compounding pharmacy’s obligation to sterilize the product before incorporating it into anything meant for distribution, but the sterilization practices are often lacking. 

The fact that compounding pharmacy practices are not regulated by the Food and Drug Administration, but by overburdened state agencies, means that compounding pharmacies can operate without any significant policing.  The NECC (New England Compounding Center) demonstrated stunningly negligent sterilization practices; the clean room was kept at drastically varying temperatures, there was debris circulating throughout the facilities from a nearby recycling plant and there was evidence of bacterial growth and mold on many of the clean room surfaces.

One of the reasons that hospitals and clinics consistently used compounding pharmacy drugs was that the injectible steroids distributed by compounding pharmacies do not contain preservatives, while the FDA-approved drug manufacturing company products do.  Preservatives are thought to possibly contribute to permanent nerve damage in patients, as well as pose a risk for brain damage in premature babies.

Unfortunately, very little was known about the fungus that caused the outbreak, E. rostratum, and it wasn’t considered to be effectively parasitic in humans.  This lack of expertise led to the medical community being poorly equipped to handle the illnesses, and as a result, many older or immune-deficient patients had to be given doses of antifungal medications that caused severe side effects.

As consumers, we like to research the products we put into our bodies, and make sure that we are getting the highest quality practicable.  However, how can we control the types of medications we have administered to us when we are in need of medical attention?  Hopefully, the different governing agencies, both local and federal, will not soon forget this medical crisis, and try to be more diligent when it comes to the wide distributions of medicines that are supposed to help, not hurt us.

By Dr. Michael Omidi 

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[1] Brown, David: The Drug in Fungal Meningitis Cases is Hard to Make and Unusually Dangerous When Contaminated The Washington Post 2/8/2013 http://articles.washingtonpost.com/2013-02-08/national/36984968_1_methylprednisolone-acetate-exserohilum-betamethasone

Meningitis and Arachnoiditis Risks

New England Compounding Center: Contaminated Batches

It is very frightening to think that the medications and drug treatments we hope will help us when we are sick or injured might actually cause problems that are immeasurably worse than the problems they were meant to cure. Even though only three batches of the drug methylprednisolone acetate have been found to be tainted with the fungi Aspergillus and Exserohilum, the medical havoc those three batches have caused haven’t yet been fully understood, and new conditions, symptoms and illnesses are appearing every day. Unfortunately, it appears that meningitis was not the only condition to have arisen from this crisis. The contaminated medications from the New England Compounding Center have caused not only fatal outbreaks of fungal meningitis, but also another dangerous condition known as arachnoiditis, for which there is no cure, and very little treatment.

What is Arachnoiditis?

Arachnoiditis is an inflammation of the membranes surrounding the spinal cord. It can be caused by the introduction of a virus, bacteria, fungus or chemical into the spinal cord, or from spinal trauma or surgery. Arachnoiditis is extremely painful, and sufferers experience numerous debilitating symptoms, including difficulty controlling limbs, inability to sit for long periods of time, numbness, inability to walk for extended periods and inability to stand for long periods and burning pain in the legs and back. Many sufferers experience incontinence and sexual dysfunction.

Epidural Injections cause Arachnoiditis

Epidural injections (the injection of steroids or other medications near the spinal column) have long been the culprit of arachnoiditis. With the increase in steroid epidural injections, so came the increase of medical complications due to spinal trauma at the injection site. Although many back pain sufferers have experienced relief from sometimes crippling pain that can even radiate into the arms and legs, many physicians believe the technique is being overused. Until the meningitis outbreak, the risk of infection wasn’t being factored into an FDA review of the potential for catastrophic neurological injuries.

Treating Arachnoiditis

Arachnoiditis is a chronic condition. Treatments and pain management techniques vary, but surgery is discouraged because it is typically a painful procedure with long recovery time and only temporary relief. Many patients have had success with different physical and pain management therapies, but it is recommended that a specialist in the area be consulted because it is not a well known or widely experienced condition, and is often misdiagnosed as a pinched nerve.

Arachnoiditis Magnified Since Meningitis Outbreak

Although there doesn’t appear to be a great deal of research into the reversal of arachnoiditis, the recent health crisis might galvanize some activity. Now, most of the efforts of medical researchers seem to be in the arena of pain management in arachnoiditis sufferers rather than cure.

Arachnoiditis Symptoms

While the symptoms of and prognosis for arachnoiditis are scary, it should be noted that the severity of the symptoms varies significantly, depending upon the location of the inflammation. Some patients are able to lead a perfectly full life with the help of persistent emotional and physical therapies, as well as regular exercise.

Physician reported to state health department about tainted batches of steroids months ago

Several months ago, a physician made her state health department aware of a tainted batch of methylprednisolone acetate, a steroid that is injected near the spinal column in order to treat some forms of chronic back pain, which seemed to be causing a violent form of fungal meningitis. This fungus was highly resistant to conventional forms of treatment, and finds the brain tissue the most hospitable environment, since the brain has low resistance to infection. Samples of the fungus have been difficult to detect in the infected patients; the most common and accurate method of detection has been extracting and testing spinal fluid. So what is this fungus, and how did it get into these medications?

Exserohilum rostratum: Cause of Infections

The fungus that caused these infections is called Exserohilum rostratum. It is highly resistant to the drug treatments, and because it is a pathogen that normally feeds on plant matter, it hasn’t received much research. It exists primarily in tropical and sub-tropical regions, but even though the laboratory was in New England, the messy environment would still be inviting to the fungus, which is airborne, and can travel in the winds from southern regions during the warmer months.

E. rostratum primarily attacks grasses. Plants have natural defensive mechanisms in place to keep the fungus from totally destroying them, but they cannot kill it outright. The fungus is like a vulture; it exists on plants and waits until the plant dies before it feeds on the remains. It can multiply very quickly; a colony can develop from a single spore in as little as two days.

What caused the meningitis outbreak?

While E. rostratum is almost never the cause of eye or sinus infections, there are increasing examples of this spore, and others related to it, causing more soft tissue infections than had ever been previously seen. Nevertheless, when the fungus was injected directly into the spinal column, it was easily carried by the spinal fluid—a nutritious and comfortable environment for the spores—into the brain, where it may have caused the strokes that killed some of the infected patients.

The sloppy conditions in which the medications were compounded would have been a welcoming environment for the spores, which can accumulate on lawn clippings and launch themselves into the air via a natural static electricity-based ejection mechanism. The fact that they got into the vials of medication isn’t surprising, under the circumstances, but why did they only contaminate some of the batches and not all of them? It is speculated that the spores were blown into the air from a nearby source on only one windy day, but no one yet knows the exact cause.

Fungal Meningitis: Dr. Pettit discuses her patients story

In September of this year, a patient with an unusually virulent case of meningitis came to the attention of Dr. April Pettit. After having been administered antibiotics, the usual treatment for bacterial meningitis, this patient did not seem to be getting better; in fact, he was steadily deteriorating. Unsure of the kind of strain she was dealing with, Dr. Pettit sent a sample of the patient’s spinal fluid for testing. The results were surprising, to say the least.

Test Results: Fungal Meningitis

The lab reported that the meningitis was of the fungal variety. Fungal meningitis is not transmissible from person to person, and is extremely difficult to diagnose; fungal meningitis can trigger strokes, and physicians do not necessarily examine stroke patients for infections. Dr. Pettit asked the patient’s family (the patient was, by now, too weak to speak)if he had received an injection for chronic back pain into his spine. Dr. Pettit immediately called the state health department with this information.

Spinal Steroid Injections Contaminated

Spinal steroid injections for treatment of back pain are a common practice; millions of people undergo this procedure every year. The steroid medication in question, methylprednisolone acetate, was contaminated in the compounding pharmacy from which it originated. Compounding pharmacies are laboratories that prepare drug solutions for clinics and hospitals. These facilities commonly mix different drugs in accordance with a particular physician’s prescriptions. These solutions are not necessarily meant for large scale consumption, but nevertheless, many compounding pharmacies mix large batches of drugs that are, in turn, purchased by hospitals and clinics. These solutions are not regulated by the Food and Drug Administration, and compounding pharmacies do not have to adhere to the same rigorous safety regulations as do regular drug manufacturing companies. These compounding pharmacies open sterile vials of drugs from the manufacturer and mix them with other solutions or repackage them in smaller doses, leaving them vulnerable to contamination. Injectable medications must be mixed in sterile conditions—the surrounding air must be sterilized as well as the surfaces—since the body cannot fight off infections introduced directly into the circulatory system as efficiently as it can through the gastrointestinal tract.

Why Hospitals Purchase from Compounding Facilities

Why would hospitals purchase large batches of unregulated, dubious drugs? Perhaps because these compounded drugs are often cheaper than the pharmaceuticals from large drug companies, or because these specialty drugs are otherwise difficult to obtain. Whatever the reasons may be, compounding is meant to be for a specific patient’s needs, not a one-size-fits-all practice.

So contaminated "it could be seen with the naked eye"

When the vials of methylprednisolone acetate were examined, the fungal contamination was so virulent it could be seen with the naked eye. Before the outbreak was discovered, more than 17,000 vials of contaminated methylprednisolone acetate were shipped to clinics and hospitals in 23 states. To date, 32 people have died as a result of exposure to the contaminated drug, including Dr. April Pettit’s patient.