The mold linked to the fungal meningitis outbreak is an unlikely pathogen that has left clinicians scrambling to diagnose and treat affected patients and wondering what to expect next.
Exserohilum rostratum is one of a class of black molds, so-called because they have melanin in their cell walls, that only rarely cause human illness and even more rarely cause invasive disease, experts told MedPage Today.
“They really prefer to infect plants,” according to Carol Kauffman, MD, of the University of Michigan in Ann Arbor.
As of Monday, according to the CDC, the outbreak has claimed 30 lives and made 429 people sick in 19 states.
E. rostratum is found pretty much everywhere in soil and decaying matter, but its most common clinical manifestation is allergic sinusitis, with occasional cases of keratitis if the mold gets into a scratch on the cornea, Kauffman said.
In rare cases, a splinter can carry the mold deep into tissue, leading to a localized infection.
That, in a sense, is what has happened in the meningitis outbreak. “Unfortunately,” Kauffman said, “it happens to be a localized infection in the central nervous system.”
The outbreak has been linked to injections of a steroid, preservative-free methylprednisolone acetate, that was contaminated with E. rostratum.
The majority of cases have involved some sort of central nervous system infection, mainly meningitis, although several patients have presented with classic stroke symptoms thought to be caused by the fungal infection.
The outbreak, which came to light in late September with a single case in Tennessee, is the largest outbreak ever of fungal meningitis, a CDC spokesman told MedPage Today.
Earlier ‘Outbreak’ Eerily Similar
There is, however, at least one historical precedent: In 2002 in North Carolina, contaminated spinal injections of a steroid caused five cases of fungal meningitis, including one that ended in death.
The report detailing the outbreak in the CDC’s Morbidity and Mortality Weekly Report is an eerie foreshadowing of recent events.
The steroid was the same, preservative-free methylprednisolone acetate, and the contaminant was Exophiala dermatitidis, a relative of E. rostratum. The substance was made by a compounding pharmacy and shipped to 11 states. And an FDA investigation called into question the pharmacy’s ability to produce sterile products.
For John Perfect, MD, of Duke University Medical Center, the current outbreak is the result of lessons not learned in 2002. A central message, he told MedPage Today, is that compounding drugs is “a tricky business” that needs keen oversight.
Perfect, one of the handful of doctors who had previously been involved in such an outbreak, said the historical precedent left little guidance for today’s doctors.
The CDC, he said, is making “recommendations on the fly” and doctors are doing the best they can with an influx of patients. “There’s nothing in the textbooks.”
It’s no wonder clinicians find themselves a little bit at sea, according to Thomas Patterson, MD, of the University of Texas Health Science Center in San Antonio.
Among the difficulties they face, Patterson told MedPage Today:
- No one really knows the optimal treatment regimen, although the CDC has made recommendations.
- It’s not clear yet if combination therapy will yield better outcomes.
- Diagnosis is difficult because in most patients cultures remain stubbornly negative, forcing doctors to rely on epidemiology and clinical presentation.
- It’s not clear why the mold invades the central nervous system.
- It’s also not clear why some people who got injections of the tainted steroid developed illness and others did not.
- Doctors don’t know yet if there will be a role for surgery in cleaning out abscesses or injection sites.
- And it’s not known why this outbreak is so much larger than the one in 2002.
The first few weeks of the outbreak have clarified one thing, Kauffman said. “There are not a lot of (drug) choices in antifungal treatment in general, she said. But in the current outbreak, “we know what choices we have” even though there is some variation from place to place.
The CDC is recommending voriconazole (Vfend) as a first-line therapy and liposomal amphotericin B as a fallback. Both drugs get into the central nervous system and are active against E. rostratum, Kauffman said.
Both drugs were used in the 2002 outbreak, she noted, so there is some experience with them in comparable circumstances.
“This organism, one would at least historically judge, might have responses similar to those seen in 2002,” Patterson said, adding that voriconazole — then a new drug — was used successfully in 2002.
But even with the CDC guidance to treat aggressively, not all outcomes are good, he said, and relapses after initial response are common.
Unexpected Complication Arises
And doctors are now beginning to report an unexpected complication that has been developing in some patients even after antifungal treatment has started — abscesses at the injection site.
Patterson praised the CDC for acting as a central sounding board and developing recommendations from the clinical experience of dozens of centers.
“It’s kind of an evolving and ongoing process where careful feedback of results is very important,” he said.
Why only five people fell sick in 2002, compared with hundreds this year, probably results from a combination of factors, the experts said — the steroid this time might have had more contaminant, the drug was shipped more widely in 2012, and the fungus itself is different and might have different characteristics.
Many fungi can cause neurologic disease, Patterson said. Indeed, the index case in this outbreak was traced to Aspergillus fumigatus, which, once inhaled, can eventually invade the central nervous system.
Aspergillus is known as an “angio-invasive” organism, a characteristic it shares with E. rostratum, Patterson said. So it might be that the mold, once injected, invaded blood vessels and was carried to the brain.
“That’s likely the reason some patients had strokes,” he said.
The compounding pharmacy involved in the current outbreak — the New England Compounding Center of Framingham, Mass. – shipped three lots of steroid in 17,000 vials to pain clinics in 23 states.
E. rostratum has been found in unopened vials from two of the three lots and the third lot is still being studied.
But only a handful of patients have lab-confirmed infection with the organism, Patterson noted, which makes the diagnosis more difficult. In most of those cases, confirmation has come from an investigational genetic test being developed by the CDC, rather than from patient cultures.
Nevertheless, “all of us hope and think that earlier diagnosis is being made,” he said.
On the positive side, Patterson added, the risk of disease seems to drop as the time from the last steroid injection increases. “As time goes on, you are – hopefully – going to have fewer and fewer patients who develop disease.”
Source: Med Page Today http://www.medpagetoday.com/Neurology/GeneralNeurology/35764?utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=WC&xid=NL_DHE_2012-11-06&eun=g514381d0r&userid=514381&[email protected]&mu_id=