Quick Action Saves Lives at Georgetown
There are roughly 5,000 species of mushrooms in the United States. Of these, approximately 100 are poisonous and sometimes are deadly when consumed. There is no Food and Drug Administration (FDA)-approved therapy for mushroom poisoning, which is relatively uncommon in the United States. The poisoning is usually the result of unsuspecting novices who consume mushrooms gathered in the wild. One of the most toxic mushrooms is the death cap (amanita phalloides), which attacks the liver and kidneys. When that happens, often the only recourse is an organ transplant, which is why the Georgetown Transplant Institute (GTI) and its research team became the focal point for an outbreak this September.
On Thursday, September 15, Georgetown University Hospital (GUH) received the first patient suffering from mushroom poisoning. He had been referred to GUH by another hospital’s intensive care unit.
Springfield, Virginia resident Frank Constantinopla picked mushrooms from his backyard to cook in a stir-fry. A native of the Philippines, Constantinopla said it was a common practice back home.
“Mr. Constantinopla was transferred to Georgetown University Hospital and we made a clinical diagnosis of mushroom poisoning,” said Jacqueline Laurin, MD, a liver transplant specialist at the transplant institute. “He had eaten the mushrooms, gotten very ill with gastrointestinal symptoms, and his liver enzymes were extremely high, meaning the mushroom toxin was poisoning his liver.”
The Investigational Drug
Dr. Laurin was aware of a drug being studied elsewhere for amatoxin poisoning, the toxin in the amanita species of mushrooms. Georgetown physicians contacted the local Poison Control Center who put them in contact with a physician in Santa Cruz, California who is conducting a clinical study for amatoxin poisoning using an intravenous preparation of milk thistle called silibinin (sold as Legalon® SIL in Germany, where the drug is already approved).
The FDA allows certain experimental compounds to be investigated and tested in humans under strict guidelines at designated centers, where use of the research protocol has been approved by the institutional review board (IRB). It is the responsibility of the IRB to protect people who participate in research of unapproved drugs, medical devices or procedures. However, neither Georgetown nor any other Baltimore-Washington-area institution had an IRB-approved research protocol for silibinin. In a situation like this, the FDA makes possible an emergency use provision even without an established research protocol.
Arrangements were made to get the drug flown and couriered to Georgetown University Hospital and Mr. Constantinopla received the drug that Thursday evening September 15.
The Georgetown University Medical Center research team at the Georgetown Transplant Institute began the process of preparing a clinical study so that if another patient would need the silibinin, there would be an approved protocol in place. The study materials would need IRB-approval. The process had not yet been completed before a second patient arrived days later at the emergency room.
The following Wednesday, a second patient, 82 year-old Walter Lantz Jr. of Frederick, Maryland was transferred to Georgetown with suspected mushroom poisoning.
GTI research personnel quickly completed the IRB application while Georgetown University Medical Center personnel called for an urgent IRB meeting by teleconference. The drug needed to be given to the patient as soon as possible.
“We do what needs to be done to deliver top notch care for the patients that come to us, and we have sufficient contacts to find out what’s out there,” said Sheila Cohen Zimmet, Senior Associate Vice President for Regulatory Affairs at GUMC. “The IRB members are willing to drop what they’re doing and make themselves available, and that’s not just Georgetown faculty—that’s community members, too. One is a retired dentist and another is a local attorney.”
The protocol was approved; and the patient began receiving the drug that evening.
"The drug used is not truly an antidote in that it reverses the effects of the toxin. What it does, it prevents it from continuing to be taken up,” explained Sorell Schwartz, PhD, chair of the IRB subcommittee on adverse effects who participated in the emergency IRB meeting.
“These gentlemen were very lucky. Because of this now approved protocol, if there are any cases of mushroom poisoning in the future, GUH is an approved referral center for this IV preparation of milk thistle,” said Dr. Laurin. “We hope the public will get the message though. Our area has seen a lot of rain and dampness in the past month meaning there are a lot of mushrooms sprouting up in people’s yards. We hope people will leave those alone.”
Said Mr. Constantinopla, “I’m lucky I’m still alive today. Without the team of doctors and Georgetown University, maybe I see St. Peter already.”
Now both men are recovering, and GUMC is monitoring their cases as part of the ongoing research of silibinin. All of the data collected will be included in the final analysis of the drug’s safety and effectiveness.
By Frank Reider, GUMC Communications