BETHESDA, MD 11 Nov 2016—The call on Sunday, August 7, was one the pharmacy department at Florida Hospital for Children in Orlando had been preparing for: an urgent request for help in treating a deadly amoebic infection.
"All of the right things happened," said pharmacy director Michael Kalita, reflecting on the survival of 16-year-old Sebastian DeLeon from infection with the free-living amoeba Naegleria fowleri.
Against the odds. DeLeon is reportedly the fourth person in the United States to survive N. fowleri infection.
The amoeba lives in fresh water and soil and normally feeds on bacteria. According to the Centers for Disease Control and Prevention (CDC), people become infected typically when they swim or dive in a lake, river, or other warm body of fresh water and N. fowleri–contaminated water enters their nose. People have also become infected from using N. fowleri–contaminated tap water for nasal irrigation.
After N. fowleri enters a person's nose, the amoeba penetrates the nasal mucous membrane and moves to the brain by way of the olfactory nerves.
The resultant disease, primary amebic meningoencephalitis, has claimed the lives of 98% of its victims, according to CDC's review of 142 U.S. cases from 1937 to 2013.
But the actual number of people who have contracted the disease is uncertain. Primary amebic meningoencephalitis is not among the diseases that healthcare providers, hospitals, and laboratories in every state must report to public health officials after identifying a case.
DeLeon's case came to national attention on August 23, when Florida Hospital for Children held a press conference.
A team effort. Humberto Liriano, the pediatric intensivist who treated DeLeon, told of the emergency department physician identifying the teenager's symptoms as those of meningitis, laboratory personnel identifying N. fowleri in the sample of cerebrospinal fluid, and "all . . . team efforts in our hospital" being directed at acquiring miltefosine, a fairly new drug marketed by a company in Orlando.
"Within 12 minutes, the drug arrived," Liriano said.
The teenager swallowed the first 50-mg capsule with water in the pediatric intensive care unit, Kalita recalled.
"That's when the medical staff decided that they were going to induce pharmaceutical coma in him as well as initiate a cooling protocol," he said.
The medical staff also ordered several drug therapies in addition to miltefosine.
"There was a whole lot going on with this patient other than this one drug," Kalita said. "So it's really hard to say what worked [and] what didn't work. Did [the therapies] work together? Did they help each other?"
With DeLeon in a coma, he said, the pharmacy staff had to figure out how hospital personnel would administer thrice-daily 50-mg doses of miltefosine, available commercially only as a capsule, to a patient unable to swallow.
The pediatric critical care pharmacy specialist and others examined the drug product's labeling, read the online literature about miltefosine, and evaluated the drug's physical and chemical properties, Kalita said. They determined that the best method of administration would be to dissolve the contents of the capsule in water and push the mixture through a nasogastric tube, which had to be inserted for that purpose.
He said the critical care pharmacy specialist also helped monitor and manage the various drugs' adverse effects.
"This patient was on a lot of different medications, and they were not benign," Kalita said, mentioning miltefosine in particular. "It's not quite as benign as people may think it is."
While declining to single out anyone by name, the pharmacy director described his professional and technical staffs as a "fantastic" group.
"They rallied around this case and made sure that everything we needed to do was done as timely as possible," Kalita said. "Our group also has an outstanding working relationship with the nursing staff and the medical staff as well as the lab."
Not the first. DeLeon was not the hospital's first N. fowleri–infected patient.
"We had a case in 2014 . . . that ended in tragedy," Kalita said, noting that the case occurred a few months before he started as the pharmacy director.
The 11-year-old victim's parents created the Jordan Smelski Foundation for Amoeba Awareness.
Part of the foundation's stated mission is to educate medical communities about the risks of N. fowleri infection and primary amebic meningoencephalitis.
The foundation, in collaboration with the hospital and two Florida counties' health departments, held Amoeba Summit 2015. Amoeba Summit 2016 occurred on September 9.
Process, preparation. Kalita said he had talked with Jordan Smelski's father about miltefosine and had been working toward the hospital carrying the product on consignment when the emergency arose.
"Like any other hospital," he said, "we have a process we go through to evaluate drugs for safety and efficacy. . . . A request [to have a drug product] has a lot of committees to go through."
And because of the consignment contract, the hospital's legal team got involved as well, he added.
Miltefosine was approved by FDA in March 2014 as a treatment for Leishmania infection but was not immediately available for purchase. Orlando-based Profounda, Inc., in September 2015 obtained the right to distribute the drug under the brand name Impavido in the United States and started doing so this past March.
Before then, the U.S. source was CDC, which announced in 2013 that it had an FDA-approved investigational new drug protocol for the use of miltefosine in treating free-living amoeba infections.
CDC said miltefosine had shown in vitro activity against free-living amoeba and, when part of the treatment regimen for a free-living amoeba infection, seemed to offer "a survival advantage" for patients.
Time matters. Kalita said his involvement in the events on August 7 began with a phone call from a staff pharmacist: "Hey, Mike, I think we might have an amoeba case."
He started making phone calls.
Todd MacLaughlan, chief executive officer at Profounda, remembered having "a very exciting 45 minutes" that day.
But, MacLaughlan readily admitted, he goes into "panic mode" whenever he receives a call about amoebic infection.
"My initial phone call activity [on the case] came from a female pharmacist," he recalled. Subsequent calls came from a CDC medical epidemiologist, the Florida Department of Health, and Kalita.
MacLaughlan, whose cell phone is the one that callers reach when they contact the company for information on obtaining Impavido, said he was not in Orlando on August 7. He told his son, the operations manager, to immediately pick up a supply and deliver it to the hospital.
Any delay in killing N. fowleri, MacLaughlan said, means the amoeba continues to "eat" the patient's brain.
He said his company, when an emergency arises, ships Impavido as soon as possible by air or land from Orlando or Indiana, where its warehouses are. Pharmacies that have not already acquired the product from the company need to email a copy of their state pharmacy license.
MacLaughlan said his attitude is that the company will deliver the potentially life-saving drug before knowing exactly how the recipient will pay.
As of October 18, he said, nine hospitals had Impavido on hand through a contingent contract.