FDA moves to curb insulin prices as pressure on manufacturers mounts

Insulin manufacturers have long been criticized for raising their list prices year after year. Now the FDA aims to make it easier to compete.

As insulin manufacturers and pharmacy benefit managers (PBM) face increasing pressure over rising list prices for the drugs millions of diabetics need to survive, the Food & Drug Administration has a plan to curb costs by spurring competition.

Insulin products have been approved as drugs under the Federal Food, Drug, and Cosmetic Act, but the FDA wants to transition insulin to an abbreviated approval pathway for licensure as biologics under the Public Health Service Act in 2020. This transition for insulin and certain other biologics follows congressional intent behind the Biologics Price Competition and Innovation Act (BPCI Act)—which was passed as part of the Affordable Care Act in 2010—outgoingFDA Commissioner Scott Gottlieb, MD, said Tuesday.

“The transition of insulin from the drug to the biologics pathway will open up these products to biosimilar competition,” Gottlieb said in a statement. “We’re already seeing robust activity among sponsors seeking to bring forward biosimilar copies of insulin.”

“Once an interchangeable insulin product is approved and available on the market, it can then be substituted for the reference product at the pharmacy, potentially leading to increased access and lower costs for patients,” Gottlieb added. “The FDA anticipates that biosimilar and interchangeable insulin products will bring the competition that’s needed to help bring affordable treatment options to patients.”

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Insulin manufacturers have long been criticized for raising their list prices year after year. Eli Lilly & Co.’s popular fast-acting insulin product Humalog had a list price of about $21 per vial when it first came to market in 1996, but that price rose incrementally over the years, to nearly $100 in 2009, then $275 last year, as Kaiser Health News reported.

Lilly said last month that it will offer a half-price authorized generic version of Humalog for $137.35 per vial—a move that Mayo Clinic hematologist Vincent Rajkumar, MD, and others have described as a gesture made for the sake of public relations.

PBMs, too, have taken action to address the public outcry. Cigna’s Express Scripts, one of the nation’s largest PBMs, said Wednesday it will give clients the option to limit monthly out-of-pocket insulin costs at $25 per month, as The Wall Street Journal‘s Joseph Walker reported. The move comes as the Trump administration has blamed PBM middlemen for a chunk of the high cost of U.S. healthcare.

Amid all of this, the FDA said Tuesday that it will host a public hearing May 13 to discuss insulin’s affordability and the plan to transition to a biosimilar evaluation and approval process.

“We understand the urgent need to address the high prices and lack of competition in the insulin market,” Gottlieb said.

“A drug that’s nearly a century old should not have a list price that increases between 15-17% annually,” he added. “American patients who rely on insulin to live deserve to have high-quality, affordable options.”

https://www.healthleadersmedia.com/innovation/fda-moves-curb-insulin-price-hikes-pressure-manufacturers-mounts

Exemptions surge as parents, doctors do ‘Hail Mary’ around vaccine laws

Parents have found end runs around the new law requiring vaccinations. And they have done so, often, with the cooperation of doctors — some not even pediatricians.

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KEY TAKEAWAYS

California law bars parents from citing personal or religious beliefs to avoid vaccinating their children. Children could be exempted only on medical grounds.

Doctors have broad authority to grant medical exemptions to vaccination, and to decide the grounds for doing so.

Some doctors are wielding that power liberally and sometimes for cash: signing dozens — even hundreds — of exemptions for children in far-off communities.

At two public charter schools in the Sonoma wine country town of Sebastopol, more than half the kindergartners received medical exemptions from state-required vaccines last school year. The cities of Berkeley, Santa Cruz, Nevada City, Arcata and Sausalito all had schools in which more than 30% of the kindergartners had been granted such medical exemptions.

Nearly three years ago, with infectious disease rates ticking up, California enacted a fiercely contested law barring parents from citing personal or religious beliefs to avoid vaccinating their children. Children could be exempted only on medical grounds, if the shots were harmful to health.

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Yet today, many of the schools that had the highest rates of unvaccinated students before the new measure continue to hold that alarming distinction. That’s because parents have found end runs around the new law requiring vaccinations. And they have done so, often, with the cooperation of doctors — some not even pediatricians. One prolific exemption provider is a psychiatrist who runs an anti-aging clinic.

Doctors in California have broad authority to grant medical exemptions to vaccination, and to decide the grounds for doing so. Some are wielding that power liberally and sometimes for cash: signing dozens — even hundreds — of exemptions for children in far-off communities.

“It’s sort of the Hail Mary of the vaccine refusers who are trying to circumvent SB 277,” the California Senate bill signed into law by Gov. Jerry Brown in 2015, said Dr. Brian Prystowsky, a Santa Rosa pediatrician. “It’s really scary stuff. We have pockets in our community that are just waiting for measles to rip through their schools.”

The number of California children granted medical exemptions from vaccinations has tripled in the past two years.

Across the nation, 2019 is shaping up to be one of the worst years for U.S. measles cases in a quarter-century, with major outbreaks in New York, Texas and Washington state, and new cases reported in 12 more states, including California. California’s experience underlines how hard it is to get parents to comply with vaccination laws meant to protect public safety when a small but adamant population of families and physicians seems determined to resist.

When Senate Bill 277 took effect in 2016, California became the third state, after Mississippi and West Virginia, to ban vaccine exemptions based on personal or religious beliefs for public and private school students. (The ban does not apply to students who are home-schooled.)

In the two subsequent years, SB 277 improved overall child vaccination rates: The percentage of fully vaccinated kindergartners rose from 92.9% in the 2015-16 school year to 95.1% in 2017-18.

But those gains stalled last year due to the dramatic rise in medical exemptions: More than 4,000 kindergartnersreceived these exemptions in the 2017-18 school year. Though the number is still relatively small, many are concentrated in a handful of schools, leaving those classrooms extremely vulnerable to serious outbreaks.

Based on widely accepted federal guidelines, vaccine exemptions for medical reasons should be exceedingly rare. They’re typically reserved for children who are allergic to vaccine components, who have had a previous reaction to a vaccine, or whose immune systems are compromised, including kids being treated for cancer. Run-of-the-mill allergies and asthma aren’t reasons to delay or avoid vaccines, according to the U.S. Centers for Disease Control and Prevention. Neither is autism.

Before California’s immunization law took effect, just a fraction of 1% of the state’s schoolchildren had medical exemptions. By last school year, 105 schools, scattered across the state, reported that 10% or more of their kindergartners had been granted medical exemptions. In 31 of those schools, 20% or more of the kindergartners had medical exemptions.

SEESAWING EXEMPTIONS

As of July 2016, California no longer allows parents to exempt their children from state-required vaccinations based on personal beliefs. Many of the same schools that once had the highest percentage of students with personal belief exemptions now lead the state in student medical exemptions.

The spike in medical exemptions is taking place amid a politically tinged, often rancorous national conversation over vaccines and personal liberty as measles resurges in the U.S. and worldwide. At least 387 cases of measles had been reported nationwide through March 28, according to the CDC. In California, 16 cases had been reported, two of them requiring hospitalization.

The problem in California, state officials say, is how the immunization law was structured. It removed the ability of parents to cite “personal belief” as a reason for exempting their children from vaccine requirements in day care and schools. Exemptions now must be authorized by a licensed physician who provides a written statement citing a medical condition that indicates immunization “is not considered safe.”

But the law does not specify the conditions that qualify a student for a medical exemption, nor does it require physicians to follow federal guidelines.

The wording has led to a kind of gray market in which parents share names of “vaccine-friendly” doctors by word of mouth or in closed Facebook groups. And some of those doctors are granting children blanket exemptions — for all time and all vaccines — citing a range of conditions not supported by federal guidelines, such as a family history of eczema or arthritis.

Amid growing concerns about suspect exemptions, the California Department of Public Health recently launched a review of schools with “biologically unlikely” numbers of medical exemptions, said the agency’s director, Dr. Karen Smith. Doctors who have written questionable exemptions will be referred to the Medical Board of California for possible investigation.

The medical board, which licenses doctors, has the authority to levy sanctions if physicians have not followed standard medical practice in examining patients or documenting specific reasons for an exemption.

In recent years, however, the board has sanctioned only one doctor for inappropriately writing a medical vaccine exemption in a case that made headlines. Since 2013, the board has received 106 complaints about potentially improper vaccine exemptions, including nine so far this year, said spokesman Carlos Villatoro.

One pending case involves Dr. Ron Kennedy, who was trained as a psychiatrist and now runs an anti-aging clinic in Santa Rosa.

Medical board investigators took the unusual step of subpoenaing 12 school districts for student medical records after receiving complaints that Kennedy was writing inappropriate exemptions. They found that Kennedy had written at least 50 exemptions, using nearly identical form letters, for students in multiple communities, including Santa Rosa, Fremont and Fort Bragg, saying that immunizations were “contraindicated” for a catchall list of conditions including lupus, learning disability, food allergies and “detoxification impairment.”

Dr. Dean Blumberg, chief of pediatric infectious diseases at UC Davis Children’s Hospital and the medical board’s expert witness, said that the exemptions issued by Kennedy appear to have been provided “without an appropriate evaluation,” according to court documents.

Kennedy has refused to respond to the board’s subpoenas seeking the medical records of three of his patients, according to court documents. The board has yet to file a formal accusation against Kennedy, and he continues to practice.

Like Kennedy, many of the doctors granting unorthodox exemptions cite their belief in parental rights or reference concerns not supported by conventional medical science. Kennedy is suing the medical board and its parent agency, the California Department of Consumer Affairs, saying the state did not have the legal right to subpoena school districts for his patients’ medical records without first informing him so he could challenge the action in court. The case is ongoing.

Kennedy declined comment to Kaiser Health News. “I don’t want to be out in the open,” he said in a brief phone exchange. “I’ve got to go. I’ve got a business to run.”

In Monterey, Dr. Douglas Hulstedt is known as the doctor to see for families seeking medical exemptions. In a brief phone interview, he said he was worried about being targeted by the state medical board. “I have stuck my neck way out there just talking with you,” he said. Hulstedt does not give exemptions to every child he examines, he said, but does believe vaccines can cause autism — a fringe viewpoint that has been debunked by multiple studies.

In March, the online publication Voice of San Diego highlighted doctors who write medical exemptions, including one physician who had written more than a third of the 486 student medical exemptions in the San Diego Unified School District. District officials had compiled a list of such exemptions and the doctors who provided them.

State Sen. Richard Pan (D-Sacramento), a pediatrician who sponsored California’s vaccine law, has been a vocal critic of doctors he says are skirting the intent of the legislation by handing out “fake” exemptions. Last month, he introduced follow-up legislation that would require the state health department to sign off on medical exemptions. The department also would have the authority to revoke exemptions found to be inconsistent with CDC guidelines.

“We cannot allow a small number of unethical physicians to put our children back at risk,” Pan said. “It’s time to stop fake medical exemptions and the doctors who are selling them.”

https://www.healthleadersmedia.com/exemptions-surge-parents-and-doctors-do-hail-mary-around-vaccine-laws

Mysterious Infection Spanning the Globe in a Climate of Secrecy

Last May, an elderly man was admitted to the Brooklyn branch of Mount Sinai Hospital for abdominal surgery. A blood test revealed that he was infected with a newly discovered germ as deadly as it was mysterious. Doctors swiftly isolated him in the intensive care unit.

The germ, a fungus called Candida auris, preys on people with weakened immune systems, and it is quietly spreading across the globe. Over the last five years, it has hit a neonatal unit in Venezuela, swept through a hospital in Spain, forced a prestigious British medical center to shut down its intensive care unit, and taken root in India, Pakistan and South Africa.

Recently C. auris reached New York, New Jersey and Illinois, leading the federal Centers for Disease Control and Prevention to add it to a list of germs deemed “urgent threats.”

The man at Mount Sinai died after 90 days in the hospital, but C. auris did not. Tests showed it was everywhere in his room, so invasive that the hospital needed special cleaning equipment and had to rip out some of the ceiling and floor tiles to eradicate it.

“Everything was positive — the walls, the bed, the doors, the curtains, the phones, the sink, the whiteboard, the poles, the pump,” said Dr. Scott Lorin, the hospital’s president. “The mattress, the bed rails, the canister holes, the window shades, the ceiling, everything in the room was positive.”

C. auris is so tenacious, in part, because it is impervious to major antifungal medications, making it a new example of one of the world’s most intractable health threats: the rise of drug-resistant infections.

Dr. Shawn Lockhart, a fungal disease expert at the Centers for Disease Control and Prevention, holding a microscope slide with inactive Candida auris collected from an American patient.CreditMelissa Golden for The New York Times

For decades, public health experts have warned that the overuse of antibiotics was reducing the effectiveness of drugs that have lengthened life spans by curing bacterial infections once commonly fatal. But lately, there has been an explosion of resistant fungi as well, adding a new and frightening dimension to a phenomenon that is undermining a pillar of modern medicine.

“It’s an enormous problem,” said Matthew Fisher, a professor of fungal epidemiology at Imperial College London, who was a co-author of a recent scientific review on the rise of resistant fungi. “We depend on being able to treat those patients with antifungals.”

Simply put, fungi, just like bacteria, are evolving defenses to survive modern medicines.

Yet even as world health leaders have pleaded for more restraint in prescribing antimicrobial drugs to combat bacteria and fungi — convening the United Nations General Assembly in 2016 to manage an emerging crisis — gluttonous overuse of them in hospitals, clinics and farming has continued.

Resistant germs are often called “superbugs,” but this is simplistic because they don’t typically kill everyone. Instead, they are most lethal to people with immature or compromised immune systems, including newborns and the elderly, smokers, diabetics and people with autoimmune disorders who take steroids that suppress the body’s defenses.

Scientists say that unless more effective new medicines are developed and unnecessary use of antimicrobial drugs is sharply curbed, risk will spread to healthier populations. A study the British government funded projects that if policies are not put in place to slow the rise of drug resistance, 10 million people could die worldwide of all such infections in 2050, eclipsing the eight million expected to die that year from cancer.

Dr. Johanna Rhodes, an infectious disease expert at Imperial College London. “We are driving this with the use of antifungicides on crops,” she said of drug-resistant germs.CreditTom Jamieson for The New York Times

In the United States, two million people contract resistant infections annually, and 23,000 die from them, according to the official C.D.C. estimate. That number was based on 2010 figures; more recent estimates from researchers at Washington University School of Medicine put the death toll at 162,000. Worldwide fatalities from resistant infections are estimated at 700,000.

Antibiotics and antifungals are both essential to combat infections in people, but antibiotics are also used widely to prevent disease in farm animals, and antifungals are also applied to prevent agricultural plants from rotting. Some scientists cite evidence that rampant use of fungicides on crops is contributing to the surge in drug-resistant fungi infecting humans.

What You Need to Know About Candida Auris

C. auris is a mysterious and dangerous fungal infection that is among a growing number of germs that have evolved defenses against common medicines. Here are some basic facts about it.

Yet as the problem grows, it is little understood by the public — in part because the very existence of resistant infections is often cloaked in secrecy.

With bacteria and fungi alike, hospitals and local governments are reluctant to disclose outbreaks for fear of being seen as infection hubs. Even the C.D.C., under its agreement with states, is not allowed to make public the location or name of hospitals involved in outbreaks. State governments have in many cases declined to publicly share information beyond acknowledging that they have had cases.

All the while, the germs are easily spread — carried on hands and equipment inside hospitals; ferried on meat and manure-fertilized vegetables from farms; transported across borders by travelers and on exports and imports; and transferred by patients from nursing home to hospital and back.

C. auris, which infected the man at Mount Sinai, is one of dozens of dangerous bacteria and fungi that have developed resistance.

A projection of the C. auris fungus on a microscope slide.CreditMelissa Golden for The New York Times

Other prominent strains of the fungus Candida — one of the most common causes of bloodstream infections in hospitals — have not developed significant resistance to drugs, but more than 90 percent of C. auris infections are resistant to at least one drug, and 30 percent are resistant to two or more drugs, the C.D.C. said.

Dr. Lynn Sosa, Connecticut’s deputy state epidemiologist, said she now saw C. auris as “the top” threat among resistant infections. “It’s pretty much unbeatable and difficult to identify,” she said.

Nearly half of patients who contract C. auris die within 90 days, according to the C.D.C. Yet the world’s experts have not nailed down where it came from in the first place.

“It is a creature from the black lagoon,” said Dr. Tom Chiller, who heads the fungal branch at the C.D.C., which is spearheading a global detective effort to find treatments and stop the spread. “It bubbled up and now it is everywhere.”

Candida Auris

A deadly, drug-resistant fungus is infecting patients in hospitals and nursing homes around the world. The fungus seems to have emerged in several locations at once, not from a single source.

EUROPE

The first large outbreak in Europe involved 72 cases in a London hospital in 2015–16.

COUNTRIES WITH

Multiple cases of

Candida auris infection

One reported case

BRITAIN

RUSSIA

CANADA

FRANCE

GERMANY

UNITED

STATES

UNITED STATES

The country has had at least 587 Candida auris infections since 2013.

SPAIN

JAPAN

CHINA

ISRAEL

KUWAIT

PAKISTAN

SOUTH

KOREA

SAUDI

ARABIA

INDIA

OMAN

PANAMA

VENEZUELA

SINGAPORE

COLOMBIA

KENYA

INDIA AND PAKISTAN

The two countries have some of the highest case counts in the world. A distinct strain appeared in Pakistan as early as 2008 and in Delhi by 2009.

CENTRAL AND

SOUTH AMERICA

The first documented outbreak in the Americas was from 2012–13 at a medical center in Venezuela. Five of 18 infected patients died.

AUSTRALIA

SOUTH

AFRICA

SOUTH AFRICA

A genetically distinct strain of Candida auris in South Africa infected at least 451 patients from 2012–16.

JAPAN

Candida auris (left) was discovered in 2009 in the infected ear of a 70-year-old Japanese woman.

By The New York Times | Sources: Centers for Disease Control and Prevention; Emerging Infectious Diseases; Emerging Microbes & Infections; Clinical Infectious Diseases; Journal of Infection; Mycoses; Doherty Institute. Image from Kazuo Satoh et al., Microbiology and Immunology

‘No need’ to tell the public

In late 2015, Dr. Johanna Rhodes, an infectious disease expert at Imperial College London, got a panicked call from the Royal Brompton Hospital, a British medical center outside London. C. auris had taken root there months earlier, and the hospital couldn’t clear it.

“‘We have no idea where it’s coming from. We’ve never heard of it. It’s just spread like wildfire,’” Dr. Rhodes said she was told. She agreed to help the hospital identify the fungus’s genetic profile and clean it from rooms.

Under her direction, hospital workers used a special device to spray aerosolized hydrogen peroxide around a room used for a patient with C. auris, the theory being that the vapor would scour each nook and cranny. They left the device going for a week. Then they put a “settle plate” in the middle of the room with a gel at the bottom that would serve as a place for any surviving microbes to grow, Dr. Rhodes said.

Only one organism grew back. C. auris.

It was spreading, but word of it was not. The hospital, a specialty lung and heart center that draws wealthy patients from the Middle East and around Europe, alerted the British government and told infected patients, but made no public announcement.

“There was no need to put out a news release during the outbreak,” said Oliver Wilkinson, a spokesman for the hospital.

This hushed panic is playing out in hospitals around the world. Individual institutions and national, state and local governments have been reluctant to publicize outbreaks of resistant infections, arguing there is no point in scaring patients — or prospective ones.

“Somehow, it made a jump almost seemingly simultaneously, and seemed to spread and it is drug resistant, which is really mind-boggling,” said Dr. Snigdha Vallabhaneni, a fungal expert and epidemiologist at the C.D.C.CreditMelissa Golden for The New York Times

Dr. Silke Schelenz, Royal Brompton’s infectious disease specialist, found the lack of urgency from the government and hospital in the early stages of the outbreak “very, very frustrating.”

“They obviously didn’t want to lose reputation,” Dr. Schelenz said. “It hadn’t impacted our surgical outcomes.”

By the end of June 2016, a scientific paper reported “an ongoing outbreak of 50 C. auris cases” at Royal Brompton, and the hospital took an extraordinary step: It shut down its I.C.U. for 11 days, moving intensive care patients to another floor, again with no announcement.

Days later the hospital finally acknowledged to a newspaper that it had a problem. A headline in The Daily Telegraph warned, “Intensive Care Unit Closed After Deadly New Superbug Emerges in the U.K.” (Later research said there were eventually 72 total cases, though some patients were only carriers and were not infected by the fungus.)

Yet the issue remained little known internationally, while an even bigger outbreak had begun in Valencia, Spain, at the 992-bed Hospital Universitari i Politècnic La Fe. There, unbeknown to the public or unaffected patients, 372 people were colonized — meaning they had the germ on their body but were not sick with it — and 85 developed bloodstream infections. A paper in the journal Mycoses reported that 41 percent of the infected patients died within 30 days.

A statement from the hospital said it was not necessarily C. auris that killed them. “It is very difficult to discern whether patients die from the pathogen or with it, since they are patients with many underlying diseases and in very serious general condition,” the statement said.

As with Royal Brompton, the hospital in Spain did not make any public announcement. It still has not.

One author of the article in Mycoses, a doctor at the hospital, said in an email that the hospital did not want him to speak to journalists because it “is concerned about the public image of the hospital.”

The secrecy infuriates patient advocates, who say people have a right to know if there is an outbreak so they can decide whether to go to a hospital, particularly when dealing with a nonurgent matter, like elective surgery.

Outside the Royal Brompton Hospital near London. By June 2016, the hospital had seen at least 50 “proven or possible” cases of C. auris, and decided to shut down its intensive care unit for 11 days to address the contamination.CreditTom Jamieson for The New York Times

“Why the heck are we reading about an outbreak almost a year and a half later — and not have it front-page news the day after it happens?” said Dr. Kevin Kavanagh, a physician in Kentucky and board chairman of Health Watch USA, a nonprofit patient advocacy group. “You wouldn’t tolerate this at a restaurant with a food poisoning outbreak.”

Health officials say that disclosing outbreaks frightens patients about a situation they can do nothing about, particularly when the risks are unclear.

“It’s hard enough with these organisms for health care providers to wrap their heads around it,” said Dr. Anna Yaffee, a former C.D.C. outbreak investigator who dealt with resistant infection outbreaks in Kentucky in which the hospitals were not publicly disclosed. “It’s really impossible to message to the public.”

Officials in London did alert the C.D.C. to the Royal Brompton outbreak while it was occurring. And the C.D.C. realized it needed to get the word to American hospitals. On June 24, 2016, the C.D.C. blasted a nationwide warning to hospitals and medical groups and set up an email address, candidaauris@cdc.gov, to field queries. Dr. Snigdha Vallabhaneni, a key member of the fungal team, expected to get a trickle — “maybe a message every month.”

Instead, within weeks, her inbox exploded.

Coming to America

In the United States, 587 cases of people having contracted C. auris have been reported, concentrated with 309 in New York, 104 in New Jersey and 144 in Illinois, according to the C.D.C.

The symptoms — fever, aches and fatigue — are seemingly ordinary, but when a person gets infected, particularly someone already unhealthy, such commonplace symptoms can be fatal.

The earliest known case in the United States involved a woman who arrived at a New York hospital on May 6, 2013, seeking care for respiratory failure. She was 61 and from the United Arab Emirates, and she died a week later, after testing positive for the fungus. At the time, the hospital hadn’t thought much of it, but three years later, it sent the case to the C.D.C. after reading the agency’s June 2016 advisory.

Candida Auris by State

Most cases in the United States have been in nursing homes in New York City, Chicago and New Jersey.

Mass.

N.Y.

Conn.

N.J.

Ill.

Ind.

Md.

Calif.

Va.

Okla.

200

Tex.

100

Fla.

25

Confirmed and

probable cases,

2013–19

1

By The New York Times | Source: Centers for Disease Control and Prevention

This woman probably was not America’s first C. auris patient. She carried a strain different from the South Asian one most common here. It killed a 56-year-old American woman who had traveled to India in March 2017 for elective abdominal surgery, contracted C. auris and was airlifted back to a hospital in Connecticut that officials will not identify. She was later transferred to a Texas hospital, where she died.

The germ has spread into long-term care facilities. In Chicago, 50 percent of the residents at some nursing homes have tested positive for it, the C.D.C. has reported. The fungus can grow on intravenous lines and ventilators.

Workers who care for patients infected with C. auris worry for their own safety. Dr. Matthew McCarthy, who has treated several C. auris patients at Weill Cornell Medical Center in New York, described experiencing an unusual fear when treating a 30-year-old man.

“I found myself not wanting to touch the guy,” he said. “I didn’t want to take it from the guy and bring it to someone else.” He did his job and thoroughly examined the patient, but said, “There was an overwhelming feeling of being terrified of accidentally picking it up on a sock or tie or gown.”

Dr. Tom Chiller, head of the fungal branch at the C.D.C. “It is a creature from the black lagoon,” he said of C. auris.CreditMelissa Golden for The New York Times

The role of pesticides?

As the C.D.C. works to limit the spread of drug-resistant C. auris, its investigators have been trying to answer the vexing question: Where in the world did it come from?

The first time doctors encountered C. auris was in the ear of a woman in Japan in 2009 (auris is Latin for ear). It seemed innocuous at the time, a cousin of common, easily treated fungal infections.

Three years later, it appeared in an unusual test result in the lab of Dr. Jacques Meis, a microbiologist in Nijmegen, the Netherlands, who was analyzing a bloodstream infection in 18 patients from four hospitals in India. Soon, new clusters of C. auris seemed to emerge with each passing month in different parts of the world.

The C.D.C. investigators theorized that C. auris started in Asia and spread across the globe. But when the agency compared the entire genome of auris samples from India and Pakistan, Venezuela, South Africa and Japan, it found that its origin was not a single place, and there was not a single auris strain.

The C.D.C. in miniature. In the United States, two million people contract resistant infections each year, and 23,000 die from them, according to the official C.D.C. estimate.CreditMelissa Golden for The New York Times

The genome sequencing showed that there were four distinctive versions of the fungus, with differences so profound that they suggested that these strains had diverged thousands of years ago and emerged as resistant pathogens from harmless environmental strains in four different places at the same time.

“Somehow, it made a jump almost seemingly simultaneously, and seemed to spread and it is drug resistant, which is really mind-boggling,” Dr. Vallabhaneni said.

There are different theories as to what happened with C. auris. Dr. Meis, the Dutch researcher, said he believed that drug-resistant fungi were developing thanks to heavy use of fungicides on crops.

Dr. Meis became intrigued by resistant fungi when he heard about the case of a 63-year-old patient in the Netherlands who died in 2005 from a fungus called Aspergillus. It proved resistant to a front-line antifungal treatment called itraconazole. That drug is a virtual copy of the azole pesticides that are used to dust crops the world over and account for more than one-third of all fungicide sales.

A 2013 paper in Plos Pathogens said that it appeared to be no coincidence that drug-resistant Aspergillus was showing up in the environment where the azole fungicides were used. The fungus appeared in 12 percent of Dutch soil samples, for example, but also in “flower beds, compost, leaves, plant seeds, soil samples of tea gardens, paddy fields, hospital surroundings, and aerial samples of hospitals.”

Dr. Meis visited the C.D.C. last summer to share research and theorize that the same thing is happening with C. auris, which is also found in the soil: Azoles have created an environment so hostile that the fungi are evolving, with resistant strains surviving.

This is similar to concerns that resistant bacteria are growing because of excessive use of antibiotics in livestock for health and growth promotion. As with antibiotics in farm animals, azoles are used widely on crops.

“On everything — potatoes, beans, wheat, anything you can think of, tomatoes, onions,” said Dr. Rhodes, the infectious disease specialist who worked on the London outbreak. “We are driving this with the use of antifungicides on crops.”

Dr. Chiller theorizes that C. auris may have benefited from the heavy use of fungicides. His idea is that C. auris actually has existed for thousands of years, hidden in the world’s crevices, a not particularly aggressive bug. But as azoles began destroying more prevalent fungi, an opportunity arrived for C. auris to enter the breach, a germ that had the ability to readily resist fungicides now suitable for a world in which fungi less able to resist are under attack.

The mystery of C. auris’s emergence remains unsolved, and its origin seems, for the moment, to be less important than stopping its spread.

Resistance and denial

For now, the uncertainty around C. auris has led to a climate of fear, and sometimes denial.

Last spring, Jasmine Cutler, 29, went to visit her 72-year-old father at a hospital in New York City, where he had been admitted because of complications from a surgery the previous month.

When she arrived at his room, she discovered that he had been sitting for at least an hour in a recliner, in his own feces, because no one had come when he had called for help to use the bathroom. Ms. Cutler said it became clear to her that the staff was afraid to touch him because a test had shown that he was carrying C. auris.

“I saw doctors and nurses looking in the window of his room,” she said. “My father’s not a guinea pig. You’re not going to treat him like a freak at a show.”

He was eventually discharged and told he no longer carried the fungus. But he declined to be named, saying he feared being associated with the frightening infection.

Senators want to intervene in transplant organ allocation policy

Two senators are eying Congress’ appropriations authority to influence a contentious debate over a change to national organ distribution policy.

The issue was raised Thursday in a Senate health appropriations panel hearing with HHS Secretary Alex Azar. Panel Chair Roy Blunt (R-Mo.) and Sen. Jerry Moran (R-Kan.) are trying to intervene against a sweeping new policy that changes the geography-based system of liver allocation to one that prioritizes the sickest patients.

Blunt told Modern Healthcare he will look at the independent board tasked with setting national organ distribution policy.

“That group has a budget, and apparently the Congress hasn’t been able to get attention yet, and we’re going to look at that budget real closely this year,” he said.

He reiterated that the budget has to do with oversight rather than funding healthcare.

“But it’s an oversight budget, and the oversight is being poorly handled, in my view,” he said.

Moran said he wants to work with Blunt on “anything we can do to get (the Health Resources and Services Administration’s) attention and ultimately getting a different and better policy than the direction that they’re going.”

The new policy for livers was approved in early December by the board of the United Network for Organ Sharing. UNOS is an independent entity made up of transplant surgeons and recipients, organ donors and others.

UNOS is contracted to the Organ Procurement and Transplantation Network, or OPTN, which is tasked by HRSA to oversee the national distribution system.

The direct federal appropriation is expected to be roughly $4.5 million of the roughly $51 million total budget for OPTN, said UNOS spokesperson Joel Newman. The majority of the network’s funding comes from a one-time fee paid by a member organization when a patient joins the waiting list for a transplant.

About 8% of the OPTN budget goes to oversight of compliance with the organ allocation policies.

Organ allocation policy is intensely political because of the huge disparities in different regions of the country between the number of available livers and the amount of people awaiting transplants. The South and Midwest tend to have more donors than recipients, while other states–notably New York and California—have the reverse situation.

For health systems, national policy can have a huge financial impact on lucrative transplant programs. Constituent hospitals put immense pressure on their congressional representatives, and since UNOS is made up of stakeholders from around the country the board spent years in gridlock as the issue simmered.

Billy Wynne, who advocates in defense of the liver policy change as executive director of the National Coalition for Transplant Equity said it will reduce waitlist-related deaths by 8%.

“That’s really the whole ballgame here,” he said.

More than 80 House lawmakers last month sent a letter to Azar articulating their support for the policy change, which is due to take effect April 30. The letter rebutted points raised by Blunt, Moran and other senators who see the change as detrimental—including Senate Majority Leader Mitch McConnell (R-Ky.) and Senate Finance Committee Chair Chuck Grassley (R-Iowa).

In July, six people awaiting transplants in regions where few livers are available sued UNOS over the policy. One plaintiff, a Medicaid patient from New York, has died from liver disease while awaiting resolution.

After the lawsuit was filed, HRSA Administrator George Sigounas weighed in, telling the OPTN president in a letter that the group needed to eliminate the regional system by UNOS’ December 2018 meeting.

On Thursday, Moran asked Azar to commit HHS to a “full public disclosure and transparent public debate” on the organ allocation process. Azar said while he was happy to work on “what that might look like” he has limited authority to intervene.

“Congress deliberately took OPTN out of my hands,” he said, adding that he believes the OPTN decision was based on a “public process with a public record.”

Moran argued that Sigounas’ letter ran counter to that claim.

“The HRSA director is the one who wrote the OPTN letter, to implement the decision that was made,” he said at the hearing.

After the hearing Moran told Modern Healthcare that despite Azar’s statements, he’s “seen HRSA encourage the adoption of this policy. That doesn’t sound hands-off to me.”

“My hope is there’s still a way to convince the folks at HHS of the errors of their way, but we’ll try to do so in the appropriations process, and the conversations will continue,” he said.

Hospitals are expected to sue against the new policy, both Blunt and Moran said.

On the legislative front, Sen. Todd Young (R-Ind.) has been working on legislation that is now in the fine-tuning stage, according to an aide.

His office said the bill is focused on “transparency, oversight and accountability,” particularly around UNOS and the organ procurement organizations around the country that are responsible for acquiring organs.

https://www.modernhealthcare.com/government/senators-want-intervene-organ-allocation-policy