The desperately ill patients who deluged the emergency room at Detroit Medical Center in March and April exhibited the telltale symptoms of the coronavirus: high fevers and infection-riddled lungs that left them gasping for air.
With few treatment options, doctors turned to a familiar intervention: broad-spectrum antibiotics, the shot-in-the-dark medications often used against bacterial infections that cannot be immediately identified. They knew antibiotics are not effective against viruses, but they were desperate, and they feared the patients could be vulnerable to life-threatening secondary bacterial infections as well.
“During the peak surge, our antibiotic use was off the charts,” said Dr. Teena Chopra, the hospital’s director of epidemiology and antibiotic stewardship, who estimated that more than 80% of arriving patients were given antimicrobial drugs. “At one point, we were afraid we would run out.”
Chopra and other doctors across the country who liberally dispensed antibiotics in the early weeks of the pandemic said they soon realized their mistake.
“Many physicians were inappropriately giving antibiotics because, honestly, they had limited choices,” she said.
Now that the initial, terrifying flood of patients in hard-hit cities has subsided, doctors across the United States are seeking to draw lessons from their overuse of antibiotics, a practice that can spur resistance to the lifesaving drugs as bacteria mutate and outsmart the drugs.
Many critically ill patients on ventilators have developed serious secondary infections. But widespread fears that coronavirus patients were especially susceptible to drug-resistant infections — a concern first described in studies from China — appear to have been misguided, according to interviews with researchers and more than a dozen doctors who have been treating patients with COVID-19.
“The fears turned out to be overblown,” said Dr. Bruce Farber, chief of infectious diseases at Northwell Health, which has cared for thousands of coronavirus patients at its 23 hospitals in New York.
For many doctors, the pandemic not only provides lessons about the judicious use of antibiotics, but it also highlights another global health threat that has been playing out in slow motion: the mounting threat of antimicrobial resistance that annually claims 700,000 lives as the world’s arsenal of antibiotics and antifungal medication lose their ability to vanquish dangerous pathogens.
In recent weeks, doctors, researchers and public health experts have been trying to turn the pandemic into a teaching moment. They warn that the same governmental inaction that helped foster the rapid, worldwide spread of the coronavirus may spur an even deadlier epidemic of drug-resistant infections that the United Nations suggests may kill 10 million by 2050 if serious action isn’t taken.
Without new antibiotics, routine surgical procedures like knee replacements and cesarean sections could become unacceptably risky, and the ensuing health crisis could spur an economic downturn to rival the global financial meltdown of 2008, the U.N. report, released last year, said.
“If there’s anything that this COVID-19 pandemic has taught the world, it is that being prepared is more cost-effective in the long run,” said Dr. Jeffrey R. Strich, a researcher at the National Institutes of Health Clinical Center and an author of a study published Thursday in Lancet Infectious Diseases that seeks to quantify the growing need for new antibiotics to treat drug-resistant infections. “Antimicrobial resistance is a problem we cannot afford to ignore.”
The pipeline for new antimicrobial drugs has become perilously dry. Over the past year, three American antibiotic developers with promising drugs have gone out of business, most of the world’s pharmaceutical giants have abandoned the field, and many of the remaining antibiotic startups in the United States are facing an uncertain future.
Such dreary financial realities are driving away investors at a time when new antimicrobial drugs are urgently needed.
“I’m worried the remaining small biotech companies won’t be here this time next year,” said Greg Frank, director of Working to Fight AMR, an advocacy group funded by the pharmaceutical industry. “The longer we wait, the deeper in the hole we’re in and the more expensive it’s going to be to solve the problem.”
The crisis, many experts say, calls for robust government intervention. In a report published in March, the U.S. Government Accountability Office documented a piecemeal federal response to antimicrobial resistance and said the Centers for Disease Control and Prevention was hobbled in addressing the problem by a lack of basic data about drug-resistant infections. As an example, it noted that the CDC tracks less than 2% of the country’s annual half-million cases of drug-resistant gonorrhea. The data doesn’t even include cases affecting women.
In addition to improved surveillance, the report recommended financial incentives for antibiotic makers as well as support for companies developing diagnostic tests that can quickly identify infections and enable doctors to prescribe the right drug.
“The bottom line is we can do better; otherwise we’re going to find ourselves facing a superbug that rivals the crisis posed by COVID-19,” said Dr. Timothy M. Persons, the GAO’s chief scientist and a lead author of the report.
Legislation in Congress to address the broken antibiotics marketplace has failed to gain traction in recent years, but public health experts are hoping the coronavirus pandemic can help break the political logjam in Washington.
“This isn’t a political issue; it’s not a problem for Republicans or Democrats — it’s a national security issue,” said Dr. Helen Boucher, an infectious disease specialist at Tufts Medical Center, who is a member of the Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria.
In the meantime, doctors fresh out of the trenches in cities walloped by the coronavirus are reappraising their overuse of antibiotics during the surge. Dr. Sudeb Dalai, an infectious disease specialist at Stanford University Hospital, said nearly every coronavirus patient he saw in those first months had been prescribed antibiotics — some by private urgent care clinics they visited before worsening symptoms sent them to the emergency room.
That impulse was not entirely unfounded, given the dearth of information about the disease and the medical literature on severe acute respiratory syndrome, Middle East respiratory syndrome and the Spanish flu of 1918-19 — viral respiratory illnesses whose victims often succumbed during pandemics to opportunistic bacterial infections.
Dalai recalled the sense of helplessness this spring as doctors scrambled to treat the mysterious pneumonias and spiking fevers. One of their first COVID-19 patients was an older man who had been showing signs of improvement and was ready for discharge when he took a sudden turn for the worse. Doctors put the man on a ventilator, but the fevers continued, prompting Dalai to prescribe several rounds of antibiotics during the five weeks he was intubated.
“Each night I went to bed wondering if I had made the right treatment decisions, worried that he would get worse throughout the night, that he might not make it until morning,” he said.
The patient survived, but Dalai came to realize that antibiotics most likely played little role in his recovery.
Still, without solid data, some doctors and researchers warn it is too soon to dismiss the dangers posed by bacterial and fungal co-infections, especially among gravely ill coronavirus patients who can spend weeks in intensive care units. As their immune systems falter, drug-resistant bacteria and fungi that bloom on hospital breathing tubes, catheters and intravenous lines can infiltrate the body and wreak havoc.
Chopra of Detroit Medical Center estimated that up to a third of coronavirus patients who died at the hospital were killed by opportunistic pathogens like C. difficile, a pernicious infection that causes uncontrolled diarrhea and is increasingly resistant to antibiotics. That figure, she said, was quite likely heightened by the poor underlying health of patients who also had diabetes or hypertension or were obese.
“Even before COVID hit, our population in Detroit was very vulnerable to drug-resistant infections,” said Chopra, a professor of infectious diseases at Wayne State University.
In Ann Arbor, Michigan, Dr. Valerie Vaughn, a hospitalist at Michigan Medicine who is studying antibiotic use in coronavirus patients, has been trying to make sense of the past few months and sharing best treatment practices through lectures posted online. In a review of more than 1,000 coronavirus cases across the state, she found that only 4% of patients admitted to the hospital had a bacterial co-infection. Most patients were nonetheless given antibiotics soon after they arrived.
“What the pandemic has shown us is that even when doctors know patients have a viral infection, they are still providing antibiotics,” she said. “It’s hard because doctors want to do something for their patients, even when it’s not the right thing to do.”
But beyond just altering doctors’ prescribing habits, Vaughn said she hopes the current health crisis will make it harder for political leaders and policymakers to ignore the need for improved surveillance and concerted action to fix the broken market for new antibiotics.
“We’ve been moving slower than we should,” she said, “but hopefully the pandemic will light a fire under people and get them to move faster.”