Late last year, one of Dr. Vance Fowler’s patients, a man in his 60s who had returned to North Carolina after visiting family in Nepal, died of a bacterial infection. He was being treated at a top US hospital with access to the strongest antibiotics. However, infections, drug-resistant strains of E. coli, have surged.
“Antibiotic resistance is a real problem that can impact our lives at any moment, with little or no warning,” said Fowler, an infectious disease expert at Duke Health. not.”
Health officials have warned the public about antibiotic resistance for decades. That’s all the more urgent in light of the upcoming report from the World Health Organization, which tallies that there are only a handful of new antibiotics in development.
Preliminary data A report released by the WHO this month paints a dire picture. Only 27 new antibiotics for the most dangerous infections are in clinical trials in drug development. In contrast, in 2020, over 1,300 cancer drugs were in clinical trials. to the report Provided by Pharmaceutical Research and Manufacturers of America, an industry association.
Of the antibiotics in clinical trials, the WHO says only six are innovative enough to overcome antibiotic resistance, and only two can target the most resistant bacteria. Officials are expected to present the full report at the European Conference on Clinical Microbiology and Infectious Diseases next month.
We also don’t know if this handful of new drugs in clinical trials will work. Between 2017 and 2021, only one new antibiotic, cefiderocol, was approved to treat the WHO superbug. most important listIncludes strains of Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacteraceae. These pathogens can cause a wide variety of serious infections in the lungs, urinary tract, ears, blood, open wounds, and even the brain and spinal cord.
rising resistance
Drug-resistant bacteria are becoming more common. in the United States alone, Centers for Disease Control and Prevention estimates More than 2.8 million people develop drug-resistant infections each year, resulting in more than 35,000 deaths. Certain drug-resistant strains of gonorrhea are on the list of urgent superbugs, as is Clostridioides difficile (C. diff), which can cause life-threatening diarrhea and colonic inflammation. The CDC estimates that 12,800 people die from his C. diff each year.
Methicillin-resistant Staphylococcus aureus (MRSA), one of the most common superbugs in the United States, kills 9,800 people each year. MRSA can spread rapidly in long-term care facilities and hospital settings. Spike 13% First year of the Covid pandemic.
Infections with drug-resistant shigella, which often cause severe diarrhea and stomach pains, are also rising at an alarming rate. In February The CDC last year 5% of Shigella infections were ‘highly drug-resistant’. This means that from 0% in 2015, they did not respond to many antibiotics.
Bacteria are not the only cause. In the United States, antifungal-resistant infections caused by the fungus Candida auris will increase by 60% in 2020, According to the CDC.
identified by WHO 12 Resistant Superbugs Considered a “priority pathogen,” CDC Track 18 listings Drug-resistant bacteria and fungi.
According to Valeria Gigante, team leader of the WHO’s Antimicrobial Resistance Division, antibiotic resistance kills more than 5 million people worldwide, more than HIV, tuberculosis and malaria combined.
Antimicrobial resistance is one of the greatest global health threats facing humanity.
“Antimicrobial resistance is one of the greatest global health threats facing humanity,” she said. “No more should we call it a silent pandemic. We should say loud and clear: it is indeed a pandemic.”
Bacteria and fungi are more likely to develop resistance the more they are exposed to antibiotics and antifungals. It had a gene that makes a protein called NDM-1 that can degrade even Currently, most E. coli strains (there are over 700) are non-lethal. But besides E. coli, several strains of Klebsiella, Enterobacter, and Acinetobacter already carry the gene, and more strains may soon acquire it, Fowler said. .
“They don’t need passports to travel,” Fowler said. And bacteria can exchange DNA “like baseball cards.”
Dr Venkatasbramanian Ramasbramanian, President of the Indian Society of Clinical Infectious Diseases said: Both countries are experiencing outbreaks of bacteria that are resistant to the strongest last resort antibiotics. “It’s just a matter of time.”
WHO says the rate of antibiotic resistance is accelerating. From 1970 to 2000, the average time it took for resistance to a new antibiotic to emerge was just two to three years longer than the 11-year average from 1930 to 1950. Antibiotics have no effect on Covid because they are caused by viruses, not bacteria.
Where are all the new drugs?
The economic model for new drugs — pharma companies invest a lot of money up front to test drugs for safety and efficacy, and then put that money back into sales after they’re approved — “it doesn’t work for antibiotics” Ramasubramanian said.
Developing a single new antibiotic can take up to 20 years and typically costs between $568 million and $700 million. PhRMAAnd only 1 in 30 of these drugs are ultimately approved to treat patients. However, unlike medicines intended for widespread use, there is an international push to reduce the use of antibiotics. Excessive or unnecessary antibiotic use increases the chances of pathogens developing resistance.
“When it comes to new antibiotics, we say, ‘Don’t use them’ or ‘Use them sparingly so they last longer,'” Ramasubramanian said. “It’s not an attractive proposition for anyone in the industry.”
Some countries have rolled out what are called “antibiotic control programs”. These encourage doctors to prescribe drugs only when there is a clear need. CDC Providing training courses and guidelines to help curb antibiotic use and stem resistance.
Even when antibiotics are really needed, they are often prescribed for only a few days or weeks, making them much less profitable than long-term daily medications for chronic conditions such as blood pressure and diabetes. increase.
“At the end of the day, the ‘supply and demand’ model doesn’t hold up to antibiotics,” says Fowler.
there is no easy answer
The world could face a “doomsday scenario” if pharmaceutical companies don’t start developing new antibiotics soon, WHO officials warn.
More people may die from infections that were once treatable, such as bacterial pneumonia, gonorrhea and salmonella. Those who need antibiotics the most, such as those with compromised immune systems and those undergoing cancer treatment, will be the most vulnerable.
“We have reached the post-antibiotic era,” Ramasbramanian warned in a March 15 statement.
Fowler, who was not involved in the WHO report, agreed with the organization’s bold use of the word “end of the world.” “WHO is 100% accurate,” he said. “I was thrilled to see them make such a strong statement because I think it’s true.”
There is no single solution to spur the development of new antibiotics, but Gigante said government funding and policies could help move the needle. For example, some countries have devised new economic models to encourage the development of antibiotics.
In the United States, lawmakers are debating a law called the Pasteur Act that would pay pharmaceutical companies to make these important new drugs available.
“It will basically be a subscription model like Netflix,” says Fowler. Pharmaceutical companies do not have to rely on minimal revenue from selling antibiotics in the commercial market. The proposed model is controversial and has not become law, but it is an example of the type of “new economic model” that WHO officials like Gigante want policymakers to explore.
US taxpayer money is already supporting some new antibiotic research. For example, Fowler heads a program called the Antimicrobial Resistance Leadership Group, which funds new trials with grants from the National Institutes of Health.
“This is a huge amount, but we need more money,” he said.
Better testing could help
Beyond calling for new antibiotics, WHO officials want to see better and faster ways to diagnose bacterial infections. Now, for his first 48 hours or so after a patient is infected, “I don’t know what bacteria I’m treating,” Fowler said.
The more quickly and accurately doctors can focus on the specific bacteria infecting their patients, the less likely they are to prescribe ineffective antibiotics, which can lead to increased resistance.
The diagnostic process involves taking a swab, sending it to a laboratory, and growing the bacteria from the swab until there is enough for testing. Then, while in the lab, we try different antibiotics to see which one works. It may take days or weeks, and the sickest patients cannot wait that long.
“There is no lack of good clinical practice, but the state of the art to treat infectious diseases in 2023 is an educated guess,” said Fowler. “It’s scary when you think about it.”
