A series exploring how research is rising to major challenges in health and society
In 2023, more than 2.4 million cases of syphilis, gonorrhea, and chlamydia were diagnosed in the United States. While this figure is undeniably high, it marks a slight improvement. According to the Centers for Disease Control and Prevention, the number of sexually transmitted infections (STIs) decreased by 1.8 percent from 2022 to 2023, with gonorrhea seeing the largest drop at 7.2 percent.
However, the number of STI diagnoses is just one facet of a larger, more complex issue. The increasing resistance of bacteria to antibiotics poses a significant threat to public health.
The Growing Threat of Antibiotic Resistance
One common treatment for STIs is doxycycline, which has been used as a prophylactic for gonorrhea, recommended for chlamydia since 2020, and as a substitute for syphilis during benzathine penicillin shortages. Yet, as Harvard immunologist Yonatan Grad notes, bacteria are evolving rapidly, developing resistance mechanisms that render antibiotics less effective.
“The increased use of doxycycline has, as we might have expected, selected for drug resistance,” Grad said.
This evolutionary arms race between bacteria and antibiotics is a fundamental challenge in medicine. Since the advent of penicillin in the 1940s, antibiotics have revolutionized medical treatment, tackling infections from urinary tract infections to meningitis. Yet, every antibiotic introduced eventually faces resistance.
The scope of the problem is staggering. In 2023, U.S. doctors wrote 252 million antibiotic prescriptions, equating to 756 prescriptions per 1,000 people, up from 613 per 1,000 in 2020. The CDC reports that over 2.8 million antimicrobial infections occur annually in the U.S., resulting in more than 35,000 deaths due to antimicrobial-resistant (AMR) infections.
Research and Development: A Race Against Time
For researchers like Grad, combating antibiotic resistance is akin to a high-stakes game of Whac-a-Mole—tracking resistance, understanding its mechanisms, and developing new drugs before bacteria adapt.
“Being able to treat these infections underlies so many aspects of medicine,” Grad emphasized. “Antibiotics are the support, the scaffolding on which medicine depends.”
Grad’s research highlights the rapid development of resistance. A study published in the New England Journal of Medicine revealed that the gene conferring resistance to tetracyclines in Neisseria gonorrhoeae surged from 10 percent in 2020 to over 30 percent by 2024.
While doxycycline remains effective for syphilis and chlamydia, the varying speed of resistance development in different pathogens presents a challenge. Some bacteria, like Mycobacterium tuberculosis and Pseudomonas aeruginosa, have developed strains so resistant that they leave doctors with few treatment options.
Strategizing Antibiotic Use
The findings raise critical questions for healthcare providers: When should new antibiotics be introduced to maximize their effectiveness before resistance inevitably develops? Traditional stewardship suggests withholding new drugs until existing ones fail. However, Grad’s 2023 research challenges this approach, suggesting that introducing new antibiotics sooner may delay resistance.
Meanwhile, Andrew Myers, Amory Houghton Professor of Chemistry, has been developing new antibiotics for over 30 years. His work focuses on creating new chemical compounds that can effectively bind to bacterial ribosomes, the complex structures essential for protein synthesis.
“Most of the antibiotics in our ‘modern’ arsenal are some 50 years old and no longer work against many emerging pathogens,” Myers said. “It’s a huge problem and it’s not as well appreciated as it should be.”
Despite significant progress, Myers’ work faces funding challenges. The termination of National Institutes of Health grants threatens the development of promising new antibiotics, potentially halting lifesaving progress.
Global Health Implications
The impact of funding cuts extends to global health infrastructure. Carole Mitnick, a professor of global health at Harvard Medical School, has observed significant reductions in funding for multidrug-resistant tuberculosis (MDR-TB) support, resulting in wasted resources and increased resistance.
“Not only is it immediately deadly and cruel not to deliver these lifesaving cures, but it sets the scene for more antimicrobial resistance,” Mitnick said.
Mitnick’s work builds on the legacy of Paul Farmer, who emphasized a social justice framework in treating MDR-TB. This approach continues to influence researchers aiming to reach marginalized populations.
Globally, MDR-TB affects about 500,000 new individuals annually, causing an estimated 150,000 deaths in 2023. The disease exemplifies the challenges of drug-resistant pathogens and the social conditions that exacerbate resistance.
Community and Advocacy Efforts
In an unexpected alliance, the fan group of video bloggers John and Hank Green, known as TBFighters, has joined the fight against MDR-TB. Their advocacy has contributed to reducing the cost of TB diagnostic tests, demonstrating the power of community engagement in public health issues.
“In my opinion, we can absolutely win the game — temporarily,” Myers concluded. “Whatever we develop, bacteria will find a way to outwit us. But I’m optimistic that the molecules we’re making could have a clinical lifetime of many decades.”
As researchers continue to innovate and adapt, the battle against antibiotic resistance remains a critical priority. The ongoing investment in research and global health infrastructure is essential to maintaining the effectiveness of antibiotics and safeguarding public health.
