Antibiotic Crisis: Hope Amid Institutional Decline
The fight against antimicrobial resistance (AMR) in sexually transmitted infections (STIs) stands at a critical crossroads. Despite a slight decline in U.S. STI rates in 2023, resistance to antibiotics continues to rise globally, particularly for gonorrhea. This creates a paradox: while we're seeing promising new treatments advancing toward approval, recent political decisions have dramatically weakened our ability to track resistance patterns. Meanwhile, funding and policy support for developing new antibiotics remain inadequate. This crisis demands urgent attention as resistant infections spread faster than new treatments can be developed, with serious implications for public health and patient care.
The Growing Threat of Antibiotic-Resistant STIs
For people living with chronic conditions or compromised immune systems, antibiotic-resistant STIs aren't just a public health statistic—they represent a serious and growing threat to wellbeing. While the Centers for Disease Control and Prevention (CDC) reported fewer gonorrhea cases in the U.S. last year, the global picture is far more concerning.
Gonorrhea is becoming increasingly resistant to our last effective treatments. In Southeast Asia, the World Health Organization (WHO) identified a three-fold increase in extensively drug-resistant gonorrhea strains in Cambodia between 2022 and 2023. These hard-to-treat infections now make up over 12% of cases in the region.
What does this mean for patients? When first-line treatments fail, people face longer infectious periods, more complex and expensive treatments, and greater risk of complications. For people living with HIV or hepatitis C, these resistant infections can further compromise health and complicate disease management.
Breakthrough Treatments on the Horizon
Despite the grim outlook, two novel antibiotics represent genuine breakthroughs in the fight against resistant STIs after decades without new gonorrhea treatments.
Zoliflodacin, developed through a Global Antibiotic Research & Development Partnership (GARDP) and Innoviva Specialty Therapeutics partnership, completed the largest Phase 3 trial ever conducted for gonorrhea, with promising results. While its 91% cure rate appears slightly lower than the current standard's 96%, zoliflodacin's significance lies in its novel mechanism of action against resistant strains and its oral administration route. As resistant gonorrhea increasingly requires injectable treatments, an effective oral option represents a major advance for both accessibility and patient care.
Equally promising is gepotidacin, developed by GSK and already FDA-approved for urinary tract infections as of March 2025. This novel antibiotic showed a 92.6% success rate against gonorrhea through its unique dual-targeting mechanism that inhibits two critical bacterial enzymes, making it effective against resistant strains. GSK plans to submit for the gonorrhea indication later in 2025.
These developments showcase complementary partnership models: GARDP's non-profit approach ensures zoliflodacin's availability in low-income countries, while gepotidacin demonstrates successful public-private partnership between GSK and BARDA. Despite these advances, the WHO reports the broader antibiotic pipeline remains critically thin, with only 12 truly innovative antibiotics among 32 in development, and just 4 targeting the most critical pathogens.
Political Decisions Undermining Public Health
In a dangerous contradiction, just as resistance is rising and new treatments are on the horizon, political decisions have severely weakened our ability to monitor and respond to these threats.
Since early 2025, the current administration has eliminated approximately 20,000 jobs across health agencies and proposed cutting the HHS budget by about 26% ($127 billion).
The impact on STI programs has been particularly severe. The Washington Post reported that all 27 scientists at the only U.S. facility capable of tracking hepatitis outbreaks were fired. Additionally, 77 CDC staff members working on STI prevention were let go, including 49 experts embedded in state health departments who provided critical support to local efforts.
Most alarming for people at risk of STIs is the closure of the specialized lab that tests gonorrhea samples for antibiotic resistance. This lab was our early warning system—without it, doctors and patients won't know which antibiotics still work until treatment failures start mounting.
Prevention Strategies: Interrupting Transmission Chains
While developing new antibiotics is critical, prevention remains essential. Doxycycline Post-Exposure Prophylaxis (DoxyPEP) has emerged as an effective tool for breaking transmission chains. The CDC now recommends that men who have sex with men and transgender women with a history of bacterial STIs use DoxyPEP after sexual encounters.
Real-world data from San Francisco showed significant declines in chlamydia and syphilis among those using DoxyPEP, though gonorrhea reductions were less dramatic. While some concerns exist about the potential for DoxyPEP to contribute to broader antibiotic resistance, current evidence suggests this approach can effectively reduce STI transmission in high-risk groups—a crucial tool while we wait for new treatments.
The Funding Gap and Market Failure
The fundamental problem in antibiotic development is an economic one: the market doesn't adequately reward the creation of new antibiotics, especially those held in reserve to combat resistance.
The experiences of both zoliflodacin and gepotidacin highlight this challenge. Zoliflodacin required non-profit involvement through GARDP to advance through clinical trials, while gepotidacin needed significant government funding through BARDA. As Henry Skinner of the AMR Action Fund notes, "The funds needed to support this ecosystem, particularly in late-stage development, won't be there in a couple of years unless something unanticipated happens."
The AMR Action Fund, backed by pharmaceutical companies, aims to invest $1 billion to bring 2-4 new antibiotics to patients by 2030. The Fund has deployed over $100 million in capital to companies developing promising antimicrobials. However, experts recognize this as a stopgap measure rather than a solution to the underlying market failure.
A more sustainable approach is proposed in the PASTEUR Act, which has been introduced in multiple congressional sessions without passing. This legislation would create subscription contracts with developers of critical antimicrobials, ensuring financial returns regardless of how sparingly the drugs are used—essentially paying for access rather than volume.
This "Netflix model" for antibiotics would help align public health needs with market incentives. However, despite bipartisan support, the Act faces an uncertain future in the current political climate of budget cutting and deregulation.
Disproportionate Impact on Vulnerable Communities
Antimicrobial resistance operates within complex syndemics, where multiple health conditions interact and amplify each other within populations experiencing social inequities. People living with HIV stand at the intersection of these overlapping epidemics.
Research shows people living with HIV have higher rates of drug-resistant gonorrhea co-infection, each condition worsening the other. This syndemic intensifies with hepatitis C—a Department of Veterans Affairs study found 37% of people with HIV were also HCV-positive, with significantly higher rates of mental health issues and substance use disorders among these co-infected patients.
Among people who inject drugs with HIV, HCV rates reach up to 71% in some settings, according to a global review. These aren't coincidental occurrences—structural factors create environments where these epidemics cluster and interact.
The dismantling of surveillance infrastructure creates a dangerous blind spot in tracking these syndemics. Without specialized CDC labs monitoring resistant gonorrhea, we've lost our early warning system for emerging resistance patterns in vulnerable communities. Simultaneously, new restrictions on health equity research effectively discourage scientists from studying social factors that increase vulnerability to antimicrobial resistance.
A Patient-Centered Path Forward
From a patient and advocate perspective, five key policy areas require immediate attention:
Restore critical infrastructure. The dismantling of STI surveillance labs has left both patients and providers flying blind. Congress must fund restoration of these capabilities and hold administration officials accountable so we can track resistance patterns, update treatment guidelines, and support state and local health departments.
Support innovative development models. The GARDP partnership for zoliflodacin and the GSK-BARDA collaboration that produced gepotidacin demonstrate effective approaches to antibiotic development. These models—balancing commercial viability with public health needs—warrant expanded funding and replication.
Implement pull incentives. The PASTEUR Act would create a subscription-based model rewarding companies for developing critically-needed antibiotics without encouraging overuse, aligning market incentives with public health priorities.
Strengthen integrated care models. People at highest risk of resistant infections often face multiple health challenges. HIV, HCV, and STI services should be integrated to address overlapping needs, following the Ryan White HIV/AIDS Program's comprehensive care model.
Expand prevention strategies. While new treatments are essential, preventing infections reduces suffering and limits resistance. Expanded access to DoxyPEP, increased STI screening in high-risk populations, and vaccine research represent critical prevention strategies.
The antimicrobial resistance crisis in STIs reveals a stunning act of self-sabotage: just as scientific innovation finally delivers promising new treatments like zoliflodacin and gepotidacin, the misguided decimation of public health infrastructure has crippled our ability to track and respond to resistant infections. This isn't poor timing—it's the cavalier dismemberment of critical surveillance systems by ill-equipped partisans wielding policy chainsaws with no regard for consequences. The resulting wreckage threatens to undo decades of progress against STIs, particularly for communities already navigating systemic barriers to care.
The path forward demands both hope and principled outrage. Patients and advocates must forcefully reject further cuts to public health infrastructure, demand immediate restoration of STI surveillance capabilities, and hold elected officials accountable for the consequences of their decisions. We must insist on passage of the PASTEUR Act to fix the broken economics of antibiotic development while ensuring that promising science reaches those who need it most, not just those with wealth, power, and access.