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.
DoxyPEP's Impact: New Evidence Shows Promise and Challenges in STI Prevention
After nearly two decades of rising sexually transmitted infection (STI) rates in the United States, the Centers for Disease Control & Prevention (CDC) 2023 surveillance report reveals a welcome shift: overall STI rates dropped by 1.8% from 2022 to 2023. Gonorrhea cases declined by 7% for the second straight year, and primary and secondary syphilis fell by 10%—marking the first significant decrease in more than two decades. While these figures offer cautious optimism, questions remain about how best to sustain momentum, especially amid ongoing concerns about antimicrobial resistance and unequal access to prevention resources.
One potentially transformative intervention gaining traction is doxycycline post-exposure prophylaxis (doxyPEP). The CDC’s 2024 guidelines recommend doxyPEP for gay, bisexual, and other men who have sex with men (MSM), as well as transgender women, who have experienced a bacterial STI in the past year. Although clinical trials showed promising efficacy against chlamydia and syphilis, real-world data underscore nuanced challenges related to resistance, health disparities, and local healthcare capacity.
The Changing Landscape of STI Prevention
Several initiatives set the stage for the recent slowdown in STI rates. The American Rescue Plan Act of 2021 provided funding to strengthen the disease intervention specialist workforce, bolstering capacity for targeted contact tracing and clinical follow-up. These efforts were amplified by new CDC recommendations that formalized doxyPEP for specific high-risk groups.
San Francisco became an early adopter of doxyPEP guidelines in October 2022, leveraging its established HIV prevention infrastructure and community partnerships. Early clinical trial data had shown marked drops in chlamydia and syphilis, prompting local officials to adopt prophylactic antibiotic use despite concerns over potential misuse and growing gonococcal resistance. Their experience would soon be mirrored and examined in other healthcare settings.
Real-World Evidence: San Francisco and Kaiser Permanente
Two new studies illuminate the impact of doxyPEP beyond controlled clinical environments. The first, conducted by the San Francisco Department of Public Health, examined STI rates before and after the city’s 2022 adoption of doxyPEP guidelines. Investigators reported a 49.6% drop in chlamydia and a 51.4% decline in early syphilis compared to what forecasts had predicted. Three sentinel STI clinics observed that 19.5% of eligible gay, bisexual, and other men who have sex with men, as well as transgender women, initiated doxyPEP—a relatively high uptake for a new intervention.
A complementary Kaiser Permanente Northern California study included more than 11,000 participants already on HIV pre-exposure prophylaxis (PrEP). Those who added doxyPEP to their prevention repertoire saw chlamydia rates fall from 9.6% to 2.0% every quarter, while syphilis rates declined from 1.7% to 0.3%. These improvements closely mirrored prior clinical trial data, underscoring doxyPEP’s real-world effectiveness in high-risk populations.
However, the two studies diverged in their findings on gonorrhea. San Francisco observed a 25.6% increase in gonorrhea cases among the doxyPEP group, while Kaiser Permanente achieved a modest 12% reduction. Even in the latter setting, the intervention had varying efficacy based on infection site, with minimal impact on pharyngeal gonorrhea. Researchers attribute these discrepancies to existing tetracycline resistance patterns, which can range from 20% in U.S. gonorrhea strains to over 50% in certain regions globally.
Key Challenges to Implementation
1. Antimicrobial Resistance
Chief among concerns is the capacity of gonorrhea and other pathogens to develop resistance to tetracyclines. A modeling study in The Lancet warns that if doxyPEP achieves very high uptake—around 90%—it could lose effectiveness within just 1.6 years. More moderate adoption might prolong utility but still faces the ever-present risk that gonococcal strains could quickly evolve. The tension between scaling up prophylaxis to curb infections and preserving antibiotic utility for the long term remains a core dilemma for public health agencies.
2. Limited Healthcare Infrastructure
Successfully rolling out doxyPEP also requires robust clinical infrastructures. San Francisco’s early adoption relied on specialized STI clinics, disease intervention specialists, and strong community engagement. Such resources are scarce in many rural areas and underresourced urban centers, where STI burdens are often high. Without targeted funding and workforce development, these regions may fail to realize the potential benefits of prophylaxis. This gap underscores why a one-size-fits-all strategy for doxyPEP is unlikely to work uniformly nationwide.
3. Cost and Insurance Access
The Kaiser Permanente experience highlighted how commercial insurance coverage can determine doxyPEP uptake. Though Kaiser found no racial or ethnic disparities in its cohort, the ability to pay for routine tests and antibiotics remains a significant hurdle for many. Nearly half of all new STIs affect patients aged 15–24, a demographic often lacking stable insurance. Safety-net providers, such as community clinics and public health agencies, will need additional resources to prevent cost barriers from fueling inequities in STI prevention.
Addressing Health Equity
Disparities in STI burden persist despite national declines. CDC data show that Black communities—though comprising just 12.6% of the population—face roughly a third of all reported STIs, and American Indian and Alaska Native populations have the highest rates of syphilis. These patterns reflect structural inequities, from healthcare access to economic stability. DoxyPEP, if expanded, could either narrow or widen these gaps, depending on implementation strategies.
For example, the San Francisco Department of Public Health’s success relied on partnerships with community-based organizations that serve LGBTQ+ populations, bilingual outreach, and peer educators who could directly address stigma. Similar culturally tailored approaches will be crucial elsewhere. Nationally, any prophylaxis effort must acknowledge social determinants of health, from limited insurance coverage to historical medical mistrust, as central issues in achieving equitable outcomes.
Policy Recommendations
Meeting these challenges head-on requires collaboration among federal agencies, healthcare systems, and local organizations. Four policy domains stand out:
Robust Surveillance and Resistance Tracking
Establish or enhance regional testing to promptly detect shifts in gonococcal resistance.
Standardize reporting on doxyPEP uptake, stratifying data by race, ethnicity, and insurance status to monitor equity.
Integrated Healthcare Delivery
Incorporate doxyPEP into existing HIV PrEP programs, leveraging shared clinical workflows for ongoing STI screening.
Provide decision-support tools to guide providers in identifying those most likely to benefit from prophylaxis and in understanding local resistance rates.
Financing and Insurance Coverage
Secure coverage mandates or subsidies so that the costs of antibiotics and regular STI tests do not fall disproportionately on those most at risk.
Offer grants or incentives for safety-net clinics to scale up prevention services, including patient education and follow-up testing.
Antimicrobial Stewardship and Patient Education
Develop guidelines for targeted doxyPEP use to minimize unnecessary exposure—especially for gonorrhea, given its evolving resistance.
Emphasize correct usage and follow-up testing in patient education to ensure prophylaxis remains effective and that potential side effects are promptly reported.
Looking Ahead: Balancing Innovation and Stewardship
DoxyPEP’s success in specific cohorts highlights how targeted prophylaxis can substantially reduce chlamydia and syphilis infections. However, higher gonococcal resistance in some locales points to the need for continual surveillance and swift policy adjustments. Achieving a balance between curbing acute STI outbreaks and safeguarding long-term antibiotic effectiveness will require:
Adaptive Guidelines: Quickly revising prescribing recommendations if local data reveal resistance spikes.
Equitable Implementation: Ensuring consistent uptake in historically underserved communities, rather than concentrating benefits among those with robust insurance.
Global Collaboration: Sharing best practices and emerging data to keep pace with evolving gonococcal strains and develop new therapeutic agents or vaccines.
Conclusion
The modest national declines in STI rates are a reminder that with strategic investments and coordinated interventions, progress is possible. DoxyPEP stands out as a promising addition to the prevention toolbox—particularly for chlamydia and syphilis—when backed by sufficient testing, monitoring, and community outreach. Yet the specter of antimicrobial resistance, along with ongoing disparities in healthcare access, underscores that a single biomedical solution must be carefully managed.
Findings from San Francisco and Kaiser Permanente prove doxyPEP can effectively reduce STI incidence in real-world settings. Whether it remains a durable tool will depend on collective commitment: policymakers must fund surveillance and outreach, clinicians must practice stewardship, and communities must engage to ensure equitable access. If implemented wisely, doxyPEP could shape a future where the burden of STIs—and the inequalities that fuel them—diminish, showcasing how targeted prevention strategies can enhance public health without jeopardizing our arsenal of antibiotics.