2024 STI Prevention Conference: Neisseria Gonorrhea Prevalence and Novel Treatment and Prevention Medications

introduction[00:00] Introduction

Hello, everyone. My name is Meena Ramchandani. I'm an infectious disease physician at the University of Washington in Seattle. This podcast is dedicated to an STI [sexually transmitted infections] literature review for health care professionals who are interested in remaining up to date on the diagnosis, management, and prevention of STIs. 

In this episode, we'll continue to review some interesting and relevant oral abstracts that were presented at the STD Prevention Conference in September of 2024 in Atlanta, Georgia, and we'll focus this session on surveillance and treatment of Neisseria gonorrhea. We'll also touch on the data around antimicrobial resistance and prevention of this organism. 

abstract-1[00:42] Abstract #1

The first abstract was presented by Dr. Le Van from the Uniformed Services University of the Health Sciences in Bethesda, Maryland, and is titled [GEIS] Gonococcal global surveillance shows multi-drug resistant isolates with common and novel patterns of resistance. This group analyzed trends in the susceptibility of Neisseria gonorrheaisolates to many different countries in the world, from Ghana, Kenya, Uganda, Thailand, the Philippines, Peru, and Georgia, and they analyzed these isolates to different antibiotics. Nine hundred sixty-two isolates were collected from individuals who were enrolled either in clinical care or public health surveillance activities from 2014 to 2022. What they found is that resistance to penicillin, ciprofloxacin, and tetracycline was over 90% for isolates from most of these countries. Overall, there has been a general increase in the number of isolates with reduced susceptibility to the cephalosporins as well. 

So, for example, five isolates from Kenya and 11 isolates from Georgia exhibited reduced susceptibility to the extended spectrum cephalosporins, or cefixime and/or ceftriaxone. And of the isolates from Kenya, four had reduced susceptibility to ceftriaxone. They also found that there has been an increase in the number of isolates resistant to gentamicin, which is a first-line antibiotic in some countries and in other countries reserved for those with an allergy to the cephalosporins. The frequency of resistance to any three antibiotics was high, but it ranged from 11% in Ghana to 92% in Peru. 

Taking a longitudinal view of phenotypic antimicrobial resistance over time, which was done in the country of Georgia, they found that there has been a steady increase in the resistance of isolates to penicillin, tetracycline, ciprofloxacin, gentamicin, and the cephalosporins from 2019 to 2022. And the resistance almost doubled for each antibiotic. For example, in 2019, resistance to tetracycline or ciprofloxacin was about 46%, but in 2022, the resistance was 88% of isolates, which was a drastic increase in a relatively short time frame. Neisseria gonorrhea isolates collected through the Gonococcal Global Surveillance Program display a concerning high frequency of resistance to multiple antibiotics and an increasing number of isolates that have reduced susceptibility to the cephalosporins and gentamicin, which are some of the main treatments that we use for Neisseria gonorrhea.

abstract-2[03:13] Abstract #2

Now that we've learned about the prevalence of antimicrobial-resistant gonorrhea worldwide, what's going on in the US? The second abstract to review was presented by Justin Holderman from the CDC and is titled Public health and laboratory activities for strengthening the U.S. response to resistant gonorrhea, also known as SURRG, from 2021 to 2022. This abstract reviewed programmatic outcome in the sixth and seventh years of SURGE, which funded eight national jurisdictions to improve local capacity to rapidly detect, as well as respond to antimicrobial-resistant gonorrhea. From 2021 to 2022, jurisdictions collected around 33,000 specimens for culture from about 25,000 patients. The specimens came from endocervical or vaginal, rectal, pharyngeal, and urine or urethral samples, so all anatomic sites and from all genders. And they came from both STD clinics as well as non-STD centers. For example, emergency departments, HIV clinics, and community health centers, and so on.

Thankfully, very few isolates only 10 in number had reduced susceptibility to ceftriaxone, and only 23 isolates had reduced susceptibility to cefixime. All isolates were successfully treated with recommended therapy per the STI treatment guidelines. In this program, Centers for Gonorrhea Excellence were formed at all SURRG sites, and they expanded the resources outside of the funded jurisdiction, as well as function as hubs for the area. Online treatment failure reporting forms were created, and the programs provided the ability to order supplies and culture of Neisseria gonorrhea, as well as developing communication strategies to share their local data with medical and public health professionals. 

Now, culturing Neisseria gonorrhea is rare in clinical settings, and that's because it's time-consuming and there's a need for specialized equipment. So, expanding access to Neisseria gonorrhea cultures is a significant benefit. They also expanded access to molecular markers that confer antibiotic resistance in Neisseria gonorrhea using nucleic acid amplification testing (or NAAT) specimens. These SURRG sites completed antimicrobial-resistant Neisseria gonorrheaoutbreak response plans, especially in areas that had no public health STI outbreak plan already in place. And so, these efforts included building relationships with emergency preparedness teams, local clinics, as well as laboratories. 

Overall, few isolates were found to have reduced susceptibility to ceftriaxone or cefixime in the SURRG program from 2021 to 2022, which is reassuring. But I'm still concerned about the worldwide prevalence of antimicrobial resistance for this organism as we mentioned in the first abstract. We know infectious diseases do not stay within a particular country or location, and it's inevitable that those isolates will at some point be present in the U.S. Therefore, continued detection and preparedness activities will be helpful to inform future prevention and control efforts. The laboratory program at the CDC is instrumental and very important part of the national surveillance of this organism, and it plays a crucial role in the control of STIs.

SURRG, which improved local capacity to rapidly detect and respond to antimicrobial-resistant gonorrhea actually ended in August of 2024. And the program has transitioned to CARGOS, which stands for Combating Antibiotic-Resistant Gonorrhea [and Other STIs]. Dr. Soge spoke about this program and other U.S.-based surveillance programs for Neisseria gonorrhea in our episode from July 15th, 2025, if you're interested in learning more.

abstract-3[06:57] Abstract #3

Now, let's turn to treatment, as there were a few interesting abstracts on the treatment of Neisseria gonorrhea that were presented at this conference. Dr. Kapoor from GSK [GlaxoSmithKline] presented antimicrobial activity of gepotidacin against Neisseria gonorrhea isolates collected from 2018 to 2021. Gepotidacin is a broad-spectrum oral antibiotic, and it inhibits the bacterial type II topoisomerases by a unique mechanism of action. The study collected around 700 Neisseria gonorrhea clinical isolates from different sites in the U.S., Australia, and India from 2019 through 2021, and it evaluated the in vitro activity of this new antibiotic against those isolates. Seventy-five percent of the isolates came from the urethra, 11% from the pharynx, 12% from rectal specimens, and 2% from cervical or vaginal specimens.

Globally, 4% of the isolates were non-susceptible to azithromycin, 17% to penicillin, 25% to tetracycline, and 46% had resistance to ciprofloxacin. None of the isolates were non-susceptible or resistant to ceftriaxone, cefixime, or spectinomycin. Spectinomycin is no longer available in the U.S., but it is available in some other countries to treat Neisseria gonorrhea. The MIC values, which stands for Minimum Inhibitory Concentration, for gepotidacin against all isolates range from less than 0.06 micrograms per milliliter to two micrograms per milliliter. The MIC-50 value, and that's the value of the minimum inhibitory concentration that inhibits the growth of at least 50% of the isolates was 0.5 micrograms per milliliter. And the MIC-90 value, which is the MIC value that inhibits at least 90% of the isolates was one microgram per milliliter. 

The majority of isolates, or 96%, were inhibited at gepotidacin MIC values of less than 1 μg/mL. The gepotidacin MIC-50 and -90 values were consistent at 0.5 and 1 μg/mL for all isolates resistant to other antibiotics. The only exception was for azithromycin non-susceptible isolates where the MIC-90 value was higher at 2 μg/mL. The isolates from the pharynx, urethra, and rectum had consistent MIC-90 values with overall isolates at 1 μg/mL. The MIC-90 value was one dilution higher for isolates from vaginal or cervical specimens, and this is encouraging because most antibiotics other than ceftriaxone seem to have less activity against Neisseria gonorrhea in the oral pharynx.

Based on the data provided, gepotidacin demonstrated potent in vitro activity against Neisseria gonorrhea isolates from three countries, including isolates that were non-susceptible to a number of antibiotics used to treat Neisseria gonorrhea, as well as isolates from the oropharynx. So, it's exciting to have new treatment options for Neisseria gonorrhea, especially isolates which demonstrate antimicrobial resistance, and an oral option, which is wonderful and makes it easier for patients to take.

abstract-4[10:13] Abstract #4

Dr. Hook from the University of Alabama presented an abstract titled Oral zoliflodacin for treatment of uncomplicated gonorrhea, subgroup analysis by race and region of the global phase 3, randomized control clinical trial. Zoliflodacin is an oral bacterial topoisomerase inhibitor and inhibits topoisomerase II with in vitro activity against Neisseria gonorrhea, including multidrug-resistant strains. It has a low propensity to develop resistance in vitro and is given as a single oral dose for uncomplicated gonorrhea. This antibiotic has a distinct binding mode from the fluoroquinolones, which allows the antibiotic to inhibit the growth of ciprofloxacin-resistant strains.

In a global randomized, phase III trial, which was done in five different countries at 16 different sites, all done at the same time using the same protocol, zoliflodacin 3 grams orally as a single dose was noninferior to the combination of an intramuscular ceftriaxone plus oral azithromycin to treat uncomplicated urogenital gonorrhea and had high cure rates. So, this abstract reviewed details of a subgroup analysis of this large global randomized study. We'll report findings on the evaluable population, which is the analysis including those people who had initial positive cultures for the organism and who returned for therapy. 

So, what they found is that in participants assigned male at birth, urogenital cure rates were extremely high. They were 97% for zoliflodacin compared to 100% in the ceftriaxone and azithromycin group. And results were similar in those assigned female at birth. Urogenital cure rates for zoliflodacin were 95% in South Africa, 98% in the U.S., 98% in the European Union, and 99% in Asia. So similar cure rates in different parts of the world. Urogenital cure rates for zoliflodacin were 95% in Black or African Americans, 98% in Whites, 99% in Asians, and 100% in other participants. At extragenital sites, zoliflodacin had a microbiological cure rate of 91% for pharyngeal gonorrhea, and 98% for rectal gonorrhea. Cure rates for zoliflodacin to treat Neisseria gonorrhea were high and comparable to the combination of ceftriaxone and azithromycin in different subgroups, including sex at birth, race, as well as region of the world. And this is encouraging information about another antibiotic that could treat Neisseria gonorrhea, especially one with a high microbiological cure rate in the oropharynx.

abstract-5[12:51] Abstract #5

Stephanie Cavallo from the Tennessee Department of Health discussed the next study titled Protective effect of reported meningococcal B vaccination BEXSERO against subsequently reported gonorrhea infections, Tennessee, 2015 to 2022. Now, let's go through some background. The meningococcal group E vaccine, also known as BEXSERO, was shown to have some protective effect of reducing the risk of subsequent gonorrhea in observational studies. So, this study used a statewide Tennessee surveillance and immunization data where they evaluated the protective effect of this vaccine against gonorrhea in a state with a largely rural population. In the study, they included persons with chlamydia infection or those negative for gonorrhea as a control group. 

In those patients who received two doses of the meningococcal group B vaccine compared to those who did not receive the vaccine, there was a 29% reduction in subsequent gonorrhea infection. When they limited follow up to two years after vaccination, they saw a 34% reduction in subsequent gonorrhea infection, suggesting a more protective effect early on. They did not see a protective effect in those who received one dose of the vaccine. So there seems to be some protective effect against subsequent gonorrhea infection among those patients immunized with two doses of the meningococcal group B vaccine compared to those who did not receive the vaccine. And this was a helpful study using statewide reportable disease and immunization data across both urban and rural areas.

summary[14:25] Summary

To conclude, I'd like to summarize some key points from this session. 

• Antimicrobial-resistant gonorrhea remains an urgent threat and multidrug-resistant Neisseria gonorrhea is common in many countries. 
• Neisseria gonorrhea isolates collected through the SURRG program from 2021 to 2022 showed few isolates with reduced susceptibility to ceftriaxone or cefixime in the U.S., and all isolates were successfully treated with therapy recommended in the STI treatment guidelines.
• Gepotidacin is a novel oral antibiotic that inhibits bacterial type two topoisomerases, and it demonstrates potent in vitro activity against Neisseria gonorrhea isolates from the U.S., Australia, and India, including isolates with antimicrobial resistance. 
• Zoliflodacin is another novel oral antibiotic that inhibits bacterial topoisomerase, and was found to be noninferior to ceftriaxone and azithromycin to treat uncomplicated urogenital gonorrhea. Cure rates were similar in subgroup analysis based on sex at birth, race, and geographical region of the world. 
• Using statewide surveillance and immunization data, and those patients who received two doses of the meningococcal B vaccine, BEXSERO, there was a 29% reduction in subsequent gonorrhea infection compared to those who were unvaccinated in Tennessee. 

credits[15:49] Credits

This podcast is brought to you by the National STD curriculum, the University of Washington STD Prevention Training Center, and is funded by the Centers for Disease Control and Prevention. Transcripts and references for this podcast series can be found on our website, the National STD Curriculum at www.std.uw.edu. Thank you for listening and have a wonderful day.