Background: Evidence from the surveillance systems of antimicrobial-resistant (AMR) gonorrhea suggests substantial variation in the prevalence of AMR gonorrhea across populations. However, little is known about the extent to which the population-level demographic, socioeconomic, and health factors (e.g., population density, poverty level, or the prevalence of other sexually-transmitted diseases) are associated with the burden of AMR gonorrhea. We developed a hierarchical Bayesian spatial–temporal logistic regression model to investigate the association between multiple spatially- and temporally-varying predictors and the proportion of isolates with resistance to each one of ciprofloxacin, penicillin, and tetracycline between 2000 and 2019 in the United States (US). Methods: The model was informed by data from the Gonococcal Isolate Surveillance Project (GISP), a sentinel surveillance system to monitor trends in the AMR gonorrhea in the US. During our study period, GISP included 112,487 isolates from the first 25 symptomatic men who have been diagnosed with urethral gonorrhea each month after attending participating sexually-transmitted disease clinics in one of about 30 select cities. Findings: Among 112,487 isolates collected between 2000 and 2019, 16.5%, 13.7%, and 22.2% were resistance to ciprofloxacin, penicillin, and tetracycline. Denser populations were associated with higher prevalence of ciprofloxacin and penicillin resistance (odd ratio (OR): 1.5, 95% with credible interval: [1.29, 1.74] and 1.36 [1.22, 1.52], respectively); West was associated with higher prevalence of ciprofloxacin resistance (OR with respect to Midwest: 14.42 [2.02, 59.27]) and Southeast was associated with higher prevalence of ciprofloxacin and penicillin resistance (OR with respect to Midwest: 6.66 [1.59, 18.20] and 7.59 [2.3, 22.94]); higher prevalence of HIV was associated with higher prevalence of ciprofloxacin and tetracycline resistance (OR: 1.18 [1.01, 1.37] and 1.14 [1.02, 1.28]); and higher incidence of gonorrhea was associated with higher prevalence of tetracycline resistance (OR: 1.08 [1.05, 1.11]). Interpretation: Geographic location and certain population-level characteristics including population density and HIV prevalence could provide insight about the population-level risk of AMR gonorrhea at a county-level. These results could guide the expansion of AMR surveillance systems or access to drug susceptibility testing in areas with characteristics associated with increased prevalence of AMR gonorrhea. Funding: US National Institutes of Health. © 2025 The Author(s)

INTRODUCTION: Neisseria gonorrhoeae (Ng) has successively developed resistance to all previously recommended antimicrobial therapies, with ceftriaxone being the last option for monotherapy of gonorrhea. Global emergence and international spread of the FC428 clone derived mosaic penA-60 allele, associated with highlevel ceftriaxone minimum inhibitory concentrations (MICs) in non FC428 clone Ng lineages, has become an increasing concern. The penA-60 allele carrying Ng was first identified in the U.S. in Las Vegas, Nevada (2019; GCWGS-102723), with a multi-locus sequence type (MLST)-1901 strain, in a non FC428 clone Ng lineage, which is associated with a historically ceftriaxone susceptible core genogroup. Later in 2022, an allele genetically similar to penA-60, mosaic penA-237, was identified in the UK (H22-722) and France (F92) with high-level ceftriaxone MICs and both belonged to MLST-1901. METHODS: In this study, we assessed phylogenomic relatedness and antimicrobial resistance (AMR) determinant profiles of these three isolates with high-level ceftriaxone MICs among a global collection of 2,104 genomes belonging to the MLST-1901 core genome cluster group 31, which includes strains separated by a locus threshold of 200 or fewer differences (Ng_cgc_200). Recombination events in and around the penA coding region were catalogued and potential sources of inter species recombinant DNA were also inferred. RESULTS: The global population structure of MLST-1901 core genogroup falls into 4 major lineages. Isolates GCWGS-10723, F92, and H22-722 clustered within Lineage 1, which was dominated by non-mosaic penA-5 alleles. These three isolates formed a clade within Lineage 1 that consisted of isolates from North America and southeast Asia. Neisseria subflava and Neisseria sicca were identified as likely progenitors of two independent recombination events that may have led to the generation of mosaic penA-60 and penA-237, within a possible non-mosaic penA-5 background. DISCUSSIONS: Our study suggests that there are multiple evolutionary pathways that could generate concerning mosaic penA alleles via homologous recombination of historically susceptible Ng lineages with Neisseria commensals. Enhanced surveillance of gonococcal strains and Neisseria commensals is crucial for understanding of the evolution of AMR, particularly in less-studied regions (e.g., Asia), where high-level ceftriaxone MICs and multi-drug resistance are more prevalent.

Despite the emergence of antimicrobial-resistant (AMR) strains of Neisseria gonorrhoeae, the treatment of gonorrhea remains empiric and according to standardized guidelines, which are informed by the national prevalence of resistant strains. Yet, the prevalence of AMR varies substantially across geographic and demographic groups. We investigated whether data from the national surveillance system of AMR gonorrhea in the US could be used to personalize the empiric treatment of gonorrhea. We used data from the Gonococcal Isolate Surveillance Project collected between 2000-2010 to train and validate machine learning models to identify resistance to ciprofloxacin (CIP), one of the recommended first-line antibiotics until 2007. We used these models to personalize empiric treatments based on sexual behavior and geographic location and compared their performance with standardized guidelines, which recommended treatment with CIP, ceftriaxone (CRO), or cefixime (CFX) between 2005-2006, and either CRO or CFX between 2007-2010. Compared with standardized guidelines, the personalized treatments could have replaced 33% of CRO and CFX use with CIP while ensuring that 98% of patients were prescribed effective treatment during 2005-2010. The models maintained their performance over time and across geographic regions. Predictive models trained on data from national surveillance systems of AMR gonorrhea could be used to personalize the empiric treatment of gonorrhea based on patients' basic characteristics at the point of care. This approach could reduce the unnecessary use of newer antibiotics while maintaining the effectiveness of first-line therapy.

Gonorrhea rates continue to rise in the United States and Neisseria gonorrhoeae's propensity to develop resistance to all therapies used for treatment has complicated the management of gonorrhea. Ceftriaxone is the only remaining highly effective recommended regimen for gonococcal treatment and few new anti-gonococcal antimicrobials are being developed. The 2021 CDC STI Treatment Guidelines increased the dose of ceftriaxone to 500 mg (1 g if ≥ 150 kg) for uncomplicated infections. It is recommended that all clinicians should be aware of antimicrobial resistant gonorrhea and be able to appropriately manage any suspected gonorrhea treatment failure case.

Rapid point-of-care tests that diagnose gonococcal infections and identify susceptibility to antibiotics enable individualized treatment. This could improve patient outcomes and slow the emergence and spread of resistance. However, little is known about the long-term impact of such diagnostics on the burden of gonorrhea and the effective lifespan of antibiotics. We used a mathematical model of gonorrhea transmission among men who have sex with men in the US to project the annual rate of reported gonorrhea cases and the effective lifespan of ceftriaxone, the recommended antibiotic for the first-line treatment of gonorrhea, as well as two previously recommended antibiotics, ciprofloxacin and tetracycline, when a rapid drug susceptibility test (DST) that reports susceptibility to ciprofloxacin and tetracycline is available. The use of a rapid DST with ≥50% sensitivity and ≥95% specificity, defined in terms of correct ascertainment of drug susceptibility and non-susceptibility status, could increase the combined effective lifespan of ciprofloxacin, tetracycline, and ceftriaxone by at least 2 years over 25 years of simulation. If test specificity is imperfect, however, the increase in the effective lifespan of antibiotics is accompanied by an increase in the rate of reported gonorrhea cases even under perfect sensitivity.

This study characterized high-quality whole-genome sequences of a sentinel, surveillance-based collection of 1710 Neisseria gonorrhoeae (GC) isolates from 2019 collected in the USA as part of the Gonococcal Isolate Surveillance Project (GISP). It aims to provide a detailed report of strain diversity, phylogenetic relationships and resistance determinant profiles associated with reduced susceptibilities to antibiotics of concern. The 1710 isolates represented 164 multilocus sequence types and 21 predominant phylogenetic clades. Common genomic determinants defined most strains' phenotypic, reduced susceptibility to current and historic antibiotics (e.g. bla (TEM) plasmid for penicillin, tetM plasmid for tetracycline, gyrA for ciprofloxacin, 23S rRNA and/or mosaic mtr operon for azithromycin, and mosaic penA for cefixime and ceftriaxone). The most predominant phylogenetic clade accounted for 21 % of the isolates, included a majority of the isolates with low-level elevated MICs to azithromycin (2.0 µg ml(-1)), carried a mosaic mtr operon and variants in PorB, and showed expansion with respect to data previously reported from 2018. The second largest clade predominantly carried the GyrA S91F variant, was largely ciprofloxacin resistant (MIC ≥1.0 µg ml(-1)), and showed significant expansion with respect to 2018. Overall, a low proportion of isolates had medium- to high-level elevated MIC to azithromycin ((≥4.0 µg ml(-1)), based on C2611T or A2059G 23S rRNA variants). One isolate carried the penA 60.001 allele resulting in elevated MICs to cefixime and ceftriaxone of 1.0 µg ml(-1). This high-resolution snapshot of genetic profiles of 1710 GC sequences, through a comparison with 2018 data (1479 GC sequences) within the sentinel system, highlights change in proportions and expansion of select GC strains and the associated genetic mechanisms of resistance. The knowledge gained through molecular surveillance may support rapid identification of outbreaks of concern. Continued monitoring may inform public health responses to limit the development and spread of antibiotic-resistant gonorrhoea.

Disseminated gonococcal infection (DGI) is a rare complication caused by the systemic dissemination of Neisseria gonorrhoeae to normally sterile anatomical sites. Little is known about the genetic diversity of DGI gonococcal strains and how they relate to other gonococcal strains causing uncomplicated mucosal infections. We used whole genome sequencing to characterize DGI isolates (n = 30) collected from a surveillance system in Georgia, United States, during 2017-2020 to understand phylogenetic clustering among DGI as well as uncomplicated uro- and extragenital gonococcal infection (UGI) isolates (n = 110) collected in Fulton County, Georgia, during 2017-2019. We also investigated the presence or absence of genetic markers related to antimicrobial resistance (AMR) as well as surveyed the genomes for putative virulence genetic factors associated with normal human-serum (NHS) resistance that might facilitate DGI. We found that DGI strains demonstrated significant genetic variability similar to the population structure of isolates causing UGI, with sporadic incidences of geographically clustered DGI strains. DGI isolates contained various AMR markers and genetic mechanisms associated with NHS resistance. DGI isolates had a higher frequency of the porB1A allele compared with UGI (67% vs 9%, P < .0001); however, no single NHS resistance marker was found in all DGI isolates. Continued DGI surveillance with genome-based characterization of DGI isolates is necessary to better understand specific factors that promote systemic dissemination.

INTRODUCTION: Neisseria gonorrhoeae has developed resistance to all first-line recommended therapies, making gonococcal antimicrobial resistance a major public health concern given limited antibiotic options currently and an even smaller antimicrobial development pipeline. Since the release of the Centers for Disease Control and Prevention (CDC) 2015 STD Treatment Guidelines, azithromycin, part of the 2015 dual-drug treatment regimen, has had a rapid rise in resistance. The 2020 CDC Gonorrhea Treatment Recommendations and the 2021 Sexually Transmitted Infections (STI) Treatment Guidelines were developed weighing the priorities of treating the individual, protecting the population, and preventing antimicrobial resistance. METHODS: Gonorrhea subject matter experts (SME) generated 8 key questions and conducted a literature review of updated data from 2013 to 2019 on gonorrhea antimicrobial resistance, treatment failures, clinical trials, and other key topics. More than 2200 abstracts were assessed, and 248 clinically relevant articles were thoroughly reviewed. SMEs also evaluated N gonorrhoeae antimicrobial resistance data from the Gonococcal Isolate Surveillance Project (GISP). EVIDENCE: Although there have been reports of ceftriaxone treatment failures internationally, GISP data suggest that ceftriaxone minimal inhibitory concentrations (MICs) have remained stable in the United States, with < 0.1% exhibiting an "alert value" MIC (> 0.25 mcg/mL). However, GISP documented a rapid rise in the proportion of isolates with an elevated MIC (≥ 2.0 mcg/mL) to azithromycin-nearly 5% in 2018. At the same time, new pharmacokinetic/pharmacodynamic data are available, and there is greater recognition of the need for antimicrobial stewardship. SUMMARY: The 2021 CDC STI Treatment Guidelines now recommend 500mg ceftriaxone intramuscularly once for the treatment of uncomplicated gonorrhea at all anatomic sites. If coinfection with chlamydia has not been excluded, cotreatment with doxycycline 100mg twice daily for 7 days should be added. Few alternative therapies exist for persons with cephalosporin allergies; there are no recommended alternative therapies for N gonorrhoeae infection of the throat.

In the absence of point-of-care gonorrhea diagnostics that report antibiotic susceptibility, gonorrhea treatment is empiric and determined by standardized guidelines. These guidelines are informed by estimates of resistance prevalence from national surveillance systems. We examined whether guidelines informed by local, rather than national, surveillance data could reduce the incidence of gonorrhea and increase the effective lifespan of antibiotics used in treatment guidelines. We used a transmission dynamic model of gonorrhea among men who have sex with men (MSM) in 16 U.S. metropolitan areas to determine whether spatially adaptive treatment guidelines based on local estimates of resistance prevalence can extend the effective lifespan of hypothetical antibiotics. The rate of gonorrhea cases in these metropolitan areas was 5,548 cases per 100,000 MSM in 2017. Under the current strategy of updating the treatment guideline when the prevalence of resistance exceeds 5%, we showed that spatially adaptive guidelines could reduce the annual rate of gonorrhea cases by 200 cases (95% uncertainty interval: 169, 232) per 100,000 MSM population while extending the use of a first-line antibiotic by 0.75 (0.55, 0.95) years. One potential strategy to reduce the incidence of gonorrhea while extending the effective lifespan of antibiotics is to inform treatment guidelines based on local, rather than national, resistance prevalence.

BACKGROUND: We investigated differences in gonococcal antimicrobial susceptibility by anatomic site among cisgender men who have sex with men (MSM) using specimens collected through CDC's enhanced Gonococcal Isolate Surveillance Project (eGISP) and Strengthening the U.S. Response to Resistant Gonorrhea (SURRG). METHODS: During January 1, 2018-December 31, 2019, 12 eGISP and 8 SURRG sites collected urogenital, pharyngeal, and rectal isolates from cisgender MSM in STD clinics. Gonococcal isolates were sent to regional laboratories for antimicrobial susceptibility testing by agar dilution. To account for correlated observations, linear mixed-effects models were used to calculate geometric mean minimum inhibitory concentrations (MICs) and mixed-effects logistic regression models were used to calculate the proportion of isolates with elevated or resistant MICs; comparisons were made across anatomic sites. RESULTS: Participating clinics collected 3,974 urethral, 1,553 rectal, and 1,049 pharyngeal isolates from 5,456 unique cisgender MSM. There were no significant differences in the geometric mean MICs for azithromycin, ciprofloxacin, penicillin, and tetracycline by anatomic site. For cefixime and ceftriaxone, geometric mean MICs for pharyngeal isolates were higher compared to anogenital isolates (p < 0.05). The proportion of isolates with elevated ceftriaxone MICs (≥0.125 μg/ml) at the pharynx (0.67%) was higher than at rectal (0.13%) and urethral (0.18%) sites (p < 0.05). CONCLUSIONS: Based on data collected from multi-jurisdictional sentinel surveillance projects, antimicrobial susceptibility patterns of N. gonorrhoeae isolates may differ among MSM at extragenital sites, particularly at the pharynx. Continued investigation into gonococcal susceptibility patterns by anatomic site may be an important strategy to monitor and detect the emergence of antimicrobial resistant gonorrhea over time.

BACKGROUND: In 2016, CDC initiated Strengthening the U.S. Response to Resistant Gonorrhea (SURRG) in multiple jurisdictions to enhance antibiotic resistant gonorrhea rapid detection and response infrastructure and evaluate the impact of key strategies. METHODS: Eight jurisdictions were funded to establish or enhance local gonococcal culture specimen collection in STD and community clinics, conduct rapid antimicrobial susceptibility testing (AST) in local laboratories, modify systems for enhanced data collection and rapid communication of results, and initiate enhanced partner services among patients with gonorrhea demonstrating elevated minimum inhibitory concentrations (MICs) to ceftriaxone, cefixime or azithromycin. RESULTS: Grantees incorporated genital, pharyngeal, and rectal gonococcal culture collection from all genders at participating clinics. During 2018-2019, grantees collected 58,441 culture specimens from 46,822 patients and performed AST on 10,814 isolates (representing 6.8% (3,412) and 8.9% (4,883) of local reported cases in 2018 and 2019 respectively). Of isolates that underwent AST, 11% demonstrated elevated azithromycin MICs; fewer than 0.5% demonstrated elevated ceftriaxone or cefixime MICs. Among patients whose infections demonstrated elevated MICs, 81.7% were interviewed for partner elicitation; however, limited new cases were identified among partners and contacts. CONCLUSIONS: As a public health model to build capacity to slow the spread of emerging resistance, SURRG successfully expanded culture collection, implemented rapid AST, and implemented an enhanced partner services investigation approach in participating jurisdictions. Findings from SURRG may enhance preparedness efforts and inform a longer-term, comprehensive, and evidence-based public health response to emerging gonococcal resistance. Continued development of innovative approaches to address emerging resistance is needed.

BACKGROUND: Gradient strip antimicrobial susceptibility testing (AST) using Etest® is conducted by local public health jurisdictions participating in the Strengthening the U.S. Response to Resistant Gonorrhea (SURRG) program to inform public health responses to resistant gonorrhea. Proficiency testing results across the participating laboratories were analyzed and a comparison of Etest® with the agar dilution method was conducted. METHODS: Laboratories participating in SURRG performed Etest® for azithromycin (AZM), cefixime (CFX), and ceftriaxone (CRO). Concurrence between minimum inhibitory concentrations (MICs) obtained with Etest® versus the agar dilution method using corresponding isolates was defined as +/- 1 double dilution. Specific levels of reduced susceptibility were termed "alerts" and included isolates with the following MICs: ≥ 2.0 μg/ml (AZM), ≥ 0.25 μg/ml (CFX), and ≥ 0.125 μg/ml (CRO). Categorical (alert/non-alert) agreement was calculated for MICs determined using Etest® and agar dilution methods. RESULTS: SURRG laboratories had high proficiency testing scores (≥98%) and low levels of inter-laboratory variations in MICs. The overall concurrence of MICs (essential agreement) determined using agar dilution and Etest® was 96% (CRO), 96% (CFX), and 95% (AZM). Depending on the antibiotic tested, between 27-66% of isolates with alert MICs determined by Etest® also had alert MICs using the reference agar dilution methodology, however most of these alert MICs were detected at threshold levels. CONCLUSIONS: This study demonstrates that MICs produced by SURRG laboratories using Etest® have a high level of concurrence with agar dilution. Although confirmation of specific alert MICs varied, Etest® facilities rapid detection and response to emerging resistant gonorrhea.

BACKGROUND: Sexual networks are difficult to construct due to incomplete sexual partner data. The proximity of people within a network may be inferred from genetically similar infections. We explored genomic data combined with partner services investigation (PSI) data to extend our understanding of sexual networks affected by Neisseria gonorrhoeae (NG). METHODS: We used 2017-2019 PSI and whole-genome sequencing (WGS) data from eight jurisdictions participating in CDC's Strengthening the United States Response to Resistant Gonorrhea (SURRG) project. Clusters were identified from sexual contacts and through genetically similar NG isolates. Sexual mixing patterns were characterized by describing the clusters by the individual's gender and gender of their sex partners. RESULTS: Our study included 4,627 diagnoses of NG infection (81% sequenced), 2,455 people received a PSI, 393 people were negative contacts of cases, and 495 contacts with unknown NG status. We identified 823 distinct clusters using PSI data combined with WGS data. Of cases that were not linked to any other case using PSI data, 37% were linked when using WGS data. Overall, 40% of PSI cases were allocated to a larger cluster when PSI and WGS data were combined compared with PSI data alone. Mixed clusters containing women, men who report sex with women, and men who report sex with men were common when using the WGS data either alone or in combination with the PSI data. CONCLUSIONS: Combining PSI and WGS data improves our understanding of sexual network connectivity.

The recent emergence of strains of Neisseria gonorrhoeae associated with treatment failures to ceftriaxone, the foundation of current treatment options, has raised concerns over a future of untreatable gonorrhea. Current global data on gonococcal strains suggest that several lineages, predominately characterized by mosaic penA alleles, are associated with elevated minimum inhibitory concentrations (MICs) to extended spectrum cephalosporins (ESCs). Here we report on whole genome sequences of 813 N. gonorrhoeae isolates collected through the Gonococcal Isolate Surveillance Project in the United States. Phylogenomic analysis revealed that one persisting lineage (Clade A, multi-locus sequence type [MLST] ST1901) with mosaic penA-34 alleles, contained the majority of isolates with elevated MICs to ESCs. We provide evidence that an ancestor to the globally circulating MLST ST1901 clones potentially emerged around the early to mid-20th century (1944, credibility intervals [CI]: 1935-1953), predating the introduction of cephalosporins, but coinciding with the use of penicillin. Such results indicate that drugs with novel mechanisms of action are needed as these strains continue to persist and disseminate globally.

BACKGROUND: The prevalence of Neisseria gonorrhoeae (GC) isolates with elevated minimum inhibitory concentrations (MICs) to various antibiotics continues to rise in the U.S. and globally. Genomic analysis provides a powerful tool for surveillance of circulating strains, antimicrobial resistance determinants, and understanding of transmission through a population. METHODS: GC isolates collected from the U.S. Gonococcal Isolate Surveillance Project (GISP) in 2018 (n=1479) were sequenced and characterized. Whole genome sequencing was used to identify sequence types, antimicrobial resistance profiles, and phylogenetic relationships across demographic and geographic populations. RESULTS: Genetic characterization identified that (1) 80% of the GC isolates were represented in 33 multilocus sequence types, (2) isolates clustered in 23 major phylogenetic clusters with select phenotypic and demographic prevalence, and (3) common antimicrobial resistance determinants associated with low-level or high-level decreased susceptibility or resistance to relevant antibiotics. CONCLUSIONS: Characterization of this 2018 GISP genomic dataset, which is the largest U.S. whole genome sequence data set to date, sets the basis for future prospective studies, and establishes a genomic baseline of GC populations for local and national monitoring.

BACKGROUND: The most recent estimates of the number of prevalent and incident sexually transmitted infections (STIs) in the United States (US) were for 2008. We provide updated estimates for 2018 using new methods. METHODS: We estimated the total number of prevalent and incident infections in the US for eight STIs: chlamydia, gonorrhea, trichomoniasis, syphilis, genital herpes, human papillomavirus (HPV), sexually transmitted hepatitis B, and sexually transmitted HIV. Updated per capita prevalence and incidence estimates for each STI were multiplied by the 2018 full resident population estimates to calculate the number of prevalent and incident infections. STI-specific estimates were combined to generate estimates of the total number of prevalent and incident STIs overall, and by gender and age group. Primary estimates are represented by medians and uncertainty intervals are represented by the 25th (Q1) and 75th (Q3) percentiles of the empirical frequency distributions of prevalence and incidence for each STI. RESULTS: In 2018, there were an estimated 67.6 (Q1=66.6, Q3=68.7) million prevalent and 26.2 (Q1=24.0, Q3=28.7) million incident STIs in the US. Chlamydia, trichomoniasis, genital herpes, and HPV comprised 97.6% of all prevalent and 93.1% of all incident STIs. Persons aged 15-24 years comprised 18.6% (12.6 million) of all prevalent infections; however, they comprised 45.5% (11.9 million) of all incident infections. CONCLUSIONS: The burden of STIs in the US is high. Almost half of incident STIs occurred in persons aged 15-24 years in 2018. Focusing on this population should be considered essential for national STI prevention efforts.

BACKGROUND: The most recent prevalence and incidence estimates for chlamydia and gonorrhea, the two most reported nationally notifiable conditions in the United States (US), were for 2008. We present updated estimates for the number of prevalent and incident chlamydial and gonococcal infections for 2018. METHODS: We estimated chlamydial prevalence directly from the 2015-2018 cycles of the National Health and Nutrition Examination Survey (NHANES) and chlamydial incidence using a mathematical model primarily informed by NHANES and case report data. Total and antimicrobial resistant (AMR) gonococcal prevalence and incidence were estimated using mathematical models primarily informed by case report and Gonococcal Isolate Surveillance Program data. Estimates were calculated for the total population, all women, and all men aged 15-39 years, stratified by age group. Primary estimates represent medians and uncertainty intervals represent the 25th (Q1) and 75th (Q3) percentiles of the empirical frequency distributions of prevalence and incidence for each infection. RESULTS: Among persons aged 15-39 years in the US in 2018, we estimate 2.35 (Q1=2.20, Q3=2.51) million prevalent and 3.98 (Q1=3.77, Q3=4.22) million incident chlamydial infections, and an estimated 209,000 (Q1=183,000, Q3=241,000) prevalent and 1.57 (Q1=1.44, Q3=1.72) million incident gonococcal infections. Of all gonococcal infections, there were 107,000 (Q1=94,000, Q3=124,000) prevalent and 804,000 (Q1=738,000, Q3=883,000) incident infections demonstrating AMR or elevated minimum inhibitory concentrations (MICs) to selected antibiotics. CONCLUSIONS: Chlamydia and gonorrhea were very common in the US in 2018. Estimates show that more than 800,000 newly acquired gonococcal infections in 2018 demonstrated resistance or elevated MICs to currently or previously recommended antibiotics.

In November 2019, the Southern Nevada Public Health Laboratory of the Southern Nevada Health District (SNHD) identified a male urethral gonococcal isolate later demonstrating reduced susceptibility to cefixime (minimum inhibitory concentration [MIC] = 2.0 μg/mL) and ceftriaxone (MIC = 1.0 μg/mL) but susceptible to azithromycin (MIC = 0.25 μg/mL). Molecular testing by CDC in the United States revealed the emerging mosaic penA60 allele, first identified in Japan in 2016 (1), which confers reduced susceptibility to cephalosporins and increases the risk for treatment failure. The penA60 allele has been identified in China (2), Canada (3,4), Denmark (5), Australia (6), France (7), and the United Kingdom (8). The Nevada case is the first identified case of a Neisseria gonorrhoeae isolate harboring the mosaic penA60 allele reported in the United States.

A2059G mutation in the 23S rRNA gene is the only reported mechanism conferring high-level azithromycin resistance (HL-AZMR) in Neisseria gonorrhoea Through U.S. gonococcal antimicrobial resistance surveillance projects, we identified four HL-AZMR gonococcal isolates lacking this mutational genotype. Genetic analysis revealed an A2058G mutation of 23S rRNA alleles in all four isolates. In vitro selected gonococcal strains with homozygous A2058G recapitulated the HL-AZMR phenotype. Taken together, we postulate that A2058G mutation confers HL-AZMR in N. gonorrhoeae.

BACKGROUND: Antibiotic-resistant gonorrhoea has been a chronic public health burden since the mid-1930s. Recent emergence of isolates resistant to the current recommended antibiotics for gonorrhoea further magnifies the threat of untreatable gonorrhoea. The lack of new, effective antibiotics highlights the need for better understanding of the population structure of Neisseria gonorrhoeae in order to provide greater insight on how to curtail the spread of antimicrobial-resistant N. gonorrhoeae. OBJECTIVES: To explore a potential application of MALDI-TOF MS to differentiate N. gonorrhoeae displaying different levels of susceptibility to the antibiotic azithromycin. METHODS: We conducted MALDI-TOF MS using the Bruker Biotyper on 392 N. gonorrhoeae isolates collected through the Gonococcal Isolate Surveillance Project (GISP) and/or the Strengthening the United States Response to Resistant Gonorrhea (SURRG) project. The MALDI-TOF MS spectra were visually analysed to assess the presence of distinctive peak(s). Statistical analysis was performed to assess the relationship between gonococcal isolates with the distinct protein peak and antibiotic susceptibility. RESULTS: In this study, we were able to differentiate N. gonorrhoeae isolates into two distinct subpopulations using MALDI-TOF MS. Isolates were distinguished by the presence or absence of a spectral peak at 11 300 Da. Notably, these two groups exhibited different levels of susceptibility to azithromycin. CONCLUSIONS: We have shown that in addition to its ability to identify N. gonorrhoeae, MALDI-TOF MS could also be used to differentiate gonococcal isolates with different levels of susceptibility to azithromycin.

In 2016, the proportion of Neisseria gonorrhoeae isolates with reduced susceptibility to azithromycin rose to 3.6%. A phylogenetic analysis of 334 N. gonorrhoeae isolates collected in 2016 revealed a single, geographically diverse lineage of isolates with MICs of 2-16 mug/mL that carried a mosaic-like mtr locus, whereas the majority of isolates with MICs >/= 16 mug/mL appeared sporadically and carried 23S rRNA mutations. Continued molecular surveillance of N. gonorrheae will identify new resistance mechanisms.

US gonorrhea rates are rising, and antibiotic-resistant Neisseria gonorrhoeae (AR-Ng) is an urgent public health threat. Since implementation of nucleic acid amplification tests for Ng identification, capacity for culturing Ng in the US has declined, along with the ability to perform culture-based antimicrobial susceptibility testing (AST). Yet, AST is critical for detecting and monitoring AR-Ng. In 2016, CDC established the Antibiotic Resistance Laboratory Network (AR Lab Network) to shore up national capacity for detecting several resistance threats including Ng. AR-Ng testing, a sub-activity of CDC's AR Lab Network, is performed in a tiered network of approximately 35 local laboratories, four regional laboratories (state public health laboratories in MD, TN, TX, WA), and CDC's national reference laboratory. Local laboratories receive specimens from approximately 60 clinics associated with the Gonococcal Isolate Surveillance Project (GISP), enhanced GISP (eGISP), and Strengthening the U.S. Response to Resistant Gonorrhea (SURRG). They isolate and ship up to 20,000 isolates to regional laboratories for culture-based agar dilution AST with seven antibiotics and for whole genome sequencing of up to 5,000 isolates. The CDC further examines concerning isolates and monitors genetic AR markers. During 2017 and 2018, the network tested 8,214 and 8,628 Ng isolates, and CDC received 531 and 646 concerning isolates, and 605 and 3,159 sequences, respectively. In summary, the AR Lab Network supported laboratory capacity for Ng-AST and associated genetic marker detection, expanding pre-existing notification and analysis systems for resistance detection. Continued, robust AST and genomic capacity can help inform national public health monitoring and intervention.