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Neisseria gonorrhoeae multilocus sequence type (ST) 9363 core-genogroup isolates have been associated with reduced azithromycin susceptibility (AZMrs) and show evidence of clonal expansion in the United States. Here, we analyze a global collection of ST-9363 core-genogroup genomes to shed light on the emergence and dissemination of this strain. The global population structure of ST-9363 core-genogroup falls into three lineages: Basal, European, and North American; with 32 clades within all lineages. Although, ST-9363 core-genogroup is inferred to have originated from Asia in the mid-19th century; we estimate the three modern lineages emerged from Europe in the late 1970s to early 1980s. The European lineage appears to have emerged and expanded from around 1986 to 1998, spreading into North America and Oceania in the mid-2000s with multiple introductions, along with multiple secondary reintroductions into Europe. Our results suggest two separate acquisition events of mosaic mtrR and mtrR promoter alleles: first during 2009–2011 and again during the 2012–2013 time, facilitating the clonal expansion of this core-genogroup with AZMrs in the United States. By tracking phylodynamic evolutionary trajectories of clades that share distinct demography as well as population-based genomic statistics, we demonstrate how recombination and selective pressures in the mtrCDE efflux operon granted a fitness advantage to establish ST-9363 as a successful gonococcal lineage in the United States and elsewhere. Although it is difficult to pinpoint the exact timing and emergence of this young core-genogroup, it remains critically important to continue monitoring it, as it could acquire additional resistance markers. [ABSTRACT FROM AUTHOR]

Background: In 2016, Centers for Disease Control and Prevention initiated Strengthening the US 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 sexually transmitted disease 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 to 2019, grantees collected 58,441 culture specimens from 46,822 patients and performed AST on 10,814 isolates (representing 6.8% [3412] and 8.9% [4883] 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. [ABSTRACT FROM AUTHOR]

Background Since 2014, Neisseria gonorrhoeae azithromycin (AZM) susceptibility has declined in the United States, but high-level AZM resistance (HL-AZMR) has been infrequent and sporadic. We describe a cluster of 14 N. gonorrhoeae isolates with HL-AZMR identified in Indianapolis over 13 months. Methods N. gonorrhoeae culture specimens (genital and extragenital) were collected from attendees of the Bell Flower Clinic. Isolates underwent antimicrobial susceptibility testing (AST) using Etest. AZM minimum inhibitory concentrations ≥256 µg/mL were classified as HL-AZMR. Local disease intervention specialists interviewed patients whose isolates demonstrated HL-AZMR and conducted partner services. Relatedness of isolates was investigated by genomic analyses. Results During 2017–2018, AST was performed in 1016 N. gonorrhoeae isolates collected at the Bell Flower Clinic. Fourteen isolates (1.4%) from 12 men collected over 13 months demonstrated HL-AZMR; all were cephalosporin susceptible. Of the 12 men, 9 were white and reported male sex partners. Nine of the men were able to be retested; all were cured with 250-mg ceftriaxone plus 1-g AZM. Two men named each other as partners; no other partners in common were reported. Genomic analysis demonstrated close relatedness of the HL-AZMR isolates and a novel combination of a mosaic- mtr R promoter along with 23S ribosomal RNA mutations that appear to have emerged from circulating strains. Conclusions The close genetic relatedness with limited epidemiologic linkages between patients highlights the challenges of gonorrhea partner investigations and suggests undetected local transmission. Local AST, rapid public health action, and epidemiologic investigations combined with genomic analysis provides a multipronged approach to understanding an outbreak of sexually transmitted disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Jurisdictions participating in Strengthening the US Response to Resistant Gonorrhea (SURRG) implemented specimen collection for culture and antimicrobial susceptibility testing from a sample of persons of all genders (at multiple anatomic sites) attending sexually transmitted disease clinics and community clinics. We describe the percentage and characteristics of patients whose isolates demonstrated reduced susceptibility (RS) to azithromycin, ceftriaxone, or cefixime.Methods: We included patients from clinics that participated in SURRG whose isolates underwent antimicrobial susceptibility testing by Etest. We defined RS as azithromycin minimum inhibitory concentrations (MICs) ≥2 μg/mL (AZM-RS), ceftriaxone MICs ≥0.125 μg/mL (CRO-RS), or cefixime MICs ≥0.25 μg/mL (CFX-RS). Patients with repeated infections appeared >1 time in the data. We calculated the frequency and percentage of patients with an isolate demonstrating RS by epidemiological characteristics.Results: During the period 2018-2019, 10,013 patients from 8 jurisdictions provided 10,735 isolates. Among 10,013 patients, 11.0% (n = 1099) had ≥1 isolate with AZM-RS (range by jurisdiction, 2.5%-18.0%). Approximately 11.3% of 8771 of patients visiting sexually transmitted disease clinics and approximately 8.8% of 1242 patients visiting community clinics had an AZM-RS isolate. Nearly 6% of 1013 females had an AZM-RS isolate; among males, the percents of patients with an AZM-RS isolate were 17.7% among 4177 men who have sex only with men and 6.1% among 3581 men who have sex only with women. Few (0.4%) patients had isolates with CFX-RS (n = 40) or CRO-RS (n = 43).Conclusions: Although infections with reduced cephalosporin susceptibility were rare, AZM-RS infections were prevalent in this sample of patients in multiple jurisdictions and across gender and gender of sex partner categories. [ABSTRACT FROM AUTHOR]