Enhancing Gonococcal Antimicrobial Resistance Surveillance in Cisgender Women, Strengthening the US Response to Resistant Gonorrhea, 2018 to 2019.

BACKGROUND: Cisgender women have been underrepresented in antibiotic-resistant gonorrhea (ARGC) surveillance systems. Three of 8 project sites (City of Milwaukee [MIL], Guilford County [GRB], Denver County [DEN]), funded under the Centers for Disease Control and Prevention's Strengthening the US Response to Resistant Gonorrhea (SURRG), focused efforts to better include cisgender women in ARGC surveillance. METHODS: MIL, GRB, and DEN partnered with diverse health care settings and developed gonorrhea culture criteria to facilitate urogenital specimen collection in cisgender women and men. Regional laboratories within the Antibiotic Resistance Laboratory Network performed agar dilution antibiotic susceptibility testing (AST) of gonococcal isolates. Data from 2018 and 2019 were analyzed. RESULTS: In SURRG, 90.5% (11,464 of 12,667) of the cisgender women from whom urogenital culture specimens were collected were from MIL, GRB, and DEN. Of women in SURRG whose gonococcal isolates underwent AST, 70% were from these 3 sites. In these 3 sites, a substantial proportion of cisgender women with positive urogenital cultures and AST were from health care settings other than sexually transmitted disease (STD) clinics (non-STD clinics; MIL, 56.0%; GRB, 80.4%; and DEN, 23.5%). Isolates with AST were obtained from 5.1%, 10.2%, and 2.4% of all diagnosed gonorrhea cases among cisgender women in MIL, GRB, and DEN, respectively, and were more often susceptible to all antibiotics than those from cisgender men from each of these sites. CONCLUSIONS: With focused efforts and partnerships with non-STD clinics, 3 SURRG sites were able to include robust ARGC surveillance from cisgender women. These findings may guide further efforts to improve gender equity in ARGC surveillance.

Strengthening the US Response to Resistant Gonorrhea: An Overview of a Multisite Program to Enhance Local Response Capacity for Antibiotic-Resistant Neisseria gonorrhoeae.

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.

Antimicrobial Susceptibility of Urogenital and Extragenital Neisseria gonorrhoeae Isolates Among Men Who Have Sex With Men: Strengthening the US Response to Resistant Gonorrhea and Enhanced Gonococcal Isolate Surveillance Project, 2018 to 2019.

BACKGROUND: We investigated differences in gonococcal antimicrobial susceptibility by anatomic site among cisgender men who have sex with men (MSM) using specimens collected through the Centers for Disease Control and Prevention's enhanced Gonococcal Isolate Surveillance Project and Strengthening the US Response to Resistant Gonorrhea. METHODS: During the period January 1, 2018-December 31, 2019, 12 enhanced Gonococcal Isolate Surveillance Project and 8 Strengthening the US Response to Resistant Gonorrhea sites collected urogenital, pharyngeal, and rectal isolates from cisgender MSM in sexually transmitted disease 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 3974 urethral, 1553 rectal, and 1049 pharyngeal isolates from 5456 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 with 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 multijurisdictional sentinel surveillance projects, antimicrobial susceptibility patterns of Neisseria 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.

Outcomes of Traditional and Enhanced Gonorrhea Partner Services in the Strengthening the US Response to Resistant Gonorrhea Project, 2017 to 2019.

INTRODUCTION: The Centers for Disease Control and Prevention implemented Strengthening the US Response to Resistant Gonorrhea (SURRG) to build local detection and response capacity and evaluate responses to antibiotic-resistant gonorrhea outbreaks, including partner services for gonorrhea. We evaluated outcomes of traditional partner services conducted under SURRG, which involved (1) counseling index patients and eliciting sexual partners; (2) interviewing, testing, and treating partners; and (3) providing partner services to partners newly diagnosed with gonorrhea. We also evaluated outcomes of enhanced partner services, which additionally involved interviewing and testing partners of persons who tested negative, and social contacts of index patients and partners. METHODS: We analyzed partner services investigation data from 8 jurisdictions participating in SURRG from 2017 to 2019. We summed total index patients, partners from traditional partner services, and partners and contacts from enhanced partner services, and calculated partner services outcomes among partners and contacts. We also visualized sexual networks from partner services data. RESULTS: Of 1242 index patients identified, 506 named at least 1 sexual partner. Traditional partner services yielded 1088 sexual partners, and 105 were newly diagnosed with gonorrhea. Enhanced partner services yielded an additional 59 sexual partners and 52 social contacts. Of those partners and contacts, 3 were newly diagnosed with gonorrhea. Network visualization revealed sparse networks with few complex partnership clusters. CONCLUSIONS: Traditional partner services for gonorrhea may be useful for eliciting, notifying, and diagnosing partners of index patients in an outbreak setting. Enhanced partner services are unlikely to be effective for eliciting, notifying, and diagnosing a substantial number of additional people.

Test of Cure Return Rate and Test Positivity, Strengthening the US Response to Resistant Gonorrhea, United States, 2018-2019.

BACKGROUND: Reduced antibiotic susceptibility (RS) in Neisseria gonorrhoeae (GC) may increase treatment failure. Conducting tests of cure (TOC) for patients with RS-GC may facilitate identification of treatment failures. METHODS: We examined 2018 to 2019 data from 8 jurisdictions participating in the US Centers for Disease Control and Prevention's Strengthening US Response to Resistant Gonorrhea project. Jurisdictions collected GC isolates and epidemiological data from patients and performed antimicrobial susceptibility testing. Minimum inhibitory concentrations of ceftriaxone, 0.125 µg/mL or greater; cefixime, 0.250 µg/mL or greater; or azithromycin, 2.0 µg/mL or greater were defined as RS. Patients with RS infections were asked to return for a TOC 8 to 10 days posttreatment. We calculated a weighted TOC return rate and described time to TOC and suspected reasons for any positive TOC results. RESULTS: Overall, 1165 patients were diagnosed with RS infections. Over half returned for TOC (weighted TOC, 61%; 95% confidence interval, 50.1%-72.6%; range by jurisdiction, 32%-80%). Test of cure rates were higher among asymptomatic (68%) than symptomatic patients (53%, P = 0.001), and men who have sex with men (62%) compared with men who have sex with women (50%; P < 0.001). Median time between treatment and TOC was 12 days (interquartile range, 9-16). Of the 31 (4.5%) TOC patients with positive results, 13 (42%) were suspected because of reinfection and 11 (36%) because of false-positive results. There were no treatment failures suspected to be due to RS-GC. CONCLUSIONS: Most patients with a RS infection returned for a TOC, though return rates varied by jurisdiction and patient characteristics. Test of cure can identify and facilitate treatment of reinfections, but false-positive TOC results may complicate interpretation and clinical management.

Implementation and Evaluation of Gradient Strip Antimicrobial Susceptibility Testing in US Public Health Laboratories to Respond to Resistant Gonorrhea.

BACKGROUND: Gradient strip antimicrobial susceptibility testing using Etest is conducted by local public health jurisdictions participating in the Strengthening the US 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/nonalert) agreement was calculated for MICs determined using Etest and agar dilution methods. RESULTS: Strengthening the US Response to Resistant Gonorrhea laboratories had high proficiency testing scores (≥98%) and low levels of interlaboratory 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% and 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.

Impact of Anatomic Site, Specimen Collection Timing, and Patient Symptom Status on Neisseria gonorrhoeae Culture Recovery.

BACKGROUND: Neisseria gonorrhoeae culture is required for antimicrobial susceptibility testing, but recovering isolates from clinical specimens is challenging. Although many variables influence culture recovery, studies evaluating the impact of culture specimen collection timing and patient symptom status are limited. This study analyzed urogenital and extragenital culture recovery data from Centers for Disease Control and Prevention's Strengthening the US Response to Resistant Gonorrhea (SURRG) program, a multisite project, which enhances local N. gonorrhoeae culture and antimicrobial susceptibility testing capacity. METHODS: Eight SURRG jurisdictions collected gonococcal cultures from patients with N. gonorrhoeae-positive nucleic acid amplification test (NAAT) results attending sexually transmitted disease and community clinics. Matched NAAT and culture specimens from the same anatomic site were collected, and culture recovery was assessed. Time between NAAT and culture specimen collection was categorized as same day, 1 to 7 days, 8 to 14 days, or ≥15 days, and patient symptoms were matched to the anatomic site where culture specimens were collected. RESULTS: From 2018 to 2019, among persons with N. gonorrhoeae-positive NAAT, urethral infections resulted in the highest culture recovery (5927 of 6515 [91.0%]), followed by endocervical (222 of 363 [61.2%]), vaginal (63 of 133 [47.4%]), rectal (1117 of 2805 [39.8%]), and pharyngeal (1019 of 3678 [27.7%]) infections. Culture recovery was highest when specimens were collected on the same day as NAAT specimens and significantly decreased after 7 days. Symptoms were significantly associated with culture recovery at urethral (P = <0.0001) and rectal (P = <0.0001) sites of infection but not endocervical, vaginal, or pharyngeal sites. CONCLUSIONS: Culture specimen collection timing and patient symptomatic status can impact culture recovery. These findings can guide decisions about culture collection protocols to maximize culture recovery and strengthen detection of antimicrobial-resistant infections.

Demographic and Epidemiological Characteristics Associated With Reduced Antimicrobial Susceptibility to Neisseria gonorrhoeae in the United States, Strengthening the US Response to Resistant Gonorrhea, 2018 to 2019.

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.

Exploring and Comparing the Structure of Sexual Networks Affected by Neisseria gonorrhoeae Using Sexual Partner Services Investigation and Genomic Data.

BACKGROUND: Sexual networks are difficult to construct because of 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 8 jurisdictions participating in Centers for Disease Control and Prevention's Strengthening the US 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 4627 diagnoses of NG infection (81% sequenced), 2455 people received a PSI, 393 people were negative contacts of cases, and 495 were contacts with an 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.

Can Diagnostic Codes in Health Care Claims Data Identify Confirmed Chlamydial and Gonococcal Infections? A Retrospective Cohort Study, 2003 to 2017.

BACKGROUND: Because most sources of administrative claims data do not contain laboratory result data, researchers rely on diagnosis codes to identify cases of disease. The validity of using diagnosis codes to identify chlamydial and gonococcal infections in administrative claims data remains largely uninvestigated. METHODS: We conducted a retrospective cohort analysis using OptumLabs Data Warehouse, which includes deidentified medical (inpatient and outpatient) claims and laboratory test results. Among males and females aged 15 to 39 years during the period 2003-2017, we identified chlamydia and gonorrhea test results and corresponding diagnosis codes. Using test results as the criterion standard, we calculated the sensitivity and specificity of chlamydia and gonorrhea diagnosis codes to identify laboratory-confirmed infections. RESULTS: We identified 9.7 million chlamydia and gonorrhea test results among 3.1 million enrollees. Of the 176,241 positive chlamydia test results, only 11,515 had a corresponding diagnosis code, for a sensitivity of 6.5 (95% confidence interval [CI], 6.4-6.7) and a specificity of 99.5 (95% CI, 99.5-99.5). Corresponding diagnosis codes were identified for 8056 of the 31,766 positive gonorrhea test results, for a sensitivity of 25.4 (95% CI, 24.9-25.8) and a specificity of 99.7 (95% CI, 99.7-99.7). CONCLUSIONS: Our findings indicate that using only International Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification diagnosis codes to identify chlamydial and gonococcal infections substantially underestimates the burden of these diseases and inaccurately classifies laboratory-confirmed infections.