A2059G mutation in the 23S rRNA gene is the only reported mechanism conferring high-level azithromycin resistance (HL-AZMR) in Neisseria gonorrhoeae 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 the A2058G mutation confers HL-AZMR in N. gonorrhoeae.
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.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.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.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.
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).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.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.Combining PSI and WGS data improves our understanding of sexual network connectivity.
Abstract Background Extragenital gonococcal infections are common among men who have sex with men (MSM); however, data comparing antimicrobial susceptibilities of urogenital and extragenital Neisseria gonorrhoeae isolates are limited. We investigated differences in gonococcal antimicrobial susceptibility by anatomic site among cisgender 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). Conclusion 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. Disclosures Olusegun O. Soge, PhD, Hologic Inc. (Grant/Research Support)SpeeDx Inc. (Grant/Research Support) Stephanie N. Taylor, MD, GARDP - GC Antibiotic Development (Scientific Research Study Investigator, To my institution.)GlaxoSmithKline (Grant/Research Support, Funds to my institution.)
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.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.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.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.
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.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.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.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.
In 2016 the U.S. Centers for Disease Control and Prevention (CDC) initiated Strengthening the U.S. Response to Resistant Gonorrhea (SURRG) in local jurisdictions to enhance antibiotic resistant gonorrhea (ARGC) rapid detection and response infrastructure and evaluate the impact of key strategies.
Approach
Eight jurisdictions were funded for five years to establish or enhance local specimen collection for gonococcal cultures in STD and community clinics, conduct rapid antibiotic susceptibility testing (AST) using Etest® in local public health laboratories, modify surveillance systems for enhanced data collection and rapid communication of AST results, and initiate partner services and investigations among patients with GC demonstrating reduced susceptibility (RS) to ceftriaxone, cefixime or azithromycin.
Outcomes/Impact
SURRG grantees incorporated robust genital, pharyngeal, and rectal gonococcal culture collection from all genders at participating clinics. During 2018–2019, grantees performed AST on >10,700 isolates with a five-day median turnaround time from specimen collection to reporting AST results to providers. Fifty-nine percent of patients with RS GC returned for a test-of-cure; no resistance-related treatment failures were detected. Among 4,511 isolates, we found ≥95% concordance (within one doubling dilution) between AST performed locally using Etest® compared to agar dilution (reference method) for ceftriaxone, cefixime and azithromycin. We conducted investigations among cases and partners, identifying >100 new GC cases. Finally, we merged epidemiologic and partner data with isolate genomic data to further explore sexual networks with GC transmission and identify opportunities for local interventions.
Innovation and Significance
SURRG successfully built clinic, laboratory, and epidemiological capacity for local ARGC rapid detection and response. Notable outcomes/innovations include establishing best practices for collecting and transporting gonococcal culture specimens, implementing Etest® in local jurisdictions, and measuring the value of containing ARGC spread through partner services. Lessons learned and project-informed identification of additional ARGC control needs at the local and national level are being used to inform CDC's ongoing ARGC control efforts.
Meat and poultry processing facilities face distinctive challenges in the control of infectious diseases, including coronavirus disease 2019 (COVID-19) (1). COVID-19 outbreaks among meat and poultry processing facility workers can rapidly affect large numbers of persons. Assessment of COVID-19 cases among workers in 115 meat and poultry processing facilities through April 27, 2020, documented 4,913 cases and 20 deaths reported by 19 states (1). This report provides updated aggregate data from states regarding the number of meat and poultry processing facilities affected by COVID-19, the number and demographic characteristics of affected workers, and the number of COVID-19-associated deaths among workers, as well as descriptions of interventions and prevention efforts at these facilities. Aggregate data on confirmed COVID-19 cases and deaths among workers identified and reported through May 31, 2020, were obtained from 239 affected facilities (those with a laboratory-confirmed COVID-19 case in one or more workers) in 23 states.* COVID-19 was confirmed in 16,233 workers, including 86 COVID-19-related deaths. Among 14 states reporting the total number of workers in affected meat and poultry processing facilities (112,616), COVID-19 was diagnosed in 9.1% of workers. Among 9,919 (61%) cases in 21 states with reported race/ethnicity, 87% occurred among racial and ethnic minority workers. Commonly reported interventions and prevention efforts at facilities included implementing worker temperature or symptom screening and COVID-19 education, mandating face coverings, adding hand hygiene stations, and adding physical barriers between workers. Targeted workplace interventions and prevention efforts that are appropriately tailored to the groups most affected by COVID-19 are critical to reducing both COVID-19-associated occupational risk and health disparities among vulnerable populations. Implementation of these interventions and prevention efforts† across meat and poultry processing facilities nationally could help protect workers in this critical infrastructure industry.
Objective. It is well documented that injection drug users (IDUs) have a high prevalence of antibodies to hepatitis C virus (HCV). Sexual transmission of HCV can occur, but studies have shown that men who have sex with men (MSM) without a history of injection drug use are not at increased risk for infection. Still, some health-care providers believe that all MSM should be routinely tested for HCV infection. To better understand the potential role of MSM in risk for HCV infection, we compared the prevalence of antibody to HCV (anti-HCV) in non-IDU MSM with that among other non-IDU men at sexually transmitted disease (STD) clinics and human immunodeficiency virus (HIV) counseling and testing sites in three cities. Methods. During 1999–2003, public health STD clinics or HIV testing programs in Seattle, San Diego, and New York City offered counseling and testing for anti-HCV for varying periods to all clients. Sera were tested using enzyme immunoassays, and final results reported using either the signal-to-cutoff ratio or recombinant immunoblot assay results. Age, sex, and risk information were collected. Prevalence ratios and 95% confidence intervals were calculated. Results. Anti-HCV prevalence among IDUs (men and women) was between 47% and 57% at each site, with an overall prevalence of 51% (451/887). Of 1,699 non-IDU MSM, 26 (1.5%) tested anti-HCV positive, compared with 126 (3.6%) of 3,455 other non-IDU men (prevalence ratio 0.42, 95% confidence interval 0.28, 0.64). Conclusion. The low prevalence of anti-HCV among non-IDU MSM in urban public health clinics does not support routine HCV testing of all MSM.
In-vitro susceptibility distributions to antibiotics can evolve over time because of emerging resistance determinants. This can affect clinical drug efficacy and interpretation of laboratory susceptibility tests. In January 2019, the Clinical Laboratory Standards Institute (CLSI) analyzed Neisseria gonorrhoeae (Ng) susceptibility parameters for ceftriaxone (CRO), cefixime (CFX) and azithromycin (AZI) to review interpretive criteria for laboratory tests.
Methods
GISP (Gonococcal Isolate Surveillance Project) is a United States national surveillance project at approximately 25 sentinel STD clinics, collecting about 5,000 yearly urethral isolates from symptomatic men. From 1987–2017, minimal inhibitory drug concentrations (MIC) of 164,506 isolates were determined by agar dilution using CLSI-recommended protocols. Susceptibility parameters were calculated with R software, and included mean MIC, 98.5% MIC indicating end of wild-type distribution, and percent isolates meeting 2019 CLSI susceptibility (S) criteria (CRO, CFX, AZI <= 0.25, 0.25, 1 μg/mL, respectively) or current GISP alert definitions (CRO, CFX, AZI ≥=0.125, 0.25, 2 μg/mL, respectively).
Results
Since 1987, only 5 isolates did not meet CRO S criteria. CRO alerts peaked at 1.05% in 1991. Mean MICs were highest in 2016 (0.013 μg/mL; 95% CI: 0.013–0.013), but compared to the mean MIC when GISP began (0.011 μg/mL; 95% CI: 0.010–0.011) the difference was less than a full drug dilution. Isolates not meeting CFX S criteria, 76 since 1987, were at a 0.17% peak in 1992, as were mean MICs. Isolates not meeting AZI S criteria were highest at 3.6% and 4.4% in 2016 and 2017, respectively, as were mean MICs.
Conclusion
Ng CRO and CFX in-vitro susceptibilities have not uniformly decreased since GISP began, while most indicators suggest declining AZI in-vitro susceptibility. CLSI reviewed these data in conjunction with clinical, pharmacokinetic/-dynamic and other international susceptibility data and kept steady (CRO, CFX) or established new (AZI) 2019 laboratory testing susceptibility criteria.
