UW Center for AIDS and STD

Publications Related to Gonorrhea from Public Health Seattle King County/UW

Rowlinson E, Stenger MR, Valentine JA, Hughes JP, Khosropour CM, Golden MR. Geographically pervasive racial disparities in Neisseria gonorrhoeae between NonHispanic Black and White US females. Sex Transm Dis. 2022 Oct 11


Background: Spatial analyses of gonorrhea morbidity among females often highlight the southeastern US but may not provide information on geographic variation in the magnitude of racial disparities; such maps also focus on geographic space, obscuring underlying population characteristics. We created a series of visualizations depicting both county-level racial disparities in female gonorrhea diagnoses and variations in population size.

Methods: We calculated county- and region-level race-specific relative rates (RelR) and between-race rate differences (RD) and rate ratios (RR) comparing gonorrhea case rates in non-Hispanic Black (NHB) vs non-Hispanic White (NHW) females. We then created proportional symbol maps with color representing counties’ RelR/RD/RR category and symbol size representing counties’ female population.

Results: Gonorrhea rates among NHB females were highest in the Midwest (718.7/100,000) and West (504.8), rates among NHW females were highest in the West (74.1) and Southeast (72.1). RDs were highest in the Midwest (654.6 excess cases/100,000) and West (430.7), while RRs were highest in the Northeast (12.4) and Midwest (11.2). Nearly all US counties had NHB female rates ≥3x those in NHW females, with NHB females in most highly populated counties experiencing ≥9-fold difference in gonorrhea rates.

Conclusions: Racial disparities in gonorrhea were not confined to the Southeast; both relative and absolute disparities were equivalent or larger in magnitude in areas of the Northeast, Midwest, and West. Our findings help counter damaging regional stereotypes, provide evidence to refocus prevention efforts to areas of highest disparities, and suggest a useful template for monitoring racial disparities as an actionable public health metric.

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Rowlinson E, Soge OO, Hughes JP, Berzkalns A, Thibault C, Kerani RP, Khosropour CM, Manhart LE, Golden MR, Barbee LA. Prior exposure to azithromycin and azithromycin resistance among persons diagnosed with Neisseria gonorrhoeae infection at a Sexual Health Clinic 2012-2019. Clin Infect Dis. 2022 Aug 24


Background: There is conflicting evidence on whether prior azithromycin (AZM) exposure is associated with reduced susceptibility to AZM (AZMRS) among persons infected with Neisseria gonorrhoeae (NG).

Methods: The study population included Public Health-Seattle & King County Sexual Health Clinic (SHC) patients with culture-positive NG infection at ≥1 anatomic site whose isolates were tested for AZM susceptibility 2012-2019. We used multivariate logistic regression to examine the association of time since last AZM prescription from the SHC in ≤12 months with subsequent diagnosis with AZMRS NG (minimum inhibitory concentration [MIC] ≥2.0 µg/ml) and used linear regression to assess the association between number of AZM prescriptions in ≤12 months and AZM MIC level, controlling for demographic, behavioral, and clinical characteristics.

Results: A total of 2,155 unique patients had 2,828 incident NG infections, 156 (6%) of which were caused by AZMRS NG. AZMRS NG was strongly associated with receipt of AZM from the SHC in the prior 29 days (adjusted odds ratio [aOR] 6.76, 95% CI 1.76-25.90), but not with receipt of AZM in the prior 30-365 days. Log AZM MIC level was not associated with the number of AZM prescriptions within ≤12 months (Adjusted correlation [aCor] 0.0004, 95% CI -0.04, 0.037), but was associated with number of prescriptions with <30 days (adjusted coefficient [aCoef] 0.56, 95% CI 0.13-0.98).

Conclusion: Recent individual-level AZM treatment is associated with subsequent AZMRS gonococcal infections. The long half-life and persistence of subtherapeutic levels of AZM may result in selection of resistant NG strains in persons with recent AZM use.

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Gieseker KE, Learner ER, Mauk K, Barbee LA, McNeil CJ, Hasty GL, Black JM, Johnson K, Nguyen TQ, Shrestha D, Pham CD, St Cyr S, Schlanger K, Kirkcaldy RD; SURRG Working Group. 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. Sex Transm Dis. 2021 Dec 1;48(12S Suppl 2):S118-S123


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.

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Schlanger K, Mauk K, Learner ER, Schillinger JA, Nishiyama M, Kohn R, Thibault C, Hermus H, Dewater J, Pabon V, Black J, St Cyr S, Pham CR, Kirkcaldy RD; SURRG Working Group. Test of Cure Return Rate and Test Positivity, Strengthening the US Response to Resistant Gonorrhea, United States, 2018-2019. Sex Transm Dis. 2021 Dec 1;48(12S Suppl 2):S167-S173


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.

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Thibault CS, Golden MR, Barbee LA, Spellman D, Soge OO, Kerani RP. Partner Elicitation After Partner Services Interviews and Reinterviews Among Patients With Antimicrobial-Resistant Gonorrhea. Sex Transm Dis. 2021 Dec 1;48(12S Suppl 2):S137-S143


Background: Partner notification services (PS) are often used to control sexually transmitted infections, but their effectiveness is limited by patients’ reluctance to name sex partners. We hypothesized that being notified of having antimicrobial-resistant Neisseria gonorrhoeae (ARGC) would make patients more likely to provide named partner information.

Methods: We used King County, Washington STD surveillance and Strengthening the US Response to Resistant Gonorrhea data to identify gonorrhea cases. Using log-binomial regression, we computed unadjusted and adjusted prevalence ratios for factors associated with naming any partners during routine PS interview vs. interview after ARGC diagnosis. Among those who completed a standard PS interview and later a reinterview after ARGC diagnosis, we compared mean numbers of reported and contactable partners at initial interview and reinterview using the Wilcoxon rank sum test.

Results: From July 2018 to October 2020, 1588 gonorrhea cases were interviewed; 103 (6%) had ARGC. After adjusting for sexual exposure, age, year, disease intervention specialist, reinterview, and diagnosing clinic, being interviewed after ARGC diagnosis remained predictive of naming ≥1 partner relative to routine PS (prevalence ratio, 2.2; 95% confidence interval, 1.6-2.9). Among 40 cases who completed a standard PS interview and later a reinterview after ARGC diagnosis, there was a modest increase in mean partners named at initial versus reinterview (1.4 vs. 1.9 per case, P = 0.09).

Conclusions: Cases interviewed after ARGC diagnosis named more contactable partners than did those undergoing routine PS. Reinterviewing patients after ARGC diagnosis provides only a modest increase in contactable partners but may be useful to limit transmission of this potentially challenging infection.

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Barbee LA. New Evidence for Antimicrobial-Resistant Gonorrhea Control Programs: Lessons Learned from the SURRG Project. Sex Transm Dis. 2021 Dec 1;48(12S Suppl 2):S93-S96

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Barbee LA, Golden MR, Thibault CS, McNeil CJ, Soge OO. Performance of Patient-collected Specimens for Neisseria gonorrhoeae Culture. Clin Infect Dis. 2021 Nov 2;73(9):e3196-e3200


Background: Neisseria gonorrhoeae culture is necessary to determine antimicrobial resistance, but typically requires specimen collection by clinicians. We sought to determine the sensitivity of patient-collected specimens for N. gonorrhoeae culture.

Methods: We performed N. gonorrhoeae cultures on paired clinician- and patient-collected specimens from the pharynx (n = 93), rectum (n = 88), endocervix/vagina (n = 89), and urethra/urine (n = 46). We calculated the percent concordance and the kappa statistics for paired-specimen results, and determined the test sensitivity for each specimen type using positivity of either specimen in a pair as a gold standard defining the presence of true infection.

Results: At least 1 specimen was positive in 26%, 31%, 61%, and 3% of paired samples in the pharynx, rectum, urethra/urine, and endocervix/vagina, respectively. Patient- and clinician-collected results were highly concordant at the pharynx (95%; kappa = 0.85), rectum (99%; kappa = 0.97), urethra/urine (83%; kappa = 0.87), and endocervix/vagina (100%; kappa = 1.0; P ≤ .005 for all comparisons). Patient-collected pharyngeal and rectal swabs and urine were 92%, 96%, and 96% sensitive, while clinician-collected specimens at these anatomic sites were 87.5%, 100%, and 94% sensitive (P > .05 for all comparisons). Among 24 urine specimens held for 4-22 hours after collection, 100% yielded concordant N. gonorrhoeae culture results, compared to immediate processing.

Conclusions: Patient- and clinician-collected specimens are comparably sensitive for N. gonorrhoeae culture. These findings suggest that patient-collected specimens could be used to expand the availability of gonococcal antimicrobial resistance testing for both clinical and surveillance purposes.

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Pham CD, Sharpe S, Schlanger K, St Cyr S, Holderman J, Steece R, Soge OO, Masinde G, Arno J, Schmerer M, Kersh EN; SURRG Working Group. Emergence of Neisseria gonorrhoeae Strains Harboring a Novel Combination of Azithromycin-Attenuating Mutations. Antimicrob Agents Chemother. 2019 Mar 27;63(4):e02313-18


The nimbleness of Neisseria gonorrhoeae to evade the effect of antibiotics has perpetuated the fight against antibiotic-resistant gonorrhea for more than 80 years. The ability to develop resistance to antibiotics is attributable to its indiscriminate nature in accepting and integrating exogenous DNA into its genome. Here, we provide data demonstrating a novel combination of the 23S rRNA A2059G mutation with a mosaic-multiple transferable resistance (mosaic-mtr) locus haplotype in 14 N. gonorrhoeae isolates with high-level azithromycin MICs (≥256 μg/ml), a combination that may confer more fitness than in previously identified isolates with high-level azithromycin resistance. To our knowledge, this is the first description of N. gonorrhoeae strains harboring this novel combination of resistance determinants. These strains were isolated at two independent jurisdictions participating in the Gonococcal Isolate Surveillance Project (GISP) and in the Strengthening the U.S. Response to Resistant Gonorrhea (SURRG) project. The data suggest that the genome of N. gonorrhoeae continues to shuffle its genetic material. These findings further illuminate the genomic plasticity of N. gonorrhoeae, which allows this pathogen to develop mutations to escape the inhibitory effects of antibiotics.

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Barbee LA, Soge OO, Katz DA, Dombrowski JC, Holmes KK, Golden MR. Increases in Neisseria gonorrhoeae With Reduced Susceptibility to Azithromycin Among Men Who Have Sex With Men in Seattle, King County, Washington, 2012-2016. Clin Infect Dis. 2018 Feb 10;66(5):712-718


Background: Antimicrobial-resistant Neisseria gonorrhoeae is a major public health threat. The Centers for Disease Control and Prevention (CDC) recommends ceftriaxone 250 mg plus azithromycin (AZM) 1 g for gonorrhea treatment. Resistance to AZM could affect gonorrhea control efforts.

Methods: Using gonococcal isolates collected at the Public Health-Seattle & King County (PHSKC) Sexually Transmitted Disease (STD) Clinic from 2012 to 2016, focusing on 2014-2016, we compared cases with the CDC AZM alert value minimum inhibitory concentration (MIC) (≥2 µg/mL) to those with AZM MIC ≤1 µg/mL, antimicrobial susceptibility profiles and clinical outcomes.

Results: In 2012 and 2013, none of the 263 patients from whom we isolated N. gonorrhoeae from the urethra were infected with organisms with an AZM MIC ≥2 µg/mL. Between 2014 and 2016, 4.4% of 926 gonorrhea cases demonstrated reduced susceptibility to AZM; 93% of these cases occurred among men who have sex with men (MSM). Among MSM, 5.0% of 2014-2016 cases demonstrated reduced susceptibility to AZM. No AZM alert value isolates had concomitant cephalosporin resistance. There were 2 potential treatment failures: 1 pharyngeal infection treated with AZM 2 g alone, and 1 pharyngeal infection that persisted after study drug.

Conclusions: Among MSM with gonorrhea in Seattle, 5% have gonorrhea with reduced susceptibility to AZM. The World Health Organization recommends changing treatment guidelines when >5% of isolates are resistant to a recommended drug. The emergence of resistant AZM gonorrhea should prompt reconsideration of current treatment recommendations, and highlights the need for new therapies for gonorrhea.

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