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

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.

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.

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.

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.

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.