Projecting the development of antimicrobial resistance in Neisseria gonorrhoeae from antimicrobial surveillance data: a mathematical modelling study.

BACKGROUND: The World Health Organization recommends changing the first-line antimicrobial treatment for gonorrhoea when ≥ 5% of Neisseria gonorrhoeae cases fail treatment or are resistant. Susceptibility to ceftriaxone, the last remaining treatment option has been decreasing in many countries. We used antimicrobial resistance surveillance data and developed mathematical models to project the time to reach the 5% threshold for resistance to first-line antimicrobials used for N. gonorrhoeae. METHODS: We used data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in England and Wales from 2000-2018 about minimum inhibitory concentrations (MIC) for ciprofloxacin, azithromycin, cefixime and ceftriaxone and antimicrobial treatment in two groups, heterosexual men and women (HMW) and men who have sex with men (MSM). We developed two susceptible-infected-susceptible models to fit these data and produce projections of the proportion of resistance until 2030. The single-step model represents the situation in which a single mutation results in antimicrobial resistance. In the multi-step model, the sequential accumulation of resistance mutations is reflected by changes in the MIC distribution. RESULTS: The single-step model described resistance to ciprofloxacin well. Both single-step and multi-step models could describe azithromycin and cefixime resistance, with projected resistance levels higher with the multi-step than the single step model. For ceftriaxone, with very few observed cases of full resistance, the multi-step model was needed to describe long-term dynamics of resistance. Extrapolating from the observed upward drift in MIC values, the multi-step model projected ≥ 5% resistance to ceftriaxone could be reached by 2030, based on treatment pressure alone. Ceftriaxone resistance was projected to rise to 13.2% (95% credible interval [CrI]: 0.7-44.8%) among HMW and 19.6% (95%CrI: 2.6-54.4%) among MSM by 2030. CONCLUSIONS: New first-line antimicrobials for gonorrhoea treatment are needed. In the meantime, public health authorities should strengthen surveillance for AMR in N. gonorrhoeae and implement strategies for continued antimicrobial stewardship. Our models show the utility of long-term representative surveillance of gonococcal antimicrobial susceptibility data and can be adapted for use in, and for comparison with, other countries.

Impact of the Early COVID-19 Pandemic on the Number of HIV Preexposure Prophylaxis Uses and the Proportion of Preexposure Prophylaxis Users Receiving Sexually Transmitted Infection Testing Services.

BACKGROUND: With the potential impact of the COVID-19 pandemic on HIV preexposure prophylaxis (PrEP) care management, we assessed the number of PrEP users and sexually transmitted infection (STI) testing-eligible PrEP users, STI testing rates, and prevalence between prepandemic (January 1, 2018-March 31, 2020) and early-pandemic (April 1, 2020-September 30, 2020) periods. METHODS: In this retrospective cohort study, a PrEP user for a given quarter is defined as either a previous PrEP user or a PrEP initiator who has at least 1-day coverage of tenofovir/emtricitabine in the given quarter. The STI testing-eligible PrEP users for a given quarter were defined as those persons whose runout date (previous dispense date + days of tenofovir/emtricitabine supply) was in the given quarter. RESULTS: The quarterly number of PrEP users increased from the first quarter of 2018 to the first quarter of 2020 and then decreased in the second and third quarter of 2020. Among STI testing-eligible PrEP users who had ≤14 days between runout and next refill date, gonorrhea and chlamydia screening testing rates were 95.1% for prepandemic and 93.4% for early pandemic ( P = 0.1011). Among all STI testing-eligible PrEP users who were tested for gonorrhea and chlamydia, gonorrhea prevalence was 6.7% for prepandemic and 5.7% for early pandemic ( P = 0.3096), and chlamydia prevalence was 7.0% for prepandemic and 5.8% for early pandemic ( P = 0.2158). CONCLUSIONS: Although the early COVID-19 pandemic resulted in lower numbers of PrEP users and PrEP initiators, individuals who remained continuous users of PrEP maintained extremely high rates of bacterial STI screening. With high STI prevalence among PrEP users, assessments of PrEP care management are continuously needed.

Increased clonality among Neisseria gonorrhoeae isolates during the COVID-19 pandemic in Amsterdam, the Netherlands.

Distancing measures during the COVID-19 lockdown led to a temporary decrease of casual sex partners among clients of the Centre for Sexual Health (CSH) in Amsterdam, the Netherlands. We investigated the effect of this change on the genotypic and phenotypic distribution of Neisseria gonorrhoeae (Ng) isolates from CSH patients. From each Ng-positive patient we sequenced one isolate, resulting in 322 isolates which constituted two groups: 181 isolates cultured from 15 January to 29 February 2020 (before the first lockdown) and 141 cultured from 15 May to 30 June 2020 (during the first lockdown). Patient characteristics showed significantly more symptomatic patients and significantly fewer reported sex partners during the lockdown. Phenotypic data showed an increase in low-level azithromycin resistance and ceftriaxone susceptibility during the lockdown, and this remained after the study period. The diversity in sequence types (STs) decreased slightly during the lockdown. A shift occurred from ST 8156 being predominant before lockdown to ST 9362 during lockdown and a remarkably low median SNP distance of 17 SNPs was found between ST 9362 isolates obtained during lockdown. These findings reflect restricted travel and the change in sexual behaviour of CSH clients during the lockdown, with a potentially increased local transmission of the ST 9362 strain during this period, which led to genotypic and phenotypic changes in the Ng population. This shows that public health measures have far-reaching consequences and should be considered in the surveillance of other infectious diseases.

The European response to control and manage multi- and extensively drug-resistant Neisseria gonorrhoeae.

Because cefixime and ceftriaxone resistance in Neisseria gonorrhoeae and gonorrhoea treatment failures were increasing, a response plan to control and manage multidrug-resistant N. gonorrhoeae (MDR-NG) in Europe was published in 2012. The three main areas of the plan were to: (i) strengthen surveillance of antimicrobial resistance (AMR), (ii) implement monitoring of treatment failures and (iii) establish a communication strategy to increase awareness and disseminate AMR results. Since 2012, several additional extensively drug-resistant N. gonorrhoeae (XDR-NG) strains have emerged, and strains with high-level ceftriaxone resistance spread internationally. This prompted an evaluation and review of the 2012 European Centre for Disease Prevention and Control (ECDC) response plan, revealing an overall improvement in many aspects of monitoring AMR in N. gonorrhoeae; however, treatment failure monitoring was a weakness. Accordingly, the plan was updated in 2019 to further support European Union/European Economic Area (EU/EEA) countries in controlling and managing the threat of MDR/XDR-NG in Europe through further strengthening of AMR surveillance and clinical management including treatment failure monitoring. The plan will be assessed biennially to ensure its effectiveness and its value. Along with prevention, diagnostic, treatment and epidemiological surveillance strategies, AMR surveillance is essential for effective control of gonorrhoea.

Unusual presentation of a periurethral abscess following infection with Neisseria gonorrhoea.

We describe an unusual case of a male patient presenting with penile and testicular swelling following an unprotected and traumatic sexual encounter. It was suspected that an isolated penile injury occurred during intercourse; however, ultrasound imaging identified an intact tunical layer and right-sided epididymo-orchitis. Following screening for sexually transmitted infections (STIs), he was discharged with antibiotics and advice to attend the Sexual Health Centre for contact tracing. He represented with a periurethral abscess and an antimicrobial-resistant (AMR) strain of Neisseria gonorrhoea was identified. Appropriate antibiotic treatment was initiated. Examination-under-anaesthesia, following abscess drainage, revealed a contained collection with no urethral fistula; however, a flat urethral lesion was seen during urethroscopy. Repeat urethroscopy and biopsy of the lesion indicated polypoid urethritis. Periurethral abscess secondary to gonococcal urethritis is a rare complication, but one that we should be suspicious of, especially with the growing incidence of AMR-STIs.

Treatment of chlamydia and gonorrhea infections during the COVID-19 pandemic using provisional Centers for Disease Control guidance.

BACKGROUND: The COVID-19 pandemic created new challenges in controlling the transmission of sexually transmitted diseases (STDs), forcing the Centers for Disease Control and Prevention (CDC) to temporarily modify recommendations. As rapid COVID-19 testing emerged, supplies for similar testing platforms, specifically Chlamydia trachomatis and Neisseria gonorrhoeae, became compromised. LOCAL PROBLEM: The local community was identified as having the highest rate of chlamydia infections in North Carolina. Concerns regarding disease transmission within the community were amplified as the project site began experiencing a critical shortage of chlamydia and gonorrhea testing kits. METHODS: This quality improvement (QI) project, conducted in an emergency department, located in an underserved area with high STD infection rates, offered a prioritized approach to STD testing and treatment during a critical time with limited testing capabilities. INTERVENTIONS: Program analysis evaluated the management of 227 patients preintervention and 218 patients postintervention with confirmed or suspected infection, using a testing and treatment algorithm to identify and treat those most likely to be infected while preserving testing supplies for those at higher risk for complications from infections. RESULTS: Test utilization decreased by 25% (p-value = .003 via t-test), whereas a significant improvement in empiric treatment, increasing from 59% (133/227) to 73% (158/218), was also observed (p-value = .002 via chi-square analysis). CONCLUSIONS: Results suggest that a testing and treatment algorithm for providers can successfully guide testing and treatment decisions, reducing onward transmission and preserving supplies for those more likely to experience complications from chlamydia and gonorrhea infections.

Tackling Antimicrobial Resistance in the Shadow of COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic is a challenge for ongoing efforts to combat antimicrobial-resistant (AMR) bacterial infections. As we learn more about COVID-19 disease and drug stewardship evolves, there is likely to be a lasting impact of increased use of antimicrobial agents and antibiotics, as well as a lack of consistent access to health care across many populations. Sexually transmitted infections have been underreported during the pandemic and are often caused by some of the most drug-resistant pathogens. In their recent article in mBio, Parzych et al. (E. M. Parzych, S. Gulati, B. Zheng, M. A. Bah, et al., mBio 12:e00242-21, 2021, https://doi.org/10.1128/mBio.00242-21) focus on protection against Neisseria gonorrhoeae infection via in vivo delivery of an antigonococcal DNA-encoded antibody that has been modified for increased complement activation. Nucleic acid approaches are highly adaptable and could be tremendously beneficial for personalized strategies to combat AMR pathogens.

Decreases in Reported Sexually Transmitted Infections During the Time of COVID-19 in King County, WA: Decreased Transmission or Screening?

BACKGROUND: In response to the COVID-19 pandemic, Washington State's Stay Home, Stay Healthy (SHSH) order was implemented on March 24, 2020. We hypothesized that pandemic mitigation measures might reduce sexually transmitted infection (STI) screening and/or transmission. METHODS: We used King County, WA STI surveillance and sexual health clinic (SHC) data from January 1, 2019, to July 31, 2020. We calculated mean weekly case counts for gonorrhea, primary and secondary (P&S) syphilis, male urethral gonorrhea, and early latent (EL) syphilis for 3 periods in 2020: pre-SHSH (January 1-March 23), SHSH (March 24-June 5), and reopening (June 6-July 31). Primary and secondary syphilis and male urethral gonorrhea were used as proxies for sexual behavior, and EL syphilis was used as a proxy for STI screening. We compared SHC visits (2019 vs. 2020) and SHC gonorrhea treatment practices (across 2020 periods). RESULTS: Compared with January to July 2019, from January to July 2020, reported cases of gonorrhea, male urethral gonorrhea, P&S syphilis, and EL syphilis decreased by 9%, 5%, 16%, and 22%, respectively. Mean weekly case counts of gonorrhea, male urethral gonorrhea, and EL syphilis decreased pre-SHSH to SHSH, but all returned to pre-SHSH levels during reopening. Sexual health clinic visits during SHSH were 55% lower in 2020 than in 2019. In the SHC during SHSH, ceftriaxone treatment of gonorrhea decreased, whereas cefixime/cefpodoxime treatment and gonorrhea treatment with no testing increased. CONCLUSIONS: Decreases in reported STIs concurrent with COVID-19 SHSH may reflect a true decline in STI transmission. However, the larger decreases in asymptomatic infections indicate that much of the observed decrease was likely due to decreased screening.