Therapy For Gonorrhea Research Articles

Assessing thresholds of resistance prevalence at which empiric treatment of gonorrhea should change among men who have sex with men in the US: A cost-effectiveness analysis.

Since common diagnostic tests for gonorrhea do not provide information about susceptibility to antibiotics, treatment of gonorrhea remains empiric. Antibiotics used for empiric therapy are usually changed once resistance prevalence exceeds a certain threshold (e.g., 5%). A low switch threshold is intended to increase the probability that an infection is successfully treated with the first-line antibiotic, but it could also increase the pace at which recommendations are switched to newer antibiotics. Little is known about the impact of changing the switch threshold on the incidence of gonorrhea, the rate of treatment failure, and the overall cost and quality-adjusted life-years (QALYs) associated with gonorrhea. We developed a transmission model of gonococcal infection with multiple resistant strains to project gonorrhea-associated costs and loss in QALYs under different switch thresholds among men who have sex with men (MSM) in the United States. We accounted for the costs and disutilities associated with symptoms, diagnosis, treatment, and sequelae, and combined costs and QALYs in a measure of net health benefit (NHB). Our results suggest that under a scenario where 3 antibiotics are available over the next 50 years (2 suitable for the first-line therapy of gonorrhea and 1 suitable only for the retreatment of resistant infections), changing the switch threshold between 1% and 10% does not meaningfully impact the annual number of gonorrhea cases, total costs, or total QALY losses associated with gonorrhea. However, if a new antibiotic is to become available in the future, choosing a lower switch threshold could improve the population NHB. If in addition, drug-susceptibility testing (DST) is available to inform retreatment regimens after unsuccessful first-line therapy, setting the switch threshold at 1% to 2% is expected to maximize the population NHB. A limitation of our study is that our analysis only focuses on the MSM population and does not consider the influence of interventions such as vaccine and common use of rapid drugs susceptibility tests to inform first-line therapy. Changing the switch threshold for first-line antibiotics may not substantially change the health and financial outcomes associated with gonorrhea. However, the switch threshold could be reduced when newer antibiotics are expected to become available soon or when in addition to future novel antibiotics, DST is also available to inform retreatment regimens.

Susceptibility of Neisseria gonorrhoeae against a dual treatment antibiotics regimen in primary health centres in Surabaya, Indonesia.

There were 82.4 million new gonorrhoea cases worldwide in 2020. Dual treatment with ceftriaxone or cefixime and azithromycin or doxycycline is currently recommended for gonorrhoea in Indonesia. However, reduced susceptibility and resistance to cephalosporins and azithromycin are increasing. We evaluated the susceptibility pattern of Neisseria gonorrhoeae to cefixime, ceftriaxone, azithromycin and doxycycline. N. gonorrhoeae isolates were obtained from 19 male participants with clinically and laboratory-confirmed gonorrhoea. Antibiotic susceptibility testing was conducted by disc diffusion and interpreted according to Clinical and Laboratory Standards Institute and Centers for Disease Control and Prevention criteria. Reduced susceptibility or resistance was observed against doxycycline in 19 isolates (100%), cefixime in six (31.6%), ceftriaxone in three (15.8%) and azithromycin in zero (0%) isolates. A dual treatment regimen with ceftriaxone and azithromycin can still be recommended as first-line therapy for gonorrhoea in Indonesia. Antibiotic susceptibility surveillance of N. gonorrhoeae should be routinely conducted.

High prevalence of ceftriaxone-resistant and XDR Neisseria gonorrhoeae in several cities of Cambodia, 2022-23: WHO Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP).

Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a global public health concern. Ceftriaxone is the last effective and recommended option for empirical gonorrhoea therapy worldwide, but several ceftriaxone-resistant cases linked to Asia have been reported internationally. During January 2022-June 2023, the WHO Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP) investigated N. gonorrhoeae AMR and epidemiological factors in patients from 10 clinical sentinel sites in Cambodia. Urethral swabs from males with urethral discharge were cultured. ETEST determined the MIC of five antimicrobials, and EGASP MIC alert values and EUCAST breakpoints were used. EGASP demographic, behavioural and clinical variables were collected using a standardized questionnaire. From 437 male patients, 306 had positive N. gonorrhoeae cultures, AMR testing and complete epidemiological data. Resistance to ceftriaxone, cefixime, azithromycin and ciprofloxacin was 15.4%, 43.1%, 14.4% and 97.1%, respectively. Nineteen (6.2%) isolates were resistant to all four antimicrobials and, accordingly, categorized as XDR N. gonorrhoeae. These XDR isolates were collected from 7 of the 10 sentinel sites. No EGASP MIC alert values for gentamicin were reported. The nationally recommended cefixime 400 mg plus azithromycin 1 g (65.4%) or ceftriaxone 1 g plus azithromycin 1 g (34.6%) was used for treatment. A high prevalence of ceftriaxone-resistant, MDR and XDR N. gonorrhoeae in several cities of Cambodia were found during 2022-23 in WHO EGASP. This necessitates expanded N. gonorrhoeae AMR surveillance, revision of the nationally recommended gonorrhoea treatment, mandatory test of cure, enhanced sexual contact notification, and ultimately novel antimicrobials for the treatment of gonorrhoea.

Bacitracin enhances ceftriaxone susceptibility of the high-level ceftriaxone-resistant gonococcal FC428 clone

ABSTRACT Neisseria gonorrhoeae is a multidrug-resistant bacterial pathogen for which ceftriaxone mono-antimicrobial therapy and ceftriaxone plus azithromycin dual-antimicrobial therapy are the only remaining effective therapies. However, ceftriaxone efficacy is threatened by the global dissemination of the high-level ceftriaxone-resistant FC428 clone, while azithromycin has in recent years been removed from the recommended dual therapy in some countries as a result of increasing (high-level) azithromycin resistance. Inclusion of an alternative second antimicrobial could be an effective strategy to protect ceftriaxone from (further) resistance development. In this study, we investigated gonococcal susceptibility to bacitracin and determined its synergistic anti-gonococcal activity with ceftriaxone. Gonococcal susceptibility to bacitracin was investigated for 449 contemporary clinical isolates using the agar dilution method. Bacitracin displayed consistent activity against the N. gonorrhoeae strain collection, with a minimum inhibitory concentration (MIC) range of 2–32 mg/L and a MIC 90 of 32 mg/L. Furthermore, bacitracin was bactericidal in time-kill assays, particularly against the tested FC428-associated isolate, which showed 10 5 -fold inactivation after 8 hours of exposure to a 4× MIC dose. Importantly, bacitracin and ceftriaxone displayed synergistic activity, with a fractional inhibitory concentration index ≤0.5 for the majority of tested strains. Finally, spot assays showed strong synergistic activity against the FC428-associated isolates, with up to 200-fold reduced plating efficacy for bacitracin combined with ceftriaxone compared with ceftriaxone only. In conclusion, bacitracin shows synergistic anti-gonococcal activity with ceftriaxone and might therefore be an interesting candidate for inclusion in a dual-antimicrobial therapy with ceftriaxone. IMPORTANCE Ceftriaxone-based antimicrobial therapies for gonorrhea are threatened by waning ceftriaxone susceptibility levels and the global dissemination of the high-level ceftriaxone-resistant gonococcal FC428 clone. Combination therapy can be an effective strategy to restrain the development of ceftriaxone resistance, and for that purpose, it is important to find an alternative antimicrobial to replace azithromycin, which has recently been removed in some countries from the recommended ceftriaxone plus azithromycin dual-antimicrobial therapy. Ideally, the second antimicrobial should display synergistic activity with ceftriaxone. We hypothesized that bacitracin might display synergistic activity with ceftriaxone because of their distinct mechanisms targeting bacterial cell wall synthesis. In this study, we showed that bacitracin indeed displays synergistic activity with ceftriaxone against Neisseria gonorrhoeae . Importantly, strains associated with the FC428 clone appeared to be particularly susceptible to the bacitracin plus ceftriaxone combination, which might therefore be an interesting dual therapy for further in vivo testing.

Novel gonorrhea strain in the United States of America leading to increase of sexually transmitted diseases load: is it an outcome of inexorable process of developing antibiotic resistance?

Novel gonorrhea strain in the United States of America leading to increase of sexually transmitted diseases load: is it an outcome of inexorable process of developing antibiotic resistance?

Sustained Transmission of Neisseria gonorrhoeae Strains with High-Level Azithromycin Resistance (MIC ≥ 256 μg/mL) in Argentina, 2018 to 2022.

Azithromycin combined with ceftriaxone is the recommended dual therapy for uncomplicated gonorrhea in many countries. Nevertheless, the increasing prevalence of azithromycin resistance compromises the effectiveness of this treatment strategy. From 2018 to 2022, we collected 13 gonococcal isolates with high-level azithromycin resistance (MIC ≥ 256 μg/mL) across Argentina. Whole-genome sequencing revealed that these isolates were mainly represented by the internationally spreading Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST) genogroup G12302, containing the 23S rRNA A2059G mutation (in all four alleles) together with mosaic mtrD and mtrR promoter 2 loci. This information is important to develop targeted public health policies to control the spread of azithromycin-resistant N. gonorrhoeae in Argentina and internationally. IMPORTANCE Azithromycin resistance in Neisseria gonorrhoeae has been increasing in numerous populations worldwide, which is of concern, as azithromycin is part of the recommended dual treatment in many countries. Here, we report 13 N. gonorrhoeae isolates with high-level azithromycin resistance (MIC ≥ 256 μg/mL). This study observed that high-level azithromycin-resistant gonococcal strains have shown sustained transmission in Argentina and are related to the successful international clone NG-MAST G12302. Genomic surveillance together with real-time tracing and data-sharing networks will be crucial in controlling the spread of azithromycin resistance in gonococcus.

Antimicrobial Activity of Auranofin, Cannabidivarin, and Tolfenamic Acid against Multidrug-Resistant Neisseria gonorrhoeae.

Alternative antimicrobial therapies are urgently required for the multidrug-resistant bacterial pathogen Neisseria gonorrhoeae, for which currently ceftriaxone is the only remaining recommended first-line therapy. Repurposing of drugs that are approved for other clinical applications offers an efficient approach for development of alternative antimicrobial therapies. Auranofin, cannabidivarin, and tolfenamic acid were recently identified to display antimicrobial activity against N. gonorrhoeae. Here, we investigated their activity against a collection of 575 multidrug-resistant clinical isolates. All three compounds displayed consistent antimicrobial activity against all isolates, including against strains associated with the high-level ceftriaxone-resistant FC428 clone, with both the mode and MIC90 for auranofin of 0.5 mg/L, while both the mode and MIC90 for cannabidivarin and tolfenamic acid were 8 mg/L. Correlations between MICs of ceftriaxone and auranofin, cannabidivarin or tolfenamic acid were low, indicating that development of cross-resistance is unlikely. Furthermore, antimicrobial synergy analysis between ceftriaxone and auranofin, cannabidivarin, or tolfenamic acid by determination of the fractional inhibitory concentration index (FICI) resulted in an interpretation of indifference. Finally, time-kill analyses showed that all three compounds are bactericidal against both the N. gonorrhoeae ATCC 49226 reference strain and an FC428-associated clinical isolate, with particularly cannabidivarin displaying rapid bactericidal activity. Overall, auranofin, cannabidivarin, and tolfenamic acid displayed consistent antimicrobial activity against multidrug-resistant N. gonorrhoeae, warranting further exploration of their suitability as alternative antimicrobials for treatment of gonococcal infections. IMPORTANCE Neisseria gonorrhoeae is a major public health concern because of the high incidence of gonorrhea and the increasingly limited options for antimicrobial therapy. Strains associated with the FC428 clone are a particular concern because they have shown global dissemination and they display high-level resistance against the currently recommended ceftriaxone therapy. Therefore, development of alternative antimicrobial therapies is urgently required to ensure treatment of gonorrhea remains available in the future. Repurposing of clinically approved drugs could be a rapid approach for the development of such alternative antimicrobials. In this study, we showed that repurposing of auranofin, cannabidivarin, and tolfenamic acid for antimicrobial therapy of gonorrhea deserves further clinical explorations because these compounds displayed consistent antimicrobial activity against a large collection of contemporary multidrug-resistant gonococcal isolates that included strains associated with the FC428 clone.

A Statewide Mixed-Methods Study of Provider Knowledge and Behavior Administering Expedited Partner Therapy for Chlamydia and Gonorrhea.

Expedited partner therapy (EPT) refers to the practice of having patients diagnosed with chlamydia or gonorrhea deliver medication directly to their partner(s) to treat them presumptively for infection. Although EPT facilitates timely treatment and prevents reinfection, it remains underused. We used findings from key informant interviews to design and implement a statewide survey to estimate knowledge and utilization of EPT and to identify barriers and facilitators to EPT among Minnesota providers. From November to December 2020, we carried out 15 interviews with health providers who currently provide EPT and coded interviews by recurring themes. We then conducted a statewide online survey on sexually transmitted infection treatment and barriers to EPT, from December 2020 to March 2021. We disseminated the survey to all licensed Minnesota health providers, and those who reported treating bacterial sexually transmitted infections in the past year were included in the study. Interview themes included the importance of direct provision of partner medication, administrative/pharmacy barriers to treatment, inclusive EPT eligibility, and patient counseling. Of the 623 health providers who completed the online survey, only 70% thought EPT was legal and only 37% currently offer EPT. Of those who did not provide EPT, 78% said they would under certain circumstances. Barriers included concerns about safety/liability of prescribing without a medical examination, administrative concerns about prescriptions, and patient acceptance. Given that over a quarter of respondents did not know expedited partner therapy (EPT)'s legal status, improving provider education may increase EPT provision. More research is needed on system-level barriers and patient acceptance of solutions identified in this study.

Moenomycin is broadly active against multidrug-resistant Neisseria gonorrhoeae and clears an infection from a murine vaginal tract infection model.

Ceftriaxone therapy for gonorrhoea has become under increasing pressure due to waning susceptibility levels and emergence of high-level resistant strains such as the FC428 clone. Moenomycin was recently identified to display potent anti-gonococcal activity against some reference strains. Therefore, the aim of this study was to investigate moenomycin in vitro and in vivo antimicrobial activity. Moenomycin in vitro antimicrobial activity was investigated against 575 clinical isolates, including strains associated with the FC428 clone, using the agar dilution method. Moenomycin in vivo activity was investigated in a mouse vaginal tract gonococcal infection model. The moenomycin MIC range for the strain collection was 0.004-0.06 mg/L, with a MIC50 of 0.016 mg/L and a MIC90 of 0.03 mg/L. The correlation between moenomycin and ceftriaxone susceptibility levels was poor (R = 0.13), while the fractional inhibitory concentration index (FICI) resulted in indifference for all tested strains. Therefore, development of cross-resistance between moenomycin and ceftriaxone is unlikely for N. gonorrhoeae. Determination of the moenomycin mode of activity against N. gonorrhoeae by time-kill assays showed that moenomycin is bactericidal, with over 104-fold inactivation observed after 4 h exposure. Finally, an intramuscular moenomycin dose of 10 mg/kg given on 2 consecutive days was able to clear a gonococcal infection in a mouse vaginal tract infection model within 1-3 days after the second dose, which was significantly faster than for mice treated with the vehicle control (P < 0.0001). Moenomycin displays potent in vitro and in vivo antimicrobial activity against N. gonorrhoeae, warranting further exploration as alternative therapy.

Factors associated with non-guideline-adherent treatment for gonorrhea and chlamydia among outpatient prescriptions in the Unites States

Background: Patients at risk for sexually transmitted infections (STI) frequently receive care at non-specialized outpatient clinics staffed by physicians and advanced practice clinicians (APCs).Methods: Retrospective cohort study including adult patients diagnosed with chlamydia and/or gonorrhea at urgent care (UC), family medicine (FM), internal medicine (IM) or obstetrics and gynecology (Ob-Gyn) clinics. The effect of type of clinician on guideline-adherent treatment was estimated using logistic regression adjusted for age, type of clinic, type of infection, and (in female patients) pregnancy status.Results: A total of 1021 patients were identified, 654 (64.1%) females and 367 (35.9%) males. Overall, 12.8% (84/654) of female patients and 19.1% (70/367) of male patients received inadequate antibiotic therapy. Among females, 63.5% (415/654) were treated by APCs and 36.5% (239/654) by physicians. Odds of inadequate therapy did not differ when comparing APCs to physicians (OR 0.83 [95% CI 0.52-1.32; p = .42]). Variables independently associated with inadequate therapy were pregnancy (OR 3.80 [95% CI 1.55-6.10; p < .001]), infection with gonorrhea (OR 2.91 [95% CI 1.65-5.10; p < .0001]) and co-infection (OR 2.63 [95% CI 1.24-5.58; p = .01]) compared to infection with chlamydia alone. Compared to UC clinics, female patients treated at Ob-Gyn clinics had lower odds of inadequate therapy (OR 0.45 [95% CI 0.22-0.90; p = .02]). Among males, odds of inadequate therapy did not differ by clinician type.Conclusions: Inadequate antibiotic therapy for chlamydia and/or gonorrhea was not associated with type of clinician. These results can help guide educational strategies and resources towards the clinical settings with the greatest gaps in adequacy of management of chlamydia and gonorrhea.

Characterization of a Neisseria gonorrhoeae Ciprofloxacin panel for an antimicrobial resistant Isolate Bank.

ObjectivesNeisseria gonorrhoeae (gonococcus) infection is one of the most commonly reported nationally notifiable conditions in the United States. Gonococcus has developed antimicrobial resistance to each previously used antibiotic for gonorrhea therapy. However, some isolates may be still susceptible to no longer recommended, yet still effective antibiotics. This in turn suggests that targeted therapy could slow resistance development to currently recommended empirical treatments. We curated a gonococcal Ciprofloxacin Antibiotic Resistance Isolate Bank panel (Cipro-panel) as a tool for validating or developing new tests to determine ciprofloxacin susceptibility.MethodThe Cipro-panel was selected using whole genome sequencing, bioinformatic tools, and antimicrobial susceptibility testing (AST) data. Isolates were further selected based on nucleotide variations in gyrA and parC genes.ResultsWe selected 14 unique N. gonorrhoeae isolates from the 2006–2012 Gonococcal Isolate Surveillance Project (GISP) collection. They represented a wide range of antimicrobial susceptibility to ciprofloxacin and commonly observed nucleotide variations of gyrA and parC genes. This Cipro-panel consists of 5 isolates with resistant phenotypes (MIC > = 1 μg/mL), 8 isolates with susceptible phenotypes (MIC < = 0.06 μg/mL), and 1 isolate falling in the Clinical and Laboratory Standards Institute defined intermediate range. Among the gyrA variations we observed a total of 18 SNPs. Four positions had nonsynonymous changes (nucleotide positions 272, 284, 1093, and 1783). The first two positions (272 and 284) have been linked previously with resistance to ciprofloxacin (i.e. amino acid positions 91 and 95). For the parC gene, we observed a total of 21 possible SNPs. Eight of those SNPs resulted in non-synonymous amino acid changes. One location (amino acid 87) has been previously reported to be associated with ciprofloxacin resistance.ConclusionsThis Cipro-Panel is useful for researchers interested in developing clinical tests related to ciprofloxacin. It could also provide additional choices for validation, quality assurance purposes and improve antibiotic usage.

First characterisation of antimicrobial susceptibility and resistance of Neisseria gonorrhoeae isolates in Qatar, 2017–2020

Limited data are available regarding antimicrobial resistance in Neisseria gonorrhoeae strains circulating in WHO Eastern Mediterranean Region (EMR). We investigated the antimicrobial susceptibility/resistance of N. gonorrhoeae isolates to five antimicrobials (ceftriaxone, azithromycin, ciprofloxacin, tetracycline, and benzylpenicillin) currently or previously used for gonorrhoea treatment in Qatar, 2017–2020. Minimum inhibitory concentrations (MICs; mg/L) of antimicrobials were determined using Etest on gonococcal isolates collected during January 1, 2017-August 30, 2020 at Hamad Medical Corporation, a national public healthcare provider. During 2017–2020, resistance in isolates from urogenital sites of 433 patients was 64.7% (95% CI: 59.5–69.6%; range: 43.9–78.7%) for ciprofloxacin, 50.7% (95% CI: 45.3–56.1%; range: 41.3–70.4%) for tetracycline, and 30.8% (95% CI: 26.3–35.6%; range: 26.7–35.8%) for benzylpenicillin. Percentage of isolates non-susceptible to azithromycin was 4.1% (95% CI: 2.0–7.4%; range: 2.7–4.8%) and all (100%) isolates were susceptible to ceftriaxone. Two (1.6%) isolates from 2019 and one (2.2%) isolate from 2020 had high-level resistance to azithromycin (MIC≥256 mg/L). Overall, 1.0% (4/418) of isolates had a ceftriaxone MIC of 0.25 mg/L, which is at the ceftriaxone susceptibility breakpoint (MIC≤0.25 mg/L). Treatment with ceftriaxone 250 mg plus azithromycin 1 g can continuously be recommended for gonorrhoea therapy in Qatar. Continued quality-assured gonococcal AMR surveillance is warranted in EMR.

Gonoroični uretritis i rezistencija na antibiotike

Urethritis is a clinical syndrome characterized by the appearance of mucopurulent or purulent urethral secretions, with or without dysuria, due to an increased number of polymorphonuclear leukocytes in the anterior urethra. Recommended therapy for uncomplicated gonorrhea of the urethra, cervix and rectum when antimicrobial susceptibility of gonococci has not been tested, is a combination of ceftrixasone 1 g intramuscularly in one dose, with azithromycin 2 g in one oral dose. Antimicrobial therapy and prevention measures are the basis of the fight against bacterial urethritis. This fight is disturbed by antimicrobial resistance, which results in unsuccessful therapy and the possibility of complications of urethritis. Resistance of Neisseria gonorrhoeae to antibiotics has been known for decades, and there is a danger that in the future certain strains of N. gonorrhoeae will be resistant to all available antimicrobials if there are no new antibiotics that will not develop resistance quickly or in the case of development of effective vaccines.

Multidrug-resistant Neisseria gonorrhoeae infection in heterosexual men with reduced susceptibility to ceftriaxone, first report in Thailand

The global rapid emergence of azithromycin/ceftriaxone resistant Neisseria gonorrhoeae threatens current recommend azithromycin/ceftriaxone dual therapy for gonorrhea to ensure effective treatment. Here, we identified the first two N. gonorrhoeae isolates with decreased ceftriaxone susceptibility in Thailand. Among 134 N. gonorrhoeae isolates collected from Thai Red Cross Anonymous Clinic, Bangkok, two isolates (NG-083 and NG-091) from urethral swab in male heterosexual patients had reduced susceptibility to ceftriaxone (MICs of 0.125 mg/L). Both were multidrug resistant and strong biofilm producers with ceftriaxone tolerance (MBEC > 128 mg/L). NG-083 and NG-091 remained susceptible to azithromycin (MIC of 1 mg/L and 0.5 mg/L, respectively). Reduced susceptibility to ceftriaxone was associated with alterations in PBP2, PBP1, PorB, MtrR, and mtrR promoter region. NG-083 belonged to sequence type (ST) 7235 and NG-091 has new allele number of tbpB with new ST. Molecular docking revealed ceftriaxone weakly occupied the active site of mosaic XXXIV penicillin-binding protein 2 variant in both isolates. Molecular epidemiology results revealed that both isolates display similarities with isolates from UK, USA, and The Netherlands. These first two genetically related gonococcal isolates with decreased ceftriaxone susceptibility heralds the threat of treatment failure in Thailand, and importance of careful surveillance.

Public health detailing to increase expedited partner therapy for chlamydia and gonorrhea in Maryland: Changes in awareness and implementation among prescribing community providers

The objective of this evaluation was to assess the use of public health detailing in a pilot program to increase Expedited Partner Therapy (EPT) uptake among community-based providers in two Maryland jurisdictions. Public health detailing is a method designed to raise awareness and increase implementation of evidence-based clinical practices by delivering educational content via one-on-one meetings with providers. EPT is a voluntary clinical practice of treating all sexual partners of patients diagnosed with STIs by prescribing medications without the provider first examining said sexual partners. The aim of EPT is to prevent STI reinfection and reduce further transmission. From April 2017 to March 2019, detailers visited community-based health care practice sites to conduct EPT detailing with providers. The effectiveness of this program was evaluated by comparing provider responses from pre- to post-detailing surveys, administered six months after detailing. Survey responses assessed EPT awareness and practices, barriers to implementation, and satisfaction with detailing. The proportion of providers (170) aware of EPT for treating chlamydia and gonorrhea increased from 61.7% (114) to 99.4% (169) (p-value < 0.001). The proportion who reported prescribing EPT increased from 63.2% (72) to 86.4% (146) (p-value < 0.001). Providers reporting no barriers to prescribing EPT increased from 30.6% (52) to 55.9% (95) (p-value < 0.001). Most providers were satisfied with detailing, 95.5% (164), and 95.3% (162) preferred this method to communicate about public health measures. Detailing appears to be a strategy to improve provider awareness of EPT, increase EPT implementation, and reduce barriers to prescribing EPT.

Antimicrobial resistance in Neisseria gonorrhoeae isolates and gonorrhoea treatment in the Republic of Belarus, Eastern Europe, 2009\u20132019

BackgroundLimited antimicrobial resistance (AMR) data for Neisseria gonorrhoeae are available in Eastern Europe. We investigated AMR in N. gonorrhoeae isolates in the Republic of Belarus from 2009 to 2019, antimicrobial treatment recommended nationally, and treatment given to patients with gonorrhoea.MethodsN. gonorrhoeae isolates (n = 522) cultured in three regions of Belarus in 2009–2019 were examined. Determination of minimum inhibitory concentrations (MICs) of eight antimicrobials was performed using Etest. Resistance breakpoints from the European Committee on Antimicrobial Susceptibility Testing were applied where available. A Nitrocefin test identified β-lactamase production. Gonorrhoea treatment for 1652 patients was also analysed. Statistical significance was determined by the Z-test, Fisher’s exact test, or Mann-Whitney U test with p-values of < 0.05 indicating significance.ResultsIn total, 27.8% of the N. gonorrhoeae isolates were resistant to tetracycline, 24.7% to ciprofloxacin, 7.0% to benzylpenicillin, 2.7% to cefixime, and 0.8% to azithromycin. No isolates were resistant to ceftriaxone, spectinomycin, or gentamicin. However, 14 (2.7%) isolates had a ceftriaxone MIC of 0.125 mg/L, exactly at the resistance breakpoint (MIC > 0.125 mg/L). Only one (0.2%) isolate, from 2013, produced β-lactamase. From 2009 to 2019, the levels of resistance to ciprofloxacin and tetracycline were relatively high and stable. Resistance to cefixime was not identified before 2013 but peaked at 22.2% in 2017. Only sporadic isolates with resistance to azithromycin were found in 2009 (n = 1), 2012 (n = 1), and 2018–2019 (n = 2). Overall, 862 (52.2%) patients received first-line treatment according to national guidelines (ceftriaxone 1 g). However, 154 (9.3%) patients received a nationally recommended alternative treatment (cefixime 400 mg or ofloxacin 400 mg), and 636 (38.5%) were given non-recommended treatment.ConclusionsThe gonococcal resistance to ciprofloxacin and tetracycline was high, however, the resistance to azithromycin was low and no resistance to ceftriaxone was identified. Ceftriaxone 1 g can continuously be recommended as empiric first-line gonorrhoea therapy in Belarus. Fluoroquinolones should not be prescribed for treatment if susceptibility has not been confirmed by testing. Timely updating and high compliance with national evidence-based gonorrhoea treatment guidelines based on quality-assured AMR data are imperative. The need for continued, improved and enhanced surveillance of gonococcal AMR in Belarus is evident.

Expedited Partner Therapy for Sexually Transmitted Infections in Minnesota: A Mixed-Methods Review of Current Practices and Barriers to Implementation

Review of Current Practices and Barriers to Implementation We examined 1) current provision of expedited partner therapy (EPT) for sexually transmitted infections (STI) and 2) barriers and facilitators to EPT provision in Minnesota to address rising chlamydia and gonorrhea rates across the state. We conducted a statewide online survey on STI treatment and barriers to Expedited Partner Therapy (EPT), or patient-delivered partner therapy for chlamydia or gonorrhea without medical evaluation of the partner. To develop survey questions and responses, we carried out 15 key informant interviews (KII) with health providers who submitted EPT protocols to the Minnesota Department of Health to understand current EPT implementation. KIIs were conducted among providers at outpatient specialty clinics (12), outpatient primary clinics (2), and a commercial pharmacy (1). EPT and direct provision of medication (8 for both) were mentioned as important for partner treatment. Almost all providers interviewed offer treatment directly (14), and insurance and prescriptions issues were most frequently cited administrative barriers (12). Online survey respondents (n=708) included 217 pharmacists, 230 nurse practitioners, 155 physicians, and 106 other health professionals from 63 of the 87 counties in Minnesota. While most providers had heard of EPT (72%), only 467 (66%) thought it was legal in Minnesota, and many were unsure if it was allowed in their clinical practice (34%). While only 175 providers currently offer EPT to patients, 329 providers indicated willingness to offer EPT under certain conditions. These conditions include legal protections for providers from liability (19%), changes to electronic health record (EHR) system alerts and EHR prescription options (18%), and pharmacy requirements to check for allergies (18%). Improving provider education about EPT legality may facilitate EPT provision in health systems to reduce the STI burden. Coordination between prescribing and dispensing providers is also important to overcome administrative barriers and to prevent adverse reactions among patients.

Reflex Detection of Ciprofloxacin Resistance in Neisseria gonorrhoeae by Use of the SpeeDx ResistancePlus GC Assay.

Resistance-guided therapy (RGT) for gonorrhea may reduce unnecessary use of broad-spectrum antibiotics. When reflexed from the Aptima Combo 2 assay, the ResistancePlus GC assay demonstrated 94.8% sensitivity and 100.0% specificity for Neisseria gonorrhoeae detection. Of the 379 concordant N. gonorrhoeae-positive samples, 86.8% were found to possess the gyrA S91F mutation, which was highly predictive for ciprofloxacin resistance and stable across 3,144 publicly available N. gonorrhoeae genomes. Our work supports the feasibility of implementing RGT for gonorrhea into routine molecular workflows.

A community-driven resource for genomic epidemiology and antimicrobial resistance prediction of Neisseria gonorrhoeae at Pathogenwatch

BackgroundAntimicrobial-resistant (AMR) Neisseria gonorrhoeae is an urgent threat to public health, as strains resistant to at least one of the two last-line antibiotics used in empiric therapy of gonorrhoea, ceftriaxone and azithromycin, have spread internationally. Whole genome sequencing (WGS) data can be used to identify new AMR clones and transmission networks and inform the development of point-of-care tests for antimicrobial susceptibility, novel antimicrobials and vaccines. Community-driven tools that provide an easy access to and analysis of genomic and epidemiological data is the way forward for public health surveillance.MethodsHere we present a public health-focussed scheme for genomic epidemiology of N. gonorrhoeae at Pathogenwatch (https://pathogen.watch/ngonorrhoeae). An international advisory group of experts in epidemiology, public health, genetics and genomics of N. gonorrhoeae was convened to inform on the utility of current and future analytics in the platform. We implement backwards compatibility with MLST, NG-MAST and NG-STAR typing schemes as well as an exhaustive library of genetic AMR determinants linked to a genotypic prediction of resistance to eight antibiotics. A collection of over 12,000 N. gonorrhoeae genome sequences from public archives has been quality-checked, assembled and made public together with available metadata for contextualization.ResultsAMR prediction from genome data revealed specificity values over 99% for azithromycin, ciprofloxacin and ceftriaxone and sensitivity values around 99% for benzylpenicillin and tetracycline. A case study using the Pathogenwatch collection of N. gonorrhoeae public genomes showed the global expansion of an azithromycin-resistant lineage carrying a mosaic mtr over at least the last 10 years, emphasising the power of Pathogenwatch to explore and evaluate genomic epidemiology questions of public health concern.ConclusionsThe N. gonorrhoeae scheme in Pathogenwatch provides customised bioinformatic pipelines guided by expert opinion that can be adapted to public health agencies and departments with little expertise in bioinformatics and lower-resourced settings with internet connection but limited computational infrastructure. The advisory group will assess and identify ongoing public health needs in the field of gonorrhoea, particularly regarding gonococcal AMR, in order to further enhance utility with modified or new analytic methods.

Is gentamicin a viable therapeutic option for treating resistant Neisseria gonorrhoeae in New South Wales?

The key issues with Neisseria gonorrhoeae infections, in Australia and elsewhere, are coincident increases in disease rates and in antimicrobial resistance (AMR), although these factors have not been shown to be correlated. Despite advances in diagnosis, control of this disease remains elusive, and incidence in Australia continues to increase. Of the Australian jurisdictions, New South Wales (NSW) has the highest N. gonorrhoeae notifications, and over the five-year period 2015-2019, notifications in NSW have increased above the national average (by 116% versus 85%, respectively). Gonococcal disease control is reliant on effective antibiotic regimens. However, escalating AMR in N. gonorrhoeae is a global health priority, as the collateral injury of untreated infections has substantive impacts on sexual and newborn health. Currently, our first-line therapy for gonorrhoea is also our last line, with no ideal alternative identified. Despite some limitations, gentamicin is licensed and readily available in Australia, and is proposed for treatment of resistant N. gonorrhoeae in national guidelines; however, supportive published microbiological data are lacking. Analysis of gonococcal resistance patterns within Australia for the period 1991-2019, including 35,000 clinical isolates from NSW, illustrates the establishment and spread of population-level resistance to all contemporaneous therapies. An analysis of gentamicin susceptibility on 2,768 N. gonorrhoeae clinical isolates from NSW, for the period 2015-2020, demonstrates that the median minimum inhibitory concentration (MIC) for gentamicin in NSW has remained low, at 4.0 mg/L, and resistance was not detected in any isolate. There has been no demonstration of MIC drift over time (p = 0.91, Kruskal-Wallis test), nor differences in MIC distributions according to patients' sex or site of specimen collection. This is the first large-scale evaluation of gentamicin susceptibility in N. gonorrhoeae in Australia. No gentamicin resistance was detected in clinical isolates, 2015-2020, hence this is likely to be an available treatment option for resistant gonococcal infections in NSW.