Gonococcal Antimicrobial Surveillance Programme Research Articles

Antimicrobial resistance in Neisseria gonorrhoeae isolates from foreign-born population in the European Gonococcal Antimicrobial Surveillance Programme

ObjectivesInternational spread has contributed substantially to the high prevalence of antimicrobial resistant (AMR) Neisseria gonorrhoeae infections worldwide. We compared the prevalence of AMR gonococcal isolates among native persons to foreign-born...

The European gonococcal antimicrobial surveillance programme (Euro-GASP) appropriately reflects the antimicrobial resistance situation for Neisseria gonorrhoeae in the European Union/European Economic Area

BackgroundEuropean Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) antimicrobial resistance (AMR) data are used to inform gonorrhoea treatment guidelines; therefore the data need to be robust and representative. We assessed the extent to which Euro-GASP reflects national measures of the AMR situation for Neisseria gonorrhoeae across the European Union/European Economic Area (EU/EEA).MethodsWe compared data from Euro-GASP with published national gonococcal AMR data from 15 countries for azithromycin, cefixime and ciprofloxacin for the period 2009 to 2013 and performed Poisson regression to identify differences (p < 0.05) between the proportions of resistant isolates. The 2014 Euro-GASP AMR data for each country (n = 19) were weighted to account for differences in the distribution of patient characteristics between Euro-GASP and EU/EEA epidemiological gonorrhoea surveillance data. Data were compared to determine whether estimates of resistance levels differed with regards to the 5% threshold used to assess the clinical utility of first-line gonorrhoea treatments. We assessed the quality of decentralised testing by comparing AMR data for isolates tested both centrally and in the participating laboratories, and by evaluating external quality assessment (EQA) performance.ResultsThere was no significant difference for azithromycin, cefixime and ciprofloxacin resistance when Euro-GASP country data were compared with data from national reports. Weighting slightly altered the Euro-GASP AMR estimates (by between − 4.7 and 4.7% from the unweighted estimates). Weighting resulted in greater changes in estimates of resistance to azithromycin (from − 9.5 to 2.7%) and ciprofloxacin (from − 14.8 to 17.9%) in countries with low isolate numbers and low completeness of reporting (n = 3). Weighting caused AMR levels to fall below or above the 5% threshold for cefixime or azithromycin, respectively in only two countries. Susceptibility category data submitted from the decentralised Euro-GASP laboratories were concordant with the Euro-GASP data (> 90%). EQA performance was also good; < 5% of the minimum inhibitory concentration (MIC) results differed by > 4-fold from the modal MIC of the EQA isolate.ConclusionsThe overall prevalence of AMR reported by Euro-GASP reflects closely the AMR situation for N. gonorrhoeae in the EU/EEA. Euro-GASP data can be used to provide robust AMR estimates to inform the European guideline for the management of gonorrhoea.

A β-lactamase-producing plasmid from Neisseria gonorrhoeae carrying a unique 6 bp deletion in blaTEM-1 encoding a truncated 24 kDa TEM-1 penicillinase that hydrolyses ampicillin slowly.

Seven structurally related β-lactamase-producing plasmids have been characterized in penicillinase-producing Neisseria gonorrhoeae (PPNG) isolates. We characterized a variant (i.e. pJRD20, Canada type) of the Africa-type (pJD5) plasmid isolated from N. gonorrhoeae strain 8903. To compare the DNA sequence of pJRD20 with that of pJD5 and pJD4 (Asia-type) and their TEM-1 β-lactamases. N. gonorrhoeae 8903 was identified as part of the Gonococcal Antimicrobial Surveillance Program in Canada. β-Lactamase production was assessed using nitrocefin. MICs were determined by agar dilution and Etest methods (CLSI). The DNA sequences of pJRD20, pJD5 and pJD4 were assembled and annotated. The structure of TEM-1 and its penicillin-binding properties were determined by in silico molecular modelling and docking. TEM-1 proteins were characterized by western blot, mass spectrometry and ampicillin hydrolysis assays. N. gonorrhoeae 8903 exhibited intermediate susceptibility to penicillin with slow β-lactamase activity (i.e. 35 min to hydrolyse nitrocefin). Except for a novel 6 bp deletion starting at the G of the ATG start codon of blaTEM-1, the DNA sequence of pJRD20 was identical to that of pJD5. The TEM-1 β-lactamase produced by pJRD20 is 24 kDa and hydrolyses ampicillin only after several hours. This unusual PPNG isolate might have been characterized as a non-PPNG owing to its low MIC of penicillin and its very slow hydrolysis of nitrocefin. Given the unusual nature of its TEM-1 β-lactamase, laboratories might consider extending the duration of nitrocefin hydrolysis assays.

Summary and Trends of the Russian Gonococcal Antimicrobial Surveillance Programme, 2005 to 2016.

The Russian Gonococcal Antimicrobial Surveillance Programme (RU-GASP) was established in 2004 and operated continuously during the years from 2005 to 2016. The aims of this study were to summarize the RU-GASP results over this 12-year period and evaluate the trends in Neisseria gonorrhoeae antimicrobial resistance in Russia. In total, 5,038 verified N. gonorrhoeae isolates from 40 participating regions were tested for susceptibility to six antimicrobials via an agar dilution method. DNA loci involved in antimicrobial resistance were identified via minisequencing or DNA microarray techniques. From 2005 to 2016, increasing susceptibility to penicillin G (from 22.6% to 63.0%), tetracycline (from 34.8% to 53.0%), and ciprofloxacin (from 50.6% to 68.6%) was observed, but resistance to these drugs remained high. The proportions of isolates nonsusceptible to azithromycin and spectinomycin peaked in 2011 and decreased thereafter. Of the isolates, only 6 and 23 were identified as nonsusceptible to ceftriaxone according to the CLSI definitions and EUCAST breakpoint (0.57% of the total population), respectively. Comparison of N. gonorrhoeae antimicrobial resistance genetic determinants in 2005 versus those in 2016 showed a significant decrease in the number of isolates carrying chromosomal mutations. The proportion of isolates with wild-type genotypes increased from 11.7% in 2005 to 30.3% in 2016. Thus, the RU-GASP can be considered a successful gonorrhea surveillance program, and the current state of N. gonorrhoeae antimicrobial resistance in Russia is less serious than that in other WHO GASP regions.

Population-Level Antimicrobial Consumption Is Associated With Decreased Antimicrobial Susceptibility in Neisseria gonorrhoeae in 24 European Countries: An Ecological Analysis.

There are substantial variations between different populations in the susceptibility of Neisseria gonorrhoeae to antimicrobials, and the reasons for this are largely unexplored. We aimed to assess whether the population-level consumption of antimicrobials is a contributory factor. Using antimicrobial susceptibility data from 24 countries in the European Gonococcal Antimicrobial Surveillance Programme and antimicrobial consumption data from the IQVIA MIDAS database, we built mixed-effects linear/logistic regression models with country-level cephalosporin, fluoroquinolone, and macrolide consumption (standard doses/1000 population/year) as the explanatory variables (from 2009 to 2015) and 1-year-lagged ceftriaxone, cefixime, azithromycin, and ciprofloxacin geometric mean minimum inhibitory concentrations (MICs) as the outcome variables (from 2010 to 2016). Positive correlations were found between the consumption of cephalosporins and the geometric mean MICs of ceftriaxone and cefixime (P < .05 for both comparisons). Fluoroquinolone consumption was positively associated with the prevalence of resistance to ciprofloxacin (P < .05). Differences in the population-level consumption of particular antimicrobials may contribute to variations in the level of antimicrobial resistance in N. gonorrhoeae in different settings. Further interventions to reduce misuse and overuse of antimicrobials in high-consumption populations and core groups are required.

Systematic review and survey of Neisseria gonorrhoeae ceftriaxone and azithromycin susceptibility data in the Asia Pacific, 2011 to 2016.

BackgroundAntimicrobial resistance in Neisseria gonorrhoeae is a global concern, with the ongoing emergence of ceftriaxone and azithromycin resistance threatening current treatment paradigms. To monitor the emergence of antimicrobial resistance in N. gonorrhoeae, the World Health Organization (WHO) Gonococcal Antimicrobial Surveillance Programme (GASP) has operated in the Western Pacific and South East Asian regions since 1992. The true burden of antimicrobial resistance remains unknown. In response, the objective of this study was to survey ceftriaxone and azithromycin susceptibility in N. gonorrhoeae across the western Pacific and south-east Asia, and interlink this data with systematically reviewed reports of ceftriaxone and azithromycin resistance.Methods and findingsThe WHO Collaborating Centre for Sexually Transmitted Infections and Antimicrobial Resistance, Sydney, coordinated annual surveys of gonococcal susceptibilities with participating laboratories, and additionally undertook a systematic review of reports detailing gonococcal ceftriaxone and azithromycin susceptibility data for locations geographically in the Asia Pacific from 2011 to 2016. It was found that surveillance of gonococcal antimicrobial resistance remains limited in the Asia Pacific, with weaker surveillance of azithromycin versus ceftriaxone. Ninety-three published reports were identified (including national reports) which documented susceptibility data for ceftriaxone and azithromycin. GASP survey data was available for 21 countries, territories or areas, and suggested MICs are increasing for ceftriaxone and azithromycin. Between 2011 and 2016, the percentage of locations reporting >5% of gonococcal isolates with MICs to ceftriaxone meeting WHO’s definition of decreased susceptibility (MIC ≥ 0.125 mg/L) increased from 14.3% to 35.3% and the percentage of locations reporting >5% of gonococcal isolates with azithromycin resistance (MIC ≥ 1 mg/L) increased from 14.3% to 38.9%. Published reports were available for several countries that did not provide GASP surveillance responses for ceftriaxone (n = 5) and azithromycin (n = 3) respectively. Over the study period, there was a 183% increase in the number of countries providing surveillance data for GASP for both ceftriaxone and azithromycin, and a 30.6% increase in ceftriaxone MIC testing across the Asia Pacific facilitated by this project.ConclusionThis study provides the first comprehensive illustration of increasing MICs to ceftriaxone in the Asia Pacific. The survey and literature review additionally detail increasing resistance to azithromycin. Further surveillance system strengthening is required to monitor these trends in order to address and curb gonococcal AMR in the region.

Establishment of a Gonococcal Antimicrobial Surveillance Programme, in Accordance With World Health Organization Standards, in Côte d'Ivoire, Western Africa, 2014-2017.

Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is compromising the treatment of gonorrhea globally. Recent AMR data are extremely limited in Africa, and mainly totally lacking in Western Africa, including Côte d'Ivoire. This study (i) established a quality-assured gonococcal antimicrobial surveillance program, according to World Health Organization quality criteria, (ii) investigated the AMR to 8 therapeutic antimicrobials in gonococcal isolates from 2014 to 2017, and (iii) provided evidence for updating the National Sexually Transmitted Disease Syndromic Management Guidelines in Côte d'Ivoire. During 2014 to 2017, gonococcal isolates were obtained from sexually active symptomatic or asymptomatic males and females in 14 sites in Côte d'Ivoire. It was a special focus on symptomatic males, and their sexual partners, due to the higher culture positivity rates in symptomatic males. Patient metadata were collected, including age, gender, sexual orientation, and symptoms. Minimum inhibitory concentrations of 8 antimicrobials were determined by Etest and interpreted using European Committee on Antimicrobial Susceptibility Testing breakpoints. β-lactamase production was detected using cefinase disks. The level of resistance, examining 212 gonococcal isolates, was as follows: 84.9% to tetracycline, 68.9% to benzylpenicillin, 62.7% to ciprofloxacin, 6.1% to azithromycin, and 1.4% to gentamicin. All isolates were susceptible to ceftriaxone, cefixime and spectinomycin. We provide the first gonococcal AMR data, quality assured according to World Health Organization standards, from Côte d'Ivoire since more than 20 years. The high ciprofloxacin resistance, which informed a revision of the national syndromic management guideline during study, and relatively high resistance to azithromycin demand an improved gonococcal antimicrobial surveillance program and increased awareness when prescribing treatment in Côte d'Ivoire.

World Health Organization Global Gonococcal Antimicrobial Surveillance Program (WHO GASP): review of new data and evidence to inform international collaborative actions and research efforts.

Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a serious public health problem, compromising the management and control of gonorrhoea globally. Resistance in N. gonorrhoeae to ceftriaxone, the last option for first-line empirical monotherapy of gonorrhoea, has been reported from many countries globally, and sporadic failures to cure especially pharyngeal gonorrhoea with ceftriaxone monotherapy and dual antimicrobial therapies (ceftriaxone plus azithromycin or doxycycline) have been confirmed in several countries. In 2018, the first gonococcal isolates with ceftriaxone resistance plus high-level azithromycin resistance were identified in England and Australia. The World Health Organization (WHO) Global Gonococcal Antimicrobial Surveillance Program (GASP) is essential to monitor AMR trends, identify emerging AMR and provide evidence for refinements of treatment guidelines and public health policy globally. Herein we describe the WHO GASP data from 67 countries in 2015-16, confirmed gonorrhoea treatment failures with ceftriaxone with or without azithromycin or doxycycline, and international collaborative actions and research efforts essential for the effective management and control of gonorrhoea. In most countries, resistance to ciprofloxacin is exceedingly high, azithromycin resistance is present and decreased susceptibility or resistance to ceftriaxone has emerged. Enhanced global collaborative actions are crucial for the control of gonorrhoea, including improved prevention, early diagnosis, treatment of index patient and partner (including test-of-cure), improved and expanded AMR surveillance (including surveillance of antimicrobial use and treatment failures), increased knowledge of correct antimicrobial use and the pharmacokinetics and pharmacodynamics of antimicrobials and effective drug regulations and prescription policies (including antimicrobial stewardship). Ultimately, rapid, accurate and affordable point-of-care diagnostic tests (ideally also predicting AMR and/or susceptibility), new therapeutic antimicrobials and, the only sustainable solution, gonococcal vaccine(s) are imperative.

Stably high azithromycin resistance and decreasing ceftriaxone susceptibility in Neisseria gonorrhoeae in 25 European countries, 2016

BackgroundThe European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) performs annual sentinel surveillance of Neisseria gonorrhoeae susceptibility to therapeutically relevant antimicrobials across the European Union/European Economic Area (EU/EEA). We present the Euro-GASP results from 2016 (25 countries), linked to patient epidemiological data, and compared with data from previous years.MethodsAgar dilution and minimum inhibitory concentration (MIC) gradient strip methodologies were used to determine the antimicrobial susceptibility (using EUCAST breakpoints) of 2660 N. gonorrhoeae isolates from 25 countries across the EU/EEA. Significance of differences compared with Euro-GASP results in previous years was analysed using Z-tests.ResultsNo isolates with resistance to ceftriaxone (MIC > 0.125 mg/L) were detected in 2016 (one in 2015). However, the proportion of isolates with decreased susceptibility to ceftriaxone (MICs from 0.03 mg/L to 0.125 mg/L) increased significantly (p = 0.01) from 2015 to 2016. There were 14 (0.5%) isolates with ceftriaxone MICs 0.125 mg/L (on the resistance breakpoint), of which one isolate was resistant to azithromycin and four showed intermediate susceptibility to azithromycin. Cefixime resistance was detected in 2.1% of isolates in 2016 compared with 1.7% in 2015 (p = 0.26) and azithromycin resistance in 7.5% in 2016 compared with 7.1% in 2015 (p = 0.74). Seven (0.3%) isolates from five countries displayed high-level azithromycin resistance (MIC≥256 mg/L) in 2016 compared with five (0.2%) isolates in 2015. Resistance rate to ciprofloxacin was 46.5% compared with 49.4% in 2015 (p = 0.06). No isolates were resistant to spectinomycin and the MICs of gentamicin remained stable compared with previous years.ConclusionsOverall AMR rates in gonococci in EU/EEA remained stable from 2015 to 2016. However, the ceftriaxone MIC distribution shifted away from the most susceptible (≤0.016 mg/L) and the proportion of isolates with decreased susceptibility to ceftriaxone increased significantly. This development is of concern as current European gonorrhoea management guideline recommends ceftriaxone 500 mg plus azithromycin 2 g as first-line therapy. With azithromycin resistance at 7.5%, the increasing ceftriaxone MICs might soon threaten the effectiveness of this therapeutic regimen and requires close monitoring.

Antimicrobial Consumption and Susceptibility of Neisseria gonorrhoeae: A Global Ecological Analysis.

Aims: The reasons why antimicrobial resistance in Neisseria gonorrhoeae has emerged explosively in certain populations but not others are poorly understood. We hypothesized that population level consumption of antimicrobials plays a role.Methods: Using susceptibility data from the World Health Organizations Global Gonococcal Antimicrobial Surveillance Programme and antimicrobial consumption data from the IMS Health MIDAS database we built linear regression models with country-level cephalosporin, macrolide, and fluoroquinolone consumption (standard doses/1,000 population/year) as the explanatory variable and 1-year lagged ceftriaxone, azithromycin, and ciprofloxacin resistance as the outcome variables. These were performed at two time points 2008/2009 and 2013/2014.Results: The association between antimicrobial resistance and consumption at the level of individual countries was positive in all six assessments. In four instances the positive associations were statistically significant (cephalosporins 2008: coefficient 0.0005 [95% confidence interval (CI) 0.0002–0.0007] and 2013: coefficient 0.0003 [95% CI 0.0002–0.0004]; macrolides 2013: coefficient 0.0005 [95% CI 0.00002–0.001]; fluoroquinolones 2013: coefficient 0.02 [95% CI 0.006–0.031]).Conclusions: Differences in population level consumption of particular antimicrobials may play a role in explaining the variations in the emergence of antimicrobial resistance in N. gonorrhoeae.

The first year of the global Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP) in Bangkok, Thailand, 2015-2016.

Antimicrobial-resistant Neisseria gonorrhoeae (NG) infection is a global public health threat, and there is a critical need to monitor patterns of resistance and risk factors. In collaboration with the World Health Organization (WHO), the U.S. Centers for Disease Control and Prevention (CDC), and the Thailand Department of Disease Control (DDC), Ministry of Public Health (MoPH) implemented the first Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP) in November 2015. Men presenting with urethritis at two clinical settings in Bangkok, Thailand (Bangrak Hospital [BH] and Silom Community Clinic @TropMed [SCC @TropMed]) provided demographic and behavioral information and had a urethral swab for Gram’s stain and NG culture collected. The NG isolates were evaluated for antimicrobial susceptibility by the Epsilometer test (Etest) to determine minimum inhibitory concentrations (MICs) for cefixime (CFM), ceftriaxone (CRO), azithromycin (AZI), gentamicin (GEN), and ciprofloxacin (CIP). From November 2015 –October 2016, 1,102 specimens were collected from 1,026 symptomatic men; 861 (78.1%) specimens were from BH and 241 (21.9%) specimens were from SCC @TropMed. Among the 1,102 specimens, 582 (52.8%) had intracellular Gram-negative diplococci and 591 (53.6%) had NG growth (i.e., NG infection); antimicrobial susceptibility testing (AST) was performed on 590 (99.8%) NG isolates. Among all symptomatic men, 293 (28.6%) had sex with men only, 430 (41.9%) were ages 18–29 years, 349 (34.0%) had antibiotic use in the last 2 weeks, and 564 (55.0%) had NG infection. Among 23 men with repeat NG infection during this first year of surveillance, 20 (87.0%) were infected twice, 2 (8.7%) were infected three times, and 1 (4.3%) was infected more than four times. All NG isolates were susceptible to CFM and CRO, and had MICs below 2 μg/mL for AZI and below 16 μg/mL for GEN. Overall, 545 (92.4%) isolates were resistant to CIP. This surveillance activity assessed individual patients, and included demographic and behavioral data linked to laboratory data. The inclusion of both individual and laboratory information in EGASP could help identify possible persistent infection and NG treatment failures. Expansion of EGASP to additional global settings is critical to assess trends and risk factors for NG, and to monitor for the emergence of resistance.

Correction: Quality assessment of the enhanced gonococcal antimicrobial surveillance program in Thailand, 2015-2016

Correction: Quality assessment of the enhanced gonococcal antimicrobial surveillance program in Thailand, 2015-2016

Public health surveillance of multidrug-resistant clones of Neisseria gonorrhoeae in Europe: a genomic survey

SummaryBackgroundTraditional methods for molecular epidemiology of Neisseria gonorrhoeae are suboptimal. Whole-genome sequencing (WGS) offers ideal resolution to describe population dynamics and to predict and infer transmission of antimicrobial resistance, and can enhance infection control through linkage with epidemiological data. We used WGS, in conjunction with linked epidemiological and phenotypic data, to describe the gonococcal population in 20 European countries. We aimed to detail changes in phenotypic antimicrobial resistance levels (and the reasons for these changes) and strain distribution (with a focus on antimicrobial resistance strains in risk groups), and to predict antimicrobial resistance from WGS data.MethodsWe carried out an observational study, in which we sequenced isolates taken from patients with gonorrhoea from the European Gonococcal Antimicrobial Surveillance Programme in 20 countries from September to November, 2013. We also developed a web platform that we used for automated antimicrobial resistance prediction, molecular typing (N gonorrhoeae multi-antigen sequence typing [NG-MAST] and multilocus sequence typing), and phylogenetic clustering in conjunction with epidemiological and phenotypic data.FindingsThe multidrug-resistant NG-MAST genogroup G1407 was predominant and accounted for the most cephalosporin resistance, but the prevalence of this genogroup decreased from 248 (23%) of 1066 isolates in a previous study from 2009–10 to 174 (17%) of 1054 isolates in this survey in 2013. This genogroup previously showed an association with men who have sex with men, but changed to an association with heterosexual people (odds ratio=4·29). WGS provided substantially improved resolution and accuracy over NG-MAST and multilocus sequence typing, predicted antimicrobial resistance relatively well, and identified discrepant isolates, mixed infections or contaminants, and multidrug-resistant clades linked to risk groups.InterpretationTo our knowledge, we provide the first use of joint analysis of WGS and epidemiological data in an international programme for regional surveillance of sexually transmitted infections. WGS provided enhanced understanding of the distribution of antimicrobial resistance clones, including replacement with clones that were more susceptible to antimicrobials, in several risk groups nationally and regionally. We provide a framework for genomic surveillance of gonococci through standardised sampling, use of WGS, and a shared information architecture for interpretation and dissemination by use of open access software.FundingThe European Centre for Disease Prevention and Control, The Centre for Genomic Pathogen Surveillance, Örebro University Hospital, and Wellcome.

Strengthening Global Surveillance for Antimicrobial Drug-Resistant Neisseria gonorrhoeae through the Enhanced Gonococcal Antimicrobial Surveillance Program.

Monitoring trends in antimicrobial drug–resistant Neisseria gonorrhoeae is a critical public health and global health security activity because the number of antimicrobial drugs available to treat gonorrhea effectively is rapidly diminishing. Current global surveillance methods for antimicrobial drug–resistant N. gonorrhoeae have many limitations, especially in countries with the greatest burden of disease. The Enhanced Gonococcal Antimicrobial Surveillance Program is a collaboration between the World Health Organization and the Centers for Disease Control and Prevention. The program aims to monitor trends in antimicrobial drug susceptibilities in N. gonorrhoeae by using standardized sampling and laboratory protocols; to improve the quality, comparability, and timeliness of gonococcal antimicrobial drug resistance data across multiple countries; and to assess resistance patterns in key populations at highest risk for antimicrobial drug–resistant gonorrhea so country-specific treatment guidelines can be informed.

High-Level Neisseria gonorrhea Resistance Detected in a Newly Implemented Surveillance Program in Kampala, Uganda

Background Neisseria gonorrhea resistance is a growing problem in Uganda with recent data showing increasing ciprofloxacin resistance up to 100% in this population. The WHO Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP) was initiated in Uganda in September 2016 to monitor resistance trends.Methods Urethral swabs were collected from men presenting with urethral discharge to the five sentinel clinic sites from September 2016 to March 2017. Samples were transported to a reference laboratory site. Presumptive identification of N. gonorrhea was based on growth of typical appearing colonies on Thayer–Martin in 5% CO2, a positive oxidase test, and observation of Gram-negative, oxidase-positive diplococci in stained smears.Results116 samples were received to the reference laboratory site of which 70 (60.3%) had positive growth for Neisseria gonorrhea. Mean age was 28.5 (range 17–60). Fifty-one participants (44%) reported at least one prior episode of gonorrhea and 42 (36%) reported antibiotic use within the previous 60 days. Of those with completed Etest (bioMerieux, Marcy-lÕEtoile, France) resistance profiles, 66 (96%) were ciprofloxacin-resistant or intermediate. One isolate was ceftriaxone-resistant by E-test but susceptible by disk diffusion.Conclusion Early results from implementation of a gonorrhea surveillance program in Uganda suggest high levels of resistance to ciprofloxacin (90%) by Etest and penicillin (93%) and tetracyclines (100%) by disk diffusion. Prior studies of gonococcal resistance in Uganda have noted increasing levels of resistance, particularly to ciprofloxacin which until 2010 was the recommended first-line empiric therapy for gonococcal infection in Uganda. Of note, discrepancies were occasionally noted between disk diffusion and Etest results, which requires further investigation. Ongoing surveillance efforts will be crucial to shape clinical guidelines and national policy.Figure 1.(a) Neisseria gonorrhea antibiotic susceptibility profile by Kirby-Bauer disk diffusion. (b) Neisseria gonorrhea antibiotic susceptibility profile by Etest. *PEN = penicillin, CXM = cefuroxime, CRO = ceftriaxone, FOX = cefoxitin, CFM = cefixime, SPT = spectinomycin, GEN = gentamicin, CIP = ciprofloxacin, TCY = tetracycline, AZM = azithromycin.Disclosures All authors: No reported disclosures.

Strengthening Global Surveillance for Antimicrobial-ResistantNeisseria gonorrhoeaethrough the Enhanced Gonococcal Antimicrobial Surveillance Program (EGASP)

Abstract Monitoring trends in antimicrobial drug–resistant Neisseria gonorrhoeae is a critical public health and global health security activity because the number of antimicrobial drugs available to treat gonorrhea effectively is rapidly diminishing. Current global surveillance methods for antimicrobial drug–resistant N. gonorrhoeae have many limitations, especially in countries with the greatest burden of disease. The Enhanced Gonococcal Antimicrobial Surveillance Program is a collaboration between the World Health Organization and the Centers for Disease Control and Prevention. The program aims to monitor trends in antimicrobial drug susceptibilities in N. gonorrhoeae by using standardized sampling and laboratory protocols; to improve the quality, comparability, and timeliness of gonococcal antimicrobial drug resistance data across multiple countries; and to assess resistance patterns in key populations at highest risk for antimicrobial drug–resistant gonorrhea so country-specific treatment guidelines can be informed.

Overall Low Extended-Spectrum Cephalosporin Resistance but high Azithromycin Resistance in Neisseria gonorrhoeae in 24 European Countries, 2015

BackgroundSurveillance of Neisseria gonorrhoeae antimicrobial susceptibility in Europe is performed through the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP), which additionally provides data to inform the European gonorrhoea treatment guideline; currently recommending ceftriaxone 500 mg plus azithromycin 2 g as first-line therapy. We present antimicrobial susceptibility data from 24 European countries in 2015, linked to epidemiological data of patients, and compare the results to Euro-GASP data from previous years.MethodsAntimicrobial susceptibility testing by MIC gradient strips or agar dilution methodology was performed on 2134 N. gonorrhoeae isolates and interpreted using EUCAST breakpoints. Patient variables associated with resistance were established using logistic regression to estimate odds ratios (ORs).ResultsIn 2015, 1.7% of isolates were cefixime resistant compared to 2.0% in 2014. Ceftriaxone resistance was detected in only one (0.05%) isolate in 2015, compared with five (0.2%) in 2014. Azithromycin resistance was detected in 7.1% of isolates in 2015 (7.9% in 2014), and five (0.2%) isolates displayed high-level azithromycin resistance (MIC ≥ 256 mg/L) compared with one (0.05%) in 2014. Ciprofloxacin resistance remained high (49.4%, vs. 50.7% in 2014). Cefixime resistance significantly increased among heterosexual males (4.1% vs. 1.7% in 2014), which was mainly attributable to data from two countries with high cefixime resistance (~11%), however rates among men-who-have-sex-with-men (MSM) and females continued to decline to 0.5% and 1%, respectively. Azithromycin resistance in MSM and heterosexual males was higher (both 8.1%) than in females (4.9% vs. 2.2% in 2014). The association between azithromycin resistance and previous gonorrhoea infection, observed in 2014, continued in 2015 (OR 2.1, CI 1.2–3.5, p < 0.01).ConclusionsThe 2015 Euro-GASP sentinel system revealed high, but stable azithromycin resistance and low overall resistance to ceftriaxone and cefixime. The low cephalosporin resistance may be attributable to the effectiveness of the currently recommended first-line dual antimicrobial therapy; however the high azithromycin resistance threatens the effectiveness of this therapeutic regimen. Whether the global use of azithromycin in mono- or dual antimicrobial therapy of gonorrhoea is contributing to the global increases in azithromycin resistance remains to be elucidated. The increasing cefixime resistance in heterosexual males also needs close monitoring.

Exploring the scope of enhanced gonococcal antimicrobial surveillance programme.

Exploring the scope of enhanced gonococcal antimicrobial surveillance programme.

Molecular epidemiology of drug-resistant Neisseria gonorrhoeae in Russia (Current Status, 2015).

BackgroundThe widespread distribution of Neisseria gonorrhoeae strains that are resistant to previously used and clinically implemented antibiotics is a significant global public health problem. In line with WHO standards, the national Gonococcal Antimicrobial Surveillance Programme (RU-GASP) has been in existence in Russia since 2004; herein, the current status (2015) is described, including associations between N. gonorrhoeae antimicrobial susceptibility, primary genetic resistance determinants and specific strain sequence types.MethodsA total of 124 N. gonorrhoeae strains obtained from 9 regions in Russia in 2015 were examined using N. gonorrhoeae Multi-Antigen Sequence Typing (NG-MAST), an antimicrobial susceptibility test according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria and an oligonucleotide microarray for the identification of mutations in the penA, ponA, rpsJ, gyrA and parC genes responsible for penicillin G, tetracycline, and fluoroquinolone resistance. Genogroup (G) isolates were evaluated based on their porB and tbpB sequence types (STs).ResultsNG-MAST analysis showed a diversified population of N. gonorrhoeae in Russia with 58 sequence types, 35 of which were described for the first time. The STs 807, 1544, 1993, 5714, 9476 and 12531, which were typical for some Russian Federation regions and several countries of the former Soviet Union, were represented by five or more isolates. The internationally widespread ST 1407 was represented by a single strain in the present study. Division into genogroups facilitated an exploration of the associations between N. gonorrhoeae sequence type, antimicrobial resistance spectra and genetic resistance determinant contents. Preliminarily susceptible (G-807, G-12531) and resistant (G-5714, G-9476) genogroups were revealed. The variability in the most frequently observed STs and genogroups in each participating region indicated geographically restricted antimicrobial susceptibility in N. gonorrhoeae populations.ConclusionsResistance or intermediate susceptibility to previously recommended antimicrobials, such as penicillin G (60.5 %), ciprofloxacin (41.1 %) and tetracycline (25 %), is common in the N. gonorrhoeae population. Based on previous reports and current data, ceftriaxone and spectinomycin should be recommended for first-line empiric antimicrobial monotherapy for gonorrhoea in Russia.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1688-7) contains supplementary material, which is available to authorized users.

The novel 2016 WHO Neisseria gonorrhoeae reference strains for global quality assurance of laboratory investigations: phenotypic, genetic and reference genome characterization.

Gonorrhoea and MDR Neisseria gonorrhoeae remain public health concerns globally. Enhanced, quality-assured, gonococcal antimicrobial resistance (AMR) surveillance is essential worldwide. The WHO global Gonococcal Antimicrobial Surveillance Programme (GASP) was relaunched in 2009. We describe the phenotypic, genetic and reference genome characteristics of the 2016 WHO gonococcal reference strains intended for quality assurance in the WHO global GASP, other GASPs, diagnostics and research worldwide. The 2016 WHO reference strains (n = 14) constitute the eight 2008 WHO reference strains and six novel strains. The novel strains represent low-level to high-level cephalosporin resistance, high-level azithromycin resistance and a porA mutant. All strains were comprehensively characterized for antibiogram (n = 23), serovar, prolyliminopeptidase, plasmid types, molecular AMR determinants, N. gonorrhoeae multiantigen sequence typing STs and MLST STs. Complete reference genomes were produced using single-molecule PacBio sequencing. The reference strains represented all available phenotypes, susceptible and resistant, to antimicrobials previously and currently used or considered for future use in gonorrhoea treatment. All corresponding resistance genotypes and molecular epidemiological types were described. Fully characterized, annotated and finished references genomes (n = 14) were presented. The 2016 WHO gonococcal reference strains are intended for internal and external quality assurance and quality control in laboratory investigations, particularly in the WHO global GASP and other GASPs, but also in phenotypic (e.g. culture, species determination) and molecular diagnostics, molecular AMR detection, molecular epidemiology and as fully characterized, annotated and finished reference genomes in WGS analysis, transcriptomics, proteomics and other molecular technologies and data analysis.