Genomic epidemiology and antimicrobial resistance of Neisseria gonorrhoeae in New Zealand

Antimicrobial-resistant Neisseria gonorrhoeae is a major threat to public health and is of particular concern in the Western Pacific Region, where the incidence of gonorrhoea is high. The Antimicrobial Resistance Surveillance Program (ARSP) has been capturing information on resistant gonorrhoea since 1996, but genomic epidemiology studies on this pathogen are lacking in the Philippines. We sequenced the whole genomes of 21 N. gonorrhoeae isolates collected in 2013–2014 by ARSP. The multilocus sequence type, multiantigen sequence type, presence of determinants of antimicrobial resistance and relatedness among the isolates were all derived from the sequence data. The concordance between phenotypic and genotypic resistance was also determined. Ten of 21 isolates were resistant to penicillin, ciprofloxacin and tetracycline, due mainly to the presence of the blaTEM gene, the S91F mutation in the gyrA gene and the tetM gene, respectively. None of the isolates was resistant to ceftriaxone or cefixime. The concordance between phenotypic and genotypic resistance was 92.38% overall for five antibiotics in four classes. Despite the small number of isolates studied, they were genetically diverse, as shown by the sequence types, the N. gonorrhoeae multiantigen sequence typing types and the tree. Comparison with global genomes placed the Philippine genomes within global lineage A and led to the identification of an international transmission route.

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Genomic Surveillance of Neisseria gonorrhoeae in the Philippines from 2013-2014

10.1101/2020.03.19.998435 ◽

2020 ◽

Author(s):

Alfred S. Villamin ◽

Silvia Argimón ◽

Manuel C. Jamoralin ◽

Karis D. Boehme ◽

Melissa L. Masim ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Neisseria Gonorrhoeae ◽

Sequence Data ◽

The Philippines ◽

Sequence Type ◽

Western Pacific ◽

Surveillance Program ◽

Genotypic Resistance ◽

Genomic Epidemiology ◽

The Western Pacific

AbstractAntimicrobial-resistant Neisseria gonorrhoeae is a major threat to public health, and of particular concern in the Western Pacific Region, where the incidence of gonorrhoea is high. The Antimicrobial Resistance Surveillance Program (ARSP) has been capturing information on resistant gonorrhoea since 1996, but studies of the genomic epidemiology of gonorrhoea in the Philippines are lacking.We sequenced the whole genomes of 21 N. gonorrhoeae isolates collected in 2013-2014 by the ARSP. The multi-locus sequence type, multi-antigen sequence type, presence of antimicrobial resistance (AMR) determinants, and relatedness between the isolates were all derived from the sequence data. The concordance between phenotypic and genotypic resistance was also determined.Ten out of 21 isolates were resistant to penicillin, ciprofloxacin and tetracycline, mostly linked to the presence of blaTEM gene, the S91F mutation in the gyrA gene, and the tetM gene, respectively. None of the isolates were resistant to azithromycin, ceftriaxone or cefixime, although we identified the A24-deletion in the mtrR promoter in one isolate. The concordance between phenotypic and genotypic resistance was 92.38% overall for 5 antibiotics in 4 classes. Despite the small number of isolates studied, they were genetically diverse, as shown by the sequence types, the NG-MAST types and the tree. Comparison with global genomes placed the Philippine genomes within global Lineage A and led to the identification of an international transmission route.This first genomic survey of N. gonorrhoeae isolates collected by ARSP will be used to contextualize ongoing prospective surveillance, and it highlights the importance of genomic surveillance in the Western Pacific and other endemic regions to understand the spread of drug-resistant gonorrhoea worldwide.

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Genomic epidemiology and antimicrobial resistance determinants of Neisseria gonorrhoeae isolates from Ukraine, 2013–2018

Apmis ◽

10.1111/apm.13060 ◽

2020 ◽

Vol 128 (7) ◽

pp. 465-475

Author(s):

Iryna Boiko ◽

Daniel Golparian ◽

Susanne Jacobsson ◽

Inna Krynytska ◽

Arkadii Frankenberg ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Neisseria Gonorrhoeae ◽

Genomic Epidemiology ◽

Resistance Determinants

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

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.739969818.793587129 ◽

2021 ◽

Author(s):

Martin Maiden ◽

Odile Harrison

Keyword(s):

Antimicrobial Resistance ◽

Neisseria Gonorrhoeae ◽

Genomic Epidemiology ◽

Resistance Prediction

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The antimicrobial resistance landscape of Neisseria gonorrhoeae in New Zealand from November 2018 to March 2019 and the role of sexual orientation in transmission

Microbial Genomics ◽

10.1099/mgen.0.000701 ◽

2021 ◽

Vol 7 (11) ◽

Author(s):

Christina Straub ◽

Callum Thirkell ◽

Audrey Tiong ◽

Rosemary Woodhouse ◽

Jenny Szeto ◽

...

Keyword(s):

New Zealand ◽

Antimicrobial Resistance ◽

Neisseria Gonorrhoeae ◽

Type Species ◽

Treatment Guidelines ◽

World Health ◽

Sexual Networks ◽

Content Type ◽

Link Type ◽

Azithromycin Resistance

The increasing use of culture independent diagnostic testing for the diagnosis of Neisseria gonorrhoeae infection has led to gaps in surveillance of antimicrobial resistance (AMR) rates due to limited availability of cultures. Our study reports the findings of a second national survey of N. gonorrhoeae in New Zealand, utilizing whole-genome sequencing (WGS) to study the population structure, prevalence of AMR, epidemiology and transmission of gonorrhoea isolates. We analysed 314 isolates and found a strong correlation between carriage of acquired resistance genes or chromosomal point mutations and phenotypic susceptibility testing results. Overall, the New Zealand rates of azithromycin resistance and decreased susceptibility to ceftriaxone remain lower than in most countries, which are part of the World Health Organization (WHO) Global Gonococcal Antimicrobial Surveillance Programme (GASP). The phylogeny provides evidence of a diverse population significantly associated with sexual behaviour groups. Transmission clustering with a ten single nucleotide polymorphism (SNP) cut-off identified 49 clusters, of which ten were solely associated with men who have sex with men (MSM), whereas remaining clusters included heterosexual patients, as well as MSM, suggesting that bridging of sexual networks is occurring. Utilizing pairwise SNP differences between isolates of the same sequence types we determined genetic variation for the three typing schemes used in this study [Multi locus sequence typing (MLST), multi-antigen sequence typing (NG-MAST), and sequence typing for antimicrobial resistance (NG-STAR)]. A median of 0.0 to 52.5 pairwise SNP differences within a single NG-STAR sequence type underlines previous findings of the superiority of the NG-STAR typing scheme in terms of genomic inherency. With our analysis incorporating epidemiological and genomic data, we were able to show a comprehensive overview of the N. gonorrhoeae population circulating in New Zealand, focussing on AMR and transmission within sexual networks. Regular surveillance studies to understand the origin, evolution and spread of AMR for gonorrhoea remain necessary to make informed decisions about public health guidelines, as the internationally rising rates of ceftriaxone and azithromycin resistance have already led to adaptation of current treatment guidelines in the UK and the USA, highlighting the importance of regular surveillance in individual countries.

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Genomic epidemiology of Neisseria gonorrhoeae elucidating the gonococcal antimicrobial resistance and lineages/sublineages across Brazil, 2015–16

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkaa318 ◽

2020 ◽

Vol 75 (11) ◽

pp. 3163-3172

Author(s):

Daniel Golparian ◽

Maria Luiza Bazzo ◽

Lisléia Golfetto ◽

Pamela Cristina Gaspar ◽

Marcos André Schörner ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Neisseria Gonorrhoeae ◽

Genomic Diversity ◽

Surveillance Program ◽

Phylogenomic Analysis ◽

Resistance Mutations ◽

Genomic Epidemiology ◽

Antimicrobial Surveillance ◽

Genomic Studies ◽

Azithromycin Resistance

Abstract Objectives Neisseria gonorrhoeae antimicrobial resistance (AMR) surveillance is imperative internationally, but only eight (22.9%) countries in the WHO Region of the Americas reported complete AMR data to the WHO Global Gonococcal Antimicrobial Surveillance Program (WHO GASP) in 2016. Genomic studies are ideal for enhanced understanding of gonococcal populations, including the spread of AMR strains. To elucidate the circulating gonococcal lineages/sublineages, including their AMR determinants, and the baseline genomic diversity among gonococcal strains in Brazil, we conducted WGS on 548 isolates obtained in 2015–16 across all five macroregions in Brazil. Methods A total of 548 gonococcal isolates cultured across Brazil in 2015–16 were genome sequenced. AMR was determined using agar dilution and/or Etest. Genome sequences of isolates from Argentina (n = 158) and the 2016 WHO reference strains (n = 14) were included in the analysis. Results We found 302, 68 and 214 different NG-MAST, MLST and NG-STAR STs, respectively. The phylogenomic analysis identified one main antimicrobial-susceptible lineage and one AMR lineage, which was divided into two sublineages with different AMR profiles. Determination of NG-STAR networks of clonal complexes was shown as a new and valuable molecular epidemiological analysis. Several novel mosaic mtrD (and mtrR and mtrE) variants associated with azithromycin resistance were identified. Conclusions We describe the first genomic baseline data to support the Brazilian GASP. The high prevalence of resistance to ciprofloxacin, tetracycline and benzylpenicillin, and the high number of isolates with mosaic penA and azithromycin resistance mutations, should prompt continued and strengthened AMR surveillance, including WGS, of N. gonorrhoeae in Brazil.

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Antimicrobial resistance in Neisseria gonorrhoeae isolates and gonorrhoea treatment in the Republic of Belarus, Eastern Europe, 2009–2019

BMC Infectious Diseases ◽

10.1186/s12879-021-06184-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Aliaksandra Aniskevich ◽

Iryna Shimanskaya ◽

Iryna Boiko ◽

Tatyana Golubovskaya ◽

Daniel Golparian ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Neisseria Gonorrhoeae ◽

Eastern Europe ◽

Treatment Guidelines ◽

Statistical Significance ◽

Antimicrobial Treatment ◽

National Guidelines ◽

First Line ◽

Exact Test ◽

The Republic

Abstract Background Limited 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. Methods N. 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. Results In 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. Conclusions The 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.

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Whole-Genome Phylogenomic Heterogeneity of Neisseria gonorrhoeae Isolates with Decreased Cephalosporin Susceptibility Collected in Canada between 1989 and 2013

Journal of Clinical Microbiology ◽

10.1128/jcm.02589-14 ◽

2014 ◽

Vol 53 (1) ◽

pp. 191-200 ◽

Cited By ~ 78

Author(s):

Walter Demczuk ◽

Tarah Lynch ◽

Irene Martin ◽

Gary Van Domselaar ◽

Morag Graham ◽

...

Keyword(s):

Neisseria Gonorrhoeae ◽

Large Scale ◽

Epidemiological Studies ◽

23S Rrna ◽

Genome Comparison ◽

Whole Genome ◽

Content Type ◽

Genomic Epidemiology ◽

High Level ◽

Sequence Types

A large-scale, whole-genome comparison of CanadianNeisseria gonorrhoeaeisolates with high-level cephalosporin MICs was used to demonstrate a genomic epidemiology approach to investigate strain relatedness and dynamics. Although current typing methods have been very successful in tracing short-chain transmission of gonorrheal disease, investigating the temporal evolutionary relationships and geographical dissemination of highly clonal lineages requires enhanced resolution only available through whole-genome sequencing (WGS). Phylogenomic cluster analysis grouped 169 Canadian strains into 12 distinct clades. While someN. gonorrhoeaemultiantigen sequence types (NG-MAST) agreed with specific phylogenomic clades or subclades, other sequence types (ST) and closely related groups of ST were widely distributed among clades. Decreased susceptibility to extended-spectrum cephalosporins (ESC-DS) emerged among a group of diverse strains in Canada during the 1990s with a variety of nonmosaicpenAalleles, followed in 2000/2001 with thepenAmosaic X allele and then in 2007 with ST1407 strains with thepenAmosaic XXXIV allele. Five genetically distinct ESC-DS lineages were associated withpenAmosaic X, XXXV, and XXXIV alleles and nonmosaic XII and XIII alleles. ESC-DS with coresistance to azithromycin was observed in 5 strains with 23S rRNA C2599T or A2143G mutations. As the costs associated with WGS decline and analysis tools are streamlined, WGS can provide a more thorough understanding of strain dynamics, facilitate epidemiological studies to better resolve social networks, and improve surveillance to optimize treatment for gonorrheal infections.

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