P232 Antimicrobial Resistance of Neisseria gonorrhoeae in Germany 2016–2020, results from the Gonococcal Resistance Network (GORENET)

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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WHO global antimicrobial resistance surveillance for Neisseria gonorrhoeae 2017–18: a retrospective observational study

The Lancet Microbe ◽

10.1016/s2666-5247(21)00171-3 ◽

2021 ◽

Author(s):

Magnus Unemo ◽

Monica M Lahra ◽

Martina Escher ◽

Sergey Eremin ◽

Michelle J Cole ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Observational Study ◽

Neisseria Gonorrhoeae ◽

Retrospective Observational Study ◽

Antimicrobial Resistance Surveillance

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Antimicrobial resistance mechanisms, MLST and NG-STAR sequence types of diverse Neisseria gonorrhoeae isolates in KwaZulu-Natal, South Africa

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00759-21 ◽

2021 ◽

Author(s):

Nireshni Mitchev ◽

Ravesh Singh ◽

Mushal Allam ◽

Stanford Kwenda ◽

Arshad Ismail ◽

...

Keyword(s):

South Africa ◽

Antimicrobial Resistance ◽

Neisseria Gonorrhoeae ◽

Point Mutations ◽

Resistance Mechanisms ◽

Public Healthcare ◽

Multiple Sequence ◽

Genotypic Analysis ◽

Kwazulu Natal ◽

Sequence Types

Objective: Antimicrobial resistance (AMR) is a major challenge to managing infectious diseases. Africa has the highest incidence of gonorrhoea but there is a lack of comprehensive data from sparse surveillance programs. This study investigated the molecular epidemiology and AMR profiles of Neisseria gonorrhoeae isolates in KwaZulu-Natal province (KZN), South Africa. Methods: Repository isolates, from patients attending public healthcare clinics for STI care, were used for phenotypic and genotypic analysis. Etest® was performed to determine antimicrobial susceptibility. Whole-genome sequencing (WGS) was used to determine epidemiology and to predict susceptibility by detecting resistance-associated genes and mutations. Results: Among the 61 isolates, multiple sequence types were identified. Six isolates were novel as determined by multilocus sequence typing. N.gonorrhoeae Sequence Typing for Antimicrobial Resistance (NG-STAR) determined 48 sequence types, of which 35 isolates had novel antimicrobial profiles. Two novel penA alleles and eight novel mtrR alleles were identified. Point mutations were detected in gyrA , parC , mtrR , penA , ponA and porB1 . This study revealed a high prevalence of AMR (penicillin 67%, tetracycline 89% and ciprofloxacin 52%). However, spectinomycin, cefixime, ceftriaxone and azithromycin remained 100% effective. Conclusion: This study is one of the first to comprehensively describe the epidemiology and AMR of N. gonorrhoeae in KZN, South Africa and Africa, using WGS. KZN has a wide strain diversity and most of these sequence types have been detected in multiple countries, however more than half of our isolates have novel antimicrobial profiles. Continued surveillance is crucial to monitor the emergence of resistance to cefixime, ceftriaxone and azithromycin.

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Antimicrobial Resistance of Neisseria gonorrhoeae Isolated from Out Patients Presenting with Urethral and Vaginal Discharges at Mbarara Regional Referral Hospital

Journal of Advances in Medicine and Medical Research ◽

10.9734/jammr/2019/v30i530198 ◽

2019 ◽

pp. 1-7

Author(s):

Judith Owokuhaisa ◽

Joel Bazira

Keyword(s):

Antimicrobial Resistance ◽

Neisseria Gonorrhoeae ◽

Test Organism ◽

Referral Hospital ◽

Cross Sectional ◽

Regional Referral Hospital ◽

Sexually Transmitted ◽

Peptone Water ◽

Phenotypic Methods ◽

Micro Organisms

Background: Gonococcus is one of the most common sexually transmitted diseases in developing countries and it has become a global health burden, hence a need for effective treatment. However, there is growing trend of antimicrobial resistant strains, in many parts of the world, to the previously effective antimicrobials thus creating serious health concerns. Setting: Mbarara Regional Referral Hospital -South-Western Uganda. Objectives: 1) To determine the prevalence of gonococcus among out patients presenting with urethral and vaginal discharges at MRRH. 2) To determine the level of antimicrobial resistance of gonococcus based on phenotypic methods at MRRH. Design: The study was cross sectional and enrolled 189 participants presenting with urethral and vaginal discharges. The urethral and endo cervical swab samples collected were cultured on Chocolate media supplemented with 5%-10% carbondioxide in candle jar (inoculated plates were placed in a jar and a burning candle placed in the same jar, then closed, by the time the candle went off, that 5%-10% carbondioxide atmosphere would have been created). Isolates obtained were identified according to the laboratory standard operating procedures. Drug Sensitivity Test (DST) on confirmed Neisseria gonorrheae isolates was performed using the Kirby Bauer technique. The colonies of the test organism were emulsified in peptone water and then inoculated on prepared sterile chocolate agar and the following discs were applied to it (Ceftriaxone discs (30µg), Erythromycin (15ug), Ciprofloxacin (10ug) and Penicillin (10IU). The plates were incubated at 37°C for 24- 48 hours under 5% carbon dioxide atmospheres. The Zone of inhibition was seen around an antibiotic disc to which the organism was sensitive. Results: Out of the 189 participants whose urethral swabs and Endo cervical swabs were cultured, 89 were positive cultures (47%), out of which 25 (28%) were found to have gonococcal infection, 64 (72%) patients had other micro-organisms. The prevalence of Neisseria Gonorrhoeae was 13%. In total, 4% of the isolates were resistant to Ceftriaxone, 28% to Ciprofloxacin, 68% to Erythromycin and 80% to Penicillin. A high percentage of resistance was observed against Penicillin (80%) and Erythromycin (68%). Conclusion: Adults aged 18 years and above who present at Mbarara Regional Referral Hospital with urethral or vaginal discharges are more likely to have a Neisseria gonorrhoeae which is resistant to Penicillin and Erythromycin.

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Differences in Neisseria gonorrhoeae population structure and antimicrobial resistance pattern between men who have sex with men and heterosexuals

Epidemiology and Infection ◽

10.1017/s095026881600234x ◽

2016 ◽

Vol 145 (2) ◽

pp. 379-385 ◽

Cited By ~ 7

Author(s):

J. SERRA-PLADEVALL ◽

M. J. BARBERÁ ◽

A. E. CALLARISA ◽

R. BARTOLOMÉ-COMAS ◽

A. ANDREU

Keyword(s):

Population Structure ◽

Antimicrobial Resistance ◽

Neisseria Gonorrhoeae ◽

Antimicrobial Susceptibility ◽

Sexual Practices ◽

Resistance Pattern ◽

High Prevalence ◽

Sex With Men ◽

Resistance Rates ◽

Sequence Types

SUMMARYThis study compared the antimicrobial susceptibility and genotypes of strains of Neisseria gonorrhoeae isolated from men who have sex with men (MSM) and from heterosexuals. One hundred and eleven strains were characterized from 107 patients, comprising 57 strains from 54 heterosexuals and 54 strains from 53 MSM. Antimicrobial resistance rates were higher in strains from heterosexual patients, with resistance to cefixime (P = 0·0159) and ciprofloxacin (P = 0·002) being significantly higher. Typing by N. gonorrhoeae multi-antigen sequence typing (NG-MAST) showed that the most prevalent sequence types (ST) and genogroups (G) respectively were ST2400, ST2992, and ST5793, and G1407, G2992, and G2400. A statistically significant association was observed for MSM and genogroups G2400 (P = 0·0005) and G2992 (P = 0·0488), and G1407 with heterosexuals (P = 0·0002). We conclude that in our region distinct populations of gonococci are circulating among subjects with different sexual practices, with their corresponding transmission patterns. Furthermore, the high prevalence of genotype G2400 in MSM, has not to our knowledge been previously described.

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Efflux Pumps in Neisseria gonorrhoeae: Contributions to Antimicrobial Resistance and Virulence

Efflux-Mediated Antimicrobial Resistance in Bacteria ◽

10.1007/978-3-319-39658-3_17 ◽

2016 ◽

pp. 439-469 ◽

Cited By ~ 8

Author(s):

William M. Shafer ◽

Edward W. Yu ◽

Corinne Rouquette-Loughlin ◽

Daniel Golparian ◽

Ann E. Jerse ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Neisseria Gonorrhoeae ◽

Efflux Pumps

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Antimicrobial Resistance Expressed by Neisseria gonorrhoeae: A Major Global Public Health Problem in the 21st Century

Emerging Infections 10 ◽

10.1128/9781555819453.ch12 ◽

2016 ◽

pp. 213-237

Author(s):

Magnus Unemo ◽

Carlos Del Rio ◽

William M. Shafer

Keyword(s):

Public Health ◽

Antimicrobial Resistance ◽

Neisseria Gonorrhoeae ◽

21St Century ◽

Health Problem ◽

Public Health Problem ◽

Global Public Health ◽

Global Public Health Problem

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Genomic analysis and antimicrobial resistance of Neisseria gonorrhoeae isolates from Vietnam in 2011 and 2015–16

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkaa040 ◽

2020 ◽

Vol 75 (6) ◽

pp. 1432-1438 ◽

Cited By ~ 2

Author(s):

Pham Thi Lan ◽

Daniel Golparian ◽

Johan Ringlander ◽

Le Van Hung ◽

Nguyen Van Thuong ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Reproductive Health ◽

Neisseria Gonorrhoeae ◽

Molecular Epidemiology ◽

Genomic Analysis ◽

Illumina Miseq ◽

Phylogenomic Analysis ◽

Asian Countries ◽

Resistant Strains ◽

A Minor

Abstract Objectives Antimicrobial resistance (AMR) in Neisseria gonorrhoeae, compromising gonorrhoea treatment, is a threat to reproductive health globally. South-East and East Asia have been major sources of emergence and subsequent international spread of AMR gonococcal strains during recent decades. We investigated gonococcal isolates from 2011 and 2015–16 in Vietnam using AMR testing, WGS and detection of AMR determinants. Methods Two hundred and twenty-nine gonococcal isolates cultured in 2015–16 (n = 121) and 2011 (n = 108) in Vietnam were examined. AMR testing was performed using Etest and WGS with Illumina MiSeq. Results Resistance among the 2015–16 isolates was as follows: ciprofloxacin, 100%; tetracycline, 79%; benzylpenicillin, 50%; cefixime, 15%; ceftriaxone, 1%; spectinomycin, 0%; and 5% were non-WT to azithromycin. Eighteen (15%) isolates were MDR. The MIC range for gentamicin was 2–8 mg/L. Among the 2015–16 isolates, 27% (n = 33) contained a mosaic penA allele, while no isolates had a mosaic penA allele in 2011. Phylogenomic analysis revealed introduction after 2011 of two mosaic penA-containing clones (penA-10.001 and penA-34.001), which were related to cefixime-resistant strains spreading in Japan and Europe, and a minor clade (eight isolates) relatively similar to the XDR strain WHO Q. Conclusions From 2011 to 2015–16, resistance in gonococci from Vietnam increased to all currently and previously used antimicrobials except ceftriaxone, spectinomycin and tetracycline. Two mosaic penA-containing clones were introduced after 2011, explaining the increased cefixime resistance. Significantly increased AMR surveillance, antimicrobial stewardship and use of WGS for molecular epidemiology and AMR prediction for gonococcal isolates in Vietnam and other Asian countries are crucial.

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Genotypic and Phenotypic Characterization of Antimicrobial Resistance in Neisseria gonorrhoeae: a Cross-Sectional Study of Isolates Recovered from Routine Urine Cultures in a High-Incidence Setting

mSphere ◽

10.1128/msphere.00373-19 ◽

2019 ◽

Vol 4 (4) ◽

Cited By ~ 1

Author(s):

Adam L. Bailey ◽

Robert F. Potter ◽

Meghan A. Wallace ◽

Caitlin Johnson ◽

Gautam Dantas ◽

...

Keyword(s):

Antibiotic Resistance ◽

Antimicrobial Resistance ◽

Neisseria Gonorrhoeae ◽

Susceptibility Testing ◽

Clinical Laboratory ◽

Phenotypic Characterization ◽

First Line ◽

Content Type ◽

Gradient Diffusion

ABSTRACT The objectives of this study were to perform genomic and phenotypic characterization of antimicrobial resistance in Neisseria gonorrhoeae isolates recovered from urine samples from patients in St. Louis, MO, USA. Sixty-four clinical isolates were banked over a 2-year period and subjected to antimicrobial susceptibility testing (AST) by Kirby-Bauer disk diffusion (penicillin, tetracycline, cefuroxime, and ciprofloxacin) and gradient diffusion (tetracycline, doxycycline, azithromycin, ceftriaxone, cefixime, ciprofloxacin, gemifloxacin, and delafloxacin). The medical records for the patients were evaluated to determine the demographics, location, and prescribed treatment regimen. Isolate draft genomes were assembled from Illumina shotgun sequencing data, and resistance determinants were identified by ResFinder and PointFinder. Of the 64 isolates, 97% were nonsusceptible to penicillin, with resistant isolates all containing the blaTEM-1b gene; 78 and 81% of isolates were nonsusceptible to tetracycline and doxycycline, respectively, with resistant isolates all containing the tet(M) gene. One isolate was classified as non-wild-type to azithromycin, and all isolates were susceptible to ceftriaxone; 89% of patients received this combination of drugs as first-line therapy. Six percent of isolates were resistant to ciprofloxacin, with most resistant isolates containing multiple gyrA and parC mutations. Correlation between disk and gradient diffusion AST devices was high for tetracycline and ciprofloxacin (R2 > 99% for both). The rates of N. gonorrhoeae antibiotic resistance in St. Louis are comparable to current rates reported nationally, except ciprofloxacin resistance was less common in our cohort. Strong associations between specific genetic markers and phenotypic susceptibility testing hold promise for the utility of genotype-based diagnostic assays to guide directed antibiotic therapy. IMPORTANCE Neisseria gonorrhoeae causes the sexually transmitted infection gonorrhea, which is most commonly diagnosed using a DNA-based detection method that does not require growth and isolation of N. gonorrhoeae in the laboratory. This is problematic because the rates of antibiotic resistance in N. gonorrhoeae are increasing, but without isolating the organism in the clinical laboratory, antibiotic susceptibility testing cannot be performed on strains recovered from clinical specimens. We observed an increase in the frequency of urine cultures growing N. gonorrhoeae after we implemented a total laboratory automation system for culture in our clinical laboratory. Here, we report on the rates of resistance to multiple historically used, first-line, and potential future-use antibiotics for 64 N. gonorrhoeae isolates. We found that the rates of antibiotic resistance in our isolates were comparable to national rates. Additionally, resistance to specific antibiotics correlated closely with the presence of genetic resistance genes, suggesting that DNA-based tests could also be designed to guide antibiotic therapy for treating gonorrhea.

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