| 1. |
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| 2. |
- Cole, Michelle J., et al.
(författare)
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Ten years of external quality assessment (EQA) of Neisseria gonorrhoeae antimicrobial susceptibility testing in Europe elucidate high reliability of data
- 2019
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Ingår i: BMC Infectious Diseases. - : BioMed Central. - 1471-2334. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Confidence in any diagnostic and antimicrobial susceptibility testing data is provided by appropriate and regular quality assurance (QA) procedures. In Europe, the European Gonococcal Antimicrobial Susceptibility Programme (Euro-GASP) has been monitoring the antimicrobial susceptibility in Neisseria gonorrhoeae since 2004. Euro-GASP includes an external quality assessment (EQA) scheme as an essential component for a quality-assured laboratory-based surveillance programme. Participation in the EQA scheme enables any problems with the performed antimicrobial susceptibility testing to be identified and addressed, feeds into the curricula of laboratory training organised by the Euro-GASP network, and assesses the capacity of individual laboratories to detect emerging new, rare and increasing antimicrobial resistance phenotypes. Participant performance in the Euro-GASP EQA scheme over a 10 year period (2007 to 2016, no EQA in 2013) was evaluated.METHODS: Antimicrobial susceptibility category and MIC results from the first 5 years (2007-2011) of the Euro-GASP EQA were compared with the latter 5 years (2012-2016). These time periods were selected to assess the impact of the 2012 European Union case definitions for the reporting of antimicrobial susceptibility.RESULTS: dilutions of the modal MIC, respectively. The most common method used was Etest on GC agar base. There was a shift to using breakpoints published by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in the latter 5 years, however overall impact on the validity of results was limited, as the percentage categorical agreement and MIC concordance changed very little between the two five-year periods.CONCLUSIONS: The high level of comparability of results in this EQA scheme indicates that high quality data are produced by the Euro-GASP participants and gives confidence in susceptibility and resistance data generated by laboratories performing decentralised testing.
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| 3. |
- Ingberg, Edvin, 1988-, et al.
(författare)
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16S metagenomics for bacterial identification versus cultures in acute pharyngotonsillitis patients and controls
- 2018
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Konferensbidrag (refereegranskat)abstract
- Background: Sore throat/pharyngotonsillitis is a very common condition. While most cases are viral, the primary bacterial pathogen is group A beta-hemolytic streptococcus (Streptococcus pyogenes). Further, Fusobacterium necrophorum has over the last decade attracted attention. rnrnSequence-based techniques continue to gain ground in medical microbiology. To describe the microbiota in a sample, either the whole genomes (metagenomics) or marker genes/genomic regions (metataxonomics), such as the 16S rRNA gene, can be sequenced. Some studies have investigated how findings from these methods correspond to conventional microbiological methods for infectious diseases, such as cultures. However, no previous study has approached the condition acute pharyngotonsillitis this way.Methods: Throat samples from patients with acute sore throat (n=129) and controls (n=86), both groups aged 15-45, were collected. DNA was extracted and the V3-V4 regions of the 16S rRNA genes were amplified using PCR. After normalization based on fragment analysis, and size selection with Ampure beads and PCR against adapter sequences coupled to the V3-V4 fragments, clonal amplifiction was performed with isothermal PCR. Finally, sequencing was performed on the Ion Torrent S5 XL. The SILVA database was used for taxonomic classification and the results were compared to culture findings for S. pyogenes and F. necrophorum, using Mann Whitney U tests.Results: Among the 215 samples, 46 patients and 1 of the controls were culture-positive for S. pyogenes. For F. necrophorum, 20 patients and 3 controls were culture-positive. Seven of the samples were culture-positive for both S. pyogenes and F. necrophorum. rnrnIn the metataxonomic analysis, S. pyogenes were significantly more abundant among patients than controls (p=0.0046), and in samples culture-positive for S. pyogenes, compared to culture-negative (p<0.0001).The percent of reads representing F. necrophorum were significantly higher in patients compared to controls (p<0.001), as well as in culture-positive samples compared to culture-negative (p<0.0001). rnrnAlthough significant differences between culture-positive and culture-negative samples were seen, even among culture-positive samples the abundance of S. pyogenes or F. necrophorum were on average low (2,1% and 10,6%, respectively) and with large variation (0-49,8% and 0-76,1%, respectively).Conclusions: Findings from a metataxonomic 16S rRNA gene analysis differed regarding species of interest between groups based on symptoms of a sore throat or culture findings. However, the results were heterogeneous and difficult to interpret for a single sample.
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| 4. |
- Jacobsson, Susanne, 1974-, et al.
(författare)
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In Vitro Activity of the Novel Pleuromutilin Lefamulin (BC-3781) and Effect of Efflux Pump Inactivation on Multidrug-Resistant and Extensively Drug-Resistant Neisseria gonorrhoeae
- 2017
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Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 61:11
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated the activity of the novel semisynthetic pleuromutilin lefamulin, inhibiting protein synthesis and growth, and the effect of efflux pump inactivation on clinical gonococcal isolates and reference strains (n = 251), including numerous multidrug-resistant and extensively drug-resistant isolates. Lefamulin showed potent activity against all gonococcal isolates, and no significant cross-resistance to other antimicrobials was identified. Further studies of lefamulin are warranted, including in vitro selection and mechanisms of resistance, pharmacokinetics/pharmacodynamics, optimal dosing, and performance in randomized controlled trials.
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| 5. |
- Saarentausta, Katariina, et al.
(författare)
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Potential impact of the COVID-19 pandemic on the national and regional incidence, epidemiology and diagnostic testing of chlamydia and gonorrhoea in Sweden, 2020
- 2022
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Munksgaard Forlag. - 0903-4641 .- 1600-0463. ; 130:1, s. 34-42
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic has challenged the societies and health care systems globally, and resulted in many social and physical distancing restrictions to limit the spread of SARS-CoV-2. These restrictions have also likely affected the frequency of intimate contacts and the spread of sexually transmitted infections (STIs). Compared to most other countries, Sweden especially in Spring-Autumn 2020 pursued mainly milder voluntary, i.e. not mandatory enforced by laws, recommended restrictions and the impacts of these on society and spread of STIs remain largely unknown. We describe the potential impact of the COVID-19 pandemic on the national and regional incidence, epidemiology and diagnostic testing of chlamydia and gonorrhoea in Sweden in 2020. Compared to 2019, we found a significant decrease in incidence of chlamydia (-4.5%) and gonorrhoea (-17.5%), and in diagnostic testing (-10.5% for chlamydia, -9.4% for gonorrhoea) in 2020. However, the decrease in chlamydia incidence, which has mainly been decreasing last 10 years, was not significant when compared with the average incidence in 2017-2019. The largest decrease in national incidence of both infections was observed among young and heterosexual patients, however some Swedish regions showed an increased incidence, particularly of chlamydia. Increased "internet-based self-sampling" testing approach partly compensated for a decreased attendance at STI clinics. Studies, including sexual behavior, prevention, reasons for attending STI health care, STIs in different anatomical sites, and management of STIs, are required to elucidate the impact of COVID-19-associated social and physical distancing restrictions on sexual activity and the incidence and epidemiology of chlamydia and gonorrhoea in Sweden.
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| 6. |
- Säll, Olof, 1980-, et al.
(författare)
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Atypical presentation of Neisseria meningitidis serogroup W disease is associated with the introduction of the 2013 strain
- 2021
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Ingår i: Epidemiology and Infection. - : Cambridge University Press. - 0950-2688 .- 1469-4409. ; 149
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Tidskriftsartikel (refereegranskat)abstract
- Since 2015, the incidence of invasive meningococcal disease (IMD) caused by serogroup W (MenW) has increased in Sweden, due to the introduction of the 2013 strain belonging to clonal complex 11. The aim of this study was to describe the clinical presentation of MenW infections, in particular the 2013 strain, including genetic associations. Medical records of confirmed MenW IMD cases in Sweden during the years 1995-2019 (n = 113) were retrospectively reviewed and the clinical data analysed according to strain. Of all MenW patients, bacteraemia without the focus of infection was seen in 44%, bacteraemic pneumonia in 26%, meningitis in 13% and epiglottitis in 8%, gastrointestinal symptoms in 48% and 4% presented with petechiae. Phylogenetic analysis was used for possible links between genetic relationship and clinical picture. The 2013 strain infections, particularly in one cluster, were associated with more severe disease compared with other MenW infections. The patients with 2013 strain infections (n = 68) were older (52 years vs. 25 years for other strains), presented more often with diarrhoea as an atypical presentation (P = 0.045) and were more frequently admitted for intensive care (P = 0.032). There is a risk that the atypical clinical presentation of MenW infections, with predominantly gastrointestinal or respiratory symptoms rather than neck stiffness or petechiae, may lead to delay in life-saving treatment.
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| 7. |
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| 8. |
- Säll, Olof, 1980-, et al.
(författare)
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Prevalence and persistence of Neisseria meningitidis carriage in Swedish university students
- 2023
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Ingår i: Epidemiology and Infection. - : Cambridge University Press. - 0950-2688 .- 1469-4409. ; 151
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Tidskriftsartikel (refereegranskat)abstract
- The bacterium Neisseria meningitidis causes life-threatening disease worldwide, typically with a clinical presentation of sepsis or meningitis, but can be carried asymptomatically as part of the normal human oropharyngeal microbiota. The aim of this study was to examine N. meningitidis carriage with regard to prevalence, risk factors for carriage, distribution of meningococcal lineages and persistence of meningococcal carriage. Throat samples and data from a self-reported questionnaire were obtained from 2744 university students (median age: 23 years) at a university in Sweden on four occasions during a 12-month period. Meningococcal isolates were characterised using whole-genome sequencing. The carriage rate among the students was 9.1% (319/3488; 95% CI 8.2-10.1). Factors associated with higher carriage rate were age ≤22 years, previous tonsillectomy, cigarette smoking, drinking alcohol and attending parties, pubs and clubs. Female gender and sharing a household with children aged 0-9 years were associated with lower carriage. The most frequent genogroups were capsule null locus (cnl), group B and group Y and the most commonly identified clonal complexes (cc) were cc198 and cc23. Persistent carriage with the same meningococcal strain for 12 months was observed in two students. Follow-up times exceeding 12 months are recommended for future studies investigating long-term carriage of N. meningitidis.
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| 9. |
- Thulin Hedberg, Sara, et al.
(författare)
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Invasive meningococcal disease in Sweden 2016
- 2017
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Ingår i: 14th Congress of the EMGM, European Meningococcal and Haemophilus Disease Society. - Prague : The European Meningococcal and Haemophilus Disease Society EMGM. - 9788090666238 ; , s. 69-69
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Invasive meningococcal disease (IMD) is notifiable in Sweden. The reporting system comprises of mandatory notification of cases and mandatory laboratory notification of samples to the Public Health Agency of Sweden, Stockholm. All samples are sent to the National Reference Laboratory for Pathogenic Neisseria, Örebro for further typing and surveillance.In 2016, 62 cases of IMD (incidence 0.6/100 000 population) were reported in Sweden. Among the patients 58 % were females and 42 % males, aged from 1 month to95 years with mean age of 42 years. The incidence was highest, as in previous years, in the age group 15-19 years (2.1/100 000 population) followed by elderly ≥80 years (1.8/100 000 population) and infants ≤1 year (1.7/100 000 population). The case fatality rate increased in 2016 to 12.9 % compared with 7.5 % in 2015, eight people died from the disease (MenW, n=3; MenY, n=2; MenB, n=2 and MenC n=1). None of the IMD cases in 2016 had any epidemiological linkage.All 62 cases of IMD were laboratory confirmed: 54 were culture-confirmed, three PCR-confirmed and in five cases further typing data are missing because no samples were sent to the National Reference Laboratory for Pathogenic Neisseria. The serogroup distribution was MenW (n=18, 31.5 %), MenY (n=18, 31.5 %), MenB (n=10, 17.5 %), MenC (n=10, 17.5 %) and one non-groupable isolate. The W:P1.5,2:F1-1:ST11 (cc11) (n=15) were predominant among the culture-confirmed meningococci during 2016 followed by Y:P1.5-2,10-1:F4-1:ST23 (cc23) (n=7) och Y:P1.5-1,2-2:F5-8:ST23 (cc23) (n=6). Antibiotic susceptibility testing was performed with Gradient test (Etest, BioMerieux). Decreased susceptibility to penicillin was seen in 30 % of the isolates (MIC >0,064 mg/L) of which one was resistant (MIC=0.5 mg/L). One of the isolates with decreased susceptibility to penicillin was also resistant to ciprofloxacin (MIC=0.125 mg/L). All other isolates were susceptible to cefotaxime, chloramphenicol, ciprofloxacin, rifampicin and meropenem. No β-lactamase producing isolates has so far been found in Sweden.To conclude, the incidence of IMD continues to be relatively low in Sweden, however, a shift in the serogroup distribution of N. meningitidisin Sweden is ongoing; the previously dominating disease-causing MenB and MenC have been replaced, first by MenY which emerged in 2009 and since 2015 also by MenW. MenW has gone from only causing invasive disease in a few, 0-6 cases per year from 1990 onwards, to now being the dominating serogroup together with MenY in Sweden 2016.
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| 10. |
- Aniskevich, Aliaksandra, et al.
(författare)
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Antimicrobial resistance in Neisseria gonorrhoeae isolates and gonorrhoea treatment in the Republic of Belarus, Eastern Europe, 2009-2019
- 2021
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Ingår i: BMC Infectious Diseases. - : BioMed Central. - 1471-2334. ; 21:1
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Tidskriftsartikel (refereegranskat)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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| 11. |
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| 12. |
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| 13. |
- Asfaw Idosa, Berhane, PhD, 1977-, et al.
(författare)
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Neisseria meningitidis-Induced Caspase-1 Activation in Human Innate Immune Cells Is LOS-Dependent
- 2019
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Ingår i: Journal of Immunology Research. - : Hindawi Publishing Corporation. - 2314-8861 .- 2314-7156.
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Tidskriftsartikel (refereegranskat)abstract
- Meningococcal disease such as sepsis and meningitidis is hallmarked by an excessive inflammatory response. The causative agent, Neisseria meningitidis, expresses the endotoxin lipooligosaccharide (LOS) that is responsible for activation of immune cells and the release of proinflammatory cytokines. One of the most potent proinflammatory cytokines, interleukin-1 (IL-1), is activated following caspase-1 activity in the intracellular multiprotein complex called inflammasome. Inflammasomes are activated by a number of microbial factors as well as danger molecules by a two-step mechanismpriming and licensing of inflammasome activationbut there are no data available regarding a role for inflammasome activation in meningococcal disease. The aim of this study was to investigate if N. meningitidis activates the inflammasome and, if so, the role of bacterial LOS in this activation. Cells were subjected to N. meningitidis, both wild-type (FAM20) and its LOS-deficient mutant (lpxA), and priming as well as licensing of inflammasome activation was investigated. The wild-type LOS-expressing parental FAM20 serogroup C N. meningitidis (FAM20) strain significantly enhanced the caspase-1 activity in human neutrophils and monocytes, whereas lpxA was unable to induce caspase-1 activity as well as to induce IL-1 release. While the lpxA mutant induced a priming response, measured as increased expression of NLRP3 and IL1B, the LOS-expressing FAM20 further increased this priming. We conclude that although non-LOS components of N. meningitidis contribute to the priming of the inflammasome activity, LOS per se is to be considered as the central component of N. meningitidis virulence, responsible for both priming and licensing of inflammasome activation.
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| 14. |
- Berçot, Béatrice, et al.
(författare)
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Ceftriaxone-resistant, multidrug-resistant Neisseria gonorrhoeae with a novel mosaic penA-237.001 gene, France, June 2022
- 2022
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Ingår i: Eurosurveillance. - : European Centre for Disease Prevention and Control. - 1025-496X .- 1560-7917. ; 27:50, s. 17-22
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Tidskriftsartikel (refereegranskat)abstract
- We report a ceftriaxone-resistant, multidrug-resistant urogenital gonorrhoea case in a heterosexual woman in France, June 2022. The woman was successfully treated with azithromycin 2 g. She had unprotected sex with her regular partner, who developed urethritis following travel to Vietnam and Switzerland. Whole genome sequencing of the gonococcal isolate (F92) identified MLST ST1901, NG-STAR CC- 199, and the novel mosaic penA-237.001, which caused ceftriaxone resistance. penA-237.001 is 98.7% identical to penA-60.001, reported in various ceftriaxone-resistant strains, including the internationally spreading FC428 clone.
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| 15. |
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| 16. |
- Birhanu, Muluken, et al.
(författare)
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Antimicrobial susceptibility in Neisseria gonorrhoeae and epidemiological data of gonorrhoea patients in five cities across Ethiopia, 2021-22
- 2024
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Ingår i: JAC - Antimicrobial Resistance. - : Oxford University Press. - 2632-1823. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a global public health concern and enhanced global gonococcal AMR surveillance is imperative. As in many African countries, regular, representative and quality-assured gonococcal AMR is lacking in Ethiopia. We describe the AMR in gonococcal isolates from five cities across Ethiopia, 2021-22, and patient epidemiological data.METHODS: Urethral discharge from males and cervical discharge from females were collected from October 2021 to September 2022. Epidemiological data were collected using a questionnaire. MIC determination (ETEST; eight antimicrobials) was performed on gonococcal isolates and EUCAST breakpoints (v13.1) were used.RESULTS: From 1142 urogenital swab samples, 299 species-identified gonococcal isolates were identified; 78.3% were from males and 21.7% from females. The median age for males and females was 25 and 23 years, respectively. Most isolates (61.2%) were identified in Addis Ababa, followed by Gondar (11.4%), Adama (10.4%), Bahir Dar (10.0%) and Jimma (7.0%). The resistance level to ciprofloxacin, tetracycline and benzylpenicillin was 97.0%, 97.0% and 87.6%, respectively, and 87.6% of isolates were producing β-lactamase. All isolates were susceptible to ceftriaxone, cefixime, azithromycin and spectinomycin. Recommended therapy [ceftriaxone (250 mg) plus azithromycin (1 g)] was used for 84.2% of patients.CONCLUSIONS: We present the first national quality-assured gonococcal AMR data from Ethiopia. Resistance levels to ciprofloxacin, tetracycline and benzylpenicillin were exceedingly high. However, all isolates were susceptible to ceftriaxone, cefixime, azithromycin and spectinomycin. In Ethiopia, it is essential to strengthen the gonococcal AMR surveillance by including further epidemiological data, more isolates from different cities, and WGS.
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| 17. |
- Boiko, Iryna, et al.
(författare)
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Antimicrobial susceptibility of Neisseria gonorrhoeae isolates and treatment of gonorrhoea patients in Ternopil and Dnipropetrovsk regions of Ukraine, 2013-2018
- 2019
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : John Wiley & Sons. - 0903-4641 .- 1600-0463. ; 127:7, s. 503-509
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major public health concern globally. However, recent gonococcal AMR data from Eastern Europe are extremely limited and no AMR data for strains spreading in Ukraine have ever been internationally published. We investigated the AMR of N. gonorrhoeae isolates in two regions of Ukraine (Ternopil 2013-2018, Dnipropetrovsk 2013-2014), and, where information was available, the treatment administered to the corresponding gonorrhoea patients. Determination of minimum inhibitory concentration (MIC) of eight antimicrobials was performed using Etest and resistance breakpoints from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) were applied. Overall, 9.3% of the examined 150 isolates were resistant to ciprofloxacin, 6.0% to tetracycline, 2.0% to azithromycin, and 0.7% to benzylpenicillin. No isolates were resistant to ceftriaxone, cefixime, spectinomycin, or gentamicin. However, one (0.7%) isolate showed a MIC value of 0.125 mg/L for both ceftriaxone and cefixime, i.e., bordering resistance. Eighty-eight (67.2%) of 131 patients were administered dual therapy (ceftriaxone 1 g plus doxycycline/clarithromycin/azithromycin/ofloxacin) and 22 (16.8%) ceftriaxone 1 g monotherapy. Worryingly, 21 (16.0%) patients received monotherapy with clarithromycin/doxycycline/azithromycin/ofloxacin/benzylpenicillin. In conclusion, the antimicrobial susceptibility of gonococcal strains spreading in Ternopil and Dnipropetrovsk, Ukraine during 2013-2018 was high. Low levels of resistance to ciprofloxacin, tetracycline, azithromycin, and benzylpenicillin were found, but no resistance to the internationally recommended ceftriaxone, cefixime, or spectinomycin. Ceftriaxone 1 g should remain as empiric first-line treatment, in dual therapy with azithromycin or doxycycline or in monotherapy. Continued and expanded gonococcal AMR surveillance in Ukraine is essential to monitor the susceptibility to particularly extended-spectrum cephalosporins, azithromycin and doxycycline.
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| 18. |
- Boiko, Iryna, et al.
(författare)
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Genomic epidemiology and antimicrobial resistance determinants of Neisseria gonorrhoeae isolates from Ukraine, 2013-2018
- 2020
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley-Blackwell. - 0903-4641 .- 1600-0463. ; 128:7, s. 465-475
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major health threat compromising the gonorrhoea treatment globally. AMR surveillance including whole genome sequencing (WGS)-based epidemiology provides ideal resolution to identify and describe AMR gonococcal clones, AMR determinants and populations, which can inform management guidelines and antimicrobial stewardship policies. Our aims were to, for the first time, elucidate the WGS-based epidemiology and characterise AMR determinants of gonococcal strains spreading in Ukraine, 2013-2018. Gonococcal isolates (n=150) from Ternopil and Dnipro, Ukraine (2013-2018) were subjected to AMR testing (Etest) for eight antimicrobials and WGS. Overall, 11.3% of isolates were resistant to ciprofloxacin, 6.0% to tetracycline and 0.7% to benzylpenicillin. No isolates were resistant to azithromycin, spectinomycin, ceftriaxone, or cefixime, but one isolate was bordering resistance to both cephalosporins. Twenty-five MLST STs, 50 NG-MAST STs, and 34 NG-STAR types were identified. The phylogenomic analysis revealed six main clusters, mostly associated with the internationally described multidrug-susceptible gonococcal lineage. Resistance to ciprofloxacin was associated with GyrA S91F and ParC S87R mutations; tetracyclines with rpsJ V57M and tetM; penicillins with mosaic penA-34.001 and β-lactamase; mtrR; PorB1b G101D, and PBP1 L421P mutations. One isolate of the multidrug-resistant NG-MAST ST1407, MLST ST1901 was found, which was bordering resistance to ceftriaxone and cefixime. The susceptibility of gonococcal strains spreading in Ternopil and Dnipro, Ukraine, 2013-2018 was surprisingly high. Continued and expanded gonococcal AMR surveillance, ideally including WGS, in Ukraine is essential. This could inform action plans and public health policies to control the spread of AMR gonococcal strains in Ukraine.
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| 19. |
- Brehony, Carina, et al.
(författare)
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Implications of Differential Age Distribution of Disease-Associated Meningococcal Lineages for Vaccine Development
- 2014
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Ingår i: Clinical and Vaccine Immunology. - : American Society for Microbiology. - 1556-6811 .- 1556-679X. ; 21:6, s. 847-853
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Tidskriftsartikel (refereegranskat)abstract
- New vaccines targeting meningococci expressing serogroup B polysaccharide have been developed, with some being licensed in Europe. Coverage depends on the distribution of disease-associated genotypes, which may vary by age. It is well established that a small number of hyperinvasive lineages account for most disease, and these lineages are associated with particular antigens, including vaccine candidates. A collection of 4,048 representative meningococcal disease isolates from 18 European countries, collected over a 3-year period, were characterized by multilocus sequence typing (MLST). Age data were available for 3,147 isolates. The proportions of hyperinvasive lineages, identified as particular clonal complexes (ccs) by MLST, differed among age groups. Subjects <1 year of age experienced lower risk of sequence type 11 (ST-11) cc, ST-32 cc, and ST-269 cc disease and higher risk of disease due to unassigned STs, 1- to 4-year-olds experienced lower risk of ST-11 cc and ST-32 cc disease, 5- to 14-year-olds were less likely to experience ST-11 cc and ST-269 cc disease, and >= 25-year-olds were more likely to experience disease due to less common ccs and unassigned STs. Younger and older subjects were vulnerable to a more diverse set of genotypes, indicating the more clonal nature of genotypes affecting adolescents and young adults. Knowledge of temporal and spatial diversity and the dynamics of meningococcal populations is essential for disease control by vaccines, as coverage is lineage specific. The nonrandom age distribution of hyperinvasive lineages has consequences for the design and implementation of vaccines, as different variants, or perhaps targets, may be required for different age groups.
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| 20. |
- Broeker, Michael, et al.
(författare)
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Meningococcal serogroup Y emergence in Europe High importance in some European regions in 2012
- 2014
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Ingår i: Human Vaccines & Immunotherapeutics. - : Landes Bioscience. - 2164-5515 .- 2164-554X. ; 10:6, s. 1725-1728
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Tidskriftsartikel (refereegranskat)abstract
- Neisseria meningitidis is differentiated into 12 distinct serogroups, of which A, B, C, W, X, and Y are medically most important and represent an important health problem in different parts of the world. The epidemiology of N. meningitidis is unpredictable over time and across geographic regions. Recent epidemiological surveillance has indicated an increase of serogroup Y invasive meningococcal disease in some parts of Europe as shown in the epidemiological data for 2010 and 2011 from various European countries previously published in this journal. 1,2 Here, data from 33 European countries is reported indicating that the emergence of serogroup Y continued in 2012 in various regions of Europe, especially in Scandinavia, while in Eastern and South-Eastern Europe the importance of serogroup Y remained low.
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| 21. |
- Cole, Michelle J., et al.
(författare)
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Is the tide turning again for cephalosporin resistance in Neisseria gonorrhoeae in Europe? : Results from the 2013 European surveillance
- 2015
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Ingår i: BMC Infectious Diseases. - London, United Kingdom : BioMed Central. - 1471-2334. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: The emerging resistance to the extended-spectrum cephalosporins (ESCs) in Neisseria gonorrhoeae together with increasing incidence of gonorrhoea cases in many countries have been global public health concerns. However, in recent years the levels of ESC resistance have decreased in several regions worldwide. We describe the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) data from 2013, and compare them to corresponding data from 2009-2012.Methods: During 2013, N. gonorrhoeae isolates from 21 participating countries were examined. Antimicrobial susceptibility testing (Etest or agar dilution) was performed for cefixime, ceftriaxone, ciprofloxacin, azithromycin, spectinomycin and gentamicin. Statistical analyses were performed to identify significant changes in resistance between years and to investigate associations between patients with resistant gonococcal isolates and collected epidemiological variables.Results: In total, 93 (4.7 %) of 1994 isolates displayed resistance to cefixime, representing an increase compared to the 3.9 % detected in 2012 (p = 0.23). Cefixime resistance was detected in 13 (61.9 %) of the 21 countries. Cefixime resistance among men who have sex with men was only 1.2 %, compared to 5.6 % and 6.1 % in females and male heterosexuals, respectively. The univariate analysis confirmed that isolates resistant to cefixime were more likely to be from females (OR 4.87, p < 0.01) or male heterosexuals (OR 5.32, p < 0.01). Seven (0.4 %) isolates displayed ceftriaxone resistance (in addition to cefixime resistance) compared to three and 10 isolates in 2012 and 2011, respectively. All 93 isolates with cefixime resistance were additionally resistant to ciprofloxacin and 16 (17.2 %) were also resistant to azithromycin. Among all tested isolates (n = 1994), the ciprofloxacin resistance level (52.9 %) was higher than in 2012 (50.1 %; p = 0.08), and azithromycin resistance (5.4 %) increased since 2012 (4.5 %; p = 0.16).Conclusions: In 2013, the ESC resistance was again slightly increasing in Europe. This emphasises the importance of implementing the actions outlined in the European and additional response plans, particularly activities strengthening the surveillance of antimicrobial resistance. Ceftriaxone combined with azithromycin remains a satisfactory option for the first-line treatment of gonorrhoea. However novel antimicrobials (new derivatives of previously developed antimicrobials or newly developed antimicrobials) for effective monotherapy or at least inclusion in new dual antimicrobial therapy regimens (combined with previously developed antimicrobials or novel antimicrobials) will likely be required.
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| 22. |
- Cole, Michelle J., et al.
(författare)
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Overall Low Extended-Spectrum Cephalosporin Resistance but high Azithromycin Resistance in Neisseria gonorrhoeae in 24 European Countries, 2015
- 2017
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Ingår i: BMC Infectious Diseases. - : BioMed Central. - 1471-2334. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: Surveillance 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.Methods: Antimicrobial 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).Results: In 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 (similar to 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).Conclusions: The 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.
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| 23. |
- Cole, Michelle J., et al.
(författare)
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The European response to control and manage multi- and extensively drug-resistant Neisseria gonorrhoeae
- 2022
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Ingår i: Eurosurveillance. - : European Centre for Disease Prevention and Control. - 1025-496X .- 1560-7917. ; 27:18, s. 37-43
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Tidskriftsartikel (refereegranskat)abstract
- Because cefixime and ceftriaxone resistance in Neisseria gonorrhoeae and gonorrhoea treatment failures were increasing, a response plan to control and manage multidrug-resistant N. gonorrhoeae (MDR-NG) in Europe was published in 2012. The three main areas of the plan were to: (i) strengthen surveillance of antimicrobial resistance (AMR), (ii) implement monitoring of treatment failures and (iii) establish a communication strategy to increase awareness and disseminate AMR results. Since 2012, several additional extensively drug-resistant N. gonorrhoeae (XDR-NG) strains have emerged, and strains with high-level ceftriaxone resistance spread internationally. This prompted an evaluation and review of the 2012 European Centre for Disease Prevention and Control (ECDC) response plan, revealing an overall improvement in many aspects of monitoring AMR in N. gonorrhoeae; however, treatment failure monitoring was a weakness. Accordingly, the plan was updated in 2019 to further support European Union/European Economic Area (EU/EEA) countries in controlling and managing the threat of MDR/XDR-NG in Europe through further strengthening of AMR surveillance and clinical management including treatment failure monitoring. The plan will be assessed biennially to ensure its effectiveness and its value. Along with prevention, diagnostic, treatment and epidemiological surveillance strategies, AMR surveillance is essential for effective control of gonorrhoea.
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| 24. |
- David, Alexandra, et al.
(författare)
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In silico gepotidacin target mining among 33 213 global Neisseria gonorrhoeae genomes from 1928 to 2023 combined with gepotidacin MIC testing of 22 gonococcal isolates with different GyrA and ParC substitutions
- 2024
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press. - 0305-7453 .- 1460-2091.
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The novel dual-target triazaacenaphthylene, gepotidacin, recently showed promising results in its Phase III randomized controlled trial for the treatment of gonorrhoea. We investigated alterations in the gepotidacin GyrA and ParC targets in gonococci by in silico mining of publicly available global genomes (n = 33 213) and determined gepotidacin MICs in isolates with GyrA A92 alterations combined with other GyrA and/or ParC alterations.Methods: We examined gonococcal gyrA and parC alleles available at the European Nucleotide Archive. MICs were determined using the agar dilution method (gepotidacin) or Etest (four antimicrobials). Models of DNA gyrase and topoisomerase IV were obtained from AlphaFold and used to model gepotidacin in the binding site.Results: GyrA A92 alterations were identified in 0.24% of genomes: GyrA A92P/S/V + S91F + D95Y/A/N (0.208%), A92P + S91F (0.024%) and A92P (0.003%), but no A92T (previously associated with gepotidacin resistance) was found. ParC D86 alterations were found in 10.6% of genomes: ParC D86N/G (10.5%), D86N + S87I (0.051%), D86N + S88P (0.012%) and D86G + E91G (0.003%). One isolate had GyrA A92P + ParC D86N alterations, but remained susceptible to gepotidacin (MIC = 0.125 mg/L). No GyrA plus ParC alterations resulted in a gepotidacin MIC > 4 mg/L. Modelling of gepotidacin binding to GyrA A92/A92T/A92P suggested that gepotidacin resistance due to GyrA A92T might be linked to the formation of a new polar contact with DNA.Conclusions: In silico mining of 33 213 global gonococcal genomes (isolates from 1928 to 2023) showed that A92 is highly conserved in GyrA, while alterations in D86 of ParC are common. No GyrA plus ParC alterations caused gepotidacin resistance. MIC determination and genomic surveillance of potential antimicrobial resistance determinants are imperative.
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| 25. |
- Day, Michaela J., et al.
(författare)
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Significant increase in azithromycin "resistance" and susceptibility to ceftriaxone and cefixime in Neisseria gonorrhoeae isolates in 26 European countries, 2019
- 2022
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Ingår i: BMC Infectious Diseases. - : BioMed Central. - 1471-2334. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The 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 2019 (26 countries), linked to patient epidemiological data, and compared with data from previous years.METHODS: Agar dilution and minimum inhibitory concentration (MIC) gradient strip methodologies were used to determine the antimicrobial susceptibility (using EUCAST clinical breakpoints, where available) of 3239 N. gonorrhoeae isolates from 26 countries across the EU/EEA. Significance of differences compared with Euro-GASP results in previous years was analysed using Z-test and the Pearson's χ2 test was used to assess significance of odds ratios for associations between patient epidemiological data and antimicrobial resistance.RESULTS: European N. gonorrhoeae isolates collected between 2016 and 2019 displayed shifting MIC distributions for; ceftriaxone, with highly susceptible isolates increasing over time and occasional resistant isolates each year; cefixime, with highly-susceptible isolates becoming increasingly common; azithromycin, with a shift away from lower MICs towards higher MICs above the EUCAST epidemiological cut-off (ECOFF); and ciprofloxacin which is displaying a similar shift in MICs as observed for azithromycin. In 2019, two isolates displayed ceftriaxone resistance, but both isolates had MICs below the azithromycin ECOFF. Cefixime resistance (0.8%) was associated with patient sex, with resistance higher in females compared with male heterosexuals and men-who-have-sex-with-men (MSM). The number of countries reporting isolates with azithromycin MICs above the ECOFF increased from 76.9% (20/26) in 2016 to 92.3% (24/26) in 2019. Isolates with azithromycin MICs above the ECOFF (9.0%) were associated with pharyngeal infection sites. Following multivariable analysis, ciprofloxacin resistance remained associated with isolates from MSM and heterosexual males compared with females, the absence of a concurrent chlamydial infection, pharyngeal infection sites and patients ≥ 25 years of age.CONCLUSIONS: Resistance to ceftriaxone and cefixime remained uncommon in EU/EEA countries in 2019 with a significant decrease in cefixime resistance observed between 2016 and 2019. The significant increase in azithromycin "resistance" (azithromycin MICs above the ECOFF) threatens the effectiveness of the dual therapy (ceftriaxone + azithromycin), i.e., for ceftriaxone-resistant cases, currently recommended in many countries internationally and requires close monitoring.
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