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"Amato-Gauci, Andrew J."
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Overall Low Extended-Spectrum Cephalosporin Resistance but high Azithromycin Resistance in Neisseria gonorrhoeae in 24 European Countries, 2015
2017
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 (~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.
Journal Article
European enhanced surveillance of invasive pneumococcal disease in 2010: Data from 26 European countries in the post-heptavalent conjugate vaccine era
2014
•We analyse data from the first European IPD enhanced surveillance in the post-PCV7 era.•In 2010 IPD notification rates were highest among children <1 and adults ≥65 years.•The most common serotypes were 19A, 1, 7F, 3, 14, 22F, 8, 4, 12F and 19F.•Non-susceptibility to erythromycin was highest at 17.6% followed by penicillin at 8.9%.•In children <5 years PCV7 serotype coverage was 19.2%, PCV10 46.1% and PCV13 73.1%.
Streptococcus pneumoniae is a leading cause of severe infectious diseases worldwide. This paper presents the results from the first European invasive pneumococcal disease (IPD) enhanced surveillance where additional and valuable data were reported and analysed. Following its authorisation in Europe in 2001 for use in children aged between two months and five years, the heptavalent pneumococcal conjugate vaccine (PCV7) was progressively introduced in the European Union (EU)/European Economic Area (EEA) countries, albeit with different schemes and policies. In mid-2010 European countries started to switch to a higher valency vaccine (PCV10/PCV13), still without a significant impact by the time of this surveillance. Therefore, this surveillance provides an overview of baseline data from the transition period between the introduction of PCV7 and the implementation of PCV10/PCV13.
In 2010, 26 EU/EEA countries reported 21 565 cases of IPD to The European Surveillance System (TESSy) applying the EU 2008 case definition. Serotype was determined in 9946/21565 (46.1%) cases. The most common serotypes were 19A, 1, 7F, 3, 14, 22F, 8, 4, 12F and 19F, accounting for 5949/9946 (59.8%) of the serotyped isolates. Data on antimicrobial susceptibility testing (AST) in the form of minimum inhibitory concentrations (MIC) were submitted for penicillin 5384/21565 (25.0%), erythromycin 4031/21565 (18.7%) and cefotaxime 5252/21565 (24.4%). Non-susceptibility to erythromycin was highest at 17.6% followed by penicillin at 8.9%.
PCV7 serotype coverage among children <5 years in Europe, was 19.2%; for the same age group, the serotype coverage for PCV10 and PCV13 were 46.1% and 73.1%, respectively.
In the era of pneumococcal conjugate vaccines, the monitoring of changing trends in antimicrobial resistance and serotype distribution are essential in assessing the impact of vaccines and antibiotic use control programmes across European countries.
Journal Article
Substantial underdiagnosis of lymphogranuloma venereum in men who have sex with men in Europe: preliminary findings from a multicentre surveillance pilot
by
Pitt, Rachel
,
Pöcher, Katharina
,
Zidovec Lepej, Snjezana
in
anogenital conditions
,
Chlamydia
,
Clinics
2020
ObjectivesUnderstanding the public health impact of lymphogranuloma venereum (LGV) in Europe is hampered by inadequate diagnostics and surveillance systems in many European countries. We developed and piloted LGV surveillance in three European countries without existing systems and performed a preliminary investigation of LGV epidemiology, where little evidence currently exists.MethodsWe recruited STI or dermatovenereology clinics and associated laboratories serving men who have sex with men (MSM) in Austria, Croatia and Slovenia, using the UK for comparison. We undertook centralised LGV testing of Chlamydia trachomatis (CT)-positive rectal swabs collected between October 2016 and May 2017 from MSM attending these clinics. Stored specimens from Austria (2015–2016) and Croatia (2014) were also tested. Clinical and sociodemographic data were collected using a standardised proforma. The ompA gene of LGV-positive specimens was sequenced.ResultsIn total, 500 specimens from CT-positive MSM were tested, and LGV positivity was 25.6% (128/500; 95% CI 22.0% to 29.6%) overall, and 47.6% (79/166; 40.1% to 55.2%) in Austria, 20.0% (3/15; 7.1% to 45.2%) in Croatia, 16.7% (1/6; 3.0% to 56.4%) in Slovenia and 14.4% (45/313; 10.9% to 18.7 %) in the UK. Proformas were completed for cases in Croatia, Slovenia and in the UK; proformas could not be completed for Austrian cases, but limited data were available from line listings. Where recorded, 83.9% (78/93) of LGV-CT cases were HIV-positive compared with 65.4% (149/228) of non-LGV-CT cases; MSM with LGV-CT were more likely to have proctitis (Austria, 91.8% vs 40.5%, p<0.001; Croatia, 100% vs 25%, p=0.04; UK, 52.4% vs 11.7%, p<0.001) than those with non-LGV-CT. Six different ompA sequences were identified, including three new variants; the L2 ompA sequence predominated (58.6%, 51/87).ConclusionsLGV is substantially underdiagnosed in MSM across Europe. Unified efforts are needed to overcome barriers to testing, establish effective surveillance, and optimise diagnosis, treatment and prevention.
Journal Article
A systematic review of post-migration acquisition of HIV among migrants from countries with generalised HIV epidemics living in Europe: mplications for effectively managing HIV prevention programmes and policy
by
Woode-Owusu, Melvina
,
Burns, Fiona M.
,
Pharris, Anastasia
in
Acquired immune deficiency syndrome
,
Adult
,
Africa, Northern
2015
Background
Migrant populations from countries with generalised HIV epidemics make up a significant proportion of all HIV/AIDS cases in many European Union and European Economic Area (EU/EEA) countries, with heterosexual transmission the predominant mode of HIV acquisition. While most of these infections are diagnosed for the first time in Europe, acquisition is believed to have predominantly occurred in the home country. A proportion of HIV transmission is believed to be occurring post-migration, and many countries may underestimate the degree to which this is occurring. Our objectives were to review the literature estimating the proportion of migrants believed to have acquired their HIV post-migration and examine which EU member states are able to provide estimates of probable country of HIV acquisition through current surveillance systems.
Methods
A systematic review was undertaken to gather evidence of sexual transmission of HIV within Europe among populations from countries with a generalised epidemic. In addition, national surveillance focal points from 30 EU/EEA Member States were asked to complete a questionnaire about surveillance methods and monitoring of the likely place of HIV acquisition among migrants.
Results & discussion
Twenty-seven papers from seven countries were included in the review and 24 countries responded to the survey. Estimates of HIV acquisition post-migration ranged from as low as 2 % among sub Saharan Africans in Switzerland, to 62 % among black Caribbean men who have sex with men (MSM) in the UK. Surveillance methods for monitoring post-migration acquisition varied across the region; a range of methods are used to estimate country or region of HIV acquisition, including behavioural and clinical markers. There is little published evidence addressing this issue, although Member States highlight the importance of migrant populations in their epidemics.
Conclusions
There is post-migration HIV acquisition among migrants in European countries but this is difficult to quantify accurately with current data. Migrant MSM appear at particular risk of HIV acquisition post-migration. Countries that identify migrants as an important part of their HIV epidemic should focus on using an objective method for assigning probable country of HIV acquisition. Robust methods to measure HIV incidence should be considered in order to inform national prevention programming and resource allocation.
Journal Article
Significant increase in azithromycin “resistance” and susceptibility to ceftriaxone and cefixime in Neisseria gonorrhoeae isolates in 26 European countries, 2019
by
Kulishev, Carina
,
Blumel, Benjamin
,
Cole, Michelle J.
in
Antibiotics
,
Antimicrobial agents
,
Antimicrobial resistance
2022
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.
Journal Article
Stably high azithromycin resistance and decreasing ceftriaxone susceptibility in Neisseria gonorrhoeae in 25 European countries, 2016
2018
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 2016 (25 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 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.
Results
No 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.
Conclusions
Overall 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.
Journal Article
The European gonococcal antimicrobial surveillance programme (Euro-GASP) appropriately reflects the antimicrobial resistance situation for Neisseria gonorrhoeae in the European Union/European Economic Area
by
Cole, Michelle J.
,
Unemo, Magnus
,
Spiteri, Gianfranco
in
Anti-Bacterial Agents - pharmacology
,
Anti-Bacterial Agents - therapeutic use
,
Antiinfectives and antibacterials
2019
Background
European 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).
Methods
We 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.
Results
There 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.
Conclusions
The 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.
Journal Article
Risk Factors for Antimicrobial-Resistant Neisseria gonorrhoeae in Europe
by
Cole, Michelle J.
,
Hoffmann, Steen
,
Unemo, Magnus
in
Adult
,
Anti-Infective Agents - administration & dosage
,
Anti-Infective Agents - pharmacology
2014
The European Gonococcal Antimicrobial Surveillance Programme performs antimicrobial resistance surveillance and is coordinated by the European Centre for Disease Prevention and Control. This study used epidemiological and behavioral data combined with the gonococcal susceptibility profiles to determine risk factors associated with harboring resistant gonococci in Europe.
From 2009 to 2011, gonococcal isolates from 21 countries were submitted to the European Gonococcal Antimicrobial Surveillance Programme for antimicrobial susceptibility testing. Patient variables associated with resistance to azithromycin, cefixime, and ciprofloxacin were identified using univariate and multivariable logistic regression analyses of odds ratios. Geometric means for ceftriaxone and cefixime minimum inhibitory concentrations (MICs) were compared for patients of different sexual orientation and sex.
A total of 5034 gonococcal isolates were tested from 2009 to 2011. Isolates exhibiting resistance to cefixime (MIC > 0.125 mg/L) and ciprofloxacin (MIC > 0.5 mg/L) were significantly associated with infection in heterosexuals (males only for ciprofloxacin), older patients (>25 years of age), or those without a concurrent chlamydial infection in the multivariable analysis. The geometric mean of cefixime and ceftriaxone MICs decreased from 2009 to 2011, most significantly for men who have sex with men, and isolates from male heterosexuals exhibited the highest MICs in 2011.
The linking of epidemiological and behavioral data to the susceptibility profiles of the gonococcal isolates has allowed those at higher risk for acquiring antimicrobial resistant Neisseria gonorrhoeae to be identified. Improved data numbers and representativeness are required before evidence-based risk groups can be identified, and subsequent focused treatments or public health intervention strategies can be initiated with confidence.
Journal Article
A Method to Estimate the Size and Characteristics of HIV-positive Populations Using an Individual-based Stochastic Simulation Model
by
Campbell, Colin
,
van Sighem, Ard
,
Phillips, Andrew
in
Bayes Theorem
,
Bisexuality
,
Computer Simulation
2016
It is important not only to collect epidemiologic data on HIV but to also fully utilize such information to understand the epidemic over time and to help inform and monitor the impact of policies and interventions. We describe and apply a novel method to estimate the size and characteristics of HIV-positive populations. The method was applied to data on men who have sex with men living in the UK and to a pseudo dataset to assess performance for different data availability. The individual-based simulation model was calibrated using an approximate Bayesian computation-based approach. In 2013, 48,310 (90% plausibility range: 39,900–45,560) men who have sex with men were estimated to be living with HIV in the UK, of whom 10,400 (6,160–17,350) were undiagnosed. There were an estimated 3,210 (1,730–5,350) infections per year on average between 2010 and 2013. Sixty-two percent of the total HIV-positive population are thought to have viral load <500 copies/ml. In the pseudo-epidemic example, HIV estimates have narrower plausibility ranges and are closer to the true number, the greater the data availability to calibrate the model. We demonstrate that our method can be applied to settings with less data, however plausibility ranges for estimates will be wider to reflect greater uncertainty of the data used to fit the model.
Journal Article