Significant increase in azithromycin “resistance” and susceptibility to ceftriaxone and cefixime in Neisseria gonorrhoeae isolates in 26 European countries, 2019

Euro-GASP network: Claudia Eder, Sonja Pleininger, Steliana Huhlescu, Irith de Baetselier, Blaženka Hunjak, Tatjana Nemeth Blažić, Panagiota Maikanti-Charalampous, Despo Pieridou, Hana Zákoucká, Helena Žemličková, Steen Hoffmann, Susan Cowan, Rita Peetso, Jelena Viktorova, Ndeindo Ndeikoundam, Beatrice Bercot, Anu Patari Sampo, Vesa Kirjavainen, Susanne Buder, Klaus Jansen, Vivi Miriagou, Eszter Balla, Mária Dudás, Guðrún Sigmundsdóttir, Lena Ros Asmundsdottir, Sinead Saab, Brendan Crowley, Anna Carannante, Paola Stefanelli, Gatis Pakarna, Violeta Mavcutko, Robert Cassar, Christopher Barbara, Francesca Vella, Alje Van Dam, Ineke Linde, Dominique Caugant, Hilde Kløvstad, Beata Mlynarczyk-Bonikowska, Maria-José Borrego, Peter Pavlik, Irena Klavs, Tanja Kustec, Julio Vazquez, Asuncion Diaz, Raquel Abad Torreblanca, Inga Velicko, Magnus Unemo, Helen Fifer, Kate TempletonBackground: 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.The study was funded by the European Centre for Disease Prevention and Control (Framework Contract No. ECDC/2017/004).info:eu-repo/semantics/publishedVersio

Cannabinoids in oral fluid following passive exposure to marijuana smoke

The concentration of tetrahydrocannabinol (THC) and its main metabolite 11-nor-Delta(9)-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) as well as cannabinol (CBN), and cannabidiol (CBD) were measured in oral fluid following realistic exposure to marijuana in a Dutch coffee-shop. Ten healthy subjects, who were not marijuana smokers, volunteered to spend 3 h in two different coffee shops in Groningen, The Netherlands. Subjects gave two oral fluid specimens at each time point: before entering the store, after 20 min, 40 min, 1 h, 2 h, and 3 h of exposure. The specimens were collected outside the shop. Volunteers left the shop completely after 3 h and also provided specimens approximately 12-22 h after beginning the exposure. The oral fluid specimens were subjected to immunoassay screening; confirmation for THC, cannabinol and cannabidiol using GC/MS; and THC-COOH using two-dimensional GC-GC/MS. THC was detectable in all oral fluid specimens taken 3 h after exposure to smoke from recreationally used marijuana. In 50% of the volunteers, the concentration at the 3 h time-point exceeded 4 ng/mL of THC, which is the current recommended cut-off concentration for immunoassay screening; the concentration of THC in 70% of the oral fluid specimens exceeded 2 ng/mL, currently proposed as the confirmatory cut-off concentration. THC-COOH was not detected in any specimens from passively exposed individuals. Therefore it is recommended that in order to avoid false positive oral fluid results assigned to marijuana use, by analyzing for only THC, the metabolite THC-COOH should also be monitored. (C) 2011 Elsevier Ireland Ltd. All rights reserved

Seropositivity to Nucleoprotein to detect mild and asymptomatic SARS-CoV-2 infections: A complementary tool to detect breakthrough infections after COVID-19 vaccination?

Background: With COVID-19 vaccine roll-out ongoing in many countries globally, monitoring of breakthrough infections is of great importance. Antibodies persist in the blood after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Since COVID-19 vaccines induce immune response to the Spike protein of the virus, which is the main serosurveillance target to date, alternative targets should be explored to distinguish infection from vaccination. Methods: Multiplex immunoassay data from 1,513 SARS-CoV-2 RT-qPCR-tested individuals (352 positive and 1,161 negative) without COVID-19 vaccination history were used to determine the accuracy of Nucleoprotein-specific immunoglobulin G (IgG) in detecting past SARS-CoV-2 infection. We also described Spike S1 and Nucleoprotein-specific IgG responses in 230 COVID-19 vaccinated individuals (Pfizer/BioNTech). Results: The sensitivity of Nucleoprotein seropositivity was 85% (95% confidence interval: 80–90%) for mild COVID-19 in the first two months following symptom onset. Sensitivity was lower in asymptomatic individuals (67%, 50–81%). Participants who had experienced a SARS-CoV-2 infection up to 11 months preceding vaccination, as assessed by Spike S1 seropositivity or RT-qPCR, produced 2.7-fold higher median levels of IgG to Spike S1 ≥ 14 days after the first dose as compared to those unexposed to SARS-CoV-2 at ≥ 7 days after the second dose (p = 0.011). Nucleoprotein-specific IgG concentrations were not affected by vaccination in infection-naïve participants. Conclusions: Serological responses to Nucleoprotein may prove helpful in identifying SARS-CoV-2 infections after vaccination. Furthermore, it can help interpret IgG to Spike S1 after COVID-19 vaccination as particularly high responses shortly after vaccination could be explained by prior exposure history

Primary care for patients with respiratory tract infection before and early on in the COVID-19 pandemic : an observational study in 16 European countries

Objective To describe primary health care (consultation characteristics and management) for patients contacting their general practitioner (GP) with a respiratory tract infection (RTI) early on in the COVID-19 pandemic in contrasting European countries, with comparison to prepandemic findings.Setting Primary care in 16 countries (79 practices), when no routine SARS-CoV-2 testing was generally available.Design and participants Before (n=4376) and early in the pandemic (n=3301), patients with RTI symptoms were registered in this prospective audit study.Outcome measures Consultation characteristics (type of contact and use of PPE) and management characteristics (clinical assessments, diagnostic testing, prescribing, advice and referral) were registered. Differences in these characteristics between countries and between pandemic and prepandemic care are described.Results Care for patients with RTIs rapidly switched to telephone/video consultations (10% in Armenia, 91% in Denmark), and when consultations were face-to-face, GPs used PPE during 97% (95% CI 96% to 98%) of contacts. Laboratory testing for SARS-CoV-2 in primary care patients with RTIs was rapidly implemented in Denmark (59%) and Germany (31%), while overall testing for C reactive protein decreased. The proportion of patients prescribed antibiotics varied considerably between countries (3% in Belgium, 48% in UK) and was lower during the pandemic compared with the months before, except for Greece, Poland and UK. GPs provided frequent and varied COVID-related advice and more frequently scheduled a follow-up contact (50%, 95% CI 48% to 52%). GPs reported a slightly higher degree of confidence in the likely effectiveness of their management in face-to-face (73% (very) confident, 95% CI 71% to 76%) than in virtual consultations (69%, 95% CI 67% to 71%).Conclusions Despite between-country variation in consultation characteristics, access to SARS-CoV-2 laboratory testing and medication prescribing, GPs reported a high degree of confidence in managing their patients with RTIs in the emerging pandemic. Insight in the highly variable pandemic responses, as measured in this multicountry audit, can aid in fine-tuning national action and in coordinating a pan-European response during future pandemic threats

Primary care for patients with respiratory tract infection before and early on in the COVID-19 pandemic: an observational study in 16 European countries

Objective To describe primary health care (consultation characteristics and management) for patients contacting their general practitioner (GP) with a respiratory tract infection (RTI) early on in the COVID-19 pandemic in contrasting European countries, with comparison to prepandemic findings. Setting Primary care in 16 countries (79 practices), when no routine SARS-CoV-2 testing was generally available. Design and participants Before (n=4376) and early in the pandemic (n=3301), patients with RTI symptoms were registered in this prospective audit study. Outcome measures Consultation characteristics (type of contact and use of PPE) and management characteristics (clinical assessments, diagnostic testing, prescribing, advice and referral) were registered. Differences in these characteristics between countries and between pandemic and prepandemic care are described. Results Care for patients with RTIs rapidly switched to telephone/video consultations (10% in Armenia, 91% in Denmark), and when consultations were face-to-face, GPs used PPE during 97% (95% CI 96% to 98%) of contacts. Laboratory testing for SARS-CoV-2 in primary care patients with RTIs was rapidly implemented in Denmark (59%) and Germany (31%), while overall testing for C reactive protein decreased. The proportion of patients prescribed antibiotics varied considerably between countries (3% in Belgium, 48% in UK) and was lower during the pandemic compared with the months before, except for Greece, Poland and UK. GPs provided frequent and varied COVID-related advice and more frequently scheduled a follow-up contact (50%, 95% CI 48% to 52%). GPs reported a slightly higher degree of confidence in the likely effectiveness of their management in face-to-face (73% (very) confident, 95% CI 71% to 76%) than in virtual consultations (69%, 95% CI 67% to 71%). Conclusions Despite between-country variation in consultation characteristics, access to SARS-CoV-2 laboratory testing and medication prescribing, GPs reported a high degree of confidence in managing their patients with RTIs in the emerging pandemic. Insight in the highly variable pandemic responses, as measured in this multicountry audit, can aid in fine-tuning national action and in coordinating a pan-European response during future pandemic threats

Seropositivity to Nucleoprotein to detect mild and asymptomatic SARS-CoV-2 infections: A complementary tool to detect breakthrough infections after COVID-19 vaccination?

BACKGROUND: With COVID-19 vaccine roll-out ongoing in many countries globally, monitoring of breakthrough infections is of great importance. Antibodies persist in the blood after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Since COVID-19 vaccines induce immune response to the Spike protein of the virus, which is the main serosurveillance target to date, alternative targets should be explored to distinguish infection from vaccination. METHODS: Multiplex immunoassay data from 1,513 SARS-CoV-2 RT-qPCR-tested individuals (352 positive and 1,161 negative) without COVID-19 vaccination history were used to determine the accuracy of Nucleoprotein-specific immunoglobulin G (IgG) in detecting past SARS-CoV-2 infection. We also described Spike S1 and Nucleoprotein-specific IgG responses in 230 COVID-19 vaccinated individuals (Pfizer/BioNTech). RESULTS: The sensitivity of Nucleoprotein seropositivity was 85% (95% confidence interval: 80–90%) for mild COVID-19 in the first two months following symptom onset. Sensitivity was lower in asymptomatic individuals (67%, 50–81%). Participants who had experienced a SARS-CoV-2 infection up to 11 months preceding vaccination, as assessed by Spike S1 seropositivity or RT-qPCR, produced 2.7-fold higher median levels of IgG to Spike S1 ≥ 14 days after the first dose as compared to those unexposed to SARS-CoV-2 at ≥ 7 days after the second dose (p = 0.011). Nucleoprotein-specific IgG concentrations were not affected by vaccination in infection-naïve participants. CONCLUSIONS: Serological responses to Nucleoprotein may prove helpful in identifying SARS-CoV-2 infections after vaccination. Furthermore, it can help interpret IgG to Spike S1 after COVID-19 vaccination as particularly high responses shortly after vaccination could be explained by prior exposure history