Gonorrhoea on the rise in Denmark since 2022: distinct clones drive increase in heterosexual individuals.

A surge in gonorrhoea in Denmark has occurred since 2022, a 46% increase from 2021. National surveillance, leveraging mandatory reporting and epidemiological data, highlights three distinct clades linked to heterosexual transmission. Despite the rise, these exhibit high susceptibility, contrasting MSM-associated strains. Geographical hotspots and age-specific patterns further illuminate transmission dynamics. The combination of genomic and epidemiological data provides novel insights into the evolving landscape of gonorrhoea, indicating potential shifts in infection dynamics and transmissibility.

Early-onset group B streptococcal infections in five Nordic countries with different prevention policies, 1995 to 2019.

BackgroundNeonatal early-onset disease caused by group B Streptococcus (GBS) is a leading cause of infant morbidity. Intrapartum antibiotic prophylaxis (IAP) is effective in preventing early-onset GBS disease, but there is no agreement on the optimal strategy for identifying the pregnant women requiring this treatment, and both risk-based prophylaxis (RBP) and GBS screening-based prophylaxis (SBP) are used.AimThe aim of this study was to evaluate the effect of SBP as a public health intervention on the epidemiology of early-onset GBS infections.MethodsIn 2012, Finland started the universal SBP, while Denmark, Iceland, Norway and Sweden continued with RBP. We conducted an interrupted time series analysis taking 2012 as the intervention point to evaluate the impact of this intervention. The incidences of early- and late-onset GBS infections during Period I (1995-2011) and Period II (2012-2019) were collected from each national register, covering 6,605,564 live births.ResultsIn Finland, a reduction of 58% in the incidence of early-onset GBS disease, corresponding to an incidence rate ratio (IRR) of 0.42 (95% CI: 0.34-0.52), was observed after 2012. At the same time, the pooled IRR of other Nordic countries was 0.89 (95% CI: 0.80-1.0), specifically 0.89 (95% CI: 0.70-1.5) in Denmark, 0.34 (95% CI: 0.15-0.81) in Iceland, 0.72 (95% CI: 0.59-0.88) in Norway and 0.97 (95% CI: 0.85-1.1) in Sweden.ConclusionsIn this ecological study of five Nordic countries, early-onset GBS infections were approximately halved following introduction of the SBP approach as compared with RBP.

Trends in invasive bacterial diseases during the first 2 years of the COVID-19 pandemic: analyses of prospective surveillance data from 30 countries and territories in the IRIS Consortium.

BACKGROUND: The Invasive Respiratory Infection Surveillance (IRIS) Consortium was established to assess the impact of the COVID-19 pandemic on invasive diseases caused by Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, and Streptococcus agalactiae. We aimed to analyse the incidence and distribution of these diseases during the first 2 years of the COVID-19 pandemic compared to the 2 years preceding the pandemic. METHODS: For this prospective analysis, laboratories in 30 countries and territories representing five continents submitted surveillance data from Jan 1, 2018, to Jan 2, 2022, to private projects within databases in PubMLST. The impact of COVID-19 containment measures on the overall number of cases was analysed, and changes in disease distributions by patient age and serotype or group were examined. Interrupted time-series analyses were done to quantify the impact of pandemic response measures and their relaxation on disease rates, and autoregressive integrated moving average models were used to estimate effect sizes and forecast counterfactual trends by hemisphere. FINDINGS: Overall, 116 841 cases were analysed: 76 481 in 2018-19, before the pandemic, and 40 360 in 2020-21, during the pandemic. During the pandemic there was a significant reduction in the risk of disease caused by S pneumoniae (risk ratio 0·47; 95% CI 0·40-0·55), H influenzae (0·51; 0·40-0·66) and N meningitidis (0·26; 0·21-0·31), while no significant changes were observed for S agalactiae (1·02; 0·75-1·40), which is not transmitted via the respiratory route. No major changes in the distribution of cases were observed when stratified by patient age or serotype or group. An estimated 36 289 (95% prediction interval 17 145-55 434) cases of invasive bacterial disease were averted during the first 2 years of the pandemic among IRIS-participating countries and territories. INTERPRETATION: COVID-19 containment measures were associated with a sustained decrease in the incidence of invasive disease caused by S pneumoniae, H influenzae, and N meningitidis during the first 2 years of the pandemic, but cases began to increase in some countries towards the end of 2021 as pandemic restrictions were lifted. These IRIS data provide a better understanding of microbial transmission, will inform vaccine development and implementation, and can contribute to health-care service planning and provision of policies. FUNDING: Wellcome Trust, NIHR Oxford Biomedical Research Centre, Spanish Ministry of Science and Innovation, Korea Disease Control and Prevention Agency, Torsten Söderberg Foundation, Stockholm County Council, Swedish Research Council, German Federal Ministry of Health, Robert Koch Institute, Pfizer, Merck, and the Greek National Public Health Organization.

Increase in invasive group A streptococcal infections and emergence of novel, rapidly expanding sub-lineage of the virulent Streptococcus pyogenes M1 clone, Denmark, 2023.

A highly virulent sub-lineage of the Streptococcus pyogenes M1 clone has been rapidly expanding throughout Denmark since late 2022 and now accounts for 30% of the new invasive group A streptococcal infections. We aimed to investigate whether a shift in variant composition can account for the high incidence rates observed over winter 2022/23, or if these are better explained by the impact of COVID-19-related restrictions on population immunity and carriage of group A Streptococcus.

COVID-19 preventive measures coincided with a marked decline in other infectious diseases in Denmark, spring 2020.

We aimed to descriptively analyse the possible impact of the national COVID-19 interventions on the incidence of common infectious diseases in Denmark during spring and summer 2020. This observational study focused on national register data on infections caused by 16 different bacterial and viral pathogens. We included new cases registered between 1 January 2016 and 31 July 2020. The weekly number of new cases were analysed with respect to the COVID-19-related interventions introduced during 2020. We found a marked decrease in infections associated with droplet transmission coinciding with the COVID-19 interventions in spring and summer 2020. These included decreases in both viral and bacterial airway infections and also decreases in invasive infections caused by Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis. There was also a reduction in cases associated with foodborne transmission during the COVID-19 lockdown period. We found no effect of the lockdown on infections by invasive beta-haemolytic streptococci group B, C and G, Staphylococcus aureus bacteraemia, Neisseria gonorrhoeae or Clostridioides difficile. In conclusion, we found that the widespread interventions such as physical distancing, less travel, hygiene measures and lockdown of schools, restaurants and workplaces together coincided with a marked decline in respiratory infections and, to a smaller extent, some foodborne-transmitted infections.

Changes in testing and incidence of Chlamydia trachomatis and Neisseria gonorrhoeae - the possible impact of the COVID-19 pandemic in the three Scandinavian countries.

BACKGROUND: This study aimed to investigate what impact the COVID-19 pandemic and its associated restrictions had on Chlamydia trachomatis and Neisseria gonorrhoeae infections in Sweden, Denmark and Norway, countries with very different governmental strategies for handling this pandemic. METHODS: Retrospective analysis of data collected via requests to Swedish regions and to health authorities in Denmark and Norway. The data were collected for the years 2018-2020 and the data from Sweden were more detailed. RESULTS: When the pandemic restrictions were installed in 2020, the number of reported chlamydia cases decreased. The decline was most pronounced in Norway 10.8% (2019: n = 28,446; 2020: n = 25,444) while it was only 3.1% in Denmark (2019: n = 35,688; 2020: n = 34,689) and 4.3% in Sweden (2019: n = 34,726; 2020: n = 33,339). Nucleic acid amplifications tests for chlamydia decreased in Sweden (10%) and Norway (18%) in 2020 compared to 2019, while in Denmark a 21% decrease was noted in April 2020 but thereafter increased to a higher level than 2019. The number of reported gonorrhoea cases decreased in Sweden (17%) and in Norway (39%) in 2020 compared to 2019, while a 21% increase was noted in Denmark. CONCLUSIONS: Pandemic restrictions had an impact on the number of reported chlamydia infections in all three countries, but only temporarily and did not seem to be correlated to the restriction levels. The number of reported gonorrhoea infections in Sweden and Norway significantly decreased but not in Denmark. Pandemic restrictions appear to have had a limited effect on the spread of chlamydia and gonorrhoea.

A Nationwide Observational Study of Chlamydia trachomatis Infections in Denmark during the COVID-19 Pandemic.

The aim of this study was to determine whether COVID-19 restrictions had an impact on Chlamydia trachomatis infections compared with 2018 and 2019. A retrospective nationwide observational study was performed using monthly incidences of laboratory-confirmed chlamydia cases and number of tests, obtained from Danish national surveillance data. Testing rates and positivity rates were compared using Poisson and logistic regression. The first Danish COVID-19 lockdown (12 March to 14 April 2020) resulted in a reduction in the number of chlamydia tests performed (rate ratio 0.72, 95% confidence interval  0.71-0.73) and a consequent reduction in the number of laboratory-identified cases (66.5 vs 88.3 per 100,000 population during the same period in 2018 to 2019). This period was followed by a return of testing and test positivity close to the level seen in 2018 to 2019. The second Danish COVID-19 lockdown (17 December to 31 March 2021) resulted in crude incidence rates of laboratory-confirmed chlamydia infection that were similar to the crude incidence rates seen during same period in 2018 to 2019. In conclusion, the Danish COVID-19 restrictions have had negligible effects on laboratory-confirmed C. trachomatis transmission.

The perinatal health challenges of emerging and re-emerging infectious diseases: A narrative review.

The world has seen numerous infectious disease outbreaks in the past decade. In many cases these outbreaks have had considerable perinatal health consequences including increased risk of preterm delivery (e.g., influenza, measles, and COVID-19), and the delivery of low birth weight or small for gestational age babies (e.g., influenza, COVID-19). Furthermore, severe perinatal outcomes including perinatal and infant death are a known consequence of multiple infectious diseases (e.g., Ebola virus disease, Zika virus disease, pertussis, and measles). In addition to vaccination during pregnancy (where possible), pregnant women, are provided some level of protection from the adverse effects of infection through community-level application of evidence-based transmission-control methods. This review demonstrates that it takes almost 2 years for the perinatal impacts of an infectious disease outbreak to be reported. However, many infectious disease outbreaks between 2010 and 2020 have no associated pregnancy data reported in the scientific literature, or pregnancy data is reported in the form of case-studies only. This lack of systematic data collection and reporting has a negative impact on our understanding of these diseases and the implications they may have for pregnant women and their unborn infants. Monitoring perinatal health is an essential aspect of national and global healthcare strategies as perinatal life has a critical impact on early life mortality as well as possible effects on later life health. The unpredictable nature of emerging infections and the potential for adverse perinatal outcomes necessitate that we thoroughly assess pregnancy and perinatal health implications of disease outbreaks and their public health interventions in tandem with outbreak response efforts. Disease surveillance programs should incorporate perinatal health monitoring and health systems around the world should endeavor to continuously collect perinatal health data in order to quickly update pregnancy care protocols as needed.

Preterm birth, stillbirth and early neonatal mortality during the Danish COVID-19 lockdown.

Using provisional or opportunistic data, three nationwide studies (The Netherlands, the USA and Denmark) have identified a reduction in preterm or extremely preterm births during periods of COVID-19 restrictions. However, none of the studies accounted for perinatal deaths. To determine whether the reduction in extremely preterm births, observed in Denmark during the COVID-19 lockdown, could be the result of an increase in perinatal deaths and to assess the impact of extended COVID-19 restrictions, we performed a nationwide Danish register-based prevalence proportion study. We examined all singleton pregnancies delivered in Denmark during the COVID-19 strict lockdown calendar periods (March 12-April 14, 2015-2020, N = 31,164 births) and the extended calendar periods of COVID-19 restrictions (February 27-September 30, 2015-2020, N = 214,862 births). The extremely preterm birth rate was reduced (OR 0.27, 95% CI 0.07 to 0.86) during the strict lockdown period in 2020, while perinatal mortality was not significantly different. During the extended period of restrictions in 2020, the extremely preterm birth rate was marginally reduced, and a significant reduction in the stillbirth rate (OR 0.69, 0.50 to 0.95) was observed. No changes in early neonatal mortality rates were found.Conclusion: Stillbirth and extremely preterm birth rates were reduced in Denmark during the period of COVID-19 restrictions and lockdown, respectively, suggesting that aspects of these containment and control measures confer an element of protection. The present observational study does not allow for causal inference; however, the results support the design of studies to ascertain whether behavioural or social changes for pregnant women may improve pregnancy outcomes. What is Known: • The aetiologies of preterm birth and stillbirth are multifaceted and linked to a wide range of socio-demographic, medical, obstetric, foetal, psychosocial and environmental factors. • The COVID-19 lockdown saw a reduction in extremely preterm births in Denmark and other high-income countries. An urgent question is whether this reduction can be explained by increased perinatal mortality. What is New: • The reduction in extremely preterm births during the Danish COVID-19 lockdown was not a consequence of increased perinatal mortality, which remained unchanged during this period. • The stillbirth rate was reduced throughout the extended period of COVID-19 restrictions.

Comorbidity Increases the Risk of Invasive Meningococcal Disease in Adults.

BACKGROUND: Risk of invasive meningococcal disease (IMD) is increased in patients with complement deficiency and human immunodeficiency virus (HIV) infection. Risk associated with comorbidity is not well described. METHODS: This was a nationwide adult case-control study. Cases for the period 1977-2018 were identified by the national meningococcus reference laboratory. Matched controls were identified by registry linkage. Comorbidities diagnosed prior to IMD were based on the International Classification of Diseases, Eighth or Tenth Revision. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated by logistic regression after adjustment for sex, age, and other comorbidities. RESULTS: We identified 1221 cases (45% male), with a median age of 45 years (interquartile range, 22-64 years). The dominant meningococcal serogroups were B (n = 738) and C (n = 337). Increased risk of IMD was associated with solid organ transplantation (SOT) (OR 40.47 [95% CI: 4.84-337.23]), hemolytic anemia (OR 7.56 [95% CI: 2.63-21.79]), renal disease (OR 2.95 [95% CI: 1.77-4.92]), liver disease (OR 2.54 [95% CI: 1.58-4.08]), cancer (OR 2.31 [95% CI: 1.85-2.89]), diabetes (OR 1.74 [95% CI: 1.27-2.39]), neurological disease (OR 1.72 [95% CI: 1.20-2.46]), and autoimmune disease (OR 1.70 [95% CI: 1.63-2.11]). Having 1, 2, and ≥3 comorbidities was associated with increased risk of IMD (ORs 1.6-3.5). Increased risk was not associated with specific serogroups. CONCLUSIONS: This study of adults with IMD over 4 decades showed increased risk of IMD associated with renal disease, immunological disorders, liver disease, cancer, and SOT ranging from a 2- to 40-fold increased risk. Vaccination may be warranted in these populations.

Recent increased incidence of invasive serogroup W meningococcal disease: A retrospective observational study.

OBJECTIVES: Neisseria meningitidis serogroup W incidence has increased. Mortality associated with serogroup W has been higher than for other serogroups. Here we report epidemiological characteristics and risks of poor outcomes associated with invasive meningococcal disease in Denmark since 1980. METHODS: All cases of invasive meningococcal disease reported from 1980-2018 were analyzed. Incidence rates by age, sex, manifestation, and serogroup were calculated. Poisson regression was used to analyze the rise in serogroup W, and multivariate logistic analysis was used to analyze risk factors for mortality. RESULTS: A total of 5825 cases were analyzed. Risk of serogroup W infection increased after 2015 compared with all previous periods. Younger (<20 years) and older age (≥60 years) was associated with an increased risk of serogroup W infection compared with being aged 20-39. Crude case fatality was 12.0%, 11.9%, 9.2%, and 7.9% for serogroups W, Y, C, and B, respectively. After adjustment for age, sex, and manifestation, 30-day mortality was comparable for serogroups. Older age and manifestation with sepsis independently predicted risk of death. CONCLUSIONS: Invasive meningococcal disease caused by serogroup W has increased, but serogroup per se was not associated with an increased risk of 30-day mortality.

Changes in the incidence of invasive disease due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis during the COVID-19 pandemic in 26 countries and territories in the Invasive Respiratory Infection Surveillance Initiative: a prospective analysis of surveillance data.

BACKGROUND: Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, which are typically transmitted via respiratory droplets, are leading causes of invasive diseases, including bacteraemic pneumonia and meningitis, and of secondary infections subsequent to post-viral respiratory disease. The aim of this study was to investigate the incidence of invasive disease due to these pathogens during the early months of the COVID-19 pandemic. METHODS: In this prospective analysis of surveillance data, laboratories in 26 countries and territories across six continents submitted data on cases of invasive disease due to S pneumoniae, H influenzae, and N meningitidis from Jan 1, 2018, to May, 31, 2020, as part of the Invasive Respiratory Infection Surveillance (IRIS) Initiative. Numbers of weekly cases in 2020 were compared with corresponding data for 2018 and 2019. Data for invasive disease due to Streptococcus agalactiae, a non-respiratory pathogen, were collected from nine laboratories for comparison. The stringency of COVID-19 containment measures was quantified using the Oxford COVID-19 Government Response Tracker. Changes in population movements were assessed using Google COVID-19 Community Mobility Reports. Interrupted time-series modelling quantified changes in the incidence of invasive disease due to S pneumoniae, H influenzae, and N meningitidis in 2020 relative to when containment measures were imposed. FINDINGS: 27 laboratories from 26 countries and territories submitted data to the IRIS Initiative for S pneumoniae (62 837 total cases), 24 laboratories from 24 countries submitted data for H influenzae (7796 total cases), and 21 laboratories from 21 countries submitted data for N meningitidis (5877 total cases). All countries and territories had experienced a significant and sustained reduction in invasive diseases due to S pneumoniae, H influenzae, and N meningitidis in early 2020 (Jan 1 to May 31, 2020), coinciding with the introduction of COVID-19 containment measures in each country. By contrast, no significant changes in the incidence of invasive S agalactiae infections were observed. Similar trends were observed across most countries and territories despite differing stringency in COVID-19 control policies. The incidence of reported S pneumoniae infections decreased by 68% at 4 weeks (incidence rate ratio 0·32 [95% CI 0·27-0·37]) and 82% at 8 weeks (0·18 [0·14-0·23]) following the week in which significant changes in population movements were recorded. INTERPRETATION: The introduction of COVID-19 containment policies and public information campaigns likely reduced transmission of S pneumoniae, H influenzae, and N meningitidis, leading to a significant reduction in life-threatening invasive diseases in many countries worldwide. FUNDING: Wellcome Trust (UK), Robert Koch Institute (Germany), Federal Ministry of Health (Germany), Pfizer, Merck, Health Protection Surveillance Centre (Ireland), SpID-Net project (Ireland), European Centre for Disease Prevention and Control (European Union), Horizon 2020 (European Commission), Ministry of Health (Poland), National Programme of Antibiotic Protection (Poland), Ministry of Science and Higher Education (Poland), Agencia de Salut Pública de Catalunya (Spain), Sant Joan de Deu Foundation (Spain), Knut and Alice Wallenberg Foundation (Sweden), Swedish Research Council (Sweden), Region Stockholm (Sweden), Federal Office of Public Health of Switzerland (Switzerland), and French Public Health Agency (France).

Molecular Identification of Invasive Non-typeable Group B Streptococcus Isolates From Denmark (2015 to 2017).

The number of invasive Streptococcus agalactiae (GBS) non-typeable (NT) isolates in Denmark received since 1999 has in general accounted for 10% of all invasive GBS isolates. We present data on 55 clinical NT isolates based on clinical manifestations, clonal relationship, antimicrobial resistance (AMR) determinants, and virulence factors. The GBS isolates included in this study were phenotypic-based NT obtained from 2015 to 2017, as well as 10 reference isolates. Whole genome sequencing (WGS) was performed on all isolates and the data were analyzed for the presence of both species specific genes, capsular genes (genotype), and other relevant genes. We furthermore compared different procedures for detection of serotype specific capsular genes. Overall we were able to genotype 54 of the 55 isolates. After retesting the isolates a phenotype was detected for 20 (36%) isolates, of which the initial phenotyping problem for 13 isolates was found to be due to a problem with serotype Ia specific antiserum. Thirty-five isolates remained phenotypic non-typeable with a majority of genotype V isolates which do not express a capsular gene. From all the Danish invasive GBS isolates from 2015 to 2017, the 35 NT isolates were all detected in the age group above 21 years with bacteremia. The 35 NT isolates belonged to six different well-known human pathogenic clonal complexes. The CDC recommended sequences for capsule genotyping were the most optimal for serotype prediction, because of the sequence simplicity and clear cutoff values. However we recommend to also use other capsular sequences for the NT isolates, if they cannot be genotyped by the CDC method.

The human natural anti-αGal antibody targets common pathogens by broad-spectrum polyreactivity.

Naturally occurring antibodies are abundant in human plasma, but their importance in the defence against bacterial pathogens is unclear. We studied the role of the most abundant of such antibodies, the antibody against terminal galactose-α-1,3-galactose (anti-αGal), in the protection against pneumococcal infections (Streptococcus pneumonia). All known pneumococcal capsular polysaccharides lack terminal galactose-α-1,3-galactose, yet highly purified human anti-αGal antibody of the IgG class reacted with 48 of 91 pneumococcal serotypes. Anti-αGal was found to contain multiple antibody subsets that possess distinct specificities beyond their general reactivity with terminal galactose-α-1,3-galactose. These subsets in concert targeted a wide range of microbial polysaccharides. We found that anti-αGal constituted up to 40% of the total antibody reactivity to pneumococci in normal human plasma, that anti-αGal drives phagocytosis of pneumococci by human neutrophils and that the anti-αGal level was twofold lower in patients prone to pneumococcal infections compared with controls. Moreover, during a 48-year period in Denmark, the 48 anti-αGal-reactive serotypes caused fewer invasive pneumococcal infections (n = 10 927) than the 43 non-reactive serotypes (n = 18 107), supporting protection on the population level. Our findings explain the broad-spectrum pathogen reactivity of anti-αGal and support that these naturally occurring polyreactive antibodies contribute significantly to human protective immunity.

A Chlamydia trachomatis 23S rRNA G1523A variant escaping detection in the Aptima Combo 2 assay (Hologic) was widespread across Denmark in July-September 2019.

Chlamydia trachomatis infection is the most common bacterial sexually transmitted infection globally, and nucleic acid amplification tests (NAATs) are recommended for highly sensitive and specific diagnosis. In early 2019, the Finnish new variant of Chlamydia trachomatis (FI-nvCT) was identified. The FI-nvCT has a C1515T mutation in the 23S rRNA gene, making it escaping detection in the Aptima Combo 2 (AC2; Hologic) NAAT, and the FI-nvCT has been subsequently reported in Sweden and Norway. In the present study, we investigated the presence of the FI-nvCT and other AC2 diagnostic-escape CT mutants in July-September 2019 in Denmark. The FI-nvCT was present but rare in Denmark. However, another AC2 diagnostic-escape CT mutant (with a 23S rRNA G1523A mutation) was found to be widespread across Denmark, accounting for 95% (76/80) of AC2 diagnostic-escape nvCT samples from five Danish CT-diagnostic laboratories. This nvCT-G1523A has previously only been detected in one single sample in the United Kingdom and Norway, respectively. It is vital to monitor the continued stability of the NAAT targets in local, national and international settings and monitor as well as appropriately analyse incidence, unexplained shifts in diagnostics rates and/or annual collections of samples diagnosed as negative/equivocal using NAATs with different target(s). Furthermore, diagnostic CT NAATs with dual target sequences are crucial, and fortunately, an updated Hologic AC2 assay including one additional target sequence is in advanced development.

The Epidemiology of Invasive Group B Streptococcus in Denmark From 2005 to 2018.

Previous epidemiology reports on invasive Streptococcus agalactiae (GBS) infections in Denmark did not include all patient age groups. The aim of this study was therefore to analyze the GBS incidence in all age groups during the period 2005-2018 and to present the serotype distribution and the antibiotic susceptibility. Data were retrieved from the Danish laboratory surveillance system, and these included data on typing and susceptibility testing for erythromycin and clindamycin. Early-onset disease (EOD) (mean incidence 0.17 per 1,000 live births) and late-onset disease (LOD) (mean incidence 0.14 per 1,000 live births) showed a low level during the period. The incidence was stable in the age groups 91 days to 4 years, 5-19 years, and 20-64 years. From 2005 to 2018, the incidence in the elderly showed a significantly increasing trend (P < 0.05), that in the 65-74 years increased from 3.23 to 8.34 per 100,000, and that in the 75+ years increased from 6.85 to 16.01 per 100,000. Erythromycin and clindamycin resistance fluctuated over the period; however, the overall trend was increasing. Data showed that EOD and LOD incidence continued to be low, whereas an increasing trend in GBS infections in the elderly was observed. The prevalence of erythromycin and clindamycin resistance increased from 2005 to 2018.

Genomic evolution of Neisseria gonorrhoeae since the preantibiotic era (1928-2013): antimicrobial use/misuse selects for resistance and drives evolution.

BACKGROUND: Multidrug-resistant Neisseria gonorrhoeae strains are prevalent, threatening gonorrhoea treatment globally, and understanding of emergence, evolution, and spread of antimicrobial resistance (AMR) in gonococci remains limited. We describe the genomic evolution of gonococci and their AMR, related to the introduction of antimicrobial therapies, examining isolates from 1928 (preantibiotic era) to 2013 in Denmark. This is, to our knowledge, the oldest gonococcal collection globally. METHODS: Lyophilised isolates were revived and examined using Etest (18 antimicrobials) and whole-genome sequencing (WGS). Quality-assured genome sequences were obtained for 191 viable and 40 non-viable isolates and analysed with multiple phylogenomic approaches. RESULTS: Gonococcal AMR, including an accumulation of multiple AMR determinants, started to emerge particularly in the 1950s-1970s. By the twenty-first century, resistance to most antimicrobials was common. Despite that some AMR determinants affect many physiological functions and fitness, AMR determinants were mainly selected by the use/misuse of gonorrhoea therapeutic antimicrobials. Most AMR developed in strains belonging to one multidrug-resistant (MDR) clade with close to three times higher genomic mutation rate. Modern N. gonorrhoeae was inferred to have emerged in the late-1500s and its genome became increasingly conserved over time. CONCLUSIONS: WGS of gonococci from 1928 to 2013 showed that no AMR determinants, except penB, were in detectable frequency before the introduction of gonorrhoea therapeutic antimicrobials. The modern gonococcus is substantially younger than previously hypothesized and has been evolving into a more clonal species, driven by the use/misuse of antimicrobials. The MDR gonococcal clade should be further investigated for early detection of strains with predispositions to develop and maintain MDR and for initiation of public health interventions.

Reduced In Vitro Susceptibility of Streptococcus pyogenes to ß-Lactam Antibiotics Associated with Mutations in the pbp2x Gene Is Geographically Widespread.

Recently, two related Streptococcus pyogenes strains with reduced susceptibility to ampicillin, amoxicillin, and cefotaxime, antibiotics commonly used to treat S. pyogenes infections, were reported. The two strains had the same nonsynonymous (amino acid-substituting) mutation in the pbp2x gene, encoding penicillin-binding protein 2X (PBP2X). This concerning report led us to investigate our library of 7,025 genome sequences of type emm1, emm28, and emm89S. pyogenes clinical strains recovered from intercontinental sources for mutations in pbp2x We identified 137 strains that, combined, had 37 nonsynonymous mutations in 36 codons in pbp2x Although to a lesser magnitude than the two previously published isolates, many of our strains had decreased susceptibility in vitro to multiple beta-lactam antibiotics. Many pbp2x mutations were found only in single strains, but 16 groups of two or more isolates of the same emm type had an identical amino acid replacement. Phylogenetic analysis showed that, with one exception, strains of the same emm type with the same amino acid replacement were clonally related by descent. This finding indicates that strains with some amino acid changes in PBP2X can successfully spread to new human hosts and cause invasive infections. Mapping of the amino acid changes onto a three-dimensional structure of the related Streptococcus pneumoniae PBP2X suggests that some substitutions are located in regions functionally important in related pathogenic bacterial species. Decreased beta-lactam susceptibility is geographically widespread in strains of numerically common emm gene subtypes. Enhanced surveillance and further epidemiological and molecular genetic study of this potential emergent antimicrobial problem are warranted.

Ten years of external quality assessment (EQA) of Neisseria gonorrhoeae antimicrobial susceptibility testing in Europe elucidate high reliability of data.

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: Antimicrobial susceptibility category agreement in each year was ≥91%. Discrepancies in susceptibility categories were generally because the MICs for EQA panel isolates were on or very close to the susceptibility or resistance breakpoints. A high proportion of isolates tested over the 10 years were within one (≥90%) or two (≥97%) MIC log2 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.