International circumpolar surveillance: update on the interlaboratory quality control program for Streptococcus pneumoniae, 2009 to 2020.

The International Circumpolar Surveillance (ICS) program is a population-based surveillance network for invasive bacterial diseases throughout Arctic countries and territories. The ICS quality control program for Streptococcus pneumoniae serotyping and antimicrobial susceptibility testing has been ongoing since 1999. Current participating laboratories include the Provincial Laboratory for Public Health in Edmonton, Alberta; Laboratoire de santé publique du Québec in Sainte-Anne-de-Bellevue, Québec; the Centers for Disease Control's Arctic Investigations Program in Anchorage, Alaska; the Neisseria and Streptococcus Reference Laboratory at Statens Serum Institut in Copenhagen, Denmark; the Department of Clinical Microbiology, Landspitali in Reykjavik, Iceland; and Public Health Agency of Canada's National Microbiology Laboratory in Winnipeg, Manitoba. From 2009 to 2020, 140 isolates of S. pneumoniae were distributed among the six laboratories as part of the quality control program. Overall serotype concordance was 96.9%, with 99.3% concordance to pool level. All participating laboratories had individual concordance rates >92% for serotype and >97% for pool. Overall concordance by modal minimum inhibitory concentration (MIC) for testing done by broth microdilution or Etest was 99.1%, and >98% for all antimicrobials tested. Categorical concordance was >98% by both CLSI and EUCAST criteria. For two laboratories performing disc diffusion, rates of concordance by modal MIC were >97% for most antimicrobials, except chloramphenicol (>93%) and trimethoprim/sulfamethoxazole (>88%). Data collected from 12 years of the ICS quality control program for S. pneumoniae demonstrate excellent (≥95%) overall concordance for serotype and antimicrobial susceptibility testing results across six laboratories. IMPORTANCE: Arctic populations experience several social and physical challenges that lead to the increased spread and incidence of invasive diseases. The International Circumpolar Surveillance (ICS) program was developed to monitor five invasive bacterial diseases in Arctic countries and territories. Each ICS organism has a corresponding interlaboratory quality control (QC) program for laboratory-based typing, to ensure the technical precision and accuracy of reference testing services for these regions, and identify and correct potential problems. Here, we describe the results of the ICS Streptococcus pneumoniae QC program, from 2009 to 2020. Excellent overall concordance was achieved for serotype and antimicrobial susceptibility testing results across six laboratories. Ongoing participation in these QC programs ensures the continuation of quality surveillance systems within Arctic populations that experience health disparities.

Characterization of Mycobacterium orygis, Mycobacterium bovis, and Mycobacterium caprae Infections in Humans in Western Canada.

Epidemiologic research on zoonotic tuberculosis historically used Mycobacterium bovis as a surrogate measure, however, increased reports of human tuberculosis caused by other animal-associated Mycobacterium tuberculosis complex members like Mycobacterium orygis necessitates their inclusion. We performed a retrospective cohort study including persons infected with any animal-lineage M. tuberculosis complex species in Alberta, Canada, from January 1995 to July 2021, identifying 42 patients (20 M. bovis, 21 M. orygis, one M. caprae). Demographic, epidemiologic and clinical characteristics were compared against persons with culture-confirmed M. tuberculosis infection. The proportion of culture-positive infections caused by M. orygis increased continuously from 2016-2020. Significantly more females at a higher median age were impacted by M. orygis, with all patients originating from South Asia. M. bovis caused significantly more extra-pulmonary disease, and disproportionately impacted young females, particularly those pregnant or post-partum. All infections were acquired abroad. These findings can aid in developing targeted public health interventions.

The association between phylogenetic lineage and the subclinical phenotype of pulmonary tuberculosis: A retrospective 2-cohort study.

BACKGROUND: Subclinical pulmonary tuberculosis (PTB) is an asymptomatic disease state between established TB infection and symptomatic (clinical) TB disease. It is present in 20-25% of PTB patients in high-income countries. Mycobacterium tuberculosis complex (MTBC) genetic heterogeneity, and differential host immunological responses, have been implicated in its pathogenesis. METHODS: To determine the association between MTBC lineage and PTB disease phenotype, we used two retrospective cohorts of PTB patients in Canada and two independent lineage attribution methods (DNA fingerprinting and genome sequencing). The first cohort, Cohort 1, consisted of consecutively diagnosed PTB patients between 2014 and 2020. The second, Cohort 2, consisted of newly-arrived foreign-born PTB patients who either were or were not referred for post-landing medical surveillance between 2004 and 2017. Univariable and multivariable logistic regression models were sequentially fitted to both cohorts, adjusting for age, sex, disease type, drug resistance and HIV. Evolution of radiographic features was correlated to lineage in Cohort 2. FINDINGS: Cohort 1 and 2 included 874 (209 subclinical) and 111 (44 subclinical) patients, respectively. In both cohorts, subclinical patients were more likely than clinical patients to have relapse/retreatment disease, be smear-negative, have longer times-to-culture positivity and to harbor an ancestral MTBC lineage (Indo-Oceanic or Mycobacterium africanum). Relapse/retreatment disease and ancestral MTBC lineage were independent predictors of subclinical disease (ORs and 95% CIs in Cohort 1, 1.85 [1.07,3.28], p < 0.029 and 2.30 [1.66,3.18], p < 0.001, respectively, and Cohort 2, 5.74 [1.37-24.06], p < 0.017 and 3.21 (1.29,7.97], p < 0.012, respectively). The geographic distribution of Indo-Oceanic strains causing subclinical disease was uneven. Non-progressive lung disease was more common in patients infected with ancestral than modern lineages in Cohort 2, 56.0% vs 25.4%, p < 0.005. INTERPRETATION: MTBC lineage is a strong predictor of PTB disease phenotype. The genetic drivers of this association, and the relative contribution of other explanatory variables, are unknown.

Genomic analysis of Streptococcus pneumoniae serogroup 20 isolates in Alberta, Canada from 1993-2019.

In the province of Alberta, Canada, invasive disease caused by Streptococcus pneumoniae serogroup 20 (serotypes 20A/20B) has been increasing in incidence. Here, we characterize provincial invasive serogroup 20 isolates collected from 1993 to 2019 alongside invasive and non-invasive serogroup 20 isolates from the Global Pneumococcal Sequencing (GPS) Project collected from 1998 to 2015. Trends in clinical metadata and geographic location were evaluated, and serogroup 20 isolate genomes were subjected to molecular sequence typing, virulence and antimicrobial resistance factor mining, phylogenetic analysis and pangenome calculation. Two hundred and seventy-four serogroup 20 isolates from Alberta were sequenced, and analysed along with 95 GPS Project genomes. The majority of invasive Alberta serogroup 20 isolates were identified after 2007 in primarily middle-aged adults and typed predominantly as ST235, a sequence type that was rare among GPS Project isolates. Most Alberta isolates carried a full-length whaF capsular gene, suggestive of serotype 20B. All Alberta and GPS Project genomes carried molecular resistance determinants implicated in fluoroquinolone and macrolide resistance, with a few Alberta isolates exhibiting phenotypic resistance to azithromycin, clindamycin, erythromycin, tetracycline and trimethoprim-sulfamethoxazole, as well as non-susceptibility to tigecycline. All isolates carried multiple virulence factors including those involved in adherence, immune modulation and nutrient uptake, as well as exotoxins and exoenzymes. Phylogenetically, Alberta serogroup 20 isolates clustered with predominantly invasive GPS Project isolates from the USA, Israel, Brazil and Nepal. Overall, this study highlights the increasing incidence of invasive S. pneumoniae serogroup 20 disease in Alberta, Canada, and provides insights into the genetic and clinical characteristics of these isolates within a global context.

Whole genome sequencing-based identification of human tuberculosis caused by animal-lineage Mycobacterium orygis.

A recently described member of the Mycobacterium tuberculosis complex (MTBC) is Mycobacterium orygis, which can cause disease primarily in animals but also in humans. Although M. orygis has been reported from different geographic regions around the world, due to a lack of proper identification techniques, the contribution of this emerging pathogen to the global burden of zoonotic tuberculosis is not fully understood. In the present work, we report single nucleotide polymorphism (SNP) analysis using whole genome sequencing (WGS) that can accurately identify M. orygis and differentiate it from other members of the MTBC species. WGS-based SNP analysis was performed for 61 isolates from different provinces in Canada that were identified as M. orygis. A total of 56 M. orygis sequences from the public databases were also included in the analysis. Several unique SNPs in the gyrB, PPE55, Rv2042c, leuS, mmpL6, and mmpS6 genes were used to determine their effectiveness as genetic markers for the identification of M. orygis. To the best of our knowledge, five of these SNPs, viz., gyrB 277 (A→G), gyrB 1478 (T→C), leuS 1064 (A→T), mmpL6 486 (T→C), and mmpS6 334 (C→G), are reported for the first time in this study. Our results also revealed several SNPs specific to other species within MTBC. The phylogenetic analysis shows that the studied genomes were genetically diverse and clustered with M. orygis sequences of human and animal origin reported from different geographic locations. Therefore, the present study provides a new insight into the high-confidence identification of M. orygis from MTBC species based on WGS data, which can be useful for reference and diagnostic laboratories.

Canadian Blood Services traceback investigation of a suspected case of transfusion-transmitted malaria.

BACKGROUND: A 4-month-old infant hospitalized since birth received multiple blood transfusions. In March 2022, Plasmodium falciparum was confirmed with nucleic acid testing. As the mother was assessed as unlikely to be the source of infection, the blood operator initiated a traceback investigation for a potential blood donor source. The patient had received 13 red blood cell (RBC) transfusions (aliquoted from 11 donors), 4 apheresis platelet (PLT) transfusions and 16 buffy coat pooled PLT transfusions. The blood operator medical team developed a supplementary malaria infection risk questionnaire to identify donors at highest risk of life-time malaria infection, based on birthplace, residence, or travel in malaria-endemic regions. RESULTS: With 79 donors initially implicated, initial focus was on donors of RBC components. The 11 RBC donors were contacted and assessed using the supplementary questionnaire. Three donors, all of whom met current malaria-related donor eligibility criteria, were deemed high risk of prior malaria infection. These donors consented to P. falciparum serology and nucleic acid testing (NAT). One donor who was born and had resided in an endemic West African country for 14 years, was positive for P. falciparum by serology (indirect fluorescent antibody test) and NAT-(Ct ≥32). Lookback of this donor's transfused fresh co-components and prior donation identified no other malaria cases. CONCLUSION: This was a probable transfusion-transmitted malaria (TTM) case from an eligible donor who in retrospect was found to have unrecognized, asymptomatic, semi-immune malaria infection, and who was potentially infectious. Blood donor lack of recall of prior malaria infection does not negate the risk of TTM from those who have lived in malaria-endemic countries.

Microbiology sampling in non-cystic fibrosis bronchiectasis cases from northern Alberta.

Non-cystic fibrosis bronchiectasis (NCFB) is a chronic respiratory disease resulting in chronic cough, thick sputum, and lower airway microbial colonization, akin to patients with cystic fibrosis (CF). NCFB is a common, yet under recognized entity which inflicts significant morbidity and mortality particularly to older individuals, with a rising prevalence in the developed world. Given that sputum cultures are a non-invasive method to characterize the lower airway microbiota in NCFB patients, for which pathogenic organisms are associated with worsened outcomes, we sought to characterize the microbiological pattern and clinical outcomes associated with sputum culture in a cohort of NCFB patients from Western Canada. A total of 20 subjects were prospectively recruited from various bronchiectasis clinics across the Greater Edmonton area. A retrospective chart review and a symptoms questionnaire was performed, gathering information not limited to symptoms, comorbidities, exacerbations, hospitalizations, sputum production, and sputum culture results over the prior 5 years. Subjects reported frequent hospitalization alongside a significant burden of symptoms. A large majority of sputum cultures grew pathogenic organisms such as Haemophilus influenzae and Pseudomonas aeruginosa. We also note the considerable waste and inefficiency associated with sputum cultures, outlining areas for which this important diagnostic modality can be improved. Accurate characterization of the airway microbiota alongside efficient delivery of health services are key to ensuring the proper treatment of individuals with NCFB, given their high disease burden and frequent hospitalization.

Genomic characterization of emerging invasive Streptococcus agalactiae serotype VIII in Alberta, Canada.

Invasive Group B Streptococcus (GBS) can infect pregnant women, neonates, and older adults. Invasive GBS serotype VIII is infrequent in Alberta; however, cases have increased in recent years. Here, genomic analysis was used to characterize fourteen adult invasive serotype VIII isolates from 2009 to 2021. Trends in descriptive clinical data and antimicrobial susceptibility results were evaluated for invasive serotype VIII isolates from Alberta. Isolate genomes were sequenced and subjected to molecular sequence typing, virulence and antimicrobial resistance gene identification, phylogenetic analysis, and pangenome determination. Multilocus sequencing typing identified eight ST42 (Clonal Complex; CC19), four ST1 (CC1), and two ST2 (CC1) profiles. Isolates were susceptible to penicillin, erythromycin, chloramphenicol, and clindamycin, apart from one isolate that displayed erythromycin and inducible clindamycin resistance. All isolates carried genes for peptide antibiotic resistance, three isolates for tetracycline resistance, and one for macrolide, lincosamide, and streptogramin resistance. All genomes carried targets currently being considered for protein-based vaccines (e.g., pili and/or Alpha family proteins). Overall, invasive GBS serotype VIII is emerging in Alberta, primarily due to ST42. Characterization and continued surveillance of serotype VIII will be important for outbreak prevention, informing vaccine development, and contributing to our understanding of the global epidemiology of this rare serotype.

The prevalence, risk factors, and public health consequences of peripheral lymph node-associated clinical and subclinical pulmonary tuberculosis.

OBJECTIVES: Relatively little is known about the prevalence, risk factors, and public health consequences of peripheral lymph node (PLN)-associated pulmonary tuberculosis (PTB). METHODS: We developed a 10-year (2010-2019) population-based cohort of PLNTB patients in Canada. We used systematically collected primary source data and expert reader chest radiograph interpretations in a multivariable logistic regression to determine associations between sputum culture positivity and demographic, clinical, and radiographic features. Public health risks were estimated among contacts of PLNTB patients. RESULTS: There were 306 patients with PLNTB, among whom 283 (92.5%) were 15-64 years of age, 159 (52.0%) were female, and 293 (95.8%) were foreign-born. Respiratory symptoms were present in 21.6%, and abnormal chest radiograph in 23.2%. Sputum culture positivity ranged from 12.9% in patients with no symptoms and normal lung parenchyma to 66.7% in patients with both. Respiratory symptoms, abnormal lung parenchyma, and HIV-coinfection (borderline) were independent predictors of sputum culture positivity (odds ratio [OR] 2.24 [95% confidence interval [CI] 1.15-4.39], P = 0.01, OR 4.78 [95% CI 2.41-9.48], P < 0.001, and OR 2.54 [95% CI 0.99-6.52], P = 0.05), respectively. Among contacts of sputum culture-positive PLNTB patients, one secondary case and 16 new infections were identified. CONCLUSION: Isochronous PTB is common in PLNTB patients. Routine screening of PLNTB patients for PTB is strongly recommended.

Compilation of 10 Years of MIRU-VNTR Data: Canadian National Tuberculosis Laboratory's Experience.

Tuberculosis is a significant cause of morbidity worldwide and is a priority at the provincial and federal levels in Canada. It is known that tuberculosis transmission networks are complex and span many years as well as different jurisdictions and countries. MIRU-VNTR is a universal tuberculosis genotyping method that utilizes a 24-loci pattern and it has shown promise in identifying inter and intrajurisdictional clusters within Canada. MIRU-VNTR data collected over 10 years from the National Reference Centre for Mycobacteriology (NRCM) were analyzed in this study. Some clusters were unique to a single province/territory, while others spanned multiple provinces and/or territories in Canada. The use of a universal laboratory test can enhance contact tracing, provide geographical information on circulating genotypes, and hence, aid in tuberculosis investigation by public health. The housing of all data on one platform, technical ease of the method, easy exchange of data between jurisdictions, and strong collaboration with laboratories and surveillance units at the provincial and federal levels have the potential to identify possible outbreaks in real time.

Invasive Pneumococcal Disease and Long-Term Mortality Rates in Adults, Alberta, Canada.

The relationship between increased short-term mortality rates after invasive pneumococcal disease (IPD) has been frequently studied. However, the relationship between IPD and long-term mortality rates is unknown. IPD patients in Alberta, Canada, had clinical data collected that were linked to administrative databases. We used Cox proportional hazards modeling, and the primary outcome was time to all-cause deaths. First IPD events were identified in 4,522 patients, who had a median follow-up of 3.2 years (interquartile range 0.8‒9.1 years). Overall all-cause mortality rates were consistently higher among cases than controls at 30 days (adjusted hazard ratio [aHR] 3.75, 95% CI 3.29-4.28), 30‒90 days (aHR 1.56, 95% CI 1.27‒1.93), and >90 days (aHR 1.43, 95% CI 1.33-1.54). IPD increases risk for short, intermediate, and long-term mortality rates regardless of age, sex, or concurrent conditions. These findings can help clinicians focus on postdischarge patient plans to limit long-term effects after acute IPD infection.

Bartonella quintana endocarditis in a child from Northern Manitoba, Canada.

We describe a case of Bartonella quintana endocarditis in an 11-year-old child from Northern Manitoba, Canada. This case demonstrates the neglected endemicity of B. quintana in Northern Canada and highlights the need for improved case finding and elucidation of specific risk factors for B. quintana infection in the Canadian North. Considering B. quintana's predominant transmission via body lice ectoparasitosis, we hypothesize that B. quintana's endemicity in Northern Canada is linked to inadequate access to suitable housing and running water among remote communities in the Canadian North.

Antimicrobial resistance (AMR) in COVID-19 patients: a systematic review and meta-analysis (November 2019-June 2021).

BACKGROUND: Pneumonia from SARS-CoV-2 is difficult to distinguish from other viral and bacterial etiologies. Broad-spectrum antimicrobials are frequently prescribed to patients hospitalized with COVID-19 which potentially acts as a catalyst for the development of antimicrobial resistance (AMR). OBJECTIVES: We conducted a systematic review and meta-analysis during the first 18 months of the pandemic to quantify the prevalence and types of resistant co-infecting organisms in patients with COVID-19 and explore differences across hospital and geographic settings. METHODS: We searched MEDLINE, Embase, Web of Science (BioSIS), and Scopus from November 1, 2019 to May 28, 2021 to identify relevant articles pertaining to resistant co-infections in patients with laboratory confirmed SARS-CoV-2. Patient- and study-level analyses were conducted. We calculated pooled prevalence estimates of co-infection with resistant bacterial or fungal organisms using random effects models. Stratified meta-analysis by hospital and geographic setting was also performed to elucidate any differences. RESULTS: Of 1331 articles identified, 38 met inclusion criteria. A total of 1959 unique isolates were identified with 29% (569) resistant organisms identified. Co-infection with resistant bacterial or fungal organisms ranged from 0.2 to 100% among included studies. Pooled prevalence of co-infection with resistant bacterial and fungal organisms was 24% (95% CI 8-40%; n = 25 studies: I2 = 99%) and 0.3% (95% CI 0.1-0.6%; n = 8 studies: I2 = 78%), respectively. Among multi-drug resistant organisms, methicillin-resistant Staphylococcus aureus, carbapenem-resistant Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and multi-drug resistant Candida auris were most commonly reported. Stratified analyses found higher proportions of AMR outside of Europe and in ICU settings, though these results were not statistically significant. Patient-level analysis demonstrated > 50% (n = 58) mortality, whereby all but 6 patients were infected with a resistant organism. CONCLUSIONS: During the first 18 months of the pandemic, AMR prevalence was high in COVID-19 patients and varied by hospital and geography although there was substantial heterogeneity. Given the variation in patient populations within these studies, clinical settings, practice patterns, and definitions of AMR, further research is warranted to quantify AMR in COVID-19 patients to improve surveillance programs, infection prevention and control practices and antimicrobial stewardship programs globally.

Ten Years of Diphtheria Toxin Testing and Toxigenic Cutaneous Diphtheria Investigations in Alberta, Canada: A Highly Vaccinated Population.

BACKGROUND: Respiratory diphtheria is a potentially fatal toxin-mediated disease that is rare among highly vaccinated populations. Cutaneous infections with toxigenic Corynebacterium diphtheriae are most commonly linked to travel to an endemic region. Corynebacterium ulcerans has emerged as a predominant, locally acquired cause of respiratory and cutaneous diphtheria in Western Europe. Recently, public health agencies from several highly vaccinated regions expanded their guidelines to investigate toxigenic cutaneous diphtheria regardless of travel history. With relatively unknown epidemiology of C diphtheriae in North America, and increasing diphtheria toxin testing over the last decade, this change could lead to substantial increases in public health investigations with unclear benefits. METHODS: This study examined the diagnostic and public health benefits of toxigenic cutaneous diphtheria investigations in the highly vaccinated population of Alberta, Canada, where travel history is not required for cutaneous diphtheria investigations. All C diphtheriae isolates collected between 2010 and 2019 were reviewed for specimen source, toxigenicity, biovar, and associated clinical and public health data. RESULTS: Of these, 5% of C diphtheriae isolates were toxigenic and 82% were isolated from cutaneous sites. Three cases of toxigenic cutaneous disease were identified, none from patients with recent travel. Contact tracing identified asymptomatic C diphtheriae colonization among 0%-26% of close contacts, with identical isolate profiles among colonized contacts and primary cases. CONCLUSIONS: Cutaneous diphtheria in nonendemic regions warrants public health investigation regardless of travel history and overall vaccination levels. This study underscores the importance of including C ulcerans in public health guidelines to assess the overall prevalence and epidemiology of toxigenic corynebacteria.

Clinical Presentations and Outcomes of Children in Canada With Recurrent Invasive Pneumococcal Disease From the IMPACT Surveillance Network.

BACKGROUND: Invasive pneumococcal disease due to Streptococcus pneumoniae can cause mortality and severe morbidity due to sepsis, meningitis and pneumonia, particularly in young children and the elderly. Recurrent invasive pneumococcal disease is rare yet serious sequelae of invasive pneumococcal disease that is associated with the immunocompromised and leads to a high mortality rate. METHOD: This retrospective study reviewed recurrent invasive pneumococcal disease cases from the Canadian Immunization Monitoring Program, ACTive (IMPACT) between 1991 and 2019, an active network for surveillance of vaccine-preventable diseases and adverse events following immunization for children ages 0-16 years. Data were collected from 12 pediatric tertiary care hospitals across all 3 eras of public pneumococcal conjugate vaccine implementation in Canada. RESULTS: The survival rate within our cohort of 180 recurrent invasive pneumococcal disease cases was 98.3%. A decrease of 26.4% in recurrent invasive pneumococcal disease due to vaccine serotypes was observed with pneumococcal vaccine introduction. There was also a 69.0% increase in the rate of vaccination in children with preexisting medical conditions compared with their healthy peers. CONCLUSION: The decrease in recurrent invasive pneumococcal disease due to vaccine-covered serotypes has been offset by an increase of non-vaccine serotypes in this sample of Canadian children.

Invasive pneumococcal disease and long-term outcomes in children: A 20-year population cohort study.

Background: Although vaccination against Streptococcus pneumoniae infections (such as invasive pneumococcal disease (IPD)) are available, challenges remain in prevention efforts. Moreover, downstream sequelae in children is relatively unknown. Thus, we aimed to evaluate short and long-term health outcomes among children with IPD. Methods: Analysis of Streptococcus pneumoniae positive isolates from sterile body sites in children (0-17 years) in Alberta (Canada) from 1999 to 2019 was performed retrospectively (n=888). Cases were age and sex-matched to hospitalized population controls. Linkage to administrative health datasets was done to determine comorbidities and healthcare related outcomes. Cox proportional hazards were used to assess differences in time to mortality and hospitalisation between cases and controls in short (<30-day), intermediate (30-90 day), long-term (>90-day) follow-up. Findings: Proportionally more deaths occurred in cases (4.8 deaths/1000 person-years (PY)) than controls (2.7 deaths/1000 PY), leading to a significant adjusted hazard ratio (aHR) of 1.80 (95% CI 1.22-2.64). This increased risk of death was influenced primarily by short-term mortality (319 vs 36 deaths/1000 PY in cases vs controls respectively, aHR 8.78 [95% CI 3.33-23.18]), as no differences were seen in intermediate (14 vs 7 deaths/1000 PY; aHR 2.03, 95% CI 0.41-10.04) or long-term time intervals (2.4 vs 2.3 deaths/1000 PY, aHR 1.03, 95% CI 0.63-1.69). Interpretation: IPD continues to negatively impact survival in children despite vaccination. Although long-term impact on mortality and hospitalisations may not be substantial, the immediate effects of IPD are significant. Funding: This work was supported by grants-in-aid from Pfizer Canada and Wyeth Canada Inc all to GJT.

Linear Regression Equations To Predict ß-Lactam, Macrolide, Lincosamide, and Fluoroquinolone MICs from Molecular Antimicrobial Resistance Determinants in Streptococcus pneumoniae.

Antimicrobial resistance in Streptococcus pneumoniae represents a threat to public health, and monitoring the dissemination of resistant strains is essential to guiding health policy. Multiple-variable linear regression modeling was used to determine the contributions of molecular antimicrobial resistance determinants to antimicrobial MICs for penicillin, ceftriaxone, erythromycin, clarithromycin, clindamycin, levofloxacin, and trimethoprim-sulfamethoxazole. Training data sets consisting of Canadian S. pneumoniae isolates obtained from 1995 to 2019 were used to generate multiple-variable linear regression equations for each antimicrobial. The regression equations were then applied to validation data sets of Canadian (n = 439) and U.S. (n = 607 and n = 747) isolates. The MICs for ß-lactam antimicrobials were fully explained by amino acid substitutions in motif regions of the penicillin binding proteins PBP1a, PPB2b, and PBP2x. Accuracies of predicted MICs within 1 doubling dilution to phenotypically determined MICs were 97.4% for penicillin, 98.2% for ceftriaxone, 94.8% for erythromycin, 96.6% for clarithromycin, 98.2% for clindamycin, 100% for levofloxacin, and 98.8% for trimethoprim-sulfamethoxazole, with an overall sensitivity of 95.8% and specificity of 98.0%. Accuracies of predicted MICs to the phenotypically determined MICs were similar to those of phenotype-only MIC comparison studies. The ability to acquire detailed antimicrobial resistance information directly from molecular determinants will facilitate the transition from routine phenotypic testing to whole-genome sequencing analysis and can fill the surveillance gap in an era of increased reliance on nucleic acid assay diagnostics to better monitor the dynamics of S. pneumoniae.

Invasive group A streptococcal disease surveillance in Canada, 2020.

Background: Invasive group A streptococcal (iGAS) disease (caused by Streptococcus pyogenes) has been a nationally notifiable disease in Canada since 2000. This report summarizes the demographics, emm types and antimicrobial resistance of iGAS infections in Canada in 2020. Methods: The Public Health Agency of Canada's National Microbiology Laboratory (Winnipeg, Manitoba) collaborates with provincial and territorial public health laboratories to conduct national surveillance of invasive S. pyogenes. Emm typing was performed on all isolates using the Centers for Disease Control and Prevention emm sequencing protocol. Antimicrobial susceptibilities were determined using Kirby-Bauer disk diffusion according to Clinical and Laboratory Standards Institute guidelines. Population-based iGAS disease incidence rates up to 2019 were obtained through the Canadian Notifiable Disease Surveillance System. Results: Overall, the incidence of iGAS disease in Canada has increased from 4.0 to 8.1 cases per 100,000 population from 2009 to 2019. The 2019 incidence represents a slight decrease from the 2018 rate of 8.6 cases per 100,000 population. A total of 2,867 invasive S. pyogenes isolates that were collected during 2020 are included in this report, representing a decrease from 2019 (n=3,194). The most common emm types in 2020 were emm49 (16.8%, n=483) and emm76 (15.0%, n=429), both increasing significantly in prevalence since 2016 (p<0.001). The former most prevalent type, emm1, decreased to 7.6% (n=217) in 2020 from 15.4% (n=325) in 2016. Antimicrobial resistance rates in 2020 included 11.5% resistance to erythromycin, 3.2% resistance to clindamycin and 1.6% nonsusceptibility to chloramphenicol. Conclusion: Though the number of collected invasive S. pyogenes isolates decreased slightly in 2020 in comparison to previous years, iGAS disease remains an important public health concern. The emm distribution in Canada has been subtly shifting over the past five years, away from common and well-known emm1 and towards emm49 and emm76. It is important to continue surveillance of S. pyogenes in Canada to monitor expanding replacement emm types, as well as outbreak clones and antimicrobial resistance.

Invasive pneumococcal disease surveillance in Canada, 2020.

Background: Invasive pneumococcal disease (IPD), which is caused by Streptococcus pneumoniae, has been a nationally notifiable disease in Canada since 2000. The use of conjugate vaccines has markedly decreased the incidence of IPD in Canada; however, the distribution of serotypes has shifted in favour of non-vaccine types. This report summarizes the demographics, serotypes and antimicrobial resistance of IPD infections in Canada in 2020. Methods: The Public Health Agency of Canada's National Microbiology Laboratory (Winnipeg, Manitoba) collaborates with provincial and territorial public health laboratories to conduct national surveillance of IPD. A total of 2,108 IPD isolates were reported in 2020. Serotyping was performed by Quellung reaction and antimicrobial susceptibilities were determined in collaboration with the University of Manitoba/Canadian Antimicrobial Resistance Alliance. Population-based IPD incidence rates were obtained through the Canadian Notifiable Disease Surveillance System. Results: Overall incidence of IPD in Canada decreased significantly from 11.5 (95% confidence interval [CI]: 10.1-13.1) to 6.0 (95% CI: 5.0-7.2), and from 10.0 (95% CI: 9.7-10.3) to 5.9 (95% CI: 5.7-6.2) cases per 100,000 from 2019 to 2020; in those younger than five years and those five years and older, respectively. The most common serotypes overall were 4 (11.2%, n=237), 3 (10.9%, n=229) and 8 (7.2%, n=151). From 2016 to 2020, serotypes with increasing trends (p<0.05) included 4 (6.4%-11.2%), 3 (9.5%-10.9%), 8 (5.2%-7.2%) and 12F (3.6%-5.7%). The overall prevalence of PCV13 serotypes increased over the same period (30.3%-34.9%, p<0.05). Antimicrobial resistance rates in 2020 included 23.0% clarithromycin and 9.9% penicillin (IV meningitis breakpoints). Multidrug-resistant IPD has significantly increased since 2016 (4.2%-9.5%, p<0.05). Conclusion: Though the incidence of IPD decreased in 2020 in comparison to previous years across all age groups, disease due to PCV13 serotypes 3 and 4, as well as non-PCV13 serotypes such as 8 and 12F, increased in prevalence. Continued surveillance of IPD is imperative to monitor shifts in serotype distribution and antimicrobial resistance.