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Background: A study was conducted in the Calgary Health Region between May 2002 and April 2004 to define the population-based epidemiological characteristics of infections caused by imipenem-resistant Pseudomonas aeruginosa and to explore the clinical outcomes due to metallo- beta -lactamase (MBL)-producing and non-MBL-producing strains.Methods: Detailed clinical information was obtained by chart review, and phenotypic and molecular characterizations were performed using the MBL E-test, polymerase chain reaction with sequencing, and pulsed-field gel electrophoresis.Results: A total of 228 patients with infections caused by imipenem-resistant P. aeruginosa were identified (annual incidence, 10.5 cases/100,000 population), with the highest incidence rate in those >or=75 years old. MBL-producing strains (98/228) were associated with higher rates of multidrug resistance and bacteremia. Ninety MBL-producing strains also produced VIM-2, 4 produced IMP-7, and 4 were unclassified. A cluster of VIM-2-producing strains was responsible for a nosocomial outbreak during 2003. The case-fatality rate was significantly higher for infections caused by MBL-producing strains than for those caused by non-MBL-producing strains (25% vs. 13%; relative risk, 1.98 [95% confidence interval, 1.00-3.90]; P=.05).Conclusion: MBL-producing P. aeruginosa strains were associated with a higher case-fatality rate and invasive disease. Our study highlights the potential importance of molecular laboratory techniques in infection control and patient care. [ABSTRACT FROM AUTHOR]

Objectives: In high-income countries hepatitis E virus (HEV) is an uncommonly diagnosed porcine-derived zoonoses. After identifying disproportionate chronic HEV infections in persons with cystic fibrosis (pwCF) postlung transplant, we sought to understand its epidemiology and potential drivers., Design: All pwCF post-transplant attending our regional CF centre were screened for HEV. HEV prevalence was compared against non-transplanted pwCF and with all persons screened for suspected HEV infection from 2016 to 2022 in Alberta, Canada. Those with chronic HEV infection underwent genomic sequencing and phylogenetic analysis. Owing to their swine derivation, independently sourced pancreatic enzyme replacement therapy (PERT) capsules were screened for HEV., Results: HEV seropositivity was similar between transplanted and non-transplanted pwCF (6/29 (21%) vs 16/83 (19%); p=0.89). Relative to all other Albertans investigated for HEV as a cause of hepatitis (n=115/1079, 10.7%), pwCF had a twofold higher seropositivity relative risk and this was four times higher than the Canadian average. Only three chronic HEV infection cases were identified in all of Alberta, all in CF lung transplant recipients (n=3/29, 10.3%). Phylogenetics confirmed cases were unrelated porcine-derived HEV genotype 3a. Ninety-one per cent of pwCF were taking PERT (median 8760 capsules/person/year). HEV RNA was detected by RT-qPCR in 44% (47/107) of PERT capsules, and sequences clustered with chronic HEV cases., Conclusion: PwCF had disproportionate rates of HEV seropositivity, regardless of transplant status. Chronic HEV infection was evident only in CF transplant recipients. HEV may represent a significant risk for pwCF, particularly post-transplant. Studies to assess HEV incidence and prevalence in pwCF, and potential role of PERT are required., Competing Interests: Competing interests: SEC: reports grants from Bristol-Myers Squibb Canada, Gilead Sciences, Genfit, Allergan, Axcella Health, and Sequana Medical and personal fees from Intercept Pharmaceuticals, Eisai, Paladin Labs, AstraZeneca and Novo Nordisk outside the submitted work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In persons with cystic fibrosis (pwCF), little is known about the prevalence or impact of HPV on quality of life and attitudes towards vaccination., Methods: We conducted a national online survey of adult pwCF. We sought to determine the prevalence of self-reported HPV infection, disease-associated complications and effects on quality of life. Additionally, we investigated factors associated with vaccination status., Results: A total of 235 adult pwCF across Canada (≥18 years, 68% female) completed the survey. Forty-eight percent of female pwCF had a history of abnormal Pap smear, with 62% self-reporting a 'no' or 'low' chance of risk of HPV-associated disease. Across participants, 12% reported at least one HPV-associated complication including anogenital warts (58%), HPV-associated malignancies (34%) and cervical dysplasia requiring colposcopy (69%). Only 19% reported discussions with their CF care provider around HPV complications. Across both sexes, pwCF experienced high psychosocial burden in the domains of 'worries and concerns', 'sexual impact' and 'self-image'. Sixty percent of adult pwCF were unvaccinated for HPV. Eighty-one percent reported never having discussed HPV vaccination with their CF care provider, with similar rates in vaccinated and unvaccinated groups. Barriers to vaccination included: lack of discussions with healthcare providers (31%), insured coverage (based on age) (19%) and perceived side effects/risk (10%)., Conclusions: Across adult pwCF, we found high prevalence of HPV disease and associated HPV-psychosocial burden and low vaccination uptake. Given the limited medical discussions reported, incorporation of HPV prevention and management should be prioritized by CF care providers as part of comprehensive multimodal care., Competing Interests: Declaration of Competing Interest There are no conflicts of interests for any authors in regard to this study., (Copyright © 2023 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Rationale: Chronic infection with Stenotrophomonas maltophilia in persons with cystic fibrosis (pwCF) has been linked to an increased risk of pulmonary exacerbations and lung function decline. We sought to establish whether baseline sputum microbiome associates with risk of S. maltophilia incident infection and persistence in pwCF., Methods: pwCF experiencing incident S. maltophilia infections attending the Calgary Adult CF Clinic from 2010-2018 were compared with S. maltophilia -negative sex, age (+/-2 years), and birth-cohort-matched controls. Infection outcomes were classified as persistent (when the pathogen was recovered in ≥50% of cultures in the subsequent year) or transient. We assessed microbial communities from prospectively biobanked sputum using V3-V4 16S ribosomal RNA (rRNA) gene sequencing, in the year preceding (Pre) ( n  = 57), at (At) ( n  = 22), and after (Post) ( n  = 31) incident infection. We verified relative abundance data using S. maltophilia -specific qPCR and 16S rRNA-targeted qPCR to assess bioburden. Strains were typed using pulse-field gel electrophoresis., Results: Twenty-five pwCF with incident S. maltophilia (56% female, median 29 years, median FEV 1 61%) with 33 total episodes were compared with 56 uninfected pwCF controls. Demographics and clinical characteristics were similar between cohorts. Among those with incident S. maltophilia infection, sputum communities did not cluster based on infection timeline (Pre, At, Post). Communities differed between the infection cohort and controls ( n  = 56) based on Shannon Diversity Index (SDI, p  = 0.04) and clustered based on Aitchison distance (PERMANOVA, p  = 0.01) prior to infection. At the time of incident S. maltophilia isolation, communities did not differ in SDI but clustered based on Aitchison distance (PERMANOVA, p  = 0.03) in those that ultimately developed persistent infection versus those that were transient. S. maltophilia abundance within sputum was increased in samples from patients (Pre) relative to controls, measuring both relative ( p  = 0.004) and absolute ( p  = 0.001). Furthermore, S. maltophilia abundance was increased in sputum at incident infection in those who ultimately developed persistent infection relative to those with transient infection, measured relatively ( p  = 0.04) or absolute ( p  = 0.04), respectively., Conclusion: Microbial community composition of CF sputum associates with S. maltophilia infection acquisition as well as infection outcome. Our study suggests sputum microbiome may serve as a surrogate for identifying infection risk and persistence risk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bowron, Acosta, Thornton, Carpentero, Waddell, Bharadwaj, Ebbert, Castañeda-Mogollón, Conly, Rabin, Surette and Parkins.)

Wastewater-based surveillance has become an important tool for research groups and public health agencies investigating and monitoring the COVID-19 pandemic and other public health emergencies including other pathogens and drug abuse. While there is an emerging body of evidence exploring the possibility of predicting COVID-19 infections from wastewater signals, there remain significant challenges for statistical modeling. Longitudinal observations of viral copies in municipal wastewater can be influenced by noisy datasets and missing values with irregular and sparse samplings. We propose an integrative Bayesian framework to predict daily positive cases from weekly wastewater observations with missing values via functional data analysis techniques. In a unified procedure, the proposed analysis models severe acute respiratory syndrome coronavirus-2 RNA wastewater signals as a realization of a smooth process with error and combines the smooth process with COVID-19 cases to evaluate the prediction of positive cases. We demonstrate that the proposed framework can achieve these objectives with high predictive accuracies through simulated and observed real data., (© 2024 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.)

Wastewater-based surveillance (WBS) has undergone dramatic advancement in the context of the coronavirus disease 2019 (COVID-19) pandemic. The power and potential of this platform technology were rapidly realized when it became evident that not only did WBS-measured SARS-CoV-2 RNA correlate strongly with COVID-19 clinical disease within monitored populations but also, in fact, it functioned as a leading indicator. Teams from across the globe rapidly innovated novel approaches by which wastewater could be collected from diverse sewersheds ranging from wastewater treatment plants (enabling community-level surveillance) to more granular locations including individual neighborhoods and high-risk buildings such as long-term care facilities (LTCF). Efficient processes enabled SARS-CoV-2 RNA extraction and concentration from the highly dilute wastewater matrix. Molecular and genomic tools to identify, quantify, and characterize SARS-CoV-2 and its various variants were adapted from clinical programs and applied to these mixed environmental systems. Novel data-sharing tools allowed this information to be mobilized and made immediately available to public health and government decision-makers and even the public, enabling evidence-informed decision-making based on local disease dynamics. WBS has since been recognized as a tool of transformative potential, providing near-real-time cost-effective, objective, comprehensive, and inclusive data on the changing prevalence of measured analytes across space and time in populations. However, as a consequence of rapid innovation from hundreds of teams simultaneously, tremendous heterogeneity currently exists in the SARS-CoV-2 WBS literature. This manuscript provides a state-of-the-art review of WBS as established with SARS-CoV-2 and details the current work underway expanding its scope to other infectious disease targets., Competing Interests: The authors declare no conflict of interest.

Objective: Sinus disease is prevalent in persons with cystic fibrosis (PwCF) and may be a reservoir of airway infection in postlung transplant (pTx) patients. The microbial composition of cystic fibrosis sinuses and its associations with chronic rhinosinusitis (CRS) is relatively unexplored. We aimed to examine the sinus and lower airway microbiome and their associations with CRS in PwCF and pTxPwCF., Study Design: Prospective single-centre study., Setting: A total of 31 sex and age (±2 years) matched PwCF and pTxPwCF., Methods: Demographic and clinical data along with sinus swabs and sputum were collected. CRS was assessed using Sinonasal Outcome Test-22 (SNOT-22) (patient reported outcome) and Lund-McKay (computed tomography sinus) scores. Samples underwent MiSeq Illumina sequencing of the universal 16S ribosomal RNA gene., Results: A total of 31 PwCF (15 pTxPwCF) were included. Aggregate airways microbiome composition was dominated by Pseudomonas (46%), Haemophilus (14%), Staphylococcus (11%), Streptococcus (10%), and Fusobacterium (6%). α-diversity was significantly lower in post-Tx samples across both sputum and sinus samples ( P  = .005). β-diversity was significantly different between sputum ( P  = .004), but not sinus ( P  = .75) samples by transplant status. While there was a trend in higher β-diversity associated with lower SNOT-22 score at time of first visit, this did not reach significance ( P  = .05)., Conclusion: Sinus and airway microbiomes differed in PwCF and pTxPwCF, but the prevalent organisms remained consistent. Elucidating the relationship of the microbiome with clinical status to better understand when to intervene accordingly is needed to optimize sinus disease management in PwCF., Competing Interests: There are no conflicts of interests for any authors in regard to this study., (© 2024 The Authors. OTO Open published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology‐Head and Neck Surgery Foundation.)

Intracavitary pulmonary aspergilloma is a persistent and life-threatening infection that carries a mortality rate of up to 15%. It occurs when Aspergillus species gain entry to an existing lung cavity. In the absence of definitive treatment, patients may succumb to severe complications such as massive hemoptysis, cachexia, or secondary infections. Aspergillomas often show limited response to antifungal medications, mainly due to insufficient drug concentrations within the cavities. Surgery is frequently the preferred treatment option, but it poses significant risks, and many individuals are ineligible due to underlying health issues. We present the most extensive non-surgical fungal ball cohort to date, managed using an innovative multimodal strategy that combines antifungal therapy before and after bronchoscopic debulking. This was a cross-sectional observational study. For those who cannot undergo surgery, our medical center has pioneered a multimodal approach to aspergilloma resection. This approach combines bronchoscopic endoscopy with antifungal therapy and has been applied successfully to more than 18 patients that are presented in this series. The median age of the cohort was 58 years (range: 32-73), with an equal sex distribution. The mean percent predicted FEV 1 was 65.3%. The mean follow-up duration was 3.6 years (range: 0.5-10 years). The cohort receiving antifungals systematically prior to debridement showed a reduction of the pre-existing cavity (40.38 mm versus 34.02 mm, p  = 0.021). Across the 18 patients during the follow-up period, 94% remained recurrence-free (defined by symptoms and radiology). Our study fills a critical knowledge gap regarding the significance of initiating antifungal treatment before bronchoscopic debulking and presents a viable approach in these cases for which there is a current unmet therapeutic need.

Staphylococcus aureus is the most prevalent cystic fibrosis (CF) pathogen. Several phenotypes are associated with worsened CF clinical outcomes including methicillin-resistance and small-colony-variants. The inoculum effect (IE) is characterized by reduced β-lactam susceptibility when assessed at high inoculum. The IE associates with worse outcomes in bacteremia and other high-density infections, and may therefore be relevant to CF. The prevalence of IE amongst a CF cohort (age ≥18 years), followed from 2013 to 2016, was investigated. Yearly methicillin-sensitive S. aureus (MSSA) isolates were screened at standard (5 × 10 5 CFU/mL) and high (5 × 10 7 CFU/mL) inoculum against narrow-spectrum anti-Staphylococcal β-lactams and those with anti-pseudomonal activity common to CF. A ≥ 4-fold increase in minimum inhibitory concentration between standard and high inoculum defined IE. Isolates underwent blaZ sequencing and genotyping and were compared against published genomes. Fifty-six percent (99/177) of individuals had MSSA infection. MSSA was observed at ≥10 5 CFU/mL in 44.8% of entry sputum samples. The prevalence of the IE was 25.0%-cefazolin; 13.5%-cloxacillin; 0%-meropenem; 1.0%-cefepime; 5.2%-ceftazidime; and 34.4%-piperacillin-tazobactam amongst baseline MSSA isolates assessed. blaZ A associated with cefazolin IE ( P = 0.0011), whereas blaZ C associated with piperacillin-tazobactam IE ( P < 0.0001). Baseline demographics did not reveal specific risk factors for IE-associated infections, nor were long-term outcomes different. Herein, we observed the IE in CF-derived MSSA disproportionally for cefazolin and piperacillin-tazobactam and this phenotype strongly associated with underlying blaZ genotype. The confirmation of CF being a high density infection, and the identification of high prevalence of MSSA with IE in CF supports the need for prospective pulmonary exacerbation treatment studies to understand the impact of this phenotype., Competing Interests: The authors declare no conflict of interest.

Wastewater-based surveillance (WBS) of infectious diseases is a powerful tool for understanding community COVID-19 disease burden and informing public health policy. The potential of WBS for understanding COVID-19's impact in non-healthcare settings has not been explored to the same degree. Here we examined how SARS-CoV-2 measured from municipal wastewater treatment plants (WWTPs) correlates with workforce absenteeism. SARS-CoV-2 RNA N1 and N2 were quantified three times per week by RT-qPCR in samples collected at three WWTPs servicing Calgary and surrounding areas, Canada (1.4 million residents) between June 2020 and March 2022. Wastewater trends were compared to workforce absenteeism using data from the largest employer in the city (>15,000 staff). Absences were classified as being COVID-19-related, COVID-19-confirmed, and unrelated to COVID-19. Poisson regression was performed to generate a prediction model for COVID-19 absenteeism based on wastewater data. SARS-CoV-2 RNA was detected in 95.5 % (85/89) of weeks assessed. During this period 6592 COVID-19-related absences (1896 confirmed) and 4524 unrelated absences COVID-19 cases were recorded. A generalized linear regression using a Poisson distribution was performed to predict COVID-19-confirmed absences out of the total number of absent employees using wastewater data as a leading indicator (P < 0.0001). The Poisson regression with wastewater as a one-week leading signal has an Akaike information criterion (AIC) of 858, compared to a null model (excluding wastewater predictor) with an AIC of 1895. The likelihood-ratio test comparing the model with wastewater signal with the null model shows statistical significance (P < 0.0001). We also assessed the variation of predictions when the regression model was applied to new data, with the predicted values and corresponding confidence intervals closely tracking actual absenteeism data. Wastewater-based surveillance has the potential to be used by employers to anticipate workforce requirements and optimize human resource allocation in response to trackable respiratory illnesses like COVID-19., Competing Interests: Declaration of competing interest The authors have declared no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Wastewater-based surveillance (WBS) has been established as a powerful tool that can guide health policy at multiple levels of government. However, this approach has not been well assessed at more granular scales, including large work sites such as University campuses. Between August 2021 and April 2022, we explored the occurrence of SARS-CoV-2 RNA in wastewater using qPCR assays from multiple complimentary sewer catchments and residential buildings spanning the University of Calgary's campus and how this compared to levels from the municipal wastewater treatment plant servicing the campus. Real-time contact tracing data was used to evaluate an association between wastewater SARS-CoV-2 burden and clinically confirmed cases and to assess the potential of WBS as a tool for disease monitoring across worksites. Concentrations of wastewater SARS-CoV-2 N1 and N2 RNA varied significantly across six sampling sites - regardless of several normalization strategies - with certain catchments consistently demonstrating values 1-2 orders higher than the others. Relative to clinical cases identified in specific sewersheds, WBS provided one-week leading indicator. Additionally, our comprehensive monitoring strategy enabled an estimation of the total burden of SARS-CoV-2 for the campus per capita, which was significantly lower than the surrounding community (p≤0.001). Allele-specific qPCR assays confirmed that variants across campus were representative of the community at large, and at no time did emerging variants first debut on campus. This study demonstrates how WBS can be efficiently applied to locate hotspots of disease activity at a very granular scale, and predict disease burden across large, complex worksites., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Stenotrophomonas maltophilia is an opportunistic pathogen infecting persons with cystic fibrosis (pwCF) and portends a worse prognosis. Studies of S. maltophilia infection dynamics have been limited by cohort size and follow-up. We investigated the natural history, transmission potential, and evolution of S. maltophilia in a large Canadian cohort of 321 pwCF over a 37-year period., Methods: One-hundred sixty-two isolates from 74 pwCF (23%) were typed by pulsed-field gel electrophoresis, and shared pulsotypes underwent whole-genome sequencing., Results: S. maltophilia was recovered at least once in 82 pwCF (25.5%). Sixty-four pwCF were infected by unique pulsotypes, but shared pulsotypes were observed between 10 pwCF. In chronic carriage, longer time periods between positive sputum cultures increased the likelihood that subsequent isolates were unrelated. Isolates from individual pwCF were largely clonal, with differences in gene content being the primary source of genetic diversity objectified by gene content differences. Disproportionate progression of CF lung disease was not observed amongst those infected with multiple strains over time (versus a single) or amongst those with shared clones (versus strains only infecting one patient). We did not observe evidence of patient-to-patient transmission despite relatedness between isolates. Twenty-four genes with ≥ 2 mutations accumulated over time were identified across 42 sequenced isolates from all 11 pwCF with ≥ 2 sequenced isolates, suggesting a potential role for these genes in adaptation of S. maltophilia to the CF lung., Discussion: Genomic analyses suggested common, indirect sources as the origins of S. maltophilia infections in the clinic population. The information derived from a genomics-based understanding of the natural history of S. maltophilia infection within CF provides unique insight into its potential for in-host evolution., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Izydorczyk, Waddell, Thornton, Conly, Rabin, Somayaji, Surette, Church and Parkins.)

Progressive obstructive lung disease secondary to chronic airway infection, coupled with impaired host immunity, is the leading cause of morbidity and mortality in cystic fibrosis (CF). Classical pathogens found in the airways of persons with CF (pwCF) include Pseudomonas aeruginosa, Staphylococcus aureus, the Burkholderia cepacia complex, Achromobacter species, and Haemophilus influenzae. While traditional respiratory-tract surveillance culturing has focused on this limited range of pathogens, the use of both comprehensive culture and culture-independent molecular approaches have demonstrated complex highly personalized microbial communities. Loss of bacterial community diversity and richness, counteracted with relative increases in dominant taxa by traditional CF pathogens such as Burkholderia or Pseudomonas , have long been considered the hallmark of disease progression. Acquisition of these classic pathogens is viewed as a harbinger of advanced disease and postulated to be driven in part by recurrent and frequent antibiotic exposure driven by frequent acute pulmonary exacerbations. Recently, CF transmembrane conductance regulator (CFTR) modulators, small molecules designed to potentiate or restore diminished protein levels/function, have been successfully developed and have profoundly influenced disease course. Despite the multitude of clinical benefits, structural lung damage and consequent chronic airway infection persist in pwCF. In this article, we review the microbial epidemiology of pwCF, focus on our evolving understanding of these infections in the era of modulators, and identify future challenges in infection surveillance and clinical management., Competing Interests: None declared., (Thieme. All rights reserved.)

The severity and progression of lung disease are highly variable across individuals with cystic fibrosis (CF) and are imperfectly predicted by mutations in the human gene CFTR, lung microbiome variation or other clinical factors. The opportunistic pathogen Pseudomonas aeruginosa ( Pa ) dominates airway infections in most CF adults. Here we hypothesized that within-host genetic variation of Pa populations would be associated with lung disease severity. To quantify Pa genetic variation within CF sputum samples, we used deep amplicon sequencing (AmpliSeq) of 209 Pa genes previously associated with pathogenesis or adaptation to the CF lung. We trained machine learning models using Pa single nucleotide variants (SNVs), microbiome diversity data and clinical factors to classify lung disease severity at the time of sputum sampling, and to predict lung function decline after 5 years in a cohort of 54 adult CF patients with chronic Pa infection. Models using Pa SNVs alone classified lung disease severity with good sensitivity and specificity (area under the receiver operating characteristic curve: AUROC=0.87). Models were less predictive of lung function decline after 5 years (AUROC=0.74) but still significantly better than random. The addition of clinical data, but not sputum microbiome diversity data, yielded only modest improvements in classifying baseline lung function (AUROC=0.92) and predicting lung function decline (AUROC=0.79), suggesting that Pa AmpliSeq data account for most of the predictive value. Our work provides a proof of principle that Pa genetic variation in sputum tracks lung disease severity, moderately predicts lung function decline and could serve as a disease biomarker among CF patients with chronic Pa infections.

Importance: Infection transmission following endoscopic retrograde cholangiopancreatography (ERCP) can occur due to persistent contamination of duodenoscopes despite high-level disinfection to completely eliminate microorganisms on the instrument., Objective: To determine (1) contamination rates after high-level disinfection and (2) technical performance of duodenoscopes with disposable elevator caps compared with those with standard designs., Design, Setting, and Participants: In this parallel-arm multicenter randomized clinical trial at 2 tertiary ERCP centers in Canada, all patients 18 years and older and undergoing ERCP for any indication were eligible., Intervention: The intervention was use of duodenoscopes with disposable elevator caps compared with duodenoscopes with a standard design., Main Outcomes and Measures: Coprimary outcomes were persistent microbial contamination of the duodenoscope elevator or channel, defined as growth of at least 10 colony-forming units of any organism or any growth of gram-negative bacteria following high-level disinfection (superiority outcome), and technical success of ERCP according to a priori criteria (noninferiority outcome with an a priori noninferiority margin of 7%), assessed by blinded reviewers., Results: From December 2019 to February 2022, 518 patients were enrolled (259 disposable elevator cap duodenoscopes, 259 standard duodenoscopes). Patients had a mean (SD) age of 60.7 (17.0) years and 258 (49.8%) were female. No significant differences were observed between study groups, including in ERCP difficulty. Persistent microbial contamination was detected in 11.2% (24 of 214) of standard duodenoscopes and 3.8% (8 of 208) of disposable elevator cap duodenoscopes (P = .004), corresponding to a relative risk of 0.34 (95% CI, 0.16-0.75) and number needed to treat of 13.6 (95% CI, 8.1-42.7) to avoid persistent contamination. Technical success using the disposable cap scope was noninferior to that of the standard scope (94.6% vs 90.7%, P = .13). There were no differences between study groups in adverse events and other secondary outcomes., Conclusions and Relevance: In this randomized clinical trial, disposable elevator cap duodenoscopes exhibited reduced contamination following high-level disinfection compared with standard scope designs, without affecting the technical performance and safety of ERCP., Trial Registration: ClinicalTrials.gov Identifier: NCT04040504.

Background: Candidemia is increasing in frequency and is associated with high mortality. We sought to determine the burden of illness, the population it affects and its resistance profile in our region., Methods: The Calgary Zone (CZ) provides all care for residents of Calgary and surrounding communities (~ 1.69 million) via five tertiary hospitals each served by a common single laboratory for acute care microbiology. All adult patients in the CZ with at least one Candida spp.-positive blood culture between January 1, 2010, and December 31, 2018, were identified using microbiological data from Calgary Lab Services, the laboratory that processes > 95% of all blood culture samples in the CZ, were reviewed for the study., Results: The overall annual incidence of candidemia among individuals living in the CZ was 3.8 per 100,000 persons (Median age 61 years (IQR 48-72) and 221/455 (47.4%) were female). C. albicans was the most common species (50.6%), followed by C. glabrata, (24.0%). No other species accounted for more than 7% of cases. Overall mortality at 30, 90, and 365 days was 32.2, 40.1, and 48.1% respectively. Mortality rate did not differ by Candida species. Of individuals who developed candidemia, more than 50% died within the next year. No new resistance pattern has emerged in the most common Candida species in Calgary, Alberta., Conclusions: In Calgary, Alberta, the incidence of candidemia has not increased in the last decade. C. albicans was the most common species and it remains susceptible to fluconazole., (© 2023. The Author(s).)

Wastewater-based SARS-CoV-2 surveillance enables unbiased and comprehensive monitoring of defined sewersheds. We performed real-time monitoring of hospital wastewater that differentiated Delta and Omicron variants within total SARS-CoV-2-RNA, enabling correlation to COVID-19 cases from three tertiary-care facilities with >2100 inpatient beds in Calgary, Canada. RNA was extracted from hospital wastewater between August/2021 and January/2022, and SARS-CoV-2 quantified using RT-qPCR. Assays targeting R203M and R203K/G204R established the proportional abundance of Delta and Omicron, respectively. Total and variant-specific SARS-CoV-2 in wastewater was compared to data for variant specific COVID-19 hospitalizations, hospital-acquired infections, and outbreaks. Ninety-six percent (188/196) of wastewater samples were SARS-CoV-2 positive. Total SARS-CoV-2 RNA levels in wastewater increased in tandem with total prevalent cases (Delta plus Omicron). Variant-specific assessments showed this increase to be mainly driven by Omicron. Hospital-acquired cases of COVID-19 were associated with large spikes in wastewater SARS-CoV-2 and levels were significantly increased during outbreaks relative to nonoutbreak periods for total SARS-CoV2, Delta and Omicron. SARS-CoV-2 in hospital wastewater was significantly higher during the Omicron-wave irrespective of outbreaks. Wastewater-based monitoring of SARS-CoV-2 and its variants represents a novel tool for passive COVID-19 infection surveillance, case identification, containment, and potentially to mitigate viral spread in hospitals., (© 2022 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Haemophilus influenzae is a Gram-negative pathobiont, frequently recovered from the airways of persons with cystic fibrosis (pwCF). Previous studies of H. influenzae infection dynamics and transmission in CF predominantly used molecular methods, lacking resolution. In this retrospective cohort study, representative yearly H. influenzae isolates from all pwCF attending the Calgary Adult CF Clinic with H. influenzae positive sputum cultures between 2002 and 2016 were typed by pulsed-field gel electrophoresis. Isolates with shared pulsotypes common to ≥ 2 pwCF were sequenced by Illumina MiSeq. Phylogenetic and pangenomic analyses were used to assess genetic relatedness within shared pulsotypes, and epidemiological investigations were performed to assess potential for healthcare associated transmission. H. influenzae infection was observed to be common (33% of patients followed) and dynamic in pwCF. Most infected pwCF exhibited serial infections with new pulsotypes (75% of pwCF with ≥ 2 positive cultures), with up to four distinct pulsotypes identified from individual patients. Prolonged infection by a single pulsotype was only rarely observed. Intra-patient genetic diversity was observed at the single-nucleotide polymorphism and gene content levels. Seven shared pulsotypes encompassing 39% of pwCF with H. influenzae infection were identified, but there was no evidence, within our sampling scheme, of direct patient-to-patient infection transmission., (© 2022. The Author(s).)

Chronic lower respiratory tract infections are a leading contributor to morbidity and mortality in persons with cystic fibrosis (pwCF). Traditional respiratory tract surveillance culturing has focused on a limited range of classic pathogens; however, comprehensive culture and culture-independent molecular approaches have demonstrated complex communities highly unique to each individual. Microbial community structure evolves through the lifetime of pwCF and is associated with baseline disease state and rates of disease progression including occurrence of pulmonary exacerbations. While molecular analysis of the airway microbiome has provided insight into these dynamics, challenges remain including discerning not only "who is there" but "what they are doing" in relation to disease progression. Moreover, the microbiome can be leveraged as a multi-modal biomarker for both disease activity and prognostication. In this article, we review our evolving understanding of the role these communities play in pwCF and identify challenges in translating microbiome data to clinical practice., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society.)

Wastewater monitoring of SARS-CoV-2 enables early detection and monitoring of the COVID-19 disease burden in communities and can track specific variants of concern. We determined proportions of the Omicron and Delta variants across 30 municipalities covering >75% of the province of Alberta (population 4.5 million), Canada, during November 2021-January 2022. Larger cities Calgary and Edmonton exhibited more rapid emergence of Omicron than did smaller and more remote municipalities. Notable exceptions were Banff, a small international resort town, and Fort McMurray, a medium-sized northern community that has many workers who fly in and out regularly. The integrated wastewater signal revealed that the Omicron variant represented close to 100% of SARS-CoV-2 burden by late December, before the peak in newly diagnosed clinical cases throughout Alberta in mid-January. These findings demonstrate that wastewater monitoring offers early and reliable population-level results for establishing the extent and spread of SARS-CoV-2 variants.

Rationale: The pathobiology of Staphylococcus aureus in non-cystic fibrosis bronchiectasis (nCFB) is poorly defined. When present at high density or "inoculum," some methicillin-sensitive S. aureus (MSSA) can inefficiently degrade antistaphylococcal β-lactam antibiotics via BlaZ penicillinases (termed the "inoculum effect" [IE]). Given the high burden of organisms in bronchiectatic airways, this is particularly relevant. Objectives: Drawing from a prospectively collected biobank, we sought to understand the prevalence, natural history, potential for transmission, and antibiotic resistance profiles among nCFB-derived MSSA isolates. Methods: All individuals attending a regional consultancy nCFB clinic with sputum collected between 1981 and 2017 were considered, and those with one or more S. aureus -positive cultures composed the cohort. Each individual's most recent biobank isolate was subjected to whole-genome sequencing (including the blaZ gene), antibacterial susceptibility testing, and comparative β-lactam testing at standard (5 × 10 5  colony-forming unit [cfu]/ml) and high (5 × 10 7  cfu/ml) inocula to assess for the IE and pronounced IE. Results: Seventy-four (35.4%) of 209 individuals had one or more sputum samples with S. aureus (68 MSSA, 6 methicillin-resistant S. aureus ). Those with S. aureus infection were more likely to be female. Among 60 of 74 MSSA isolates subjected to whole-genome sequencing, no evidence of transmission was identified, although specific multilocus sequence typing types were prevalent, including ST-1, ST-15, ST-30, and ST-45. Antibiotic resistance was uncommon, except for macrolides (∼20%). Among the 60 MSSA samples, the prevalence of IE and pronounced IE was observed to be drug specific: meropenem (0% and 0%, respectively), cefepime (3% and 5%, respectively), ceftazidime (8% and 0%, respectively), cloxacillin (12% and 0%, respectively), cefazolin (23% and 0%, respectively), and piperacillin-tazobactam (37% and 17%, respectively). The cefazolin IE was associated with blaZ type A ( P  < 0.01) and ST-30 ( P  < 0.01), whereas the piperacillin-tazobactam IE was associated with type C blaZ ( P  < 0.001) and ST-15 ( P  < 0.05). Conclusions: S. aureus infection was common, although no evidence of transmission was apparent in our nCFB cohort. Although routine susceptibility testing did not identify significant resistance, inoculum-related resistance was found to be relevant for commonly used nCFB antibiotics, including cefazolin and piperacillin-tazobactam. Given previous associations between IEs and negative patient outcomes, further work is warranted to understand how this phenotype impacts nCFB disease progression.

Wastewater-based epidemiology (WBE) is an emerging surveillance tool that has been used to monitor the ongoing COVID-19 pandemic by tracking SARS-CoV-2 RNA shed into wastewater. WBE was performed to monitor the occurrence and spread of SARS-CoV-2 from three wastewater treatment plants (WWTP) and six neighborhoods in the city of Calgary, Canada (population 1.44 million). A total of 222 WWTP and 192 neighborhood samples were collected from June 2020 to May 2021, encompassing the end of the first-wave (June 2020), the second-wave (November end to December 2020) and the third-wave of the COVID-19 pandemic (mid-April to May 2021). Flow-weighted 24-hour composite samples were processed to extract RNA that was then analyzed for two SARS-CoV-2-specific regions of the nucleocapsid gene, N1 and N2, using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Using this approach SARS-CoV-2 RNA was detected in 98.06% (406/414) of wastewater samples. SARS-CoV-2 RNA abundance was compared to clinically diagnosed COVID-19 cases organized by the three-digit postal code of affected individuals' primary residences, enabling correlation analysis at neighborhood, WWTP and city-wide scales. Strong correlations were observed between N1 & N2 gene signals in wastewater and new daily cases for WWTPs and neighborhoods. Similarly, when flow rates at Calgary's three WWTPs were used to normalize observed concentrations of SARS-CoV-2 RNA and combine them into a city-wide signal, this was strongly correlated with regionally diagnosed COVID-19 cases and clinical test percent positivity rate. Linked census data demonstrated disproportionate SARS-CoV-2 in wastewater from areas of the city with lower socioeconomic status and more racialized communities. WBE across a range of urban scales was demonstrated to be an effective mechanism of COVID-19 surveillance., (Copyright © 2022. Published by Elsevier Ltd.)

Human papillomavirus (HPV) is the principal risk factor for cervical cancer. Transplant recipients are at a disproportionate risk of HPV complications. We conducted a single-centre, retrospective study of adult female cystic fibrosis (CF) lung transplant recipients between 2008 and 2021. We observed 12 of 34 (35.3%) with ≥1 abnormal pap smear (median age: 26.7 years). Complications included refractory anogenital warts (n=3), vulvectomy (n=2) and cervical cancer (n=4), with two deaths from metastatic disease. None with HPV morbidity was vaccinated. Lung transplant recipients had greater odds of cervical dysplasia relative to controls (OR, 3.98; 95% CI 1.17 to 11.82). CF care providers must prioritise HPV vaccination to attenuate potential future morbidity and mortality., Competing Interests: Competing interests: CT is supported by a Cystic Fibrosis Foundation Fellowship. RS has no conflicts relevant to this work but serves on Cystic Fibrosis Foundation and Cystic Fibrosis Canada advisory committees. AC has worked with Merck in an advisory capacity and serves an advisory role for Immunize Canada. MDP has no conflicts relevant to this work but serves as Vice Chair for Cystic Fibrosis Canada’s Research Advisory Committee., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Pyogenic liver abscess (PLA), although uncommon in North America, is associated with significant morbidity and mortality. We sought to re-examine the epidemiology, risk factors, and outcomes of PLA in a large, diverse Canadian health zone., Methods: All Calgary Health Zone (CHZ) residents aged ≥20 with PLA between 2015 and 2017 were identified. Incidence and mortality rates were calculated using census data. Risk factors for PLA were identified using a multivariate analysis. Data was compared to 1999-2003 data, also collected in the CHZ., Results: There were 136 patients diagnosed with PLA between 2015 and 2017. Incidence rate during this period increased significantly relative to 1999-2003 (3.7 vs 2.3 cases/100,000 population, p < 0.01), however, mortality rates remained similar. The microbiological composition of PLA did not change over this 15-year time period but the number of antimicrobial resistant isolates did increase (8% vs 1%, p = 0.04). The greatest risk factors for PLA relative to general populations included current malignancy, liver-transplant, end-stage renal disease, and cirrhosis. Thirty-day mortality was 7.4% and independent risk factors included polymicrobial bacteremia, absence of abscess drainage, congestive-heart failure, a history of liver disease, and admission bilirubin., Conclusions: Pyogenic liver abscess is a health concern with rising incidence rate. The increasing prevalence of comorbidities in our population and factors that are associated with risk of PLA suggests this will continue to be an emerging diagnosis of concern. Increasing prevalence of antibiotic resistant organisms compounding unclear optimal treatment regimens is an issue that requires urgent study., (© 2021. The Author(s).)

SARS-CoV-2 has been detected in wastewater and its abundance correlated with community COVID-19 cases, hospitalizations and deaths. We sought to use wastewater-based detection of SARS-CoV-2 to assess the epidemiology of SARS-CoV-2 in hospitals. Between August and December 2020, twice-weekly wastewater samples from three tertiary-care hospitals (totaling > 2100 dedicated inpatient beds) were collected. Hospital-1 and Hospital-2 could be captured with a single sampling point whereas Hospital-3 required three separate monitoring sites. Wastewater samples were concentrated and cleaned using the 4S-silica column method and assessed for SARS-CoV-2 gene-targets (N1, N2 and E) and controls using RT-qPCR. Wastewater SARS-CoV-2 as measured by quantification cycle (Cq), genome copies and genomes normalized to the fecal biomarker PMMoV were compared to the total daily number of patients hospitalized with active COVID-19, confirmed cases of hospital-acquired infection, and the occurrence of unit-specific outbreaks. Of 165 wastewater samples collected, 159 (96%) were assayable. The N1-gene from SARS-CoV-2 was detected in 64.1% of samples, N2 in 49.7% and E in 10%. N1 and N2 in wastewater increased over time both in terms of the amount of detectable virus and the proportion of samples that were positive, consistent with increasing hospitalizations at those sites with single monitoring points (Pearson's r = 0.679, P < 0.0001, Pearson's r = 0.799, P < 0.0001, respectively). Despite increasing hospitalizations through the study period, nosocomial-acquired cases of COVID-19 (Pearson's r = 0.389, P < 0.001) and unit-specific outbreaks were discernable with significant increases in detectable SARS-CoV-2 N1-RNA (median 112 copies/ml) versus outbreak-free periods (0 copies/ml; P < 0.0001). Wastewater-based monitoring of SARS-CoV-2 represents a promising tool for SARS-CoV-2 passive surveillance and case identification, containment, and mitigation in acute- care medical facilities., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the development of life-threatening COVID-19 are believed to disproportionately affect certain at-risk populations. However, it is not clear whether individuals with cystic fibrosis (CF) are at a higher risk of COVID-19 or its adverse consequences. Recurrent respiratory viral infections are often associated with perturbation and pulmonary exacerbations of CF as evidenced by the significant morbidity observed in CF individuals during the 2009 H1N1 pandemic. The primary goal of this review was to systematically survey published accounts of COVID-19 in CF and determine if individuals with CF are disproportionally affected by SARS-CoV-2 and development of COVID-19., Methods: We conducted a systematic literature search using EMBASE and Medline between April 28 and December 10, 2020. Six evaluable studies reporting on a total of 339 individuals with CF who developed COVID-19 were included in this study., Results: We found that although individuals with CF generally experience acute exacerbations of lung disease from infectious agents, COVID-19 incidence estimates in CF appear to be lower than in the general population. However, there are reports of subsets of CF, such as those who had organ transplants, that may experience a more severe COVID-19 course. Potential protective mechanisms in the CF population include pre-pandemic social isolation practices, infection prevention and control knowledge, altered expression of angiotensin-converting enzyme, and the use of certain medications., Conclusions: Although individuals with CF are at risk of acute exacerbations often precipitated by respiratory tract viral infections, published evidence to date indicated that individuals with CF do not experience higher risks of contracting SARS-CoV-2 infection. However, there is evidence that some subsets within the CF population, including those post-transplantation, may experience a more severe clinical course. As SARS-CoV-2 variants are identified and the pandemic goes through additional waves of disease outbreaks, ongoing monitoring of the risk of COVID-19 in individuals with CF is required.

Background: Azithromycin is commonly prescribed drug for individuals with cystic fibrosis (CF), with demonstrated benefits in reducing lung function decline, exacerbation occurrence and improving nutrition. As azithromycin has antimicrobial activity against components of the uncultured microbiome and increasingly the CF microbiome is implicated in disease pathogenesis - we postulated azithromycin may act through its manipulation. Herein we sought to determine if the CF microbiome changed following azithromycin use and if clinical benefit observed during azithromycin use associated with baseline community structure., Results: Drawing from a prospectively collected biobank we identified patients with sputum samples prior to, during and after initiating azithromycin and determined the composition of the CF microbial community by sequencing the V3-V4 region of the 16S rRNA gene. We categorized patients as responders if their rate of lung function decline improved after azithromycin initiation. Thirty-eight adults comprised our cohort, nine who had not utilized azithromycin in at least 3 years, and 29 who were completely naïve. We did not observe a major impact in the microbial community structure of CF sputum in the 2 years following azithromycin usage in either alpha or beta-diversity metrics. Seventeen patients (45%) were classified as Responders - demonstrating reduced lung function decline after azithromycin. Responders who were naïve to azithromycin had a modest clustering effect distinguishing them from those who were non-Responders, and had communities enriched with several organisms including Stenotrophomonas, but not Pseudomonas., Conclusions: Azithromycin treatment did not associate with subsequent large changes in the CF microbiome structure. However, we found that baseline community structure associated with subsequent azithromycin response in CF adults.

Infective endocarditis (IE) has been increasingly recognized as an important complication of Staphylococcus aureus bacteremia (SAB), leading to a low threshold for echocardiography and extended treatment with anti-staphylococcal agents. However, outside of IE, many indications for prolonged anti-staphylococcal therapy courses are present. We sought to determine the frequency in which findings from a transesophageal echocardiogram (TEE) changed clinical SAB management in a large Canadian health region. Residents (> 18 years) with SAB from 2012 to 2014 who underwent transthoracic echocardiogram (TTE) and TEE were assessed. Patients potentially benefiting from an extended course of anti-staphylococcal agents were defined a priori. Patient demographics, treatment (including surgical), and clinical outcomes were extracted and evaluated. Of the 705 episodes of SAB that underwent a screening echocardiogram, 203 episodes underwent both a TTE and TEE, of which 92.1% (187/203) contained an a priori indication for extended anti-staphylococcal therapy. Regardless of TEE results, actual duration of therapy did not differ in SAB episodes that had ≥ 1 extended anti-staphylococcal therapy criteria (36.7 days, IQR 23.4-48.6 vs. 43.8 days, IQR 33.3-49.5, p = 0.17). Additionally, there were no cases in which TEE was utilized as the sole reason to shorten duration of therapy or proceed to surgery for those with SAB. Routine performance of TEE may be unnecessary in all SAB as many patients have pre-existing indications for extended anti-staphylococcal therapy independent of TEE findings. An algorithm to selectively identify cases of SAB that would benefit from TEE can reduce resource and equipment expenditure and patient risks associated with TEE.

Importance: Although health care workers (HCWs) are at higher risk of acquiring coronavirus disease 2019 (COVID-19), it is unclear whether they are at risk of poorer outcomes., Objective: To evaluate the association between HCW status and outcomes among patients hospitalized with COVID-19., Design, Setting, and Participants: This retrospective, observational cohort study included consecutive adult patients hospitalized with a diagnosis of laboratory-confirmed COVID-19 across 36 North American centers from April 15 to June 5, 2020. Data were collected from 1992 patients. Data were analyzed from September 10 to October 1, 2020., Exposures: Data on patient baseline characteristics, comorbidities, presenting symptoms, treatments, and outcomes were collected, including HCW status., Main Outcomes and Measures: The primary outcome was a requirement for mechanical ventilation or death. Multivariable logistic regression was performed to yield adjusted odds ratios (AORs) and 95% CIs for the association between HCW status and COVID-19-related outcomes in a 3:1 propensity score-matched cohort, adjusting for residual confounding after matching., Results: In total, 1790 patients were included, comprising 127 HCWs and 1663 non-HCWs. After 3:1 propensity score matching, 122 HCWs were matched to 366 non-HCWs. Women comprised 71 (58.2%) of matched HCWs and 214 (58.5%) of matched non-HCWs. Matched HCWs had a mean (SD) age of 52 (13) years, whereas matched non-HCWs had a mean (SD) age of 57 (17) years. In the matched cohort, the odds of the primary outcome, mechanical ventilation or death, were not significantly different for HCWs compared with non-HCWs (AOR, 0.60; 95% CI, 0.34-1.04). The HCWs were less likely to require admission to an intensive care unit (AOR, 0.56; 95% CI, 0.34-0.92) and were also less likely to require an admission of 7 days or longer (AOR, 0.53; 95% CI, 0.34-0.83). There were no differences between matched HCWs and non-HCWs in terms of mechanical ventilation (AOR, 0.66; 95% CI, 0.37-1.17), death (AOR, 0.47; 95% CI, 0.18-1.27), or vasopressor requirements (AOR, 0.68; 95% CI, 0.37-1.24)., Conclusions and Relevance: In this propensity score-matched multicenter cohort study, HCW status was not associated with poorer outcomes among hospitalized patients with COVID-19 and, in fact, was associated with a shorter length of hospitalization and decreased likelihood of intensive care unit admission. Further research is needed to elucidate the proportion of HCW infections acquired in the workplace and to assess whether HCW type is associated with outcomes.

Background: Inhaled tobramycin powder/solution (TIP/S) use has resulted in improved clinical outcomes in patients with cystic fibrosis (CF) with chronic Pseudomonas aeruginosa . However, TIP/S effect on the CF sputum microbiome has not been explored. We hypothesised that TIP/S has additional 'off-target' effects beyond merely P. aeruginosa and that baseline microbiome prior to initiation of therapy is associated with subsequent patient response., Methods: We drew sputum samples from a prospectively collected biobank. Patients were included if they had one sputum sample in the 18 months before and after TIP/S. Bacterial 16S rRNA gene profiling was used to characterise the sputum microbiome., Results: Forty-one patients met our inclusion criteria and 151 sputum samples were assessed. At baseline, median age was 30.4 years (IQR 24.2-35.2) and forced expiratory volume in 1 (FEV 1 ) second was 57% predicted (IQR 44-74). Nineteen patients were defined a priori as responders having no net decrease in FEV 1 in the year following TIP/S. No significant changes were observed in key microbiome metrics of alpha (within-sample) or beta (between-sample) diversity for samples collected before and after TIP/S. However, significant beta-diversity (Bray-Curtis) differences were noted at baseline between patients based on response status. Notably, responders were observed to have a higher abundance of Staphylococcus in pretherapy baseline samples., Conclusions: Our longitudinal study demonstrates that the sputum microbiome of patients with CF is relatively stable following inhaled tobramycin over many months. Intriguingly, our findings suggest that baseline microbiome may associate with patient response to TIP/S-suggesting the sputum microbiome could be used to personalise therapy., Competing Interests: Competing interests: MDP, HR and MS have received research support from CF Canada, CIHR and Gilead., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Tick-borne relapsing fever (TBRF) is an infection caused by Borrelia spirochetes. In North America, Borrelia hermsii is the most common cause for TBRF. This vector-borne disease is transmitted by Ornithodoros hermsi , a soft-bodied tick found in high altitudes in northwestern United States and southwestern Canada. Once bitten by the tick and infected by B. hermsii , episodes of fever alternating with afebrile periods can occur. A case of TBRF in a pregnant host was complicated by Jarisch-Herxheimer reaction requiring critical care. This case emphasizes the importance of maintaining a high index of suspicion in TBRF. Clinician recognition, diagnosis and treatment of TBRF as well as public awareness of strategies to prevent tick bites should be strengthened., Competing Interests: Competing interests: None. The case was presented in part at the Clinical Grand Rounds, European Congress of Clinical Microbiology & Infectious Diseases 2019, Amsterdam Noord, the Netherlands.

Pseudomonas aeruginosa is the archetypal cystic fibrosis (CF) pathogen. However, the clinical course experienced by infected individuals varies markedly. Understanding these differences is imperative if further improvements in outcomes are to be achieved. Multiple studies have found that patients infected with epidemic P. aeruginosa (ePA) strains may have a worse clinical prognosis than those infected with unique, non-clonal strains. Additionally, the traditionally uncultured CF lung bacterial community (i.e., CF microbiome) may further influence the outcome. We sought to identify if these two important variables, not identified through routine culture, associate and together may contribute to disease pathogenesis. Patients were classified as being infected with Prairie Epidemic ePA (PES) or a non-clonal strain, unique PA strains (uPA), through a retrospective assessment of a comprehensive strain biobank using a combination of PFGE and PES-specific PCR. Patients were matched to age, sex, time-period controls and sputum samples from equivalent time periods were identified from a sputum biobank. Bacterial 16S rRNA gene profiling and Pseudomonas qPCR was used to characterize the respiratory microbiome. We identified 31 patients infected with PES and matched them with uPA controls. Patients infected with PES at baseline have lower microbial diversity (P = 0.02) and higher P. aeruginosa relative abundance ( P < 0.005). Microbial community structure was found to cluster by PA strain type, although it was not the main determinant of community structure as additional factors were also found to be drivers of CF community structure. Communities from PES infected individuals were enriched with Pseudomonas, Streptococcus and Prevotella OTUs. The disproportionate disease experienced by ePA infected CF patients may be mediated through a combination of pathogen-pathogen factors as opposed to strictly enhanced virulence of infecting P. aeruginosa strains., (Copyright © 2020 Acosta, Waddell, Heirali, Somayaji, Surette, Workentine, Rabin and Parkins.)

Escherichia coli is frequently isolated from the respiratory secretions of cystic fibrosis (CF) patients yet is not considered a classical CF pathogen. Accordingly, little is known about the natural history of this organism in the CF airways, as well as the potential for patient-to-patient transmission. Patients attending the Calgary Adult CF Clinic (CACFC) between January 1983 and December 2016 with at least one E. coli -positive sputum culture were identified by retrospective review. Annual E. coli isolates from the CACFC biobank from each patient were typed by pulsed-field gel electrophoresis (PFGE) and isolates belonging to shared pulsotypes were sequenced. Single nucleotide polymorphism (SNP) and phylogenetic analysis were used to investigate the natural history of E. coli infection and identify potential transmission events. Forty-five patients with E. coli -positive sputum cultures were identified. Most patients had a single infection episode with a single pulsotype, while replacement of an initial pulsotype with a second was observed in three patients. Twenty-four had E. coli recovered from their sputum more than once and 18 patients had persistent infections ( E. coli carriage >6 months with ≥3 positive cultures). Shared pulsotypes corresponded to known extraintestinal pathogenic E. coli strains: ST-131, ST-73, and ST-1193. Phylogenetic relationships and SNP distances among isolates within shared pulsotypes were consistent with independent acquisition of E. coli by individual patients. Most recent common ancestor date estimates of isolates between patients were inconsistent with patient-to-patient transmission. E. coli infection in CF is a dynamic process that appears to be characterized by independent acquisition within our patient population and carriage of unique sets of strains over time by individual patients., (Copyright © 2020 Izydorczyk, Waddell, Edwards, Greysson-Wong, Surette, Somayaji, Rabin, Conly, Church and Parkins.)

Amplicon sequencing (for example, of the 16S rRNA gene) identifies the presence and relative abundance of microbial community members. However, metagenomic sequencing is needed to identify the genetic content and functional potential of a community. Metagenomics is challenging in samples dominated by host DNA, such as those from the skin, tissue and respiratory tract. Here, we combine advances in amplicon and metagenomic sequencing with culture-enriched molecular profiling to study the human microbiota. Using the cystic fibrosis lung as an example, we cultured an average of 82.13% of the operational taxonomic units representing 99.3% of the relative abundance identified in direct sequencing of sputum samples; importantly, culture enrichment identified 63.3% more operational taxonomic units than direct sequencing. We developed the PLate Coverage Algorithm (PLCA) to determine a representative subset of culture plates on which to conduct culture-enriched metagenomics, resulting in the recovery of greater taxonomic diversity-including of low-abundance taxa-with better metagenome-assembled genomes, longer contigs and better functional annotations when compared to culture-independent methods. The PLCA is also applied as a proof of principle to a previously published gut microbiota dataset. Culture-enriched molecular profiling can be used to better understand the role of the human microbiota in health and disease.

Purpose: Staphylococcus aureus bacteremia (SAB) is associated with significant morbidity and mortality. We sought to re-define the burden, epidemiology and mortality-associated risk factors of SAB in a large Canadian health region., Methods: Residents (> 18 years) experiencing SAB from 2012 to 2014 were assessed. Incidence rates were calculated using civic census results. Factors associated with 30-day mortality were determined through multivariate logistic regression. Incidence and risk factors for SAB were compared to 2000-2006 data., Results: 780 residents experienced 840 episodes of SAB (MRSA; 20%). Incidence rates increased from 23.5 to 32.0 cases/100,000 from 2012 to 2014; [IRR 1.15 (95% CI 1.07-1.23); p < 0.001]. Compared to a decade ago, incidence of SAB has increased [IRR 1.28 (95% CI 1.21-1.36); p < 0.001] despite minimal change in nosocomial SAB. MRSA proportion did not change through the study (p = 0.3), but did increase relative to a decade ago (20.0% vs 11.0%, p < 0.001). Thirty-day mortality rates were 30.6% and 21.3% for MRSA and MSSA, respectively (p = 0.01), similar to rates from 2000 to 2006. Several clinical, demographic, and biochemical factors were independently associated with SAB mortality., Conclusions: SAB is common within our population resulting in significant mortality. Incidence rates of SAB are increasing in our health region; however, 30-day mortality rates remain stable.

Background: Analysis of " emerging " pathogens in cystic fibrosis (CF) lung disease has focused on unique pathogens that are rare in other human diseases or are drug resistant. Escherichia coli is recovered in the sputum of up to 25% of patients with CF, yet little is known about the epidemiology or clinical impact of infection., Methods: We studied patients attending a Canadian adult CF clinic who had positive sputum cultures for E coli from 1978 to 2016. Infection was categorized as transient or persistent (≥3 positive sputum cultures, spanning >6 months). Those with persistent infection were matched 2:1 with age, sex, and time-period controls without history of E coli infection, and mixed-effects models were used to assess pulmonary exacerbation (PEx) frequency, lung function decline, hospitalization, and intravenous antibiotic days., Results: Forty-five patients (12.3%) had E coli recovered from sputum samples between 1978 and 2016, and 18 patients (40%) developed persistent infection. Nine patients (24%) had PEx at incident infection, and increased bioburden was predictive of exacerbation ( P = .03). Risk factors for persistent infection included lower nutritional status ( P < .001) and lower lung function ( P = .009), but chronic infection with Pseudomonas aeruginosa was protective. There was no difference in annual lung function decline, need for hospitalization or intravenous antibiotics, or risk of PEx in patients with persistent infection., Conclusions: Persistent E coli infection was frequent and was more common in CF patients with low nutritional status and lung function. However, this does not predict clinical decline. Multicenter studies would allow better characterization of the epidemiology and clinical impact of E coli infection., (© The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: Peripherally inserted central catheters (PICCs) are a mainstay of nonpermanent vascular access devices. In this study, we assessed patients displaying anaphylaxis or anaphylactoid reactions to the PowerPICC SOLO and Groshong PICC (Bard Access Systems) using the Sherlock tip locating system (TLS)., Methods: Patients from 2 tertiary-care hospitals were systematically monitored over 4 years for adverse events following the insertion of a PICC using the Sherlock TLS. Insertion data were also collected using the BioFlo PICC (Angiodynamics)from a third hospital site and from The Ottawa Hospital over 4 years as an additional comparator. Three definitions of anaphylaxis and anaphylactoid reactions were utilized, and the Cohen κ was used to assess interrater agreement. Analysis of reactions among the patient cohorts was performed using the χ2 test with Yates correction or the Fisher exact test as appropriate., Results: Among 8,257 insertions using the TLS PICCs, 37 potential reactions (0.45%) were recorded. Using specific definitions for anaphylaxis or anaphylactoid reactions, 54.1%-91.9% met criteria. Comparator populations using data from Calgary (n = 491) and Ottawa (n = 7,889) using the BioFlo PICC insertion found no reactions. Anaphylactic or anaphylactoid reactions were significantly associated with the PowerPICC SOLO and Groshong PICC with the TLS compared to the BioFlo PICC (P < .0001) across all definitions. The largest subset of patients experiencing adverse reactions had cystic fibrosis (CF) (n = 4, 10.8%)., Conclusion: Our study results demonstrate significant adverse events associated with the PowerPICC SOLO and Groshong PICC using the Sherlock TLS inserted across a range of patient populations. The incidence rate of anaphylaxis or anaphylactoid reactions in the CF population at our center is significantly higher than in non-CF patients (P < .001).

Background: To improve clinical outcomes, cystic fibrosis (CF) patients with chronic Pseudomonas aeruginosa infections are prescribed inhaled anti-pseudomonal antibiotics. Although, a diverse microbial community exists within CF airways, little is known about how the CF microbiota influences patient outcomes. We hypothesized that organisms within the CF microbiota are affected by inhaled-antibiotics and baseline microbiome may be used to predict therapeutic response., Methods: Adults with chronic P. aeruginosa infection from four clinics were observed during a single 28-day on/off inhaled-aztreonam cycle. Patients performed serial sputum collection, CF-respiratory infection symptom scores (CRISS), and spirometry. Patients achieving a decrease of ≥2 CRISS by day 28 were categorized as subjective responders (SR). The airway microbiome was defined by Illumina MiSeq analysis of the 16S rRNA gene., Results: Thirty-seven patients (median 37.4 years and FEV 1 44% predicted) were enrolled. No significant cohort-wide changes in the microbiome were observed between on/off AZLI cycles in either alpha- or beta-diversity metrics. However, at an individual level shifts were apparent. Twenty-one patients (57%) were SR and fourteen patients did not subjectively respond. While alpha-diversity metrics did not associate with response, patients who did not subjectively respond had a higher abundance of Staphylococcus and Streptococcus, and lower abundance of Haemophilus., Conclusions: The CF microbiome is relatively resilient to AZLI perturbations. However, associated changes were observed at the individual patient level. The relative abundance of key "off-target" organisms associated with subjective improvements suggesting that the microbiome may be used as a tool to predict patient response - potentially improving outcomes., (Copyright © 2019. Published by Elsevier B.V.)

Background: Staphylococcus aureus bacteriuria (SABU) may represent multiple processes ranging from asymptomatic colonization to a marker of S. aureus bacteremia (SAB). Our objective was to describe SABU at a population-based level and determine patient characteristics associated with SAB., Methods: A retrospective study was performed using electronic databases. All urine cultures positive for S. aureus between 2010 and 2013 within the Calgary Health Zone were included. Patient characteristics were compared among patients with and without SAB and risk factors identified using multiple logistic regression modeling., Results: A total of 2540 urine cultures positive for S. aureus from 2054 patients were analyzed. The incidence of SABU was greatest among geriatric males with multiple comorbidities. SAB occurred in 175 (6.9%) of SABU patients. Those with SAB were more likely to be hospitalized, male, have a recent urinary procedure, have pure S. aureus culture in urine, and have laboratory findings suggesting systemic infection. Patients with isolated SABU were more likely to be ≥65 years, have dementia, and have abnormal urinalyses with pyuria and urine nitrites. In-hospital mortality in patients with SABU and SABU+SAB was 9.2% and 17.5%, respectively. Patients with SABU detected ≥48 hours before SAB had the highest risk of death., Conclusions: Less than 7% of patients with SABU have or will develop SAB. Characteristics associated with SABU were identified that established higher risk for systemic infection. Investigating SABU patients with these characteristics for systemic infection is warranted because a delay in diagnosis is associated with increased mortality., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

A diverse microbiota exists within the airways of individuals with non-cystic fibrosis bronchiectasis (nCFB). How the lung microbiome evolves over time, and whether changes within the microbiome correlate with future disease progression is not yet known. We assessed the microbial community structure of 133 serial sputa and subsequent disease course of 29 nCFB patients collected over a span of 4-16 years using 16S rRNA paired-end sequencing. Interestingly, no significant shifts in the microbial community of individuals were observed during extended follow-up suggesting the microbiome remains relatively stable over prolonged periods. Samples that were Pseudomonas aeruginosa culture positive displayed markedly different microbial community structures compared to those that were positive for Haemophilus influenzae. Importantly, patients with sputum of lower microbial community diversity were more likely to experience subsequent lung function decline as defined by annual change in ≥-1 FEV 1 % predicted. Shannon diversity values <1 were more prevalent in patients with FEV 1 decline (P = 0.002). However, the relative abundance of particular core microbiota constituents did not associate with risk of decline. Here we present data confirming that the microbiome of nCFB individuals is generally stable, and that microbiome-based measurements may have a prognostic role as biomarkers for nCFB.

In response to the occurrence of antibiotic resistance, there has been rapid developments in the field of metal-based antimicrobials. Although it is largely assumed that metals provide broad-spectrum microbial efficacy, studies have shown that this is not always the case. Therefore, in this study, we compared the susceptibilities of 93 clinical isolates belonging to the species Escherichia coli , Pseudomonas aeruginosa and Staphylococcus aureus against six metals, namely aluminum, copper, gallium, nickel, silver and zinc. To provide qualitative comparative information, the resulting zones of growth inhibition were compared to the minimal inhibitory concentrations of three indicator strains E . coli ATCC 25922, P. aeruginosa ATCC 27853 and S. aureus ATCC 25923. Here, we demonstrate that the metal efficacies were species- and isolate-specific. Only several isolates were either resistant or sensitive to all of the six metals, with great variability found between isolates. However, the greatest degree of similarity was found with the E . coli isolates. In contrast, the susceptibilities of the remaining two collections, S. aureus and P. aeruginosa , were more highly dispersed. Using this information, we have shown that metals are not equal in their efficacies. Hence, their use should be tailored against a particular microorganism and care should be taken to ensure the use of the correct concentration., Competing Interests: The authors declare no conflict of interest.

Background: Staphylococcus aureus bacteremia (SAB) is associated with significant morbidity and mortality. We sought to identify factors associated with infectious diseases consultation (IDC) and understand how IDC associates with SAB patient management and outcomes., Methods: A multicentre retrospective study was performed between 2012 and 2014 in a large Canadian Health Zone in order to determine factors associated with IDC and performance of key quality of care determinants in SAB management and clinical outcomes. Factors subject to quality of care determinants were established a priori and studied for associations with IDC and 30-day all-cause mortality using multivariable analysis., Results: Of 961 SAB episodes experienced by 892 adult patients, 605 episodes received an IDC. Patients receiving IDC were more likely to have prosthetic valves and joints and to have community-acquired and known sources of SAB, but increasing age decreased IDC occurrence. IDC was the strongest independent predictor for quality of care performance metrics, including repeat blood cultures and echocardiography. Mortality at 30 days was 20% in the cohort, and protective factors included IDC, achievement of source control, targeted therapy within 48 hours, and follow-up blood cultures but not the performance of echocardiography., Conclusions: There were significant gaps between the treatments and investigations that patients actually received for SAB and what is considered the optimal management of their condition. IDC is associated with improved attainment of targeted SAB quality of care determinants and reduced mortality rates. Based on our findings, we propose a policy of mandatory IDC for all cases of SAB to improve patient management and outcomes., Competing Interests: The authors have nothing to disclose., (Copyright © 2019, Association of Medical Microbiology and Infectious Disease Canada (AMMI Canada).)

Background: Antimicrobial susceptibility testing (AST) is a cornerstone of infection management. Cystic fibrosis (CF) treatment guidelines recommend AST to select antimicrobial treatments for CF airway infection but its utility in this setting has never been objectively demonstrated., Methods: We conducted a systematic review of primary published articles designed to address two PICO (patient, intervention, comparator, outcome) questions: 1) "For individuals with CF, is clinical response to antimicrobial treatment of bacterial airways infection predictable from AST results available at treatment initiation?" and 2) "For individuals with CF, is clinical response to antimicrobial treatment of bacterial airways infection affected by the method used to guide antimicrobial selection?" Relationships between AST results and clinical response (changes in pulmonary function, weight, signs and symptoms of respiratory tract infection, and time to next event) were assessed for each article and results were compared across articles when possible., Results: Twenty-five articles describing the results of 20 separate studies, most of which described Pseudomonas aeruginosa treatment, were identified. Thirteen studies described pulmonary exacerbation (PEx) treatment and seven described 'maintenance' of chronic bacterial airways infection. In only three of 16 studies addressing PICO question #1 was there a suggestion that baseline bacterial isolate antimicrobial susceptibility was associated with clinical response to treatment. None of the four studies addressing PICO question #2 suggested that antimicrobial selection methods influenced clinical outcomes., Conclusions: There is little evidence that AST predicts the clinical outcome of CF antimicrobial treatment, suggesting a need for careful consideration of current AST use by the CF community., (Copyright © 2019 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: Complex polymicrobial communities infect cystic fibrosis (CF) lower airways. Generally, communities with low diversity, dominated by classical CF pathogens, associate with worsened patient status at sample collection. However, it is not known if the microbiome can predict future outcomes. We sought to determine if the microbiome could be adapted as a biomarker for patient prognostication., Methods: We retrospectively assessed prospectively collected sputum from a cohort of 104 individuals aged 18-22 to determine factors associated with progression to early end-stage lung disease (eESLD; death/transplantation <25 years) and rapid pulmonary function decline (>-3%/year FEV 1 over the ensuing 5 years). Illumina MiSeq paired-end sequencing of the V3-V4 region of the 16S rRNA was used to define the airway microbiome., Results: Based on the primary outcome analysed, 17 individuals (16%) subsequently progressed to eESLD. They were more likely to have sputum with low alpha diversity, dominated by specific pathogens including Pseudomonas . Communities with abundant Streptococcus were observed to be protective. Microbial communities clustered together by baseline lung disease stage and subsequent progression to eESLD. Multivariable analysis identified baseline lung function and alpha diversity as independent predictors of eESLD. For the secondary outcomes, 58 and 47 patients were classified as rapid progressors based on absolute and relative definitions of lung function decline, respectively. Patients with low alpha diversity were similarly more likely to be classified as experiencing rapid lung function decline over the ensuing 5 years when adjusted for baseline lung function., Conclusions: We observed that the diversity of microbial communities in CF airways is predictive of progression to eESLD and disproportionate lung function decline and may therefore represent a novel biomarker., Competing Interests: Competing interests: MDP, HRR and MGS have received research funding from Gilead Sciences. MDP and HRR have participated in advisory boards and/or performed consulting work for Vertex but both declined honoraria. NA, AH, RS, MLW and CDS have no conflicts to declare., (© Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Chronic lower airway infection with Pseudomonas aeruginosa is a major contributor to morbidity and mortality in individuals suffering from the genetic disease cystic fibrosis (CF). Whereas it was long presumed that each patient independently acquired unique strains of P. aeruginosa present in their living environment, multiple studies have since demonstrated that shared strains of P. aeruginosa exist among individuals with CF. Many of these shared strains, often referred to as clonal or epidemic strains, can be transmitted from one CF individual to another, potentially reaching epidemic status. Numerous epidemic P. aeruginosa strains have been described from different parts of the world and are often associated with an antibiotic-resistant phenotype. Importantly, infection with these strains often portends a worse prognosis than for infection with nonclonal strains, including an increased pulmonary exacerbation rate, exaggerated lung function decline, and progression to end-stage lung disease. This review describes the global epidemiology of clonal P. aeruginosa strains in CF and summarizes the current literature regarding the underlying biology and clinical impact of globally important CF clones. Mechanisms associated with patient-to-patient transmission are discussed, and best-evidence practices to prevent infections are highlighted. Preventing new infections with epidemic P. aeruginosa strains is of paramount importance in mitigating CF disease progression., (Copyright © 2018 American Society for Microbiology.)