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KEY POINTS Clinical presentation in persons infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from asymptomatic to the life-threatening respiratory distress that can occur with coronavirus disease 2019 (COVID-19).[1][1] Diagnosis of acute or new cases of SARS-CoV-2

From 2014–2019, invasive pulmonary aspergillosis complicated 7.2% (0–23.1% in different influenza seasons) of cases of influenza-associated respiratory failure in Edmonton, Alberta. Disease outcomes ranged from survival without therapy to death despite antifungals. Clinician vigilance, longitudinal local surveillance, and refined criteria to identify patients requiring therapy are needed.

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: I 2 =99%) and 0·3% (95% CI: 0·1-0·6%; n=8 studies: I 2 =78%), respectively. Among multi-drug resistant organisms, methicillin-resistant Staphylococcus aureus, carbapenem-resistant Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and 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 was moderately prevalent 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. Funding: The Antimicrobial Resistance - One Health Consortium is funded through the Major Innovation Fund Program of the Ministry of Jobs, Economy, and Innovation (JEI), Government of Alberta, Canada. Declaration of Interest: We declare no competing interests.

In 2018 to 2019, PCR for carbapenemases in routine Gram-negative isolates submitted to the National Microbiology Laboratory revealed an increase in IMP-type metalloenzyme-positive isolates, mostly among Morganellaceae Whole-genome sequencing revealed that 23 Morganellaceae harbored blaIMP-27 within a chromosomal Tn7 element. Phylogenomics indicated diversity of isolates but also the presence of a few clonal isolates dispersed geographically. These isolates may be difficult to detect due to carbapenem susceptibility and false-negative results in phenotypic testing.IMPORTANCE Over the last decade or so, the frequency of isolation of clinical carbapenemase-producing organisms (CPOs) has increased among health care-associated infections. This may seriously compromise antimicrobial therapy, as carbapenems are considered the last line of defense against these organisms. The ability of carbapenemases to hydrolyze most β-lactams in addition to the co-occurrence of mechanisms of resistance to other classes of antimicrobials in CPOs can leave few options for treating infections. The class B metalloenzymes are globally distributed carbapenemases, and the most commonly found include the NDM, VIM, and IMP types. Our study describes a sudden emergence of IMP-27-harboring Morganellaceae during 2018 to 2019 in Canada. There is a paucity of literature on IMP-27 isolates, and our data bolster the information on the genetic context, antimicrobial profiles, and phylogenomics of this group of CPOs.

RationalePulmonary aspergillosis may complicate COVID-19 and contribute to excess mortality in intensive care unit (ICU) patients. The incidence is unclear because of discordant definitions across studies.ObjectiveWe sought to review the incidence, diagnosis, treatment, and outcomes of COVID-19-associated pulmonary aspergillosis (CAPA), and compare research definitions.MethodsWe systematically reviewed the literature for ICU cohort studies and case series including ≥ patients with CAPA. We calculated pooled incidence. Patients with sufficient clinical details were reclassified according to 4 standardized definitions (Verweij, White, Koehler, and Bassetti).MeasurementsCorrelations between definitions were assessed with Spearman’s rank test. Associations between antifungals and outcome were assessed with Fisher’s Exact test.Main Results38 studies (35 cohort studies and 3 case series) were included. Among 3,297 COVID-19 patients in ICU cohort studies, 313 were diagnosed with CAPA (pooled incidence 9.5%). 197 patients had patient-level data allowing reclassification. Definitions had limited correlation with one another (ρ=0.330 to 0.621, pConclusionsThe reported incidence of CAPA is exaggerated by use of non-standard definitions. Further research should focus on identifying patients likely to benefit from antifungals.

ObjectivesUnderstanding the epidemiology of invasive Candida infections is essential to patient management decisions and antifungal stewardship practices. This study characterized the species distribution and antifungal susceptibilities of prospectively collected isolates of Candida species causing bloodstream infections (BSIs) in patients admitted to tertiary care hospitals located in 14 cities across 8 of the 10 Canadian provinces between 2011 and 2016.MethodsAntifungal susceptibility testing was performed by broth microdilution using CLSI methods, breakpoints and epidemiological cut-off values. DNA sequencing of fks loci was performed on all echinocandin-non-susceptible isolates.ResultsCandida albicans (49.6%), Candida glabrata (20.8%) and Candida parapsilosis complex (12.0%) were the most common species out of 1882 isolates associated with BSIs. Candida tropicalis (5.2%), Candida krusei (4.3%), Candida dubliniensis (4.1%), Candida lusitaniae (1.4%) and Candida guilliermondii (1.1%) were less frequently isolated. Between 2011 and 2016, the proportion of C. albicans significantly decreased from 60.9% to 42.1% (P ConclusionsAntifungal resistance in contemporary isolates of Candida causing BSIs in Canada is uncommon. However, the proportion of C. glabrata isolates has increased and echinocandin resistance in this species has emerged. Ongoing surveillance of local hospital epidemiology and appropriate antifungal stewardship practices are necessary to preserve the utility of available antifungal agents.

Testing of staphylococci other than Staphylococcus aureus (SOSA) for mecA-mediated resistance is challenging. Isolates of Staphylococcus capitis, Staphylococcus haemolyticus, Staphylococcus hominis, and Staphylococcus warneri were evaluated by cefoxitin and oxacillin broth microdilution (BMD), disk diffusion (DD), and PBP2a immunoassay, and the results were compared to mecA PCR results. No phenotypic susceptibility test correlated well with PCR results across all species, although the PBP2a immunoassay yielded 100% correlation. Oxacillin BMD testing by current Clinical and Laboratory Standards Institute (CLSI) SOSA breakpoints led to 2.1% very major errors (VMEs) and 7.1% major errors (ME). Adjusting this breakpoint up by a dilution (susceptible, ≤0.5 μg/ml; resistant, ≥1.0 μg/ml) led to 2.8% VMEs and 0.3% MEs. Among species evaluated, S. haemolyticus had unacceptable VMEs with this new breakpoint (6.4%), as did S. hominis (4.0%). MEs were acceptable by this new breakpoint, ranging from 0 to 1.2%. Oxacillin DD yielded high ME rates (20.7 to 21.7%) using CLSI or European Committee on Antimicrobial Susceptibility Testing breakpoints. VMEs ranged from 0 to 5.3%. Cefoxitin BMD led to 4.9% VMEs and 1.6% MEs. Cefoxitin DD performed best when interpreted with the CLSI SOSA breakpoint, with 1.0% VMEs and 2.9% MEs. This study led CLSI to adjust the oxacillin MIC breakpoints for SOSA. Laboratories should be aware that no individual phenotypic test correlates well across all species of SOSA with mecA PCR results. Molecular testing for mecA or evaluation for PBP2a is the preferred approach.

POINTS CLES Chez les personnes ayant contracte le coronavirus du syndrome respiratoire aigu severe 2 (SRAS-CoV-2), le tableau clinique varie de l’absence de symptomes a la detresse respiratoire gravissime qui accompagne la maladie a coronavirus 2019 (COVID-19)[1][1]. A l’heure actuelle

Summary Background The classic geographical range of histoplasmosis in North America primarily includes the states and provinces adjacent to the Ohio, Mississippi, and St Lawrence riverways. Although Alberta, Canada is not typically considered a region of risk for histoplasmosis, cases with suspected local acquisition have been reported. We aimed to investigate the epidemiology and geographical distribution of cases of histoplasmosis in Alberta to assess evidence for local acquisition of infections, using genomic analysis for corroboration. Methods We did an epidemiological and genomic investigation, in which laboratory-confirmed cases of histoplasmosis were reviewed in Alberta from 2011, when the disease became reportable, until 2018. We used data attained from Alberta Health. Travel and exposure histories and clinical features were reviewed. Definite local acquisition was defined as a case without previous travel outside Alberta or associated with a common-source outbreak within the province, whereas probable local acquisition was a sporadic case with travel outside Alberta but compelling local exposures. Genomes of selected case isolates were analysed, including those from cases suspected to have been locally acquired and imported. Findings Between Jan 1, 2011, and June 30, 2018, 45 cases of histoplasmosis were identified. Participants had a median age of 53 years (range 17–77) and 32 [71%] were male. Among 34 patients with documented travel histories, ten (29%) had never left the province. 11 cases were of definite local acquisition, including eight cases from three common-source outbreaks and three sporadic cases in patients who had never travelled outside Alberta. The common-source outbreaks all involved exposure to bats or their droppings in chimneys or attics of private dwellings or churches. Four patients had travelled outside Alberta but compelling evidence was seen for local exposure to bat guano. Genome sequencing showed that isolates from cases of definite and probable local acquisition clustered together and were genetically distinct from isolates from suspected imported cases and other published isolates. Interpretation Using epidemiological and genomic analyses, we established that cases of histoplasmosis have been acquired in Alberta, thus expanding the geographical range of Histoplasma spp much further northwest than was previously appreciated. Histoplasmosis should be considered in patients with compatible symptoms outside areas of classic geographical risk. Funding None.

From 2015 to 2017, 11 confirmed brucellosis cases were reported in New York City, leading to 10 Brucella exposure risk events (Brucella events) in 7 clinical laboratories (CLs). Most patients had traveled to countries where brucellosis is endemic and presented with histories and findings consistent with brucellosis. CLs were not notified that specimens might yield a hazardous organism, as the clinicians did not consider brucellosis until they were notified that bacteremia with Brucella was suspected. In 3 Brucella events, the CLs did not suspect that slow-growing, small Gram-negative bacteria might be harmful. Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS), which has a limited capacity to identify biological threat agents (BTAs), was used during 4 Brucella events, which accounted for 84% of exposures. In 3 of these incidents, initial staining of liquid media showed Gram-positive rods or cocci, including some cocci in chains, suggesting streptococci. Over 200 occupational exposures occurred when the unknown isolates were manipulated and/or tested on open benches, including by procedures that could generate infectious aerosols. During 3 Brucella events, the CLs examined and/or manipulated isolates in a biological safety cabinet (BSC); in each CL, the CL had previously isolated Brucella. Centers for Disease Control and Prevention recommendations to prevent laboratory-acquired brucellosis (LAB) were followed; no seroconversions or LAB cases occurred. Laboratory assessments were conducted after the Brucella events to identify facility-specific risks and mitigations. With increasing MALDI-TOF MS use, CLs are well-advised to adhere strictly to safe work practices, such as handling and manipulating all slow-growing organisms in BSCs and not using MALDI-TOF MS for identification until BTAs have been ruled out.

Whole-genome sequencing (WGS) of Staphylococcus aureus is increasingly used as part of infection prevention practices. In this study, we established a long-read technology-based WGS screening program of all first-episode methicillin-resistant Staphylococcus aureus (MRSA) blood infections at a major urban hospital., Whole-genome sequencing (WGS) of Staphylococcus aureus is increasingly used as part of infection prevention practices. In this study, we established a long-read technology-based WGS screening program of all first-episode methicillin-resistant Staphylococcus aureus (MRSA) blood infections at a major urban hospital. A survey of 132 MRSA genomes assembled from long reads enabled detailed characterization of an outbreak lasting several months of a CC5/ST105/USA100 clone among 18 infants in a neonatal intensive care unit (NICU). Available hospital-wide genome surveillance data traced the origins of the outbreak to three patients admitted to adult wards during a 4-month period preceding the NICU outbreak. The pattern of changes among complete outbreak genomes provided full spatiotemporal resolution of its progression, which was characterized by multiple subtransmissions and likely precipitated by equipment sharing between adults and infants. Compared to other hospital strains, the outbreak strain carried distinct mutations and accessory genetic elements that impacted genes with roles in metabolism, resistance, and persistence. This included a DNA recognition domain recombination in the hsdS gene of a type I restriction modification system that altered DNA methylation. Transcriptome sequencing (RNA-Seq) profiling showed that the (epi)genetic changes in the outbreak clone attenuated agr gene expression and upregulated genes involved in stress response and biofilm formation. Overall, our findings demonstrate the utility of long-read sequencing for hospital surveillance and for characterizing accessory genomic elements that may impact MRSA virulence and persistence.

The goal of this document was to provide Canadian laboratories with a framework for consistent reporting and monitoring of multidrug resistant organisms (MDRO) and extensively drug resistant organisms (XDRO) for common gram-negative pathogens. This is the final edition of the interim recommendations, which were modified after one year of broad consultative review. This edition represents a consensus of peer-reviewed information and was co-authored by the Canadian Public Health Laboratory Network and the Canadian Association of Clinical Microbiology and Infectious Diseases. There are two main recommendations. The first recommendation provides standardized definitions for MDRO and XDRO for gram-negative organisms in clinical specimens. These definitions were limited to antibiotics that are commonly tested clinically and, to reduce ambiguity, resistance (rather than non-susceptibility) was used to calculate drug resistance status. The second recommendation identifies the use of standardized laboratory reporting of organisms identified as MDRO or XDRO. Through the broad consultation, which included public health and infection prevention and control colleagues, these definitions are ready to be applied for policy development. Both authoring organizations intend to review these recommendations regularly as antibiotic resistance testing evolves in Canada.

We report three cases of hospital-acquired mucormycosis in heart and lung transplant patients over a 6-month period. Traditional epidemiological investigation tools were used to look for a common link between patients to explain the outbreak. Genome sequencing of each fungal strain was used to supplement the investigation. By disproving a close genetic link between infecting strains of mucormycosis, we were able to conclude the outbreak investigation. Genome sequencing is a novel tool that can be used in addition to traditional epidemiologic investigations to help determine linkage of patients during outbreak investigations.

Objectives To identify the β-lactamase responsible for the positive detection of carbapenemase production in four clinical isolates of Pseudomonas aeruginosa that were negative by PCR for KPC, OXA-48, NDM, VIM, IMP, GES and NMC/IMI carbapenemase genes. Methods WGS using short-read and long-read methods was used to characterize the isolates. Bioinformatic analysis was used to identify the potential gene encoding a carbapenemase. Cloning, antimicrobial susceptibility testing and biochemical and phenotypic characterization were used to determine metallo-enzyme activity. Single-nucleotide variant (SNV) typing was used to determine strain relatedness. Conjugation experiments were used to determine transmissibility of the novel carbapenemase-encoding gene. Results WGS analysis revealed a novel class B β-lactamase gene, blaCAM-1 (Central Alberta Metallo-β-lactamase), located in a 73 kb integrative element, named IMEPaCAM-1, in the chromosome of four clinical isolates of P. aeruginosa. The cloned blaCAM-1 gene conferred carbapenem resistance to Escherichia coli TOP10. The four isolates, which were all closely related, were from three patients, all of whom spent time in the same hospital in 2008 and/or 2009. IMEPaCAM-1 could not be transferred by conjugation. Conclusions A novel metallo-enzyme, CAM-1, is encoded on an integrative element, IMEPaCAM-1, located in the chromosome of clinical isolates of P. aeruginosa. No additional isolates harbouring CAM-1 have been identified in Alberta since 2007.

Candida auris is a fungal pathogen that recently emerged and rapidly spread around the globe. It is now in Canada. C. auris can cause invasive disease with high mortality rates, is frequently resistant to one or more classes of antifungals, and can be difficult to identify in some clinical microbiology laboratories. C. auris can also involve prolonged colonization of patients’ skin and contamination of surrounding environments, resulting in nosocomial outbreaks in hospitals and long-term care facilities. Clinicians, infection prevention and control practitioners and public health officials should be aware of how to mitigate the threat posed by this pathogen. Index cases of C. auris should be suspected in patients with invasive candidiasis and recent hospitalization in global regions where C. auris is prevalent, as well as in patients who fail to respond to empiric antifungal therapy and from whom unidentified or unusual Candida species have been isolated. If a case of C. auris infection or colonization is identified or suspected, the following should take place: notification of local public health authorities and infection prevention and control practitioners; placement of colonized or infected patients in single rooms with routine contact precautions; daily and terminal environmental disinfection with a sporicidal agent; contact tracing and screening for C. auris transmission; and referral of suspicious or confirmed isolates to provincial laboratories. Patients with symptomatic disease should be treated with an echinocandin pending the results of antifungal susceptibility testing, preferably in consultation with an infectious disease specialist. Through the vigilance of front-line health care workers and microbiologists, robust infection prevention and control practices, and local and national surveillance efforts, C. auris can be detected quickly, infections managed and transmissions prevented to protect patients in our health care system.

We thank Dr. Yeung for his interest in our primer for Canadian clinicians on Candida auris .[1][1],[2][2] Given word-limit constraints, we were unable to elaborate further in our article, and so we welcome the opportunity to provide clarification regarding limitations in the ability of diagnostic

Background Histoplasmosis is a serious fungal infection caused by the geographically restricted, dimorphic fungus Histoplasma capsulatum. In Canada, the geographic range of H. capsulatum is classically thought to be restricted to southern parts of Ontario and Quebec. Over the past decade, histoplasmosis has occasionally been diagnosed in patients in Alberta without travel to areas of known geographic risk (Figure 1). We studied the epidemiology and geographic distribution of histoplasmosis in Alberta to assess evidence for locally-acquired infections. Methods We retrospectively reviewed all laboratory-confirmed (culture, antigen and/or immunodiffusion positive) cases of histoplasmosis diagnosed from January 1, 2011 to June 30, 2018. Data collected by public health and clinical charts were reviewed for clinical presentation, exposure and travel histories, and geographic distribution of cases. Cases of histoplasmosis in patients who had not left Alberta or associated with a local point source were classified as definite local acquisition; cases in patients with remote travel but with local exposures and appropriate timing of disease onset were deemed “probable” cases of local infection. University of Alberta’s Research Ethics Board approved this study. Results We identified 45 laboratory-confirmed cases of histoplasmosis, including 17 cases that were locally acquired. Among these, there were 12 cases of definite local acquisition, including 8 patients from 3 point-source outbreaks—all involving exposure to bats and/or their droppings in chimneys or attics of private dwellings or churches—and 4 sporadic cases in patients who had never traveled. Of the other 5 cases probably acquired in Alberta, patients had previously traveled (n = 4) or travel history was incomplete (n = 1) but local exposures preceding infection were considered compelling. The mean incidence rate of locally acquired infection was 0.062/100,000 population with incidence increasing since 2014. Table 1 shows features of locally acquired cases. Conclusion This study, for the first time, establishes Alberta as a region of geographic risk for histoplasmosis. The diagnosis should be considered in patients with compatible symptoms and exposure history, even in the absence of travel. Disclosures All authors: No reported disclosures.

To assess the impact of MALDI-TOF MS coupled with antimicrobial stewardship on clinical outcomes for pediatric inpatients with bloodstream infections.Outcomes of pediatric inpatients were compared before and after MALDI-TOF MS implementation. Outcomes measured included time until organism identification and susceptibility, duration of antibiotics, patient length of stay (LOS), mortality and hospital costs.210 and 135 patient events were compared pre- and post-intervention. Average time to organism identification decreased from 41 to 11 hours (P = 0.0001). Time to i) susceptibilities decreased from 50.8 to 37.7 hours (P = 0.0001), ii) de-escalation of antibiotics decreased from 58 to 23 hours (P = 0.0001), iii) discontinuation of unnecessary antibiotics decreased from 49 to 20 hours (P = 0.0001). Infection-related LOS decreased from 10.5 to 8.37 days (P = 0.006). No significant differences were seen for other outcomes.MALDI-TOF MS identification of bacteria from blood culture broth improves time to appropriate antibiotic treatment for pediatric inpatients.

We report the first documented isolation of Wohlfahrtiimonas chitiniclastica from a human in the United States. Initially misidentified as Acinetobacter lwoffii by Vitek-2, the isolate was subsequently identified as W . chitiniclastica by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) and 16S rRNA gene sequencing. While the clinical significance of the isolate in this case is unclear, it highlights the superior performance of MALDI-TOF MS for bacterial identification.

Background Antimicrobial resistance has emerged as a major threat to global public health. Thus, the surveillance of changes in antimicrobial resistance in local and global settings is a paramount necessity. While many studies have tracked antimicrobial resistance, only a small percentage surveyed ocular isolates. The purpose of this study was to report the in vitro susceptibility of bacterial pathogens isolated from ocular samples in New York, NY from 2010 to 2015. Methods A retrospective review of ocular isolates was conducted. All organisms were collected by 25 separate inpatient wards and outpatient clinics, and were analyzed by the clinical microbiology laboratory at Mount Sinai Hospital. Clinical Laboratory and Standards Institute (CLSI) guidelines were followed for susceptibility testing and breakpoint interpretations. Results A total of 549 bacterial organisms were isolated from 1664 cultures (33%) during the 6-year study period. Of these, 358 isolates (65.2%) underwent susceptibility testing. 182 (50.8%) isolates were Gram-positive. The most common Gram-positive bacterium was Staphylococcus aureus (62.1%). Methicillin-resistance decreased in S. aureus isolates (31.3% in 2010, 14.1% in 2015) but was without significant change (p = 0.25). When analyzing all S. aureus isolates recovered during the study period, there were significantly more methicillin-resistant S. aureus (MRSA) isolates resistant to fluoroquinolones (p

The occurrence and significance of Haemophilus spp. isolated from the genitourinary tract are not well known. Herein, we describe the clinical significance and characteristics of Haemophilus influenzae type b genogroup strains isolated from genitourinary tract specimens from an adult male veteran patient population and, in particular, their associations with prostatitis and epididymitis.

Introduction: Species of the genus Kocuria are Gram-positive cocci of the family Micrococcacceae that are ubiquitous in the environment and part of the normal skin and oral flora in humans. A paucity of cases have been reported of Kocuria as human pathogens and there are currently no evidence-based guidelines for managing these uncommon infections. Case presentation: We present two paediatric cases of central line infections with species of the genus Kocuria that required line removal despite antimicrobial therapy. Conclusion: Species of the genus Kocuria are uncommon human pathogens that have rarely been reported to cause opportunistic infections in both adult and paediatric populations. The cases presented here add to the growing body of literature documenting the pathogenicity of these organisms and the possible need for line removal to achieve clinical cure in central line-associated bacteraemia caused by species of the genus Kocuria.

Herein we present evidence for the therapeutic potential of colonization factor (CF)-specific egg yolk antibodies (IgY) for potentially treating acute and recurring Clostridium difficile infection (CDI) in humans. The study involved cloning, expressing as 6×His-tagged proteins in Escherichia coli, and Ni-affinity purifying three previously identified CFs (FliC, FliD and Cwp84) from C. difficile. The recombinant CF antigens were then used to immunize Leghorn chickens and CF-specific IgY antibodies were prepared from their eggs. The specificity and titre of the resulting C. difficile CF-specific IgY antibodies were assessed by ELISA and Western immunoblotting techniques. The antibodies were also screened for their ability to inhibit C. difficile adherence to human colon-derived T84 cells, and, based on these findings, one of them (FliD-specific IgY) was evaluated for its potential to prevent C. difficile-mediated morbidity and mortality in Syrian hamsters. The results revealed that purified FliD-specific IgY significantly protected hamsters from C. difficile strain 630 infection relative to control animals treated with carbonate buffer alone or IgY produced from unimmunized chicken eggs. The results suggest that egg yolk preparations obtained from chickens immunized with recombinant C. difficile CFs may represent another safe and cost-effective treatment option in humans suffering from acute or recurring CDI.

Burkholderia pseudomallei is the causative agent of melioidosis, a disease that can vary in severity from fulminant sepsis to chronic infection with fatality rates of up to 42% ([1][1], [2][2]). As world travel has increased, so have melioidosis rates in travelers to countries where melioidosis is

Background Guidelines currently provide conflicting recommendations regarding the diagnosis of group A streptococcal (GAS) pharyngitis in adults. Clinical guidelines state that negative rapid antigen detection tests (RADTs) do not require confirmation by a backup method in adults, whereas laboratory-based guidelines mandate confirmation of a negative RADT in patients of all ages. The objective of this study was to assess the utility of reflexive culture following a negative RADT in adolescents and adults with suspected GAS pharyngitis. Methods A retrospective analysis of 726 patients, aged ≥13 years, with negative RADTs and positive GAS throat cultures, was performed between 1 January 2000 and 31 December 2011 at 2 academic medical centers in Seattle, Washington. Complication rates, treatment, modified Centor score, and bacterial burden in patients with negative RADTs and positive GAS throat cultures were assessed. Results Modified Centor scores ≥2 were observed in 55% of patients with a negative RADT and positive GAS culture. Of these, 77% of patients had a moderate or heavy bacterial burden (≥2+). RADTs failed to detect some patients who presented with serious complications of GAS pharyngitis: 29 (4.0%) had peritonsillar abscesses and 2 (0.28%) were diagnosed with acute rheumatic fever. Providers found culture results to be useful for initiating antibiotic therapy or confirming a clinical diagnosis. Antibiotic treatment was prescribed in 68.7% of patients, with culture-directed initiation of therapy documented in 43.5%. Conclusions Reflexive GAS culture is clinically useful when RADTs are negative. RADTs fail to detect a substantial number of adult patients with clinically significant pharyngitis who can benefit from treatment.

Clostridium difficile , a major cause of hospital-acquired diarrhea, triggers disease through the release of two toxins, toxin A (TcdA) and toxin B (TcdB). These toxins disrupt the cytoskeleton of the intestinal epithelial cell, increasing intestinal permeability and triggering the release of inflammatory mediators resulting in intestinal injury and inflammation. The most prevalent animal model to study TcdA/TcdB-induced intestinal injury involves injecting toxin into the lumen of a surgically generated “ileal loop.” This model is time-consuming and exhibits variability depending on the expertise of the surgeon. Furthermore, the target organ of C. difficile infection (CDI) in humans is the colon, not the ileum. In the current study, we describe a new model of CDI that involves intrarectal instillation of TcdA/TcdB into the mouse colon. The administration of TcdA/TcdB triggered colonic inflammation and neutrophil and macrophage infiltration as well as increased epithelial barrier permeability and intestinal epithelial cell death. The damage and inflammation triggered by TcdA/TcdB isolates from the VPI and 630 strains correlated with the concentration of TcdA and TcdB produced. TcdA/TcdB exposure increased the expression of a number of inflammatory mediators associated with human CDI, including interleukin-6 (IL-6), gamma interferon (IFN-γ), and IL-1β. Finally, we were able to demonstrate that TcdA was much more potent at inducing colonic injury than was TcdB but TcdB could act synergistically with TcdA to exacerbate injury. Taken together, our data indicate that the intrarectal murine model provides a robust and efficient system to examine the effects of TcdA/TcdB on the induction of inflammation and colonic tissue damage in the context of human CDI.