scholarly journals Performance Evaluation of the Luminex Aries C. difficile Assay in Comparison to Two Other Molecular Assays within a Multihospital Health Care Center

2019 ◽  
Vol 57 (11) ◽  
Author(s):  
Stefan Juretschko ◽  
Ryhana Manji ◽  
Reeti Khare ◽  
Shubhagata Das ◽  
Sherry Dunbar
Keyword(s):  
Care Center ◽  
Hospital Setting ◽  
The United States ◽  
Turnaround Time ◽  
Sample Number ◽  
Content Type ◽  
Health Care Center ◽  
Clostridioides Difficile ◽  
Comparison Results ◽  
Hands On

ABSTRACT Clostridioides difficile infection (CDI) remain a serious issue in the United States. Fast and accurate diagnosis of CDI is paramount to achieve immediate infection control initiation, triaging, and isolation, as well as appropriate antibiotic treatment. However, both, over- and underdiagnosis can lead to adverse patient outcomes, such as unnecessary administration of antibiotics or unwanted spread of spores in any hospital setting, respectively. In this prospective study, we evaluated the FDA-cleared Aries C. difficile assay and compared its performance and workflow characteristics to those of the BD Max Cdiff and Xpert C. difficile/Epi assays. Out of 302 samples tested, 55 (18.2%) samples were positive, and 234 (77.5%) samples were negative for C. difficile by all three testing methods. Comparison results showed a positive and negative percent agreement (PPA and NPA, respectively) between the Aries and Xpert assays of 95.2% (59/62) and 99.2% (238/240), respectively. The PPA and NPA between the Aries and BD Max assays were 91.8% (56/61) and 96.6% (230/238), respectively. Invalid result rates were determined to be 2.6% for the BD Max assay, 1.0% for the Aries assay, and 0% for the Xpert assay. Hands-on time (HoT) and total turnaround time (TAT) varied considerably depending on the sample number and instrument throughput. The HoT ranged from 1.2 to 3.5 min per sample, and the TAT was 1 to 2.3 h. Overall, the results demonstrated that the Aries assay is a rapid and sensitive method for the diagnosis of CDI in clinical laboratories.

scholarly journals Impact of Rapid PCR Influenza Testing on the Rate of Inpatient Admissions During Influenza Season at a Tertiary-Care Center

2020 ◽  
Vol 41 (S1) ◽  
pp. s263-s264
Author(s):  
Jordan Polistico ◽  
Avnish Sandhu ◽  
Teena Chopra ◽  
Erin Goldman ◽  
Jennifer LeRose ◽  
...  
Keyword(s):  
Influenza Season ◽  
Care Center ◽  
Tertiary Care ◽  
The United States ◽  
Turnaround Time ◽  
Care Hospital ◽  
Tertiary Care Center ◽  
Pediatric Hospital ◽  
Rapid Pcr ◽  
The Impact

Background: Influenza causes a high burden of disease in the United States, with an estimate of 960,000 hospitalizations in the 2017–2018 flu season. Traditional flu diagnostic polymerase chain reaction (PCR) tests have a longer (24 hours or more) turnaround time that may lead to an increase in unnecessary inpatient admissions during peak influenza season. A new point-of-care rapid PCR assays, Xpert Flu, is an FDA-approved PCR test that has a significant decrease in turnaround time (2 hours). The present study sought to understand the impact of implementing a new Xpert Flu test on the rate of inpatient admissions. Methods: A retrospective study was conducted to compare rates of inpatient admissions in patients tested with traditional flu PCR during the 2017–2018 flu season and the rapid flu PCR during the 2018–2019 flu season in a tertiary-care center in greater Detroit area. The center has 1 pediatric hospital (hospital A) and 3 adult hospitals (hospital B, C, D). Patients with influenza-like illness who presented to all 4 hospitals during 2 consecutive influenza seasons were analyzed. Results: In total, 20,923 patients were tested with either the rapid flu PCR or the traditional flu PCR. Among these, 14,124 patients (67.2%) were discharged from the emergency department and 6,844 (32.7%) were admitted. There was a significant decrease in inpatient admissions in the traditional flu PCR group compared to the rapid flu PCR group across all hospitals (49.56% vs 26.6% respectively; P < .001). As expected, a significant proportion of influenza testing was performed in the pediatric hospital, 10,513 (50.2%). A greater reduction (30% decrease in the rapid flu PCR group compared to the traditional flu PCR group) was observed in inpatient admissions in the pediatric hospital (Table 1) Conclusions: Rapid molecular influenza testing can significantly decrease inpatient admissions in a busy tertiary-care hospital, which can indirectly lead to improved patient quality with easy bed availability and less time spent in a private room with droplet precautions. Last but not the least, this testing method can certainly lead to lower healthcare costs.Funding: NoneDisclosures: None

scholarly journals Spo0A Suppresses sin Locus Expression in Clostridioides difficile

mSphere ◽  
2020 ◽  
Vol 5 (6) ◽  
Author(s):  
Babita Adhikari Dhungel ◽  
Revathi Govind
Keyword(s):  
Diarrheal Disease ◽  
Toxin Production ◽  
The United States ◽  
Upstream Region ◽  
Pcr Analysis ◽  
Bacterial Cells ◽  
Master Regulator ◽  
Content Type ◽  
Clostridioides Difficile

ABSTRACT Clostridioides difficile is the leading cause of nosocomial infection and is the causative agent of antibiotic-associated diarrhea. The severity of the disease is directly associated with toxin production, and spores are responsible for the transmission and persistence of the organism. Previously, we characterized sin locus regulators SinR and SinR′ (we renamed it SinI), where SinR is the regulator of toxin production and sporulation. The SinI regulator acts as its antagonist. In Bacillus subtilis, Spo0A, the master regulator of sporulation, controls SinR by regulating the expression of its antagonist, sinI. However, the role of Spo0A in the expression of sinR and sinI in C. difficile had not yet been reported. In this study, we tested spo0A mutants in three different C. difficile strains, R20291, UK1, and JIR8094, to understand the role of Spo0A in sin locus expression. Western blot analysis revealed that spo0A mutants had increased SinR levels. Quantitative reverse transcription-PCR (qRT-PCR) analysis of its expression further supported these data. By carrying out genetic and biochemical assays, we show that Spo0A can bind to the upstream region of this locus to regulates its expression. This study provides vital information that Spo0A regulates the sin locus, which controls critical pathogenic traits such as sporulation, toxin production, and motility in C. difficile. IMPORTANCE Clostridioides difficile is the leading cause of antibiotic-associated diarrheal disease in the United States. During infection, C. difficile spores germinate, and the vegetative bacterial cells produce toxins that damage host tissue. In C. difficile, the sin locus is known to regulate both sporulation and toxin production. In this study, we show that Spo0A, the master regulator of sporulation, controls sin locus expression. Results from our study suggest that Spo0A directly regulates the expression of this locus by binding to its upstream DNA region. This observation adds new detail to the gene regulatory network that connects sporulation and toxin production in this pathogen.

scholarly journals Homologous Recombination in Clostridioides difficile Mediates Diversification of Cell Surface Features and Transport Systems

mSphere ◽  
2020 ◽  
Vol 5 (6) ◽  
Author(s):  
Hannah D. Steinberg ◽  
Evan S. Snitkin
Keyword(s):  
Cell Wall ◽  
Homologous Recombination ◽  
Sugar Transport ◽  
The United States ◽  
Strain Typing ◽  
Cell Wall Proteins ◽  
Genetic Loci ◽  
Content Type ◽  
Clostridioides Difficile ◽  
Host Pathogen

ABSTRACT Illness caused by the pathogen Clostridioides difficile is widespread and can range in severity from mild diarrhea to sepsis and death. Strains of C. difficile isolated from human infections exhibit great genetic diversity, leading to the hypothesis that the genetic background of the infecting strain at least partially determines a patient’s clinical course. However, although certain strains of C. difficile have been suggested to be associated with increased severity, strain typing alone has proved insufficient to explain infection severity. The limited explanatory power of strain typing has been hypothesized to be due to genetic variation within strain types, as well as genetic elements shared between strain types. Homologous recombination is an evolutionary mechanism that can result in large genetic differences between two otherwise clonal isolates, and also lead to convergent genotypes in distantly related strains. More than 400 C. difficile genomes were analyzed here to assess the effect of homologous recombination within and between C. difficile clades. Almost three-quarters of single nucleotide variants in the C. difficile phylogeny are predicted to be due to homologous recombination events. Furthermore, recombination events were enriched in genes previously reported to be important to virulence and host-pathogen interactions, such as flagella, cell wall proteins, and sugar transport and metabolism. Thus, by exploring the landscape of homologous recombination in C. difficile, we identified genetic loci whose elevated rates of recombination mediated diversification, making them strong candidates for being mediators of host-pathogen interaction in diverse strains of C. difficile. IMPORTANCE Infections with C. difficile result in up to half a million illnesses and tens of thousands of deaths annually in the United States. The severity of C. difficile illness is dependent on both host and bacterial factors. Studying the evolutionary history of C. difficile pathogens is important for understanding the variation in pathogenicity of these bacteria. This study examines the extent and targets of homologous recombination, a mechanism by which distant strains of bacteria can share genetic material, in hundreds of C. difficile strains and identifies hot spots of realized recombination events. The results of this analysis reveal the importance of homologous recombination in the diversification of genetic loci in C. difficile that are significant in its pathogenicity and host interactions, such as flagellar construction, cell wall proteins, and sugar transport and metabolism.

Hospital-level high-risk antibiotic use in relation to hospital-associated Clostridioides difficile infections: Retrospective analysis of 2016–2017 data from US hospitals

2019 ◽  
Vol 40 (11) ◽  
pp. 1229-1235 ◽  
Author(s):  
Ying P. Tabak ◽  
Arjun Srinivasan ◽  
Kalvin C. Yu ◽  
Stephen G. Kurtz ◽  
Vikas Gupta ◽  
...  
Keyword(s):  
High Risk ◽  
Hospital Setting ◽  
Antibiotic Use ◽  
The United States ◽  
Fourth Generation ◽  
Teaching Hospitals ◽  
Clostridioides Difficile ◽  
Positive Stool ◽  
Days Of Therapy ◽  
Assay Result

AbstractObjective:Antibiotics are widely used by all specialties in the hospital setting. We evaluated previously defined high-risk antibiotic use in relation to Clostridioides difficile infections (CDIs).Methods:We analyzed 2016–2017 data from 171 hospitals. High-risk antibiotics included second-, third-, and fourth-generation cephalosporins, fluoroquinolones, carbapenems, and lincosamides. A CDI case was a positive stool C. difficile toxin or molecular assay result from a patient without a positive result in the previous 8 weeks. Hospital-associated (HA) CDI cases included specimens collected >3 calendar days after admission or ≤3 calendar days from a patient with a prior same-hospital discharge within 28 days. We used the multivariable Poisson regression model to estimate the relative risk (RR) of high-risk antibiotic use on HA CDI, controlling for confounders.Results:The median days of therapy for high-risk antibiotic use was 241.2 (interquartile range [IQR], 192.6–295.2) per 1,000 days present; the overall HA CDI rate was 33 (IQR, 24–43) per 10,000 admissions. The overall correlation of high-risk antibiotic use and HA CDI was 0.22 (P = .003), and higher correlation was observed in teaching hospitals (0.38; P = .002). For every 100-day (per 1,000 days present) increase in high-risk antibiotic therapy, there was a 12% increase in HA CDI (RR, 1.12; 95% CI, 1.04–1.21; P = .002) after adjusting for confounders.Conclusions:High-risk antibiotic use is an independent predictor of HA CDI. This assessment of poststewardship implementation in the United States highlights the importance of tracking trends of antimicrobial use over time as it relates to CDI.

scholarly journals Clinical and Genomic Epidemiology of Carbapenem-Nonsusceptible Citrobacter spp. at a Tertiary Health Care Center over 2 Decades

2020 ◽  
Vol 58 (9) ◽  
Author(s):  
Ahmed Babiker ◽  
Daniel R. Evans ◽  
Marissa P. Griffith ◽  
Christi L. McElheny ◽  
Mohamed Hassan ◽  
...  
Keyword(s):  
Health Care ◽  
Clinical Epidemiology ◽  
Medical Center ◽  
Care Center ◽  
Carbapenem Resistance ◽  
Time Frame ◽  
Content Type ◽  
Health Care Center ◽  
Genomic Epidemiology ◽  
Genes Encoding

ABSTRACT Carbapenem-nonsusceptible Citrobacter spp. (CNSC) are increasingly recognized as health care-associated pathogens. Information regarding their clinical epidemiology, genetic diversity, and mechanisms of carbapenem resistance is lacking. We examined microbiology records of adult patients at the University of Pittsburgh Medical Center (UMPC) Presbyterian Hospital (PUH) from 2000 to 2018 for CNSC, as defined by ertapenem nonsusceptibility. Over this time frame, the proportion of CNSC increased from 4% to 10% (P = 0.03), as did daily defined carbapenem doses/1,000 patient days (6.52 to 34.5; R2 = 0.831; P < 0.001), which correlated with the observed increase in CNSC (lag = 0 years; R2 = 0.660). Twenty CNSC isolates from 19 patients at PUH and other UPMC hospitals were available for further analysis, including whole-genome short-read sequencing and additional antimicrobial susceptibility testing. Of the 19 patients, nearly all acquired CNSC in the health care setting and over half had polymicrobial cultures containing at least one other organism. Among the 20 CNSC isolates, Citrobacter freundii was the predominant species identified (60%). CNSC genomes were compared with genomes of carbapenem-susceptible Citrobacter spp. from UPMC and with other publicly available CNSC genomes. Isolates carrying genes encoding carbapenemases (blaKPC-2, blaKPC-3, and blaNDM-1) were also long-read sequenced, and their carbapenemase-encoding plasmid sequences were compared with one another and with publicly available sequences. Phylogenetic analysis of 102 UPMC Citrobacter genomes showed that CNSC from our setting did not cluster together. Similarly, a global phylogeny of 64 CNSC genomes showed a diverse population structure. Our findings suggest that both local and global CNSC populations are genetically diverse and that CNSC harbor carbapenemase-encoding plasmids found in other Enterobacterales.

scholarly journals Molecular Characterization by Using Next-Generation Sequencing of Plasmids ContainingblaNDM-7in Enterobacteriaceae from Calgary, Canada

2015 ◽  
Vol 60 (3) ◽  
pp. 1258-1263 ◽  
Author(s):  
L. Chen ◽  
G. Peirano ◽  
T. Lynch ◽  
K. D. Chavda ◽  
D. B. Gregson ◽  
...  
Keyword(s):  
United States ◽  
Risk Factors ◽  
Escherichia Coli ◽  
Horizontal Transmission ◽  
Hospital Setting ◽  
The United States ◽  
Content Type ◽  
Molecular Studies ◽  
Enterobacter Hormaechei ◽  
Generation Sequencing

EnterobacteriaceaewithblaNDM-7are relatively uncommon and had previously been described in Europe, India, the United States, and Japan. This study describes the characteristics ofEnterobacteriaceae(Klebsiella pneumoniae[n= 2],Escherichia coli[n= 2],Serratia marcescens[n= 1], andEnterobacter hormaechei[n= 1] isolates) withblaNDM-7obtained from 4 patients from Calgary, Canada, from 2013 to 2014. The 46,161-bp IncX3 plasmids withblaNDM-7are highly similar to otherblaNDM-harboring IncX3 plasmids and, interestingly, showed identical structures within the different isolates. This finding may indicate horizontal transmission within our health region, or it may indicate contact with individuals from areas of endemicity within the hospital setting. Patients infected or colonized with bacteria containingblaNDM-7IncX3 plasmids generate infection control challenges. Epidemiological and molecular studies are required to better understand the dynamics of transmission, the risk factors, and the reservoirs for bacteria harboringblaNDM-7. To the best of our knowledge, this is the first report ofS. marcescensandE. hormaecheiwithblaNDM-7.

scholarly journals Immune Profiling To Predict Outcome of Clostridioides difficile Infection

mBio ◽  
2020 ◽  
Vol 11 (3) ◽  
Author(s):  
Mayuresh M. Abhyankar ◽  
Jennie Z. Ma ◽  
Kenneth W. Scully ◽  
Andrew J. Nafziger ◽  
Alyse L. Frisbee ◽  
...  
Keyword(s):  
Prediction Model ◽  
Risk Prediction ◽  
Mortality Risk ◽  
The United States ◽  
Host Bacterium ◽  
Clinical Parameters ◽  
Content Type ◽  
Clostridioides Difficile ◽  
Tnf Α ◽  
Immune Profiling

ABSTRACT There is a pressing need for biomarker-based models to predict mortality from and recurrence of Clostridioides difficile infection (CDI). Risk stratification would enable targeted interventions such as fecal microbiota transplant, antitoxin antibodies, and colectomy for those at highest risk. Because severity of CDI is associated with the immune response, we immune profiled patients at the time of diagnosis. The levels of 17 cytokines in plasma were measured in 341 CDI inpatients. The primary outcome of interest was 90-day mortality. Increased tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), C-C motif chemokine ligand 5 (CCL-5), suppression of tumorigenicity 2 receptor (sST-2), IL-8, and IL-15 predicted mortality by univariate analysis. After adjusting for demographics and clinical characteristics, the mortality risk (as indicated by the hazard ratio [HR]) was higher for patients in the top 25th percentile for TNF-α (HR = 8.35, P = 0.005) and IL-8 (HR = 4.45, P = 0.01) and lower for CCL-5 (HR = 0.18, P ≤ 0.008). A logistic regression risk prediction model was developed and had an area under the receiver operating characteristic curve (AUC) of 0.91 for 90-day mortality and 0.77 for 90-day recurrence. While limited by being single site and retrospective, our work resulted in a model with a substantially greater predictive ability than white blood cell count. In conclusion, immune profiling demonstrated differences between patients in their response to CDI, offering the promise for precision medicine individualized treatment. IMPORTANCE Clostridioides difficile infection is the most common health care-associated infection in the United States with more than 20% patients experiencing symptomatic recurrence. The complex nature of host-bacterium interactions makes it difficult to predict the course of the disease based solely on clinical parameters. In the present study, we built a robust prediction model using representative plasma biomarkers and clinical parameters for 90-day all-cause mortality. Risk prediction based on immune biomarkers and clinical variables may contribute to treatment selection for patients as well as provide insight into the role of immune system in C. difficile pathogenesis.

scholarly journals Type 3 Immunity during Clostridioides difficile Infection: Too Much of a Good Thing?

2019 ◽  
Vol 88 (1) ◽  
Author(s):  
Mahmoud M. Saleh ◽  
William A. Petri
Keyword(s):  
The United States ◽  
Lymphoid Cells ◽  
Interleukin 17 ◽  
Gastrointestinal Infections ◽  
Content Type ◽  
Animal Models Of Disease ◽  
Interleukin 22 ◽  
Inflammatory Conditions ◽  
Clostridioides Difficile ◽  
Type 3

ABSTRACT Clostridioides (formerly known as Clostridium) difficile is the leading cause of hospital-acquired gastrointestinal infections in the United States and one of three urgent health care threats identified by the Centers for Disease Control and Prevention. C. difficile disease is mediated by the production of toxins that disrupt the epithelial barrier and cause a robust host inflammatory response. Studies in humans as well as animal models of disease have shown that the type of immune response generated against the infection dictates the outcome of disease, often irrespective of bacterial burden. Much of the focus on immunity during C. difficile infection (CDI) has been on type 3 immunity because of the established role for this arm of the immune system in other gastrointestinal inflammatory conditions such as inflammatory bowel disease (IBD). For example, interleukin-22 (IL-22) production by group 3 innate lymphoid cells (ILC3s) protects against pathobionts translocating across the epithelium during CDI. On the other hand, interleukin-17 (IL-17) production by Th17 cells increases CDI-associated mortality. Additionally, neutropenia has been associated with increased susceptibility to CDI in humans, but increased neutrophilia in mouse models correlates with host pathology. Taking the data together, these findings suggest dual roles for type 3 immune responses during infection. Here, we review the complex role of type 3 immunity during CDI and delineate what is known about innate and adaptive cellular immunity as well as the downstream effector cytokines known to be important during this infection.

scholarly journals Evaluation of the Liat Cdiff Assay for Direct Detection of Clostridioides difficile Toxin Genes within 20 Minutes

2019 ◽  
Vol 57 (6) ◽  
Author(s):  
David J. Hetem ◽  
Ingrid Bos-Sanders ◽  
Roel H. T. Nijhuis ◽  
Sven Tamminga ◽  
Livia Berlinger ◽  
...  
Keyword(s):  
Infection Control ◽  
Direct Detection ◽  
Point Of Care ◽  
Reference Method ◽  
Turnaround Time ◽  
Control Measures ◽  
Content Type ◽  
Infection Control Measures ◽  
Clostridioides Difficile ◽  
The Difference

ABSTRACT Clostridioides difficile is the main causative agent of antibiotic-associated diarrhea. Prompt diagnosis is required for initiation of timely infection control measures and appropriate adjustment of antibiotic treatment. The cobas Cdiff assay for use on the cobas Liat system enables a diagnostic result in 20 minutes. A total of 252 prospective (n = 150) and retrospective (n = 102) stool specimens from The Netherlands, France, and Switzerland were tested on the cobas Cdiff assay using the Xpert C. difficile assay as a reference method. The overall positive and negative percent agreement (PPA and NPA, respectively) of the cobas Cdiff assay compared with the Xpert C. difficile assay was 98.0% (100/102; 95% confidence interval [CI], 93.1% to 99.5%) and 94.0% (141/150; 95% CI, 89.0% to 96.8%), respectively. When comparing the PPAs of cobas Cdiff and Xpert C. difficile with culture, the results were 91.7% (55/60; 95% CI, 81.9% to 96.4%) and 85.0% (51/60; 95% CI, 73.9% to 91.9%), respectively. The difference was not statistically significant. The cobas Cdiff assay offers a very rapid alternative for diagnosing C. difficile infection. The 20-minute turnaround time provides the potential for point-of-care testing so that adequate infection control measures can be initiated promptly.

scholarly journals Methicillin-Resistant Staphylococcus aureus Sequence Type (ST) 5 Isolates from Health Care and Agricultural Sources Adhere Equivalently to Human Keratinocytes

2017 ◽  
Vol 84 (2) ◽  
Author(s):  
Samantha J. Hau ◽  
Steven Kellner ◽  
Kirsten C. Eberle ◽  
Ursula Waack ◽  
Susan L. Brockmeier ◽  
...  
Keyword(s):  
Public Health ◽  
Staphylococcus Aureus ◽  
Human Skin ◽  
Hospital Setting ◽  
Human Keratinocytes ◽  
The United States ◽  
Sequence Type ◽  
Methicillin Resistant ◽  
Content Type

ABSTRACT Staphylococcus aureus is part of the nasal microbiome of many humans and has become a significant public health burden due to infections with antibiotic-resistant strains, including methicillin-resistant S. aureus (MRSA) strains. Several lineages of S. aureus, including MRSA, are found in livestock species and can be acquired by humans through contact with animals. These livestock-associated MRSA (LA-MRSA) isolates raise public health concerns because of the potential for livestock to act as reservoirs for MRSA outside the hospital setting. In the United States, swine harbor a mixed population of LA-MRSA isolates, with the sequence type 398 (ST398), ST9, and ST5 lineages being detected. LA-MRSA ST5 isolates are particularly concerning to the public health community because, unlike the isolates in the ST398 and ST9 lineages, isolates in the ST5 lineage are a significant cause of human disease in both the hospital and community settings globally. The ability of swine-associated LA-MRSA ST5 isolates to adhere to human keratinocytes in vitro was investigated, and the adherence genes harbored by these isolates were evaluated and compared to those in clinical MRSA ST5 isolates from humans with no swine contact. The two subsets of isolates adhered equivalently to human keratinocytes in vitro and contained an indistinguishable complement of adherence genes that possessed a high degree of sequence identity. Collectively, our data indicate that, unlike LA-MRSA ST398 isolates, LA-MRSA ST5 isolates do not exhibit a reduced genotypic or phenotypic capacity to adhere to human keratinocytes. IMPORTANCE Our data indicate that swine-associated livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) ST5 isolates are as capable of adhering to human skin and have the same genetic potential to adhere as clinical MRSA ST5 isolates from humans. This suggests that humans in contact with livestock have the potential to become colonized with LA-MRSA ST5 isolates; however, the genes that contribute to the persistence of S. aureus on human skin were absent in LA-MRSA ST5 isolates. The data presented here are important evidence in evaluating the potential risks that LA-MRSA ST5 isolates pose to humans who come into contact with livestock.

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