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Castillo Almeida NE, Gomez CA. Acute diarrhea in the hospitalized immunocompromised patient: what is new on diagnostic and treatment? Curr Opin Crit Care 2024; 30:456-462. [PMID: 39034915 PMCID: PMC11377059 DOI: 10.1097/mcc.0000000000001191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/23/2024]
Abstract
PURPOSE OF REVIEW This article aims to provide an intuitive framework for diagnosing and managing healthcare-associated diarrhea (HCAD) in the immunocompromised (IC) host. RECENT FINDINGS Our understanding of diarrhea in hospitalized IC patients has significantly evolved. However, the challenge lies in distinguishing between these patients' numerous causes of diarrhea. The incorporation of gastrointestinal (GI) multiplex polymerase chain reaction (PCR) panels has led to a paradigm shift in our approach to diarrhea. However, using these panels judiciously is of utmost importance, as their misuse can lead to over-testing, overtreatment, and increased hospital costs. We propose a stepwise diagnostic algorithm that ensures diagnostic stewardship, optimal patient care, and resource utilization. SUMMARY Diarrhea is a common complication in hospitalized IC patients and is associated with significant morbidity and rare mortality. The advent of new diagnostics, such as GI multiplex PCR panels, holds promise in facilitating the detection of recognized pathogens and may allow for improved outcomes using pathogen-targeted therapy.
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Affiliation(s)
- Natalia E Castillo Almeida
- Department of Internal Medicine, Division of Infectious Diseases, University of Nebraska Medical Center, Omaha, Nebraska, USA
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Cocco P, Smith AF, Davies KA, Rooney CM, West RM, Shinkins B. Early Economic Modeling to Inform a Target Product Profile: A Case Study of a Novel Rapid Test for Clostridioides difficile Infection. MDM Policy Pract 2024; 9:23814683241293739. [PMID: 39583088 PMCID: PMC11585019 DOI: 10.1177/23814683241293739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 09/11/2024] [Indexed: 11/26/2024] Open
Abstract
Background. Target product profiles (TPPs) specify the essential properties tests must have to be able to address an unmet clinical need. Aim. To explore how early economic modeling can help to define TPP specifications based on cost-effectiveness considerations using the example of a new rapid diagnostic for Clostridioides difficile infection (CDI), a contagious health care-associated infection causing potentially fatal diarrhea. Methods. A resource-constrained simulation model was developed to compare a hypothetical test for CDI with current practice (i.e., test with glutamate dehydrogenase enzyme immunoassay first; if positive, test with polymerase chain reaction and cytotoxicity assay) for adult individuals with suspected CDI at the Leeds Teaching Hospital National Health System (NHS) Trust in the United Kingdom. Parameters are taken from UK-based observational data collected between 2018 and 2021, published literature, and expert opinion. A methodological framework was developed 1) to derive minimum diagnostic sensitivity and specificity and maximum price for different test turnaround-time values based on cost-effectiveness considerations from the health care perspective using the National Institute of Health Care Excellence willingness-to-pay threshold of £20,000 per quality-adjusted life-years and 2) to test their robustness using a series of sensitivity analyses. Results. A new rapid test for CDI with a 15-min turnaround time would require a minimum diagnostic sensitivity and specificity both equal to 96% and a maximum price of £44 to maintain cost-effectiveness compared with standard of care. Conclusions. This study provides a framework to inform the essential test properties based on cost-effectiveness considerations and to isolate the most influential model parameters and scenarios via a series of sensitivity analyses. These specifications, in turn, could be used to inform future TPPs for tests. Highlights Target product profiles (TPPs) for new medical tests provide test developers with performance benchmarks and technical requirements for new tests. Early economic evaluation has already been used to identify acceptable ranges for certain performance requirements for new tests. Currently, however, early economic evaluation methods are yet to be used in the context of TPP development, and there is no guidance as to how this could and should be done.A de novo approach was developed to identify the minimum performance requirements and maximum costs for new tests, based on cost-effectiveness considerations, while also isolating most influential parameters. The added value of this framework lies in structuring early economic evaluation methods as a means of informing transparent, evidence-based minimum TPP performance specifications while also accounting as much as possible for the (inevitable) uncertainty surrounding the minimum performance requirements.This study represents the first application of early economic modeling as a means of deriving the minimum performance specifications for a novel point-of-care test for Clostridioides difficile infection as set out in a future TPP.
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Affiliation(s)
- Paola Cocco
- Academic Unit of Health Economics, Leeds Diagnosis and Screening Unit, Leeds Institute for Health Sciences, University of Leeds, Leeds, UK
| | - Alison Florence Smith
- Academic Unit of Health Economics, Leeds Diagnosis and Screening Unit, Leeds Institute for Health Sciences, University of Leeds, Leeds, UK
- Academic Unit of Health Economics, Leeds Diagnosis and Screening Unit, Leeds Institute for Health Sciences, NIHR Leeds In Vitro Diagnostics Co-operative (MIC), University of Leeds, Leeds, UK
| | - Kerrie Ann Davies
- Academic Unit of Health Economics, Leeds Diagnosis and Screening Unit, Leeds Institute for Health Sciences, NIHR Leeds In Vitro Diagnostics Co-operative (MIC), University of Leeds, Leeds, UK
- Healthcare Associated Infections Research Group, Leeds Teaching Hospitals NHS Trust, and University of Leeds, Leeds, UK
- NIHR Leeds In Vitro Diagnostics Co-operative (MIC), Leeds Teaching Hospitals NHS Trust, and University of Leeds, Leeds, UK
- European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Clostridioides difficile – ESGCD
| | - Christopher Michael Rooney
- Healthcare Associated Infections Research Group, Leeds Teaching Hospitals NHS Trust, and University of Leeds, Leeds, UK
| | | | - Bethany Shinkins
- Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry, UK
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Lim VW, Tomaru T, Chua B, Ma Y, Yanagihara K. Budget Impact Analysis of Adopting a One-Step Nucleic Acid Amplification Testing (NAAT) Alone Diagnostic Pathway for Clostridioides difficile in Japan Compared to a Two-Step Algorithm with Glutamate Dehydrogenase/Toxin Followed by NAAT. Diagnostics (Basel) 2023; 13:diagnostics13081463. [PMID: 37189564 DOI: 10.3390/diagnostics13081463] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Revised: 04/06/2023] [Accepted: 04/15/2023] [Indexed: 05/17/2023] Open
Abstract
Clostridioides difficile infection (CDI) is a major healthcare-associated infection that leads to a significant health economic burden in Japan. Using a decision tree model, we evaluated the budget impact of adopting a one-step nucleic acid amplification test (NAAT) alone pathway compared to a two-step diagnostic algorithm with glutamate dehydrogenase (GDH) and toxin antigen, followed by NAAT. The analysis was conducted from the government payer's perspective for 100,000 symptomatic, hospitalized adults requiring a CDI diagnostic test. One-way sensitivity analysis was conducted for all data inputs. The NAAT alone strategy costed JPY 225,886,360 (USD 2,424,714) more, but was more effective, resulting in 1749 more patients accurately diagnosed and 91 fewer deaths compared to the two-step algorithm. Additionally, the NAAT alone pathway costed JPY 26,146 (USD 281) less per true positive CDI diagnosed. The total budget impact, and cost per CDI diagnosed was most sensitive to GDH sensitivity in one-way sensitivity analysis, where a lower GDH sensitivity resulted in greater cost savings with the NAAT alone pathway. Findings from this budget impact analysis can guide the adoption of a NAAT alone pathway for CDI diagnosis in Japan.
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Affiliation(s)
- Vanessa W Lim
- Health Economics and Outcomes Research, Becton Dickinson Holdings Pte. Ltd., 2 International Business Park Road, Singapore 609930, Singapore
| | - Takeshi Tomaru
- Health Economics and Outcomes Research, Nippon Becton Dickinson Company, Ltd., Akasaka Garden City 15-1, Akasaka 4-Chome, Minato-ku, Tokyo 107-0052, Japan
| | - Brandon Chua
- Health Economics and Outcomes Research, Becton Dickinson Holdings Pte. Ltd., 2 International Business Park Road, Singapore 609930, Singapore
- Saw Swee Hock School of Public Health, National University of Singapore, 12 Science Drive 2, #10-02, Singapore 117549, Singapore
| | - Yan Ma
- Health Economics and Outcomes Research, Becton Dickinson Holdings Pte. Ltd., 2 International Business Park Road, Singapore 609930, Singapore
| | - Katsunori Yanagihara
- Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University Hospital, Sakamoto 1-12-4, Nagasaki City 852-8523, Japan
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Doolan CP, Louie T, Lata C, Larios OE, Stokes W, Kim J, Brown K, Beck P, Deardon R, Pillai DR. Latent class analysis for the diagnosis of Clostridioides difficile infection. Clin Infect Dis 2020; 73:e2673-e2679. [PMID: 33053174 DOI: 10.1093/cid/ciaa1553] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Clostridioides difficile infection (CDI) is an opportunistic disease that lacks a gold standard test. Nucleic acid amplification tests (NAATs) such as real-time PCR demonstrate excellent an limit of detection (LOD) whereas antigenic methods are able to detect free toxin. Latent class analysis (LCA) provides an unbiased statistical approach to resolving true disease. METHODS A cross-sectional study was conducted with suspected CDI patients (n=96). Four commercial real-time PCR tests, toxin antigen detection by enzyme immunoassay (EIA), toxigenic culture, and fecal calprotectin were performed. CDI clinical diagnosis was determined by consensus majority of three experts. LCA was performed using laboratory and clinical variables independent of any gold standard. RESULTS Six LCA models were generated to determine CDI probability using four variables including toxin EIA, toxigenic culture, clinical diagnosis, and fecal calprotectin levels. Three defined zones as a function of real-time PCR cycle threshold (Ct) were identified using LCA: CDI likely (>90% probability), equivocal (<90% and >10%), CDI unlikely (<10%). A single model comprising toxigenic culture, clinical diagnosis, and toxin EIA showed the best fitness. The following Ct cut-offs for four commercial test platforms were obtained using this model to delineate three CDI probability zones: [GeneXpert ® : 24.00, 33.61], [Simplexa ® 28.97, 36.85], [Elite MGB ® 30.18, 37.43], and [BD Max ™ 27.60, 34.26]. CONCLUSION The clinical implication of applying LCA to CDI is to report Ct values assigned to probability zones based on the commercial real-time PCR platform. A broad range of equivocation suggests clinical judgement is essential to the confirmation of CDI.
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Affiliation(s)
- Cody P Doolan
- Clinical Section of Microbiology, Alberta Precision Laboratories, Calgary, AB, Canada.,Department of Microbiology, Immunology, and Infectious Diseases, University of Calgary, AB, Canada.,Department Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada
| | - Thomas Louie
- Clinical Section of Infectious Diseases, Department of Medicine, University of Calgary, Calgary, AB, Canada
| | | | - Oscar E Larios
- Clinical Section of Microbiology, Alberta Precision Laboratories, Calgary, AB, Canada.,Department Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada.,Clinical Section of Infectious Diseases, Department of Medicine, University of Calgary, Calgary, AB, Canada
| | - William Stokes
- Clinical Section of Microbiology, Alberta Precision Laboratories, Calgary, AB, Canada.,Department Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada.,Clinical Section of Infectious Diseases, Department of Medicine, University of Calgary, Calgary, AB, Canada
| | - Joseph Kim
- Clinical Section of Infectious Diseases, Department of Medicine, University of Calgary, Calgary, AB, Canada
| | - Kristen Brown
- Clinical Section of Microbiology, Alberta Precision Laboratories, Calgary, AB, Canada.,Department Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada.,Clinical Section of Infectious Diseases, Department of Medicine, University of Calgary, Calgary, AB, Canada
| | - Paul Beck
- Clinical Section of Gastroenterology, Department of Medicine, University of Calgary, Calgary, AB, Canada
| | - Rob Deardon
- Department of Mathematics and Statistics, Faculty of Science, University of Calgary, Calgary, AB, Canada.,Department of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada
| | - Dylan R Pillai
- Clinical Section of Microbiology, Alberta Precision Laboratories, Calgary, AB, Canada.,Department of Microbiology, Immunology, and Infectious Diseases, University of Calgary, AB, Canada.,Department Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada.,Clinical Section of Infectious Diseases, Department of Medicine, University of Calgary, Calgary, AB, Canada
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Xuan S, Zangwill KM, Ni W, Ma J, Hay JW. Cost-Effectiveness Analysis of Four Common Diagnostic Methods for Clostridioides difficile Infection. J Gen Intern Med 2020; 35:1102-1110. [PMID: 32016703 PMCID: PMC7174536 DOI: 10.1007/s11606-019-05487-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Revised: 07/08/2019] [Accepted: 09/23/2019] [Indexed: 12/18/2022]
Abstract
BACKGROUND No studies have evaluated the cost-effectiveness of single and two-step different diagnostic test strategies for Clostridioides difficile infection (CDI), including direct and indirect costs. OBJECTIVE To evaluate the cost-effectiveness of commonly available diagnostic tests for CDI including nucleic acid amplification testing (NAAT) alone, glutamate dehydrogenase followed by enzyme immunoassay for toxin (GDH/EIA), GDH then NAAT (GDH/NAAT), and NAAT then EIA (NAAT/EIA). DESIGN Decision tree model from the US societal perspective with inputs derived from the literature. Willingness-to-pay threshold was set at $150,000 per quality-adjusted life year (QALY) gained. To assess the impact of uncertainty in model inputs on the findings, we performed one-way and probabilistic sensitivity analyses. PARTICIPANTS We conducted the analysis to represent a population aged 65 years old with diarrhea who received a CDI diagnostic test. MAIN MEASURES Incremental cost-effectiveness ratios (ICER) and incremental net monetary benefits (INMB). KEY RESULTS NAAT alone was the most cost-effective approach overall; GDH/NAAT was the most cost-effective two-step option. NAAT alone led to the highest QALYs gained, at an incremental cost of $54,547 (vs. GDH/NAAT), $55,410 (vs. GDH/EIA), and $50,231 (vs. NAAT/EIA) per QALY gained. NAAT/EIA was not cost-effective compared to any other strategy. GDH/NAAT resulted in a higher QALY compared to GDH/EIA, at an incremental cost of $96,841 per QALY gained. Variability in the likelihood of comorbidities, CDI probability, and age at disease onset did not substantially change the results. One-way sensitivity analyses showed that results were most sensitive to likelihood of recurrence, followed by CDI mortality rate and probability of severe CDI. Probabilistic sensitivity analyses explored known uncertainties in the base case and confirmed the robustness of the results. CONCLUSIONS NAAT alone and GDH/NAAT (among the two-step options) were the most cost-effective diagnostic test approaches for CDI.
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Affiliation(s)
- Si Xuan
- Leonard D. Schaeffer Center for Health Policy and Economics, University of Southern California, Los Angeles, CA, USA.,Department of Pharmaceutical and Health Economics, School of Pharmacy, University of Southern California, Los Angeles, CA, USA
| | - Kenneth M Zangwill
- Division of Pediatric Infectious Diseases and Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA, USA
| | - Weiyi Ni
- Leonard D. Schaeffer Center for Health Policy and Economics, University of Southern California, Los Angeles, CA, USA.,Department of Pharmaceutical and Health Economics, School of Pharmacy, University of Southern California, Los Angeles, CA, USA
| | - Junjie Ma
- Department of Pharmacotherapy, University of Utah, Salt Lake City, UT, USA
| | - Joel W Hay
- Leonard D. Schaeffer Center for Health Policy and Economics, University of Southern California, Los Angeles, CA, USA. .,Department of Pharmaceutical and Health Economics, School of Pharmacy, University of Southern California, Los Angeles, CA, USA.
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Carroll KC, Mizusawa M. Laboratory Tests for the Diagnosis of Clostridium difficile. Clin Colon Rectal Surg 2020; 33:73-81. [PMID: 32104159 PMCID: PMC7042017 DOI: 10.1055/s-0039-3400476] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Clostridium (reclassified as " Clostridioides ") difficile is an anaerobic, gram-positive bacterium that causes significant disease through elaboration of two potent toxins in patients whose normal gut microbiota has been altered through antimicrobial or chemotherapeutic agents (dysbiosis). The optimum method of laboratory diagnosis is still somewhat controversial. Recent practice guidelines published by professional societies recommend a two-step approach beginning with a test for glutamate dehydrogenase (GDH), followed by a toxin test and/or a nucleic acid test. Alternatively, in institutions where established clinical algorithms guide testing, a nucleic acid test alone is acceptable. Nucleic acid tests are the methods of choice in approximately 50% of laboratories in the United States. These tests are considered as the most sensitive methods for detection of C. difficile in stool and are the least specific. Because of the lower specificity with nucleic acid tests, some clinicians believe that toxin enzyme immunoassays are better predictors of disease, despite their known poor performance in certain patient populations. This review will discuss the advantages and disadvantages of the currently available test methods for the diagnosis of C. difficile with a brief mention of some novel assays that are currently in clinical trials.
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Affiliation(s)
- Karen C. Carroll
- Division of Medical Microbiology, Department of Pathology, the Johns Hopkins University School of Medicine, Baltimore, Maryland
- Address for correspondence Karen C. Carroll, MD Division of Medical Microbiology, Department of Pathology, the Johns Hopkins University School of MedicineMeyer B1-193, 600 North Wolfe Street, Baltimore MD 21287
| | - Masako Mizusawa
- Section of Infectious Diseases, Department of Internal Medicine, University of Missouri, Kansas City, Missouri
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Madden GR, Poulter MD, Sifri CD. Diagnostic stewardship and the 2017 update of the IDSA-SHEA Clinical Practice Guidelines for Clostridium difficile Infection. Diagnosis (Berl) 2018; 5:119-125. [PMID: 29990306 PMCID: PMC7066535 DOI: 10.1515/dx-2018-0012] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2018] [Accepted: 06/08/2018] [Indexed: 01/05/2023]
Abstract
Diagnostic stewardship is an increasingly recognized means to reduce unnecessary tests and diagnostic errors. As a leading cause of healthcare-associated infection for which accurate laboratory diagnosis remains a challenge, Clostridium difficile offers an ideal opportunity to apply the principles of diagnostic stewardship. The recently updated 2017 Infectious Diseases Society of America (IDSA)-Society for Healthcare Epidemiology of America (SHEA) Clinical Practice Guidelines for C. difficile infection now recommend separate diagnostic strategies depending on whether an institution has adopted diagnostic stewardship in test decision making. IDSA-SHEA endorsement of diagnostic stewardship for C. difficile highlights the increasing role of diagnostic stewardship in hospitals. In this opinion piece, we introduce the concept of diagnostic stewardship by discussing the new IDSA-SHEA diagnostic recommendations for laboratory diagnosis of C. difficile . We outline recent examples of diagnostic stewardship, challenges to implementation, potential downsides and propose future areas of study.
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Affiliation(s)
- Gregory R. Madden
- Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, VA, USA
| | - Melinda D. Poulter
- Clinical Microbiology Laboratory, Department of Pathology, University of Virginia Health System, Charlottesville, VA, USA
| | - Costi D. Sifri
- Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, P.O. Box 800473, Charlottesville, VA 22908-0473, USA; Office of Hospital Epidemiology/ Infection Prevention and Control, University of Virginia Health System, Charlottesville, VA, USA
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Quantitative Thresholds Enable Accurate Identification of Clostridium difficile Infection by the Luminex xTAG Gastrointestinal Pathogen Panel. J Clin Microbiol 2018; 56:JCM.01885-17. [PMID: 29643194 DOI: 10.1128/jcm.01885-17] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2017] [Accepted: 03/26/2018] [Indexed: 12/18/2022] Open
Abstract
Clostridium difficile colonizes the gastrointestinal (GI) tract, resulting in either asymptomatic carriage or a spectrum of diarrheal illness. If clinical suspicion for C. difficile is low, stool samples are often submitted for analysis by multiplex molecular assays capable of detecting multiple GI pathogens, and some institutions do not report this organism due to concerns for high false-positive rates. Since clinical disease correlates with organism burden and molecular assays yield quantitative data, we hypothesized that numerical cutoffs could be utilized to improve the specificity of the Luminex xTAG GI pathogen panel (GPP) for C. difficile infection. Analysis of cotested liquid stool samples (n = 1,105) identified a GPP median fluorescence intensity (MFI) value cutoff of ≥1,200 to be predictive of two-step algorithm (2-SA; 96.4% concordance) and toxin enzyme immunoassay (EIA) positivity. Application of this cutoff to a second cotested data set (n = 1,428) yielded 96.5% concordance. To determine test performance characteristics, concordant results were deemed positive or negative, and discordant results were adjudicated via chart review. Test performance characteristics for the MFI cutoff of ≥150 (standard), MFI cutoff of ≥1,200, and 2-SA were as follows (respectively): concordance, 95, 96, and 97%; sensitivity, 93, 78, and 90%; specificity, 95, 98, and 98%; positive predictive value, 67, 82, and 81%;, and negative predictive value, 99, 98, and 99%. To capture the high sensitivity for organism detection (MFI of ≥150) and high specificity for active infection (MFI of ≥1,200), we developed and applied a reporting algorithm to interpret GPP data from patients (n = 563) with clinician orders only for syndromic panel testing, thus enabling accurate reporting of C. difficile for 95% of samples (514 negative and 5 true positives) irrespective of initial clinical suspicion and without the need for additional testing.
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Legaria MC, Rollet R, Di Martino A, Castello L, Barberis C, Rossetti MA, Guardati MC, Fernández Canigia L, Carloni G, Litterio M, Rocchi M, Anchart EG, Trejo FM, Minnaard J, Klajn D, Predari SC. Detection of toxigenic Clostridioides [Clostridium] difficile: Usefulness of two commercially available enzyme immunoassays and a PCR assay on stool samples and stool isolates. Rev Argent Microbiol 2017; 50:36-44. [PMID: 28988901 DOI: 10.1016/j.ram.2017.01.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2016] [Revised: 12/19/2016] [Accepted: 01/13/2017] [Indexed: 02/07/2023] Open
Abstract
The best laboratory diagnostic approach to detect Clostridioides [Clostridium] difficile infection (CDI) is a subject of ongoing debate. With the aim of evaluating four laboratory diagnostic methods, 250 unformed stools from patients with suspected CDI submitted to nine medical center laboratories from November 2010 to December 2011, were studied using: (1) an immunochromatographic rapid assay test that combines the qualitative determination of glutamate dehydrogenase (GDH) plus toxins A and B (QAB), the CDIFF QUIK CHEK COMPLETE assay; (2) an enzyme immunoassay for qualitative determination of toxins A and B, the RIDASCREEN™ C. difficile Toxin A/B assay (RAB); (3) a PCR for the toxin B gene assay (PCR); and (4) the toxigenic culture (TC). C. difficile isolates from direct toxin negative stools by QAB, RAB and PCR were evaluated for toxigenicity by the same direct tests, in order to assess the contribution of the TC (QAB-TC, RAB-TC, PCR-TC). A combination of the cell culture cytotoxicity neutralization assay (CCCNA) in stools, and the same assay on isolates from direct negative samples (CCCNA-TC) was considered the reference method (CCCNA/CCCNA-TC). Of the 250 stools tested, 107 (42.8%) were positive by CCCNA/CCCNA-TC. The GDH and PCR/PCR-TC assays were the most sensitive, 91.59% and 87.62%, respectively. The QAB, RAB, QAB/QAB-TC and RAB/RAB-TC had the highest specificities, ca. 95%. A negative GDH result would rule out CDI, however, its low positive likelihood ratio (PLR) of 3.97 indicates that a positive result should always be complemented with the detection of toxins. If the RAB, QAB, and PCR assays do not detect toxins from direct feces, the toxigenic culture should be performed. In view of our results, the most accurate and reliable methods to be applied in a clinical microbiology laboratory were the QAB/QAB-TC, and RAB/RAB-TC, with PLRs >10 and negative likelihood ratios <0.30.
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Affiliation(s)
- María C Legaria
- Subcomisión de Bacterias Anaerobias de la Sociedad Argentina de Bacteriología, Micología y Parasitología Clínicas - Asociación Argentina de Microbiología, Ciudad Autónoma de Buenos Aires (CABA), Argentina; Hospital General de Agudos Dr. Enrique Tornú, CABA, Argentina.
| | - Raquel Rollet
- Subcomisión de Bacterias Anaerobias de la Sociedad Argentina de Bacteriología, Micología y Parasitología Clínicas - Asociación Argentina de Microbiología, Ciudad Autónoma de Buenos Aires (CABA), Argentina; Hospital de Infecciosas Dr. Francisco Javier Muñiz, CABA, Argentina
| | - Ana Di Martino
- Subcomisión de Bacterias Anaerobias de la Sociedad Argentina de Bacteriología, Micología y Parasitología Clínicas - Asociación Argentina de Microbiología, Ciudad Autónoma de Buenos Aires (CABA), Argentina; Sanatorio de la Trinidad Mitre, CABA, Argentina
| | - Liliana Castello
- Subcomisión de Bacterias Anaerobias de la Sociedad Argentina de Bacteriología, Micología y Parasitología Clínicas - Asociación Argentina de Microbiología, Ciudad Autónoma de Buenos Aires (CABA), Argentina; Instituto de Investigaciones Médicas Alfredo Lanari, Universidad de Buenos Aires, CABA, Argentina
| | - Claudia Barberis
- Subcomisión de Bacterias Anaerobias de la Sociedad Argentina de Bacteriología, Micología y Parasitología Clínicas - Asociación Argentina de Microbiología, Ciudad Autónoma de Buenos Aires (CABA), Argentina; Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, CABA, Argentina
| | - María A Rossetti
- Subcomisión de Bacterias Anaerobias de la Sociedad Argentina de Bacteriología, Micología y Parasitología Clínicas - Asociación Argentina de Microbiología, Ciudad Autónoma de Buenos Aires (CABA), Argentina; Hospital Interzonal General de Agudos Presidente Perón, Avellaneda, Provincia de Buenos Aires, Argentina
| | - María C Guardati
- Subcomisión de Bacterias Anaerobias de la Sociedad Argentina de Bacteriología, Micología y Parasitología Clínicas - Asociación Argentina de Microbiología, Ciudad Autónoma de Buenos Aires (CABA), Argentina; Hospital de Emergencias Dr. Clemente Álvarez, Rosario, Provincia de Santa Fe, Argentina
| | - Liliana Fernández Canigia
- Subcomisión de Bacterias Anaerobias de la Sociedad Argentina de Bacteriología, Micología y Parasitología Clínicas - Asociación Argentina de Microbiología, Ciudad Autónoma de Buenos Aires (CABA), Argentina; Hospital Alemán, CABA, Argentina
| | - Graciela Carloni
- Subcomisión de Bacterias Anaerobias de la Sociedad Argentina de Bacteriología, Micología y Parasitología Clínicas - Asociación Argentina de Microbiología, Ciudad Autónoma de Buenos Aires (CABA), Argentina; Facultad de Ciencias Veterinarias, Universidad de Buenos Aires, CABA, Argentina
| | - Mirta Litterio
- Subcomisión de Bacterias Anaerobias de la Sociedad Argentina de Bacteriología, Micología y Parasitología Clínicas - Asociación Argentina de Microbiología, Ciudad Autónoma de Buenos Aires (CABA), Argentina; Hospital Nacional de Pediatría Dr. Prof. Juan P. Garrahan, CABA, Argentina
| | - Marta Rocchi
- Hospital Nacional de Clínicas de Córdoba, Córdoba, Argentina
| | - Eduardo G Anchart
- Centro de Especialidades Médicas Ambulatorias de Rosario MH Zuasnábar (Cemar), Secretaría de Salud Pública de Rosario, Provincia de Santa Fe, Argentina
| | - Fernando M Trejo
- Centro de Investigación y Desarrollo en Criotecnología de Alimentos (CIDCA) - Cátedra de Microbiología Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Provincia de Buenos Aires, Argentina
| | - Jessica Minnaard
- Centro de Investigación y Desarrollo en Criotecnología de Alimentos (CIDCA) - Cátedra de Microbiología Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Provincia de Buenos Aires, Argentina
| | - Diana Klajn
- Hospital General de Agudos Dr. Enrique Tornú, CABA, Argentina
| | - Silvia C Predari
- Subcomisión de Bacterias Anaerobias de la Sociedad Argentina de Bacteriología, Micología y Parasitología Clínicas - Asociación Argentina de Microbiología, Ciudad Autónoma de Buenos Aires (CABA), Argentina; Instituto de Investigaciones Médicas Alfredo Lanari, Universidad de Buenos Aires, CABA, Argentina
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The Impact of a Computerized Clinical Decision Support Tool on Inappropriate Clostridium difficile Testing. Infect Control Hosp Epidemiol 2017; 38:1204-1208. [DOI: 10.1017/ice.2017.161] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
OBJECTIVETo evaluate the effectiveness of a computerized clinical decision support intervention aimed at reducing inappropriate Clostridium difficile testingDESIGNRetrospective cohort studySETTINGUniversity of Pennsylvania Health System, comprised of 3 large tertiary-care hospitalsPATIENTSAll adult patients admitted over a 2-year periodINTERVENTIONProviders were required to use an order set integrated into a commercial electronic health record to order C. difficile toxin testing. The order set identified patients who had received laxatives within the previous 36 hours and displayed a message asking providers to consider stopping laxatives and reassessing in 24 hours prior to ordering C. difficile testing. Providers had the option to continue or discontinue laxatives and to proceed with or forgo testing. The primary endpoint was the change in inappropriate C. difficile testing, as measured by the number of patients who had C. difficile testing ordered while receiving laxatives.RESULTSCompared to the 1-year baseline period, the intervention resulted in a decrease in the proportion of inappropriate C. difficile testing (29.6% vs 27.3%; P=.02). The intervention was associated with an increase in the number of patients who had laxatives discontinued and did not undergo C. difficile testing (5.8% vs 46.4%; P<.01) and who had their laxatives discontinued and underwent testing (5.4% vs 35.2%; P<.01). We observed a nonsignificant increase in the proportion of patients with C. difficile related complications (5.0% vs 8.9%; P=.11).CONCLUSIONSA C. difficile order set was successful in decreasing inappropriate C. difficile testing and improving the timely discontinuation of laxatives.Infect Control Hosp Epidemiol 2017;38:1204–1208
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11
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Vila J. New molecular diagnostic tools in traveller's diarrhea. J Travel Med 2017; 24:S23-S28. [PMID: 28520995 DOI: 10.1093/jtm/taw071] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2016] [Accepted: 09/16/2016] [Indexed: 12/31/2022]
Abstract
Traveller's diarrhea can be caused by bacteria, protozoa, helminths and viruses. Globally, the most common causes of traveller's diarrhea are two pathotypes of Escherichia coli (enterotoxigenic and enteroaggregative) and Shigella, although there are significant variations according to the geographic area visited. While traveller's diarrhea is usually a mild, self-limiting disease, half of the travellers with traveller's diarrhea have some limitation in their activities during the journey and up to 10% present persistent diarrhea or other complications, making microbiological diagnosis necessary. The aim of this article is to describe the application of new molecular diagnostic tools mainly based on multiplex PCR, including their advantages and disadvantages as well as the current gaps that requiring further study.
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Affiliation(s)
- Jordi Vila
- Department of Clinical Microbiology, Biomedical Diagnostic Centre (CDB), Hospital Clinic, School of Medicine, University of Barcelona, Villarroel, 170, 08036 Barcelona, Spain.,ISGlobal, Barcelona Centre for International Health Research (CRESIB), Barcelona, Spain
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Martínez-Meléndez A, Camacho-Ortiz A, Morfin-Otero R, Maldonado-Garza HJ, Villarreal-Treviño L, Garza-González E. Current knowledge on the laboratory diagnosis of Clostridium difficile infection. World J Gastroenterol 2017; 23:1552-1567. [PMID: 28321156 PMCID: PMC5340807 DOI: 10.3748/wjg.v23.i9.1552] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2016] [Revised: 01/21/2017] [Accepted: 02/17/2017] [Indexed: 02/06/2023] Open
Abstract
Clostridium difficile (C. difficile) is a spore-forming, toxin-producing, gram-positive anaerobic bacterium that is the principal etiologic agent of antibiotic-associated diarrhea. Infection with C. difficile (CDI) is characterized by diarrhea in clinical syndromes that vary from self-limited to mild or severe. Since its initial recognition as the causative agent of pseudomembranous colitis, C. difficile has spread around the world. CDI is one of the most common healthcare-associated infections and a significant cause of morbidity and mortality among older adult hospitalized patients. Due to extensive antibiotic usage, the number of CDIs has increased. Diagnosis of CDI is often difficult and has a substantial impact on the management of patients with the disease, mainly with regards to antibiotic management. The diagnosis of CDI is primarily based on the clinical signs and symptoms and is only confirmed by laboratory testing. Despite the high burden of CDI and the increasing interest in the disease, episodes of CDI are often misdiagnosed. The reasons for misdiagnosis are the lack of clinical suspicion or the use of inappropriate tests. The proper diagnosis of CDI reduces transmission, prevents inadequate or unnecessary treatments, and assures best antibiotic treatment. We review the options for the laboratory diagnosis of CDI within the settings of the most accepted guidelines for CDI diagnosis, treatment, and prevention of CDI.
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Point-Counterpoint: What Is the Optimal Approach for Detection of Clostridium difficile Infection? J Clin Microbiol 2017; 55:670-680. [PMID: 28077697 DOI: 10.1128/jcm.02463-16] [Citation(s) in RCA: 99] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
INTRODUCTIONIn 2010, we published an initial Point-Counterpoint on the laboratory diagnosis of Clostridium difficile infection (CDI). At that time, nucleic acid amplification tests (NAATs) were just becoming commercially available, and the idea of algorithmic approaches to CDI was being explored. Now, there are numerous NAATs in the marketplace, and based on recent proficiency test surveys, they have become the predominant method used for CDI diagnosis in the United States. At the same time, there is a body of literature that suggests that NAATs lack clinical specificity and thus inflate CDI rates. Hospital administrators are taking note of institutional CDI rates because they are publicly reported. They have become an important metric impacting hospital safety ratings and value-based purchasing; hospitals may have millions of dollars of reimbursement at risk. In this Point-Counterpoint using a frequently asked question approach, Ferric Fang of the University of Washington, who has been a consistent advocate for a NAAT-only approach for CDI diagnosis, will discuss the value of a NAAT-only approach, while Christopher Polage of the University of California Davis and Mark Wilcox of Leeds University, Leeds, United Kingdom, each of whom has recently written important articles on the value of toxin detection in the diagnosis, will discuss the impact of toxin detection in CDI diagnosis.
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Failure of Risk-Adjustment by Test Method for C. difficile Laboratory-Identified Event Reporting. Infect Control Hosp Epidemiol 2016; 38:109-111. [PMID: 27745553 DOI: 10.1017/ice.2016.227] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Using an algorithm including both enzyme immunoassay (EIA) and nucleic acid amplification (NAAT) for Clostridium difficile infection (CDI) diagnosis, we found that the use of NAAT versus EIA almost doubled our hospital-onset CDI laboratory-identified (LabID) event standardized infection ratio (SIR). We recommend that the current risk adjustment approach be modified. Infect Control Hosp Epidemiol 2016:1-3.
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Abstract
ABSTRACT
Gastrointestinal infections in the immunocompromised host are caused by the common bacterial, viral, fungal, and parasitic agents that also cause infections in the immunocompetent host. Of special consideration is that immunocompromised patients may be at increased risk for infection or disease severity and by pathogens not seen in the competent host. This chapter reviews the various agents, risk factors, and diagnostic approaches to detect gastrointestinal infections in this patient population.
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Zboromyrska Y, Vila J. Advanced PCR-based molecular diagnosis of gastrointestinal infections: challenges and opportunities. Expert Rev Mol Diagn 2016; 16:631-40. [PMID: 26986537 DOI: 10.1586/14737159.2016.1167599] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Acute infections of the gastrointestinal tract are among the most common infectious diseases. The etiological agents of gastroenteritis may be bacteria, viruses or protozoa. Identification of the etiological agents of acute diarrhea is important for the treatment and management of diarrheal diseases. Conventional stool culture for bacteria shows a low sensitivity and requires more than 24 hours. In addition, other approaches to detect viruses and protozoa mainly involve antigen detection, but this is not available for all enteropathogens, and microscopic observation requires training and is of low sensitivity. In this review, the authors describe currently available molecular methods to detect different enteropathogens and analyze the main advantages and disadvantages of these methods for laboratory diagnosis of gastroenteritis.
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Affiliation(s)
- Yuliya Zboromyrska
- a Department of Clinical Microbiology, Biomedical Diagnostic Centre (CDB), Hospital Clínic, School of Medicine , University of Barcelona , Barcelona , Spain.,b ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic, University of Barcelona , Barcelona , Spain
| | - Jordi Vila
- a Department of Clinical Microbiology, Biomedical Diagnostic Centre (CDB), Hospital Clínic, School of Medicine , University of Barcelona , Barcelona , Spain.,b ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic, University of Barcelona , Barcelona , Spain
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Aronoff DM. Building a Better Crystal Ball for Predicting Complications of Clostridium difficile Infection. Clin Infect Dis 2015; 61:1789-91. [PMID: 26338793 DOI: 10.1093/cid/civ751] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2015] [Accepted: 08/11/2015] [Indexed: 01/04/2023] Open
Affiliation(s)
- David M Aronoff
- Department of Internal Medicine, Division of Infectious Diseases Department of Microbiology and Immunology, University of Michigan, Ann Arbor
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Olesen B, Hallberg H, Bangsborg J, Jensen JN, Jarløv JO. A new approach to recognition of Clostridium difficile infections with community onset. Clin Microbiol Infect 2015; 21:e55-6. [PMID: 25895635 DOI: 10.1016/j.cmi.2015.04.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2015] [Accepted: 04/09/2015] [Indexed: 01/05/2023]
Affiliation(s)
- B Olesen
- Department of Clinical Microbiology, Herlev University Hospital, Copenhagen, Denmark.
| | - H Hallberg
- Department of Clinical Microbiology, Herlev University Hospital, Copenhagen, Denmark
| | - J Bangsborg
- Department of Clinical Microbiology, Herlev University Hospital, Copenhagen, Denmark
| | - J N Jensen
- Department of Clinical Microbiology, Herlev University Hospital, Copenhagen, Denmark
| | - J O Jarløv
- Department of Clinical Microbiology, Herlev University Hospital, Copenhagen, Denmark
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