Differences in outcome according to Clostridium difficile testing method: a prospective multicentre diagnostic validation study of C difficile infection
TL;DR: A new diagnostic category of potential C difficile excretor (cytotoxigenic culture positive but cytotoxin assay negative) could be used to characterise patients with diarrhoea that is probably not due to C diffICile infection, but who can cause cross-infection.
Abstract: Summary Background Diagnosis of Clostridium difficile infection is controversial because of many laboratory methods, compounded by two reference methods. Cytotoxigenic culture detects toxigenic C difficile and gives a positive result more frequently (eg, because of colonisation, which means that individuals can have the bacterium but no free toxin) than does the cytotoxin assay, which detects preformed toxin in faeces. We aimed to validate the reference methods according to clinical outcomes and to derive an optimum laboratory diagnostic algorithm for C difficile infection. Methods In this prospective, multicentre study, we did cytotoxigenic culture and cytotoxin assays on 12 420 faecal samples in four UK laboratories. We also performed tests that represent the three main targets for C difficile detection: bacterium (glutamate dehydrogenase), toxins, or toxin genes. We used routine blood test results, length of hospital stay, and 30-day mortality to clinically validate the reference methods. Data were categorised by reference method result: group 1, cytotoxin assay positive; group 2, cytotoxigenic culture positive and cytotoxin assay negative; and group 3, both reference methods negative. Findings Clinical and reference assay data were available for 6522 inpatient episodes. On univariate analysis, mortality was significantly higher in group 1 than in group 2 (72/435 [16·6%] vs 20/207 [9·7%], p=0·044) and in group 3 (503/5880 [8·6%], p Interpretation We noted no increase in mortality when toxigenic C difficile alone was present. Toxin (cytotoxin assay) positivity correlated with clinical outcome, and so this reference method best defines true cases of C difficile infection. A new diagnostic category of potential C difficile excretor (cytotoxigenic culture positive but cytotoxin assay negative) could be used to characterise patients with diarrhoea that is probably not due to C difficile infection, but who can cause cross-infection. Funding Department of Health and Health Protection Agency, UK.
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Centers for Disease Control and Prevention1, Colorado Department of Public Health and Environment2, Oregon Health Authority3, University of Rochester4, Veterans Health Administration5, Yale University6, University of New Mexico7, Maryland Department of Health8, University of California, San Francisco9
TL;DR: In this article, the authors used regression models to calculate estimates of national incidence and total number of infections, first recurrences, and deaths within 30 days after the diagnosis of C. difficile infection.
Abstract: Background The magnitude and scope of Clostridium difficile infection in the United States continue to evolve. Methods In 2011, we performed active population- and laboratory-based surveillance across 10 geographic areas in the United States to identify cases of C. difficile infection (stool specimens positive for C. difficile on either toxin or molecular assay in residents ≥1 year of age). Cases were classified as community-associated or health care–associated. In a sample of cases of C. difficile infection, specimens were cultured and isolates underwent molecular typing. We used regression models to calculate estimates of national incidence and total number of infections, first recurrences, and deaths within 30 days after the diagnosis of C. difficile infection. Results A total of 15,461 cases of C. difficile infection were identified in the 10 geographic areas; 65.8% were health care–associated, but only 24.2% had onset during hospitalization. After adjustment for predictors of disease incidence, the estimated number of incident C. difficile infections in the United States was 453,000 (95% confidence interval [CI], 397,100 to 508,500). The incidence was estimated to be higher among females (rate ratio, 1.26; 95% CI, 1.25 to 1.27), whites (rate ratio, 1.72; 95% CI, 1.56 to 2.0), and persons 65 years of age or older (rate ratio, 8.65; 95% CI, 8.16 to 9.31). The estimated number of first recurrences of C. difficile infection was 83,000 (95% CI, 57,000 to 108,900), and the estimated number of deaths was 29,300 (95% CI, 16,500 to 42,100). The North American pulsed-field gel electrophoresis type 1 (NAP1) strain was more prevalent among health care–associated infections than among community-associated infections (30.7% vs. 18.8%, P<0.001) Conclusions C. difficile was responsible for almost half a million infections and was associated with approximately 29,000 deaths in 2011. (Funded by the Centers for Disease Control and Prevention.)
2,209 citations
Centers for Disease Control and Prevention1, United States Department of Veterans Affairs2, Loyola University Medical Center3, Mount Sinai St. Luke's and Mount Sinai Roosevelt4, Johns Hopkins University School of Medicine5, Children's Hospital of Philadelphia6, Washington University in St. Louis7, University of Houston8, Beth Israel Deaconess Medical Center9, McGill University Health Centre10, Boston Children's Hospital11, Leeds Teaching Hospitals NHS Trust12
TL;DR: This guideline updates recommendations regarding epidemiology, diagnosis, treatment, infection prevention, and environmental management on Clostridium difficile infection in adults and includes recommendations for children.
Abstract: A panel of experts was convened by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) to update the 2010 clinical practice guideline on Clostridium difficile infection (CDI) in adults. The update, which has incorporated recommendations for children (following the adult recommendations for epidemiology, diagnosis, and treatment), includes significant changes in the management of this infection and reflects the evolving controversy over best methods for diagnosis. Clostridium difficile remains the most important cause of healthcare-associated diarrhea and has become the most commonly identified cause of healthcare-associated infection in adults in the United States. Moreover, C. difficile has established itself as an important community pathogen. Although the prevalence of the epidemic and virulent ribotype 027 strain has declined markedly along with overall CDI rates in parts of Europe, it remains one of the most commonly identified strains in the United States where it causes a sizable minority of CDIs, especially healthcare-associated CDIs. This guideline updates recommendations regarding epidemiology, diagnosis, treatment, infection prevention, and environmental management.
1,851 citations
Cites background or result from "Differences in outcome according to..."
...That said, the results support the findings by Planche and colleagues discussed below [185]....
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...a “sensitive” toxin A/B enzyme immunoassay [185], and this has been national UK policy since 2012....
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...In a multivariate logistic regression model, group 1 patients were older and had greater leukocytosis, serum creatinine rise, depressed albumin, and 30-day mortality compared with group 3 [185]....
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...to clinical outcomes in an attempt to derive the optimal diagnostic laboratory method [185]....
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TL;DR: This article reviews the pathogenesis, epidemiology, diagnosis, and treatment of this nosocomial and potentially fatal infectious diarrhea, as well as the associated risk factors.
Abstract: This article reviews the pathogenesis, epidemiology, diagnosis, and treatment of this nosocomial and potentially fatal infectious diarrhea, as well as the associated risk factors New treatments include fecal microbiota transplantation for disease that is resistant to vancomycin
1,479 citations
TL;DR: An update and review on the comparative effectiveness of the currently available treatment modalities of CDI is given, thereby providing evidence-based recommendations on this issue.
1,075 citations
Additional excerpts
...difficile diagnostic testing [15]....
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TL;DR: The prevalence of health care–associated infections was lower in 2015 than in 2011, largely owing to reductions in the prevalence of surgical‐site and urinary tract infections.
Abstract: Background A point-prevalence survey that was conducted in the United States in 2011 showed that 4% of hospitalized patients had a health care–associated infection. We repeated the survey ...
656 citations
References
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01 Jan 1993TL;DR: This article presents bootstrap methods for estimation, using simple arguments, with Minitab macros for implementing these methods, as well as some examples of how these methods could be used for estimation purposes.
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TL;DR: Hosmer and Lemeshow as discussed by the authors provide an accessible introduction to the logistic regression model while incorporating advances of the last decade, including a variety of software packages for the analysis of data sets.
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TL;DR: Applied Logistic Regression, Third Edition provides an easily accessible introduction to the logistic regression model and highlights the power of this model by examining the relationship between a dichotomous outcome and a set of covariables.
Abstract: \"A new edition of the definitive guide to logistic regression modeling for health science and other applicationsThis thoroughly expanded Third Edition provides an easily accessible introduction to the logistic regression (LR) model and highlights the power of this model by examining the relationship between a dichotomous outcome and a set of covariables. Applied Logistic Regression, Third Edition emphasizes applications in the health sciences and handpicks topics that best suit the use of modern statistical software. The book provides readers with state-of-the-art techniques for building, interpreting, and assessing the performance of LR models. New and updated features include: A chapter on the analysis of correlated outcome data. A wealth of additional material for topics ranging from Bayesian methods to assessing model fit Rich data sets from real-world studies that demonstrate each method under discussion. Detailed examples and interpretation of the presented results as well as exercises throughout Applied Logistic Regression, Third Edition is a must-have guide for professionals and researchers who need to model nominal or ordinal scaled outcome variables in public health, medicine, and the social sciences as well as a wide range of other fields and disciplines\"--
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TL;DR: The purpose of this article is to serve as an introduction to ROC graphs and as a guide for using them in research.
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Book•
07 Mar 2008TL;DR: Applied Survival Analysis, Second Edition is an ideal book for graduate-level courses in biostatistics, statistics, and epidemiologic methods and serves as a valuable reference for practitioners and researchers in any health-related field or for professionals in insurance and government.
Abstract: THE MOST PRACTICAL, UP-TO-DATE GUIDE TO MODELLING AND ANALYZING TIME-TO-EVENT DATANOW IN A VALUABLE NEW EDITION Since publication of the first edition nearly a decade ago, analyses using time-to-event methods have increase considerably in all areas of scientific inquiry mainly as a result of model-building methods available in modern statistical software packages. However, there has been minimal coverage in the available literature to9 guide researchers, practitioners, and students who wish to apply these methods to health-related areas of study. Applied Survival Analysis, Second Edition provides a comprehensive and up-to-date introduction to regression modeling for time-to-event data in medical, epidemiological, biostatistical, and other health-related research. This book places a unique emphasis on the practical and contemporary applications of regression modeling rather than the mathematical theory. It offers a clear and accessible presentation of modern modeling techniques supplemented with real-world examples and case studies. Key topics covered include: variable selection, identification of the scale of continuous covariates, the role of interactions in the model, assessment of fit and model assumptions, regression diagnostics, recurrent event models, frailty models, additive models, competing risk models, and missing data. Features of the Second Edition include: Expanded coverage of interactions and the covariate-adjusted survival functions The use of the Worchester Heart Attack Study as the main modeling data set for illustrating discussed concepts and techniques New discussion of variable selection with multivariable fractional polynomials Further exploration of time-varying covariates, complex with examples Additional treatment of the exponential, Weibull, and log-logistic parametric regression models Increased emphasis on interpreting and using results as well as utilizing multiple imputation methods to analyze data with missing values New examples and exercises at the end of each chapter Analyses throughout the text are performed using Stata Version 9, and an accompanying FTP site contains the data sets used in the book. Applied Survival Analysis, Second Edition is an ideal book for graduate-level courses in biostatistics, statistics, and epidemiologic methods. It also serves as a valuable reference for practitioners and researchers in any health-related field or for professionals in insurance and government.
3,507 citations