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Franza M, Varricchio R, Alloisio G, De Simone G, Di Bella S, Ascenzi P, di Masi A. Zebrafish ( Danio rerio) as a Model System to Investigate the Role of the Innate Immune Response in Human Infectious Diseases. Int J Mol Sci 2024; 25:12008. [PMID: 39596075 PMCID: PMC11593600 DOI: 10.3390/ijms252212008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Revised: 10/30/2024] [Accepted: 11/03/2024] [Indexed: 11/28/2024] Open
Abstract
The zebrafish (Danio rerio) has emerged as a valuable model for studying host-pathogen interactions due to its unique combination of characteristics. These include extensive sequence and functional conservation with the human genome, optical transparency in larvae that allows for high-resolution visualization of host cell-microbe interactions, a fully sequenced and annotated genome, advanced forward and reverse genetic tools, and suitability for chemical screening studies. Despite anatomical differences with humans, the zebrafish model has proven instrumental in investigating immune responses and human infectious diseases. Notably, zebrafish larvae rely exclusively on innate immune responses during the early stages of development, as the adaptive immune system becomes fully functional only after 4-6 weeks post-fertilization. This window provides a unique opportunity to isolate and examine infection and inflammation mechanisms driven by the innate immune response without the confounding effects of adaptive immunity. In this review, we highlight the strengths and limitations of using zebrafish as a powerful vertebrate model to study innate immune responses in infectious diseases. We will particularly focus on host-pathogen interactions in human infections caused by various bacteria (Clostridioides difficile, Staphylococcus aureus, and Pseudomonas aeruginosa), viruses (herpes simplex virus 1, SARS-CoV-2), and fungi (Aspergillus fumigatus and Candida albicans).
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Affiliation(s)
- Maria Franza
- Department of Sciences, Roma Tre University, 00146 Roma, Italy; (M.F.); (R.V.); (G.A.); (G.D.S.); (P.A.)
| | - Romualdo Varricchio
- Department of Sciences, Roma Tre University, 00146 Roma, Italy; (M.F.); (R.V.); (G.A.); (G.D.S.); (P.A.)
| | - Giulia Alloisio
- Department of Sciences, Roma Tre University, 00146 Roma, Italy; (M.F.); (R.V.); (G.A.); (G.D.S.); (P.A.)
| | - Giovanna De Simone
- Department of Sciences, Roma Tre University, 00146 Roma, Italy; (M.F.); (R.V.); (G.A.); (G.D.S.); (P.A.)
| | - Stefano Di Bella
- Clinical Department of Medical, Surgical and Health Sciences, Trieste University, 34127 Trieste, Italy;
| | - Paolo Ascenzi
- Department of Sciences, Roma Tre University, 00146 Roma, Italy; (M.F.); (R.V.); (G.A.); (G.D.S.); (P.A.)
- Accademia Nazionale dei Lincei, 00165 Roma, Italy
| | - Alessandra di Masi
- Department of Sciences, Roma Tre University, 00146 Roma, Italy; (M.F.); (R.V.); (G.A.); (G.D.S.); (P.A.)
- Centro Linceo Interdisciplinare “Beniamino Segre”, Accademia Nazionale dei Lincei, 00165 Roma, Italy
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Rafalko N, Webster JL, Jacob G, Kutzler MA, Goldstein ND. Generalizability of predictive models for Clostridioides difficile infection, severity and recurrence at an urban safety-net hospital. J Hosp Infect 2024; 146:10-20. [PMID: 38219834 DOI: 10.1016/j.jhin.2024.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 12/21/2023] [Accepted: 01/01/2024] [Indexed: 01/16/2024]
Abstract
INTRODUCTION Predictive models for Clostridioides difficile infection can identify high-risk patients and aid clinicians in preventing infection. Issues of generalizability regarding current predictive models have been acknowledged but, to the authors' knowledge, have never been quantified. METHODS C. difficile infection, severity and recurrence predictive models were created using multi-variate logistic regression through case-control sampling from an urban safety-net hospital. Models were validated using five-fold cross-validation, and inverse probability weights (IPW) based on two different catchment area definitions were used to improve external validity. Akaike Information Criterion (AIC), area under the receiver operating characteristic curve (AUROC), and sensitivity and specificity with bootstrapped confidence intervals (CI) were used to assess and compare model fit and performance. RESULTS Changes in performance before and after weighting were small across all models, although differences were more apparent after weighting the recurrence model (AUROC values of 0.78, 0.76 and 0.71 for the unweighted and two weighted models, respectively). Overall, the infection model performed the best (AUROC 0.82, 95% CI 0.78-0.85), followed by the recurrence model (AUROC 0.78, 95% CI 0.69-0.86) and then the severity model (AUROC 0.70, 95% CI 0.63-0.78). CONCLUSIONS The performance of the models after weighting did not change drastically, suggesting that the models predicting C. difficile infection, severity and recurrence may not be impacted by patient selection factors. However, other researchers may wish to consider addressing these catchment forces using IPW.
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Affiliation(s)
- N Rafalko
- Department of Epidemiology and Biostatistics, Drexel University Dornsife School of Public Health, Philadelphia, PA, USA
| | - J L Webster
- Department of Epidemiology and Biostatistics, Drexel University Dornsife School of Public Health, Philadelphia, PA, USA
| | - G Jacob
- Department of Epidemiology and Biostatistics, Drexel University Dornsife School of Public Health, Philadelphia, PA, USA
| | - M A Kutzler
- Department of Medicine, Drexel University College of Medicine, Philadelphia, PA, USA
| | - N D Goldstein
- Department of Epidemiology and Biostatistics, Drexel University Dornsife School of Public Health, Philadelphia, PA, USA.
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Patterson WM, Fajnzylber J, Nero N, Hernandez AV, Deshpande A. Diagnostic prediction models to identify patients at risk for healthcare-facility-onset Clostridioides difficile: A systematic review of methodology and reporting. Infect Control Hosp Epidemiol 2024; 45:174-181. [PMID: 37665104 PMCID: PMC10877537 DOI: 10.1017/ice.2023.185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 06/29/2023] [Accepted: 07/12/2023] [Indexed: 09/05/2023]
Abstract
OBJECTIVE To systematically review the methodology, performance, and generalizability of diagnostic models for predicting the risk of healthcare-facility-onset (HO) Clostridioides difficile infection (CDI) in adult hospital inpatients (aged ≥18 years). BACKGROUND CDI is the most common cause of healthcare-associated diarrhea. Prediction models that identify inpatients at risk of HO-CDI have been published; however, the quality and utility of these models remain uncertain. METHODS Two independent reviewers evaluated articles describing the development and/or validation of multivariable HO-CDI diagnostic models in an inpatient setting. All publication dates, languages, and study designs were considered. Model details (eg, sample size and source, outcome, and performance) were extracted from the selected studies based on the CHARMS checklist. The risk of bias was further assessed using PROBAST. RESULTS Of the 3,030 records evaluated, 11 were eligible for final analysis, which described 12 diagnostic models. Most studies clearly identified the predictors and outcomes but did not report how missing data were handled. The most frequent predictors across all models were advanced age, receipt of high-risk antibiotics, history of hospitalization, and history of CDI. All studies reported the area under the receiver operating characteristic curve (AUROC) as a measure of discriminatory ability. However, only 3 studies reported the model calibration results, and only 2 studies were externally validated. All of the studies had a high risk of bias. CONCLUSION The studies varied in their ability to predict the risk of HO-CDI. Future models will benefit from the validation on a prospective external cohort to maximize external validity.
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Affiliation(s)
- William M. Patterson
- Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, United States
| | - Jesse Fajnzylber
- Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, United States
| | - Neil Nero
- Education Institute, Floyd D. Loop Alumni Library, Cleveland Clinic, Cleveland, Ohio, United States
| | - Adrian V. Hernandez
- Health Outcomes, Policy, and Evidence Synthesis (HOPES) Group, University of Connecticut School of Pharmacy, Storrs, Connecticut, United States
- Unidad de Revisiones Sistemáticas y Meta-análisis (URSIGET), Vicerrectorado de Investigación, Universidad San Ignacio de Loyola (USIL), Lima, Peru
| | - Abhishek Deshpande
- Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, United States
- Center for Value-Based Care Research, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio, United States
- Department of Infectious Diseases, Respiratory Institute, Cleveland Clinic, Cleveland, Ohio, United States
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Ying LD, Chao GF, Canner J, Graetz E, Ghiassi S, Schwartz JS, Zolfaghari EJ, Schneider EB, Gibbs KE. The Degree of Preoperative Hypoalbuminemia Is Associated with Risk of Postoperative Complications in Metabolic and Bariatric Surgery Patients. Obes Surg 2024; 34:51-70. [PMID: 37994997 DOI: 10.1007/s11695-023-06944-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Revised: 10/26/2023] [Accepted: 11/08/2023] [Indexed: 11/24/2023]
Abstract
BACKGROUND The incidence and impact of hypoalbuminemia in bariatric surgery patients is poorly characterized. We describe its distribution in laparoscopic sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) patients undergoing primary or revision surgeries and assess its impact on postoperative complications. METHODS The Metabolic and Bariatric Surgery Quality Improvement Program Database (2015 to 2021) was analyzed. Hypoalbuminemia was defined as Severe (< 3 g/dL), Moderate (3 ≤ 3.5 g/dL), Mild (3.5 ≤ 4 g/dL), or Normal (≥ 4 g/dL). Multivariable logistic regression was performed to calculate odds ratios of postoperative complications compared to those with Normal albumin after controlling for procedure, age, gender, race, body mass index, functional status, American Society of Anesthesia class, and operative length. RESULTS A total of 817,310 patients undergoing Primary surgery and 69,938 patients undergoing Revision/Conversion ("Revision") surgery were analyzed. The prevalence of hypoalbuminemia was as follows (Primary, Revision): Severe, 0.3%, 0.6%; Moderate, 5.2%, 6.5%; Mild, 28.3%, 31.4%; Normal, 66.2%, 61.4%. Primary and Revision patients with hypoalbuminemia had a significantly higher prevalence (p < 0.01) of several co-morbidities, including hypertension and insulin-dependent diabetes. Any degree of hypoalbuminemia increased the odds ratio of several complications in Primary and Revision patients, including readmission, intervention, and reoperation. In Primary patients, all levels of hypoalbuminemia also increased the odds ratio of unplanned intubation, intensive care unit admission, and venous thromboembolism requiring therapy. CONCLUSION Over 30% of patients present with hypoalbuminemia. Even mild hypoalbuminemia was associated with an increased rate of several complications including readmission, intervention, and reoperation. Ensuring nutritional optimization, especially prior to revision surgery, may improve outcomes in this challenging population.
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Affiliation(s)
- Lee D Ying
- Department of Surgery, Yale New Haven Hospital, New Haven, CT, USA.
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Mumoli N, Bonaventura A, Marchesi C, Cei M, Morbidoni L, Donatiello I, Mazzone A, Dentali F. A new score to predict Clostridioides difficile infection in medical patients: a sub-analysis of the FADOI-PRACTICE study. Intern Emerg Med 2023; 18:2003-2009. [PMID: 37633862 DOI: 10.1007/s11739-023-03395-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 08/08/2023] [Indexed: 08/28/2023]
Abstract
Medical divisions are at high risk of Clostridioides difficile infection (CDI) due to patients' frailty and complexity. This sub-analysis of the FADOI-PRACTICE study included patients presenting with diarrhea either at admission or during hospitalization. CDI diagnosis was confirmed when both enzyme immunoassay and A and B toxin detection were found positive. The aim of this sub-analysis was the identification of a new score to predict CDI in hospitalized, medical patients. Five hundred and seventy-two patients with diarrhea were considered. More than half of patients was female, 40% on antibiotics in the previous 4 weeks and 60% on proton pump inhibitors (PPIs). CDI diagnosis occurred in 103 patients (18%). Patients diagnosed with CDI were older, more frequently of female sex, recently hospitalized and bed-ridden, and treated with antibiotics and PPIs. Through a backward stepwise logistic regression model, age > 65 years, female sex, recent hospitalization, recent antibiotic therapy, active cancer, prolonged hospital stay (> 12 days), hypoalbuminemia (albumin < 3 g/dL), and leukocytosis (white blood cells > 9 × 10^9/L) were found to independently predict CDI occurrence. These variables contributed to building a clinical prognostic score with a good sensitivity and a modest specificity for a value > 3 (79% and 58%, respectively; AUC 0.75, 95% CI 0.71-0.79, p < 0.001), that identified low-risk (score ≤ 3; 42.5%) and high-risk (score > 3; 57.5%) patients. Although some classical risk factors were confirmed to increase CDI occurrence, the changing landscape of CDI epidemiology suggests a reappraisal of common risk factors and the development of novel risk scores based on local epidemiology.
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Affiliation(s)
- Nicola Mumoli
- Department of Internal Medicine, Ospedale Fornaroli, ASST Ovest Milanese, Magenta, MI, Italy.
| | - Aldo Bonaventura
- Department of Internal Medicine, Ospedale di Circolo and Fondazione Macchi, ASST Sette Laghi, Varese, Italy
| | - Chiara Marchesi
- Department of Internal Medicine, Legnano Hospital, ASST Ovest Milanese, Legnano, MI, Italy
| | - Marco Cei
- Department of Internal Medicine, Cecina Hospital, Cecina, LI, Italy
| | - Laura Morbidoni
- Department of Internal Medicine, Senigallia Hospital, Senigallia, AN, Italy
| | | | - Antonino Mazzone
- Department of Internal Medicine, Legnano Hospital, ASST Ovest Milanese, Legnano, MI, Italy
| | - Francesco Dentali
- Department of Medicine and Surgery, Insubria University, Varese, Italy
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Miller AC, Arakkal AT, Sewell DK, Segre AM, Tholany J, Polgreen PM. Comparison of Different Antibiotics and the Risk for Community-Associated Clostridioides difficile Infection: A Case-Control Study. Open Forum Infect Dis 2023; 10:ofad413. [PMID: 37622034 PMCID: PMC10444966 DOI: 10.1093/ofid/ofad413] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Accepted: 07/31/2023] [Indexed: 08/26/2023] Open
Abstract
Background Antibiotics are the greatest risk factor for Clostridioides difficile infection (CDI). Risk for CDI varies across antibiotic types and classes. Optimal prescribing and stewardship recommendations require comparisons of risk across antibiotics. However, many prior studies rely on aggregated antibiotic categories or are underpowered to detect significant differences across antibiotic types. Using a large database of real-world data, we evaluate community-associated CDI risk across individual antibiotic types. Methods We conducted a matched case-control study using a large database of insurance claims capturing longitudinal health care encounters and medications. Case patients with community-associated CDI were matched to 5 control patients by age, sex, and enrollment period. Antibiotics prescribed within 30 days before the CDI diagnosis along with other risk factors, including comorbidities, health care exposures, and gastric acid suppression were considered. Conditional logistic regression and a Bayesian analysis were used to compare risk across individual antibiotics. A sensitivity analysis of antibiotic exposure windows between 30 and 180 days was conducted. Results We identified 159 404 cases and 797 020 controls. Antibiotics with the greatest risk for CDI included clindamycin and later-generation cephalosporins, and those with the lowest risk included minocycline and doxycycline. We were able to differentiate and order individual antibiotics in terms of their relative level of associated risk for CDI. Risk estimates varied considerably with different exposure windows considered. Conclusions We found wide variation in CDI risk within and between classes of antibiotics. These findings ordering the level of associated risk across antibiotics can help inform tradeoffs in antibiotic prescribing decisions and stewardship efforts.
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Affiliation(s)
- Aaron C Miller
- University of Iowa, Carver College of Medicine, Iowa City, Iowa, USA
| | - Alan T Arakkal
- University of Iowa, College of Public Health, Iowa City, Iowa, USA
| | - Daniel K Sewell
- University of Iowa, College of Public Health, Iowa City, Iowa, USA
| | - Alberto M Segre
- Department of Computer Science, University of Iowa, Iowa City, Iowa, USA
| | - Joseph Tholany
- University of Iowa, Carver College of Medicine, Iowa City, Iowa, USA
| | - Philip M Polgreen
- University of Iowa, Carver College of Medicine, Iowa City, Iowa, USA
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A comparative analysis of machine learning approaches to predict C. difficile infection in hospitalized patients. Am J Infect Control 2022; 50:250-257. [PMID: 35067382 DOI: 10.1016/j.ajic.2021.11.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 11/03/2021] [Accepted: 11/06/2021] [Indexed: 11/24/2022]
Abstract
BACKGROUND Interventions to better prevent or manage Clostridioides difficile infection (CDI) may significantly reduce morbidity, mortality, and healthcare spending. METHODS We present a retrospective study using electronic health record data from over 700 United States hospitals. A subset of hospitals was used to develop machine learning algorithms (MLAs); the remaining hospitals served as an external test set. Three MLAs were evaluated: gradient-boosted decision trees (XGBoost), Deep Long Short Term Memory neural network, and one-dimensional convolutional neural network. MLA performance was evaluated with area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, diagnostic odds ratios and likelihood ratios. RESULTS The development dataset contained 13,664,840 inpatient encounters with 80,046 CDI encounters; the external dataset contained 1,149,088 inpatient encounters with 7,107 CDI encounters. The highest AUROCs were achieved for XGB, Deep Long Short Term Memory neural network, and one-dimensional convolutional neural network via abstaining from use of specialized training techniques, resampling in isolation, and resampling and output bias in combination, respectively. XGBoost achieved the highest AUROC. CONCLUSIONS MLAs can predict future CDI in hospitalized patients using just 6 hours of data. In clinical practice, a machine-learning based tool may support prophylactic measures, earlier diagnosis, and more timely implementation of infection control measures.
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Rao K, Dubberke ER. Can prediction scores be used to identify patients at risk of Clostridioides difficile infection? Curr Opin Gastroenterol 2022; 38:7-14. [PMID: 34628418 DOI: 10.1097/mog.0000000000000793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
PURPOSE OF REVIEW To describe the current state of literature on modeling risk of incident and recurrent Clostridioides difficile infection (iCDI and rCDI), to underscore limitations, and to propose a path forward for future research. RECENT FINDINGS There are many published risk factors and models for both iCDI and rCDI. The approaches include scores with a limited list of variables designed to be used at the bedside, but more recently have also included automated tools that take advantage of the entire electronic health record. Recent attempts to externally validate scores have met with mixed success. SUMMARY For iCDI, the performance largely hinges on the incidence, which even for hospitalized patients can be low (often <1%). Most scores fail to achieve high accuracy and/or are not externally validated. A challenge in predicting rCDI is the significant overlap with risk factors for iCDI, reducing the discriminatory ability of models. Automated electronic health record-based tools show promise but portability to other centers is challenging. Future studies should include external validation and consider biomarkers to augment performance.
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Affiliation(s)
- Krishna Rao
- Division of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
| | - Erik R Dubberke
- Division of Infectious Diseases, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
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Goncuoglu C, Guven GS, Sener B, Demirkan K. Effect of gastric acid suppression on Clostridioides difficile-induced diarrhea and appropriateness of gastric acid suppressors in hospitalized patients: A matched case-control study. Arab J Gastroenterol 2021; 22:292-296. [PMID: 34531136 DOI: 10.1016/j.ajg.2021.06.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 05/05/2021] [Accepted: 06/30/2021] [Indexed: 11/24/2022]
Abstract
BACKGROUND AND STUDY AIMS The effects of gastric acid suppressors (GASs) on Clostridioides difficile infection remain controversial. Moreover, studies have shown that GASs are overused. This study was designed to evaluate the effects of GAS use on the risk of C. difficile-induced diarrhea (CDID) development and to investigate the appropriate use of GASs. PATIENTS AND METHODS In this observational case-control study, patients hospitalized between January 2010 and December 2016 who had diarrhea after 3 days of hospitalization were included. The study (n = 122) and control (n = 122) groups were matched according to the patients' hospitalization dates and departments. RESULTS No significant difference in CDID development was observed between the study and control groups. However, GAS use was excessive in the study and control groups (usage rates were 90.2% and 91.8%, respectively) (p > 0.05). Most proton pump inhibitors and histamine-2 receptor antagonists were used without an appropriate indication. Surprisingly, the use of nonsteroidal anti-inflammatory drugs for 7 days and longer showed a significant difference between the study and control groups (p < 0.05). Additionally, significant differences in enteral feeding, oral nutritional support products, carbapenem, penicillin, glycopeptide antibiotics, antifungals, hypoalbuminemia, and increased leukocyte levels were observed between the study and control groups (p < 0.05). CONCLUSION A significant difference in CDID development was not detected. The use of non-steroidal anti-inflammatory drugs for 7 days and longer was a risk factor for CDID development. Additionally, an excessive inappropriate use of GASs was observed. Clinicians should be cautious of all these factors, which may increase the risk of CDID development.
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Affiliation(s)
- Cansu Goncuoglu
- Hacettepe University, Faculty of Pharmacy, Department of Clinical Pharmacy, P.O. Box 06100, Sıhhiye, Ankara, Turkey.
| | - Gulay Sain Guven
- Hacettepe University, Faculty of Medicine, Department of Internal Medicine, P.O. Box 06100, Sıhhiye, Ankara, Turkey
| | - Burcin Sener
- Hacettepe University, Faculty of Medicine, Department of Medical Microbiology, P.O. Box 06100, Sıhhiye, Ankara, Turkey
| | - Kutay Demirkan
- Hacettepe University, Faculty of Pharmacy, Department of Clinical Pharmacy, P.O. Box 06100, Sıhhiye, Ankara, Turkey
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Kaako A. Evaluating the efficacy of best practice alerts to improve Clostridium difficile early detection in hospital settings: A 6-month interim analysis of the 2-year prospective study. Avicenna J Med 2021; 8:87-91. [PMID: 30090747 PMCID: PMC6057162 DOI: 10.4103/ajm.ajm_85_17] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Introduction: Clostridium difficile infection (CDI) is a leading cause of hospital-associated gastrointestinal illness with high burden on the health-care system. Design: Observational, retrospective, prospective, pre- and post-intervention study on the incidence and prevalence rates of CDIs. The primary outcome is the healthcare-onset CDIs (HO-CDIs) incidence rate and proportion. Methods: Best practice alerts (BPAs) for CDI were developed in electronic medical records and released on July 13, 2016. When high-risk patients for CDI are identified, BPAs are triggered requiring nurses to order contact isolation and stool studies followed by other subsequent BPAs encouraging providers to de-escalate antibiotics and order probiotics. Data on admission count, patient-days, CDIs categories prevalence, and incidence rates were collected for the 24-month preintervention and will be collected for the 24-month postintervention period. Results: An interim analysis comparing the data from the first 6-month postintervention period with the average 6-month data of the preintervention period showed that short-term BPAs use is associated with significant increase in the overall CDI infection rate (71.47 vs. 38.38, P < 0.0001), incidence rate (53.81 vs. 28.76, P < 0.0001), overall prevalence rate (1.86 vs. 1.32, P = 0.001), and admission prevalence rate (1.10 vs. 0.70, P < 0.0001). Despite the observed overall shift from HO toward CO; no statistically significant difference in the HO-CDI event number and proportion was detected (28 [21.4%] vs. 22 [29.1%], P = 0.094). Conclusion: Short-term BPAs use is associated with significant increase in the overall CDI incidence and prevalence along with a non-statistically significant decline in HO-CDI proportion. Final analysis with full sample size is essential to provide a better picture about the long-term effect.
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Affiliation(s)
- Ahmad Kaako
- Department of Medicine, Mercy Hospital, Fort Smith, AR, USA
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Buchrits S, Gafter-Gvili A, Bishara J, Atamna A, Ayada G, Eynath Y, Avni T. The Importance of Abnormal Platelet Count in Patients with Clostridioides difficile Infection. J Clin Med 2021; 10:jcm10132957. [PMID: 34209348 PMCID: PMC8268691 DOI: 10.3390/jcm10132957] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 05/28/2021] [Accepted: 06/25/2021] [Indexed: 12/29/2022] Open
Abstract
Background: Clostridium difficile infection (CDI) causes morbidity and mortality. Platelets have been increasingly recognized as an important component of innate and adaptive immunity. We aimed to assess the incidence of thrombocytopenia and thrombocytosis in CDI and the effect of an abnormal platelet count on clinical outcomes. Methods: This single-center, retrospective cohort study consisted of all adult patients hospitalized in Rabin Medical Center between 1 January 2013 and 31 December 2018 with laboratory confirmed CDI. The primary outcome was 30-day all-cause mortality. Risk factors for 30-day all-cause mortality were identified by univariable and multivariable analyses, using logistic regression. Results: A total of 527 patients with CDI were included. Among them 179 (34%) had an abnormal platelet count: 118 (22%) had thrombocytopenia and 61 (11.5%) had thrombocytosis. Patients with thrombocytosis were similar to control patients other than having a significantly higher white blood cell count at admission. Patients with thrombocytopenia were younger than control patients and were more likely to suffer from malignancies, immunosuppression, and hematological conditions. In a multivariable analysis, both thrombocytosis (OR 1.89, 95% CI 1.01–3.52) and thrombocytopenia (OR 1.70, 95% CI 1.01–2.89) were associated with 30-days mortality, as well as age, hypoalbuminemia, acute kidney injury, and dependency on activities of daily living. A sensitivity analysis restricted for patients without hematological malignancy or receiving chemotherapy revealed increased mortality with thrombocytosis but not with thrombocytopenia. Conclusions: In this retrospective study of hospitalized patients with CDI, we observed an association between thrombocytosis on admission and all-cause mortality, which might represent a marker for disease severity. Patients with CDI and thrombocytopenia also exhibited increased mortality, which might reflect their background conditions and not the severity of the CDI. Future studies should assess thrombocytosis as a severity marker with or without the inclusion of the WBC count.
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Affiliation(s)
- Shira Buchrits
- Internal Medicine Department A, Rabin Medical Center, Beilinson Hospital, Petah-Tikva 49100, Israel; (A.G.-G.); (Y.E.); (T.A.)
- Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv 69978, Israel; (J.B.); (A.A.)
- Correspondence: ; Tel.: +972-50-633-2223
| | - Anat Gafter-Gvili
- Internal Medicine Department A, Rabin Medical Center, Beilinson Hospital, Petah-Tikva 49100, Israel; (A.G.-G.); (Y.E.); (T.A.)
- Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv 69978, Israel; (J.B.); (A.A.)
| | - Jihad Bishara
- Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv 69978, Israel; (J.B.); (A.A.)
- Infectious Disease Unit, Rabin Medical Center, Beilinson Hospital, Petah-Tikva 49100, Israel
| | - Alaa Atamna
- Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv 69978, Israel; (J.B.); (A.A.)
- Infectious Disease Unit, Rabin Medical Center, Beilinson Hospital, Petah-Tikva 49100, Israel
- Internal Medicine Department C, Rabin Medical Center, Beilinson Hospital, Petah-Tikva 49100, Israel;
| | - Gida Ayada
- Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv 69978, Israel; (J.B.); (A.A.)
- Internal Medicine Department C, Rabin Medical Center, Beilinson Hospital, Petah-Tikva 49100, Israel;
| | - Yair Eynath
- Internal Medicine Department A, Rabin Medical Center, Beilinson Hospital, Petah-Tikva 49100, Israel; (A.G.-G.); (Y.E.); (T.A.)
- Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv 69978, Israel; (J.B.); (A.A.)
| | - Tomer Avni
- Internal Medicine Department A, Rabin Medical Center, Beilinson Hospital, Petah-Tikva 49100, Israel; (A.G.-G.); (Y.E.); (T.A.)
- Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv 69978, Israel; (J.B.); (A.A.)
- Infectious Disease Unit, Rabin Medical Center, Beilinson Hospital, Petah-Tikva 49100, Israel
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12
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Eberly MD, Susi A, Adams DJ, Love CS, Nylund CM. Epidemiology and Outcomes of Patients With Healthcare Facility-Onset Clostridioides difficile Infection. Mil Med 2021; 187:e915-e920. [PMID: 33772561 DOI: 10.1093/milmed/usab116] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 03/12/2021] [Accepted: 03/19/2021] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND Clostridioides difficile infection (CDI) has become a rising public health threat. Our study aims to characterize the epidemiology and measure the attributable cost, length of stay, and in-hospital mortality of healthcare facility-onset Clostridioides difficile infection (HO-CDI) among patients in the U.S. Military Health System (MHS). METHODS We performed a case-control and cross-sectional inpatient study of HO-CDI using MHS database billing records. Cases included those who were at least 18 years of age admitted to a military treatment facility with a stool sample positive for C. difficile obtained >3 days after admission. Risk factors in the preceding year were identified. Patient case-mix adjusted outcomes including in-hospital mortality, length of stay, and hospitalization cost were evaluated by high-dimensional propensity score adjusted logistic regression. RESULTS Among 474,518 admissions within the MHS from 2008 to 2015, we identified 591 (0.12%) patients with HO-CDI and found a significant increase in the trend of HO-CDI over the 7-year study period (P < .001). Patients with HO-CDI had significantly higher hospitalization cost (attributable difference $66,044, P < .001), prolonged hospital stay (attributable difference 12.4 days, P < 0.001), and increased odds of in-hospital mortality (case-mix adjusted odds ratio 1.98; 95% CI, 1.43-2.74). CONCLUSIONS Healthcare facility-onset Clostridioides difficile infection is rising in patients within the MHS and is associated with increased length of stay, hospital costs, and in-hospital mortality. We identified a significantly increased burden of hospitalization among patients admitted with HO-CDI, highlighting the importance of infection control and antimicrobial stewardship initiatives aimed at decreasing the spread of this pathogen.
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Affiliation(s)
- Matthew D Eberly
- Department of Pediatrics, Uniformed Services University, Bethesda, MD 20814, USA
| | - Apryl Susi
- Department of Pediatrics, Uniformed Services University, Bethesda, MD 20814, USA
| | - Daniel J Adams
- Department of Pediatrics, Uniformed Services University, Bethesda, MD 20814, USA.,Department of Pediatrics, Naval Medical Center Portsmouth, Portsmouth, VA 23708, USA
| | | | - Cade M Nylund
- Department of Pediatrics, Uniformed Services University, Bethesda, MD 20814, USA
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Comorbidity and severity-of-illness risk adjustment for hospital-onset Clostridioides difficile infection using data from the electronic medical record. Infect Control Hosp Epidemiol 2020; 42:955-961. [PMID: 33327970 DOI: 10.1017/ice.2020.1344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
OBJECTIVE To determine whether electronically available comorbidities and laboratory values on admission are risk factors for hospital-onset Clostridioides difficile infection (HO-CDI) across multiple institutions and whether they could be used to improve risk adjustment. PATIENTS All patients at least 18 years of age admitted to 3 hospitals in Maryland between January 1, 2016, and January 1, 2018. METHODS Comorbid conditions were assigned using the Elixhauser comorbidity index. Multivariable log-binomial regression was conducted for each hospital using significant covariates (P < .10) in a bivariate analysis. Standardized infection ratios (SIRs) were computed using current Centers for Disease Control and Prevention (CDC) risk adjustment methodology and with the addition of Elixhauser score and individual comorbidities. RESULTS At hospital 1, 314 of 48,057 patient admissions (0.65%) had a HO-CDI; 41 of 8,791 patient admissions (0.47%) at community hospital 2 had a HO-CDI; and 75 of 29,211 patient admissions (0.26%) at community hospital 3 had a HO-CDI. In multivariable regression, Elixhauser score was a significant risk factor for HO-CDI at all hospitals when controlling for age, antibiotic use, and antacid use. Abnormal leukocyte level at hospital admission was a significant risk factor at hospital 1 and hospital 2. When Elixhauser score was included in the risk adjustment model, it was statistically significant (P < .01). Compared with the current CDC SIR methodology, the SIR of hospital 1 decreased by 2%, whereas the SIRs of hospitals 2 and 3 increased by 2% and 6%, respectively, but the rankings did not change. CONCLUSIONS Electronically available patient comorbidities are important risk factors for HO-CDI and may improve risk-adjustment methodology.
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14
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Stevens VW, Russo EM, Young-Xu Y, Leecaster M, Zhang Y, Zhang C, Yu H, Cai B, Gonzalez EN, Gerding DN, Lawrence J, Samore MH. Identification of patients at risk of Clostridioides difficile infection for enrollment in vaccine clinical trials. Vaccine 2020; 39:536-544. [PMID: 33334614 DOI: 10.1016/j.vaccine.2020.12.016] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Revised: 11/12/2020] [Accepted: 12/03/2020] [Indexed: 11/30/2022]
Abstract
BACKGROUND Clostridioides difficile infection (CDI) is an important cause of diarrheal disease associated with increasing morbidity and mortality. Efforts to develop a preventive vaccine are ongoing. The goal of this study was to develop an algorithm to identify patients at high risk of CDI for enrollment in a vaccine efficacy trial. METHODS We conducted a 2-stage retrospective study of patients aged ≥ 50 within the US Department of Veterans Affairs Health system between January 1, 2009 and December 31, 2013. Included patients had at least 1 visit in each of the 2 years prior to the study, with no CDI in the past year. We used multivariable logistic regression with elastic net regularization to identify predictors of CDI in months 2-12 (i.e., days 31 - 365) to allow time for antibodies to develop. Performance was measured using the positive predictive value (PPV) and the area under the curve (AUC). RESULTS Elements of the predictive algorithm included age, baseline comorbidity score, acute renal failure, recent infections or high-risk antibiotic use, hemodialysis in the last month, race, and measures of recent healthcare utilization. The final algorithm resulted in an AUC of 0.69 and a PPV of 3.4%. CONCLUSIONS We developed a predictive algorithm to identify a patient population with increased risk of CDI over the next 2-12 months. Our algorithm can be used prospectively with clinical and administrative data to facilitate the feasibility of conducting efficacy studies in a timely manner in an appropriate population.
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Affiliation(s)
- Vanessa W Stevens
- VA Salt Lake City Health Care System, 500 Foothill Dr, Salt Lake City, UT 84148, United States; Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, 30 N 1900 E, Salt Lake City, UT 84132, United States.
| | - Ellyn M Russo
- Clinical Epidemiology Program, Veterans Affairs Medical Center, 163 Veterans Dr, White River Junction, VT 05009, United States
| | - Yinong Young-Xu
- Clinical Epidemiology Program, Veterans Affairs Medical Center, 163 Veterans Dr, White River Junction, VT 05009, United States; Department of Psychiatry, Geisel School of Medicine at Dartmouth, One Medical Center Drive Lebanon, NH 03756, United States
| | - Molly Leecaster
- VA Salt Lake City Health Care System, 500 Foothill Dr, Salt Lake City, UT 84148, United States; Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, 30 N 1900 E, Salt Lake City, UT 84132, United States
| | - Yue Zhang
- VA Salt Lake City Health Care System, 500 Foothill Dr, Salt Lake City, UT 84148, United States; Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, 30 N 1900 E, Salt Lake City, UT 84132, United States
| | - Chong Zhang
- VA Salt Lake City Health Care System, 500 Foothill Dr, Salt Lake City, UT 84148, United States; Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, 30 N 1900 E, Salt Lake City, UT 84132, United States
| | - Holly Yu
- Pfizer Inc., 500 Arcola Rd, Collegeville, PA 19426, United States
| | - Bing Cai
- Pfizer Inc., 500 Arcola Rd, Collegeville, PA 19426, United States
| | - Elisa N Gonzalez
- Pfizer Inc., 500 Arcola Rd, Collegeville, PA 19426, United States
| | - Dale N Gerding
- Edward Hines Jr. VA Hospital, 5000 5th Ave, Hines, IL 60141, United States
| | - Jody Lawrence
- Pfizer Inc., 500 Arcola Rd, Collegeville, PA 19426, United States
| | - Matthew H Samore
- VA Salt Lake City Health Care System, 500 Foothill Dr, Salt Lake City, UT 84148, United States; Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, 30 N 1900 E, Salt Lake City, UT 84132, United States
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Tonon F, Di Bella S, Grassi G, Luzzati R, Ascenzi P, di Masi A, Zennaro C. Extra-Intestinal Effects of C.difficile Toxin A and B: An In Vivo Study Using the Zebrafish Embryo Model. Cells 2020; 9:2575. [PMID: 33271969 PMCID: PMC7760802 DOI: 10.3390/cells9122575] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 11/27/2020] [Accepted: 11/29/2020] [Indexed: 12/18/2022] Open
Abstract
C.difficile infection (CDI) is not a merely "gut-confined" disease as toxemia could drive the development of CDI-related extra-intestinal effects. These effects could explain the high CDI-associated mortality, not just justified by diarrhea and dehydration. Here, the extra-intestinal effects of toxin A (TcdA) and B (TcdB) produced by C. difficile have been studied in vivo using the zebrafish embryo model. Noteworthy, protective properties of human serum albumin (HSA) towards toxins-induced extra-intestinal effects were also addressed. Zebrafish embryos were treated with TcdA, TcdB and/or HSA at 24 h post-fertilization. Embryos were analyzed for 48 h after treatment to check vital signs and morphological changes. Markers related to cardio-vascular damage and inflammation were evaluated by Real-Time quantitative PCR and/or western blotting. Both toxins induced cardiovascular damage in zebrafish embryos by different mechanisms: (i) direct toxicity (i.e., pericardial edema, cardiac chambers enlargement, endothelial alteration); (ii) increased hormonal production and release (i.e., atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)), (iii) alteration of the vascular system through the increase of the vascular endothelial growth factor (VEGF-A) levels, as well as of its receptors, (iv) pro-inflammatory response through high cytokines production (i.e., CXCL8, IL1B, IL6 and TNFα) and (v) cell-mediated damage due to the increase in neutrophils number. In addition to cardiovascular damage, we observe skin alteration and inflammation. Finally, our data indicate a protective effect of HSA toward the toxins induced extra-intestinal effects. Together, our findings can serve as a starting point for humans' studies to substantiate and understand the extra-intestinal effects observed in CDI patients.
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Affiliation(s)
- Federica Tonon
- Department of Medical, Surgery and Health Sciences, University of Trieste, 34149 Trieste, Italy; (S.D.B.); (R.L.); (C.Z.)
| | - Stefano Di Bella
- Department of Medical, Surgery and Health Sciences, University of Trieste, 34149 Trieste, Italy; (S.D.B.); (R.L.); (C.Z.)
| | - Gabriele Grassi
- Department of Life Sciences, University of Trieste, 34128 Trieste, Italy;
| | - Roberto Luzzati
- Department of Medical, Surgery and Health Sciences, University of Trieste, 34149 Trieste, Italy; (S.D.B.); (R.L.); (C.Z.)
| | - Paolo Ascenzi
- Department of Sciences, Roma Tre University, 00154 Rome, Italy; (P.A.); (A.d.M.)
| | - Alessandra di Masi
- Department of Sciences, Roma Tre University, 00154 Rome, Italy; (P.A.); (A.d.M.)
| | - Cristina Zennaro
- Department of Medical, Surgery and Health Sciences, University of Trieste, 34149 Trieste, Italy; (S.D.B.); (R.L.); (C.Z.)
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Kamboj M, Gennarelli RL, Brite J, Sepkowitz K, Lipitz-Snyderman A. Risk for Clostridiodes difficile Infection among Older Adults with Cancer. Emerg Infect Dis 2020; 25. [PMID: 31442017 PMCID: PMC6711221 DOI: 10.3201/eid2509.181142] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
To assess whether risk for Clostridiodes difficile infection (CDI) is higher among older adults with cancer, we conducted a retrospective cohort study with a nested case-control analysis using population-based Surveillance, Epidemiology, and End Results-Medicare linked data for 2011. Among 93,566 Medicare beneficiaries, incident CDI and odds for acquiring CDI were higher among patients with than without cancer. Specifically, risk was significantly higher for those who had liquid tumors and higher for those who had recently diagnosed solid tumors and distant metastasis. These findings were independent of prior healthcare-associated exposure. This population-based assessment can be used to identify targets for prevention of CDI.
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17
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Puro N, Joseph R, Zengul FD, Cochran KJ, Camins BC, Ray M. Predictors of Hospital-Acquired Clostridioides difficile Infection: A Systematic Review. J Healthc Qual 2020; 42:127-135. [PMID: 31821178 DOI: 10.1097/jhq.0000000000000236] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Clostridioides difficile infections (CDIs) have been identified as a major health concern due to the high morbidity, mortality, and cost of treatment. The aim of this study was to review the extant literature and identify the various patient-related, medication-related, and organizational risk factors associated with developing hospital-acquired CDIs in adult patients in the United States. METHODS A systematic review of four (4) online databases, including Scopus, PubMed, CINAHL, and Cochrane Library, was conducted to identify empirical studies published from 2007 to 2017 pertaining to risk factors of developing hospital-acquired CDIs. FINDINGS Thirty-eight studies (38) were included in the review. Various patient-level and medication-related risk factors were identified including advanced patient age, comorbidities, length of hospital stay, previous hospitalizations, use of probiotic medications and proton pump inhibitors. The review also identified organizational factors such as room size, academic affiliation, and geographic location to be significantly associated with hospital-acquired CDIs. CONCLUSION Validation of the factors associated with high risk of developing hospital-acquired CDIs identified in this review can aid in the development of risk prediction models to identify patients who are at a higher risk of developing CDIs and developing quality improvement interventions that might improve patient outcomes by minimizing risk of infection.
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Predicting hospital-onset Clostridium difficile using patient mobility data: A network approach. Infect Control Hosp Epidemiol 2019; 40:1380-1386. [PMID: 31656216 DOI: 10.1017/ice.2019.288] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
OBJECTIVE To examine the relationship between unit-wide Clostridium difficile infection (CDI) susceptibility and inpatient mobility and to create contagion centrality as a new predictive measure of CDI. DESIGN Retrospective cohort study. METHODS A mobility network was constructed using 2 years of patient electronic health record data for a 739-bed hospital (n = 72,636 admissions). Network centrality measures were calculated for each hospital unit (node) providing clinical context for each in terms of patient transfers between units (ie, edges). Daily unit-wide CDI susceptibility scores were calculated using logistic regression and were compared to network centrality measures to determine the relationship between unit CDI susceptibility and patient mobility. RESULTS Closeness centrality was a statistically significant measure associated with unit susceptibility (P < .05), highlighting the importance of incoming patient mobility in CDI prevention at the unit level. Contagion centrality (CC) was calculated using inpatient transfer rates, unit-wide susceptibility of CDI, and current hospital CDI infections. The contagion centrality measure was statistically significant (P < .05) with our outcome of hospital-onset CDI cases, and it captured the additional opportunities for transmission associated with inpatient transfers. We have used this analysis to create easily interpretable clinical tools showing this relationship as well as the risk of hospital-onset CDI in real time, and these tools can be implemented in hospital EHR systems. CONCLUSIONS Quantifying and visualizing the combination of inpatient transfers, unit-wide risk, and current infections help identify hospital units at risk of developing a CDI outbreak and, thus, provide clinicians and infection prevention staff with advanced warning and specific location data to inform prevention efforts.
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19
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Kamiyama D, Weng BH, Donnelley MA, Zhu E, Brown J. Use of a Clostridium difficileclinical prediction rule to facilitate antimicrobial stewardship. J Infect Prev 2019. [DOI: 10.1177/1757177419846589] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
In this study, we assessed whether a Clostridium difficile clinical prediction rule could be used to facilitate antimicrobial stewardship in an acute care hospital. We found that patients with higher scores were more likely to receive unnecessary antimicrobials and had the greatest potential for antimicrobial stewardship interventions. This novel method has the potential to expedite antimicrobial stewardship efforts, particularly for complex patients, in health care institutions.
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Affiliation(s)
- Davin Kamiyama
- Department of Pharmacy, University of California, Davis Medical Center, Sacramento, USA
| | - Bruce H Weng
- Division of Infectious Diseases, University of California, Davis Medical Center, Sacramento, USA
| | - Monica A Donnelley
- Department of Pharmacy, University of California, Davis Medical Center, Sacramento, USA
| | - Elizabeth Zhu
- Department of Pharmacy, University of California, Davis Medical Center, Sacramento, USA
| | - Jennifer Brown
- Division of Infectious Diseases, University of California, Davis Medical Center, Sacramento, USA
- Department of Hospital Epidemiology and Infection Prevention, University of California, Davis Medical Center, Sacramento, USA
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20
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Attributable costs and length of stay of hospital-acquired Clostridioides difficile: A population-based matched cohort study in Alberta, Canada. Infect Control Hosp Epidemiol 2019; 40:1135-1143. [PMID: 31342884 DOI: 10.1017/ice.2019.178] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE To determine the attributable cost and length of stay of hospital-acquired Clostridioides difficile infection (HA-CDI) from the healthcare payer perspective using linked clinical, administrative, and microcosting data. DESIGN A retrospective, population-based, propensity-score-matched cohort study. SETTING Acute-care facilities in Alberta, Canada. PATIENTS Admitted adult (≥18 years) patients with incident HA-CDI and without CDI between April 1, 2012, and March 31, 2016. METHODS Incident cases of HA-CDI were identified using a clinical surveillance definition. Cases were matched to noncases of CDI (those without a positive C. difficile test or without clinical CDI) on propensity score and exposure time. The outcomes were attributable costs and length of stay of the hospitalization where the CDI was identified. Costs were expressed in 2018 Canadian dollars. RESULTS Of the 2,916 HA-CDI cases at facilities with microcosting data available, 98.4% were matched to 13,024 noncases of CDI. The total adjusted cost among HA-CDI cases was 27% greater than noncases of CDI (ratio, 1.27; 95% confidence interval [CI], 1.21-1.33). The mean attributable cost was $18,386 (CAD 2018; USD $14,190; 95% CI, $14,312-$22,460; USD $11,046-$17,334). The adjusted length of stay among HA-CDI cases was 13% greater than for noncases of CDI (ratio, 1.13; 95% CI, 1.07-1.19), which corresponds to an extra 5.6 days (95% CI, 3.10-8.06) in length of hospital stay per HA-CDI case. CONCLUSIONS In this population-based, propensity score matched analysis using microcosting data, HA-CDI was associated with substantial attributable cost.
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21
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Leal J, Ronksley P, Henderson EA, Conly J, Manns B. Predictors of mortality and length of stay in patients with hospital-acquired Clostridioides difficile infection: a population-based study in Alberta, Canada. J Hosp Infect 2019; 103:85-91. [PMID: 30991081 DOI: 10.1016/j.jhin.2019.04.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2019] [Accepted: 04/08/2019] [Indexed: 12/17/2022]
Abstract
In a population-based, five-year retrospective cohort study of 5304 adult patients with hospital-acquired Clostridioides difficile infection across Alberta (N=101 hospitals), 30-day all-cause and attributable mortality were 12.2% and 4.5%, respectively. Patients >75 years of age had the highest odds of attributable mortality (odds ratio (OR) 9.34, 95% confidence interval (CI) 2.92-29.83) and largest difference in mean length of stay (11.7 days, 95% CI 8.2-15.2). A novel finding was that elevated white blood cell count at admission was associated with reduced attributable mortality (OR 0.67, 95% CI 0.50-0.90) which deserves further study. Advancing age was incrementally and significantly associated with all outcomes.
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Affiliation(s)
- J Leal
- Department of Community Health Sciences, University of Calgary, Calgary, Canada; Infection Prevention and Control, Alberta Health Services, Calgary, Canada
| | - P Ronksley
- Department of Community Health Sciences, University of Calgary, Calgary, Canada; O'Brien Institute for Public Health, University of Calgary and Alberta Health Services, Canada
| | - E A Henderson
- Department of Community Health Sciences, University of Calgary, Calgary, Canada; Infection Prevention and Control, Alberta Health Services, Calgary, Canada
| | - J Conly
- Department of Medicine, University of Calgary, Calgary, Canada; Departments of Microbiology, Immunology, and Infectious Diseases, Pathology and Laboratory Medicine, University of Calgary, Calgary, Canada; O'Brien Institute for Public Health, University of Calgary and Alberta Health Services, Canada; Synder Institute for Chronic Diseases, University of Calgary and Alberta Health Services, Calgary, Canada
| | - B Manns
- Department of Community Health Sciences, University of Calgary, Calgary, Canada; Department of Medicine, University of Calgary, Calgary, Canada; O'Brien Institute for Public Health, University of Calgary and Alberta Health Services, Canada; Libin Cardiovascular Institute, University of Calgary, Calgary, Canada.
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Marley C, El Hahi Y, Ferreira G, Woods L, Ramirez Villaescusa A. Evaluation of a risk score to predict future Clostridium difficile disease using UK primary care and hospital data in Clinical Practice Research Datalink. Hum Vaccin Immunother 2019; 15:2475-2481. [PMID: 30945972 PMCID: PMC6816380 DOI: 10.1080/21645515.2019.1589288] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
We evaluated the applicability of a Clostridium difficile infection (CDI) risk index developed for patients at hospital discharge to identify persons at high-risk of CDI in a primary care population. This retrospective observational study used data from the UK Clinical Practice Research Datalink, linked with Hospital Episodes Statistics. The risk index was based on the following patient characteristics: age, previous hospitalizations, days in hospital, and prior antibiotics use. Individual risk scores were calculated by summing points assigned to pre-defined categories for each characteristic. We assessed the association of risk factors with CDI by multivariate logistic regression. The estimated CDI incidence rate was 4/10,000 and 2/10,000 person-years in 2008 and 2012, respectively. On an index with a maximal risk of 19, a cut-off for high risk of ≥7 had sensitivity, specificity and positive predictive values of 80%, 87% and 12%, respectively. A high-risk person had a ~ 35% higher risk of CDI than a low-risk person. Multivariate risk factor analysis indicated a need to reconsider the relative risk scores. The CDI risk index can be applied to the UK primary care population and help identify study populations for vaccine development studies. Reassessing the relative weights assigned to risk factors could improve the index performance in this setting.
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Affiliation(s)
| | | | | | - Laura Woods
- Department of Non communicable disease epidemiology, London School of Hygiene & Tropical medicine , London , UK
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Figueroa Castro CE, Munoz-Price LS. Advances in Infection Control for Clostridioides (Formerly Clostridium) difficile Infection. CURRENT TREATMENT OPTIONS IN INFECTIOUS DISEASES 2019. [DOI: 10.1007/s40506-019-0179-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Olsen MA, Stwalley D, Demont C, Dubberke ER. Increasing Age Has Limited Impact on Risk of Clostridium difficile Infection in an Elderly Population. Open Forum Infect Dis 2018; 5:ofy160. [PMID: 30046643 PMCID: PMC6054265 DOI: 10.1093/ofid/ofy160] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Accepted: 07/11/2018] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Numerous studies have found increased risk of Clostridium difficile infection (CDI) with increasing age. We hypothesized that increased CDI risk in an elderly population is due to poorer overall health status with older age. METHODS A total of 174 903 persons aged 66 years and older coded for CDI in 2011 were identified using Medicare claims data. The comparison population consisted of 1 453 867 uninfected persons. Potential risk factors for CDI were identified in the prior 12 months and organized into categories, including infections, acute noninfectious conditions, chronic comorbidities, frailty indicators, and health care utilization. Multivariable logistic regression models with CDI as the dependent variable were used to determine the categories with the biggest impact on model performance. RESULTS Increasing age was associated with progressively increasing risk of CDI in univariate analysis, with 5-fold increased risk of CDI in 94-95-year-old persons compared with those aged 66-67 years. Independent risk factors for CDI with the highest effect sizes included septicemia (odds ratio [OR], 4.1), emergency hospitalization(s) (OR, 3.9), short-term skilled nursing facility stay(s) (OR, 2.7), diverticulitis (OR, 2.2), and pneumonia (OR, 2.1). Exclusion of age from the full model had no impact on model performance. Exclusion of acute noninfectious conditions followed by frailty indicators resulted in lower c-statistics and poor model fit. Further exclusion of health care utilization variables resulted in a large drop in the c-statistic. CONCLUSIONS Age did not improve CDI risk prediction after controlling for a wide variety of infections, other acute conditions, frailty indicators, and prior health care utilization.
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Affiliation(s)
- Margaret A Olsen
- Department of Medicine, Washington University School of Medicine, St. Louis, Missouri
- Department of Surgery, Washington University School of Medicine, St. Louis, Missouri
| | - Dustin Stwalley
- Department of Medicine, Washington University School of Medicine, St. Louis, Missouri
| | | | - Erik R Dubberke
- Department of Medicine, Washington University School of Medicine, St. Louis, Missouri
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Audet LA, Bourgault P, Rochefort CM. Associations between nurse education and experience and the risk of mortality and adverse events in acute care hospitals: A systematic review of observational studies. Int J Nurs Stud 2018; 80:128-146. [PMID: 29407346 DOI: 10.1016/j.ijnurstu.2018.01.007] [Citation(s) in RCA: 89] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2017] [Revised: 12/29/2017] [Accepted: 01/16/2018] [Indexed: 12/17/2022]
Abstract
OBJECTIVES To provide knowledge from the summarization of the evidence on the: a) associations between nurse education and experience and the occurrence of mortality and adverse events in acute care hospitals, and; b) benefits to patients and organizations of the recent Institute of Medicine's recommendation that 80% of registered nurses should be educated at the baccalaureate degree by 2020. DATA SOURCES A systematic search of English and French literature was conducted in six electronic databases: 1) Medline, 2) PubMed, 3) CINAHL, 4) Scopus, 5) Campbell, and 6) Cochrane databases. Additional studies were identified by searching bibliographies, prior reviews, and by contacting authors. REVIEW METHOD Studies were included if they: a) were published between January 1996 and August 2017; b) were based on a quantitative research design; c) examined the associations between registered nurse education or experience and at least one independently measured adverse event, and; d) were conducted in an adult acute care setting. Data were independently extracted, analysed, and synthesized by two authors and discrepancies were resolved by consensus. The methodological heterogeneity of the reviewed studies precluded the use of meta-analysis techniques. However, the methodological quality of each study was assessed using the STROBE criteria. FINDINGS Among 2109 retrieved articles, 27 studies (24 cross-sectional and three longitudinal studies) met our inclusion criteria. These studies examined 18 distinct adverse events, with mortality and failure to rescue being the most frequently investigated events. Overall, higher levels of education were associated with lower risks of failure to rescue and mortality in 75% and 61.1% of the reviewed studies pertaining to these adverse events, respectively. Nurse education was inconsistently related to the occurrence of the other events, which were the focus of only a small number of studies. Only one study examined the 80% threshold proposed by the Institute of Medicine and found evidence that it is associated with lower odds of hospital readmission and shorter lengths of stay, but unrelated to mortality. Nurse experience was inconsistently related to adverse event occurrence. CONCLUSION While evidence suggests that higher nurse education is associated with lower risks of mortality and failure to rescue, longitudinal studies are needed to better ascertain these associations and determine the specific thresholds that minimize risks. Further studies are needed to better document the association of nurse education and experience with other nursing-sensitive adverse events, as well as the benefits to patients and organizations of the Institute of Medicine's recommendation.
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Affiliation(s)
- Li-Anne Audet
- University of Sherbrooke, School of Nursing, Faculty of Medicine and Health Sciences, Sherbrooke, Quebec, Canada; Centre de recherche de l'Hôpital Charles-Le Moyne, Longueuil, Québec, Canada; Centre de recherche du Centre hospitalier universitaire de Sherbrooke, Sherbrooke, Québec, Canada
| | - Patricia Bourgault
- University of Sherbrooke, School of Nursing, Faculty of Medicine and Health Sciences, Sherbrooke, Quebec, Canada; Centre de recherche du Centre hospitalier universitaire de Sherbrooke, Sherbrooke, Québec, Canada
| | - Christian M Rochefort
- University of Sherbrooke, School of Nursing, Faculty of Medicine and Health Sciences, Sherbrooke, Quebec, Canada; Centre de recherche de l'Hôpital Charles-Le Moyne, Longueuil, Québec, Canada; Centre de recherche du Centre hospitalier universitaire de Sherbrooke, Sherbrooke, Québec, Canada.
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Shah K, Curtin BF, Chu C, Hwang D, Flasar MH, von Rosenvinge E. Characteristics of Clostridium difficile infection in patients hospitalized with myelodysplastic syndrome or acute myelogenous leukemia. World J Clin Oncol 2017; 8:398-404. [PMID: 29067276 PMCID: PMC5638715 DOI: 10.5306/wjco.v8.i5.398] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2017] [Revised: 06/07/2017] [Accepted: 07/17/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate factors associated with Clostridium difficile infection (CDI) and outcomes of CDI in the myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) population.
METHODS After IRB approval, all MDS/AML patients hospitalized at the University of Maryland Greenebaum Comprehensive Cancer Center between August 2011 and December 2013 were identified. Medical charts were reviewed for demographics, clinical information, development of CDI, complications of CDI, and mortality. Patients with CDI, defined as having a positive stool PCR done for clinical suspicion of CDI, were compared to those without CDI in order to identify predictors of disease. A t-test was used for comparison of continuous variables and chi-square or Fisher’s exact tests were used for categorical variables, as appropriate.
RESULTS Two hundred and twenty-three patients (60.1% male, mean age 61.3 years, 13% MDS, 87% AML) had 594 unique hospitalizations during the study period. Thirty-four patients (15.2%) were diagnosed with CDI. Factors significantly associated with CDI included lower albumin at time of hospitalization (P < 0.0001), prior diagnosis of CDI (P < 0.0001), receipt of cytarabine-based chemotherapy (P = 0.015), total days of neutropenia (P = 0.014), and total days of hospitalization (P = 0.005). Gender (P = 0.10), age (P = 0.77), proton-pump inhibitor use (P = 0.73), receipt of antibiotics (P = 0.66), and receipt of DNA hypomethylating agent-based chemotherapy (P = 0.92) were not significantly associated with CDI.
CONCLUSION CDI is common in the MDS/AML population. Factors significantly associated with CDI in this population include low albumin, prior CDI, use of cytarabine-based chemotherapy, and prolonged neutropenia. In this study, we have identified a subset of patients in which prophylaxis studies could be targeted.
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Affiliation(s)
- Kamini Shah
- Division of Infectious Diseases, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, United States
| | - Bryan F Curtin
- Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 21201, United States
| | - Christopher Chu
- Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, United States
| | - Daniel Hwang
- Department of Medicine, University of Maryland School of Medicine, Baltimore 21201, MD, United States
| | - Mark H Flasar
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine and VA Maryland Health Care System, Baltimore, MD 21201, United States
| | - Erik von Rosenvinge
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine and VA Maryland Health Care System, Baltimore, MD 21201, United States
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Identification of novel risk factors for community-acquired Clostridium difficile infection using spatial statistics and geographic information system analyses. PLoS One 2017; 12:e0176285. [PMID: 28510584 PMCID: PMC5433765 DOI: 10.1371/journal.pone.0176285] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2016] [Accepted: 04/07/2017] [Indexed: 02/04/2023] Open
Abstract
Background The rate of community-acquired Clostridium difficile infection (CA-CDI) is increasing. While receipt of antibiotics remains an important risk factor for CDI, studies related to acquisition of C. difficile outside of hospitals are lacking. As a result, risk factors for exposure to C. difficile in community settings have been inadequately studied. Main objective To identify novel environmental risk factors for CA-CDI Methods We performed a population-based retrospective cohort study of patients with CA-CDI from 1/1/2007 through 12/31/2014 in a 10-county area in central North Carolina. 360 Census Tracts in these 10 counties were used as the demographic Geographic Information System (GIS) base-map. Longitude and latitude (X, Y) coordinates were generated from patient home addresses and overlaid to Census Tracts polygons using ArcGIS; ArcView was used to assess “hot-spots” or clusters of CA-CDI. We then constructed a mixed hierarchical model to identify environmental variables independently associated with increased rates of CA-CDI. Results A total of 1,895 unique patients met our criteria for CA-CDI. The mean patient age was 54.5 years; 62% were female and 70% were Caucasian. 402 (21%) patient addresses were located in “hot spots” or clusters of CA-CDI (p<0.001). “Hot spot” census tracts were scattered throughout the 10 counties. After adjusting for clustering and population density, age ≥ 60 years (p = 0.03), race (<0.001), proximity to a livestock farm (0.01), proximity to farming raw materials services (0.02), and proximity to a nursing home (0.04) were independently associated with increased rates of CA-CDI. Conclusions Our study is the first to use spatial statistics and mixed models to identify important environmental risk factors for acquisition of C. difficile and adds to the growing evidence that farm practices may put patients at risk for important drug-resistant infections.
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Fountain EM, Moses MC, Park LP, Woods CW, Arepally GM. Thrombocytopenia in hospitalized patients with severe clostridium difficile infection. J Thromb Thrombolysis 2017; 43:38-42. [PMID: 27614757 DOI: 10.1007/s11239-016-1423-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Clostridium difficile infection (CDI) is a common cause of nosocomial diarrhea and colitis. The incidence and prognostic significance of thrombocytopenia as related to mode of acquisition (hospital vs. community), NAP1/027 strain, and disease severity has not been examined. We performed a single-institution retrospective analysis of all adult inpatients from 2013 to 2014 diagnosed with CDI during their hospitalization to document the incidence/prevalence of thrombocytopenia and associated outcomes. Severe disease was defined by a composite endpoint of inpatient death, death within 30 days of discharge, presence of septic shock, or need for colectomy during hospitalization. Of the 533 patients diagnosed with CDI, moderate thrombocytopenia (platelet count <100 × 109/L at time of CDI diagnosis) was present in 15 % of the total cohort and incident thrombocytopenia developed in 3 % of patients after admission. Thrombocytopenia was more common in hospital-acquired disease and associated with increased length of stay, but was not associated with treatment failure. Those with moderate thrombocytopenia were more likely to have severe disease, after controlling for white blood cell count, albumin, and creatinine. Moderate thrombocytopenia is associated with poor prognosis and is a potential risk stratification tool for severe CDI.
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Affiliation(s)
- Eric M Fountain
- Department of Medicine, Duke University Medical Center, Durham, NC, USA.
| | - Maggie C Moses
- Department of Medicine, Duke University Medical Center, Durham, NC, USA
| | - Lawrence P Park
- Department of Medicine, Duke University Medical Center, Durham, NC, USA.,Division of Infectious Disease, Duke University Medical Center, Durham, NC, USA
| | - Christopher W Woods
- Department of Medicine, Duke University Medical Center, Durham, NC, USA.,Division of Infectious Disease, Duke University Medical Center, Durham, NC, USA
| | - Gowthami M Arepally
- Department of Medicine, Duke University Medical Center, Durham, NC, USA.,Division of Hematology, Duke University Medical Center, Durham, NC, USA
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Clostridium difficile in an Urban, University-Affiliated Long-Term Acute-Care Hospital. Infect Control Hosp Epidemiol 2016; 38:294-299. [PMID: 27923419 DOI: 10.1017/ice.0000-0.291] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
OBJECTIVES To describe the characteristics and impact of Clostridium difficile infection (CDI) in a long-term acute-care hospital (LTACH). DESIGN Retrospective matched cohort study. SETTING A 38-bed, urban, university-affiliated LTACH. METHODS The characteristics of LTACH-onset CDI were assessed among patients hospitalized between July 2008 and October 2015. Patients with CDI were matched to concurrently hospitalized patients without a diagnosis of CDI. Severe CDI was defined as CDI with 2 or more of the following criteria: age ≥65 years, serum creatinine ≥2 mg/dL, or peripheral leukocyte count ≥20,000 cells/μL. A conditional Poisson regression model was developed to determine characteristics associated with a composite primary outcome of 30-day readmission to an acute-care hospital, or mortality. RESULTS The overall incidence of CDI was 21.4 cases per 10,000 patient days, with 27% of infections classified as severe. Patients with CDI had a mean age of 70 years (SD, 14 years), a mean Charlson comorbidity index of 3.6 (SD, 2.0), a median length of stay of 33 days (interquartile range [IQR], 24-45 days), and a median time between admission and CDI diagnosis of 16 days (IQR, 9-23 days). The most commonly prescribed antibiotic preceding a CDI diagnosis was a cephalosporin, with median duration of 8 days (IQR, 4-14 days). In multivariate analysis, CDI was not significantly associated with the primary outcome (relative risk, 0.97; 95% CI, 0.59-1.58). CONCLUSIONS Incidence of CDI in an urban, university-affiliated LTACH was high. Future research should focus on infection prevention measures to decrease the burden of CDI in this complex patient population. Infect Control Hosp Epidemiol 2017;38:294-299.
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Influence of antibiotics and case exposure on hospital-acquired Clostridium difficile infection independent of illness severity. J Hosp Infect 2016; 95:400-409. [PMID: 27825674 DOI: 10.1016/j.jhin.2016.10.007] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2016] [Accepted: 10/07/2016] [Indexed: 11/22/2022]
Abstract
BACKGROUND Previous studies of the association between antibiotic exposure and risk of hospital-acquired Clostridium difficile-associated infection (CDI) have not fully accounted for patient severity of illness, and competing risks. AIM To determine the potential effects of interventions on hospital-acquired CDI risk. METHODS All adults admitted to a teaching hospital between 2004 and 2014 for more than two days were included. Exposures to all antibiotics and cases of CDI were determined. Patients were followed until discharge from hospital, death, or acquisition of hospital-acquired CDI (defined as positive toxin assay in unformed stool >2 days following admission). Multivariable proportional hazards competing-risks modelling with time-dependent covariates was used, accounting for patient severity of illness using the Escobar model. FINDINGS In all, 208,104 patients were studied. Hospital-acquired CDI risk was 0.46 events per 1000 patient-days, decreasing significantly during the study period. Compared to the 5th percentile hospital death risk (0.02%), patients with a 50% risk of death in hospital had an adjusted hazard ratio (aHR) of hospital-acquired CDI of 5.5. Exposure to some antibiotics significantly increased hospital-acquired CDI risk, being highest for carbapenems (aHR: 1.47 after one week of continuous exposure) and intravenous vancomycin (aHR: 1.53). On the ward, sharing a room with other patients newly diagnosed with CDI significantly increased the risk of subsequent disease (aHR: 1.16 on CDI diagnosis day). CONCLUSION The primary determinant of hospital-acquired CDI was patient severity of illness. Exposure to both antibiotics and other patients with CDI significantly increased the subsequent risk of hospital-acquired CDI but this risk was small relative to patient severity of illness.
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Effects of a predictive preventive model for prevention of Clostridium difficile infection in patients in intensive care units. Am J Infect Control 2016; 44:421-4. [PMID: 26775936 DOI: 10.1016/j.ajic.2015.11.010] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2015] [Revised: 11/02/2015] [Accepted: 11/05/2015] [Indexed: 12/19/2022]
Abstract
BACKGROUND Health care-acquired Clostridium difficile infection (HACDI) is associated with adverse outcomes at both the organization and patient level. Factors that increase risk for development of HACDI have been identified. Objectives of this study were to develop a predictive screening tool to identify patients at risk for HACDI and implement a bundle of mitigation interventions. METHODS A predictive screening tool was developed based on risk factors identified in the literature and validated by retrospective analysis of all HACDI cases occurring in critically ill patients during 2013. The tool was used to screen all patients admitted to an intensive care unit. Evidence-based interventions (bundle) were implemented for patients identified as being at high risk for HACDI. Effectiveness of the model was measured by reduction of HACDI rate during the intervention period compared with the preintervention period. RESULTS During the 12-month intervention period 217 high-risk patients were identified as infected with Clostridium difficile. Sixty-two of these met exclusion criteria, resulting in a study population of 157 patients. During the preintervention phase, 10 cases of HACDI occurred (overall incidence rate, 14.7). During the 12-month study period, 2 cases of HACDI were identified (incidence rate, 3.12). The reduction was statistically significant. CONCLUSION A strategy for identifying patients at increased risk and implementation of multidisciplinary risk-mitigation strategies is effective in reducing incidence of HACDI.
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Di Bella S, di Masi A, Turla S, Ascenzi P, Gouliouris T, Petrosillo N. The Protective Role of Albumin in Clostridium difficile Infection: A Step Toward Solving the Puzzle. Infect Control Hosp Epidemiol 2015; 36:1478-1479. [PMID: 26456662 DOI: 10.1017/ice.2015.221] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Affiliation(s)
- Stefano Di Bella
- 1Infectious Diseases Division,"San Gerardo de' Tintori" Hospital,Monza,Italy
| | | | - Simona Turla
- 2Department of Science,Roma Tre University,Rome,Italy
| | - Paolo Ascenzi
- 3Interdepartmental Laboratory for Electron Microscopy,Roma Tre University,Rome,Italy
| | - Theodore Gouliouris
- 4Department of Infectious Diseases,Addenbrooke's Hospital,Cambridge,United Kingdom
| | - Nicola Petrosillo
- 52Infectious Diseases Division,National Institute for Infectious Diseases "L. Spallanzani,"Rome,Italy
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A Potential Cellular Explanation for the Increased Risk of Clostridium difficile Infection Due to Hypoalbuminemia: Reply Di Bella et al. Infect Control Hosp Epidemiol 2015; 36:1480. [PMID: 26456896 DOI: 10.1017/ice.2015.235] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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