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Sohal A, Chaudhry H, Singla P, Sharma R, Kohli I, Dukovic D, Prajapati D. The burden of Clostridioides difficile on COVID-19 hospitalizations in the USA. J Gastroenterol Hepatol 2023; 38:590-597. [PMID: 36662626 DOI: 10.1111/jgh.16128] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 12/25/2022] [Accepted: 01/17/2023] [Indexed: 01/21/2023]
Abstract
BACKGROUND AND AIM Clostridioides difficile infection (CDI) is the leading cause of hospital acquired-infectious diarrhea in the USA. In this study, we assess the prevalence and impact of CDI in COVID-19 hospitalizations in the USA. METHODS We used the 2020 National Inpatient Sample database to identify adult patients with COVID-19. The patients were stratified into two groups based on the presence of CDI. The impact of CDI on outcomes such as in-hospital mortality, ICU admission, shock, acute kidney injury (AKI), and sepsis rates. Multivariate regression analysis was performed to assess the effects of CDI on outcomes. RESULTS The study population comprised 1581 585 patients with COVID-19. Among these, 0.65% of people had a CDI. There was a higher incidence of mortality in patients with COVID-19 and CDI compared with patients without COVID-19 (23.25% vs 13.33%, P < 0.001). The patients with COVID-19 and CDI had a higher incidence of sepsis (7.69% vs 5%, P < 0.001), shock (23.59% vs 8.59%, P < 0.001), ICU admission (25.54% vs 12.28%, P < 0.001), and AKI (47.71% vs 28.52%, P < 0.001). On multivariate analysis, patients with CDI had a statistically significant higher risk of mortality than those without (aOR = 1.47, P < 0.001). We also noted a statistically significant higher risk of sepsis (aOR = 1.47, P < 0.001), shock (aOR = 2.7, P < 0.001), AKI (aOR = 1.55, P < 0.001), and ICU admission (aOR = 2.16, P < 0.001) in the study population. CONCLUSIONS Our study revealed the prevalence of CDI in COVID-19 patients was 0.65%. Although the prevalence was low, its presence is associated with worse outcomes and higher resource utilization.
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Affiliation(s)
- Aalam Sohal
- Liver Institute Northwest, Seattle, Washington, USA
| | - Hunza Chaudhry
- Department of Internal Medicine, University of California, San Francisco, Fresno, California, USA
| | - Piyush Singla
- Dayanand Medical College and Hospital, Punjab, India
| | | | - Isha Kohli
- Graduate School of Public Health, Icahn School of Medicine, New York, New York, USA
| | - Dino Dukovic
- Ross University School of Medicine, Bridgetown, Barbados
| | - Devang Prajapati
- Department of Gastroenterology and Hepatology, University of California, San Francisco, Fresno, California, USA
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Kim YI, Yu CS, Kim YS, Kim CW, Lee JL, Yoon YS, Park IJ, Lim SB, Kim JC. Clostridium difficile infection after ileostomy closure and anastomotic failure in rectal cancer surgery patients. BJS Open 2022; 6:zrac026. [PMID: 35445239 PMCID: PMC9021405 DOI: 10.1093/bjsopen/zrac026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2021] [Revised: 01/08/2022] [Accepted: 02/02/2022] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Diverting ileostomy during resection of rectal cancer is frequently performed in patients at risk of anastomotic failure. Clostridium difficile infection (CDI) is reported to be frequent in patients who receive ileostomy closure with a questionable association to postoperative anastomosis leak. The primary aim of this study was to determine the incidence of CDI following ileostomy closure in patients who underwent rectal cancer surgery; the secondary aim was to assess the rate of postileostomy closure CDI in patients who presented with leakage at the original colorectal anastomosis site. METHODS Medical records of patients with rectal cancer who underwent ileostomy closure between January 2015 and December 2019 were retrospectively reviewed. All patients had previously received resection and anastomosis for primary rectal cancer with diverting ileostomy. Data regarding CDI incidence, preoperative status, perioperative management, and clinical outcomes were collected. CDI positivity was determined by direct real-time PCR and enzyme-linked fluorescent assays for detecting toxin A and B.Statistical analyses were computed for CDI risk factors. RESULTS A total of 1270 patients were included and 208 patients were tested for CDI owing to colitis-related symptoms. The incidence of CDI was 3.6 per cent (46 patients). Multivariable analysis for CDI risk factors identified adjuvant chemotherapy (hazard ratio (HR) 2.28; P = 0.034) and colorectal anastomosis leakage prior to CDI (HR 3.75; P = 0.008). Finally, patients with CDI showed higher colorectal anastomosis leakage risk in multivariable analysis after ileostomy closure (HR 6.922; P = 0.001). CONCLUSION Patients with CDI presented with a significantly higher rate of colorectal anastomosis leakage prior to ileostomy closure.
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Affiliation(s)
- Young Il Kim
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea
| | - Chang Sik Yu
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea
| | - Yang Soo Kim
- Department of Infectious Diseases, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea
| | - Chan Wook Kim
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea
| | - Jong Lyul Lee
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea
| | - Yong Sik Yoon
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea
| | - In Ja Park
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea
| | - Seok-Byung Lim
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea
| | - Jin Cheon Kim
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea
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Al Moussawi H, Alsheikh M, Kamar K, Awada Z, Hosry J, Deeb L. Beyond Pain Relief: Is Opioids Use Safe in Clostridium difficile Infection? Gastroenterology Res 2021; 14:275-280. [PMID: 34804271 PMCID: PMC8577597 DOI: 10.14740/gr1453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 09/23/2021] [Indexed: 11/16/2022] Open
Abstract
Background Clostridium difficile infection (CDI) is a common condition in hospitalized patients. In the USA, there has been an alarming rise in the use of opioids for analgesia during hospitalization. Due to their antiperistalsis effect, opioids can increase absorption of bacterial toxins. Our study aimed to highlight any correlation between opioids use in CDI and morbidity, mortality, and duration of hospitalization. Methods A retrospective study was performed, and data were collected from 321 hospitalized patients with CDI. The dosage of opioids received in the first 4 days following diagnosis was calculated. Patients were divided into two groups (control group vs. opioid group). Reassessment of severity of disease on day 4 was performed. Complications, hospital mortality, readmissions for CDI within 3 months, length of stay, and disposition at discharge were compared. Results The opioid arm consisted of 169 patients, and 152 patients served as controls. On day 4, the number of patients with severe disease was significantly higher in the opioid group versus controls (78 (46.1%) vs. 37 (24%), respectively, P < 0.01), and complications including ileus, high white blood cell count, and need for vasopressors were significantly higher in the opioid group (27.8% versus 16.4%, P = 0.01). Control group patients were more likely to be discharged home (47% vs. 33%, P = 0.04), while opioid group required predominantly long-term facilities care after discharge. Conclusion Opioid usage for analgesia in CDI increases the risk for severe disease, complications, longer hospitalization, readmission rates, hospital mortality and discharge to a long-term facility.
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Affiliation(s)
- Hassan Al Moussawi
- Department of Gastroenterology, Staten Island University Hospital, Northwell Health, Staten Island, NY, USA
| | - Mira Alsheikh
- Department of Gastroenterology, Staten Island University Hospital, Northwell Health, Staten Island, NY, USA
| | - Khalil Kamar
- Department of Medicine, Staten Island University Hospital, Northwell Health, Staten Island, NY, USA
| | - Zeinab Awada
- Department of Medicine, Staten Island University Hospital, Northwell Health, Staten Island, NY, USA
| | - Jeff Hosry
- Department of Medicine, Staten Island University Hospital, Northwell Health, Staten Island, NY, USA
| | - Liliane Deeb
- Department of Gastroenterology, Staten Island University Hospital, Northwell Health, Staten Island, NY, USA
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Engevik MA, Engevik AC, Engevik KA, Auchtung JM, Chang-Graham AL, Ruan W, Luna RA, Hyser JM, Spinler JK, Versalovic J. Mucin-Degrading Microbes Release Monosaccharides That Chemoattract Clostridioides difficile and Facilitate Colonization of the Human Intestinal Mucus Layer. ACS Infect Dis 2021; 7:1126-1142. [PMID: 33176423 DOI: 10.1021/acsinfecdis.0c00634] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
It is widely accepted that the pathogen Clostridioides difficile exploits an intestinal environment with an altered microbiota, but the details of these microbe-microbe interactions are unclear. Adherence and colonization of mucus has been demonstrated for several enteric pathogens and it is possible that mucin-associated microbes may be working in concert with C. difficile. We showed that C. difficile ribotype-027 adheres to MUC2 glycans and using fecal bioreactors, we identified that C. difficile associates with several mucin-degrading microbes. C. difficile was found to chemotax toward intestinal mucus and its glycan components, demonstrating that C. difficile senses the mucus layer. Although C. difficile lacks the glycosyl hydrolases required to degrade mucin glycans, coculturing C. difficile with the mucin-degrading Akkermansia muciniphila, Bacteroides thetaiotaomicron, and Ruminococcus torques allowed C. difficile to grow in media that lacked glucose but contained purified MUC2. Collectively, these studies expand our knowledge on how intestinal microbes support C. difficile.
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Affiliation(s)
- Melinda A. Engevik
- Department of Pathology & Immunology, Baylor College of Medicine Houston Texas 77030, United States
- Department of Pathology, Texas Children’s Hospital Houston Texas 77030, United States
| | - Amy C. Engevik
- Department of Surgery, Vanderbilt University School of Medicine, Nashville Tennessee 37232, United States
- Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville Tennessee 37232, United States
| | - Kristen A. Engevik
- Department of Molecular Virology and Microbiology, Baylor College of Medicine Houston Texas 77030, United States
| | - Jennifer M. Auchtung
- Department of Molecular Virology and Microbiology, Baylor College of Medicine Houston Texas 77030, United States
- Department of Food Science and Technology, University of Nebraska—Lincoln, Lincoln Nebraska 68588, United States
| | - Alexandra L. Chang-Graham
- Department of Molecular Virology and Microbiology, Baylor College of Medicine Houston Texas 77030, United States
| | - Wenly Ruan
- Department of Pathology & Immunology, Baylor College of Medicine Houston Texas 77030, United States
- Department of Pathology, Texas Children’s Hospital Houston Texas 77030, United States
| | - Ruth Ann Luna
- Department of Pathology & Immunology, Baylor College of Medicine Houston Texas 77030, United States
- Department of Pathology, Texas Children’s Hospital Houston Texas 77030, United States
| | - Joseph M. Hyser
- Department of Molecular Virology and Microbiology, Baylor College of Medicine Houston Texas 77030, United States
| | - Jennifer K. Spinler
- Department of Pathology & Immunology, Baylor College of Medicine Houston Texas 77030, United States
- Department of Pathology, Texas Children’s Hospital Houston Texas 77030, United States
| | - James Versalovic
- Department of Pathology & Immunology, Baylor College of Medicine Houston Texas 77030, United States
- Department of Pathology, Texas Children’s Hospital Houston Texas 77030, United States
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Immunogenicity and Protection from Receptor-Binding Domains of Toxins as Potential Vaccine Candidates for Clostridium difficile. Vaccines (Basel) 2019; 7:vaccines7040180. [PMID: 31717334 PMCID: PMC6963439 DOI: 10.3390/vaccines7040180] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Revised: 11/04/2019] [Accepted: 11/06/2019] [Indexed: 01/05/2023] Open
Abstract
The receptor-binding domains (RBDs) located in toxin A and toxin B of Clostridium difficile are known to be nontoxic and immunogenic. We need to develop a new type vaccine based on RBDs. In this study, we expressed and purified recombinant proteins (named RBD-TcdA and RBD-TcdB) as vaccine candidates containing the RBDs of toxin A and toxin B, respectively, from the C. difficile reference strain VPI10463. The immunogenicity and protection of the vaccine candidates RBD-TcdA, RBD-TcdB, and RBD-TcdA/B was evaluated by ELISA and survival assays. The data indicated that mice immunized with all vaccine candidates displayed potent levels of RBD-specific serum IgG. Following intramuscular immunization of mice with RBD-TcdA and/or RBD-TcdB, these vaccine candidates triggered immune responses that protected mice compared to mice immunized with aluminum hydroxide alone. Taken together, the results of this study reveal that recombinant proteins containing RBDs of C. difficile toxins can be used for vaccine development. Additionally, we found that an RBD-TcdA/B vaccine can elicit a stronger humoral immune response and provide better immunoprotection than the univalent vaccines. This RBD vaccine candidate conferred significant protection against disease symptoms and death caused by toxins from a wild-type C. difficile strain.
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Zhang D, Prabhu VS, Marcella SW. Attributable Healthcare Resource Utilization and Costs for Patients With Primary and Recurrent Clostridium difficile Infection in the United States. Clin Infect Dis 2019; 66:1326-1332. [PMID: 29360950 PMCID: PMC5905590 DOI: 10.1093/cid/cix1021] [Citation(s) in RCA: 82] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2017] [Accepted: 12/12/2017] [Indexed: 12/28/2022] Open
Abstract
Background The economic burden of Clostridium difficile infection (CDI), the leading cause of nosocomial infectious diarrhea, is not well understood. The objective of this study was to estimate the healthcare resource utilization (HCRU) and costs attributable to primary CDI and recurrent CDI (rCDI). Methods This is a database (MarketScan) study. Patients without CDI were matched 1:1 by propensity score to those with primary CDI but no recurrences to obtain HCRU and costs attributable to primary CDI. Patients with primary CDI but no recurrences were matched 1:1 by propensity score to those with primary CDI plus 1 recurrence in order to obtain HCRU and costs attributable to rCDI. Adjusted estimates for incremental cumulative hospitalized days and healthcare costs over a 6-month follow-up period were obtained by generalized linear models with a Poisson or gamma distribution and a log link. Bootstrapping was used to obtain 95% confidence intervals (CIs). Results A total of 55504 eligible CDI patients were identified. Approximately 25% of these CDI patients had rCDI. The cumulative hospitalized days attributable to primary CDI and rCDI over the 6-month follow-up period were 5.20 days (95% CI, 5.01–5.39) and 1.95 days (95% CI, 1.48–2.43), respectively. The healthcare costs attributable to primary CDI and rCDI over the 6-month follow-up period were $24205 (95% CI, $23436–$25013) and $10580 (95% CI, $8849–$12446), respectively. Conclusions The HCRU and costs attributable to primary CDI and rCDI are quite substantial. It is necessary to reduce the burden of CDI, especially rCDI.
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Affiliation(s)
- Dongmu Zhang
- Center for Observational and Real-World Evidence, Merck & Co, Inc, Kenilworth, New Jersey
| | - Vimalanand S Prabhu
- Center for Observational and Real-World Evidence, Merck & Co, Inc, Kenilworth, New Jersey
| | - Stephen W Marcella
- Center for Observational and Real-World Evidence, Merck & Co, Inc, Kenilworth, New Jersey
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Verheyen E, Dalapathi V, Arora S, Patel K, Mankal PK, Kumar V, Lung E, Kotler DP, Grinspan A. High 30-day readmission rates associated with Clostridiumdifficile infection. Am J Infect Control 2019; 47:922-927. [PMID: 30777388 DOI: 10.1016/j.ajic.2019.01.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Revised: 01/14/2019] [Accepted: 01/15/2019] [Indexed: 01/05/2023]
Abstract
BACKGROUND Clostridium difficile infection (CDI) is a leading cause of community-onset and healthcare-associated infection, with high recurrence rates, and associated high morbidity and mortality. We report national rates, leading causes, and predictors of hospital readmission for CDI. METHODS Retrospective study of data from the 2013 Nationwide Readmissions Database of patients with a primary diagnosis of CDI and re-hospitalization within 30-days. A multivariate regression model was used to identify predictors of readmission. RESULTS Of 38,409 patients admitted with a primary diagnosis of CDI, 21% were readmitted within 30-days, and 27% of those patients were readmitted with a primary diagnosis of CDI. Infections accounted for 47% of all readmissions. Female sex, anemia/coagulation defects, renal failure/electrolyte abnormalities and discharge to home (versus facility) were 12%, 13%, 15%, 36%, respectively, more likely to be readmitted with CDI. CONCLUSIONS We found that 1-in-5 patients hospitalized with CDI were readmitted to the hospital within 30-days. Infection comprised nearly half of these readmissions, with CDI being the most common etiology. Predictors of readmission with CDI include female sex, history of renal failure/electrolyte imbalances, anemia/coagulation defects, and being discharged home. CDI is associated with a high readmission risk, with evidence of several predictive risks for readmission.
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Yu SC, Lai AM, Smyer J, Flaherty J, Mangino JE, McAlearney AS, Yen PY, Moffatt-Bruce S, Hebert CL. Novel Visualization of Clostridium difficile Infections in Intensive Care Units. ACI OPEN 2019; 3:e71-e77. [PMID: 33598637 DOI: 10.1055/s-0039-1693651] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Accurate and timely surveillance and diagnosis of healthcare-facility onset Clostridium difficile infection (HO-CDI) is vital to controlling infections within the hospital, but there are limited tools to assist with timely outbreak investigations. OBJECTIVES To integrate spatiotemporal factors with HO-CDI cases and develop a map-based dashboard to support infection preventionists (IPs) in performing surveillance and outbreak investigations for HO-CDI. METHODS Clinical laboratory results and Admit-Transfer-Discharge data for admitted patients over two years were extracted from the Information Warehouse of a large academic medical center and processed according to Center for Disease Control (CDC) National Healthcare Safety Network (NHSN) definitions to classify Clostridium difficile infection (CDI) cases by onset date. Results were validated against the internal infection surveillance database maintained by IPs in Clinical Epidemiology of this Academic Medical Center (AMC). Hospital floor plans were combined with HO-CDI case data, to create a dashboard of intensive care units. Usability testing was performed with a think-aloud session and a survey. RESULTS The simple classification algorithm identified all 265 HO-CDI cases from 1/1/15-11/30/15 with a positive predictive value (PPV) of 96.3%. When applied to data from 2014, the PPV was 94.6% All users "strongly agreed" that the dashboard would be a positive addition to Clinical Epidemiology and would enable them to present Hospital Acquired Infection (HAI) information to others more efficiently. CONCLUSIONS The CDI dashboard demonstrates the feasibility of mapping clinical data to hospital patient care units for more efficient surveillance and potential outbreak investigations.
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Affiliation(s)
- Sean C Yu
- Washington University, St. Louis, MO, USA
| | | | - Justin Smyer
- Ohio State University Wexner Medical Center, Columbus, OH, USA
| | | | - Julie E Mangino
- Ohio State University Wexner Medical Center, Columbus, OH, USA
| | | | - Po-Yin Yen
- Washington University, St. Louis, MO, USA
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Peprah D, Chiu AS, Jean RA, Pei KY. Comparison of Outcomes Between Total Abdominal and Partial Colectomy for the Management of Severe, Complicated Clostridium Difficile Infection. J Am Coll Surg 2019; 228:925-930. [PMID: 30576799 PMCID: PMC6535364 DOI: 10.1016/j.jamcollsurg.2018.11.015] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2018] [Revised: 11/30/2018] [Accepted: 11/30/2018] [Indexed: 11/25/2022]
Abstract
BACKGROUND Patients with severe, complicated Clostridium difficile infection (CDI) may ultimately require a colectomy. Although associated with high morbidity and mortality, a total colectomy has been the mainstay of surgical treatment. However, small studies have suggested partial colectomy may provide equivalent outcomes. We compared the outcomes of partial and total colectomy for CDI in a nationwide database. STUDY DESIGN We performed a retrospective study using the American College of Surgeons National Surgical Quality Improvement Project (NSQIP). Patients with a primary diagnosis of Clostridium difficile colitis from 2007 to 2015, who underwent a total abdominal or partial colectomy, were analyzed. Postoperative mortality rate, complications, and length of stay were evaluated. Logistic regression controlling for patient and clinical factors evaluated the impact of type of operation performed. RESULTS There were 733 colectomies for CDI, of which 151 (20.6%) were partial colectomies. Patients with a partial colectomy had a slightly higher 30-day mortality rate (37.1%) compared with total abdominal colectomy patients (34.7%, p = 0.58). However, logistic regression controlling for patient factors demonstrated no statistically significant difference for partial colectomy in 30-day mortality (odds ratio [OR] 1.21, 95% CI 0.76 to 1.96) or complication rate (OR 0.92, 95% CI 0.51 to 1.62) compared with total colectomy. There was no difference in days to surgery (4.6 partial vs 5.0 total, p = 0.70). Total abdominal colectomy trended toward a longer postoperative stay (18.0 vs 15.1 days for partial, p = 0.08). CONCLUSIONS In a national database, a significant percentage of operations for CDI are partial colectomies. There were no significant differences found in mortality or complications between partial and total colectomy for severe complicated CDI.
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Affiliation(s)
- David Peprah
- Department of Surgery, Yale School of Medicine, New Haven, CT
| | | | - Raymond A Jean
- Department of Surgery, Yale School of Medicine, New Haven, CT; National Clinician Scholars Program, Department of Internal Medicine, Yale School of Medicine, New Haven, CT
| | - Kevin Y Pei
- Department of Surgery, Section of General Surgery, Trauma and Surgical Critical Care, Yale School of Medicine, New Haven, CT; Department of Surgery, Texas Tech University Health Sciences Center, Lubbock, TX.
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Han S, Soylu MC, Kirimli CE, Wu W, Sen B, Joshi SG, Emery CL, Au G, Niu X, Hamilton R, Krevolin K, Shih WH, Shih WY. Rapid, label-free genetic detection of enteropathogens in stool without genetic isolation or amplification. Biosens Bioelectron 2019; 130:73-80. [PMID: 30731348 PMCID: PMC6469511 DOI: 10.1016/j.bios.2019.01.025] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Revised: 12/22/2018] [Accepted: 01/12/2019] [Indexed: 12/13/2022]
Abstract
Current genetic detection methods require gene isolation, gene amplification and detection with a fluorescent-tagged probe. They typically require sophisticated equipment and expensive fluorescent probes, rendering them not widely available for rapid acute infection diagnoses at the point of care to ensure timely treatment of the diseases. Here we report a rapid genetic detection method that can detect the bacterial gene directly from patient stools using a piezoelectric plate sensor (PEPS) in conjunction with a continuous flow system with two temperature zones. With stools spiked with sodium dodecyl sulfate (SDS) in situ bacteria lysing and DNA denaturation occurred in the high-temperature zone whereas in situ specific detection of the denatured DNA by the PEPS occurred in the lower-temperature zone. The outcome was a rapid genetic detection method that directly detected bacterial genes from stool in < 40 min without the need of gene isolation, gene amplification, or expensive fluorescent tag but with polymerase chain reaction (PCR) sensitivity. In 40 blinded patient stools, it detected the toxin B gene of Clostridium difficile with 95% sensitivity and 95% specificity. The all-electrical, label-free nature of the detection further supports its potential as a low-cost genetic test that can be used at the point of care.
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Affiliation(s)
- Song Han
- School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, PA 19104, USA
| | - Mehmet C Soylu
- School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, PA 19104, USA
| | - Ceyhun E Kirimli
- School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, PA 19104, USA
| | - Wei Wu
- Department of Materials Science and Engineering, Drexel University, PA 19104, USA
| | - Bhaswati Sen
- Department of Microbiology and Immunology, Drexel University, Philadelphia, PA 10102, USA
| | - Suresh G Joshi
- Department of Microbiology and Immunology, Drexel University, Philadelphia, PA 10102, USA
| | | | - Giang Au
- School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, PA 19104, USA
| | - Xiaomin Niu
- School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, PA 19104, USA
| | - Richard Hamilton
- Department of Emergency Medicine, Drexel University, Philadelphia, PA 10102, USA
| | - Kyle Krevolin
- Microbiology & SIVM Laboratories, Hahnemann University Hospital, Philadelphia, PA 10102, USA
| | - Wei-Heng Shih
- Department of Materials Science and Engineering, Drexel University, PA 19104, USA
| | - Wan Y Shih
- School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, PA 19104, USA.
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Kelly CP, Chong Nguyen C, Palmieri LJ, Pallav K, Dowd SE, Humbert L, Seksik P, Bado A, Coffin B, Rainteau D, Kabbani T, Duboc H. Saccharomyces boulardii CNCM I-745 Modulates the Fecal Bile Acids Metabolism During Antimicrobial Therapy in Healthy Volunteers. Front Microbiol 2019; 10:336. [PMID: 30881353 PMCID: PMC6407479 DOI: 10.3389/fmicb.2019.00336] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Accepted: 02/08/2019] [Indexed: 02/04/2023] Open
Abstract
Saccharomyces boulardii CNCM I-745 (SB) is a probiotic yeast used to lower the incidence of antibiotic-associated Clostridium difficile (C. difficile) infection, though its mechanism of action remains unclear. Cholic acid is a primary bile acid, which triggers the germination and promotes the growth of C. difficile. The intestinal microbiota transforms primary into secondary bile acids. This study examined (1) the antimicrobial-induced alteration of fecal bile acid content, and (2) whether the concomitant administration of SB influences this transformation. This is an ancillary work from a randomized study, which revealed that SB modulates fecal microbiota dysbiosis during antibiotic treatment. Healthy subjects were randomly assigned to (1) SB only, (2) amoxicillin-clavulanate (AC), (3) SB plus AC, or (4) no treatment. We analyzed fecal concentrations of BA by high performance liquid chromatography/tandem mass spectrometry. Compared to the untreated or the SB-treated groups, AC decreased the percentage of fecal secondary BA significantly (days 3 and 7). When SB and AC were administered concomitantly, this decrease in secondary BA was no longer significant. Following treatment with AC, a significant peak of fecal CA was measured on days 3 and 7, which was prevented by the concomitant administration of SB. AC administered to healthy volunteers altered the microbial transformation of primary BA, decreased secondary BA, and increased CA. The latter was prevented by the concomitant administration of SB and AC, suggesting a potent mechanism protection conferred by SB against post-antimicrobial C. difficile infection. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT01473368.
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Affiliation(s)
- Ciaran Patrick Kelly
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | | | - Lola Jade Palmieri
- INSERM U1057, Université Pierre et Marie Curie, Paris, France
- Louis-Mourier Hospital, APHP – University Paris VII, Paris, France
| | - Kumar Pallav
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Scot E. Dowd
- Molecular Research, Shalltower, TX, United States
| | - Lydie Humbert
- INSERM U1057, Université Pierre et Marie Curie, Paris, France
| | - Philippe Seksik
- INSERM U1057, Université Pierre et Marie Curie, Paris, France
| | - Andre Bado
- Inserm UMR1149, DHU Unity – Paris Diderot University, Paris, France
| | - Benoit Coffin
- Inserm UMR1149, DHU Unity – Paris Diderot University, Paris, France
- Louis-Mourier Hospital, APHP – University Paris VII, Paris, France
| | | | - Toufic Kabbani
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Henri Duboc
- Inserm UMR1149, DHU Unity – Paris Diderot University, Paris, France
- Louis-Mourier Hospital, APHP – University Paris VII, Paris, France
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12
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Balsells E, Shi T, Leese C, Lyell I, Burrows J, Wiuff C, Campbell H, Kyaw MH, Nair H. Global burden of Clostridium difficile infections: a systematic review and meta-analysis. J Glob Health 2019; 9:010407. [PMID: 30603078 PMCID: PMC6304170 DOI: 10.7189/jogh.09.010407] [Citation(s) in RCA: 184] [Impact Index Per Article: 30.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Background Clostridium difficile is a leading cause of morbidity and mortality in several countries. However, there are limited evidence characterizing its role as a global public health problem. We conducted a systematic review to provide a comprehensive overview of C. difficile infections (CDI) rates. Methods Seven databases were searched (January 2016) to identify studies and surveillance reports published between 2005 and 2015 reporting CDI incidence rates. CDI incidence rates for health care facility-associated (HCF), hospital onset-health care facility-associated, medical or general intensive care unit (ICU), internal medicine (IM), long-term care facility (LTCF), and community-associated (CA) were extracted and standardized. Meta-analysis was conducted using a random effects model. Results 229 publications, with data from 41 countries, were included. The overall rate of HCF-CDI was 2.24 (95% confidence interval CI = 1.66-3.03) per 1000 admissions/y and 3.54 (95%CI = 3.19-3.92) per 10 000 patient-days/y. Estimated rates for CDI with onset in ICU or IM wards were 11.08 (95%CI = 7.19-17.08) and 10.80 (95%CI = 3.15-37.06) per 1000 admission/y, respectively. Rates for CA-CDI were lower: 0.55 (95%CI = 0.13-2.37) per 1000 admissions/y. CDI rates were generally higher in North America and among the elderly but similar rates were identified in other regions and age groups. Conclusions Our review highlights the widespread burden of disease of C. difficile, evidence gaps, and the need for sustainable surveillance of CDI in the health care setting and the community.
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Affiliation(s)
- Evelyn Balsells
- Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.,Joint first authorship
| | - Ting Shi
- Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.,Joint first authorship
| | - Callum Leese
- Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK
| | - Iona Lyell
- Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK
| | - John Burrows
- Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK
| | | | - Harry Campbell
- Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK
| | - Moe H Kyaw
- Sanofi Pasteur, Swiftwater, Pennsylvania, USA.,Joint last authorship
| | - Harish Nair
- Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.,Joint last authorship
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13
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Karamanos E, Gupta AH, Stanton CN, Mohamed A, Patton JH, Schmoekel N. Clostridium Difficile-Associated Infection in Trauma Patients: Development of the Clostridium Difficile Influencing Factors (CDIF) Score. Perm J 2019; 22:18-013. [PMID: 30201088 DOI: 10.7812/tpp/18-013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
CONTEXT Clostridium difficile-associated infection (CDAI) can result in longer hospitalization, increased morbidity, and higher mortality rates for surgical patients. The impact on trauma patients is unknown, however. OBJECTIVE To assess the effect of CDAI on trauma patients and develop a scoring system to predict CDAI in that population. METHODS Records of all trauma patients admitted to a Level I Trauma Center from 2001 to 2014 were retrospectively reviewed. Presence of CDAI was defined as evidence of positive toxin or polymerase chain reaction. Patients with CDAI were matched to patients without CDAI using propensity score matching on a ratio of 1:3. MAIN OUTCOME MEASURES Primary outcome was inhospital mortality. Secondary outcomes included length of stay and need for mechanical ventilation. A decision-tree analysis was performed to develop a predicting model for CDAI in the study population. RESULTS During the study period, 11,016 patients were identified. Of these, 50 patients with CDAI were matched to 150 patients without CDAI. There were no differences in admission characteristics and demographics. Patients in whom CDAI developed had significantly higher mortality (12% vs 4%, p < 0.01), need for mechanical ventilation (57% vs 23%, p < 0.01), and mean hospital length of stay (15.3 [standard deviation 1.4]) days vs 2.1 [0.6] days, p < 0.0). CONCLUSION In trauma patients, CDAI results in significant morbidity and mortality. The C difficile influencing factor score is a useful tool in identifying patients at increased risk of CDAI.
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Affiliation(s)
- Efstathios Karamanos
- Surgeon in the Division of Acute Care Surgery in the Department of Surgery at Henry Ford Hospital in Detroit, MI
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14
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Cho JC, Crotty MP, Pardo J. Ridinilazole: a novel antimicrobial for Clostridium difficile infection. Ann Gastroenterol 2018; 32:134-140. [PMID: 30837785 PMCID: PMC6394264 DOI: 10.20524/aog.2018.0336] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Accepted: 11/07/2018] [Indexed: 12/12/2022] Open
Abstract
Clostridium difficile (C. difficile) infection remains a global healthcare threat worldwide and the limited options available for its treatment are of particular concern. Ridinilazole is one potential future agent, as it demonstrates rapid bactericidal activity against C. difficile. Current studies show that ridinilazole has a lower propensity for collateral damage to the gut microbiome and appears to diminish the production of C. difficile toxins. Results from phase II studies demonstrate that patients receiving ridinilazole had a higher sustained clinical response compared with patients receiving vancomycin (66.7% vs. 42.4%; P=0.0004). Adverse reactions were similar between ridinilazole and vancomycin (40% vs. 56%, respectively), with most being gastrointestinal-related. Nausea (20%) and abdominal pain (12%) were the most commonly reported adverse reactions associated with ridinilazole. Phase II study results are promising and future availability of phase III trial results will help further delineate the role and value of ridinilazole.
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Affiliation(s)
- Jonathan C Cho
- College of Pharmacy, The University of Texas at Tyler, Tyler, TX (Jonathan C. Cho), USA
| | - Matthew P Crotty
- Department of Pharmacy, Methodist Dallas Medical Center, Dallas, TX (Matthew P. Crotty), USA
| | - Joe Pardo
- Department of Pharmacy, North FL/South GA Veterans Health System, Gainesville, FL (Joe Pardo), USA
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15
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ASID/ACIPC position statement - Infection control for patients with Clostridium difficile infection in healthcare facilities. Infect Dis Health 2018; 24:32-43. [PMID: 30691583 DOI: 10.1016/j.idh.2018.10.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2018] [Revised: 10/08/2018] [Accepted: 10/08/2018] [Indexed: 01/05/2023]
Abstract
BACKGROUND In 2011, the Australasian Society for Infectious Diseases (ASID) and the Australian Infection Control Association (AICA), now known as the Australasian College of Infection Prevention and Control (ACIPC), produced a position statement on infection control requirements for preventing and controlling Clostridium difficile infection (CDI) in healthcare settings. METHODS The statement updated in 2017 to reflect new literature available .The authors reviewed the 2011 position statement and critically appraised new literature published between 2011 and 2017 and relevant current infection control guidelines to identify where new evidence had become available or best practice had changed. RESULTS The position statement was updated incorporating the new findings. A draft version of the updated position statement was circulated for consultation to members of ASID and ACIPC. The authors responded to all comments received and updated the position statement. CONCLUSIONS This updated position statement emphasizes the importance of health service organizations having evidence-based infection prevention and control programs and comprehensive antimicrobial stewardship programs, to ensure the risk of C. difficile acquisition, transmission and infection is minimised.
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16
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Clinical, operational, and financial impact of an ultraviolet-C terminal disinfection intervention at a community hospital. Am J Infect Control 2018; 46:1224-1229. [PMID: 29934205 DOI: 10.1016/j.ajic.2018.05.012] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2018] [Revised: 05/17/2018] [Accepted: 05/17/2018] [Indexed: 11/20/2022]
Abstract
BACKGROUND Hospital-acquired infections (HAIs) are a significant contributor to adverse patient outcomes and excess cost of inpatient care. Adjunct ultraviolet-C (UV-C) disinfection may be a viable strategy for reducing HAIs. This study aimed to measure the clinical, operational, and financial impact of a UV-C terminal disinfection intervention in a community hospital setting. METHODS Using a pre-post study design, we compared the HAI rates of 5 multidrug-resistant bacteria (Acinetobacter baumannii, Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and Pseudomonas aeruginosa) from 6 culture sites before and after a 12-month facility-wide UV-C intervention. To measure impact of UV-C disinfection on hospital operations, mean inpatient emergency room wait time was calculated. Finally, we conducted a cost saving analysis to evaluate the financial benefits of the intervention. RESULTS Overall, 245 HAIs among 13,177 inpatients were observed during a 12-month intervention period, with an incidence rate of 3.94 per 1,000 patient days. This observed HAIs incidence was 19.2% lower than the preintervention period (4.87 vs 3.94 per 1,000 patient days; P = .006). The intervention did not adversely impact emergency department admissions (297.9 vs 296.2 minutes; P = .18) and generated a direct cost savings of $1,219,878 over a 12-month period. CONCLUSIONS The UV-C disinfection intervention was associated with a statistically significant facility-wide reduction of multidrug-resistant HAIs and generated substantial direct cost savings without adversely impacting hospital operations.
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17
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Al-Mazrou AM, Hyde LZ, Suradkar K, Kiran RP. Effect of Inclusion of Oral Antibiotics with Mechanical Bowel Preparation on the Risk of Clostridium Difficile Infection After Colectomy. J Gastrointest Surg 2018; 22:1968-1975. [PMID: 29967968 DOI: 10.1007/s11605-018-3837-3] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2018] [Accepted: 06/02/2018] [Indexed: 01/31/2023]
Abstract
BACKGROUND/PURPOSE While the use of oral antibiotic (OA) for bowel preparation is gaining popularity, it is unknown whether it increases the risk of Clostridium difficile infection (CDI). This study aimed to evaluate the impact of OA on the development of CDI after colectomy. METHODS Patients who underwent colectomy from the ACS-NSQIP data (2015 and 2016) were included. Patients who received OA as bowel preparation were compared to those who did not with respect to demographics, comorbidities, primary diagnosis, procedure type and approach, and 30-day postoperative complications. Multivariable analysis was performed to characterize the association between OA and CD infection after colectomy. A sub-group analysis was also conducted for patients who did not develop any postoperative infectious complication. RESULTS Of 36,374 included patients, 18,177 (50%) received OA and 527 (1.4%) developed CDI for the whole cohort. OA group had more younger, functionally independent and obese patients with lower American Society of Anesthesiologists and wound class. Smoking, diabetes, hypertension, dyspnea or ventilator-dependence, congestive heart failure, disseminated cancer, bleeding disorder, and perioperative transfusion were significantly higher for non-OA group. Mechanical bowel preparation, minimally invasive surgery, conversion to open and operative duration ≥ 180 min were more prevalent in the OA group. The OA group had significantly reduced occurrence of CDI; superficial, deep, and organ space infections; wound disruption; anastomotic leak; reoperation; and infections including sepsis, septic shock, pneumonia, and urinary tract infection. On multivariable analysis, OA reduced the odds for CDI after colectomy (OR = 0.6, 95% CI = [0.5-0.8]). For patients who did not develop infectious postoperative complications, OA was associated with lower risk of CDI (OR = 0.7, CI = [0.5-0.9]). While complications, reoperation, and readmission rates were the same, postoperative ileus and hospital stay were significantly lower for those who developed CDI after receiving OA when compared to non-OA. CONCLUSION The use of OA as bowel preparation may reduce, rather than increase, the risk of 30-day CDI after colectomy. This effect may partly be due to the other recovery advantages associated with oral antibiotics. These data further support current data recommending the use of oral antibiotics for bowel preparation before colectomy.
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Affiliation(s)
- Ahmed M Al-Mazrou
- Division of Colorectal Surgery, Herbert Irving Pavilion, New York-Presbyterian Hospital/Columbia University Medical Center, 161 Fort Washington Avenue, Floor 8, New York, NY, 10032, USA
| | - Laura Z Hyde
- Division of Colorectal Surgery, Herbert Irving Pavilion, New York-Presbyterian Hospital/Columbia University Medical Center, 161 Fort Washington Avenue, Floor 8, New York, NY, 10032, USA
| | - Kunal Suradkar
- Division of Colorectal Surgery, Herbert Irving Pavilion, New York-Presbyterian Hospital/Columbia University Medical Center, 161 Fort Washington Avenue, Floor 8, New York, NY, 10032, USA
| | - Ravi P Kiran
- Division of Colorectal Surgery, Herbert Irving Pavilion, New York-Presbyterian Hospital/Columbia University Medical Center, 161 Fort Washington Avenue, Floor 8, New York, NY, 10032, USA.
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18
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Silvetti S, Landoni G. Is Clostridium difficile the new bugaboo after cardiac surgery? J Thorac Dis 2018; 10:S3278-S3280. [PMID: 30370137 DOI: 10.21037/jtd.2018.08.99] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Simona Silvetti
- Department of Pediatric Intensive Care Unit and Cardiac Anesthesia, IRCCS Giannina Gaslini Institute, Genoa, Italy
| | - Giovanni Landoni
- Department of Cardiac Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
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19
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Effect of the Synthetic Bile Salt Analog CamSA on the Hamster Model of Clostridium difficile Infection. Antimicrob Agents Chemother 2018; 62:AAC.02251-17. [PMID: 30012758 DOI: 10.1128/aac.02251-17] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Accepted: 07/01/2018] [Indexed: 12/15/2022] Open
Abstract
Clostridium difficile infection (CDI) is the leading cause of antibiotic-associated diarrhea and has gained worldwide notoriety due to emerging hypervirulent strains and the high incidence of recurrence. We previously reported protection of mice from CDI using the antigerminant bile salt analog CamSA. Here we describe the effects of CamSA in the hamster model of CDI. CamSA treatment of hamsters showed no toxicity and did not affect the richness or diversity of gut microbiota; however, minor changes in community composition were observed. Treatment of C. difficile-challenged hamsters with CamSA doubled the mean time to death, compared to control hamsters. However, CamSA alone was insufficient to prevent CDI in hamsters. CamSA in conjunction with suboptimal concentrations of vancomycin led to complete protection from CDI in 70% of animals. Protected animals remained disease-free at least 30 days postchallenge and showed no signs of colonic tissue damage. In a delayed-treatment model of hamster CDI, CamSA was unable to prevent infection signs and death. These data support a putative model in which CamSA reduces the number of germinating C. difficile spores but does not keep all of the spores from germinating. Vancomycin halts division of any vegetative cells that are able to grow from spores that escape CamSA.
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20
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A Retrospective Study Analyzing the Appropriateness of Initial Treatment of Clostridium difficile in Patients with Active Malignancy. Gastroenterol Res Pract 2018; 2018:7192728. [PMID: 29991944 PMCID: PMC5994314 DOI: 10.1155/2018/7192728] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2017] [Accepted: 04/19/2018] [Indexed: 01/05/2023] Open
Abstract
Background Clostridium difficile infection (CDI) is the leading cause of hospital-associated gastrointestinal illness. Previous studies reported that patients with active malignancy are at high risk for CDIs, and yet they are still classified as nonsevere CDI and initially treated with metronidazole. Our aim is to investigate the need for the escalation of antibiotic therapy in patients with CDI and active cancer treated with oral metronidazole versus oral vancomycin. Methods This is a retrospective study of adult patients admitted with CDI and any underlying active malignancy at Beaumont Hospital, Royal Oak, Michigan, from January 2008 to December 2014. Inclusion criteria included age > 18 years old, polymerase chain reaction- (PCR-) proven CDI, and active malignancy. Results 197 patients were included in the final analysis. 44.8% of the metronidazole group required escalation of therapy compared to 15.2% in the vancomycin group (p value = 0.001). 29.8% of the combination group (metronidazole and vancomycin) underwent deescalation of antibiotics, which was significantly higher compared to 2.2% of patients in the vancomycin group (p value < 0.001). Discussion Our results support the initial use of vancomycin or a combination (metronidazole and vancomycin) versus metronidazole in patients with CDI and active malignancy.
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21
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Delanois RE, George NE, Etcheson JI, Gwam CU, Mistry JB, Mont MA. Risk Factors and Costs Associated With Clostridium difficile Colitis in Patients With Prosthetic Joint Infection Undergoing Revision Total Hip Arthroplasty. J Arthroplasty 2018; 33:1534-1538. [PMID: 29273290 DOI: 10.1016/j.arth.2017.11.035] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2017] [Revised: 11/13/2017] [Accepted: 11/20/2017] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND With the increased demand for primary total hip arthroplasty (THA) and corresponding rise in revision procedures, it is imperative to understand the factors contributing to the development of Clostridium difficile colitis. We aimed to provide a detailed analysis of: (1) the incidence of; (2) the demographics, lengths of stay, and total costs for; and (3) the risk factors and mortality associated with the development of C. difficile colitis after revision THA. METHODS The National Inpatient Sample database was queried for all individuals diagnosed with a periprosthetic joint infection and who underwent all-component revision THA between 2009 and 2013 (n = 40,876). Patients who developed C. difficile colitis during their inpatient hospital stay were identified. Multilevel logistic regression analysis was conducted to assess the association between hospital- and patient-specific characteristics and the development of C. difficile colitis. RESULTS The overall incidence of C. difficile colitis after revision THA was 1.7%. These patients were significantly older (74 vs 65 years), had greater lengths of hospital stay (19 vs 9 days), accumulated greater costs ($51,641 vs $28,282), and were more often treated in an urban hospital compared to their counterparts who did not develop C. difficile colitis (P < .001 for all). Patients with colitis also had a significantly higher in-hospital mortality compared to those without (5.6% vs 1.4%; P < .001). CONCLUSION While C. difficile colitis infection is an uncommon event following revision THA, it can have potentially devastating consequences. Our analysis demonstrates that this infection is associated with a longer hospital stay, higher costs, and greater in-hospital mortality.
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Affiliation(s)
- Ronald E Delanois
- Rubin Institute for Advanced Orthopedics, Center for Joint Preservation and Replacement, Sinai Hospital of Baltimore, Baltimore, Maryland
| | - Nicole E George
- Rubin Institute for Advanced Orthopedics, Center for Joint Preservation and Replacement, Sinai Hospital of Baltimore, Baltimore, Maryland
| | - Jennifer I Etcheson
- Rubin Institute for Advanced Orthopedics, Center for Joint Preservation and Replacement, Sinai Hospital of Baltimore, Baltimore, Maryland
| | - Chukwuweike U Gwam
- Rubin Institute for Advanced Orthopedics, Center for Joint Preservation and Replacement, Sinai Hospital of Baltimore, Baltimore, Maryland
| | - Jaydev B Mistry
- Department of Orthopaedic Surgery, SUNY Downstate Medical Center, Brooklyn, New York
| | - Michael A Mont
- Department of Orthopaedic Surgery, Cleveland Clinic, Cleveland, Ohio
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Claeys KC, Hopkins TL, Vega AD, Heil EL. Fluoroquinolone Restriction as an Effective Antimicrobial Stewardship Intervention. Curr Infect Dis Rep 2018; 20:7. [PMID: 29572691 DOI: 10.1007/s11908-018-0615-z] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
PURPOSE OF REVIEW Fluoroquinolones are a commonly prescribed antibiotic class that has come under scrutiny in recent years due to mounting evidence of association between adverse drug events, C. difficile infection and isolation of antibiotic-resistant bacteria. RECENT FINDINGS Inpatient antimicrobial stewardship (AMS) programs have a toolbox of potential interventions to curb inappropriate antibiotic use, prevent antibiotic-associated adverse drug events, and avoid unnecessary costs of care. Fluoroquinolone restriction policies in the acute care setting have demonstrated beneficial effects, including decreased rates of C. difficile infection and ESBL-producing Enterobacteriaceae. However, a simple blanket restriction policy may "squeeze the antibiotic balloon" and will likely be insufficient if not implemented in conjunction with other AMS interventions. There is a growing body of evidence to support formulary restriction of fluoroquinolones in the acute care setting to decrease rates of C. difficile infection and development of ESBL-producing organisms. Data on how to best implement these restrictions or how to implement outside of acute care settings is limited.
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Affiliation(s)
- Kimberly C Claeys
- Department of Pharmacy Practice and Science, University of Maryland School of Pharmacy, N423, Baltimore, MD, 21201, USA. .,Department of Pharmacy, University of Maryland Medical Center, Baltimore, MD, USA.
| | - Teri L Hopkins
- Department of Pharmacy, South Texas Veterans Health Care System, San Antonio, TX, USA
| | - Ana D Vega
- Department of Pharmacy Practice and Science, University of Maryland School of Pharmacy, N423, Baltimore, MD, 21201, USA
| | - Emily L Heil
- Department of Pharmacy Practice and Science, University of Maryland School of Pharmacy, N423, Baltimore, MD, 21201, USA.,Department of Pharmacy, University of Maryland Medical Center, Baltimore, MD, USA
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23
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Deshpande A, Pant C, Olyaee M, Donskey CJ. Hospital readmissions related to Clostridium difficile infection in the United States. Am J Infect Control 2018; 46:346-347. [PMID: 29050906 DOI: 10.1016/j.ajic.2017.08.043] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2017] [Revised: 08/29/2017] [Accepted: 08/29/2017] [Indexed: 11/17/2022]
Abstract
Using a national readmissions database, we report a significant burden of Clostridium difficile-associated readmissions in the United States manifested as a high rate of rehospitalizations and substantial hospital stays and costs.
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Affiliation(s)
- Abhishek Deshpande
- Medicine Institute Center for Value Based Care, Cleveland Clinic, Cleveland, OH; Department of Infectious Diseases, Medicine Institute, Cleveland Clinic, Cleveland, OH
| | - Chaitanya Pant
- Division of Gastroenterology, Hepatology and Motility, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS.
| | - Mojtaba Olyaee
- Division of Gastroenterology, Hepatology and Motility, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS
| | - Curtis J Donskey
- Geriatric Research, Education and Clinical Center, Cleveland Veterans Affairs Medical Center, Cleveland, OH
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24
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Yanke E, Moriarty H, Carayon P, Safdar N. A qualitative, interprofessional analysis of barriers to and facilitators of implementation of the Department of Veterans Affairs' Clostridium difficile prevention bundle using a human factors engineering approach. Am J Infect Control 2018; 46:276-284. [PMID: 29269166 DOI: 10.1016/j.ajic.2017.08.027] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Revised: 08/22/2017] [Accepted: 08/22/2017] [Indexed: 11/16/2022]
Abstract
BACKGROUND Clostridium difficile infection (CDI) is increasingly prevalent, severe, and costly. Adherence to infection prevention practices remains suboptimal. More effective strategies to implement guidelines and evidence are needed. METHODS Interprofessional focus groups consisting of physicians, resident physicians, nurses, and health technicians were conducted for a quality improvement project evaluating adherence to the Department of Veterans Affairs' (VA) nationally mandated C difficile prevention bundle. Qualitative analysis with a visual matrix display identified barrier and facilitator themes guided by the Systems Engineering Initiative for Patient Safety model, a human factors engineering approach. RESULTS Several themes, encompassing both barriers and facilitators to bundle adherence, emerged. Rapid turnaround time of C difficile polymerase chain reaction testing was a facilitator of timely diagnosis. Too few, poorly located, and cluttered sinks were barriers to appropriate hand hygiene. Patient care workload and the time-consuming process of contact isolation precautions were also barriers to adherence. Multiple work system components serve as barriers to and facilitators of adherence to the VA CDI prevention bundle among an interprofessional group of health care workers. Organizational factors appear to significantly influence bundle adherence. CONCLUSION Interprofessional perspectives are needed to identify barriers to and facilitators of bundle implementation, which is a necessary first step to address adherence to bundled infection prevention practices.
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Affiliation(s)
- Eric Yanke
- Department of Medicine, William S. Middleton Memorial Veterans Hospital, Madison, WI
| | - Helene Moriarty
- Villanova University College of Nursing, Villanova, PA; Department of Nursing, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA
| | - Pascale Carayon
- Department of Industrial and Systems Engineering, Center for Quality and Productivity Improvement, University of Wisconsin-Madison, Madison, WI
| | - Nasia Safdar
- Department of Medicine, William S. Middleton Memorial Veterans Hospital and Division of Infectious Diseases, Madison, WI; University of Wisconsin Medical School and Infection Control Department, University of Wisconsin-Madison, Madison, WI.
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25
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Reveles KR, Backo JL, Corvino FA, Zivkovic M, Broderick KC. Fidaxomicin versus Vancomycin as a First-Line Treatment for Clostridium difficile-Associated Diarrhea in Specific Patient Populations: A Pharmacoeconomic Evaluation. Pharmacotherapy 2017; 37:1489-1497. [PMID: 29044643 PMCID: PMC11323253 DOI: 10.1002/phar.2049] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
OBJECTIVES The reduction in recurrent Clostridium difficile-associated diarrhea (CDAD) with fidaxomicin therapy may reduce hospital readmissions and lead to lower overall CDAD costs. However, studies assessing the cost-effectiveness of fidaxomicin as first-line therapy from the U.S. hospital perspective are lacking. This study evaluated the costs associated with utilizing fidaxomicin or vancomycin as a first-line therapy for CDAD in specific patient populations from a U.S. hospital perspective. METHODS A decision-analytic model was developed to estimate total costs (hospitalization and drug costs) associated with using fidaxomicin or vancomycin as first-line therapy for a first episode and up to two recurrences of CDAD in five patient populations: general population, elderly, patients receiving concomitant antibiotics, and patients with renal impairment or cancer. RESULTS The total cost of CDAD treatment using fidaxomicin first line in the general population was $14,442 per patient versus $14,179 per patient with vancomycin first line. In subgroup analyses, fidaxomicin use resulted in total hospital cost savings of $616 per patient in patients with cancer and $312 in patients with concomitant antibiotic use; vancomycin use was associated with total hospital cost savings of $243 per patient in the elderly and $371 in patients with renal impairment. CONCLUSIONS Fidaxomicin as first-line CDAD therapy is associated with similar total costs as compounded vancomycin oral solution in the general population. In elderly and renally impaired patients, slight increases in hospital cost were observed with fidaxomicin therapy, and in patients with cancer or concomitant antibiotic use, hospital cost savings were observed.
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Affiliation(s)
- Kelly R. Reveles
- College of Pharmacy, The University of Texas at Austin, Austin, Texas
- Pharmacotherapy Education and Research Center, University of Texas Health Science Center at San Antonio, San Antonio, Texas
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Attributable Cost of Clostridium difficile Infection in Pediatric Patients. Infect Control Hosp Epidemiol 2017; 38:1472-1477. [PMID: 29173236 DOI: 10.1017/ice.2017.240] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
OBJECTIVES The attributable cost of Clostridium difficile infection (CDI) in children is unknown. We sought to determine a national estimate of attributable cost and length of stay (LOS) of CDI occurring during hospitalization in children. DESIGN AND METHODS We analyzed discharge records of patients between 2 and 18 years of age from the Agency for Healthcare Research and Quality (AHRQ) Kids' Inpatient Database. We created a logistic regression model to predict CDI during hospitalization based on demographic and clinical characteristics. Predicted probabilities from the logistic regression model were then used as propensity scores to match 1:2 CDI to non-CDI cases. Charges were converted to costs and compared between patients with CDI and propensity-score-matched controls. In a sensitivity analysis, we adjusted for LOS as a confounder by including it in both the propensity score and a generalized linear model predicting cost. RESULTS We identified 8,527 pediatric hospitalizations (0.53%) with a diagnosis of CDI and 1,597,513 discharges without CDI. In our matched cohorts, the attributable cost of CDI occurring during a hospitalization ranged from $1,917 to $8,317, depending on whether model was adjusted for LOS. When not adjusting for LOS, CDI-associated hospitalizations cost 1.6 times more than non-CDI associated hospitalizations. Attributable LOS of CDI was approximately 4 days. CONCLUSIONS Clostridium difficile infection in hospitalized children is associated with an economic burden similar to adult estimates. This finding supports a continued focus on preventing CDI in children as a priority. Pediatric CDI cost analyses should account for LOS as an important confounder of cost. Infect Control Hosp Epidemiol 2017;38:1472-1477.
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Chintanaboina J, Navabi S, Suchniak-Mussari K, Stern B, Bedi S, Lehman EB, Tinsley A. Predictors of 30-Day Mortality in Hospitalized Patients with Clostridium difficile Infection. South Med J 2017; 110:546-549. [PMID: 28771654 DOI: 10.14423/smj.0000000000000687] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
OBJECTIVES Clostridium difficile infection (CDI) is a significant cause of morbidity and mortality and is the most common nosocomial infection in the United States, with associated annual costs of approximately $3 billion. The epidemiology of CDI has changed with the identification of novel risk factors for incident and recurrent CDI. The aim of this study was to identify the predictors of 30-day mortality in hospitalized patients with CDI. METHODS We identified all of the patients diagnosed as having CDI from January 2011 to December 2014 at our university-setting hospital. Data were extracted using electronic medical records and chart review. The data of all of the patients who died within 30 days of incident CDI were compared with those who survived beyond 30 days of incident CDI. A multivariable logistic regression model was created for mortality after finding a subset of significant predictor variables by making bivariate comparisons also using logistic regression. RESULTS A total of 893 patients were diagnosed as having CDI during the study period. The mean age was 62 years and 49.5% were women. The mean length of hospital stay was 11.73 days. Of the 893 patients with CDI, 98 (10.97%) died within 30 days of incident CDI. CDI recurrence was noted in 76 patients (8.51%). On multivariate logistic regression analysis, peptic ulcer disease, advanced age, Charlson comorbidity index, and intensive care unit status were found to be significantly associated with 30-day mortality. There was no significant association between acid suppression and CDI mortality. CONCLUSIONS Advanced age, Charlson comorbidity index, intensive care unit status, and peptic ulcer disease are predictors of all-cause 30-day mortality in hospitalized patients with CDI.
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Affiliation(s)
- Jayakrishna Chintanaboina
- From the Department of Gastroenterology, Division of General Internal Medicine, Penn State Hershey Medical Center, Hershey, Pennsylvania
| | - Seyedehsan Navabi
- From the Department of Gastroenterology, Division of General Internal Medicine, Penn State Hershey Medical Center, Hershey, Pennsylvania
| | - Kristen Suchniak-Mussari
- From the Department of Gastroenterology, Division of General Internal Medicine, Penn State Hershey Medical Center, Hershey, Pennsylvania
| | - Benjamin Stern
- From the Department of Gastroenterology, Division of General Internal Medicine, Penn State Hershey Medical Center, Hershey, Pennsylvania
| | - Simranjit Bedi
- From the Department of Gastroenterology, Division of General Internal Medicine, Penn State Hershey Medical Center, Hershey, Pennsylvania
| | - Erik B Lehman
- From the Department of Gastroenterology, Division of General Internal Medicine, Penn State Hershey Medical Center, Hershey, Pennsylvania
| | - Andrew Tinsley
- From the Department of Gastroenterology, Division of General Internal Medicine, Penn State Hershey Medical Center, Hershey, Pennsylvania
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Shen NT, Leff JA, Schneider Y, Crawford CV, Maw A, Bosworth B, Simon MS. Cost-Effectiveness Analysis of Probiotic Use to Prevent Clostridium difficile Infection in Hospitalized Adults Receiving Antibiotics. Open Forum Infect Dis 2017; 4:ofx148. [PMID: 29230429 PMCID: PMC5692276 DOI: 10.1093/ofid/ofx148] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2017] [Accepted: 07/17/2017] [Indexed: 02/07/2023] Open
Abstract
Background Systematic reviews with meta-analyses and meta-regression suggest that timely probiotic use can prevent Clostridium difficile infection (CDI) in hospitalized adults receiving antibiotics, but the cost effectiveness is unknown. We sought to evaluate the cost effectiveness of probiotic use for prevention of CDI versus no probiotic use in the United States. Methods We programmed a decision analytic model using published literature and national databases with a 1-year time horizon. The base case was modeled as a hypothetical cohort of hospitalized adults (mean age 68) receiving antibiotics with and without concurrent probiotic administration. Projected outcomes included quality-adjusted life-years (QALYs), costs (2013 US dollars), incremental cost-effectiveness ratios (ICERs; $/QALY), and cost per infection avoided. One-way, two-way, and probabilistic sensitivity analyses were conducted, and scenarios of different age cohorts were considered. The ICERs less than $100000 per QALY were considered cost effective. Results Probiotic use dominated (more effective and less costly) no probiotic use. Results were sensitive to probiotic efficacy (relative risk <0.73), the baseline risk of CDI (>1.6%), the risk of probiotic-associated bactermia/fungemia (<0.26%), probiotic cost (<$130), and age (>65). In probabilistic sensitivity analysis, at a willingness-to-pay threshold of $100000/QALY, probiotics were the optimal strategy in 69.4% of simulations. Conclusions Our findings suggest that probiotic use may be a cost-effective strategy to prevent CDI in hospitalized adults receiving antibiotics age 65 or older or when the baseline risk of CDI exceeds 1.6%.
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Affiliation(s)
- Nicole T Shen
- Division of Gastroenterology and Hepatology, Department of Medicine
| | - Jared A Leff
- Department of Healthcare Policy and Research, and
| | | | - Carl V Crawford
- Division of Gastroenterology and Hepatology, Department of Medicine
| | - Anna Maw
- Hospitalist Medicine Section, Division of General Internal Medicine, Department of Medicine, University of Colorado, Denver
| | - Brian Bosworth
- Division of Gastroenterology, Department of Medicine, New York University, New York
| | - Matthew S Simon
- Department of Healthcare Policy and Research, and.,Division of Infectious Diseases, Department of Medicine, Weill Cornell Medical College, New York, New York
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Tian JH, Glenn G, Flyer D, Zhou B, Liu Y, Sullivan E, Wu H, Cummings JF, Elllingsworth L, Smith G. Clostridium difficile chimeric toxin receptor binding domain vaccine induced protection against different strains in active and passive challenge models. Vaccine 2017; 35:4079-4087. [DOI: 10.1016/j.vaccine.2017.06.062] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2017] [Revised: 06/19/2017] [Accepted: 06/20/2017] [Indexed: 12/17/2022]
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Housman E, Livings SE, Knee A, Schimmel J. Improving Management of Hospitalized Adults With Uncomplicated Cellulitis or Cutaneous Abscess. Open Forum Infect Dis 2017; 4:ofx094. [PMID: 29497628 PMCID: PMC5781223 DOI: 10.1093/ofid/ofx094] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2017] [Accepted: 06/08/2017] [Indexed: 01/03/2023] Open
Abstract
Implementation of a guideline for the management of hospitalized adults with uncomplicated skin and soft-tissue infections may decrease unnecessary antibiotic use. For cellulitis, treatment with vancomycin and broad-spectrum antibiotics decreased significantly. For cutaneous abscess, treatment with broad-spectrum antibiotics decreased significantly. There were no differences in rates of treatment failure, recurrence, or adverse events.
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Affiliation(s)
| | - Sarah E Livings
- Department of Pharmacy, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania
| | | | - Jennifer Schimmel
- Division of Infectious Diseases, Baystate Medical Center, Springfield, Massachusetts; and
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Shen NT, Maw A, Tmanova LL, Pino A, Ancy K, Crawford CV, Simon MS, Evans AT. Timely Use of Probiotics in Hospitalized Adults Prevents Clostridium difficile Infection: A Systematic Review With Meta-Regression Analysis. Gastroenterology 2017; 152:1889-1900.e9. [PMID: 28192108 DOI: 10.1053/j.gastro.2017.02.003] [Citation(s) in RCA: 196] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2016] [Revised: 01/28/2017] [Accepted: 02/03/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS Systematic reviews have provided evidence for the efficacy of probiotics in preventing Clostridium difficile infection (CDI), but guidelines do not recommend probiotic use for prevention of CDI. We performed an updated systematic review to help guide clinical practice. METHODS We searched MEDLINE, EMBASE, International Journal of Probiotics and Prebiotics, and The Cochrane Library databases for randomized controlled trials evaluating use of probiotics and CDI in hospitalized adults taking antibiotics. Two reviewers independently extracted data and assessed risk of bias and overall quality of the evidence. Primary and secondary outcomes were incidence of CDI and adverse events, respectively. Secondary analyses examined the effects of probiotic species, dose, timing, formulation, duration, and study quality. RESULTS We analyzed data from 19 published studies, comprising 6261 subjects. The incidence of CDI in the probiotic cohort, 1.6% (54 of 3277), was lower than of controls, 3.9% (115 of 2984) (P < .001). The pooled relative risk of CDI in probiotic users was 0.42 (95% confidence interval, 0.30-0.57; I2 = 0.0%). Meta-regression analysis demonstrated that probiotics were significantly more effective if given closer to the first antibiotic dose, with a decrement in efficacy for every day of delay in starting probiotics (P = .04); probiotics given within 2 days of antibiotic initiation produced a greater reduction of risk for CDI (relative risk, 0.32; 95% confidence interval, 0.22-0.48; I2 = 0%) than later administration (relative risk, 0.70; 95% confidence interval, 0.40-1.23; I2 = 0%) (P = .02). There was no increased risk for adverse events among patients given probiotics. The overall quality of the evidence was high. CONCLUSIONS In a systematic review with meta-regression analysis, we found evidence that administration of probiotics closer to the first dose of antibiotic reduces the risk of CDI by >50% in hospitalized adults. Future research should focus on optimal probiotic dose, species, and formulation. Systematic Review Registration: PROSPERO CRD42015016395.
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Affiliation(s)
- Nicole T Shen
- Division of Gastroenterology and Hepatology, Weill Department of Medicine, Weill Cornell Medicine, New York, New York.
| | - Anna Maw
- Hospitalist Medicine Section, Division of General Internal Medicine, Department of Medicine, University of Colorado, Denver, Colorado
| | - Lyubov L Tmanova
- Samuel J. Wood Library and CV Starr Biomedical Information Center, Weill Cornell Medical College, New York, New York
| | - Alejandro Pino
- NewYork-Presbyterian-Weill Cornell Medical Center, New York, New York
| | - Kayley Ancy
- NewYork-Presbyterian-Weill Cornell Medical Center, New York, New York
| | - Carl V Crawford
- Division of Gastroenterology and Hepatology, Weill Department of Medicine, Weill Cornell Medicine, New York, New York
| | - Matthew S Simon
- Section of Hospital Medicine, Division of General Internal Medicine, Weill Department of Medicine, Weill Cornell Medicine, New York, New York; Division of Infectious Diseases, Weill Department of Medicine, Weill Cornell Medicine, New York, New York
| | - Arthur T Evans
- Section of Hospital Medicine, Division of General Internal Medicine, Weill Department of Medicine, Weill Cornell Medicine, New York, New York
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Yu K, Bi N, Xiong C, Cai S, Long Z, Guo Z, Gu G. Synthesis of Defined and Functionalized Glycans of Lipoteichoic Acid: A Cell Surface Polysaccharide from Clostridium difficile. Org Lett 2017; 19:3123-3126. [PMID: 28548838 DOI: 10.1021/acs.orglett.7b01242] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Two structurally defined, functionalized glycans of lipoteichoic acid (LTA, also known as PS-III) from C. difficile, which have one or two repeating units of LTA linked to the core trisaccharide, were efficiently synthesized via a convergent [2 + 3] or [2 + 2 + 3] strategy. The α-linkage of both N-acetylglucosamine residues in the repeating unit were constructed with glycosyl imidates of azidosugars as donors, while the phosphodiester bridges between the oligosaccharides were fashioned using H-phosphonate chemistry. Both synthetic targets contained a 3-aminopropyl group at the core trisaccharide reducing end, facilitating their conjugation to other biomolecules to afford conjugates useful for various biological studies and applications.
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Affiliation(s)
- Kang Yu
- National Glycoengineering Research Center and Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University , 27 Shanda Nan Lu, Jinan 250100, China
| | - Ningning Bi
- National Glycoengineering Research Center and Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University , 27 Shanda Nan Lu, Jinan 250100, China
| | - Chenghe Xiong
- National Glycoengineering Research Center and Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University , 27 Shanda Nan Lu, Jinan 250100, China
| | - Shuihong Cai
- Qidong Dongyue Pharmaceutical Company, 268 Shanghai Road, Qidong, Jiangsu 226200, China
| | - Zhongzhu Long
- Qidong Dongyue Pharmaceutical Company, 268 Shanghai Road, Qidong, Jiangsu 226200, China
| | - Zhongwu Guo
- National Glycoengineering Research Center and Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University , 27 Shanda Nan Lu, Jinan 250100, China.,Department of Chemistry, University of Florida , 214 Leigh Hall, Gainesville, Florida 32611, United States
| | - Guofeng Gu
- National Glycoengineering Research Center and Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University , 27 Shanda Nan Lu, Jinan 250100, China
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Costs of Clostridium difficile infection in pediatric operations: A propensity score–matching analysis. Surgery 2017; 161:1376-1386. [DOI: 10.1016/j.surg.2016.10.020] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2016] [Revised: 09/12/2016] [Accepted: 10/07/2016] [Indexed: 12/17/2022]
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Liubakka A, Vaughn BP. Clostridium difficile Infection and Fecal Microbiota Transplant. AACN Adv Crit Care 2017; 27:324-337. [PMID: 27959316 DOI: 10.4037/aacnacc2016703] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Clostridium difficile infection (CDI) is a major source of morbidity and mortality for hospitalized patients. Although most patients have a clinical response to existing antimicrobial therapies, recurrent infection develops in up to 30% of patients. Fecal microbiota transplant is a novel approach to this complex problem, with an efficacy rate of nearly 90% in the setting of multiple recurrent CDI. This review covers the current epidemiology of CDI (including toxigenic and nontoxigenic strains, risk factors for infection, and recurrent infection), methods of diagnosis, existing first-line therapies in CDI, the role of fecal microbiota transplant for multiple recurrent CDIs, and the potential use of fecal microbial transplant for patients with severe or refractory infection.
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Affiliation(s)
- Alyssa Liubakka
- Alyssa Liubakka is an Internal Medicine Resident, Department of Medicine, University of Minnesota, 420 Delaware Street SE, MMC 284, Minneapolis, MN 55455 (e-mail: ). Byron P. Vaughn is an Assistant Professor of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, and part of the Microbiota Therapeutics Program, University of Minnesota, Minneapolis, Minnesota
| | - Byron P Vaughn
- Alyssa Liubakka is an Internal Medicine Resident, Department of Medicine, University of Minnesota, 420 Delaware Street SE, MMC 284, Minneapolis, MN 55455 (e-mail: ). Byron P. Vaughn is an Assistant Professor of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, and part of the Microbiota Therapeutics Program, University of Minnesota, Minneapolis, Minnesota
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Barkin JA, Sussman DA, Fifadara N, Barkin JS. Clostridium difficile Infection and Patient-Specific Antimicrobial Resistance Testing Reveals a High Metronidazole Resistance Rate. Dig Dis Sci 2017; 62:1035-1042. [PMID: 28116592 DOI: 10.1007/s10620-017-4462-9] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2016] [Accepted: 01/16/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Clostridium difficile (CD) infection (CDI) causes marked morbidity and mortality, accounting for large healthcare expenditures annually. Current CDI treatment guidelines focus on clinical markers of patient severity to determine the preferred antibiotic regimen of metronidazole versus vancomycin. The antimicrobial resistance patterns for patients with CD are currently unknown. AIM The aim of this study was to define the antimicrobial resistance patterns for CD. METHODS This study included all patients with stools sent for CD testing to a private laboratory (DRG Laboratory, Alpharetta, Georgia) in a 6-month period from across the USA. Patient data was de-identified, with only age, gender, and zip-code available per laboratory protocol. All samples underwent PCR testing followed by hybridization for CD toxin regions A and B. Only patients with CD-positive PCR were analyzed. Antimicrobial resistance testing using stool genomic DNA evaluated presence of imidazole- and vancomycin-resistant genes using multiplex PCR gene detection. RESULTS Of 2743, 288 (10.5%) stool samples were positive for CD. Six were excluded per protocol. Of 282, 193 (69.4%) were women, and average age was 49.4 ± 18.7 years. Of 282, 62 were PCR positive for toxins A and B, 160 for toxin A positive alone, and 60 for toxin B positive alone. Antimicrobial resistance testing revealed 134/282 (47.5%) patients resistant to imidazole, 17 (6.1%) resistant to vancomycin, and 9 (3.2%) resistant to imidazole and vancomycin. CONCLUSIONS CD-positive patients with presence of imidazole-resistant genes from stool DNA extract was a common phenomenon, while vancomycin resistance was uncommon. Similar to treatment of other infections, antimicrobial resistance testing should play a role in CDI clinical decision-making algorithms to enable more expedited and cost-effective delivery of patient care.
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Affiliation(s)
- Jodie A Barkin
- Division of Gastroenterology, Department of Medicine, Leonard M. Miller School of Medicine, University of Miami, 1120 NW 14th Street, Clinical Research Building, Suite 1116, Miami, FL, 33136, USA.
| | - Daniel A Sussman
- Division of Gastroenterology, Department of Medicine, Leonard M. Miller School of Medicine, University of Miami, 1120 NW 14th Street, Clinical Research Building, Suite 1116, Miami, FL, 33136, USA
| | - Nimita Fifadara
- DRG Laboratory, 2001 Westside Parkway, Suite 240, Alpharetta, GA, 30004, USA
| | - Jamie S Barkin
- Division of Gastroenterology, Department of Medicine, Leonard M. Miller School of Medicine, University of Miami, 1120 NW 14th Street, Clinical Research Building, Suite 1116, Miami, FL, 33136, USA
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Patel I, Wungjiranirun M, Theethira T, Villafuerte-Galvez J, Castillo N, Akbari M, Alonso CD, Leffler DA, Kelly CP. Lack of adherence to SHEA-IDSA treatment guidelines for Clostridium difficile infection is associated with increased mortality. J Antimicrob Chemother 2017; 72:574-581. [PMID: 28115504 PMCID: PMC6074846 DOI: 10.1093/jac/dkw423] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2016] [Revised: 09/01/2016] [Accepted: 09/08/2016] [Indexed: 01/05/2023] Open
Abstract
OBJECTIVES The objective of this study was to determine our institution's compliance with 2010 Society for Healthcare Epidemiology of America and IDSA Clostridium difficile infection (CDI) treatment guidelines and their respective outcomes. METHODS We collected clinical parameters, laboratory values, antibiotic therapy and clinical outcomes from the electronic medical records for all patients hospitalized at our institution with a diagnosis of CDI from December 2012 to November 2013. We specifically evaluated whether SHEA-IDSA treatment guidelines were followed and evaluated the associations between guideline adherence and severe outcomes including mortality. RESULTS We identified 230 patients with CDI meeting inclusion criteria during the study period. Of these, 124 (54%) were appropriately treated, 46 (20%) were under-treated and 60 (26%) were over-treated. All-cause 90 day mortality was 17.4% overall; 43.5% in the under-treated group versus 12.9% in those appropriately treated (P < 0.0001) and 10.9% in those appropriately treated plus over-treated (P < 0.0001). Similarly, 90 day mortality attributed to CDI was 21.7% in those under-treated versus 8.9% in those appropriately treated (P = 0.03) and 8.2% in those either appropriately treated or over-treated (P = 0.015). Severe-complicated CDI occurred in 46 patients. In this subgroup, there was a non-significant trend towards increased mortality in under-treated patients (56.7%) compared with appropriately treated patients (37.5%, P = 0.35). Under-treatment was also associated with a higher rate of CDI-related ICU transfer (17.4% versus 4.8% in those appropriately treated, P = 0.023). CONCLUSIONS Adherence to CDI treatment guidelines is associated with improved outcomes especially in those with severe disease. Increased emphasis on provision of appropriate, guideline-based CDI treatment appears warranted.
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Affiliation(s)
- I Patel
- Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - M Wungjiranirun
- Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - T Theethira
- Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - J Villafuerte-Galvez
- Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - N Castillo
- Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - M Akbari
- Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - C D Alonso
- Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - D A Leffler
- Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - C P Kelly
- Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA
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Mulki R, Baumann AJ, Alnabelsi T, Sandhu N, Alhamshari Y, Wheeler DS, Perloff S, Katz PO. Body mass index greater than 35 is associated with severe Clostridium difficile infection. Aliment Pharmacol Ther 2017; 45:75-81. [PMID: 27790736 DOI: 10.1111/apt.13832] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2016] [Revised: 08/02/2016] [Accepted: 09/27/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND Obesity has been implicated in the acquisition of Clostridium difficile infections (CDI), however, no study has investigated whether there is a correlation between body mass index (BMI) and CDI severity. AIM To determine whether obesity, as measured by BMI correlates with severe hospital-onset or community-onset CDI. METHODS Patients admitted with CDI at a tertiary-care center from January 2013 to June 2015 were identified. The cohort was stratified by onset of disease using the National Healthcare Safety Network criteria, and by severity using the 2013 American College of Gastroenterology guidelines. Multivariate logistic regression was used to determine independent predictors of severe CDI. RESULTS A total of 196 met the inclusion criteria, of which 57.1% (112) met criteria for severe disease. Overall, BMI >35 kg/m2 was 1.7-fold more likely to be associated with severe CDI compared to a BMI 20-35 kg/m2 (P < 0.005), and was an independent predictor of severe CDI (P = 0.038). In patients with community-onset-CDI and hospital-onset-CDI, a BMI >35 kg/m2 was associated with a 1.96-fold and 1.48 greater rate of severe CDI compared to a BMI 20-35 kg/m2 (P = 0.004 and 0.048), and was an independent predictor of severe CDI in these cohorts (P = 0.039 and 0.027) respectively. CONCLUSION This study has identified an association between body mass index and Clostridium difficile infection severity. A BMI>35 kg/m2 is an independent risk factor for severe community-onset and hospital-onset Clostridium difficile infections.
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Affiliation(s)
- R Mulki
- Department of Internal Medicine, Einstein Medical Center, Philadelphia, PA, USA
| | - A J Baumann
- Department of Gastroenterology and Hepatology, University of Florida, Gainesville, FL, USA
| | - T Alnabelsi
- Department of Internal Medicine, Einstein Medical Center, Philadelphia, PA, USA
| | - N Sandhu
- Department of Internal Medicine, Einstein Medical Center, Philadelphia, PA, USA
| | - Y Alhamshari
- Department of Internal Medicine, Einstein Medical Center, Philadelphia, PA, USA
| | - D S Wheeler
- Department of Internal Medicine, Einstein Medical Center, Philadelphia, PA, USA
| | - S Perloff
- Division of Infectious Disease, Einstein Medical Center, Philadelphia, PA, USA
| | - P O Katz
- Division of Gastroenterology and Hepatology, Einstein Medical Center, Philadelphia, PA, USA
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van Beurden YH, Bomers MK, van der Werff SD, Pompe EAPM, Spiering S, Vandenbroucke-Grauls CMJE, Mulder CJJ. Cost analysis of an outbreak of Clostridium difficile infection ribotype 027 in a Dutch tertiary care centre. J Hosp Infect 2016; 95:421-425. [PMID: 28169013 DOI: 10.1016/j.jhin.2016.12.019] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2016] [Accepted: 12/22/2016] [Indexed: 12/19/2022]
Abstract
BACKGROUND The economic impact of Clostridium difficile infection (CDI) on the healthcare system is significant. From May 2013 to May 2014, an outbreak of C. difficile ribotype 027 occurred in a Dutch tertiary care hospital, involving 72 patients. The primary aim of this study was to provide insight into the financial burden that this CDI outbreak brought upon this hospital. METHODS A retrospective analysis was performed to estimate the costs of a one-year-long C. difficile ribotype 027 outbreak. Medical charts were reviewed for patient data. In addition, all costs associated with the outbreak control measures were collected. FINDINGS The attributable costs of the whole outbreak were estimated to be €1,222,376. The main contributing factor was missed revenue due to increased length of stay of CDI patients and closure of beds to enable contact isolation of CDI patients (36%). A second important cost component was extra surveillance and activities of the Department of Medical Microbiology and Infection Control (25%). CONCLUSION To the authors' knowledge, this is the first study to provide insight into the attributable costs of CDI in an outbreak setting, and to delineate the major cost items. It is clear that the economic consequences of CDI are significant. The high costs associated with a CDI outbreak should help to justify the use of additional resources for CDI prevention and control.
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Affiliation(s)
- Y H van Beurden
- Department of Medical Microbiology and Infection Control, VU University Medical Centre, Amsterdam, The Netherlands; Department of Gastroenterology and Hepatology, VU University Medical Centre, Amsterdam, The Netherlands.
| | - M K Bomers
- Department of Internal Medicine, VU University Medical Centre, Amsterdam, The Netherlands
| | - S D van der Werff
- Department of Medical Microbiology and Infection Control, VU University Medical Centre, Amsterdam, The Netherlands
| | - E A P M Pompe
- Division of Acute Care, VU University Medical Centre, Amsterdam, The Netherlands
| | - S Spiering
- Department of Gastroenterology and Hepatology, VU University Medical Centre, Amsterdam, The Netherlands
| | - C M J E Vandenbroucke-Grauls
- Department of Medical Microbiology and Infection Control, VU University Medical Centre, Amsterdam, The Netherlands
| | - C J J Mulder
- Department of Gastroenterology and Hepatology, VU University Medical Centre, Amsterdam, The Netherlands
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Durham DP, Olsen MA, Dubberke ER, Galvani AP, Townsend JP. Quantifying Transmission of Clostridium difficile within and outside Healthcare Settings. Emerg Infect Dis 2016; 22:608-16. [PMID: 26982504 PMCID: PMC4806959 DOI: 10.3201/eid2204.150455] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
To quantify the effect of hospital and community-based transmission and control measures on Clostridium difficile infection (CDI), we constructed a transmission model within and between hospital, community, and long-term care-facility settings. By parameterizing the model from national databases and calibrating it to C. difficile prevalence and CDI incidence, we found that hospitalized patients with CDI transmit C. difficile at a rate 15 (95% CI 7.2-32) times that of asymptomatic patients. Long-term care facility residents transmit at a rate of 27% (95% CI 13%-51%) that of hospitalized patients, and persons in the community at a rate of 0.1% (95% CI 0.062%-0.2%) that of hospitalized patients. Despite lower transmission rates for asymptomatic carriers and community sources, these transmission routes have a substantial effect on hospital-onset CDI because of the larger reservoir of hospitalized carriers and persons in the community. Asymptomatic carriers and community sources should be accounted for when designing and evaluating control interventions.
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Guillemin I, Marrel A, Beriot-Mathiot A, Doucet C, Kazoglou O, Luxemburger C, Reygrobellet C, Arnould B. How do Clostridium difficile infections affect nurses' everyday hospital work: A qualitative study. Int J Nurs Pract 2016; 21 Suppl 2:38-45. [PMID: 26125573 DOI: 10.1111/ijn.12166] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
This qualitative study explored the impact of Clostridium difficile infections on nurses' everyday work in the hospital. Twelve nurses (six in France and six in the United States) were interviewed in depth using a semi-structured interview guide. Thematic analysis of the interviews was performed. Managing diarrhoea and taking precautionary measures for infection control were the two most inconvenient aspects nurses reported with C. difficile patient management. Precautions included contact isolation, hand hygiene and reorganization/coordination of nursing care and ward. Precautions were time consuming and significantly increased nurses' workload when combined with caring for patients with uncontrollable, frequent bouts of diarrhoea. Management of C. difficile infection is extremely burdensome for nurses in their everyday work and disruptive to hospital organizations as a whole. Prevention of C. difficile infections, together with coordinated team work and communication, would therefore contribute to decreasing nurses' workload and the burden to health-care facilities associated with caring for these patients.
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Affiliation(s)
| | - Alexia Marrel
- PROs and ClinROs, HEOR and Strategic Market Access, Mapi, Lyon, France
| | | | | | | | | | | | - Benoit Arnould
- PROs and ClinROs, HEOR and Strategic Market Access, Mapi, Lyon, France
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Rees CA, Shen A, Hill JE. Characterization of the Clostridium difficile volatile metabolome using comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2016; 1039:8-16. [DOI: 10.1016/j.jchromb.2016.11.009] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2016] [Revised: 09/05/2016] [Accepted: 11/05/2016] [Indexed: 10/20/2022]
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Yu H, Baser O, Wang L. Burden of Clostridium difficile-associated disease among patients residing in nursing homes: a population-based cohort study. BMC Geriatr 2016; 16:193. [PMID: 27884118 PMCID: PMC5123396 DOI: 10.1186/s12877-016-0367-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Accepted: 11/16/2016] [Indexed: 01/11/2023] Open
Abstract
Background Clostridium difficile (C. difficile) infection (CDI) is the leading cause of nosocomial diarrhea in the United States. This study aimed to examine the incidence of CDI and evaluate mortality and economic burden of CDI in an elderly population who reside in nursing homes (NHs). Methods This was a population-based retrospective cohort study focusing on US NHs by linking Medicare 5% sample, Medicaid, Minimum Data Set (MDS) (2008–10). NH residents aged ≥65 years with continuous enrollment in Medicare and/or Medicaid Fee-for-Service plan for ≥12 months and ≥2 quarterly MDS assessments were eligible for the study. The incidence rate was calculated as the number of CDI episodes by 100,000 person-years. A 1:4 propensity score matched sample of cohorts with and without CDI was generated to assess mortality and health care costs following the first CDI. Results Among 32,807 NH residents, 941 residents had ≥1 episode of CDI in 2009, with an incidence of 3359.9 per 100,000 person-years. About 30% CDI episodes occurred in the hospital setting. NH residents with CDI (vs without CDI) were more likely to have congestive heart failure, renal disease, cerebrovascular disease, hospitalizations, and outpatient antibiotic use. During the follow-up period, the 30-day (14.7% vs 4.3%, P < 0.001), 60-day (22.7% vs 7.5%, P < 0.001), 6-month (36.3% vs 18.3%, P < 0.001), and 1-year mortality rates (48.2% vs 31.1%, P < 0.001) were significantly higher among the CDI residents vs non-CDI residents. Total health care costs within 2 months following the first CDI episode were also significantly higher for CDI residents ($28,621 vs $13,644, P < 0.001). Conclusions CDI presents a serious public health issue in NHs. Mortality, health care utilization, and associated costs were significant following incident CDI episodes. Electronic supplementary material The online version of this article (doi:10.1186/s12877-016-0367-2) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Holly Yu
- Pfizer Inc, Arcola Road, Collegeville, PA, 19426, USA.
| | - Onur Baser
- Center for Innovation & Outcomes Research, Department of Surgery, Columbia University, New York, NY, USA.,STATinMED Research, New York, NY, USA
| | - Li Wang
- STATinMED Research, Plano, TX, USA
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Interspecies Interactions between Clostridium difficile and Candida albicans. mSphere 2016; 1:mSphere00187-16. [PMID: 27840850 PMCID: PMC5103046 DOI: 10.1128/msphere.00187-16] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2016] [Accepted: 09/30/2016] [Indexed: 12/14/2022] Open
Abstract
Candida albicans and Clostridium difficile are two opportunistic pathogens that reside in the human gut. A few studies have focused on the prevalence of C. albicans in C. difficile-infected patients, but none have shown the interaction(s) that these two organisms may or may not have with each other. In this study, we used a wide range of different techniques to better understand this interaction at a macroscopic and microscopic level. We found that in the presence of C. albicans, C. difficile can survive under ambient aerobic conditions, which would otherwise be toxic. We also found that C. difficile affects the hypha formation of C. albicans, most likely through the excretion of p-cresol. This ultimately leads to an inability of C. albicans to form a biofilm. Our study provides new insights into interactions between C. albicans and C. difficile and bears relevance to both fungal and bacterial disease. The facultative anaerobic polymorphic fungus Candida albicans and the strictly anaerobic Gram-positive bacterium Clostridium difficile are two opportunistic pathogens residing in the human gut. While a few studies have focused on the prevalence of C. albicans in C. difficile-infected patients, the nature of the interactions between these two microbes has not been studied thus far. In the current study, both chemical and physical interactions between C. albicans and C. difficile were investigated. In the presence of C. albicans, C. difficile was able to grow under aerobic, normally toxic, conditions. This phenomenon was neither linked to adherence of bacteria to hyphae nor to biofilm formation by C. albicans. Conditioned medium of C. difficile inhibited hyphal growth of C. albicans, which is an important virulence factor of the fungus. In addition, it induced hypha-to-yeast conversion. p-Cresol, a fermentation product of tyrosine produced by C. difficile, also induced morphological effects and was identified as an active component of the conditioned medium. This study shows that in the presence of C. albicans, C. difficile can persist and grow under aerobic conditions. Furthermore, p-cresol, produced by C. difficile, is involved in inhibiting hypha formation of C. albicans, directly affecting the biofilm formation and virulence of C. albicans. This study is the first detailed characterization of the interactions between these two gut pathogens. IMPORTANCECandida albicans and Clostridium difficile are two opportunistic pathogens that reside in the human gut. A few studies have focused on the prevalence of C. albicans in C. difficile-infected patients, but none have shown the interaction(s) that these two organisms may or may not have with each other. In this study, we used a wide range of different techniques to better understand this interaction at a macroscopic and microscopic level. We found that in the presence of C. albicans, C. difficile can survive under ambient aerobic conditions, which would otherwise be toxic. We also found that C. difficile affects the hypha formation of C. albicans, most likely through the excretion of p-cresol. This ultimately leads to an inability of C. albicans to form a biofilm. Our study provides new insights into interactions between C. albicans and C. difficile and bears relevance to both fungal and bacterial disease.
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A Comprehensive Study of Costs Associated With Recurrent Clostridium difficile Infection. Infect Control Hosp Epidemiol 2016; 38:196-202. [PMID: 27817758 DOI: 10.1017/ice.2016.246] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Clostridium difficile infection (CDI) is the most common healthcare-associated infection and is associated with considerable morbidity. Recurrent CDI is a key contributing factor to this morbidity. Despite an estimated 83,000 recurrences annually in the United States, there are few accurate estimates of costs associated with recurrent CDI. OBJECTIVE We performed this study (1) to identify the health consequences of recurrent CDI including need for repeat hospitalization, intensive care unit (ICU) stay, and surgery; (2) to determine costs associated with recurrent CDI and identify determinants of such costs; and (3) to compare the outcomes and costs of recurrent CDI to those who develop reinfection. METHODS We identified all patients with confirmed recurrent CDI between January to December 2013 at a single referral center. Healthcare burden associated with recurrence including diagnostic testing, pharmacologic treatment, and inpatient and outpatient healthcare visits were identified in the 12 months following the first recurrence. Total healthcare costs were calculated, and the predictors of high healthcare utilization were identified. RESULTS Our study population included 98 patients with recurrent CDI. The median interval between the initial infection and recurrence was 37 days. The mean age of the cohort was 67 years, two-thirds were women (62%), and the mean Charlson index was 8.6. During the year following the first recurrence of CDI, each patient underwent a mean of 4.4 stool C. difficile toxin tests and received a mean of 2.5 prescriptions for oral vancomycin (range, 0-6). Most patients (84%) with recurrence had a CDI-related hospitalization, and 6% underwent colectomy. The mean total CDI-associated cost was $34,104 per patient, with hospitalization costs accounting for 68%, surgery 20%, and drug treatment 8% of this cost, respectively. Extrapolating to the United States overall, we estimate an annual cost of $2.8 billion related to recurrent CDI. CONCLUSION Recurrent CDI is associated with considerable morbidity and cost. Infect Control Hosp Epidemiol 2017;38:196-202.
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Malik DJ, Shaw CM, Shama G, Clokie MRJ, Rielly CD. An Investigation into the Inactivation Kinetics of Hydrogen Peroxide Vapor Against Clostridium difficile Endospores. CHEM ENG COMMUN 2016. [DOI: 10.1080/00986445.2016.1223058] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Affiliation(s)
- D. J. Malik
- Department of Chemical Engineering, Loughborough University, Loughborough, Leicester, LE11 3TU, UK
| | - C. M. Shaw
- Department of Chemical Engineering, Loughborough University, Loughborough, Leicester, LE11 3TU, UK
| | - G. Shama
- Department of Chemical Engineering, Loughborough University, Loughborough, Leicester, LE11 3TU, UK
| | - M. R. J. Clokie
- Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, LE1 9HN, UK
| | - C. D. Rielly
- Department of Chemical Engineering, Loughborough University, Loughborough, Leicester, LE11 3TU, UK
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Mortality and Costs in Clostridium difficile Infection Among the Elderly in the United States. Infect Control Hosp Epidemiol 2016; 37:1331-1336. [DOI: 10.1017/ice.2016.188] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
OBJECTIVETo examine attributable mortality and costs of Clostridium difficile infection (CDI) in the Medicare population.DESIGNA population-based cohort study among US adults aged at least 65 years in the 2008–2010 Medicare 5% sample, with follow-up of 12 months.PATIENTSIncident CDI episode was defined by the International Classification of Diseases, Ninth Revision, Clinical Modification code of 008.45 and no other occurrences within the preceding 12 months. To quantify the adjusted mortality and costs we developed a 1:1 propensity-matched sample of CDI and non-CDI patients.RESULTSAmong 1,165,165 patients included, 6,838 (0.6%) had a CDI episode in 2009 (82.5% healthcare-associated). Patients with CDI were older (mean [SD] age, 81.0±8.0 vs 77.0±7.7 years, P<.001), were more likely to come from the Northeast (27.4% vs 18.6%, P<.001), and had a higher comorbidity burden (Charlson score, 4.6±3.3 vs 1.7±2.1, P<.001). Hospitalizations (63.2% vs 6.0%, P<.001) and antibiotics (33.9% vs 12.5%, P<.001) within the prior 90 days were more common in the group with CDI. In the propensity-adjusted analysis, CDI was associated with near doubling of both mortality (42.6% vs 23.4%, P<.001) and total healthcare costs ($64,807±$66,480 vs $38,128±$46,485, P<.001).CONCLUSIONSAmong elderly patients, CDI is associated with an increase in adjusted mortality and healthcare costs following a CDI episode. Nationwide annually this equals 240,000 patients with CDI, 46,000 potential deaths, and more than $6 billion in costs.Infect Control Hosp Epidemiol 2016;1–6
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Zhang S, Palazuelos-Munoz S, Balsells EM, Nair H, Chit A, Kyaw MH. Cost of hospital management of Clostridium difficile infection in United States-a meta-analysis and modelling study. BMC Infect Dis 2016; 16:447. [PMID: 27562241 PMCID: PMC5000548 DOI: 10.1186/s12879-016-1786-6] [Citation(s) in RCA: 220] [Impact Index Per Article: 24.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2016] [Accepted: 08/18/2016] [Indexed: 12/18/2022] Open
Abstract
Background Clostridium difficile infection (CDI) is the leading cause of infectious nosocomial diarrhoea but the economic costs of CDI on healthcare systems in the US remain uncertain. Methods We conducted a systematic search for published studies investigating the direct medical cost associated with CDI hospital management in the past 10 years (2005–2015) and included 42 studies to the final data analysis to estimate the financial impact of CDI in the US. We also conducted a meta-analysis of all costs using Monte Carlo simulation. Results The average cost for CDI case management and average CDI-attributable costs per case were $42,316 (90 % CI: $39,886, $44,765) and $21,448 (90 % CI: $21,152, $21,744) in 2015 US dollars. Hospital-onset CDI-attributable cost per case was $34,157 (90 % CI: $33,134, $35,180), which was 1.5 times the cost of community-onset CDI ($20,095 [90 % CI: $4991, $35,204]). The average and incremental length of stay (LOS) for CDI inpatient treatment were 11.1 (90 % CI: 8.7–13.6) and 9.7 (90 % CI: 9.6–9.8) days respectively. Total annual CDI-attributable cost in the US is estimated US$6.3 (Range: $1.9–$7.0) billion. Total annual CDI hospital management required nearly 2.4 million days of inpatient stay. Conclusions This review indicates that CDI places a significant financial burden on the US healthcare system. This review adds strong evidence to aid policy-making on adequate resource allocation to CDI prevention and treatment in the US. Future studies should focus on recurrent CDI, CDI in long-term care facilities and persons with comorbidities and indirect cost from a societal perspective. Health-economic studies for CDI preventive intervention are needed. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-1786-6) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Shanshan Zhang
- Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Medical School, Teviot Place, Edinburgh, EH8 9AG, UK. .,Department of Preventive Dentistry, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Beijing, 100081, China.
| | | | - Evelyn M Balsells
- Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Medical School, Teviot Place, Edinburgh, EH8 9AG, UK
| | - Harish Nair
- Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Medical School, Teviot Place, Edinburgh, EH8 9AG, UK
| | - Ayman Chit
- Sanofi Pasteur, Swiftwater, PA, USA.,Lesli Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada
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Accessory Gene Regulator-1 Locus Is Essential for Virulence and Pathogenesis of Clostridium difficile. mBio 2016; 7:mBio.01237-16. [PMID: 27531912 PMCID: PMC4992976 DOI: 10.1128/mbio.01237-16] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
UNLABELLED Clostridium difficile infection (CDI) is responsible for most of the definable cases of antibiotic- and hospital-associated diarrhea worldwide and is a frequent cause of morbidity and mortality in older patients. C. difficile, a multidrug-resistant anaerobic pathogen, causes disease by producing toxins A and B, which are controlled by an accessory gene regulator (Agr) quorum signaling system. Some C. difficile strains encode two Agr loci in their genomes, designated agr1 and agr2 The agr1 locus is present in all of the C. difficile strains sequenced to date, whereas the agr2 locus is present in a few strains. The functional roles of agr1 and agr2 in C. difficile toxin regulation and pathogenesis were unknown until now. Using allelic exchange, we deleted components of both agr loci and examined the mutants for toxin production and virulence. The results showed that the agr1 mutant cannot produce toxins A and B; toxin production can be restored by complementation with wild-type agr1 Furthermore, the agr1 mutant is able to colonize but unable to cause disease in a murine CDI model. These findings have profound implications for CDI treatment because we have uncovered a promising therapeutic target for the development of nonantibiotic drugs to treat this life-threatening emerging pathogen by targeting the toxins directly responsible for disease. IMPORTANCE Within the last decade, the number of cases of C. difficile infections has been increasing exponentially in the United States, resulting in about 4.8 billion U.S. dollars in health care costs annually. As a multidrug-resistant, spore-forming, anaerobic pathogen, C. difficile overpopulates the colon after the gut microbiota has been altered by antibiotic therapy. With increasing resistance to antibiotic treatment of C. difficile infections, patients are experiencing higher costs of health care and a lower quality of life as treatment options decrease. During infection, C. difficile produces toxins A and B, which directly cause disease. As a result, the toxins have become promising nonantibiotic treatment targets. Here, we have identified a pathway responsible for activating the production of the toxins. This important finding opens up a unique therapeutic target for the development of a novel nonantibiotic therapy for C. difficile infections.
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CodY-Dependent Regulation of Sporulation in Clostridium difficile. J Bacteriol 2016; 198:2113-30. [PMID: 27246573 DOI: 10.1128/jb.00220-16] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2016] [Accepted: 05/22/2016] [Indexed: 01/05/2023] Open
Abstract
UNLABELLED Clostridium difficile must form a spore to survive outside the gastrointestinal tract. The factors that trigger sporulation in C. difficile remain poorly understood. Previous studies have suggested that a link exists between nutritional status and sporulation initiation in C. difficile In this study, we investigated the impact of the global nutritional regulator CodY on sporulation in C. difficile strains from the historical 012 ribotype and the current epidemic 027 ribotype. Sporulation frequencies were increased in both backgrounds, demonstrating that CodY represses sporulation in C. difficile The 027 codY mutant exhibited a greater increase in spore formation than the 012 codY mutant. To determine the role of CodY in the observed sporulation phenotypes, we examined several factors that are known to influence sporulation in C. difficile Using transcriptional reporter fusions and quantitative reverse transcription-PCR (qRT-PCR) analysis, we found that two loci associated with the initiation of sporulation, opp and sinR, are regulated by CodY. The data demonstrate that CodY is a repressor of sporulation in C. difficile and that the impact of CodY on sporulation and expression of specific genes is significantly influenced by the strain background. These results suggest that the variability of CodY-dependent regulation is an important contributor to virulence and sporulation in current epidemic isolates. This report provides further evidence that nutritional state, virulence, and sporulation are linked in C. difficile IMPORTANCE This study sought to examine the relationship between nutrition and sporulation in C. difficile by examining the global nutritional regulator CodY. CodY is a known virulence and nutritional regulator of C. difficile, but its role in sporulation was unknown. Here, we demonstrate that CodY is a negative regulator of sporulation in two different ribotypes of C. difficile We also demonstrate that CodY regulates known effectors of sporulation, Opp and SinR. These results support the idea that nutrient limitation is a trigger for sporulation in C. difficile and that the response to nutrient limitation is coordinated by CodY. Additionally, we demonstrate that CodY has an altered role in sporulation regulation for some strains.
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