Clostridium difficile infection (CDI) is one of the most common healthcare-associated infections in the United States. Its incidence has been increasing in the recent years despite preventative measures. CDI increases annual expenses by 1.5 billion dollars. Cancer patients are at higher risk to acquire CDI, as explained by their frequent exposure to risk factors. CDI in cancer patients is associated with higher mortality rates and prolonged hospitalization. Furthermore, CDI affects the course of the disease by delaying treatments such as chemotherapy. Chemotherapeutics drugs are considered independent risk factors for CDI. This review discusses Clostridium difficile infection in cancer patients, including those who are receiving chemotherapy. Herein, we summarize recent data regarding the epidemiology, risk factors, including chemotherapy regimens, pathogenesis, diagnostic techniques and treatment options, including newer agents. Method: A literature search was performed using the PubMed and Google Scholar databases. The MeSH terms utilized in different combinations were 'clostridium difficile', 'neoplasia/cancer/oncology', 'chemotherapy', 'diagnosis', and 'treatment', in addition to looking up each treatment option individually to generate a comprehensive search. The articles were initially screened by title alone, followed by screening through abstracts. Full texts of pertinent articles (including letters to editors, case reports, case series, cohort studies, and clinical trials) were included in this review.

Clostridium difficile is a clinically problematic pathogen and continues to persist within the healthcare system. Presentation of disease symptoms ranges from mild to severe diarrhoea, through to fulminant pseudomembranous colitis. Approximately 20% of patients will suffer from recurrent episodes and of all patients who die from C. difficile related causes, approximately 41% of death certificates mention C. difficile as an underlying cause of death, and this poses a significant burden on healthcare facilities. Three methods of investigation were employed to develop a more comprehensive understanding of both the host and isolate association with the outcomes of C. difficile infection; mortality and recurrence. These methods were; analysing patient clinical data to try and identify host markers of infection outcomes, evaluating C. difficile type association with infection outcomes, and genetically and phenotypically characterising the clinically relevant C. difficile isolates associated to these outcomes. During this study statistical analysis of clinical data revealed that there were four variables; white cell count, serum albumin, C-reactive protein and respiratory rate, which were prognostic of mortality in patients with C. difficile infection. Threshold levels of these variables were used to create a clinical prediction rule to classify patients with C. difficile infection who were more 'at risk' from mortality, with statistical significance in both a derivation and validation cohort. However, analysis was unable to determine variables prognostic of recurrent infection. Due to small sample sizes of some groups of isolates, no groups of C. difficile isolates were significantly associated with increased recurrent infection or mortality during this study. Some groups of isolates were associated with primary only infection and/or low mortality. There was a non-significant trend in particular C. difficile isolate groups being associated with infection outcome; a panel of representative isolates was therefore chosen to be characterised in more detail. Phenotypic and genetic analysis of a panel of sixteen C. difficile isolates revealed isolate specific differences in toxin production, conservation of transposable elements and SNP abundances, which may have played a role in infection outcome. Isolate motility and antibiotic resistance profiles were not statistically significantly different between isolates within a particular group of C. difficile types. One hypothesis from the collective results obtained during this study suggests that the phenotypic and genotypic changes in isolates may have facilitated differences in their interaction with the host. In turn, the host specific inflammatory response to the infecting C. difficile isolate may have played a role in host outcomes. Research conducted during this study has begun to assess which host specific responses may be important in determining the outcome of C. difficile infection, and which C. difficile isolate characteristics may in part also contribute. However, the assessment of both host and isolate association to infection outcomes would benefit from further investigation in a larger cohort, in order to prove or refute conclusively any hypothesises generated in this study.

Introduction: Clostridium difficile infection (CDI) is a common hospital-acquired infection and a financial burden on the healthcare system. There is a need to reduce its impact on patients and the entire health system. More accurate estimates of the financial impact of CDI will assist hospitals in creating better CDI reduction strategies with limited resources. Previous research has not sufficiently accounted for the skewed nature of hospital cost data, baseline patient mortality risk, and the time-varying nature of CDI. Objective: We conducted a retrospective cohort study to estimate the cost impact of hospital-acquired CDI from the hospital perspective, using a number of analytical approaches. Method: We used clinical and administrative data for inpatients treated at The Ottawa Hospital to construct an analytical data set. Our primary outcome was direct costs and our primary exposure was hospital-acquired CDI. We performed the following analyses: Ordinary least square regression and generalized linear regression as time-fixed methods, and Kaplan-Meier survival curve and Cox regression models as time-varying methods. Results: A total of 49,888 admissions were included in this study (mean (SD) age of 64.6 ± 17.8 years, median (IQR) baseline mortality risk of 0.04 (0.01-0.14)). 360 (0.73%) patients developed CDI. Estimates of incremental cost due to CDI were substantially higher when using time-fixed methods than time-varying methods. Using methods that appropriately account for the time-varying nature of the exposure, the estimated incremental cost due to CDI was $8,997 per patient. In contrast, estimates from time-fixed methods ranged from $49,150 to $55,962: about a six fold difference. Conclusion: Estimates of hospital costs are strongly influenced by the time-varying nature of CDI as well as baseline mortality risk. If studies do not account for these factors, it is likely that the impact of hospital-acquired CDI will be overestimated.

Introduction: Clostridium difficile infection (CDI) is a common hospital-acquired infection and a financial burden on the healthcare system. There is a need to reduce its impact on patients and the entire health system. More accurate estimates of the financial impact of CDI will assist hospitals in creating better CDI reduction strategies with limited resources. Previous research has not sufficiently accounted for the skewed nature of hospital cost data, baseline patient mortality risk, and the time-varying nature of CDI. Objective: We conducted a retrospective cohort study to estimate the cost impact of hospital-acquired CDI from the hospital perspective, using a number of analytical approaches. Method: We used clinical and administrative data for inpatients treated at The Ottawa Hospital to construct an analytical data set. Our primary outcome was direct costs and our primary exposure was hospital-acquired CDI. We performed the following analyses: Ordinary least square regression and generalized linear regression as time-fixed methods, and Kaplan-Meier survival curve and Cox regression models as time-varying methods. Results: A total of 49,888 admissions were included in this study (mean (SD) age of 64.6 ± 17.8 years, median (IQR) baseline mortality risk of 0.04 (0.01-0.14)). 360 (0.73%) patients developed CDI. Estimates of incremental cost due to CDI were substantially higher when using time-fixed methods than time-varying methods. Using methods that appropriately account for the time-varying nature of the exposure, the estimated incremental cost due to CDI was $8,997 per patient. In contrast, estimates from time-fixed methods ranged from $49,150 to $55,962: about a six fold difference. Conclusion: Estimates of hospital costs are strongly influenced by the time-varying nature of CDI as well as baseline mortality risk. If studies do not account for these factors, it is likely that the impact of hospital-acquired CDI will be overestimated.

The number of cases of Clostridium difficile infection (CDI) has been increasing globally. CDI is the main cause of nosocomial diarrhoea, which may be life-threatening in complicated cases, and also costs the health care societies millions of pounds annually. The predominant types and their resistance to antibiotics have been changing and one of the major selective pressures which causes this is antimicrobial use. Although much is known about the role of the toxins in pathogenesis of CDI, the role of immunogenic cell wall components is unclear. They may play a role in colonisation and pathology and a study of these could clarify the infection process. It is therefore important to study the immune responses against these bacterial wall components from different strains and their effects on stimulation of leukocytes to produce cytokines and chemokines. This study was divided into four parts: 1. An epidemiological study to determine frequencies of the predominant types of C. difficile, thus 140 C. difficile isolates from surgical patients and their environment during 2009 were investigated to define their PCR ribotype. This utilised capillary sequencing gel electrophoresis for their analysis. 2. The determination of antimicrobial susceptibility to six antibiotics (ampicillin, erythromycin, tetracycline, metronidazole, moxifloxacin and vancomycin) was assessed and MIC determination by agar dilutions. 3. Investigation of host immunity to molecules with conserved molecular patterns. Surface-layer proteins (SLPs), lipocarbohydrate (LC) and flagellar proteins were separated and purified from five ribotypes of C. difficile (001, 002, 027, 078 and106) predominant in Scotland. a) The immune responses to these molecules were assessed by ELISA by exposing serum of patients and healthy donors and measuring specific IgG levels. b) Innate immunity was investigated by distinguishing responses of a macrophage cell line (THP1) to the above molecules. Induction of interleukins (IL)-1β, IL-6, IL- 8, IL-10 and IL-12 interleukins and TNF-α was detected by ELISA. In this study 15 different ribotypes were identified. The most frequent were 001, 020, 106 ribotypes (52.8%, 7.4% and 5.7%), respectively, while 13 isolates could not be assigned a ribotype. However, all isolates were sensitive to vancomycin, metronidazole and moxifloxacin, but 74.28% of isolates were resistant to erythromycin. The IgG level against bacterial antigens (SLPs, LC and flagella proteins) in donors’ serum showed almost normal distribution to all antigens from the different ribotypes and the sensitivity of the assays was increased by raising the concentration of antigens. Levels to SLPs were generally the highest, but the flagellar protein exceeded the SLPs of the 027 ribotype. The donors, controls, patients and carrier sera gave similar results. The greatest induction of interleukins was obtained using 50μg of antigen with the THP-1 cells activated with 50ng of PMA. The highest induction of all antigens was for IL-10. The highest values for the control LPS was with IL-12. But the best effect for SLPs of 027 was for IL-10 (109.1ng/ml), while the weakest for TNF for SLPs of 027 (4.7ng/ml). In general the IL-1β, IL-6, IL-8 and TNF concentrations ranged from 4.7-60ng/ml for all antigens and in contrast IL-12 and IL-10 average ranged 11- 109.1ng/ml. To conclude, the prevalence of C. difficile and their antibiotic susceptibility are constantly changing. IgG antibodies to SLPs and flagellar proteins from the hypervirulent ribotype 027 were highest in the community and hospitalized individuals. The molecules of conserved molecular patterns are immunogenic with various levels of response in the monocytic THP1 cells. SLPs were best in inducing interleukins. Flagellar proteins from 027 ribotypes accompanied SLPs in IL-10 induction levels. Consequently SLPs and flagellar proteins from 027 ribotypes appeared the best immunogenic bacterial molecules.

Clostridium difficile infection (CDI) has proven to be a constantly evolving disease periodically posing new diagnostic and clinical dilemmas. Different regions of the world have reported specific local genomic characteristics of the infecting strains, which may be related to variation in disease presentation and outcome. This study was performed to determine the clinical and molecular features of severe, recurrent and community-associated disease in the Lothian region of Scotland, UK among patients diagnosed from August 2010-July 2011. Three hundred and thirty-five patients with laboratory confirmed CDI were studied for epidemiological features, clinical presentation, and laboratory markers. They were followed up for one year to determine recurrence and mortality. Four hundred and thirty-two episodes were recorded. Ribotypes, presence of toxin genes and MLVA subtypes of isolates from these episodes were determined. During the course of the study, PCR ribotype 078 was identified as an important emerging type and concerns of “hypervirulence” were raised when an outbreak was recorded in 2012. This ribotype was studied to compare its clinical and molecular characteristics with other endemic ribotypes and between its own outbreak-related and endemic subtypes. Asymptomatic children were also sampled to determine their role as pools of potential pathogens. Severe episodes accounted for 40.4% of total and 29.3% patients had multiple episodes on record. One-year mortality was 32.8% of which CDI was listed on 25.5% death certificates. Ribotype 078 was confirmed in 6.8% episodes. Community-associated disease was identified in 25.3% patients, which differed significantly from hospital-associated disease in the number of antibiotics and gastrointestinal manipulation prior to CDI. Endemic PCR ribotype 078 caused significantly less recurrent disease and more community- associated disease when compared to the most prevalent ribotype 001. Patients who died from ribotype 078 within 30d had a lower Charlson comorbidity index than ribotype 001 counterparts suggesting that the former may infect healthier patients. MLVA subtyping of ribotype 078 proved useful in identifying epidemiological relationships during the outbreak. CDI had contributed to the death of 50% of all patients infected with the outbreak related ribotype 078 strain compared to 14.3% of those infected with the endemic strains. This study documents the changing epidemiology of CDI in the region and demonstrates differences in epidemic and endemic disease.

Class of 2009 Abstract / OBJECTIVES: The purpose of the study was to determine the rate of Clostridium difficile infections (CDI) in hospitalized patients and the various factors that were associated with the risk of developing CDI by examining patient discharge data for hospitals in 37 states in the United States using Healthcare Cost and Utilization Project (HCUP). METHODS: Patient discharge information for all patients obtained using HCUP census for the years 2002-2005, either for primary or secondary (all-listed) occurrences of CDI using the ICD-9-CM code (008.45) specific for intestinal infections due to C. difficile, were included in the study. Regression analysis, either Generalized Linear Model log-link or power-link, or a logistic regression was employed to control for the multiple independent variables. RESULTS: The incidence rate for CDI was 9.4% for the years 2002-2005. Among the concomitant diagnoses and procedures, essential hypertension, volume depletion, congestive heart failure, urinary tract infection and venous catheterization were the top 5. The length of stay (LOS) for CDI was associated with being Black, Hispanic or Other race category, number of diagnoses and procedures, primary expected payer of Medicaid, private insurance and other (including worker’s compensation, CHAMPUS,CHAMPVA etc), and all groups classified based on median household income category for patient’s zip code. Predictors of CDI related to inpatient total hospital charges were being female, race (other than black), number of diagnoses and procedures, Death, LOS, patient location and with self-pay and no charge categories as primary expected payer. Predictors of higher CDI related inpatient hospital deaths were age, female sex, Hispanic race, number of diagnoses and procedures, LOS and having Medicaid, self-pay or other as primary expected payer. CONCLUSIONS: LOS, inpatient total hospital charges, and inpatient mortality were dependent on several patient and other characteristics.

Controlling norovirus transmission in units with immunocompromised patients is challenging. We present a cluster of norovirus cases that occurred on a stem-cell transplant unit and the prevention efforts that were implemented to limit the outbreak. Protocols developed to control this cluster may provide a model for other facilities. / National Institutes of Health / Revisión por pares

Fecal microbiota transplantation (FMT) is the process by which fecal suspension from a healthy individual is transferred into the gastrointestinal tract of another individual in an attempt to cure certain diseases. This transplantation process has been accredited as being a potential remedy for a growing number of diseases that have been associated with gut microbial imbalances. Interest in FMT has largely been driven by the science community’s increasing interest in the gut microbiome and its role in potentially regulating a multitude of different functions and processes within the human body. One disease that has been found to respond exceptionally well to FMT treatments is Clostridium difficile infection (CDI). However, while FMT has demonstrated high cure rates for CDI, this transplantation process is no panacea. In fact, the results from FMT treatments on other diseases, such as Inflammatory Bowel Disease (IBD), have not been as impressive as CDI’s. This review will examine the existing literature surrounding FMT usage on IBD and will propose a series of experiments and studies needed to truly test the safety and efficacy of FMT for IBD patients. This review will also reference current literature documenting FMT treatments for CDI as a comparative tool for investigating if this form of bacteriotherapy is indeed a viable therapeutic option for treating IBD.

A review of literature related to community-acquired Clostridium difficile- associated disease (CA-CDAD) was conducted. Information was collected from Cumulative Index to Nursing and Allied Health (CINAHL) and MEDLINE-EBSCOhost databases. Clinical practice recommendations were obtained from the CDC. Studies were examined for epidemiology of infection due to C. difficile in the community and interventions to reduce transmission. Findings demonstrated a mirroring of to CA-CDAD to community-acquired Methicillin-resistant Staphylococcus aureus (MRSA). Multiple studies found underlying gastrointestinal disorders and use of cephalosporin antibiotics to be a risk factor. Another identified risk factor was use of gastric acid suppressive drugs. Also, no particular C. difficile strain was more likely to cause recurrence. Many positive cases for CA-CDAD lacked traditional risk factors such as recent antibiotic exposure. To reduce transmission of community-acquired MRSA the CDC recommends MRSA should be considered in the differential diagnosis of soft skin tissue infections. Clinicians should also collect specimens for culture and antimicrobial susceptibility testing from all patients with abscesses. The CDC recommends clinicians should teach their patients to limit transmission and ask about similar cases in household members and close contacts. Therefore, to reduce transmission of CA-COAD, Clostridium difficile- associated disease should be considered in the differential diagnosis of diarrhea. Clinicians should collect specimens for culture based on patient history & current clinical presentation for patients with diarrhea. It is important that patients be taught the proper hygiene and cleaning protocols to reduce transmission