Risk Of C. Difficile Infection Research Articles

972. Asymptomatic Carriage of Clostridiodes difficile and Risk of Subsequent Infection

Background C. difficile is one of the most common healthcare-associated infections in the United States. Studies of patients with asymptomatic carriage of toxigenic C. difficile have reported conflicting results on the risk of subsequent C. difficile infection (CDI). Older studies suggest that the risk was low and colonization may be protective. Subsequent studies indicate that asymptomatic carriers have a 6-fold greater risk of developing CDI. The aims of our study were to assess the burden of asymptomatic C. difficile carriage and risk of subsequent CDI.MethodsAdult inpatients at NorthShore University HealthSystem, Illinois hospitals between August 1, 2017 and February 28, 2018 were eligible for the study. Focused admission screening of patients at high risk of C. difficile carriage was performed: (1) history of CDI or colonization, (2) prior hospitalization past 2 months, or (3) admission from a long-term care facility. A rectal swab was collected and tested using the cobas® Cdif Test (Roche) real-time PCR. The development of hospital onset CDI (HO-CDI) in colonized patients was monitored prospectively for at least 2 months. HO-CDI testing of colonized patients was performed using the Cepheid GeneXpert RT-PCR. HO-CDI was defined as patients hospitalized for at least 72 hours with 3 or more episodes of diarrhea/24 hours, in the absence of other potential causes of diarrhea. Patient demographics were collected using a standardized form and data analyzed using VassarStats.ResultsThere were 6,104 patients enrolled in the study and 528 (8.7%) were positive on admission for toxigenic C. difficile carriage. The mean age of colonized patients was 75.5 years (range 24–103) and 56.4% (298 patients) were females. Of 528 colonized patients, 21 (4%) had a positive CDI test. A total of 7 patients (1.3%) developed HO-CDI. Mean time to positive HO-CDI was 46.1 days (range 5–120 days). Of 5,576 patients that were negative for C difficile carriage on admission, 14 (0.3%) patients developed HO-CDI. The relative risk of HO-CDI was 5.28 (95% CI: 2.14–13.03, P = 0.05).ConclusionWe found that 8.7% of at-risk admissions were asymptomatic toxigenic C. difficile carriers. While only 1.3% developed HO-CDI, asymptomatic carriers had a 5 times higher risk of subsequent CDI compared with non-carriers.Disclosures All authors: No reported disclosures.

616. Vancomycin Is Frequently Administered to Hematopoietic Cell Transplant Recipients Without a Provider Documented Indication and Correlates with Microbiome Disruption and Adverse Events

BackgroundThe gut microbiome of hematopoietic cell transplant (HCT) recipients correlates with the risk of acute graft- vs.-host disease (aGVHD). IV vancomycin is the most commonly used nonprophylactic antibiotic in HCT recipients at our center. We evaluated indications for vancomycin use and impact of vancomycin exposure on the microbiome.MethodsAntibiotic exposures and provider-documented indications for vancomycin use were assessed through chart review. We assessed adherence to guideline-based recommendations for vancomycin use for courses during neutropenic fever. Weekly stool samples collected from HCT patients before and up to 100 days post-transplant in a previously described cohort had bacterial composition determined from 16S rRNA amplicons analyzed with a phylogeny classifier and was correlated with vancomycin exposure using mixed effects modeling to correct for overlapping and repeated antibiotic exposures.ResultsThirty-seven of 70 (53%) of patients received vancomycin over 61 courses with a mean duration of 8 days; 14 (23%) of these courses were with neutropenic fever. No indication was documented by the provider for 21 (34%) vancomycin courses (Figure 1). Almost half of all courses given for neutropenic fever did not meet guideline indications (Figure 2). Adverse effects occurred in 19 (31%) of vancomycin courses, including 11 (18%) associated with acute kidney injury.Vancomycin was associated with reduced relative abundance of organisms correlated with reduced risk of subsequent severe acute graft vs. host disease and Clostridium scindens, an organism protective against C. difficile infection (CDI) (Figure 3, in bold).ConclusionIndications for vancomycin were poorly documented and infrequently guideline based. Adverse events occurred in 1 in 3 courses of vancomycin. Vancomycin correlated with microbiome changes which have been associated with increased risk for aGVHD and CDI. Disclosures S. Pergam, Merck: Consultant, Consulting fee.

1155. Excessive Movement, Unnecessary Contamination: Clostridium difficile Patients in the Hospital

BackgroundThe environmental contamination of Clostridium difficile in acute care hospital rooms is associated with increased risk of infection for subsequent patients. Patients that stay in a room following a patient with a C. difficile infection (CDI) have an increased risk of CDI compared with patients whose previous resident did not have CDI. The objective of this study was characterize the room movement of CDI patients in a Level 1 Trauma Medical Center.MethodsA patient with CDI was defined as an inpatient with a positive C. difficile test through rapid serology, C. difficile polymerase chain reaction (PCR) or multiplex-stool PCR from March 2017 to March 2018. Patients were classified as either community-onset (CO, positive test <4 days after admission) or hospital-onset (HO, positive test ≥4 days after admission). Additionally, the number of rooms each CDI patient resided in during one admission following a positive C. difficile test was determined and the proportion of patients who stayed in one to two rooms or at least three rooms per visit was calculated.ResultsThere were a total of 244 CDI patients identified (172: CO, 72: HO) between March 2017 and March 2018. The mean time from admission to positive test was 12.4 hours post-admission for CO-CDI patients and 251.1 hours for HO-CDI patients. Almost 40% of HO-CDI patients (36.1%, n = 72) stayed in at least three rooms during their hospital admission compared with <30% of CO-CDI patients (28.4%, n = 172).ConclusionThe current state of room movement with CDI patients is suboptimal, resulting in increased infection risk for subsequent patients. A multi-faceted intervention to address this problem is essential to achieve an optimal goal of 1–2 rooms per hospital stay for a CDI patient. Quality improvement projects include (1) notification of patient movement to nursing leadership, (2) alerts to nursing supervisors of potential CDI patients before room transfer, and (3) earlier diagnosis of community-onset C. difficile.Disclosures All authors: No reported disclosures.

Outcomes and Mortality in Post-Operative C. difficile Infection: A Single Center Study

Introduction: C. difficile infection (CDI) is the most common cause of nosocomial diarrhea. Post-op patients (pts) have a distinctly increased risk of CDI and outcomes of such CDI are being actively investigated. We aimed to examine the time from surgery to first post-op CDI (i.e. index CDI) and to assess outcomes of post-op CDI among 3 major surgical categories, Gastrointestinal (GI), Vascular (Vasc), and Orthopedic (Ortho). Methods: We performed a retrospective study of pts who had surgery in one of 3 categories (GI, Ortho, and Vasc) and who developed CDI within 90 days of surgery. GI subgroups (intestinal [small intestine and colon], non-intestinal hollow viscera [stomach and gallbladder], and solid organ) were also analyzed. Pt characteristics between time of surgery and CDI were compared using ANOVA (for continuous variables) and Chi-squared test (for categorical variables). CDI recurrence rates were compared between groups using a Chi-squared test. Time from surgery to index CDI, all-cause mortality, and mortality related to CDI complications within 90 days after index CDI were analyzed using Kaplan-Meier curves and log-rank tests. Statistical significance was set at P<0.05. Results: We included 518 post-surgical pts (GI, n=187; Vasc, n=192; Ortho, n=139). Pts were older in Ortho and Vasc groups than in the GI group (Table 1). Compared with GI and Ortho, Vasc pts were more likely to be diabetic, have renal disease, and be immunocompromised at index CDI time. Compared with GI and Vasc, recent use of PPIs was less likely in Ortho pts. Use of antibiotics in the preceding 3 months was higher in Ortho and Vasc patients compared with GI pts. GI pts developed CDI sooner than Vasc pts after surgery (P=0.01); no other pairwise difference was noted (Figure 1). Among GI subgroups, nonintestinal hollow visceral procedures were complicated by CDI sooner than were intestinal procedures (P=0.02) (Figure 2). CDI recurrence was not significantly different between groups. All-cause mortality and mortality related to complications within 90 days from index CDI were higher in Vasc pts compared with GI pts (P=0.003 and 0.0032, respectively); no other pairwise difference was noted.191_A Figure 1. Patient Demographics and Clinical Characteristics at the time of CDI191_B Figure 2. Time from surgery to index CDI among post-surgical Gastrointestinal, Orthopedic, and Vascular patientsConclusion: Pts developed CDI sooner after GI surgery, especially non-intestinal hollow visceral surgery. Pts had higher all-cause mortality and mortality from complications of CDI at 90 days after Vasc surgery compared with GI surgery. There were no differences in mortality in Ortho pts compared with Vasc and GI pts.191_C Figure 3. Time from surgery to index CDI among post-surgical Gastrointestinal subgroups

EXAMINING RISK OF C DIFFICILE INFECTION WITH USE OF PROTON PUMP INHIBITOR VS H2 RECEPTOR ANTAGONIST

SESSION TITLE: Miscellaneous Critical Care SESSION TYPE: Original Investigations PRESENTED ON: 10/10/2018 07:30 AM - 08:30 AM PURPOSE: Clostridium difficile is a spore forming gram positive anaerobic bacteria that colonizes the large intestine and can cause colitis in susceptible populations, especially those with recent antibiotic use. Antibiotic therapy commonly leads to C. difficile infection (CDI) by alteration of the normal gut flora. More recently, usage of proton pump inhibitors (PPIs) have been shown to play a considerable role in this process as well. Studies have shown lower risks in H2 receptor antagonists (H2RAs) in comparison, however up to 73% of acid suppressant therapies (AST) have been found to be unnecessary in the hospital. We undertook a retrospective observational study to look at the prevalence of H2RA and PPI use in a patient population with confirmed laboratory diagnosis of CDI. METHODS: Hospital databases were accessed from January 1, 2014 to June 30, 2017 using the hospital Vigilanz software. Patients with a positive C. difficile toxin test, performed greater than or equal to 3 days after initial hospital admission, were defined as HA-CDI. Those with positive test performed prior to the 3 day mark were considered community acquired and excluded from the study. Rates of positive C. difficile toxin tests for each group were calculated. RESULTS: The study found 125 CDI cases confirmed by laboratory analysis. The average age of patients with CDI was 65 years, the study group consisted of 63/125 (50.4%) males and 62/125 (49.6%) females. 108/125 (86.4%) of patients were on AST. 81/108 (75%) of those on AST were taking H2RAs, of which 46/81 (56.8%) were on H2RA monotherapy. 63/108 (58.33%) of patients on AST were taking PPIs, of which 28/63 (44.44%) were on PPI monotherapy. Of the 74 patients with CDI who either taking H2RA or PPI, 46/74 (62.16%) were on H2RA therapy and 28/74 (37.84%) were on PPI therapy. Incidence of CDI with H2RA therapy was higher than with PPI therapy; this was not statistically significant (p =0.112). CONCLUSIONS: Studies have suggested that incidence of CDI is higher among patients who are on PPI as compared to those on H2RA. Our study failed to show this difference. Our preliminary study has several limitations as a small retrospective study with limited duration. Antibiotic regimen were also not taken into consideration. However, this study does hold value in providing feasibility for larger future studies. 32% of the patients with CDI were on both therapies at one point during the study period. Thus, a study may be undertaken in order to compare rates of CDI between PPI versus those de-escalated to H2RA from PPI, given a larger sample size is available. Furthermore, the role of de-escalation of both antibiotics and AST in decreasing the risk of CDI should also be explored. CLINICAL IMPLICATIONS: Unnecessary overuse of AST among hospitalized patients should be avoided. DISCLOSURES: No relevant relationships by Janay Bailey, source=Web Response No relevant relationships by Harmeet Deol, source=Web Response No relevant relationships by Mathew Kalapurayil, source=Web Response No relevant relationships by Alok Shrestha, source=Web Response No relevant relationships by Raghujit Singh, source=Web Response Speaker/Speaker's Bureau relationship with Sunovian Please note: $5001 - $20000 Added 11/20/2017 by Salim Surani, source=Web Response, value=Honoraria Advisory Committee Member relationship with Astra Zeneca Please note: $5001 - $20000 Added 11/20/2017 by Salim Surani, source=Web Response, value=Consulting fee

Establishment of an Endogenous Clostridium difficile Rat Infection Model and Evaluation of the Effects of Clostridium butyricum MIYAIRI 588 Probiotic Strain.

Clostridium difficile is well known as an agent responsible for pseudomembranous colitis and antibiotic-associated diarrhea. The hamster model utilizing an oral route for infection of C. difficile has been considered to be the standard model for analysis of C. difficile infection (CDI) but this model exhibits differences to human CDI, most notably as most hamsters die without exhibiting diarrhea. Therefore, we attempted to develop a new non-lethal and diarrheal rat CDI model caused by endogenous C. difficile using metronidazole (MNZ) and egg white. In addition, the effects of probiotic strain Clostridium butyricum MIYAIRI 588 (CBM) on CDI were examined using this model. Syrian Golden hamsters received clindamycin phosphate orally at 30 mg/kg on 5 days before challenge with either C. difficile VPI10463 (hypertoxigenic strain) or KY34 (low toxigenic clinical isolate). Mortality and the presence of diarrhea were observed twice a day for the duration of the experiment. Wistar rats received 10% egg white dissolved in drinking water for 1 week ad libitum following intramuscular administration of 200 mg/kg MNZ twice a day for 3 days. Diarrhea score was determined for each day and fecal water content, biotin concentration, and cytotoxin titer in feces were examined. More than 70% of hamsters orally infected with C. difficile died without exhibiting diarrhea regardless of toxigenicity of strain. The rats receiving egg white after MNZ administration developed diarrhea due to overgrowth of endogenous C. difficile. This CDI model is non-lethal and diarrheal, and some rats in this model were spontaneously cured. The incidence of diarrhea was significantly decreased in C. butyricum treated rats. These results indicate that the CDI model using egg white and MNZ has potentially better similarity to human CDI, and implies that treatment with C. butyricum may reduce the risk of CDI.

Chlorhexidine bathing and Clostridium difficile infection in a surgical intensive care unit

BackgroundClostridium difficile is the most common causative pathogen for hospital-acquired infections in the intensive care unit. This study evaluated the effect of chlorhexidine bathing every other day in preventing hospital-acquired C. difficile infection (CDI) using data from the CHlorhexidine Gluconate BATHing (CHG-BATH) randomized trial. MethodsThe primary endpoint was the proportion of patients acquiring CDIs among patients at risk for incident CDIs. Infections detected >48 h after randomization were classified as incident CDIs. Infections detected before or within 48 h of randomization were classified as prevalent CDIs. ResultsOf 38 patients (11.7%) who met criteria for potential CDI and underwent adjudication, 24 (7.4%) received oral or enema vancomycin, 18 (5.5%) had a positive C. difficile molecular assay, 14 (4.3%) received an International Classification of Diseases, Ninth Revision, Clinical Modification code for CDI, and 2 (0.6%) had possible pseudomembranous colitis on histopathology reports. The prevalence of CDI was 3.7% (6 of 164) in the soap and water arm and 4.3% (7 of 161) in the chlorhexidine arm. Compared with daily soap and water bathing, 2% chlorhexidine bathing every other day was not associated with the prevention of hospital-acquired CDI (1.3% [2 of 152] soap and water versus 2.0% [3 of 148] chlorhexidine, P = 0.68). ConclusionsIt is inconclusive if there was an association between chlorhexidine bathing and incidence of CDI among surgical intensive care unit patients in this study as statistical power was limited. There are limited published data evaluating the association between chlorhexidine bathing and CDI, and this study provides data for future systematic reviews and meta-analyses.

Clostridium difficile Infections: A Global Overview of Drug Sensitivity and Resistance Mechanisms.

Clostridium difficile (C. difficile) is the most prevalent causative pathogen of healthcare-associated diarrhea. Notably, over the past 10 years, the number of Clostridium difficile outbreaks has increased with the rate of morbidity and mortality. The occurrence and spread of C. difficile strains that are resistant to multiple antimicrobial drugs complicate prevention as well as potential treatment options. Most C. difficile isolates are still susceptible to metronidazole and vancomycin. Incidences of C. difficile resistance to other antimicrobial drugs have also been reported. Most of the antibiotics correlated with C. difficile infection (CDI), such as ampicillin, amoxicillin, cephalosporins, clindamycin, and fluoroquinolones, continue to be associated with the highest risk for CDI. Still, the detailed mechanism of resistance to metronidazole or vancomycin is not clear. Alternation in the target sites of the antibiotics is the main mechanism of erythromycin, fluoroquinolone, and rifamycin resistance in C. difficile. In this review, different antimicrobial agents are discussed and C. difficile resistance patterns and their mechanism of survival are summarized.

Prevalence of Clostridium difficile infection among the patients attending a tertiary care teaching hospital.

Clostridium difficile, a most important nosocomial enteric pathogen, is recognized globally as responsible for antibiotic-associated diarrhea and colitis. It is associated with considerable morbidity and mortality due to widespread use of antibiotics. The study was done to determine the prevalence of C. difficile infection (CDI) among the patients attending a tertiary care teaching hospital in Puducherry. We performed a prospective cohort study in Mahatma Gandhi Medical College and Research Institute. Around 150 patients were evaluated along with the patient details. C. difficile toxin detection was done as per the standard algorithm using the C. Diff Quik Chek Complete® assay (TECHLAB, Blacksburg, VA, USA). Analysis was done using statistics software (SPSS 16.0, SPSS Inc., Chicago, IL, USA). The prevalence of CDI was found to be 4%. More toxin-positive cases were between 50 and 60 years of age, and there was no difference in gender. Intensive Care Unit showed more toxin-positive cases; however, there was no significant association between the occurrence of CDI and the primary diagnosis of the patients. The prevalence of CDI in our hospital was found to be 4%, which was relatively lower compared to other Indian studies. However, awareness of the risk factors may assist in identifying patients at higher risk for CDI, guide implementation of appropriate preventive measures, and modulate potential intervention measure during management.

Does Obesity Influence the Risk of C. difficile Infection Among Patients with Ulcerative Colitis?

Introduction: Patients with ulcerative colitis (UC) are at an increased risk C. difficile infection (CDI) compared with the general population. Recent data suggests that obesity also increases the risk of CDI. The purpose of this study was to examine whether obesity influences the risk of CDI among patients with UC. Methods: We performed a retrospective cross-sectional study of 636 patients with ulcerative colitis seen at an outpatient gastroenterology clinic between January 1, 2014 and December 31, 2015. Electronic medical records (EMR), available after 2010, were reviewed for UC patients. Body mass index (BMI) was used to define underweight (BMI < 18.5), normal weight (18.5≤BMI < 25), overweight (25≤BMI < 30), and obese (BMI≥30). Unpaired t-test, chi-squared analysis, and ANOVA were used for between-group comparisons. Multivariate logistic regression included age, gender, tobacco use, UC disease duration, TNF or vedolizumab exposure, and vitamin D deficiency. Log likelihood ratio test for linear trend was used to evaluate BMI and CDI risk. Results: Cohort demographics included average patient age 54 (SD 17), 48% male, 4.3% active tobacco use, UC disease duration 15.2 years (SD 12.5), and 318 (51%) with extensive UC, and did not differ between patients with and without CDI. 114 (18%) were classified as obese, 232 (36%) overweight, 274 (43%) normal weight, and 16 (2.5%) underweight. Nineteen patients (3.0%) developed CDI during the study period, 5 (26%) of which were hospitalized within 6 months prior to CDI. Three patients had Mayo 0 endoscopic subscore and histologic remission within one year of CDI diagnosis. At time of CDI diagnosis, 5 (26%) were on antibiotics, 5 (26%) were on TNF (2 on combination therapy with thiopurine), and 1 on tofacitinib. Six (32%) patients developed UC flare attributed to CDI. CDI risk was not affected by BMI (OR 0.90, 95% CI 0.79-1.02). Compared to normal weight patients, risk of CDI was not influenced by obesity (OR 0.64, 95% CI 0.15-2.67), or being overweight (OR 0.33, 95% CI 0.08-1.32) or underweight (OR 3.08, 95% CI 0.44-21.81). There was no significant trend towards CDI risk based on BMI category. Ever use of TNF therapy was associated with CDI on univariate (OR 5.41, 95% CI 2.13-13.71) and multivariate (OR 7.91, 95% CI 2.71-23.07) analyses. Conclusion: Although limited by low prevalence of CDI, obesity does not appear to influence the risk of CDI among patients with UC.

5-Aminosalicylic Acid (5-ASA) Usage During C. difficile Infection (CDI) Is Associated with Decreased ICU Admission and Improved Long-term Outcomes

Introduction: Pts with Inflammatory bowel disease (IBD) are at increased risk for CDI. 5-ASA effects on the small bowel and colonic mucosa may be protective against CDI. We hypothesize that pts with CDI who are chronically on a 5-ASA have better outcomes compared with those not on a 5-ASA. Methods: We identified consecutive pts with a +C. difficile toxin assay and symptomatic diarrhea at Yale-New Haven Hospital between 4/10 and 5/14. For each patient, we recorded demographics, medical co-morbidities, lab data at diagnosis, treatments and outcomes (ICU admission, 90-day readmission, 6 and 12-month mortality). Pts were grouped into those on a 5-ASA (CDI+5-ASA) and those not on a 5-ASA (CDI-5-ASA) and subsequently compared (SPSS 23.0). Results: We identified 796 patients with CDI; 19 (3.0%) were receiving a 5-ASA and 777 (97.0%) were not. CDI+5-ASA were younger (54.4±24.2, 65.1±17.9 years, p=0.012) with a lower Charlson comorbidity score (1.94±1.8, 3.08±2.4, p=0.04). No other differences in demographics were observed. At the time of diagnosis, CDI+5-ASA were more likely to have IBD (100% vs. 2.1%, p < 0.001) without differences in biologic (10.5% vs. 20.0%, p=0.63) or Immuno-modulator use (15.8%, 0%, p=0.24). Vital signs and serologies at presentation were similar among the cohorts, with a trend for increased CT abdomen (42.1%, 22.9%, p=0.06) in CDI+5-ASA. Treatment patterns did not vary among the cohorts. CDI+5-ASA were less likely to require ICU admission at diagnosis (5.3%, 32.1%, p=0.01) or during hospitalization (5.3%, 38%, p=0.003). In a logistic regression, controlling for Charlson co-morbidity score and age, CDI+5-ASA were less likely to be admitted to the ICU at diagnosis (OR, 0.132; CI, 0.02-1.0, p=0.05), require any ICU admission during hospitalization (OR, 0.11; CI, 0.01-0.8, p=0.03) or be readmitted within 90 days (OR, 0.31; CI, 0.10-0.97, p=0.044). CDI+5-ASA were less likely to be readmitted within 90 days (21.1%, 42.2%, p=0.006) or die within 6 (0%, 3.3%, p=0.02) or 12-months (0%, 30.2%, p=0.01). Conclusion: CDI+5-ASA have less severe outcomes compared with CDI-5-ASA independent of age and co-morbidities. The lower ICU requirement and mortality in CDI+5-ASA may be due to 5-ASA effect on the host microbiome, reduction of colonic inflammatory response or direct inhibitory effects on C. difficile toxins.

Identification of population at risk for future Clostridium difficile infection following hospital discharge to be targeted for vaccine trials

BackgroundEfforts to develop a Clostridium difficile vaccine are underway; identification of patients at risk for C. difficile infection (CDI) is critical to inform vaccine trials. We identified groups at high risk of CDI≥28 days after hospital discharge. MethodsHospital discharge data and pharmacy data from two large academic centers, in New York and Connecticut, were linked to active population-based CDI surveillance data from the Emerging Infections Program (EIP). Adult residents of the EIP surveillance area were included if they had an inpatient stay at a study hospital without prior history of CDI. The primary outcome was CDI by either toxin or molecular assay ≥28 days after an index hospitalization. Important predictors of CDI≥28 days post discharge were initially identified through a Cox proportional hazards model (stepwise backward selection) using a derivation cohort; final model parameters were used to develop a risk score evaluated in the validation cohort. ResultsOf the 35,186 index hospitalizations, 288 (0.82%) had CDI≥28 days post discharge. After parameter selection, age, number of hospitalizations in the prior 90 days, admission diagnosis, and the use of 3rd/4th generation cephalosporin, clindamycin or fluoroquinolone antibiotic classes remained in the model. Using the validation cohort, the risk score was predictive (p<0.001) with a c-score of 0.75. Based on the distribution of scores in the derivation cohort, we divided the patients into low and high risk groups. In the high risk group, 1.6% experienced CDI≥28 days post discharge compared to 0.3% among our low risk group. ConclusionsOur study identified specific parameters for a risk score that can be applied at discharge to identify a patient population whose risk of CDI≥28 days following an acute care hospitalization was 5 times greater than other patients.

In vitro augmented photodynamic bactericidal activity of tetracycline and chitosan against Clostridium difficile KCTC5009 in the planktonic cultures

Infection with Clostridium difficile (C. difficile) causes a severe colitis with high recurrence. Treatment of C. difficile infection (CDI) is based on antibiotics in spite of the increase of resistance. To interrupt the vicious cycles such as new antibiotics treatment and appearance of resistance strains, photodynamic therapy (PDT) might be a possible alternative therapy for CDI. Tetracycline (TC) has been used as a broad spectrum antibiotic with low risk of CDI and a photosensitizer (PS) in PDT. In vitro PDT against C. difficile was conducted using UVA and TC as a PS before in vivo study. To enhance the photodynamic antibacterial activity of TC, we applied chitosan as a boostering agent. Bactericidal effects after PDT, were measured by counting viable cells, DNA damage and membrane integrity. At 1mg/mL of TC, chitosan treatment combined with PDT, increased the bactericidal effect by >10,000-fold of the effect of PDT alone. Membrane damage and cellular DNA damage demonstrated by EMA-qPCR were also greater in the group treated with PDT+chitosan than in that treated PDT alone. The present study showed that PDT using a combination of TC and chitosan is an effective method for killing C. difficile.

C. difficile-Associated Risk of Death Score (CARDS): A Novel Risk Score to Predict Mortality Among Hospitalized Patients With C. difficile Infection: ACG Fellow Award

Introduction:C. difficile infection (CDI) is the leading health care-associated infection in the United States with significant associated mortality. Existing treatments for CDI vary in their absolute and relative efficacy based on severity of underlying disease; yet there are few objectively derived severity scores. Furthermore, development of an accurate scoring system to define severity across large administrative databases additionally allows for important comparisons in outcomes across populations and over time. Our aim was to develop a novel CDI risk score to predict mortality for clinicians and epidemiologists entitled: C. difficile associated risk of death score (CARDS). Methods: We obtained data from the 2011 nationwide inpatient sample (NIS) database, the largest source of all-payer hospital discharge information in the United States capturing data from 1,049 hospitals within 46 states. Standard international classification of disease, 9th Edition (ICD-9) was used to identify all patients with CDI (008.45). Multivariate logistic regression was utilized to identify independent predictors of mortality in patients with CDI. A risk score was calculated by assigning a numeric weight to each parameter based on their odds ratio (OR). Predictive properties of model discrimination were assessed using the c-statistic and CARDS compared to standard models. Results: We identified 343,982 hospitalizations with an associated diagnosis of CDI, 8% of whom died in the hospital. The 8 CARDS predictors identified on multivariate analysis were age, cardiopulmonary disease, malignancy, diabetes, inflammatory bowel disease, acute renal failure, liver disease, and intensive care admission (ICU) admission, with weights ranging from -1 (for diabetes) to 5 (for ICU admission). The overall risk score in the cohort ranged from 0 to 18. Mortality increased significantly as CARDS increased. CDI-associated mortality was 1% with CARDS=0; 4% with CARDS=5; 20% with CARDS=10; 47% with CARDS=15 and 100% with CARDS=18. The predictive test characteristic for CARDS was robust (c-statistic=0.77). CARDS performed better than age, sex, and Charlson co-morbidity index model (c-statistic=0.64) or age, sex, Charlson co-morbidity index, and ICU admission model (c-statistic= 0.73) in predicting CDI-associated mortality in hospitalized patients. Conclusion: CARDS is a promising risk score to predict mortality among hospitalized with CDI. It may be useful to stratify CDI severity and compare outcomes over time and across settings using administrative data. Disclosure - Dr. Ananthakrishnan - Scientific advisory board of Cubist Pharmaceuticals.

Clostridium difficile: Deleterious Impact on Hematopoietic Stem Cell Transplantation

C. difficile infection (CDI), the most common cause of hospital-acquired diarrhea, is very frequent after hematopoietic stem cell transplantation (HSCT). Recent publications suggest it affects between 6% and 20% of HSCT recipients during the first year and is more common following allogeneic transplant (allo-HSCT). The best diagnostic strategy remains to be defined, but molecular testing for the toxin genes by polymerase chain reaction (PCR) seems to be replacing the traditional enzyme immunoassays (EIA). The higher sensitivity of the PCR may result in increased measured incidence of disease. C. difficile infection typically occurs during the first month after HSCT. Although the course of CDI after HSCT does not seem to be different than in other hospitalized patients, it may result in worsening of bowel graft versus host disease (GVHD) after allo-HSCT. Current evidence suggests a reciprocal effect by which GVHD may increase the risk of CDI and C. difficile disease may increase the risk of GVHD. Metronidazole was the treatment most commonly used in all recent series, followed by the combination metronidazole and oral vancomycin. There is minimal information on the use of fidaxomicin in HSCT recipients. Regarding stool transplant, there is one case report of successful use of this modality in an HSCT recipient. These two newer approaches will certainly be investigated in the future.

Mortality in patients with Clostridium difficile infection correlates with host pro-inflammatory and humoral immune responses

Host anti-toxin immune responses play important roles in Clostridium difficile disease and outcome. The relationship between host immune and inflammatory responses during severe C. difficile infection (CDI) and the risk of mortality has yet to be defined. We aimed to investigate the host systemic IgG anti-toxin immune responses, the in vitro cytotoxicity of the infecting C. difficile ribotyped strain, and the host inflammatory markers and their relationship to CDI disease severity and risk of mortality. Inflammatory markers, co-morbidities and CDI outcomes were recorded in a prospective cohort of 150 CDI cases. Serum anti-cytotoxin A (TcdA) and anti-TcdB IgG titres were measured by ELISA and the infecting C. difficile isolate was ribotyped and the in vitro cytotoxin titre assessed. A low median anti-TcdA IgG titre was significantly associated with 30-day all-cause mortality (P<0.05). Ribotype 027 isolates were significantly more toxinogenic than other ribotypes (P<0.00001). High cytotoxin titres correlated with increased inflammatory markers but also higher anti-TcdA and -TcdB (P<0.05) IgG responses resulting in a lower risk of mortality. On multivariate analysis, predictors of mortality were peak white cell count >20 × 10(9) l(-1) [odds ratio (OR) 11.53; 95 % confidence interval (CI) 2.38-55.92], creatinine concentration >133 µmol l(-1) (OR 6.54; 95 % CI 1.47-29.07), Horn's index >3 (OR 4.09; 95 % CI 0.76-22.18) and low anti-TcdA IgG (OR 0.97; 95 % CI 0.95-0.99), but not ribotype, cytotoxin titre or anti-TcdB IgG. Thus, host pro-inflammatory and humoral responses correlate with the cytotoxin titre of the infecting strain and effective anti-toxin immune responses reduce the risk of mortality.

Probiotics Plus Antibiotics Increased C. difficile Risk

SAN DIEGO – The concomitant use of probiotics and antibiotics already associated with Clostridium difficile infections increased the risk of developing C. difficile by nearly threefold, a single-center retrospective study showed. “We were very surprised by this finding,” Justine E. Dickson, PharmD, said in an interview. Dr. Dickson and her colleagues at Yale–New Haven Hospital evaluated 389 adult inpatients who received high-risk antibiotics for 5 days or more. High-risk antibiotics investigated included ceftriaxone, ciprofloxacin, clindamycin, imipenem-cilastatin, levofloxacin, and meropenem. Formulary probiotics investigated were Lactobacillus GG and Saccharomyces boulardii. Of the 389 patients, 246 (63%) received antibiotics alone while 143 (37%) received antibiotics and a probiotic. A total of 20 patients (5%) developed a C. difficile infection (CDI) within 90 days of antibiotic use. The average duration of high-risk antibiotic use was 7.3 days among those who received probiotics and 7.7 days among those in the antibiotics-only group. Dr. Dickson, who is now a pharmacy resident at the University Hospital in Cincinnati, reported at the annual IDWeek meeting that the incidence of CDI was 8.4% among patients who received probiotics compared with 3.3% in the antibiotics-only group. Levofloxacin was the most common high-risk antibiotic used by patients who developed a CDI, in 65% of cases. The risk of developing CDI among patients who received probiotics was 2.7 times higher than in patients in the antibiotics-only group, a difference that reached statistical significance. After controlling for the use of levofloxacin (the researchers initially speculated that this antibiotic might be a key culprit), they found that the relative risk remained similar, at 2.6 times higher among patients who received probiotics. When the researchers factored in the concomitant use of proton pump inhibitors, the incidence of CDI did not differ among patients in the antibiotics-only group, but the concomitant use of probiotics further increased the risk of CDI, “which may suggest a potential interaction between these two drug classes,” the researchers wrote in their abstract, which was presented during a poster session. The investigators stated that they had no relevant financial conflict to disclose. Editor's NoteHere's something distinctly counterintuitive. It's a small, single-site, retrospective, obviously not-randomized, not-placebo-controlled study, but it gives me pause to consider whether I am doing the right thing by reflexively ordering probiotics with these high-risk antibiotics in my nursing home residents.To date, the literature has not shown a compelling advantage to the use of probiotics, but there is at least some work suggesting that they are of benefit, and this is the first I've seen of something suggesting that outcomes are significantly worse (at least if you consider a C. diff. infection a bad outcome). I hope more work is being done in this area.–Karl Steinberg, MD, CMD, Editor in Chief Here's something distinctly counterintuitive. It's a small, single-site, retrospective, obviously not-randomized, not-placebo-controlled study, but it gives me pause to consider whether I am doing the right thing by reflexively ordering probiotics with these high-risk antibiotics in my nursing home residents. To date, the literature has not shown a compelling advantage to the use of probiotics, but there is at least some work suggesting that they are of benefit, and this is the first I've seen of something suggesting that outcomes are significantly worse (at least if you consider a C. diff. infection a bad outcome). I hope more work is being done in this area. –Karl Steinberg, MD, CMD, Editor in Chief

Epidemiology and Outcomes of Clostridium difficile Infections in Hematopoietic Stem Cell Transplant Recipients

Background. Clostridium difficile is the leading cause of infectious diarrhea among hospitalized patients and is a major concern for patients undergoing hematopoietic stem cell transplantation (HSCT). Risk factors and the natural history of C. difficile infection (CDI) are poorly understood in this population. Methods. We performed a retrospective nested case-control study to describe the epidemiology, timing, and risk factors for CDI among adult patients who received HSCTs at our center from January 2003 through December 2008. Results. The overall 1-year incidence of CDI was 9.2% among HSCTs performed (n = 999). The median time to diagnosis of CDI was short among both autologous and allogeneic HSCT recipients (6.5 days and 33 days, respectively). Risk factors for CDI in allogeneic HSCT recipients included receipt of chemotherapy prior to conditioning for HSCT, broad-spectrum antimicrobial use, and acute graft-versus-host disease (GVHD; adjusted odds ratio [AOR], 4.45; 95% confidence interval [CI], 1.54-12.84; P = .006). There was a strong relationship between early CDI and subsequent development of gastrointestinal tract GVHD in the year following allogeneic HSCT (P < .001). Gastrointestinal GVHD was also strongly associated with an increased risk for recurrent CDI (AOR, 4.23 [95% CI, 1.20-14.86]; P = .02). Conclusions. These results highlight the high incidence and early timing of CDI after HSCT. Early timing, coupled with the noted risk of pretransplant chemotherapy, suggests that the natural history of disease in some patients may involve colonization prior to HSCT. A potentially important interplay between CDI and GVHD involving the gastrointestinal tract was observed.

CSI: a severity index for Clostridium difficile infection at the time of admission

Clostridium difficile is a common cause of nosocomial diarrhoea in the USA. To develop a score model that would help to identify severe versus mild or moderate C. difficile infection (CDI) upon admission we performed a retrospective cohort study. Between January 2004 and December 2007, 255 patients met inclusion criteria for this study. Severe CDI was defined as cases that required colectomy, intensive care unit management, ended in death, or hospitalisation of >10 days. Data recorded included past medical history, physical examination on admission, laboratory data and imaging/colonoscopy data. To create the CDI severity index (CSI) score, we included four risk factors for severe CDI that were identified by univariate analysis: history of malignancy, white blood cell count at admission >20,000/dL, blood albumin <3.0mg/dL, and creatinine at admission >1.5-fold the baseline value. One point was assigned to each of the risk factors. As indicated by a c-statistic of 0.78, the CSI score predicted severe CDI much better than chance (c-statistics of 0.50). The risk of developing severe CDI increased by a factor of 2.9 (95% CI: 1.82-4.59) for each 1-point increase in the CSI score. A CSI score with a cut-off value of 2 had a sensitivity and specificity of 82% and 65%, respectively. The CSI score may quantify the risk of severe CDI at the time of admission, and help in early identification of patients who may benefit from more aggressive treatment.

Evaluation of Hospital Room Assignment and Acquisition of Clostridium difficile Infection

Clostridium difficile spores persist in hospital environments for an extended period. We evaluated whether admission to a room previously occupied by a patient with C. difficile infection (CDI) increased the risk of acquiring CDI. Retrospective cohort study. Medical intensive care unit (ICU) at a tertiary care hospital. Patients admitted from January 1, 2005, through June 30, 2006, were evaluated for a diagnosis of CDI 48 hours after ICU admission and within 30 days after ICU discharge. Medical, ICU, and pharmacy records were reviewed for other CDI risk factors. Admitted patients who did develop CDI were compared with admitted patients who did not. Among 1,844 patients admitted to the ICU, 134 CDI cases were identified. After exclusions, 1,770 admitted patients remained for analysis. Of the patients who acquired CDI after admission to the ICU, 4.6% had a prior occupant without CDI, whereas 11.0% had a prior occupant with CDI (P = .002). The effect of room on CDI acquisition remained a significant risk factor (P = .008) when Kaplan-Meier curves were used. The prior occupant's CDI status remained significant (p = .01; hazard ratio, 2.35) when controlling for the current patient's age, Acute Physiology and Chronic Health Evaluation III score, exposure to proton pump inhibitors, and antibiotic use. A prior room occupant with CDI is a significant risk factor for CDI acquisition, independent of established CDI risk factors. These findings have implications for room placement and hospital design.