Mild Clostridium Difficile Infection Research Articles

EP492 - Fulminant Clostridium difficile infection post reversal of ileostomy

Abstract Aims Clostridium difficile infection (CDI) is an important cause of diarrhoea in hospitalized patients, varying from mild to fulminant forms. Fulminant CDI subsequent to the reversal of ileostomy, despite negative C. difficile toxin, is rare. Results We present the case of a 75-year-old male with a history of atrial fibrillation, chronic obstructive pulmonary disease and hypertension, who underwent elective ileostomy reversal following an emergency laparotomy and end ileostomy for acute diverticular bleed two years prior. Initially uncomplicated, the patient developed mild CDI on postoperative day 4 with white cell count of 18.6×109/L, evolving rapidly to severe CDI by day 6, characterized by worsening abdominal pain, worsening leukocytosis (30×109/L), and acute kidney injury stage 1. Patient was started on Vancomycin and Metronidazole, Computed Tomography (CT) scan showed uncomplicated sigmoid colitis. Despite aggressive antibiotic therapy and fluid resuscitation, the patient deteriorated on day 8, presenting with fulminant CDI, hypotension, elevated lactate of 2.6 and leukocytes of 46×109/L. Subsequent CT Imaging revealed pneumatosis coli. At that point, the patient's NELA score was 53.4%. The patient was stabilised by the critical care team prior to emergency subtotal colectomy and end ileostomy due to suspected colonic perforation. Surgical finding showed transverse colon inflammation with a hepatic flexure abscess. Patient required 14-day intensive care unit stay and 13 days of ward management before he is fit for rehab. Conclusion This case highlights the potential for fulminant CDI post-ileostomy reversal and highlights the challenges in managing such complications, necessitating prompt recognition and interventions to mitigate adverse outcomes.

Fidaxomicin compared with vancomycin and metronidazole for the treatment of Clostridioides (Clostridium) difficile infection: A network meta-analysis

We conducted a systematic review of the literature and network meta-analysis (NMA) to compare the relative effectiveness of antibiotic treatments for Clostridioides (Clostridium) difficile infection (CDI) including vancomycin (VCM), metronidazole (MTZ) and fidaxomicin (FDX). Eligible studies were randomised controlled trials (RCTs) including adults with any severity of CDI that was treated with VCM, MTZ or FDX. The NMA was performed using a Bayesian framework, using a fixed-effects model.The searches identified seven publications for inclusion, which provided five RCTs for VCM versus MTZ, and three RCTs for FDX versus VCM. The NMA showed that for clinical cure rate, there was no difference for FDX versus VCM, and there was a significant difference in favour of FDX versus MTZ (odds ratio [OR]: 1.77; 95% credible interval [CrI] 1.11, 2.83]). For recurrence rate, there was a significant difference in favour of FDX versus both VCM (OR: 0.50; 95% CrI: 0.37, 0.68) and MTZ (OR: 0.44; 95% CrI: 0.27, 0.72). For sustained cure (clinical cure without recurrence), there was a significant difference in favour of FDX versus VCM (OR: 1.61; 95% CrI: 1.27, 2.05) and MTZ (OR: 2.39; 95% CrI: 1.65, 3.47).These findings suggest that FDX and VCM are effective first-line treatments for mild or moderate CDI, whereas MTZ is not, and FDX may be more effective at preventing CDI recurrence than VCM.

223 Does “Prior Appendectomy” Affect the Outcomes of Clostridium difficile Infection in Hospitalized Patients? A Retrospective Review and Analysis

INTRODUCTION: Clostridium difficile infection (CDI) is prevalent in hospitalized patients and accounts for significant morbidity and mortality. Management and outcomes of these patients depend on the severity of CDI. Current classification of severity of CDI includes parameters that depict its inflammatory response. We attempted to study the influence of prior appendectomy on severity and outcomes of CDI. METHODS: We conducted a retrospective chart review of 1248 patients admitted to our institute between 2008 and 2016, whose stool tested positive for Clostridium difficile toxin. Baseline characteristics, comorbidities, and lab values were extracted from the EMR. Information regarding prior appendectomy was obtained from medical documentation and abdominal imaging, whichever was available. Patients were grouped into those with prior appendectomy (group A) and those without (group B). In-hospital Mortality was defined as death during the same hospital admission as CDI. Severity was defined as per the Infectious Diseases Society of America guidelines. The primary outcomes were to 1) assess all-cause in-patient mortality and 2) severity of CDI, attributable to prior appendectomy. RESULTS: There were a total of 1248 patients of which 13.5% (n = 175) had a history of prior appendectomy. The mean age was similar in both groups (57 years), and baseline characteristics were comparable. There was a female preponderance (60.06%) in group A. The dominant patient race was African American (36.6% in group A and 39.8% in group B). All lab parameters were similar in both groups, except WBC counts, which were higher amongst patients with appendectomy (13 vs. 11, ±8) (P 0.013). Group A patients were more likely to have a severe presentation of CDI (40%, n = 68), whereas group B had mostly mild CDI (45.9%, n = 492). Prior appendectomy did affect the severity status, although statistical significance was not achieved (P 0.057). There was no statistical difference in mortality either, with 25 deaths in group A (14.3%) and 169 in group B (15.8%) (P 0.62). Regression analysis performed to ascertain independent predictors of all-cause mortality in CDI did not identify prior appendectomy as a risk factor. CONCLUSION: Prior appendectomy status may affect the severity of CDI and hence the need for colectomy. However, we did not observe a difference in mortality associated with prior appendectomy. Since the prevalence of prior appendectomy was low in our study, larger population studies are needed to establish significant outcomes.

Prevalence of Clostridium difficile infection among hospitalized inflammatory bowel disease patients in Greece.

Inflammatory bowel disease (IBD) is an independent risk factor for Clostridium difficile infection (CDI), which is associated significantly with disease severity. We aimed to determine the rates of CDI among hospitalized IBD patients in major tertiary referral hospitals in Greece. A retrospective analysis was carried out of stool cultures from hospitalized patients investigated for diarrhea, during 2016, tested for CDI with glutamate dehydrogenase (GDH) and toxins A and B. In total, 6932 patients were tested for CDI; 894 were positive for GDH (12.89%) and 339 were also positive for C. difficile toxin (4.89%). The prevalence of CDI among all hospitalized patients was 1.6/1000 patient-days. Among these, there were 401 IBD patients, and 62 were positive for GDH (15.46%) and 30 were also positive for C. difficile toxin (7.48%). The prevalence of CDI in IBD patients was 2.5/1000 patient-days, significantly higher than in non-IBD hospitalized patients (30/401 vs. 309/6531, P=0.013). Among the 30 IBD patients (ulcerative colitis=18, Crohn's disease=12) with CDI, six were receiving biologics, three were on corticosteroids [one combined with azathioprine (AZA) and one combined with 5-ASA], nine were on AZA monotherapy and 12 were on 5-ASA monotherapy. The prevalence of CDI among patients receiving AZA monotherapy was significantly higher than in patients receiving other medications (9/68 vs. 21/333, P=0.047). Mild CDI (n=28) was treated with metronidazole and/or vancomycin, whereas severe CDI (n=2) was treated with vancomycin. The prevalence of CDI is higher in hospitalized IBD patients than those without IBD and AZA monotherapy increases the risk of CDI.

Effect of using fidaxomicin on recurrent Clostridium difficile infection

Fidaxomicin is a macrocyclic antibiotic licensed for treating Clostridium difficile infection (CDI). In the UK, fidaxomicin is often reserved for severe CDI or recurrences. At Queen Elizabeth Hospital Birmingham, all courses of fidaxomicin during 2017/2018 were reviewed. Thirty-eight patients received fidaxomicin, of which 64% responded to treatment when fidaxomicin was given during the first episode of mild CDI. Conversely, all patients with recurrent CDI failed treatment with fidaxomicin. There were mixed results for the use of fidaxomicin for severe CDI, with only 42% of patients responding. These results suggest that fidaxomicin is best suited as a treatment for mild CDI during a patient's first episode.

What Is the Role for Metronidazole in the Treatment of Clostridium difficile Infection? Results From a National Cohort Study of Veterans With Initial Mild Disease

Metronidazole may still be an appropriate therapeutic option for mild Clostridium difficile infection (CDI) in select patients, but data are limited to guide clinicians in identifying these patients. Our 2-stage study included a national cohort of Veterans with a first episode of mild CDI (2010-2014). First, among those treated with metronidazole, we identified predictors of success, defined as absence of all-cause mortality or recurrence 30 days posttreatment, using multivariable unconditional logistic regression. Second, among a subgroup of patients with characteristics predictive of success identified in the first stage, we compared clinical outcomes among those treated with metronidazole compared with vancomycin, using Cox proportional hazards models for time to 30-day all-cause mortality, CDI recurrence, and failure. Among 3656 patients treated with metronidazole, we identified 3282 patients with success and 374 patients without success (failure). Younger age was the only independent predictor of success. Age ≤65 years was associated with an odds of success 1.63 times higher (95% confidence interval [CI], 1.29-2.06) than age >65 years. Among 115 propensity score-matched pairs ≤65 years of age, no significant differences were observed between metronidazole and vancomycin (reference) for all-cause mortality (hazard ratio [HR], 0.29 [95% CI, .06-1.38]), CDI recurrence (HR, 0.62 [95% CI, .26-1.49]), or failure (HR, 0.50 [95% CI, .23-1.07]). Among patients ≤65 years of age with initial mild CDI, clinical outcomes were similar with metronidazole and vancomycin. These data suggest that metronidazole may be considered for the treatment of initial mild CDI among patients 65 years of age or younger.

490. Comparison of Clostridium difficile Infection Outcomes by Diagnostic Testing Method

BackgroundUS laboratories are increasingly using nucleic acid amplification tests (NAAT) to diagnose Clostridium difficile infection (CDI) due to their increased sensitivity over toxin enzyme immunoassays (EIA), but NAATs may be more likely than toxin EIAs to detect colonization rather than true disease. Limited data indicate patients positive by toxin EIA (toxin+) have worse outcomes than those positive by NAAT (NAAT+) only, suggesting toxin EIA detects true infection more often than NAAT. We used multisite CDI surveillance data from the Centers for Disease Control and Prevention’s Emerging Infections Program to compare clinical course and outcomes between toxin+ and NAAT+ only patients.MethodsA case was defined as a positive C. difficile test in a person ≥1 year old with no positive tests in the prior 8 weeks. Cases detected during 2014–2015 by a testing algorithm using toxin EIA and NAAT were classified as toxin+ or NAAT+ only. Medical charts were reviewed. Death data were obtained from state death registries. Multivariable logistic regression models were used to compare CDI recurrence and 90-day mortality between the two groups, adjusting for age, sex, race, Charlson comorbidity index, and receipt of oral vancomycin. For the outcome of recurrence, we also adjusted for history of CDI in the prior 6 months.ResultsOf 4,878 cases, 2160 (44%) were toxin+ and 2,718 (56%) were NAAT+ only. Toxin+ cases were more likely than NAAT+ only cases to be ≥65 years old (48% vs. 38%; P < 0.0001), have white blood cells ≥15,000/µL (483/1,539 [31%] vs. 423/1,978 [21%]; P < 0.0001), and have received oral vancomycin ≤3 days of diagnosis (32% vs. 29%; P = 0.03). Comparing toxin+ to NAAT+ only cases, 21% vs. 11% had a recurrence (P < 0.0001), of which 71% vs. 33% had a toxin+ recurrence (P < 0.0001), and 10% vs. 9% died ≤90 days of diagnosis (P = 0.12). In multivariable analysis, a toxin+ result was associated with recurrence (adjusted odds ratio [aOR]: 1.89, 95% CI: 1.61–2.22) but not with 90-day mortality (aOR: 0.99; 95% CI: 0.81–1.22).ConclusionToxin+ CDI is more severe by some markers and more likely to recur as toxin+. However, there was no difference in adjusted mortality, which may reflect an effect on mortality in NAAT+ only cases from mild CDI, receipt of unnecessary CDI treatment, or other factors.Disclosures G. Dumyati, Seres: Scientific Advisor, Consulting fee.

Beyond Pain Relief: Is Narcotic Analgesia Safe During Clostridium difficile Infection?

Introduction: Majority of patients with Clostridium Difficile infection (CDI) receive opioids for analgesia during hospitalization. Due to their antiperistaltic effect, opioids could alter the gut microbiome and enhance absorption of bacterial toxins. There has been scarce reports implicating that opioids use may worsen prognosis in CDI, but association and causality are not sorted out yet. Our study aims to highlight any correlation, independent of severity of disease, between opioids use in CDI and outcomes such as morbidity, mortality, and duration of hospitalization. Methods: A retrospective study was done on 321 patients with CDI who were divided into 2 groups based on total dose of morphine equivalent (ME) received during first 4 days: control ≤10 mg and opioid >10 mg. After adjusting for severity at diagnosis, reassessment of severity and complications on day 4, hospital mortality, readmission for CDI within 3 months, length of stay (LOS), and disposition were compared between the study arms. Regression analysis was conducted to control for confounding factors. Results: The opioid arm consisted of 150 patients while 171 patients served as control. Independent of disease severity at diagnosis, opioid group showed significant worsening at day 4 (49.3%vs23.9%,p<0.01,OR:3.08), increased WBC, creatinine, complications (28.6%vs16.9%,p=0.01,OR:1.96), and longer LOS (mild CDI:13.4%vs8.3%,p< 0.001;severe CDI:18%vs9.1%,p< 0.001). In opioid arm, a higher dose of ME was associated with more complications (p=0.002). Hospital mortality in opioid group was significantly higher (17.3%vs9.3%,p=0.03,OR:2). However, this significant difference was not replicated when we controlled for baseline severity. Readmission for CDI within 3 months was higher in patients with mild CDI receiving>10 mg ME (25%vs7%,p=0.04).Control patients were likely to be discharged home while opioid group required predominantly long term facilities care (48.5%vs30%,p<0.01,OR:2.2). Conclusion: Opioid usage for analgesia in CDI independently increases the risk for severe disease, complications, hospital stay, readmission rates and discharge to a long term facility. This could have detrimental effects on patient care and healthcare expenditure. On the other hand, mortality was not influenced by opioid usage which denies any causality effect of opioids on mortality. Heightened awareness is warranted to consider alternative agents for analgesia in CDI. Larger randomized trials are needed to shed more light on this subject.215_A Figure 1. Outcomes in Patients Receiving Opioids versus Controls215_B Figure 2. Number of complications versus Opioid Dosage

Should We Reconsider Eliminating Metronidazole as Therapy for Clostridium difficileColitis?

Introduction: The new guidelines published in Clinical Infectious Disease in 4/18 recommend vancomycin or fidaxomicin for initial treatment of even mild Clostridium difficile infection (CDI) rather than metronidazole due to higher cure rates. However along with cost concerns, treatment failures need be considered. Our recent research analyzed the risk factors responsible for fulminant CDI requiring fecal microbiota transplant (FMT). The results of our study regarding metronidazole prompted us to think more about these new guidelines and raised the question of if we should reconsider eliminating metronidazole as initial therapy for CDI. Methods: A retrospective chart review was conducted to collect data on patients with CDI responding to antibiotic therapy alone (Group A) vs patients with fulminant recurrent CDI requiring FMT (Group B). The data was analyzed using a logistic regression model to associate the two groups with multiple variables including age, sex, comorbidities, antibiotic use as therapy for CDI, number of recurrences, inpatient status at time of initial infection, and PPI use. Odds ratios corresponding to each covariate were reported with a 95% confidence interval and significance level of 0.05. Results: 152 total subjects were reviewed with 87 in Group A and 66 in Group B. Significant differences found between the two groups included history of ASHD, type of antibiotic used, inpatient status at the time of initial infection, and number of recurrences (the latter having no estimated odds ratio due to sparse information). No significant differences were found between the two groups regarding age, sex, diabetes, hypertension, CVA, chronic kidney disease, appendectomy status, and PPI use. Conclusion: Our results indicated history of ASHD and inpatient status at the time of initial infection were significantly associated with lower risks (0.08OR and 0.43OR, respectively) of fulminant CDI requiring FMT. Additionally, metronidazole treatment of CDI was also associated with a significantly lower (0.3OR) risk of developing fulminant CDI. In contrast, the use of vancomycin and fidaxomicin were both associated with a higher risk (16.29OR and 6.71OR, respectively) of developing fulminant CDI. Thus, it is important to consider treatment failure when recommending vancomycin or fidaxomicin over metronidazole as initial therapy; while these therapies may be associated with a higher cure rate, it may be at the expense of more fulminant infections requiring FMT.2740 Figure 1. Odds Ratios for fulminant CDI requiring FMT according to choice of antibiotic therapy

Incidence, course, and outcome of Clostridium difficile infection in children with hematological malignancies or undergoing hematopoietic stem cell transplantation

Clostridium difficile infection (CDI) is one of the most common causes of nosocomial infectious diarrhea in children during anticancer therapy or undergoing hematopoietic stem cell transplantation (HSCT) in Europe. Immunosuppression in these patients is a risk factor for CDI. Malignant diseases, age, acute graft-versus-host disease (aGVHD), HLA mismatch, or use of total body irradiation may play an important role in CDI course. The aim of this study was to evaluate the incidence, course, and outcome of CDI in children treated for malignancy or undergoing HSCT. Between 2012 and 2015, a total number of 1846 patients were treated for malignancy in Polish pediatric oncological centers (PHO group) and 342 underwent transplantation (HSCT group). In PHO group, episodes of CDI occurred in 210 patients (14%). The incidence of CDI was higher in patients with hematological malignancies in comparison to that with solid tumors. Patients with acute myeloblastic leukemia had shorter time to episode of CDI than those with acute lymphoblastic leukemia. Patients over 5 years and treated for acute leukemia had more severe clinical course of disease in PHO group. In HSCT group, CDI occurred in 29 (8%) patients. The incidence of CDI was higher in patients transplanted for acute leukemia. The recurrence rate was 14.7% in PHO and 20.7% in HSCT patients. CDI incidence was highest in patients with hematological malignancies. Most of patients experienced mild CDI. Age < 5 years and diagnosis other than acute leukemia were the positive prognostic factors influencing clinical CDI course.

Toxin positivity and tcdB gene load in broad-spectrum Clostridium difficile infection.

This study aimed to evaluate the clinical significance of toxin positivity and toxin gene load, and the relation between them in the broad spectrum of Clostridium difficile infection (CDI) including colonization, significant diarrhea, and severe disease. We included 2671 fecal samples submitted for CDI diagnosis and 180 samples from healthy individuals. The clinical spectrum was categorized as category I (toxigenic C. difficile positive without clinical CDI criteria), category II (mild CDI), and category III (severe CDI). Clinical parameters were compared based on toxin EIA and tcdB C t values. C t values of tcdB PCR for predicting toxin EIA positivity were assessed using receiver-operating characteristic (ROC) curves. The median C t values of tcdB PCR and toxin positivity were not significantly correlated with clinical spectrum of CDI (27.5, 28.2, and 26.1 for tcdB C t and 55.0, 56.6, and 60.9% for toxin EIA positivity in category I, II, and III, respectively, P>0.05). There were significant differences in the tcdB C t values between toxin EIA-positive and -negative groups (P<0.001). Optimal cutoff for the tcdB C t value for estimating toxin EIA positivity was 26.3 with 79.3% sensitivity and 83.6% specificity with good area under the curves (AUC, 0.848). The C t values successfully predicted toxin EIA positivity and could be used as a surrogate for toxin EIA positivity in the diagnostic algorithm and routine analysis. Further studies are needed to validate the clinical significance of tcdB PCR C t value in toxigenic C. difficile colonization and infection.

Differences in Clinical Characteristics and Outcomes of Patients with Community-Onset Clostridium difficile Infection who Tested Positive by EIA Compared with NAAT through a Two-Step Algorithm

BackgroundThe low sensitivity of toxin enzyme immunoassay (EIA) for the diagnosis of Clostridium difficile infection (CDI) motivated many laboratories to add nucleic acid amplification tests (NAAT) to their testing protocol. However, NAAT do not distinguish between colonization and infection, and indiscriminant testing could lead to over treatment of CDI.MethodsActive, population-based CDI surveillance has been conducted through the Emerging Infections Program in Bernalillo County, NM since 2011, with test type collected at the individual level since 2014. Community-onset (CO) CDI cases with a first positive test diagnosed by a two-step algorithm (concurrent EIA/GDH, with discordant results reflexed to NAAT) in 2014–2015 were included. We analyzed clinical characteristics and outcomes of patients EIA positive compared with NAAT positive. Demographics, risk factors, treatment, and outcomes were assessed through medical record review.ResultsAmong 1,063 cases, 559 (52.6%) were EIA positive only and 504 (47.4%) were NAAT positive only. Of those with stool collected as a hospital inpatient, 57% were NAAT positive (P < 0.001); this increased from 43.4% if tested the day of admission to 61.4% when tested on day three. Conversely, 38.6% of patients with stool collected in an emergency department were NAAT positive (P = 0.004). Fewer cases with complicated outcomes were NAAT positive (40.7%, P = 0.023). Among those with no documentation of recent antibiotic use, 64.3% were NAAT positive (P < 0.001), and 67.8% of cases with no CDI treatment were NAAT positive (P = 0.005). Only 28.3% percent of cases with recurrent CDI were initially NAAT positive (P < 0.001).ConclusionEIA negative and NAAT positive CO-CDI cases tended to have a milder clinical presentation than those that were EIA positive. This suggests that some patients positive only by NAAT may have mild CDI or be colonized, rather than infected, with C. difficile. These individuals were less likely to have complicated outcomes, have recent documented antibiotic use, be treated for CDI, or have a recurrent CDI episode than those positive by EIA. Longer hospital stay correlated with increased proportion of testing NAAT positive. Providers may benefit from considering testing protocol and clinical correlation when assessing patients with positive C. difficile test results.Disclosures All authors: No reported disclosures.

Clostridium difficile: Infection, diagnosis and treatment with antimicrobial drugs : A review article

Clostridium difficile infection (CDI) is increasing problem in healthcare, associated with high incidence, mortality, and costs in hospitalized patients. Dramatic increases in the incidence and severity of healthcare-associated C. difficile infection have occurred since the last decade, including elderly population, young adults, pregnant females, infants and children. C. difficile infections are mainly linked to the prolonged use of wide-spectrum antibiotics that disrupt the intestinal microbiota equilibrium. Toxigenic strains of C. difficile commonly produce two clostridial toxins, toxins A (TcdA) and B (TcdB), to which disease symptoms are attributed. Few strains of C. difficile may also produce another more powerful binary toxin associated with high fatality. The clinical manifestations of infection with toxin-producing strains of C. difficile range from symptomless carriage, to mild or moderate watery-bloody diarrhea, and few percentage developed fulminant and sometimes fatal pseudomembranous colitis. Complications that have been associated with CDI include dehydration, electrolyte disturbances, toxic megacolon, bowel perforation, hypotension, renal failure, systemic inflammatory response syndrome, sepsis, and death. The most important step in treating CDI is immediately discontinuing use of offending antimicrobial drug. Both metronidazole and vancomycin are equally effective for the treatment of mild CDI, but vancomycin is superior for treating patients with severe C. difficile disease. Recently, fidaxomicin proved to be superior to other drugs in treatment of patients who are at high risk for CDI relapse.

Clostridium difficile infection in hospitalized patients at a Czech tertiary center: analysis of epidemiology, clinical features, and risk factors of fulminant course.

Clostridium difficile infection (CDI) has been increasing in incidence, with significant morbidity and mortality, and is subject to geographical and institutional variability. We aimed to characterize epidemiology and clinical manifestations of CDI in a Czech tertiary care center and to identify risk factors of fulminant course. All adult patients hospitalized with primary CDI in a 3-year period were retrospectively identified. Epidemiological and clinically descriptive data were extracted from medical records. Multivariate analysis was used to identify the risk factors of fulminant course. The relationship between incidence of CDI and antibiotic consumption was evaluated. Overall, 183 CDI patients, median age 67 years, were enrolled. Hospital-acquired CDI was present in 85% of cases. The incidence of CDI was 1/10,000 patient-days. Hospital-acquired CDI hospital mortality was 22.4%. Severe CDI (SCDI) was identified in 15.8% of patients, with 62% mortality. SCDI patients had longer onset of symptoms to diagnosis interval compared with mild CDI (P=0.05). Multivariate analysis showed that SCDI patients were older (P=0.018), and more frequently had abnormal abdominal physical findings (P=0.001), higher inflammatory markers (P<0.001), higher creatinine (P=0.002), and lower albumin (P<0.001) than patients with mild CDI. Analysis of antibiotic consumption at departments with the highest incidence of CDI showed a trend toward higher incidence of CDI associated with penicillin use (P=0.08) and a negative correlation of CDI incidence with nitroimidazoles consumption (P=0.03). CDI is less frequent in the conditions studied compared with literary data; however, the fulminant form has a very high mortality. Delayed recognition and treatment is a crucial determinant of the severity of CDI. The association between CDI and antibiotic consumption is less clear.

Clostridium difficile infection in hospitalized cancer patients.

e20707 Background: The incidence and severity of Clostridium difficileinfection (CDI) has significantly increased over the past decade. Although the epidemiology and treatment of CDI is well elucidated in the non-oncology population, it is poorly understood among cancer patients. CDI prevention is particularly important for patients with cancer, because diarrhea often results in dose reductions or delays of chemotherapy or radiotherapy. Methods: We performed a retrospective study to assess the incidence and severity of C. difficile infection among adult cancer patients admitted to the Oncology Service at “12 de Octubre” University Hospital, from January 2009 to March 2013. All inpatients with diarrhea underwent testing for the presence of C. difficile (enzyme immunoassay for toxins A and B). Chemotherapy administered, and antibiotics used before the development of CDI symptoms, was noted. Results: Of the 230 admitted patients during the 4-year study period, the overall incidence of CDI was 9.6% (N=22). Of these, 8 (36.4%) and 14 patients (63.6%) were deemed to have mild and moderate CDI, respectively. Patients with CDI (N=5, 22.7%) suffered more severe complications than patients with other enteric infections (N=2, 15.4%). There was a slight trend between previous use of antibiotics and CDI (P= 0.09), however we found no relationship between CDI and previous administration of corticosteroids or proton pump inhibitors. With regards to outcome of chemotherapy, patients with platinum-based therapy were more affected by CDI (N=19, 86.3%), and four of them died. Conclusions: Despite a potential decrease in the incidence of CDI in the last years, this infection still contributes substantially to morbidity and possibly mortality in this vulnerable patient population. There was no relationship between gastrointestinal cancer and CDI. Use of carboplatin chemotherapy was significantly associated with CDI, and CDI was more frequent in gynecologic cancer patients, as these patients are more frequently treated with this therapy. Our study supports the possibility of platinum-based chemotherapy as a risk factor for CDI although the reason for the effect is not clear.

Vancomycin, Metronidazole, or Tolevamer for Clostridium difficile Infection: Results From Two Multinational, Randomized, Controlled Trials

Clostridium difficile infection (CDI) is a common complication of antibiotic therapy that is treated with antibiotics, contributing to ongoing disruption of the colonic microbiota and CDI recurrence. Two multinational trials were conducted to compare the efficacy of tolevamer, a nonantibiotic, toxin-binding polymer, with vancomycin and metronidazole. Patients with CDI were randomly assigned in a 2:1:1 ratio to oral tolevamer 9 g (loading dose) followed by 3 g every 8 hours for 14 days, vancomycin 125 mg every 6 hours for 10 days, or metronidazole 375 mg every 6 hours for 10 days. The primary endpoint was clinical success, defined as resolution of diarrhea and absence of severe abdominal discomfort for more than 2 consecutive days including day 10. In a pooled analysis, 563 patients received tolevamer, 289 received metronidazole, and 266 received vancomycin. Clinical success of tolevamer was inferior to both metronidazole and vancomycin (P < .001), and metronidazole was inferior to vancomycin (P = .02; 44.2% [n = 534], 72.7% [n = 278], and 81.1% [n = 259], respectively). Clinical success in patients with severe CDI who received metronidazole was 66.3% compared with vancomycin, which was 78.5%. (P = .059). A post-hoc multivariate analysis that excluded tolevamer found 3 factors that were strongly associated with clinical success: vancomycin treatment, treatment-naive status, and mild or moderate CDI severity. Adverse events were similar among the treatment groups. Tolevamer was inferior to antibiotic treatment of CDI, and metronidazole was inferior to vancomycin. Trial Registration. clinicaltrials.gov NCT00106509 and NCT00196794.

European Society of Clinical Microbiology and Infectious Diseases: Update of the Treatment Guidance Document for Clostridium difficile Infection

In 2009 the first European Society of Clinical Microbiology and Infection (ESCMID) treatment guidance document for Clostridium difficile infection (CDI) was published. The guideline has been applied widely in clinical practice. In this document an update and review on the comparative effectiveness of the currently available treatment modalities of CDI is given, thereby providing evidence-based recommendations on this issue. A computerized literature search was carried out to investigate randomized and non-randomized trials investigating the effect of an intervention on the clinical outcome of CDI. The Grades of Recommendation Assessment, Development and Evaluation (GRADE) system was used to grade the strength of our recommendations and the quality of the evidence. The ESCMID and an international team of experts from 11 European countries supported the process. To improve clinical guidance in the treatment of CDI, recommendations are specified for various patient groups, e.g. initial non-severe disease, severe CDI, first recurrence or risk for recurrent disease, multiple recurrences and treatment of CDI when oral administration is not possible. Treatment options that are reviewed include: antibiotics, toxin-binding resins and polymers, immunotherapy, probiotics, and faecal or bacterial intestinal transplantation. Except for very mild CDI that is clearly induced by antibiotic usage antibiotic treatment is advised. The main antibiotics that are recommended are metronidazole, vancomycin and fidaxomicin. Faecal transplantation is strongly recommended for multiple recurrent CDI. In case of perforation of the colon and/or systemic inflammation and deteriorating clinical condition despite antibiotic therapy, total abdominal colectomy or diverting loop ileostomy combined with colonic lavage is recommended.