Diverting Loop Ileostomy for Clostridium Difficile Colitis: A Systematic Review and Meta-analysis.

Diverting loop ileostomy (DLI) with colonic lavage has been proposed as an alternative to total abdominal colectomy (TAC) for fulminant Clostridium difficile infection (CDI). Controversy exists regarding the mortality benefit and outcomes of this surgical approach. We conducted a MEDLINE database search for articles between 1999 and 2019 pertaining to DLI for the surgical treatment of CDI. Five articles met the inclusion criteria. Four studies were retrospective and one was a prospective matched cohort study. 3683 patients were included in the 5 studies; 733 patients (20%) underwent DLI, while 2950 patients (80%) underwent TAC. The only shared outcome measure across all 5 studies was mortality. The overall mortality rate for the entire cohort undergoing both procedures was 30.3%. There was no statistically significant difference in pooled mortality between DLI and TAC (OR: .73; 95% CI, .45-1.2; P = .22). Reporting of other postoperative outcomes was variable. Fulminant CDI remains a life-threatening condition with high mortality. Loop ileostomy may be a viable surgical alternative to total colectomy with similar mortality; however, further work is needed to determine specific patient characteristics that warrant routine use of DLI.

Acid suppression therapy, gastrointestinal bleeding and infection in acute pancreatitis - An international cohort study.

BACKGROUND: Acid suppressing drugs (ASD) are generally used in acute pancreatitis (AP); however, large cohorts are not available to understand their efficiency and safety. Therefore, our aims were to evaluate the association between the administration of ASDs, the outcome of AP, the frequency of gastrointestinal (GI) bleeding and GI infection in patients with AP. METHODS: We initiated an international survey and performed retrospective data analysis on AP patients hospitalized between January 2013 and December 2018. RESULTS: Data of 17,422 adult patients with AP were collected from 59 centers of 23 countries. We found that 23.3% of patients received ASDs before and 86.6% during the course of AP. ASDs were prescribed to 57.6% of patients at discharge. ASD administration was associated with more severe AP and higher mortality. GI bleeding was reported in 4.7% of patients, and it was associated with pancreatitis severity, mortality and ASD therapy. Stool culture test was performed in 6.3% of the patients with 28.4% positive results. Clostridium difficile was the cause of GI infection in 60.5% of cases. Among the patients with GI infections, 28.9% received ASDs, whereas 24.1% were without any acid suppression treatment. GI infection was associated with more severe pancreatitis and higher mortality. CONCLUSIONS: Although ASD therapy is widely used, it is unlikely to have beneficial effects either on the outcome of AP or on the prevention of GI bleeding during AP. Therefore, ASD therapy should be substantially decreased in the therapeutic management of AP.

Early Colectomy Saves Lives in Toxic Megacolon Due to Clostridium difficile Infection.

OBJECTIVE: The purpose of the study was to evaluate whether early colectomy in patients who have toxic megacolon due to Clostridium difficile colitis reduces mortality. METHODS: The study was performed using the American College of Surgeons National Surgical Quality Improvement Program database from 2012 to 2016. All patients 18 to 89 years of age who underwent colectomy for toxic megacolon resulting from C. difficile colitis were included in the study. Other variables included in the study were patient demography, comorbidities, and outcomes. Patients who underwent colectomy before the presentation of septic shock (early group) were compared with patients who underwent colectomy after the onset of septic shock (late group). The main outcome of the study is 30-day all-cause mortality. Because there were some significant differences found in patient baseline characteristics in the univariate analysis, the propensity score of each patient was calculated and pair-matched analysis was performed. All P values are reported as 2-sided, and P < 0.05 was considered statistically significant. RESULTS: One hundred sixty-three patients met the inclusion criteria of the study. Approximately 85% of the patients underwent total abdominal colectomy. The average age of the patients was 65 years old, 51% of the patients were female, and 66% of the patients were white. The overall 30-day mortality was approximately 39%. The mortality rate of patients who underwent colectomy early compared to late was 13 (21%) vs 28 (45%), P = 0.009. The absolute risk difference was 0.24 with 95% CI: 0.07-0.42. CONCLUSIONS: There was a reduction of 24% in 30-day mortality when colectomies were performed before the development of septic shock.

A systematic review and meta-analysis of diverting loop ileostomy versus total abdominal colectomy for the treatment of Clostridium difficile colitis.

BACKGROUND: Clostridium difficile is an increasingly common source of in-patient morbidity and mortality. We aim to assess the effects of diverting loop ileostomy (DLI) versus total abdominal colectomy (TAC) for Clostridium difficile colitis (CDC), in terms of mortality and morbidity. METHODS: Systematic literature search was performed using PubMed, Embase, Cochrane, and Web of Science databases for randomized and non-randomized studies comparing DLI and TAC for fulminant CDC. Meta-analysis was carried out for mortality and postoperative complications. RESULTS: Five non-randomized studies qualified for inclusion in the quantitative synthesis. In total, 3683 patients were allocated to DLI (n = 733) or TAC (n = 2950). The overall mortality was equivalent (OR 0.73; 95% CI 0.45-1.20; P = 0.22). Regarding secondary outcomes, the pooled analysis revealed the following equivalent rates of postoperative events: thromboembolism (OR 0.45; 95% CI 0.14-1.43; P = 0.18), acute renal failure (OR 1.71; 95% CI 0.91-3.23; P = 0.10), surgical site infection (OR 0.95; 95% CI 0.11-8.59; P = 0.97), pneumonia (OR 0.98; 95% CI 0.36-2.66; P = 0.97), urinary tract infection (OR 0.81; 95% CI 0.26-2.52; P = 0.72), and reoperation (OR 0.95; 95% CI 0.50-1.82; P = 0.78). The ostomy reversal rate was significantly higher in DLI (OR 12.55; 95% CI 3.31-47.55; P = 0.0002). CONCLUSIONS: The overall morbidity and mortality rates between DLI and TAC for the treatment of CDC seemed to be equivalent. Evidence from a randomized controlled trial is needed to clarify the timing and understand the impact of DLI for CDC.

Temporal trends of inpatient C. difficile infections within the Veterans Health Administration hospitals: An analysis of the effect of molecular testing, time to testing, and mandatory reporting.

BACKGROUND: Clostridium difficile infection (CDI) is a reportable hospital metric associated with significant healthcare expenditures. The epidemiology of CDI is pivotal to the implementation of preventative measures. OBJECTIVE: To portray temporal CDI trends in Veterans Health Administration (VA) hospitals. DESIGN: A retrospective analysis of veterans who had stool testing for C. difficile. SETTING: VA acute-care hospitals within the continental United States. METHODS: Data were mined from the VA's Corporate Data Warehouse. CDI is reported per 10,000 patient days. RESULTS: From 2006 to 2016, 472,346 patients had C. difficile testing. Overall, decreases in incidence of total CDI (16.81 to 13.66) and hospital-onset healthcare facility-associated (HO-HCFA) CDI (10.87 to 6.41) were observed. Temporal increases in the incidence of total and HO-HCFA CDI were associated with the increased use of molecular testing (P < .0001). Decreased use of fluoroquinolones (P < .0001), clindamycin (P = .0006), and third-generation cephalosporins (P = .0002) correlated with decreased rates of CDI, but VA mandatory reporting did not influence CDI rates (P = .24). The overall crude 30-day mortality of patients with CDI decreased from 2.17 deaths per 10,000 patient days in 2006 to 1.41 in 2016. The frequency of International Classification of Disease, Ninth/Tenth Revision (ICD-9/10) discharge diagnosis for CDI was 73.3%. CONCLUSION: Molecular testing was associated with increased incidence of CDI. Controlling CDI is likely multifactorial. Although the VA initiative to report cases of hospital-acquired CDI was not significant in our model, the advent of stewardship programs throughout the VA and reductions in the use of third-generation cephalosporins, fluoroquinolones, and clindamycin were significantly associated with reduced rates of CDI.

IL-33 drives group 2 innate lymphoid cell-mediated protection during Clostridium difficile infection.

Clostridium difficile (C. difficile) incidence has tripled over the past 15 years and is attributed to the emergence of hypervirulent strains. While it is clear that C. difficile toxins cause damaging colonic inflammation, the immune mechanisms protecting from tissue damage require further investigation. Through a transcriptome analysis, we identify IL-33 as an immune target upregulated in response to hypervirulent C. difficile. We demonstrate that IL-33 prevents C. difficile-associated mortality and epithelial disruption independently of bacterial burden or toxin expression. IL-33 drives colonic group 2 innate lymphoid cell (ILC2) activation during infection and IL-33 activated ILC2s are sufficient to prevent disease. Furthermore, intestinal IL-33 expression is regulated by the microbiota as fecal microbiota transplantation (FMT) rescues antibiotic-associated depletion of IL-33. Lastly, dysregulated IL-33 signaling via the decoy receptor, sST2, predicts C. difficile-associated mortality in human patients. Thus, IL-33 signaling to ILC2s is an important mechanism of defense from C. difficile colitis.

A possible association between statin use and improved Clostridioides difficile infection mortality in veterans.

Clostridioides difficile infection (CDI) is the most common cause of nosocomial diarrhea and places a significant burden on patients and the health care system. Statins could lead to improvements in CDI clinical response due their pleiotropic effects, including immunomodulatory and lipid-lowering effects; however, few studies have assessed this association. The primary objective of this study was to compare CDI health outcomes in statin users and non-users in a national cohort of patients. This was a retrospective cohort study of all adult CDI patients receiving care from the Veterans Health Administration from 2002 to 2014. Patients were divided into two groups based on statin exposure 90 days prior to and during their first CDI encounter. CDI health outcomes, including mortality and CDI recurrence, were compared using a propensity-score matched cohort of statin users and non-users and multivariable logistic regression. A total of 26,149 patients met study inclusion criteria, of which 173 statins-users and 173 non-users were propensity score matched. Thirty-day mortality was significantly lower among statins users with CDI (12.7%) compared to non-users (20.2%) (aOR 0.34; 95% CI 0.16-0.72). Sixty-day CDI recurrence was non-significantly lower among statin-users (9.0%) compared to non-users (16.6%) (aOR 0.68; 95% CI 0.29-1.59). In this nationally-representative study of veterans with CDI, statin use was associated with lower 30-day mortality compared to non-use. Statin use was not associated with 60-day CDI recurrence.

Clostridioides difficile Colonization Is Differentially Associated With Gut Microbiome Profiles by Infant Feeding Modality at 3-4 Months of Age.

Colonization with Clostridioides difficile occurs in up to half of infants under the age of 3 months, is strongly influenced by feeding modality and is largely asymptomatic. In spite of this, C. difficile's presence has been associated with susceptibility to chronic disease later in childhood, perhaps by promoting or benefiting from changes in infant gut microbiome development, including colonization with pathogenic bacteria and disrupted production of microbial bioactive metabolites and proteins. In this study, the microbiomes of 1554 infants from the CHILD Cohort Study were described according to C. difficile colonization status and feeding mode at 3-4 months of age. C. difficile colonization was associated with a different gut microbiome profile in exclusively breastfed (EBF) vs. exclusively formula fed (EFF) infants. EBF infants colonized with C. difficile had an increased relative abundance of Firmicutes and Proteobacteria, decreased relative abundance of Bifidobacteriaceae, greater microbiota alpha-diversity, greater detectable fecal short chain fatty acids (SCFA), and lower detectable fecal secretory Immunoglobulin A (sIgA) than those not colonized. Similar but less pronounced differences were seen among partially breastfed infants (PBF) but EFF infants did not possess these differences in the gut microbiome according to colonization status. Thus, breastfed infants colonized with C. difficile appear to possess a gut microbiome that differs from non-colonized infants and resembles that of EFF infants, but the driving force and direction of this association remains unknown. Understanding these compositional differences as drivers of C. difficile colonization may be important to ensure future childhood health.

The predictive value of quantitative nucleic acid amplification detection of Clostridium difficile toxin gene for faecal sample toxin status and patient outcome.

BACKGROUND: Laboratory diagnosis of Clostridium difficile infection (CDI) remains unsettled, despite updated guidelines. We investigated the potential utility of quantitative data from a nucleic acid amplification test (NAAT) for C. difficile toxin gene (tg) for patient management. METHODS: Using data from the largest ever C. difficile diagnostic study (8853 diarrhoeal samples from 7335 patients), we determined the predicative value of C. difficile tgNAAT (Cepheid Xpert C.diff) low cycle threshold (CT) value for patient toxin positive status, CDI severity, mortality and CDI recurrence. Reference methods for CDI diagnosis were cytotoxicity assay (CTA) and cytotoxigenic culture (CTC). RESULTS: Of 1281 tgNAAT positive faecal samples, 713 and 917 were CTA and CTC positive, respectively. The median tgNAAT CT for patients who died was 25.5 vs 27.5 for survivors (p = 0.021); for toxin-positivity was 24.9 vs 31.6 for toxin-negative samples (p<0.001) and for patients with a recurrence episode was 25.6 vs 27.3 for those who did not have a recurrent episode (p = 0.111). Following optimal cut-off determination, low CT was defined as ≤25 and was significantly associated with a toxin-positive result (P<0.001, positive predictive value 83.9%), presence of PCR-ribotype 027 (P = 0.025), and mortality (P = 0.032). Recurrence was not associated with low CT (p 0.111). CONCLUSIONS: Low tgNAAT CT could indicate CTA positive patients, have more severe infection, increased risk of mortality and possibly recurrence. Although, the limited specificity of tgNAAT means it cannot be used as a standalone test, it could augment a more timely diagnosis, and optimise management of these at-risk patients.

Evaluation of risk factors for a fulminant Clostridium difficile infection after cardiac surgery: a single-center, retrospective cohort study.

BACKGROUND: Clostridium difficile (CD) is the most common pathogen causing nosocomial diarrhea. The clinical presentation ranges from mild diarrhea to severe complications, including pseudomembranous colitis, toxic megacolon, sepsis, and multi-organ failure. When the disease takes a fulminant course, death ensues rapidly in severe and complex cases. Preventive screening or current prophylactic therapies are not useful. Therefore, this study was conducted to detect risk factors for a fulminant CD infection (CDI) in patients undergoing cardiac surgery. METHODS: Between April 1999 and April 2011, a total of 41,466 patients underwent cardiac surgery at our institution. A review of our hospital database revealed 1256 patients (3.0%) with post-operative diarrheal disease who tested positive for CD; these patients comprised the cohort of this observational study. A fulminant CDI occurred in 153 of these patients (12.2%), which was diagnosed on the basis of gastrointestinal complications, e.g. pseudomembranous colitis, and/or the need for post-cardiac surgery laparotomy. Demographic, peri-operative, and survival data were analyzed, and predictors of a fulminant CDI were assessed by binary logistic regression analysis. RESULTS: The 30-day mortality was 6.1% (n = 77) for the entire cohort, with significantly higher mortality among patients with a fulminant CDI (21.6% vs. 4.0%, p <  0.001). Overall mortality (27.7%, n = 348) was also higher for patients with a fulminant course of the disease (63.4% vs. 22.8%, p <  0.001), and a laparotomy was required in 36.6% (n = 56) of the fulminant cases. Independent predictors of a fulminant CDI were: diabetes mellitus type 2 (OR 1.74, CI 1.15-2.63, p = 0.008), pre-operative ventilation (OR 3.52, CI 1.32-9.35, p = 0.012), utilization of more than 8 units of red blood cell concentrates (OR 1.95, CI 1.01-3.76, p = 0.046) or of more than 5 fresh-frozen plasma units (OR 3.38, CI 2.06-5.54, p <  0.001), and a cross-clamp time > 130 min (OR 1.93, CI 1.12-3.33, p = 0.017). CONCLUSIONS: We identified several independent risk factors for the development of a fulminant CDI after cardiac surgery. Close monitoring of high-risk patients is important in order to establish an early onset of therapy and thus to prevent a CDI from developing a fulminant course after cardiac surgery.

Frailty Predicts Morbidity and Mortality after Colectomy for Clostridium difficile Colitis.

Frailty has been noted as a powerful predictive preoperative tool for 30-day postoperative complications. We sought to evaluate the association between frailty and postoperative outcomes after colectomy for Clostridium difficile colitis. The National Surgical Quality and Improvement Program cross-institutional database was used for this study. Data from 470 patients with a diagnosis of C. difficile colitis were used in the study. Modified frailty index (mFI) is a previously described and validated 11-variable frailty measure used with the National Surgical Quality and Improvement Program to assess frailty. Outcome measures included serious morbidity, overall morbidity, and Clavien IV (requiring ICU) and Clavien V (mortality) complications. The median age was 70 years and body mass index was 26.9 kg/m2. 55.6 per cent of patients were females. 98.5 per cent of patients were assigned American Society of Anesthesiologists Class III or higher. The median mFI was 0.27 (0-0.63). Because mFI increased from 0 (non-frail) to 0.55 and above, the overall morbidity increased from 53.3 per cent to 84.4 per cent and serious morbidity increased from 43.3 per cent to 78.1 per cent. The Clavien IV complication rate increased from 30.0 per cent to 75.0 per cent. The mortality rate increased from 6.7 per cent to 56.2 per cent. On a multivariate analysis, mFI was an independent predictor of overall morbidity (AOR: 13.0; P < 0.05), mortality (AOR: 8.8; P = 0.018), cardiopulmonary complications (AOR: 6.8; P = 0.026), and prolonged length of hospital stay (AOR: 6.6; P = 0.045). Frailty is associated with increased risk of complications in C. difficile colitis patients undergoing colectomy. mFI is an easy-to-use tool and can play an important role in the risk stratification of these patients who generally have significant morbidity and mortality to begin with.

Clostridium difficile co-infection in inflammatory bowel disease is associated with significantly increased in-hospital mortality.

OBJECTIVE: Inflammatory bowel disease (IBD) patients with Clostridium difficile co-infection (CDCI) have an increased risk of morbidity and mortality. We aim to evaluate the impact of CDCI on in-hospital outcomes among adults with IBD hospitalized in the USA. PATIENTS AND METHODS: Using the 2007-2013 Nationwide Inpatient Sample, hospitalizations among US adults with Crohn's disease (CD), ulcerative colitis (UC) and CDCI were identified using ICD-9 coding. Hospital charges, hospital length of stay (LOS), and in-hospital mortality was stratified by CD and UC and compared using χ-testing and Student's t-test. Predictors of hospital charges, LOS, and in-hospital mortality were evaluated with multivariate regression models and were adjusted for age, sex, race/ethnicity, year, insurance status, hospital characteristics, and CDCI. RESULTS: Among 224 500 IBD hospitalizations (174 629 CD and 49 871 UC), overall prevalence of CDCI was 1.22% in CD and 3.41% in UC. On multivariate linear regression, CDCI was associated with longer LOS among CD [coefficient: 5.30, 95% confidence interval (CI): 4.61-5.99, P<0.001] and UC (coefficient 4.08, 95% CI: 3.54-4.62, P<0.001). Higher hospital charges associated with CDCI were seen among CD (coefficient: $35 720, 95% CI: $30 041-$41 399, P<0.001) and UC (coefficient: $26 009, 95% CI: $20 970-$31 046, P<0.001). On multivariate logistic regression, CDCI was associated with greater risk of in-hospital mortality (CD: odds ratio: 2.74, 95% CI: 1.94-3.87, P<0.001; UC: OR: 5.50, 95% CI: 3.83-7.89, P<0.001). CONCLUSION: Among US adults with CD and UC related hospitalizations, CDCI is associated with significantly greater in-hospital mortality and greater healthcare utilization.

How Common-and How Serious- Is Clostridium difficile Colitis After Geriatric Hip Fracture? Findings from the NSQIP Dataset.

BACKGROUND: Patients with geriatric hip fractures may be at increased risk for postoperative Clostridium difficile colitis, which can cause severe morbidity and can influence hospital quality metrics. However, to our knowledge, no large database study has calculated the incidence of, factors associated with, and effect of C. difficile colitis on geriatric patients undergoing hip fracture surgery. QUESTIONS/PURPOSES: To use a large national database with in-hospital and postdischarge data (National Surgical Quality Improvement Program [NSQIP®]) to (1) determine the incidence and timing of C. difficile colitis in geriatric patients who underwent surgery for hip fracture, (2) identify preoperative and postoperative factors associated with the development of C. difficile colitis in these patients, and (3) test for an association between C. difficile colitis and postoperative length of stay, 30-day readmission, and 30-day mortality. PATIENTS AND METHODS: This is a retrospective study. Patients who were 65 years or older who underwent hip fracture surgery were identified in the 2015 NSQIP database. The primary outcome was a diagnosis of C. difficile colitis during the 30-day postoperative period. Preoperative and procedural factors were tested for association with the development of C. difficile colitis through a backward stepwise multivariate model. Perioperative antibiotic type and duration were not included in the model, as this information was not recorded in the NSQIP. The association between C. difficile colitis and postoperative length of stay, 30-day readmission, and 30-day mortality were tested through multivariate regressions, which adjusted for preoperative and procedural characteristics such as age, comorbidities, and surgical procedure. A total of 6928 patients who were 65 years or older and underwent hip fracture surgery were identified. RESULTS: The incidence of postoperative C. difficile colitis was 1.05% (95% CI, 0.81%-1.29%; 73 of 6928 patients). Of patients who had C. difficile colitis develop, 64% (47 of 73 patients) were diagnosed postdischarge and 79% (58 of 73 patients) did not have a preceding infectious diagnosis. Preoperative factors identifiable before surgery that were associated with the development of C. difficile colitis included admission from any type of chronic care facility (versus admitted from home; relative risk [RR] = 1.98; 95% CI, 1.11-3.55; p = 0.027), current smoker within 1 year (RR = 1.95; 95% CI, 1.03-3.69; p = 0.041), and preoperative anemia (RR = 1.76; 95% CI, 1.07-2.92; p = 0.027). Patients who had pneumonia (RR = 2.58; 95% CI, 1.20-5.53; p = 0.015), sepsis (RR = 4.20; 95% CI, 1.27-13.82; p = 0.018), or "any infection" (RR = 2.26; 95% CI, 1.26-4.03; p = 0.006) develop after hip fracture were more likely to have C. difficile colitis develop. Development of C. difficile colitis was associated with greater postoperative length of stay (22 versus 5 days; p < 0.001), 30-day readmission (RR = 3.41; 95% CI, 2.17-5.36; p < 0.001), and 30-day mortality (15% [11 of 73 patients] versus 6% [439 of 6855 patients]; RR = 2.16; 95% CI, 1.22-3.80; p = 0.008). CONCLUSIONS: C. difficile colitis is a serious infection after hip fracture surgery in geriatric patients that is associated with 15% mortality. Patients at high risk, such as those admitted from any type of chronic care facility, those who had preoperative anemia, and current smokers within 1 year, should be targeted with preventative measures. From previous studies, these measures include enforcing strict hand hygiene with soap and water (not alcohol sanitizers) if a provider is caring for patients at high risk and those who are C. difficile-positive. Further, other studies have shown that certain antibiotics, such as fluoroquinolones and cephalosporins, can predispose patients to C. difficile colitis. These medications perhaps should be avoided when prescribing prophylactic antibiotics or managing infections in patients at high risk. Future prospective studies should aim to determine the best prophylactic antibiotic regimens, probiotic formula, and discharge timing that minimize postoperative C. difficile colitis in patients with hip fractures. LEVEL OF EVIDENCE: Level III, therapeutic study.

A Surgical Clostridium-Associated Risk of Death Score Predicts Mortality After Colectomy for Clostridium difficile.

BACKGROUND: A Clostridium difficile-associated risk of death score was recently developed and validated by using a national cohort of both nonsurgical and surgical patients admitted with C difficile infection. However, risk scores specifically derived from surgical cohorts and designed for patients with C difficile infection are currently unavailable. OBJECTIVE: The aim of this study was to develop a risk of death score for patients with C difficile infection who are being considered for total abdominal colectomy because of the failure of medical therapy. DESIGN: This is a retrospective cohort study. SETTINGS: This study was conducted with the use of a national database. PATIENTS: All patients undergoing total colectomy for C difficile infection were identified in the National Surgical Quality Improvement Program database from 2005 to 2014. MAIN OUTCOME MEASURES: Variables similar to the original scoring system were used in multivariable analyses to determine the risk of 30-day mortality for patients, and a model was constructed to estimate the predicted probability of mortality after surgery. RESULTS: Of 532 patients who underwent surgery, 32.7% experienced 30-day postoperative mortality. Patient covariates associated with significantly increased mortality included age greater than 80 years (OR 5.5, p = 0.003), need for preoperative mechanical ventilation (OR 3.1, p < 0.001), chronic steroid use (OR 2.9, p < 0.001), underlying cardiopulmonary disease (OR 2.0, p = 0.001), and acute renal failure (OR=1.7, p = 0.03). These and other comorbidities, including hepatic disease, a cancer diagnosis, and both insulin- and noninsulin-dependent diabetes mellitus, were used to construct a model to estimate the predicted probability of mortality, which ranged from 8.0% to 96.1% based on individual comorbidity profiles. These estimates differed substantially when compared with those obtained using the National Surgical Quality Improvement Program risk calculator, which estimated the risk of mortality among surgical patients as being consistently lower. LIMITATIONS: This study was limited by its retrospective design. CONCLUSIONS: Our surgical scoring system allows preoperative risk stratification for patients being evaluated for colectomy for C difficile infection, potentially helping to avoid futile surgery. See Video Abstract at http://links.lww.com/DCR/A434.

The role of purified Clostridium difficile glucosylating toxins in disease pathogenesis utilizing a murine cecum injection model.

Most pathogenic Clostridium difficile produce two major exotoxins TcdA and TcdB, in the absence of which the bacterium is non-pathogenic. While it is important to investigate the role of each toxin in the pathogenesis of C. difficile infection (CDI) using isogenic strains, it is impossible to precisely control the expression levels of individual toxins and exclude bacterial factors that may contribute to the toxins' effects during infection. In this study, we utilized an acute intestinal disease model by injecting purified toxins directly into mouse cecum after a midline laparotomy. We evaluated the physical condition of mice by clinical score and survival, and the intestinal tissue damage and inflammation by histology. Depending on the dose of the toxins, mice developed mild to severe colitis, experienced diarrhea or rapidly died. We found that both purified TcdA and TcdB were able to induce clinical disease, intestinal inflammation, and tissue damage that resembled CDI. TcdA was significantly faster in inducing intestinal inflammation and tissue damage, and was approximately five times more potent than TcdB in terms of inducing severe gut disease and death outcomes in mice. Moreover, we found that the two toxins had significant synergistic effects on disease induction. Comparison of the in vivo toxicity of TcdB from clinical strains revealed that TcdB from an epidemic RT 027 strain was more toxic than the others. Our study thus demonstrates that both TcdA and TcdB, independent of other factors from C. difficile bacterium, are able to cause disease that resembles CDI and highlights the importance of targeting both toxins for vaccines and therapeutics against the disease.

[Antimicrobial susceptibilities and molecular characterization of toxin-positive Clostridium difficile isolates: the first report on the presence of hypervirulent strains from Turkey]. / Toksin Pozitif Clostridium difficile Izolatlarinin Antimikrobiyal Duyarliliklari ve Moleküler Karakterizasyonu: Türkiye'den Hipervirülan Suslarin Varligi ile Iliskili Ilk Bildirim.

Clostridium difficile infection is one of the most important hospital-acquired infections. Infections caused by hypervirulent C.difficile strains which produce toxins at high levels, have higher morbidity and mortality rates, more complications and relapses. They are characterized by higher sporulation ratios and resistance rates for fluoroquinolones. In order to prevent serious morbidities, mortalities and remarkable increase in health costs, highly pathogenic C.difficile strains must be identified before causing severe outbreaks. The aim of this study was to determine the antimicrobial susceptibilities and molecular characteristics of 61 C.difficile strains isolated by culture from toxin-positive fecal samples of patients who were admitted to three different laboratories in Ankara, between September 2012 and November 2014. Antimicrobial susceptibilities were determined by using gradient test strips and results were interpreted according to the current CLSI and EUCAST criteria. The presence of toxin genes was investigated by polymerase chain reaction (PCR), and mutations in the tcdC gene were determined by sequence analysis following PCR amplification. Genetic characterization of one hypervirulent strain was performed by Public Health Institution of Turkey using the GenoType CDiff (Hain Lifescience, Germany) test. All strains were susceptible to vancomycin and metronidazole. Three (4.9%) isolates were resistant to moxifloxacin with a minimum inhibitory concentration (MIC) of > 8 µg/ml. The MIC50 and MIC90 values for erythromycin and clindamycin were 1.5-3 µg/ml, and 2-4 µg/ml, respectively. All strains carried the tcdA and tcdB genes, and 1 (1.6%) was positive for the binary-toxin (cdtA and cdtB) genes. The binary-toxin positive strain carried a 54 bp deletion as well as a single nucleotide change in the tcdC gene. Various single nucleotide changes were found in the tcdC gene of 12 strains (19.6%). Our results have shown that, hypervirulent strains exist in our country, but we have no evidence for the presence of ribotype 027 yet. On the other hand, when the increasing incidence of these strains through out the world is taken into consideration, it would be of great importance to perform surveillance studies and characterize the isolated strains.

Protection of Hamsters from Mortality by Reducing Fecal Moxifloxacin Concentration with DAV131A in a Model of Moxifloxacin-Induced Clostridium difficile Colitis.

Lowering the gut exposure to antibiotics during treatments can prevent microbiota disruption. We evaluated the effects of an activated charcoal-based adsorbent, DAV131A, on the fecal free moxifloxacin concentration and mortality in a hamster model of moxifloxacin-induced Clostridium difficile infection. A total of 215 hamsters receiving moxifloxacin subcutaneously (day 1 [D1] to D5) were orally infected at D3 with C. difficile spores. They received various doses (0 to 1,800 mg/kg of body weight/day) and schedules (twice a day [BID] or three times a day [TID]) of DAV131A (D1 to D8). Moxifloxacin concentrations and C. difficile counts were determined at D3, and mortality was determined at D12 We compared mortality rates, moxifloxacin concentrations, and C. difficile counts according to DAV131A regimen and modeled the links between DAV131A regimen, moxifloxacin concentration, and mortality. All hamsters that received no DAV131A died, but none of those that received 1,800 mg/kg/day died. Significant dose-dependent relationships between DAV131A dose and (i) mortality, (ii) moxifloxacin concentration, and (iii) C. difficile count were evidenced. Mathematical modeling suggested that (i) lowering the moxifloxacin concentration at D3, which was 58 µg/g (95% confidence interval [CI] = 50 to 66 µg/g) without DAV131A, to 17 µg/g (14 to 21 µg/g) would reduce mortality by 90%; and (ii) this would be achieved with a daily DAV131A dose of 703 mg/kg (596 to 809 mg/kg). In this model of C. difficile infection, DAV131A reduced mortality in a dose-dependent manner by decreasing the fecal free moxifloxacin concentration.

Loop ileostomy versus total colectomy as surgical treatment for Clostridium difficile-associated disease: An Eastern Association for the Surgery of Trauma multicenter trial.

OBJECTIVES: The mortality of patients with Clostridium difficile-associated disease (CDAD) requiring surgery continues to be very high. Loop ileostomy (LI) was introduced as an alternative procedure to total colectomy (TC) for CDAD by a single-center study. To date, no reproducible results have been published. The objective of this study was to compare these two procedures in a multicentric approach to help the surgeon decide what procedure is best suited for the patient in need. METHODS: This was a retrospective multicenter study conducted under the sponsorship of the Eastern Association for the Surgery of Trauma. Demographics, medical history, clinical presentation, APACHE score, and outcomes were collected. We used the Research Electronic Data Capture tool to store the data. Mann-Whitney (continuous data) and Fisher exact (categorical data) were used to compare TC with LI. Logistic regression was performed to determine predictors of mortality. A propensity score analysis was done to control for potential confounders and determine adjusted mortality rates by procedure type. RESULTS: We collected data from 10 centers of patients who presented with CDAD requiring surgery between July 1, 2010 and July 30, 2014. Two patients died during the surgical procedure, leaving 98 individuals in the study. The overall mortality was 32%, and 75% had postoperative complications. Median age was 64.5 years; 59% were male. Concerning preoperative patient conditions, 54% were on pressors, 47% had renal failure, and 36% had respiratory failure. When comparing TC and LI, there was no statistical difference regarding these conditions. Univariate preprocedure predictors of mortality were age, lactate, timing of operation, vasopressor use, and acute renal failure. There was no statistical difference between the APACHE score of patients undergoing either procedure (TC, 22 vs LI, 16). Adjusted mortality (controlled for preprocedure confounders) was significantly lower in the LI group (17.2% vs 39.7%; p = 0.002). CONCLUSIONS: This is the first multicenter study comparing TC with LI for the treatment of CDAD. In this study, LI carried less mortality than TC. In patients without contraindications, LI should be considered for the surgical treatment of CDAD. LEVEL OF EVIDENCE: Therapeutic study, level III.

Recurrent Clostridium difficile infection among Medicare patients in nursing homes: A population-based cohort study.

We explored the epidemiology and outcomes of Clostridium difficile infection (CDI) recurrence among Medicare patients in a nursing home (NH) whose CDI originated in acute care hospitals.We conducted a retrospective, population-based matched cohort combining Medicare claims with Minimum Data Set 3.0, including all hospitalized patients age ≥65 years transferred to an NH after hospitalization with CDI 1/2011-11/2012. Incident CDI was defined as ICD-9-CM code 008.45 with no others in prior 60 days. CDI recurrence was defined as (within 60 days of last day of CDI treatment): oral metronidazole, oral vancomycin, or fidaxomicin for ≥3 days in part D file; or an ICD-9-CM code for CDI (008.45) during a rehospitalization. Cox proportional hazards and linear models, adjusted for age, gender, race, and comorbidities, examined mortality within 60 days and excess hospital days and costs, in patients with recurrent CDI compared to those without.Among 14,472 survivors of index CDI hospitalization discharged to an NH, 4775 suffered a recurrence. Demographics and clinical characteristics at baseline were similar, as was the risk of death (24.2% with vs 24.4% without). Median number of hospitalizations was 2 (IQR 1-3) among those with and 0 (IQR 0-1) among those without recurrence. Adjusted excess hospital days per patient were 20.3 (95% CI 19.1-21.4) and Medicare reimbursements $12,043 (95% CI $11,469-$12,617) in the group with a recurrence.Although recurrent CDI did not increase the risk of death, it was associated with a far higher risk of rehospitalization, excess hospital days, and costs to Medicare.