Concept: Pseudomembranous colitis
In 1958, doctors in Denver administered feces by enema to their patients with fulminant, life-threatening pseudomembranous enterocolitis.(1) The goal of this infusion of donor feces (also termed fecal microbiota transplantation [FMT]) was to “re-establish the balance of nature” within the intestinal flora to correct the disruption caused by antibiotic treatment. They reported “immediate and dramatic” responses and concluded that “this simple yet rational therapeutic method should be given more extensive clinical evaluation.” During the ensuing 50 years, the association between Clostridium difficile infection and pseudomembranous enterocolitis was established, and effective antimicrobial treatments were identified. Despite these advances, C. difficile became . . .
Metronidazole hydrochloride has historically been considered first-line therapy for patients with mild to moderate Clostridium difficile infection (CDI) but is inferior to vancomycin hydrochloride for clinical cure. The choice of therapy may likewise have substantial consequences on other downstream outcomes, such as recurrence and mortality, although these secondary outcomes have been less studied.
To determine pre-/intraoperative risk factors for anastomotic leak after colon resection for cancer and to create a practical instrument for predicting anastomotic leak risk.
BACKGROUND: Although enhanced recovery pathways (ERPs) may permit early recovery and discharge after laparoscopic colorectal surgery (LC), most publications report that the mean hospital stay is 4 and 6 days. This study evaluates the addition of a transversus abdominis plane (TAP) block to the standard ERP. METHODS: In this study, 35 consecutive elective patients received a TAP block at the end of LC. The patients were matched by operation, diagnosis, age, gender, and body mass index (BMI) with 35 recent cases and followed in a prospective institutional review board (IRB)-approved database. All the patients were managed with a standardized ERP. The surgeon placed TAP blocks under laparoscopic guidance that infiltrated 15 ml of 0.5 % Marcaine on both sides of the abdomen. RESULTS: The cases included 8 low pelvic anastomoses, 4 proctectomies with or without an ileal pouch anal anastomosis, 5 sigmoid/left colectomies, 13 ileocolic/right colectomies, 1 total colectomy, and 5 others. The mean age was 59 years for the TAP group and 64.1 years for the control group (p = 0.21). The mean hospital stay was 2 days for the TAP patients and 3 days for the control patients (p = 0.000013). Of the 35 TAP patients, 13 went home on postoperative day (POD) 1 (37 %), 12 on POD 2 (34 %), 8 on POD 3 (23 %), and the remainder on POD 4. Of the 35 control patients, 1 went home on POD 1 (3 %), 10 on POD 2 (29 %), 10 on POD 3 (29 %), 11 on POD 4 (31 %), and the remainder on POD 5 to 8. The TAP patients required fewer narcotics postoperatively than the control patients (respective mean morphine equivalents, 31.08 vs. 85.41; p = 0.01). DISCUSSION: A bilateral TAP block significantly improved the results of an established ERP for patients undergoing LC. Surgeon-administered TAP blocks may be an economical and efficient method for improving the results of LC.
CDT (Clostridium difficile transferase) is a binary, actin ADP-ribosylating toxin frequently associated with hypervirulent strains of the human enteric pathogen C. difficile, the most serious cause of antibiotic-associated diarrhea and pseudomembranous colitis. CDT leads to the collapse of the actin cytoskeleton and, eventually, to cell death. Low doses of CDT result in the formation of microtubule-based protrusions on the cell surface that increases the adherence and colonization of C. difficile. The lipolysis-stimulated lipoprotein receptor (LSR) is the host cell receptor for CDT and our aim was to gain a deeper insight into the interplay between both proteins. We show that CDT interacts with the extracellular, Ig-like domain of LSR with an affinity in the nanomolar range. We identified LSR splice variants in the colon carcinoma cell line HCT116 and disrupted the LSR gene in these cells by applying the CRISPR-Cas9 technology. LSR truncations ectopically expressed in LSR knockout cells indicated that intracellular parts of LSR are not essential for plasma membrane targeting of the receptor and cellular uptake of CDT. By generating a series of N- and C-terminal truncations of the binding component of CDT (CDTb), we found that amino acids 757 to 866 of CDTb are sufficient for binding to LSR. With a transposon-based, random mutagenesis approach we identified potential LSR-interacting epitopes in CDTb. This study increases our understanding about the interaction between CDT and its receptor LSR, which is key to the development of anti-toxin strategies for preventing cell entry of the toxin.
Our primary objective was to demonstrate the utility and feasibility of the intraoperative assessment of colon and rectal perfusion using fluorescence angiography (FA) during left-sided colectomy and anterior resection. Anastomotic leak (AL) after colorectal resection increases morbidity, mortality, and, in cancer cases, recurrence rates. Inadequate perfusion may contribute to AL. The PINPOINT Endoscopic Fluorescence Imaging System allows for intraoperative assessment of anastomotic perfusion.
BACKGROUND: Antibiotics are widely prescribed; however they can cause disturbances in gastrointestinal flora which may lead to reduced resistance to pathogens such as Clostridium difficile (C. difficile). Probiotics are live organisms thought to balance the gastrointestinal flora. OBJECTIVES: The primary objectives were to assess the efficacy and safety of probiotics for preventing Clostridium difficile-associated diarrhea (CDAD) or C. difficile infection in adults and children. SEARCH METHODS: On February 21, 2013 we searched PubMed (1966-2013), EMBASE (1966-2013), Cochrane Central Register of Controlled Trials (The Cochrane Library 2013, Issue 1), CINAHL (1982-2013), AMED (1985-2013), and ISI Web of Science. Additionally, we conducted an extensive grey literature search including contact with industry representatives. SELECTION CRITERIA: Randomized controlled (placebo, alternative prophylaxis, or no treatment control) trials investigating probiotics (any strain, any dose) for prevention of CDAD, or C. difficile infection were considered for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently and in duplicate extracted data and assessed risk of bias using pre-constructed, and piloted, data extraction forms. Any disagreements were resolved by a third adjudicator. For articles published in abstract form only, further information was sought by contacting principal authors. The primary outcome was the incidence of CDAD. Secondary outcomes included the incidence of C. difficile infection, adverse events, antibiotic-associated diarrhea (AAD) and length of hospital stay. Dichotomous outcomes (e.g. incidence of CDAD) were pooled using a random-effects model to calculate the relative risk and corresponding 95% confidence interval (95% CI). Continuous outcomes (e.g. length of hospital) were pooled using a random-effects model to calculate the mean difference and corresponding 95% CI. Sensitivity analyses were conducted to explore the impact of missing data on efficacy and safety outcomes. For the sensitivity analyses, we assumed that the event rate for those participants in the control group who had missing data was the same as the event rate for those participants in the control group who were successfully followed. For the probiotic group we calculated effects using the following assumed ratios of event rates in those with missing data in comparison to those successfully followed: 1.5:1, 2:1, 3:1, and 5:1. To explore possible explanations for heterogeneity, a priori subgroup analysis were conducted on probiotic species, dose, adult versus pediatric population, and risk of bias.The overall quality of the evidence supporting each outcome was assessed using the GRADE criteria. MAIN RESULTS: A total of 1871 studies were identified with 31 (4492 participants) meeting eligibility requirements for our review. Overall 11 studies were rated as a high risk of bias due mostly to missing outcome data. A complete case analysis (i.e. participants who completed the study) of those trials investigating CDAD (23 trials, 4213 participants) suggests that probiotics significantly reduce this risk by 64%. The incidence of CDAD was 2.0% in the probiotic group compared to 5.5% in the placebo or no treatment control group (RR 0.36; 95% CI 0.26 to 0.51). Sixteen of 23 trials had missing CDAD data ranging from 5% to 45%. These results proved robust to sensitivity analyses of plausible and worst-plausible assumptions regarding missing outcome data and were similar whether considering trials in adults versus children, lower versus higher doses, different probiotic species, or higher versus lower risk of bias. Our judgment is that the overall evidence warrants moderate confidence in this large relative risk reduction. We downgraded the overall quality of evidence for CDAD to ‘moderate’ due to imprecision. There were few events (154) and the calculated optimal information size (n = 8218) was more than the total sample size. With respect to the incidence of C. difficile infection, a secondary outcome, pooled complete case results from 13 trials (961 participants) did not show a statistically significant reduction. The incidence of C. difficile infection was 12.6% in the probiotics group compared to 12.7% in the placebo or no treatment control group (RR 0.89; 95% CI 0.64 to 1.24). Adverse events were assessed in 26 studies (3964 participants) and our pooled complete case analysis indicates probiotics reduce the risk of adverse events by 20% (RR 0.80; 95% CI 0.68 to 0.95). In both treatment and control groups the most common adverse events included abdominal cramping, nausea, fever, soft stools, flatulence, and taste disturbance. For the short-term use of probiotics in patients that are not immunocompromised or severely debilitated, we consider the strength of this evidence to be moderate. AUTHORS' CONCLUSIONS: Based on this systematic review and meta-analysis of 23 randomized controlled trials including 4213 patients, moderate quality evidence suggests that probiotics are both safe and effective for preventing Clostridium difficile-associated diarrhea.
We present a novel methodology to construct a Boolean dynamic model from time series metagenomic information and integrate this modeling with genome-scale metabolic network reconstructions to identify metabolic underpinnings for microbial interactions. We apply this in the context of a critical health issue: clindamycin antibiotic treatment and opportunistic Clostridium difficile infection. Our model recapitulates known dynamics of clindamycin antibiotic treatment and C. difficile infection and predicts therapeutic probiotic interventions to suppress C. difficile infection. Genome-scale metabolic network reconstructions reveal metabolic differences between community members and are used to explore the role of metabolism in the observed microbial interactions. In vitro experimental data validate a key result of our computational model, that B. intestinihominis can in fact slow C. difficile growth.
Systematic reviews have provided evidence for the efficacy of probiotics in preventing Clostridium difficile infection (CDI), but guidelines do not recommend probiotic use for prevention of CDI. We performed an updated systematic review to help guide clinical practice.
Fidaxomicin is sporicidal and may be associated with a reduced time to resolution of diarrhoea when used to treat patients with Clostridium difficile infection (CDI). This study investigated whether fidaxomicin for treatment of all patients with CDI reduced C. difficile environmental contamination. Surfaces in the rooms of 66 hospitalized patients treated with metronidazole and/or vancomycin and 68 hospitalized patients treated with fidaxomicin were sampled. Patients treated with fidaxomicin were less likely to contaminate their environment (25/68, 36.8%) than patients treated with metronidazole and/or vancomycin (38/66 57.6%) (P = 0.02). Treatment with fidaxomicin was associated with reduced environmental contamination with C. difficile.