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Clostridioides difficile infection (CDI) is a major health-care burden and increasingly seen in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Increased antibiotic use, alteration in host defenses, and gastric acid suppression are some of the etiologies for increased risk of CDI in these populations. Patients with CKD/ESRD have a higher risk of initial episode, recurrence, and development of severe CDI than those without CKD or ESRD. Diagnosis and management of CDI in patients with CKD/ESRD are similar to that in the general population. The mortality, length of stay, and health-care costs are higher in patients with CDI and CKD/ESRD. Antimicrobial stewardship with reduction in antibiotic use along with infection-control measures such as contact isolation and hand hygiene with soap and water is essential in the control and prevention of CDI in patients with CKD/ESRD., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background & Aims: 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., Methods: We searched MEDLINE, EMBASE, International Journal of Probiotics and Prebiotics, and The Cochrane Library databases for randomized controlled trials evaluating use of probiotics and CDI in hospitalized adults taking antibiotics. Two reviewers independently extracted data and assessed risk of bias and overall quality of the evidence. Primary and secondary outcomes were incidence of CDI and adverse events, respectively. Secondary analyses examined the effects of probiotic species, dose, timing, formulation, duration, and study quality., Results: We analyzed data from 19 published studies, comprising 6261 subjects. The incidence of CDI in the probiotic cohort, 1.6% (54 of 3277), was lower than of controls, 3.9% (115 of 2984) (P < .001). The pooled relative risk of CDI in probiotic users was 0.42 (95% confidence interval, 0.30-0.57; I 2  = 0.0%). Meta-regression analysis demonstrated that probiotics were significantly more effective if given closer to the first antibiotic dose, with a decrement in efficacy for every day of delay in starting probiotics (P = .04); probiotics given within 2 days of antibiotic initiation produced a greater reduction of risk for CDI (relative risk, 0.32; 95% confidence interval, 0.22-0.48; I 2  = 0%) than later administration (relative risk, 0.70; 95% confidence interval, 0.40-1.23; I 2  = 0%) (P = .02). There was no increased risk for adverse events among patients given probiotics. The overall quality of the evidence was high., Conclusions: In a systematic review with meta-regression analysis, we found evidence that administration of probiotics closer to the first dose of antibiotic reduces the risk of CDI by >50% in hospitalized adults. Future research should focus on optimal probiotic dose, species, and formulation. Systematic Review Registration: PROSPERO CRD42015016395., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Antibiotic-associated infection with the bacterial pathogen Clostridium difficile is a major cause of morbidity and increased health care costs. C difficile infection follows disruption of the indigenous gut microbiota by antibiotics. Antibiotics create an environment within the intestine that promotes C difficile spore germination, vegetative growth, and toxin production, leading to epithelial damage and colitis. Studies of patients with C difficile infection and animal models have shown that the indigenous microbiota can inhibit expansion and persistence of C difficile. Although the specific mechanisms of these processes are not known, they are likely to interfere with key aspects of the pathogen's physiology, including spore germination and competitive growth. Increasing our understanding of how the intestinal microbiota manage C difficile could lead to better means of controlling this important nosocomial pathogen., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Prevention of recurrent Clostridium difficile infection (CDI) is a substantial therapeutic challenge. A previous prospective study of 63 patients with CDI identified risk factors associated with recurrence. This study aimed to develop a prediction rule for recurrent CDI using the above derivation cohort and prospectively evaluate the performance of this rule in an independent validation cohort., Methods: The clinical prediction rule was developed by multivariate logistic regression analysis and included the following variables: age>65 years, severe or fulminant illness (by the Horn index), and additional antibiotic use after CDI therapy. A second rule combined data on serum concentrations of immunoglobulin G (IgG) against toxin A with the clinical predictors. Both rules were then evaluated prospectively in an independent cohort of 89 patients with CDI., Results: The clinical prediction rule discriminated between patients with and without recurrent CDI, with an area under the curve of the receiver-operating-characteristic curve of 0.83 (95% confidence interval [CI]: 0.70-0.95) in the derivation cohort and 0.80 (95% CI: 0.67-0.92) in the validation cohort. The rule correctly classified 77.3% (95% CI: 62.2%-88.5%) and 71.9% (95% CI: 59.2%-82.4%) of patients in the derivation and validation cohorts, respectively. The combined rule performed well in the derivation cohort but not in the validation cohort (area under the curve of the receiver-operating-characteristic curve, 0.89 vs 0.62; diagnostic accuracy, 93.8% vs 69.2%, respectively)., Conclusions: We prospectively derived and validated a clinical prediction rule for recurrent CDI that is simple, reliable, and accurate and can be used to identify high-risk patients most likely to benefit from measures to prevent recurrence.

Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Its effects are mediated by C difficile toxins A and B. Recent outbreaks of severe colitis have been associated with a new strain of the bacterium that produces large amounts of the toxins. Although oral metronidazole and oral vancomycin can be used to treat C difficile-associated disease, intraluminal vancomycin is preferable for more severe C difficile colitis. Early surgical intervention can improve outcomes with fulminant colitis, although overall mortality remains high.

Background & Aims: Recurrent C difficile -associated diarrhea (CDAD) is associated with a lack of protective immunity to C difficile toxins. A parenteral C difficile vaccine containing toxoid A and toxoid B was reported previously to be safe and immunogenic in healthy volunteers. Our aim was to examine whether the vaccine is also well tolerated and immunogenic in patients with recurrent CDAD., Methods: Subjects received 4, 50-microg intramuscular inoculations of the C difficile vaccine over an 8-week period. Serum antitoxin antibodies were measured by ELISA, and toxin neutralizing activity was evaluated using the tissue culture cytotoxin assay., Results: Three patients with multiple episodes of recurrent CDAD were vaccinated. Two of the 3 showed an increase in serum IgG antitoxin A antibodies (3-fold and 4-fold increases, respectively) and in serum IgG antitoxin B antibodies (52-fold and 20-fold, respectively). Both also developed cytotoxin neutralizing activity against toxin A and toxin B. Prior to vaccination, the subjects had required nearly continuous treatment with oral vancomycin for 7, 9, and 22 months, respectively, to treat recurrent episodes of CDAD. After vaccination, all 3 subjects discontinued treatment with oral vancomycin without any further recurrence., Conclusions: A C difficile toxoid vaccine induced immune responses to toxins A and B in patients with CDAD and was associated with resolution of recurrent diarrhea. The results of this study support the feasibility of active vaccination against C difficile and its toxins in high-risk individuals but must be validated in larger, randomized, controlled trials.

C difficile has emerged as an important cause of diarrheic disease in horses. C difficile diarrhea is usually diagnosed in mature horses, mostly when they are treated with antimicrobials and hospitalized. It is important for clinicians at veterinary hospitals to have knowledge about the organism and the infection. To prevent C difficile diarrhea, judicious use of antimicrobials is important, as is minimizing different stress factors at the animal hospital or clinic. Infected horses must be isolated. Routine examination for C difficile and toxin A or B is recommended in horses with antibiotic-associated diarrhea. When treating foals for R equi pneumonia, it is important to avoid accidental ingestion of erythromycin by the dams. To reduce the number of environmental spores, thorough cleaning and surface disinfection of the animal hospital and clinic are important. Routine handwashing should be performed by all staff.

Sequential antimicrobial therapy is not new, but confusion about the timing and nature of the switch often negates perceived advantages. A common problem is the choice of oral antibiotic to follow empirical administration of an intravenous second or third generation cephalosporin. Where guidelines do not exist, particularly when data are lacking as the the best option, the Delphi technique of obtaining a consensus agreement by review of a series of case histories is recommended. Majority verdicts are used to determine what is acceptable practice, and as such the approach is also suitable for audit. Savings through reduced drug acquisition costs and shorter lengths of stay have been highlighted. However, other less obvious potential benefits of sequential antimicrobial therapy include reduced incidence of intravascular catheter infection because of shorter line dwell times and less endoluminal contamination. Sequential antimicrobial therapy may also be used as part of a policy to reduce the selective pressure, particularly due to cephalosporin use, for endemic hospital pathogens such as Clostridium difficile and extended spectrum producing gram-negative baccilli.

During the past two decades, necrotizing enterocolitis has emerged as a major cause of mortality and morbidity in premature infants. The specific cause of the disease remains enigmatic, but several putative risk factors provide clues to a pathophysiology that seems to be multifactorial. With the use of newly developed scientific tools, an understanding of the basic pathophysiologic cascade that causes necrotizing enterocolitis is emerging, providing hope for improved treatment and prevention.

Necrotizing enterocolitis (NEC) remains a major cause of morbidity and mortality in premature infants. An incomplete understanding of its pathogenesis has hampered efforts to devise an effective preventative strategy. New insights into the pathogenesis of NEC, particularly at the cellular and biochemical level, however, offer a rational basis for the development of new approaches to this disease.

Cortisone acetate is known to accelerate maturation of the immature intestine. The effect of prenatal administration of cortisone acetate on the morbidity and mortality of necrotizing enterocolitis was examined in a rat pup model. Pregnant rats were administered cortisone acetate, 20 mg/100 g of body weight, or normal saline by daily IP injection from day 18-21 of gestation. Rat pups were taken from the mothers before suckling was initiated, fed a simulated rat milk formula, and subjected to daily ischemic insults to produce an animal model of necrotizing enterocolitis. Both morbidity and the mortality rates were significantly improved with prenatal cortisone treatment. Maturation of the intestinal mucosal barrier was accelerated with the cortisone treatment as measured by decreased serum concentrations of a fed antigen, ovalbumin. Aerobic bacterial colonization of the small intestine and translocation of bacteria to the liver were decreased in the pups pretreated with steroids. These changes observed in a rat model of necrotizing enterocolitis may explain the decreased incidence of necrotizing enterocolitis in human infants born to mothers who received corticosteroids late in gestation.

Clindamycin and lincomycin produced a lethal enterocolitis in 65 of 67 Syrian hamsters. The administration of oral or parenteral vancomycin to recipients of clindamycin or lincomycin was uniformly protective in 49 patients. These results suggest that certain bacteria play a role in the pathogenesis of enterocolitis in this model.

There is a broad spectrum of presentations and severity of necrotizing enterocolitis. Because it may have several different causes, ncerotizing enterocolitis may be a syndrome rather than a specific disease. The triad of formula feeding, intestinal ischemia, and bacterial growth may be part of the pathogenesis of necrotizing enterocolitis. Bacteria are of central importance for the production of pneumatosis, a prerequisite of which is formula feeding. Bacteria may also contribute to the intestinal injury seen after ischemia. However, the disease in the low risk patient seen during an epidemic associated with a single organism is probably caused by a primary gastrointestinal infection. On the other hand, in the stressed newborn infant with mucosal injury the presence of the appropriate bacteria may be all that is needed to initiate the chain of events leading to necrotizing enterocolitis. Figure 2 illustrates the importance of bacteria in all the causes proposed to be involved in the pathogenesis of necrotizing enterocolitis. Whether bacteria are primary or secondary agents, necrotizing enterocolitis should always be approached therapeutically as an infectious disease.