Faecal microbiota transplantation in the treatment of recurrent intestinal Clostridioides difficile infection - a ten-year single-center experience.

Clostridioides difficile (Clostridium difficile in older taxonomy) is a gram-positive anaerobic and bacteria enabled by endospores. Clostridioides difficile is currently the main cause of nosocomial infections in developed countries. Due to the high probability of developing bacterial resistance to treatment and the numerous recurrences in multiple chronic conditions in older adults of our society it causes a widespread medical problem. Faecal microbiota transplantation (FMT) is a highly effective method for treating recurrent intestinal Clostridioides difficile infections (CDI). With this method the potential mechanism of effect is the transmission of a complex intestinal ecosystem, including vital microorganisms, from the donor to the recipient. Presenting the results of monocentric prospective monitoring: Primary aim of the study was to evaluate long-term remission (the continued absence of clinical manifestations of CDI 3 months after FMT administration). The secondary aim of the study was to monitor the short-term remission in the 7 days after FMT administration. Demographic data, information about CDI and the details of therapy were obtained and completed by the treating physician of each patient or by targeted questioning of the patient or their family. We used clinical monitoring to determine the effect of the treatment. The examinations of stool donors and the preparation for a faecal microbiota transplantation were performed according to the currently valid guidelines of the Czech Society of Infectious Diseases for the treatment of the recurrent bacterial infection Clostridioides difficile with faecal microbiota transplantation. The follow-ups took place from February 2011 to July 2021 in the gastroenterology department at the AGEL Ostrava-Vítkovice Hospital and included 116 patients with their first and subsequent recurrence of CDI that were treated with faecal bacteriotherapy. The median age of our patients was 71 years old (the youngest was 19 years old, the oldest 103 years old). 69 women and 47 men took part in the study. 56 patients had their first recurrence of CDI, 41 had a second attack, and 20 patients had a third and subsequent recurrences. In 62 patients (53.4 %), the route of FMT administration was a local enema into the left colon. With 37 patients (31.9 %) we used a colonoscopy after standard anterograde bowel preparation. With 12 patients (10.3 %) gastroscopy administration (deep into the duodenum) was used. 4 patients (3.5 %) were given a nasoenteral tube and one patient (0.9 %) was administered FMT per percutaneous endoscopic gastrostomy (PEG). We applied a frozen universal donor FMT in 81 patients (69.8 %), and a freshly prepared FMT from a person living in the same household was used in 35 patients (30.1 %). The secondary endpoint (the absence of clinical manifestations of CDI within 7 days of FMT administration) was achieved with 102 patients (87.9 %) in our study. The fulfilment of the primary endpoint (the development of long-term remission) was observed with 93 patients (80.2 %). An early administration of FMT appears to be a significant predictor of treatment effect (p = 0.05; OR 5.11; 95% CI 1.65-15.8). Faecal microbiota transplantation is an effective and safe therapy for recurrent intestinal Clostridioides difficile infection, and it respects the up-to-date guidelines for treatment. Of the 116 patients included in our study with first and subsequent CDI, we achieved long-term remission in 80.2 % of them. An early administration of FMT appears to be a significant predictor of treatment effect.

History of Cholecystectomy and Risk of Clostridium Difficile Infection.

BACKGROUND: Cholecystectomy affects bile acid physiology. There is growing evidence that both primary and secondary bile acids play a role in the pathogenesis of Clostridium difficile infections (CDIs). AIMS: The aim of this study is to elucidate the relationship and risk of CDI in patients with cholecystectomy. METHODS: We performed a matched cohort study of patients in an integrated healthcare system in Northern California from January 2000 to December 2018. Patients with cholecystectomy (cases, n = 12,617) identified based on Current Procedure Terminology codes were age- and sex-matched to patients without cholecystectomy (controls, n = 37,851). We excluded those with history of CDI at baseline and calculated the hazard ratio (HR) for development of CDI after adjusting for confounders. RESULTS: We found total of 351 incident CDI during average of 4.66 years of follow-up among cases and controls. In multivariate analysis, cholecystectomy was associated with elevated risk of CDI (HR 1.53, 95% confidence interval 1.14-2.04) compared with controls. Stratified analysis shows this effect does not differ according use of proton pump inhibitors (Pinteraction = 0.142), antibiotics (Pinteraction = 0.387), and hospitalization (Pinteraction = 0.252). CONCLUSIONS: Cholecystectomy is associated with mild increased risk of incident CDI, but this effect is not influenced by use of proton pump inhibitors, antibiotics, or hospitalization. Future prospective studies should be conducted to validate these findings and evaluate bile acid changes after a cholecystectomy.

Risk Factors of Clostridium Difficile Infection After Spinal Surgery: National Health Insurance Database.

The purpose of this study was to evaluate risk factors of Clostridium Difficile infection (CDI) after spinal surgery using the Health Insurance Review and Assessment Service (HIRA) data. The incidence of postoperative CDI was investigated using HIRA data from 2012 to 2016. Cases involving CDI that occurred within a 30-day postoperative period were identified. Risk factors, including age, sex, comorbidities, postoperative infection, spinal surgery procedure, type of antibiotic, and duration of antibiotic use, were evaluated. Duration of hospital stay, medical cost, and mortality were also evaluated. In total, 71,322 patients were included. Presumed cases of CDI were identified in 57 patients, with CDI rate of 0.54 per 10,000 patient days. Advanced age, staged operation, postoperative infection, and the use of multiple antibiotics were significant risk factors. First-generation cephalosporins were shown to be associated with a lower incidence of CDI. CDI was also associated with longer hospital stays and increased medical cost, and it was an independent risk factor for increased mortality. Extra attention should be paid to patients at high risk for the development of postoperative CDI, and unnecessary use of multiple antibiotics should be avoided. Level of Evidence: Level III, retrospective cohort study.

Outbreak of Murine Infection with Clostridium difficile Associated with the Administration of a Pre- and Perinatal Methyl Donor Diet.

Between October 2016 and June 2017, a C57BL/6J mouse colony that was undergoing a pre- and perinatal methyl donor supplementation diet intervention to study the impact of parental nutrition on offspring susceptibility to disease was found to suffer from an epizootic of unexpected deaths. Necropsy revealed the presence of severe colitis, and further investigation linked these outbreak deaths to a Clostridium difficile strain of ribotype 027 that we term 16N203. C. difficile infection (CDI) is associated with antibiotic use in humans. Current murine models of CDI rely on antibiotic pretreatment to establish clinical phenotypes. In this report, the C. difficile outbreak occurs in F1 mice linked to alterations in the parental diet. The diagnosis of CDI in the affected mice was confirmed by cecal/colonic histopathology, the presence of C. difficile bacteria in fecal/colonic culture, and detection of C. difficile toxins. F1 mice from parents fed the methyl supplementation diet also had significantly reduced survival (P < 0.0001) compared with F1 mice from parents fed the control diet. When we tested the 16N203 outbreak strain in an established mouse model of antibiotic-induced CDI, we confirmed that this strain is pathogenic. Our serendipitous observations from this spontaneous outbreak of C. difficile in association with a pre- and perinatal methyl donor diet suggest the important role that diet may play in host defense and CDI risk factors.IMPORTANCEClostridium difficile infection (CDI) has become the leading cause of infectious diarrhea in hospitals worldwide, owing its preeminence to the emergence of hyperendemic strains, such as ribotype 027 (RT027). A major CDI risk factor is antibiotic exposure, which alters gut microbiota, resulting in the loss of colonization resistance. Current murine models of CDI also depend on pretreatment of animals with antibiotics to establish disease. The outbreak that we report here is unique in that the CDI occurred in mice with no antibiotic exposure and is associated with a pre- and perinatal methyl supplementation donor diet intervention study. Our investigation subsequently reveals that the outbreak strain that we term 16N203 is an RT027 strain, and this isolated strain is also pathogenic in an established murine model of CDI (with antibiotics). Our report of this spontaneous outbreak offers additional insight into the importance of environmental factors, such as diet, and CDI susceptibility.

Clostridium difficile extraintestinal abscess: a rare complication.

Extraintestinal Clostridium difficile is rare. A 74-year-old man with a history of ulcerative colitis presented after a fall. Trauma work-up showed liver cirrhosis. Two days later he developed abdominal pain, distension, diarrhoea and leucocytosis. Stool tested positive for C. difficile CT abdomen showed pancolitis with toxic megacolon. Total abdominal colectomy and ileostomy with a rectal stump was performed. He was discharged, but was readmitted with sepsis. CT abdomen showed a 10.4×7.2 cm fluid collection in the pelvis. C. difficile stool was negative. CT-guided abscess drainage grew C. difficile Barium enema was negative for communication from the rectal stump to the abscess. The patient was treated with metronidazole for 2 weeks. In summary, extraintestinal C. difficile can develop from recent antibiotics use, gastrointestinal surgery and microperforations from toxic megacolon. We recommend abscess drainage, concomitant treatment with metronidazole and or vancomycin, and reimaging of abscess location 2-4 weeks after cessation of antibiotics.

Clostridium difficile infection induced by pregabalin-associated agranulocytosis.

A 33-year-old man who had recently undergone surgery for cervical spondylotic myelopathy was prescribed pregabalin for neuralgia, and the dose was increased to 600 mg/day during hospitalization. However, the patient was diagnosed with a Clostridium difficile infection on day 34 after admission. A complete blood count showed agranulocytosis (neutrophil count: 105/µL). We did not observe any changes in vital signs, a relative increase in band cells, or intestinal edema. The patient's agranulocytosis resolved after withdrawing pregabalin. This is the first reported case of agranulocytosis associated with pregabalin. Periodic monitoring of the white blood cell count is therefore considered to be useful in patients receiving high-dose pregabalin therapy.

Higher plasma vitamin D is associated with reduced risk of Clostridium difficile infection in patients with inflammatory bowel diseases.

BACKGROUND: Patients with inflammatory bowel diseases (IBD) have an increased risk of clostridium difficile infection (CDI). Cathelicidins are anti-microbial peptides that attenuate colitis and inhibit the effect of clostridial toxins. Plasma calcifediol [25(OH)D] stimulates production of cathelicidins. AIM: To examine the association between plasma 25(OH)D and CDI in patients with IBD. METHODS: From a multi-institutional IBD cohort, we identified patients with at least one measured plasma 25(OH)D. Our primary outcome was development of CDI. Multivariate logistic regression models adjusting for potential confounders were used to identify independent effect of plasma 25(OH)D on risk of CDI. RESULTS: We studied 3188 IBD patients of whom 35 patients developed CDI. Patients with CDI-IBD were older and had greater co-morbidity. The mean plasma 25(OH)D level was significantly lower in patients who developed CDI (20.4 ng/mL) compared to non-CDI-IBD patients (27.1 ng/mL) (P = 0.002). On multivariate analysis, each 1 ng/mL increase in plasma 25(OH)D was associated with a 4% reduction in risk of CDI (OR 0.96, 95% CI 0.93-0.99, P = 0.046). Compared to individuals with vitamin D >20 ng/mL, patients with levels <20 ng/mL were more likely to develop CDI (OR 2.27, 95% CI 1.16-4.44). The mean plasma 25(OH)D in patients with CDI who subsequently died was significantly lower (12.8 ± 8.1 ng/mL) compared to those who were alive at the end of follow-up (24.3 ± 13.2 ng/mL) (P = 0.01). CONCLUSIONS: Higher plasma calcifediol [25(OH)D] is associated with reduced risk of C. difficile infection in patients with IBD. Further studies of therapeutic supplementation of vitamin D in patients with inflammatory bowel disease and C. difficile infection may be warranted.

Clostridia in premature neonates' gut: incidence, antibiotic susceptibility, and perinatal determinants influencing colonization.

BACKGROUND: Although premature neonates (PN) gut microbiota has been studied, data about gut clostridial colonization in PN are scarce. Few studies have reported clostridia colonization in PN whereas Bacteroides and bifidobacteria have been seldom isolated. Such aberrant gut microbiota has been suggested to be a risk factor for the development of intestinal infections. Besides, PN are often treated by broad spectrum antibiotics, but little is known about how antibiotics can influence clostridial colonization based on their susceptibility patterns. The aim of this study was to report the distribution of Clostridium species isolated in feces from PN and to determine their antimicrobial susceptibility patterns. Additionally, clostridial colonization perinatal determinants were analyzed. RESULTS: Of the 76 PN followed until hospital discharge in three French neonatal intensive care units (NICUs), 79% were colonized by clostridia. Clostridium sp. colonization, with a high diversity of species, increased throughout the hospitalization. Antibiotic courses had no effect on the clostridial colonization incidence although strains were found susceptible (except C. difficile) to anti-anaerobe molecules tested. However, levels of colonization were decreased by either antenatal or neonatal (during more than 10 days) antibiotic courses (p = 0.006 and p = 0.001, respectively). Besides, incidence of colonization was depending on the NICU (p = 0.048). CONCLUSION: This study shows that clostridia are part of the PN gut microbiota. It provides for the first time information on the status of clostridia antimicrobial susceptibility in PN showing that strains were susceptible to most antibiotic molecules. Thus, the high prevalence of this genus is not linked to a high degree of resistance to antimicrobial agents or to the use of antibiotics in NICUs. The main perinatal determinant influencing PN clostridia colonization appears to be the NICU environment.

Update on medication abortion.

This article provides an overview of medication abortion in the United States 6 years after the approval of mifepristone (RU486; Mifeprex; Danco Laboratories, LLC, New York, NY) by the US Food and Drug Administration (FDA). The adoption of mifepristone is considered in the context of epidemiologic data on abortion, abortion access, and the safety of abortion. The risks of medication and aspiration abortion are discussed in the context of abortion-related mortality, recent experience with obstetric and gynecologic infection with Clostridium sordellii, and the limits of scientific knowledge on the incidence of this infection in women. Innovative protocols studied since FDA approval of mifepristone are presented, and implications for clinical practice are discussed.

Albumin, length of stay, and proton pump inhibitors: key factors in Clostridium difficile-associated disease in nursing home patients.

OBJECTIVES: To identify risk factors for Clostridium difficile-associated disease (CDAD) in nursing home patients. DESIGN: Retrospective chart reviews. SETTING: Long-term care facility with 347 beds and an additional 180 sub-acute care beds, adjacent to an academic tertiary care hospital center. PARTICIPANTS: Twenty-five patients had documented diagnosis of CDAD. Eighty-four percent were female, 76% white, 16% black, 4% Asian, and 4% Hispanic. Age ranged between 60 and 97 years (mean: 82.2 years). The control group had 28 patients, 68% were female, 89% white, and 11% black. Age ranged between 61 and 101 years (mean: 82.3 years). MEASUREMENTS: Length of stay at the facility, initial presenting symptoms, white blood cell count at the time of diagnosis, serum albumin level prior to the start of antibiotics, body mass index calculated from weight and height, presence or absence of dementia, history of diabetes mellitus and colonic disease, activity of daily living data include mobility, toileting and eating, use of percutaneous enterogastrostomy feeding, antibiotic administration, namely, type and duration, use of enema and laxatives, and use of proton pump inhibitors. RESULTS: Episodes of CDAD occurred mainly within the first year of admission to our facility, with a mean of 6 months, whereas the mean length of stay was 25 months in the control group (t = 3.452; df = 51; P < .01). Albumin level was another major risk factor for CDAD, with an overwhelming 68% of CDAD patients having albumin levels below 3 g/dL (mean 2.68 g/dL) compared with a mean of 3.22 g/dL in the control group (t = 4.210; df = 51; P < .001). The third significant risk factor was the use of proton pump inhibitors, 60% versus 32%, respectively (chi(2) = 4.137; df = 1; P < .05). Levofloxacin was the most frequently prescribed antibiotic (37%). Surprisingly, factors not associated with CDAD included dementia, diabetes mellitus, colonic disease, use of enema, use of laxatives, weight and body metabolic index, duration of previous antibiotic therapy for unrelated infection, mobility, toileting, and method of eating. CONCLUSION: A low albumin level, a recent admission to a nursing facility, and the use of proton pump inhibitors should be considered as probable risk factors for CDAD when assessing institutionalized patients with diarrhea. These findings may facilitate the timely and efficient management of CDAD in nursing home patients.

Occult gastrointestinal malignancies producing metastatic Clostridium septicum infections in diabetic patients.

BACKGROUND: Clostridial soft-tissue infections usually occur from traumatic injury but may be related to unrecognized gastrointestinal malignancy. Overwhelming sepsis with Clostridium septicum developed in five diabetic patients within 24 hours of onset of disease, and their course is reviewed. METHODS: The personal experience of the author in four cases is reviewed. RESULTS: Patients were seen within 12 to 24 hours of the onset of the disease with painful, rapidly spreading, gas-producing infection of the lower extremity (three patients), upper extremity (one patient), or pelvis (one patient), with severe sepsis in four of five patients. Three of the five patients had pertinent past histories that should have led to the prevention of the disease. CONCLUSIONS: Urgent laparotomy should be performed in otherwise healthy diabetic patients who had rapidly progressive, necrotizing, gas-producing infections with no obvious source. Metastatic spread can recur if the focus is not eradicated. All diabetic patients with guaiac-positive stools should have a gastrointestinal evaluation, including colonoscopy if barium enema is normal.

Effects of Eimeria brunetti infection and dietary zinc on experimental induction of necrotic enteritis in broiler chickens.

Broilers infected with Eimeria brunetti and given dietary zinc were examined for experimental induction of necrotic enteritis. Inoculation with sporulated E. brunetti oocysts at 7 days of age was followed by 5 consecutive days of oral inoculation with cultured Clostridium perfringens. Feed was supplemented with zinc at 1000 ppm. Upon necropsy of broilers 6 days after coccidial inoculation, necrotic enteritis was found in 20% (2/10) of birds given both organisms and dietary zinc. Coccidial lesion scores were also highest in that group. Birds infected with E. brunetti and C. perfringens with no dietary zinc had significantly higher coccidiosis lesion scores (P less than 0.05) than groups inoculated with E. brunetti only, regardless of zinc supplementation. Alpha toxin levels in intestinal contents were low in groups infected with both organisms, regardless of zinc supplementation. Zinc was tested for effects of alpha toxin production in vitro. In the mid-log phase (6 hours incubation), a high level of alpha toxin was produced in zinc-supplemented media, but this was lost quickly in the presence of trypsin. Addition of zinc partly protected the toxin from the action of trypsin.

Clostridial endocarditis. Report of a case caused by Clostridium bifermentans and review of the literature.

A case of Clostridium bifermentans endocarditis occurred in a 23-year-old man who was an intravenous drug user. There was no history of preexisting valvular heart disease. He was initially treated with high-dose penicillin G potassium but remained bacteremic for a ten-day period. The bacteremia resolved when the therapy was changed to metronidazole hydrochloride. A review of the 16 reported cases of clostridial endocarditis showed no predisposing host factor to the development of the disease. Penicillin is the treatment of choice for clostridial endocarditis, but metronidazole should be considered as an alternate therapy for treatment that fails.

Distant nontraumatic clostridial myonecrosis and malignancy.

Distant nontraumatic clostridial myonecrosis in association with malignancy is an uncommon disorder, with only 14 well-documented cases previously reported in the English literature. Clostridium perfringens and C. septicum are the most common organisms, usually gaining access to the circulation through an ulcerated lesion of the small bowel or colon. A case report of this syndrome caused by C. histolyticum is presented with a review of the literature.

Clostridial myonecrosis.

Clostridial infections, particularly myonecrosis, can be fulminant and fatal; they often arise without an obvious history of trauma. The cardinal diagnostic clues (Figure 3) must be recognized so that specific therapy can be initiated promptly and mortality can be minimized. Aggressive medical care, including crystalloid fluid therapy and antibiotics, must be initiated quickly. Vasopressors should be avoided. Antitoxin has no role in contemporary care. Early hyperbaric oxygenation is beneficial, but it should be preceded by decompressive fasciotomy if limb edema is marked. Otherwise, definitive debridement or amputation is best delayed until after hyperbaric therapy is begun. Regionalization of care and long transport times also must be considered seriously in determining the therapeutic approach.

Clostridium septicum infection in childhood leukemia: report of a case and review of the literature.

Overwhelming Clostridium septicum infection is a rare occurrence in children. It is seen almost exclusively as a complication of acute leukemia. A high index of suspicion in the leukemic child with an acute abdomen is the key to early diagnosis and improved survival. A case in a 13-year-old girl with acute myelogenous leukemia is reported and six pediatric cases in the literature were reviewed.