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Background: The medical treatment of ulcerative colitis (UC) includes the use of biological agents such as vedolizumab, a gut-selective alpha4beta7 (ɑ4β7) antagonist. The mechanism of action of vedolizumab involves interfering with leukocyte trafficking into the gut vasculature, which halts inflammation. Due to this mechanism of action, concerns have arisen regarding an increased risk of gut infections, specifically, clostridium difficile infection (CDI). The aim is to provide clarity regarding the association between the use of vedolizumab as a therapy for ulcerative colitis and the risk of developing CDI., Methods: A systematic literature review was conducted, starting with the scoping search, followed by backward snowballing parallel with keyword-based search to identify related articles. A quality assessment was conducted on the initially selected articles and excluded low-quality papers., Results: Pooled analyses indicated that there was no significant association between the use of vedolizumab and the risk of developing CDI (effect size = 0.03 [-0.02, 0.07])., Conclusions: Vedolizumab does not increase the risk of CDI in patients with UC. Further studies are needed to confirm these findings., (Copyright © 2024 Copyright: © 2024 Saudi Journal of Gastroenterology.)

Background: Recurrent Clostridioides difficile infection (rCDI) occurs frequently, and concomitant antibiotic (CA) during the initial episode for treatment of non-CDI is a major risk factor. We sought to address the comparative efficacy of fidaxomicin versus vancomycin in the setting of CA during the initial CDI episode., Methods: We conducted a randomized, controlled, open-label trial at 2 hospitals in Ann Arbor, Michigan. We consecutively consented and enrolled hospitalized patients ≥18 years old with diarrhea, a positive test for C. difficile, and ≥1 qualifying CA. Complicated CDI, CDI treatment for >24 hours prior to enrollment, and planned long-term (>12 weeks) CA use were notable exclusions. Clinical cure was defined as resolution of diarrhea for 2 consecutive days maintained until 2 days after therapy, and rCDI as recurrent diarrhea with positive testing ≤30 days after initial treatment. Patients were randomized to fidaxomicin or vancomycin., Results: Baseline characteristics were similar in the 2 groups of 144 patients. Rates of clinical cure (73% vs 62.9%, P = .195) and rCDI (3.3% vs 4.0%; P > .99) were similar for fidaxomicin and vancomycin in the intention-to-treat and per-protocol cohorts, respectively. Only 4 patients developed rCDI., Conclusions: In this study of patients with CDI receiving CA, a numerically higher proportion were cured with fidaxomicin versus vancomycin, but this result did not reach statistical significance. Overall recurrence was lower than anticipated in both arms compared with previous studies that did not extend duration of CDI treatment during CA., Clinical Trials Registration: www.clinicaltrials.gov (NCT02692651)., Competing Interests: Potential conflicts of interest. K. R. is supported, in part, by an investigator-initiated grant from Merck & Co, Inc, and he has consulted for Seres Therapeutics, Inc, Rebiotix, Inc, and Summit Therapeutics, Inc. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Newer antibiotics that specifically target Clostridioides difficile while preserving the host microbiome have emerged to treat C. difficile infection (CDI): cadazolid, fidaxomicin, ridinilazole, and surotomycin. The aim of the present study was to perform a systematic review and meta-analysis of efficacy for each antibiotic., Methods: Only randomized clinical trials of patients being treated for Clostridioides disease infection were included. Studies were sought in MEDLINE, EMBASE, the Cochrane Register of Controlled Trials, ClinicalTrials.gov, and the World Health Organization clinical trials register portal (up to December 9, 2022). Sustained clinical cure was the outcome of treatment comparison, defined as the resolution of diarrhea without recurrence. Vancomycin was the standard treatment comparator. Meta-analysis was performed for each antibiotic. The overall certainty of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-classified as either high, moderate, low, or very low., Results: Fourteen eligible studies were included in the meta-analysis with 4837 patients from 773 sites. Cadazolid did not increase sustained clinical cure relative to vancomycin (risk ratio (RR) 1.04, 95% confidence intervals (CI) 0.96-1.13; moderate-certainty evidence). Fidaxomicin demonstrated a significant increase (RR 1.14, 95% CI 1.07-1.21; low-certainty evidence). In one phase 2 study, ridinilazole demonstrated a significant increase in sustained clinical cure (RR 1.71, 95% CI 1.01-2.91; very low-quality evidence). Surotomycin did not show significant improvement (RR 1.05, 95% CI 0.96-1.14; moderate-certainty evidence)., Conclusions: Fidaxomicin (in seven studies) demonstrated significant improvement in achieving sustained clinical cure. A limitation of this study may that more studies are needed to compare fidaxomicin with other antibiotics., (© 2023. Springer Nature Switzerland AG.)

The literature regarding Clostridioides difficile infection (CDI) in left ventricular assist devices (LVADs) patients is limited. Therefore, we aimed to characterize the clinical course, risk factors, management, and outcomes of LVAD patients who developed CDI. Adult patients who underwent LVAD placement during 2010-2022 and developed CDI were included. To determine risk factors and outcomes, we matched CDI patients with LVAD patients who did not develop CDI. Each CDI case was matched with up to two control subjects by age, sex, and time from LVAD implantation. Forty-seven of 393 LVAD patients (12.0%) developed CDI. The median time from LVAD implantation to CDI was 147 days (interquartile range 22.5-647.0). The most common CDI treatment was oral vancomycin (n = 26, 55.3%). Thirteen patients (27.7%) required treatment extension because of a lack of clinical response. Three patients (6.4%) developed recurrent CDI. When 42 cases were matched to 79 control subjects, antibiotic exposure within 90 days was significantly associated with CDI (adjusted odds ratio 5.77; 95% confidence interval, 1.87-17.74; p = 0.002). Moreover, CDI was associated with 1 year mortality (adjusted hazard ratio 2.62; 95% confidence interval, 1.18-5.82; p = 0.018). This infection occurs most often within the first year after LVAD implantation and was associated with 1 year mortality. Antibiotic exposure is an important risk for CDI., Competing Interests: Disclosure: S.D.S. received consulting fees from Abbot and Medtronic. R.R.R. received grants (funds to the institution) from Gilead, Roche, Regeneron. He is a member of the Data Safety Monitoring Board (Novartis) and Endpoint Adjudication Committee (Allovir) and the Board of Directors of the American Society of Transplantation. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

Background: There are uncertainties regarding associations of prior proton pump inhibitor (PPI) use with susceptibility for COVID-19 and risks associated with SARS-CoV-2 infection. We aimed to evaluate the associations of prior PPI use with outcomes in hospitalized patients with COVID-19., Research Design and Methods: We have retrospectively evaluated a total of 5959 consecutively hospitalized patients with COVID-19 from a tertiary-level institution in the period 3/2020-6/2021. Associations of prior PPI use with outcomes of in-hospital mortality, mechanical ventilation, intensive care unit stay, venous thromboembolism, arterial thrombosis, major bleeding, bacteremia, and Clostridioides difficile infection (C. diff.) were evaluated in entire and case-matched cohorts., Results: Among 5959 evaluated patients, there were 1967 (33%) PPI users. In an entire cohort, prior PPI use was associated with higher in-hospital mortality and higher occurrence of C. diff. Association of prior PPI use with mortality diminished, whereas association with C. diff. persisted after multivariable adjustments. In a matched cohort, prior PPI use was associated only with higher risk of C. diff. but not other outcomes in line with multivariable analysis., Conclusions: Although prior PPI use might not have a significant impact on clinical course and mortality of SARS-CoV-2 infection, it may predispose patients to the development of complications like higher occurrence of C. diff. and thus substantially impact the course of treatment.

What Is Already Known: •The rate and severity of Clostridioides difficile infection (CDI) has increased throughout North America, the United Kingdom, and Europe. •Scattered evidence about the association of CDI with antidepressant medications use exists in the literature so far. What are the new findings: •The risk of Clostridioides difficile infection is higher in patients who are on mirtazapine, nortriptyline, or trazodone. •The prevalence rate of Clostridioides difficile infection in patients who were using antidepressant medications and the ones who did not, increased with age. Background - During the past decade, Clostridioides difficile infection (CDI) has become the most common cause of antibiotic-associated diarrhea. Several risk factors have been implicated. Scattered evidence about the association of CDI with antidepressant medications use exists in the literature so far. Therefore, we aim to investigate whether the risk of developing CDI is increased in hospitalized patients using antidepressant medications.Methods - Patients who were hospitalized were included in our cohort. We excluded individuals aged less than 18 years. A multivariate regression analysis was performed to calculate the risk of CDI accounting for potential confounders. Results - The risk of CDI in hospitalized patients was increased in individuals diagnosed with inflammatory bowel disease (OR: 4.44; 95%CI: 4.35-4.52), and in patients using clindamycin (OR: 1.55; 95%CI: 1.53-1.57), beta-lactam antibiotics (OR: 1.62; 95%CI: 1.60-1.64), PPI (OR: 3.27; 95%CI: 3.23-3.30), trazodone (OR: 1.31; 95%CI: 1.29-1.33), nortriptyline (OR: 1.25; 95%CI: 1.21-1.28), and mirtazapine (OR: 2.50; 95%CI: 2.46-2.54). After controlling for covariates, the risk of CDI was not increased in patients who were taking fluoxetine (OR: 0.94; 95%CI: 0.92-0.96). Conclusion - In contrary to fluoxetine; mirtazapine, nortriptyline, and trazodone were associated with increased risk of CDI in hospitalized patients.

Objective: The aim of this study was to analyze and identify documented infections and possible risk factors for Clostridioides difficile infections in children with cancer., Methods: This is a retrospective case-control study, carried out in a pediatric cancer hospital, covering the years 2016-2019. Matching was performed by age and underlying disease, and for each case, the number of controls varied from 1 to 3. Logistic regression models were used to assess risk factors., Results: We analyzed 63 cases of documented infection by C. difficile and 125 controls. Diarrhea was present in all cases, accompanied by fever higher than 38°C in 52.4% of the patients. Mortality was similar among cases (n=4; 6.3%) and controls (n=6; 4.8%; p=0.7). In all, 71% of patients in the case group and 53% in the control group received broad-spectrum antibiotics prior to the infection. For previous use of vancomycin, the Odds Ratio for C. difficile infection was 5.4 (95% confidence interval [95%CI] 2.3-12.5); for meropenem, 4.41 (95%CI 2.1-9.2); and for cefepime, 2.6 (95%CI 1.3-5.1). For the antineoplastic agents, the Odds Ratio for carboplatin was 2.7 (95%CI 1.2-6.2), melphalan 9.04 (95%CI 1.9-42.3), busulfan 16.7 (95%CI 2.1-134.9), and asparaginase 8.97 (95%CI 1.9-42.9)., Conclusions: C. difficile symptomatic infection in children with cancer was associated with previous hospitalization and the use of common antibiotics in cancer patients, such as vancomycin, meropenem, and cefepime, in the last 3 months. Chemotherapy drugs, such as carboplatin, melphalan, busulfan, and asparaginase, were also risk factors.

Objective: To determine the risk and prognostic factors for Clostridioides difficile infection (CDI)., Patients and Methods: Prospective, case-control study with 61 cases and 64 controls, aged ≥2 years with diarrhoea, carried out in Castilla-La Mancha Health Care Area for 14 months. The diagnosis was made by immunochromatography technics (glutamate dehydrogenase and toxin A/B), confirming discordant cases by isothermal amplification. Demographic variables, comorbidities, type of acquisition, previous administration of antibiotics, antacids and immunosuppressants, and evolution were collected. The data were analysed using the chi-square test and the effect of risk and prognostic factors was quantified using an odds ratio with 95% confidence intervals., Results: Hospital admission 4 weeks prior to infection, hypoalbuminemia, and previous administration of antibiotics were identified as independent risk factors for CDI. Presenting these 3 factors constitutes nearly 3-fold increase in the risk of becoming infected. A greater number of hospital admissions in the 4-12 weeks prior to CDI were found in the group of nosocomial acquisition. Although there was a greater tendency to recurrence and an unfavourable prognosis among nosocomial cases, these differences were not significant. We found that fever and hospital admission in the 4 weeks prior to infection were unfavourable prognostic factors of CDI., Conclusions: The independent risk factors for CDI were: Hospital admission in the 4 weeks prior to infection, hypoalbuminemia, and previous administration of antibiotics. Fever and hospitalisation in the previous 4 weeks were also identified as prognostic factors of unfavourable evolution., (Copyright © 2022. Publicado por Elsevier España, S.L.U.)

Antibiotic exposure is a crucial risk factor for community-acquired Clostridioides difficile infection (CA-CDI). However, the relative risks associated with specific antibiotics may vary over time, and the absolute risks have not been clearly established. This is a retrospective cohort study. Adults were included if they received an outpatient antibiotic prescription within the IBM MarketScan databases between 2008 and 2020. The primary exposure was an outpatient antibiotic prescription, and the receipt of doxycycline was used as the reference comparison. The primary outcome was CA-CDI, defined as the presence of an International Classification of Diseases (ICD) diagnosis code for CDI within 90 days of receiving an outpatient antibiotic prescription, and subsequent treatment for CDI. There were 36,626,794 unique patients who received outpatient antibiotics, including 11,607 (0.03%) who developed CA-CDI. Relative to doxycycline, the antibiotics conferring the highest risks for CA-CDI were clindamycin (adjusted odds ratio [aOR], 8.81; 95% confidence interval [CI], 7.76 to 10.00), cefdinir (aOR, 5.86; 95% CI, 5.03 to 6.83), cefuroxime (aOR, 4.57; 95% CI, 3.87 to 5.39), and fluoroquinolones (aOR, 4.05; 95% CI, 3.58 to 4.59). Among older patients with CA-CDI risk factors, nitrofurantoin was also associated with CA-CDI (aOR, 3.05; 95% CI, 1.92 to 4.84), with a smaller number needed to harm, compared to the fluoroquinolones. While clindamycin, cefuroxime, and fluoroquinolone use declined from 2008 to 2020, nitrofurantoin use increased by 40%. Clindamycin was associated with the greatest CA-CDI risk, overall. Among older patients with an elevated baseline risk for CA-CDI, multiple antibiotics, including nitrofurantoin, had strong associations with CA-CDI. These results may guide antibiotic selection and future stewardship efforts.

Purpose: There is a lack of real-world evidence of the comparative effectiveness of fidaxomicin versus vancomycin or metronidazole for treating patients with Clostridium difficile (CDI) infection. No systematic evidence comparing these treatment regimens using real-world observational studies was published up to date. The goal of this study is to compare the fidaxomicin and vancomycin/metronidazole regimens in terms of treatment outcomes in CDI patients., Methods: Systematic and comprehensive search was carried out in the following databases and search engines: EMBASE, Cochrane, MEDLINE, ScienceDirect, and Google Scholar from 1954 until January 2022. Newcastle-Ottawa (NO) scale was used to assess the risk of bias. Meta-analysis was carried out using random effects model, and pooled odds ratios (OR) with 95% confidence interval (CI) were reported., Results: A total of 10 studies satisfied the inclusion criteria, most of them were with poorer quality. The pooled OR was 0.40 (95% CI: 0.09-1.68; I 2  = 82.4%) for clinical cure and 2.02 (95% CI: 0.36-11.39; I 2  = 88.4%) for sustained cure. We reported pooled OR of 0.69 (95% CI: 0.40-1.20; I 2  = 65.7%) for the recurrence rate, 2.81 (95% CI: 1.08-7.29; I 2  = 70.6%) for the treatment failure, and 0.73 (95% CI: 0.50-1.07; I 2  = 0%) for all-cause mortality between patients that received fidaxomicin and vancomycin. The pooled OR was 0.71 (95% CI: 0.05-9.47; I 2  = 69.6%) in terms of recurrence between patients receiving fidaxomicin and metronidazole., Conclusion: Fidaxomicin and vancomycin/metronidazole regimens did not have significant difference in terms of treatment outcomes, such as clinical cure, sustained cure, recurrence, and all-cause mortality. However, there was significantly higher risk of treatment failure in CDI patients taking fidaxomicin., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Objective: Immune-mediated diarrhea and colitis (IMDC) is a common adverse event in cancer patients receiving immune checkpoint inhibitors (ICIs). Gastrointestinal (GI) infections can co-occur with IMDC, and its impact on the course and outcome of IMDC remains unclear., Patients and Methods: We retrospectively reviewed cancer patients who received ICIs and developed IMDC between January 2015 and September 2019. GI multiplex panel is used to assess GI infection. The study group included patients with positive infection except those who are only positive for Clostridioides difficile or cytomegalovirus. The control group is IMDC patients with negative infection using frequency matching. Patients' disease course and outcome were compared between groups., Results: A total of 72 patients with IMDC were included: 22 in the study group and 50 as control. Escherichia coli of different pathotypes was observed in 17 patients. Five patients had viral infections, for example, adenovirus, norovirus, and sapovirus. Patients with GI infections more frequently had grade 3 or 4 colitis (43% vs. 18%, P=0.041). Overall, GI infections were not associated with different risks of IMDC recurrence or overall survival. Antibiotics treatment did not affect the requirement for infliximab or vedolizumab but relate to a higher risk of IMDC recurrence (50.0% vs. 0.0%, P=0.015)., Conclusions: In our study, concomitant GI infections are associated with more severe symptoms in IMDC patients. Antimicrobial treatment did not circumvent the need for immunosuppressive therapy for IMDC or improve the clinical outcome. Concomitant GI infection was not associated with a higher risk of IMDC recurrence or poor overall survival., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Proton-pump inhibitors (PPIs) have been reported to increase the risk of community-associated Clostridium difficile infection (CDI), but the association remains disputed., Methods: A nationwide cohort study among adults in Denmark, 2010-2013, linking register data on C. difficile testing, filled prescriptions, and patient characteristics. All incident episodes of community-associated CDI (ie, positive culture, molecular assay, or toxin test in individuals without previous hospitalization in the prior 12 weeks and without a positive test for C. difficile in the prior 8 weeks) were identified in the Danish National Microbiological Database. Self-controlled case-series analyses were used to estimate incidence rate ratios (IRRs) for community-associated CDI, comparing periods with and without exposure to PPIs. By design, models took fixed confounders such as chronic disease, genetics, and socioeconomic status into account; further, time-varying confounders, including hospital stay and antibiotic and corticosteroid use were adjusted for., Results: 3583 episodes of community-associated CDI were identified, of which 964 occurred during current use of PPIs, 324 occurred 0-6 months after treatment cessation, 123 occurred 6-12 months after treatment cessation, and 2172 occurred during time periods without use of PPIs. The adjusted IRR was 2.03 (95% confidence interval, 1.74-2.36), comparing use of PPI with nonuse. The increased risk remained elevated in later time periods: 1.54 (1.31-1.80) for 0-6 months, 1.24 (1.00-1.53) for 6-12 months after current use., Conclusions: Use of PPIs was associated with moderately increased risk of community-associated CDI. The risk remained elevated up to 1 year after PPI treatment had ended., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Purpose of Review: To explore the evidence for an association between penicillin allergy, antibiotic prescribing and Clostridioides difficile (CDI) infection., Recent Findings: Several studies have highlighted the differences in antibiotic prescribing in penicillin allergic patients and the impact on rates of C. difficile infection., Summary: Penicillin allergy leads to higher incidences of prescriptions for antibiotics that are known to predispose to CDI. In turn CDI is more common in patients with penicillin allergy. Penicillin allergy is often erroneously ascribed to patients and should be challenged.

Background & Aims: Clostridioides difficile toxin A (TcdA) activates the innate immune response. TcdA co-purifies with DNA. Toll-like receptor 9 (TLR9) recognizes bacterial DNA to initiate inflammation. We investigated whether DNA bound to TcdA activates an inflammatory response in murine models of C difficile infection via activation of TLR9., Methods: We performed studies with human colonocytes and monocytes and macrophages from wild-type and TLR9 knockout mice incubated with TcdA or its antagonist (ODN TTAGGG) or transduced with vectors encoding TLR9 or small-interfering RNAs. Cytokine production was measured with enzyme-linked immunosorbent assay. We studied a transduction domain of TcdA (TcdA 57-80 ), which was predicted by machine learning to have cell-penetrating activity and confirmed by synchrotron small-angle X-ray scattering. Intestines of CD1 mice, C57BL6J mice, and mice that express a form of TLR9 that is not activated by CpG DNA were injected with TcdA, TLR9 antagonist, or both. Enterotoxicity was estimated based on loop weight to length ratios. A TLR9 antagonist was tested in mice infected with C difficile. We incubated human colon explants with an antagonist of TLR9 and measured TcdA-induced production of cytokines., Results: The TcdA 57-80 protein transduction domain had membrane remodeling activity that allowed TcdA to enter endosomes. TcdA-bound DNA entered human colonocytes. TLR9 was required for production of cytokines by cultured cells and in human colon explants incubated with TcdA. TLR9 was required in TcdA-induced mice intestinal secretions and in the survival of mice infected by C difficile. Even in a protease-rich environment, in which only fragments of TcdA exist, the TcdA 57-80 domain organized DNA into a geometrically ordered structure that activated TLR9., Conclusions: TcdA from C difficile can bind and organize bacterial DNA to activate TLR9. TcdA and TcdA fragments remodel membranes, which allows them to access endosomes and present bacterial DNA to and activate TLR9. Rather than inactivating the ability of DNA to bind TLR9, TcdA appears to chaperone and organize DNA into an inflammatory, spatially periodic structure., (Copyright © 2020 AGA Institute. All rights reserved.)

Study Design: Retrospective database review., Objective: The aim of this study was to determine the incidence of Clostridium difficile infection (CDI) within 90 days following elective spine surgery; examine risk factors associated with its development; and evaluate the impact of CDI on postoperative outcomes., Summary of Background Data: Although previous studies provided valuable insight into the rate of CDI following spine surgery and associated risk factors, to date no study has evaluated the role preoperative antibiotics use plays in the development of CDI, as well as its impact on 90-day outcomes., Methods: A retrospective database review of Humana patients ages 20 to 84 years who underwent elective spine surgery between 2008 and 2016 was conducted. Following exclusion criteria, the population was divided into patients who developed CDI within 90 days of surgery and those who did not. All risk factors and outcomes were analyzed using multivariate regression., Results: A total of 63,667 patients met study criteria. Ninety-day incidence of CDI was 0.68%. Notable medical risk factors (P < 0.05) included preoperative fluoroquinolone use (odds ratio [OR] 1.40), advanced age (OR 1.86), chronic kidney disease stage I/II (OR 1.76) and III-V (OR 1.98), decompensated chronic liver disease (OR 3.68), and hypoalbuminemia (OR 3.15). Combined anterior-posterior cervical (OR 2.74) and combined anterior-posterior lumbar (OR 2.43) approaches and procedures spanning more than eight levels (OR 3.99) were associated with the highest surgical risk (P < 0.05) of CDI. CDI was associated with a 12.77-day increase in length of stay (P < 0.05) and increased risk of readmission (OR 6.08, P < 0.05) and mortality (OR 8.94, P < 0.05)., Conclusion: Following elective spine surgery, CDI increases risk of readmission and mortality. In addition to preoperative fluoroquinolone use, novel risk factors associated with the highest risk of CDI included decompensated chronic liver disease, posterior approaches, and multilevel involvement. Perioperative optimization of modifiable risk factors may help to prevent occurrence of CDI., Level of Evidence: 3.

Background: The study's objective was to investigate the incidence and risk factors associated with Clostridioides difficile (previously known as Clostridium) infection (CDI) in children with inflammatory bowel disease (IBD) in the province of Manitoba., Methods: Our longitudinal population-based cohort was comprised of all children and young adults aged <17 years diagnosed with IBD in the Canadian province of Manitoba between 2011 and 2019. The diagnosis of CDI was confirmed based on the Triage C. difficile immunoassay and polymerase chain reaction assay to detect the presence of toxigenic C. difficile. The Fisher exact test was used to examine the relationship between categorical variables. A Cox regression model was used to estimate the risk of CDI development in IBD patients., Results: Among 261 children with IBD, 20 (7.7%) developed CDI with an incidence rate of 5.04 cases per 1000 person-years, and the median age at diagnosis (interquartile range) was 12.96 (9.33-15.81) years. The incidence rates of CDI among UC and CD patients were 4.16 cases per 1000 person-years and 5.88 cases per 1000 person-years, respectively (P = 0.46). Compared with children without CDI, those who had CDI were at increased risk of future exposure to systemic corticosteroids (adjusted hazard ratio [aHR], 4.38; 95% confidence interval [CI], 1.46-13.10) and anti-tumor necrosis factor (anti-TNF) biologics (aHR, 3.31; 95% CI, 1.11-9.90). The recurrence rate of CDI in our pediatric IBD population was 25%., Conclusions: Our findings confirm that children with IBD are at high risk of developing CDI, which may predict future escalation of IBD therapy., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Clostridium difficile infection is one of the most common causes of diarrhea in healthcare facilities. More studies are needed to identify patients at high risk of C difficile infection in our community., Objectives: Estimate the prevalence of C difficile infection among adult patients and evaluate the risk factors associated with infection., Design: Retrospective record review., Setting: Tertiary academic medical center in Jeddah., Patients and Methods: Eligible patients were adults (≥18 years old) with confirmed C difficile diagnosis between January 2013 and May 2018., Main Outcome Measures: Prevalence rate and types of risk factors., Sample Size: Of 1886 records, 129 patients had positive lab results and met the inclusion criteria., Results: The prevalence of C difficile infection in our center over five years was 6.8%. The mean (SD) age was 56 (18) years, and infection was more prevalent in men (53.5%) than in women (46.5%). The most common risk factors were use of proton-pump inhibitors (PPI) and broad-spectrum antibiotics. The overlapping exposure of both PPIs and broad-spectrum antibiotics was 56.6%. There was no statistically significant difference between the type of PPI ( P =.254) or antibiotic ( P =.789) and the onset of C difficile infection., Conclusion: The overall C difficile infection prevalence in our population was low compared to Western countries. The majority of the patients who developed C difficile infection were using PPIs and/or antibiotics. No differences were observed in the type of antibiotic or PPI and the onset of C difficile infection development. Appropriate prescribing protocols for PPIs and antibiotics in acute settings are needed., Limitations: Single center and retrospective design., Conflict of Interest: None.

Background: Clostridioides difficile infection (CDI) has a high recurrent infection rate. Faecal microbiota transplantation (FMT) has been used successfully to treat recurrent CDI, but much remains unknown about the human gut microbiota response to replacement therapies. In this study, antibiotic-mediated dysbiosis of gut microbiota and bacterial growth dynamics were investigated by two quantitative methods: real-time quantitative PCR (qPCR) and direct culture enumeration, in triple-stage chemostat models of the human colon. Three in vitro models were exposed to clindamycin to induce simulated CDI. All models were treated with vancomycin, and two received an FMT. Populations of total bacteria, Bacteroides spp., Lactobacillus spp., Enterococcus spp., Bifidobacterium spp., C. difficile, and Enterobacteriaceae were monitored using both methods. Total clostridia were monitored by selective culture. Using qPCR analysis, we additionally monitored populations of Prevotella spp., Clostridium coccoides group, and Clostridium leptum group., Results: Both methods showed an exacerbation of disruption of the colonic microbiota following vancomycin (and earlier clindamycin) exposure, and a quicker recovery (within 4 days) of the bacterial populations in the models that received the FMT. C. difficile proliferation, consistent with CDI, was also observed by both qPCR and culture. Pearson correlation coefficient showed an association between results varying from 98% for Bacteroides spp., to 62% for Enterobacteriaceae., Conclusions: Generally, a good correlation was observed between qPCR and bacterial culture. Overall, the molecular assays offer results in real-time, important for treatment efficacy, and allow the monitoring of additional microbiota groups. However, individual quantification of some genera (e.g. clostridia) might not be possible without selective culture.

Background: Unnecessary antibiotic use (AU) contributes to increased rates of Clostridioides difficile infection (CDI). The impact of antibiotic restriction on hospital-onset CDI (HO-CDI) has not been assessed in a large group of US acute care hospitals (ACHs)., Methods: We examined cross-sectional and temporal associations between rates of hospital-level AU and HO-CDI using data from 549 ACHs. HO-CDI was defined as a discharge with a secondary International Classification of Diseases, Ninth Revision, Clinical Modification code for CDI (008.45), and treatment with metronidazole or oral vancomycin > 3 days after admission. Analyses were performed using multivariable generalized estimating equation models adjusting for patient and hospital characteristics., Results: During 2006-2012, the unadjusted annual rates of HO-CDI and total AU were 7.3 per 10 000 patient-days (PD) (95% confidence interval [CI], 7.1-7.5) and 811 days of therapy (DOT)/1000 PD (95% CI, 803-820), respectively. In the cross-sectional analysis, for every 50 DOT/1000 PD increase in total AU, there was a 4.4% increase in HO-CDI. For every 10 DOT/1000 PD increase in use of third- and fourth-generation cephalosporins or carbapenems, there was a 2.1% and 2.9% increase in HO-CDI, respectively. In the time-series analysis, the 6 ACHs with a ≥30% decrease in total AU had a 33% decrease in HO-CDI (rate ratio, 0.67 [95% CI, .47-.96]); ACHs with a ≥20% decrease in fluoroquinolone or third- and fourth-generation cephalosporin use had a corresponding decrease in HO-CDI of 8% and 13%, respectively., Conclusions: At an ecologic level, reductions in total AU, use of fluoroquinolones, and use of third- and fourth-generation cephalosporins were each associated with decreased HO-CDI rates., (Published by Oxford University Press for the Infectious Diseases Society of America 2019.)

Background: Clostridioides difficile infection is a relatively rare cause of diarrhoea in children, but there are frequent recurrences when it occurs, despite targeted antibiotic treatment., Case Descriptions: A 2-year-old boy with concomitant motility disorder and a 14-year-old girl with Down syndrome experienced several infections with C. difficile, respectively after the use of antibiotics for otitis media and extended use of antibiotics in addition to chemotherapy. Both were treated successfully with faecal transplants., Conclusion: Clostridioides difficile infections occur in children, mainly after extended use of antibiotics or when the immune system is impaired. In case of recurring C. difficile infections, children can be treated safely and effectively with faecal transplants.

Objectives: To assess the effectiveness of Lactobacillus reuteri DSM 17938 for the prevention of diarrhoea and antibiotic-associated diarrhoea (AAD) in children., Methods: Hospitalized children who received antibiotics were assigned by a computer-generated list to receive L. reuteri (at 2 × 10 8  CFU) or placebo, twice daily, for the duration of antibiotic treatment. Follow up was for 1 week after antibiotic cessation. The primary outcome measures were diarrhoea and AAD. Both were defined according to one of three definitions (i) three or more loose or watery stools per day for ≥48 h; (ii) three or more loose or watery stools per day for ≥24 h; or (iii) two or more loose or watery stools per day for ≥24 h. For AAD, it had to be diarrhoea caused by Clostridium difficile or otherwise unexplained diarrhoea., Results: A total of 250 children were randomized and 247 were analysed (L. reuteri n = 123, placebo n = 124; median age 4 months). The occurrences of diarrhoea and AAD were similar in both groups, regardless of the definition used. Using the strictest definition (i.e. definition (i)), the occurrence of diarrhoea in the L. reuteri group was 25 (20%) compared with 16 (13%) in the placebo group (absolute risk reduction -0.07 (-0.17 to 0.02). The occurrence of AAD was 14 (11.4%) in the L. reuteri group compared with 8 (6.5%) in the placebo group (absolute risk reduction -0.05 (-0.13 to 0.02)). The groups were similar with respect to all secondary outcome measures, including adverse events., Conclusions: Lactobacillus reuteri was not effective in the prevention of diarrhoea or AAD in children., (Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Diarrhea post-antibiotic use is primarily attributed to Clostridium difficile infection (CDI)-induced mucosal lesions, and evidence of CDI in patients undergoing chemotherapy without prior antibiotic treatment is also increasing. However, few studies have investigated the relationship between chemotherapy use and diarrhea. This study aimed to determine whether the incidence of CDI increased in patients with lung cancer undergoing chemotherapy even without prior antibiotic treatment., Methods: We conducted a retrospective study and investigated the presence of Clostridium difficile (C. difficile) and its toxins in patients who experience diarrhea during chemotherapy. If grade 2 or higher diarrhea was noted, a stool culture was performed to detect anaerobic organisms and C. difficile toxins A and B., Results: A total of 345 consecutive patients (492 in terms of chemotherapy regimens) were enrolled in the study. Grade 2 or higher diarrhea was observed in patients using 36 (7.3%) of these regimens, among which CDI without prior antibiotic exposure was confirmed in patients using 8 regimens (22.2%)., Conclusions: CDI may remain undetected in patients undergoing chemotherapy even in those who had not received antibiotic treatment previously, unless due attention is paid to its possibility. Testing for C. difficile toxins is highly recommended to expedite timely treatment for diarrhea in such patients. Further studies are needed to clarify the relationship between chemotherapy drug use and CDI to facilitate prevention.

Proton pump inhibitors (PPIs) are commonly prescribed for treatment of acid-related gastrointestinal disorders. PPI use is approved for a duration of 2 to 12 weeks, depending on complication and severity. Many users lack an appropriate indication for continued therapy past the recommended duration. Long-term PPI use is associated with several adverse drug events, including acute interstitial nephritis, fractures, and Clostridium difficile-associated diarrhea (CDAD). Cautious prescribing and regular monitoring is essential, especially for older adults, as they may be at higher risk for these adverse effects. Deprescribing, defined as lowering dosage, switching to as-needed use, or complete discontinuation, should be considered for many PPI users. Patient education is critical. Alternative therapy considerations include histamine-2-receptor antagonists, as they are found to be associated with reduced CDAD and fracture events. Additional strategies include tapering off PPIs and modifying lifestyle to reduce the potential rebound hypersecretion that may occur as a result of discontinuation. The most significant lifestyle modification is weight loss. Additional lifestyle interventions include upright head of bed elevation, avoiding meals close to bedtime, and avoiding high-fat meals within two to three hours of reclining.

Antibiotic-associated diarrhoea is among the most common adverse events related to antibiotic use. Most cases are mild, but Clostridium difficile infection causes a spectrum of disease, ranging from occasional diarrhoea to colitis, toxic megacolon, and potentially death. Recent developments in our understanding of the biology of the gut microbiota have provided new insights into the pathogenesis of these conditions, and have revealed a role for manipulation of the gut microbiota as a novel therapeutic approach. This review will give an overview of the assessment of these conditions, before focusing on the rapidly developing area of their treatment., (© Royal College of Physicians 2018. All rights reserved.)

Clostridium difficile is an opportunistic diarrhoeal pathogen, and C. difficile infection (CDI) represents a major health care concern, causing an estimated 15,000 deaths per year in the United States alone 1 . Several enteric pathogens, including C. difficile, leverage inflammation and the accompanying microbial dysbiosis to thrive in the distal gut 2 . Although diet is among the most powerful available tools for affecting the health of humans and their relationship with their microbiota, investigation into the effects of diet on CDI has been limited. Here, we show in mice that the consumption of microbiota-accessible carbohydrates (MACs) found in dietary plant polysaccharides has a significant effect on CDI. Specifically, using a model of antibiotic-induced CDI that typically resolves within 12 days of infection, we demonstrate that MAC-deficient diets perpetuate CDI. We show that C. difficile burdens are suppressed through the addition of either a diet containing a complex mixture of MACs or a simplified diet containing inulin as the sole MAC source. We show that switches between these dietary conditions are coincident with changes to microbiota membership, its metabolic output and C. difficile-mediated inflammation. Together, our data demonstrate the outgrowth of MAC-utilizing taxa and the associated end products of MAC metabolism, namely, the short-chain fatty acids acetate, propionate and butyrate, are associated with decreased C. difficile fitness despite increased C. difficile toxin expression in the gut. Our findings, when placed into the context of the known fibre deficiencies of a human Western diet, provide rationale for pursuing MAC-centric dietary strategies as an alternate line of investigation for mitigating CDI.

We report a case of Clostridium difficile infection in a patient with hidradenitis suppurativa who was taking clindamycin and rifampin. Clostridium difficile infection treatment prompted discontinuation of the medication. Clostridium difficile infection is known to develop after antibiotic treatment, such as clindamycin, but has rarely been associated with anti-tuberculosis agents, such as rifampin. Clinicians should be aware of the risk of Clostridium difficile infection in patients with hidradenitis suppurativa, even in those receiving rifampin.

In the last few decades, proton-pump inhibitors have become the mainstay of the treatment of acid-related disorders. Despite their efficacy, these drugs are not without risks. Recently several articles have been published on their long-term adverse effects. Among these adverse effects, the higher risk of bone fractures, the vitamin B 12 and magnesium deficiencies and the higher risk of Clostridium difficile infection may be relevant. As these drugs are prescribed more and more frequently all over the world, the knowledge of the long-term adverse effects is very important not only for the specialists but for the general practitioners as well. In this review, the authors discuss the recent findings in this field, emphasising that the long-term use of these drugs must be based on an adequate and strong indication. Orv Hetil. 2018; 159(19): 735-740.

Interest in administration of probiotics to prevent antibiotic-associated diarrhoea (AAD) in hospitalized patients is increasing. We determined the cost of antibiotic-associated diarrhoea in hospital settings for non-complicated and Clostridium difficile (C.diff) complicated AAD, and performed a health-economic analysis of AAD prevention with S. boulardii CNCM I-745 (S. boulardii) from data collected in 1 university and 3 regional hospitals in Flanders. Using a decision tree analytic model, costs and effects of S. boulardii for AAD prevention are calculated. Incremental costs due to AAD, including increased length of hospitalization, were calculated using bottom-up and top-down costing approaches from a hospital, healthcare payer (HCP) and societal perspective. Model robustness was tested using sensitivity analyses. Additional costs per hospitalized patient range from € 277.4 (hospital) to € 2,150.3 (societal) for non-complicated and from € 588.8 (hospital) to € 2,239.1 (societal) for C. diff. complicated AAD. Using S. boulardii as AAD prevention results in cost savings between € 50.3 (bottom-up) and € 28.1 (topdown) per patient treated with antibiotics from the HCP perspective; and € 95.2 and € 14.7 per patient from the societal and hospital perspectives. Our analysis shows the potential for using S. boulardii as AAD prophylactic treatment in hospitalized patients. Based on 831,655 hospitalizations with antibiotic administration in 2014 and € 50.3 cost saving per patient on antibiotics, generalized use of S. boulardii could result in total annual savings up to € 41.8 million for the Belgian HCP., (© Acta Gastro-Enterologica Belgica.)

Rationale: Clostridium difficile infection (CDI) is a symptomatic infection due to the spore-forming bacterium, C. difficile. Asymptomatic C. difficile colonization is the stage in absence of symptoms, with a prevalence of 1.4% to 21% on hospital admission. Proton-pump inhibitors (PPIs) was implicated as a novel potential contributor to CDI. PPIs injection could make asymptomatic C. difficile colonization progress to C. difficile associated diarrhea (CDAD)., Patient Concerns: A postoperative colon cancer patient, who had been taking omeprazole for 4 years after operation, got asymptomatic C. difficile colonization. When he developed clinical symptoms of digestive tract, tumor recurrence was first suspected and intravenous omeprazole was prescribed, which ultimately led to progression to symptomatic CDI. In this report, we tell the confusing differential diagnosis of cancer-associated diseases and CDAD, and discuss the possibility of solving the PPIs overuse problem by making clinical pathway of PPIs use in Chinese hospitals., Diagnoses: CDAD, incomplete intestinal obstruction, postoperation of colon cancer., Intervention: Electrolyte replacement and rehydration. Parenteral nutrition support. Omeprazole was prescribed but withdrawn later, and oral vancomycin was given at a dose of 0.25 g 4 times per day for 10 days., Outcomes: Diarrhea was resolved, so long as the acid reflux and vomiting., Lessons: We have 2 lessons here: Be aware of PPIs induced CDI, especially the asymptomatic C. difficile colonization. Making clinical pathway specified on PPIs use by pharmacists could be a practical way to solve the problem of PPIs overuse.

Background/aims: Although proton pump inhibitors (PPIs) have been widely used for the prevention and treatment of stress gastric ulcers in hospital settings, there are concerns that PPIs increase the risk of Clostridium difficile infection (CDI). However, little is known about the risk of CDI following PPI and histamine-2 receptor antagonist (H2RA) use. We evaluated the comparative hospital-acquired CDI occurrence risk associated with the concurrent use of PPIs versus H2RAs., Methods: A systematic search of PubMed, MEDLINE/Ovid, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, and Google Scholar through August 19, 2016, identified 12 studies that reported the hospital-acquired CDI occurrence following H2RA and PPI use for the prevention and treatment of stress gastric ulcers. Random-effects pooled odds ratios and 95% confidence intervals were estimated. Heterogeneity was measured using I ², and a meta-regression analysis was conducted. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to assess the overall quality of the evidence., Results: A total of 74,132 patients from 12 observational studies were analyzed. Compared to H2RAs, PPIs increased the risk of CDI by 38.6% (pooled odds ratio, 1.386; 95% confidence interval, 1.152 to 1.668; p=0.001; I ²=42.81%). Subgroup analyses of the purpose of study medication use, study site, and study design confirmed the consistency of a greater CDI risk with PPIs than with H2RAs. The overall quality of evidence was rated as low., Conclusions: The use of PPIs for both the prevention and treatment of stress ulcers was associated with a 38.6% increased risk of hospital-acquired CDI occurrence compared to H2RA use.

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 [D 1 ] to D 5 ) were orally infected at D 3 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 (D 1 to D 8 ). Moxifloxacin concentrations and C. difficile counts were determined at D 3 , and mortality was determined at D 12 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 D 3 , 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., (Copyright © 2017 American Society for Microbiology.)

Background: Bacteriuria contributes to antibiotic overuse through treatment of asymptomatic bacteriuria (ASB) and long durations of therapy for symptomatic urinary tract infections (UTIs), yet large-scale evaluations of bacteriuria management among inpatients are lacking., Methods: Inpatients with bacteriuria were classified as asymptomatic or symptomatic based on established criteria applied to data collected by manual chart review. We examined frequency of treatment of ASB, factors associated with treatment of ASB, durations of therapy, and frequency of complications including Clostridium difficile infection, readmission, and all-cause mortality within 28 days of discharge., Results: Among 2225 episodes of bacteriuria, 64% were classified as ASB. After excluding patients with non-UTI indications for antibiotics, 72% of patients with ASB received antibiotics. When evaluating only patients not meeting SIRS criteria, 68% of patients with ASB received antibiotics. The mean (±SD) days of antibiotic therapy for ASB, cystitis, CA-UTI and pyelonephritis were 10.0 (4.5), 11.4 (4.7), 12.0 (6.1), and 13.6 (5.3), respectively. In sum, 14% of patients with ASB were treated for greater than 14 days, and fluoroquinolones were the most commonly used empiric antibiotic for ASB [245/691 (35%)]. Complications were rare but more common among patients with ASB treated with antibiotics., Conclusions: The majority of bacteriuria among inpatient veterans is due to ASB with high rates of treatment of ASB and prolonged durations of therapy for ASB and symptomatic UTIs., (Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Previous studies of the association between antibiotic exposure and risk of hospital-acquired Clostridium difficile-associated infection (CDI) have not fully accounted for patient severity of illness, and competing risks., Aim: To determine the potential effects of interventions on hospital-acquired CDI risk., Methods: All adults admitted to a teaching hospital between 2004 and 2014 for more than two days were included. Exposures to all antibiotics and cases of CDI were determined. Patients were followed until discharge from hospital, death, or acquisition of hospital-acquired CDI (defined as positive toxin assay in unformed stool >2 days following admission). Multivariable proportional hazards competing-risks modelling with time-dependent covariates was used, accounting for patient severity of illness using the Escobar model., Findings: In all, 208,104 patients were studied. Hospital-acquired CDI risk was 0.46 events per 1000 patient-days, decreasing significantly during the study period. Compared to the 5 th percentile hospital death risk (0.02%), patients with a 50% risk of death in hospital had an adjusted hazard ratio (aHR) of hospital-acquired CDI of 5.5. Exposure to some antibiotics significantly increased hospital-acquired CDI risk, being highest for carbapenems (aHR: 1.47 after one week of continuous exposure) and intravenous vancomycin (aHR: 1.53). On the ward, sharing a room with other patients newly diagnosed with CDI significantly increased the risk of subsequent disease (aHR: 1.16 on CDI diagnosis day)., Conclusion: The primary determinant of hospital-acquired CDI was patient severity of illness. Exposure to both antibiotics and other patients with CDI significantly increased the subsequent risk of hospital-acquired CDI but this risk was small relative to patient severity of illness., (Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Clostridium difficile is recognised worldwide as the main cause of infectious bacterial antibiotic-associated diarrhoea in hospitals and other healthcare settings. The aim of this study was to first survey C. difficile prevalence during the summer of 2014 at the Central University Hospital of Asturias (Spain). By typing the isolates obtained, it was then possible to compare the ribotype distribution at the Spanish hospital with results from the St Luc University Hospital in Belgium over the same period. The prevalence of positive cases reported in Spain and Belgium was 12.3% and 9.3% respectively. The main PCR-ribotypes previously described in Europe were found in both hospitals, including 078, 014, 012, 020 and 002. In the Spanish hospital, most of the C. difficile-positive samples were referred from oncology, acute care and general medicine services. In the Belgian hospital the majority of positive samples were referred from the paediatric service. However, a high percentage of isolates from this service were non-toxigenic. This study finds that the presence and detection of C. difficile in paediatric and oncology services requires further investigation., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Antibiotics are frequently prescribed in hospitalized and in outpatients. We review four important aspects for their daily prescription. In elderly patients, the prescription should take into account changes in the volume of distribution and the usual decline in renal function even in the absence of chronic kidney disease. Particular antibiotics can trigger infection with Clostridium difficile. We discuss actual and novel strategies for its prevention. Renal toxicity of antibiotics includes acute tubular necrosis, interstitial nephritis and crystals obstructing renal tubule, depending on the class of antibiotics. Plasmatic levels of particular antibiotics should be measured either at trough or at peak levels depending of the antibiotic prescribed., Competing Interests: les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Purpose: Results of a pharmacist-driven protocol to decrease proton pump inhibitor (PPI) use in non-intensive care unit (ICU) hospitalized adults are presented., Methods: This concurrent preintervention and postintervention study included subjects at least 18 years of age receiving PPIs while hospitalized in general medical or surgical beds. Patients were identified for inclusion in the postintervention group using a daily list of hospitalized patients with active PPI orders. A pharmacist evaluated these subjects for PPI appropriateness, and then recommended discontinuing or changing PPIs to histamine H2-receptor antagonists. Per protocol, the pharmacist could change PPIs to H2-antagonists if prescribers did not respond to recommendations. Preintervention group patients were gathered retrospectively and treated as the retrospective control group. Patients were excluded if they had cumulative ICU or ICU step-down stays of at least two days, had predefined appropriate indications for PPIs, or were not evaluated within one day of PPI orders. The primary outcome was the rate of PPI use. Secondary objectives included rates of prescriber acceptance of pharmacist recommendations and hospital-onset Clostridium difficile infections (HO-CDI)., Results: PPIs were discontinued in 66.0% (n = 62) of postintervention group patients compared to 41.1% (n = 39) of the preintervention group (absolute risk reduction, 24.9%; p = 0.001). In the postintervention group, 31.9% (n = 30) of recommendations were accepted, whereas 11.7% (n = 11) were rejected. No subjects in either group were diagnosed with HO-CDI during the study period., Conclusion: The pharmacist-driven protocol described in this study decreased PPI use in non-ICU hospitalized adults., (Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

Recognised as the leading cause of nosocomial antibiotic-associated diarrhoea, the incidence of Clostridium difficile infection (CDI) remains high despite efforts to improve prevention and reduce the spread of the bacterium in healthcare settings. In the last decade, many studies have focused on the epidemiology and rapid diagnosis of CDI. In addition, different typing methods have been developed for epidemiological studies. This review explores the history of C. difficile and the current scope of the infection. The variety of available laboratory tests for CDI diagnosis and strain typing methods are also examined., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Several adverse effects associated with long-term PPI therapy have been reported. These potential risks or side effects have included hypergastrinemia, carcinoid formation, devel- opment of gastric cancer, bacterial overgrowth, Clostridium difficile infection, pneumonia, bone fracture and malabsorption of vitamin B12 and iron. I explain each of these adverse events based on the guideline for GERD in both Japan and US, multiple meta-analyses and systematic review previously published.

Background/aims: Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) are commonly prescribed for stress ulcer prophylaxis (SUP) in critically ill patients. Several studies have suggested that the use of PPIs is a potential risk factor for Clostridium difficile infection (CDI). We compared the incidences of CDI in the PPI group and H2RA group for SUP in critically ill patients., Methods: From August 2005 to July 2012, the incidences of CDI were retrospectively analyzed in patients who were admitted directly to intensive care units and stayed for more than 3 days. SUP-related CDI was defined as a CDI diagnosed during the SUP period. Patient clinical data were analyzed to identify potential risk factors for SUP-related CDI., Results: Of the 1,005 patients enrolled (444 patients received PPI and 561 received H2RA), 38 (3.8%) were diagnosed with SUP-related CDI. The incidence of SUP-related CDI was considerably higher in patients who received PPI than in those who received H2RA (6.7% vs 1.8%). PPI use for SUP (odds ratio [OR], 3.3; confidence interval [CI], 1.5 to 7.1; p=0.003) and diabetes mellitus (OR, 2.3; CI, 1.2 to 4.7; p=0.019) were independent risk factors for SUP-related CDI., Conclusions: PPI therapy is associated with a higher risk of SUP-related CDI than H2RA therapy in critically ill patients.

Antibiotics have been the most important risk factor for Clostridium difficile infection (CDI). However, only data from non-randomised studies have been reviewed. We sought to evaluate the risk for development of CDI associated with the major antibiotic classes by analysing data from randomised controlled trials (RCTs). The PubMed, Cochrane and Scopus databases were searched and the references of selected RCTs were also hand-searched. Eligible studies should have compared only one antibiotic versus another administered systemically. Inclusion of studies comparing combinations of antibiotics was allowed only if the second antibiotic was the same or from the same class or if it was administered in a subset of the enrolled patients who were equally distributed in the two arms. Only a minority of the selected RCTs (79/1332; 5.9%) reported CDI episodes. Carbapenems were associated with more CDI episodes than fluoroquinolones [risk ratio (RR) = 2.44, 95% confidence interval (CI) 1.32-4.49] and cephalosporins (RR = 2.24, 95% CI 1.46-3.42), but not penicillins (RR = 2.53, 95% CI 0.87-7.41). Cephalosporins were associated with more CDIs than penicillins (RR = 2.36, 95% CI 1.32-4.23) and fluoroquinolones (RR = 2.84, 95% CI 1.60-5.06). There was no difference in CDI frequency between fluoroquinolones and penicillins (RR = 1.34, 95% CI 0.55-3.25). Finally, clindamycin was associated with more CDI episodes than cephalosporins and penicillins (RR = 3.92, 95% CI 1.15-13.43). In conclusion, data from RCTs showed that clindamycin and carbapenems were associated with more CDIs than other antibiotics., (Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Objectives: Clostridium difficile infection (CDI) is strongly associated with anti-biotic treatment, and community-acquired pneumonia (CAP) is the leading indication for anti-biotic prescription in hospitals. This study assessed the incidence of and risk factors for CDI in a cohort of patients hospitalized with CAP., Methods: We analysed data from a prospective, observational cohort of patients with CAP in Edinburgh, UK. Patients with diarrhoea were systematically screened for CDI, and risk factors were determined through time-dependent survival analysis., Results: Overall, 1883 patients with CAP were included, 365 developed diarrhoea and 61 had laboratory-confirmed CDI. The risk factors for CDI were: age (hazard ratio [HR], 1.06 per year; 95% confidence interval [CI], 1.03-1.08), total number of antibiotic classes received (HR, 3.01 per class; 95% CI, 2.32-3.91), duration of antibiotic therapy (HR, 1.09 per day; 95% CI, 1.00-1.19 and hospitalization status (HR, 13.1; 95% CI, 6.0-28.7). Antibiotic class was not an independent predictor of CDI when adjusted for these risk factors (P > 0.05 by interaction testing)., Conclusions: These data suggest that reducing the overall antibiotic burden, duration of antibiotic treatment and duration of hospital stay may reduce the incidence of CDI in patients with CAP., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Clostridium difficile infection (CDI) is one of the leading causes of hospital-acquired infections in recent times. Hematopoietic stem cell transplantation (HSCT) confers increased risk for CDI because of prolonged hospital stay, immunosuppression, the need to use broad-spectrum antibiotics and a complex interplay of preparative regimen and GvHD-induced gut mucosal damage. Our study evaluated risk factors (RF) for recurrent CDI in HSCT recipients given the ubiquity of traditional RF for CDI in this population. Of the 499 allogeneic HSCT recipients transplanted between 2005 and 2012, 61 (12%) developed CDI within 6 months before transplant or 2 years after transplant and were included in the analysis. Recurrent CDI occurred in 20 (33%) patients. One year incidence of CDI recurrence was 31%. Multivariable analyses identified the number of antecedent antibiotics other than those used to treat CDI as the only significant RF for recurrence (hazard ratio 1.96, 95% confidence interval 1.09-3.52, P=0.025). Most recurrences occurred within 6 months of the first CDI, and the recurrence of CDI was associated with a trend for increased risk of mortality. This prompts the need for further investigation into secondary prophylaxis to prevent recurrent CDI.

Background: Proton-pump inhibitors (PPIs) are commonly used among medical inpatients, both for prophylaxis against upper gastrointestinal bleeding (UGIB) and continuation of outpatient use. While PPIs reduce the risk of UGIB, they also appear to increase the risk of hospital-acquired pneumonia (HAP) and Clostridium difficile infection (CDI). Depending upon the underlying risks of these conditions and the changes in those risks with PPIs, use of proton-pump inhibitors may lead to a net benefit or net harm among medical inpatients., Objective: We aimed to determine the net impact of PPIs on hospital mortality among medical inpatients., Design: A microsimulation model, using literature-derived estimates of the risks of UGIB, HAP, and CDI among medical inpatients, along with the changes in risk associated with PPI use for each of these outcomes. The primary outcome was change in inpatient mortality., Participants: Simulated general medical inpatients outside the intensive care unit (ICU)., Main Measure: Change in overall mortality during hospitalization., Key Results: New initiation of PPI therapy led to an increase in hospital mortality in about 90% of simulated patients. Continuation of outpatient PPI therapy on admission led to net increase in hospital mortality in 79% of simulated patients. Results were robust to both one-way and multivariate sensitivity analyses, with net harm occurring in at least two-thirds of patients in all scenarios., Conclusions: For the majority of medical inpatients outside the ICU, use of PPIs likely leads to a net increase in hospital mortality. Even in patients at particularly high risk of UGIB, only those at the very lowest risk of HCAP and CDI should be considered for prophylactic PPI use. Continuation of outpatient PPIs may also increase expected hospital mortality. Apart from patients with active UGIB, use of PPIs in hospitalized patients should be discouraged., Competing Interests: Compliance with Ethical Standards Conflicts of interest The authors declare that they do not have a conflict of interest.