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The most common cause of antibiotic-associated diarrhea is Clostridium difficile infection (CDI). Recurrent C. difficile infection (rCDI) often occurs after successful treatment of CDI. Due to the increased incidence and the difficulty in treating rCDI, it is becoming an important clinical issue. Identifying risk factors is helpful for early detection, treatment, and prevention of rCDI. Advanced age, use of antibiotics, gastric acid suppression, and infection with a hypervirulent strain are currently regarded as the major risk factors for rCDI. Several treatment modalities, including vancomycin, fidaxomicin, and fecal microbiota transplant (FMT), are suggested for rCDI treatment. However, there is currently no definitive treatment method with sufficient evidence for rCDI. Recent studies have focused on FMT and have shown positive results for rCDI. Prevention of rCDI by measures such as hand washing and isolation of patients is very important. However, these preventive measures are often overlooked in clinical practice. Here, we review the risk factors, treatment, and prevention of rCDI.

Background: Clostridium difficile-associated diarrhea (CDAD) is common during hematopoietic stem-cell transplantation (HSCT) and is associated with increased morbidity and mortality. We evaluated fidaxomicin for prevention of CDAD in HSCT patients., Methods: In this double-blind study, subjects undergoing HSCT with fluoroquinolone prophylaxis stratified by transplant type (autologous/allogeneic) were randomized to once-daily oral fidaxomicin (200 mg) or a matching placebo. Dosing began within 2 days of starting conditioning or fluoroquinolone prophylaxis and continued until 7 days after neutrophil engraftment or completion of fluoroquinolone prophylaxis/clinically-indicated antimicrobials for up to 40 days. The primary endpoint was CDAD incidence through 30 days after study medication. The primary endpoint analysis counted confirmed CDAD, receipt of CDAD-effective medications (for any indication), and missing CDAD assessment (for any reason, including death) as failures; this composite analysis is referred to as "prophylaxis failure" to distinguish from the pre-specified sensitivity analysis, which counted only confirmed CDAD (by toxin immunoassay or nucleic acid amplification test) as failure., Results: Of 611 subjects enrolled, 600 were treated and analyzed. Prophylaxis failure was similar in fidaxomicin and placebo recipients (28.6% vs 30.8%; difference 2.2% [-5.1, 9.5], P = .278). However, most failures were due to non-CDAD events. Confirmed CDAD was lower in fidaxomicin vs placebo recipients (4.3% vs 10.7%; difference 6.4% [2.2, 10.6], P = .0014). Drug-related adverse events occurred in 15.0% of fidaxomicin recipients and 20.0% of placebo recipients., Conclusions: While no difference was demonstrated between arms in the primary analysis, results of the sensitivity analysis demonstrated that fidaxomicin significantly reduced the incidence of CDAD in HSCT recipients., Clinical Trials Registration: NCT01691248.

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: Despite advancements, recurrent Clostridium difficile infections (CDI) remain an urgent public health threat with insufficient response rates to currently approved antibiotic therapies. Microbiota-based treatments appear effective, but rigorous clinical trials are required to optimize dosing strategies and substantiate long-term safety., Methods: This randomized, double-blind, placebo-controlled phase 2B trial enrolled adults with 2 or more CDI recurrences to receive: 2 doses of RBX2660, a standardized microbiota-based drug (group A); 2doses of placebo (group B); or 1 dose of RBX2660 followed by 1 dose of placebo (group C). Efficacy was defined as prevention of recurrent CDI for 8 weeks following treatment. Participants who had a recurrence within 8 weeks were eligible to receive up to 2 open-label RBX2660 doses. The primary endpoint was efficacy for group A compared to group B. Secondary endpoints included the efficacy of group C compared to group B, combined efficacy in the blinded and open-label phases, and safety for 24 months., Results: The efficacy for groups A, B, and C were 61%, 45%, and 67%, respectively. The primary endpoint was not met (P = .152). One RBX2660 dose (group C) was superior to placebo (group B; P = .048), and the overall efficacy (including open-label response) for RBX2660-treated participants was 88.8%. Adverse events did not differ significantly among treatment groups., Conclusions: One, but not 2, doses of RBX2660 was superior to placebo in this randomized, placebo-controlled trial. These data provide important insights for a larger phase 3 trial and continued clinical development of RBX2660., Clinical Trials Registration: NCT02299570.

Background: Over 70% of patients are prescribed antibiotics during their intensive care (ICU) admission. The gut microbiome is dramatically altered early in an ICU stay, increasing the risk for antibiotic associated diarrhea (AAD) and Clostridium difficile infections (CDI). Evidence suggests that some probiotics are effective in the primary prevention of AAD and CDI. Aim: To demonstrate safety and feasibility of a probiotic drink in ICU patients. Methods: ICU patients initiated on antibiotics were recruited, and matched with contemporary controls. Study patients received two bottles daily of a drink containing 10 billion Lactobacillus casei which was bolused via feeding tube. Tolerance to probiotics and enteral nutrition, development of adverse events, and incidence of AAD was recorded. CDI rates were followed for 30 days post antibiotic treatment. Results: Thirty-two patients participated in the trial. There were no serious adverse events in the probiotic group, compared to three in the control group. AAD was documented in 12.5% of the probiotic group and 31.3% in the control group. One patient in the probiotic group developed CDI compared to three in the control group. Discussion: A probiotic containing drink can safely be delivered via feeding tube and should be considered as a preventative measure for AAD and CDI in ICU.

Background: The choice of antibiotics for systemic infections in patients with a high risk of Clostridium difficile infection (CDI) remains a clinical practice dilemma. Although some studies suggest that tetracyclines may be associated with a lower risk of CDI than other antibiotics, other results are conflicting. We conducted a systematic review and metaanalysis of studies that assessed the risk of CDI with tetracyclines compared to other antibiotics., Methods: We conducted a systematic search of Medline, Embase, and Web of Science from January 1978 through December 2016 to include studies that assessed the association between tetracycline use and risk of CDI. Weighted summary estimates were calculated using generalized inverse variance with a random-effects model using RevMan 5.3. Study quality was assessed using the Newcastle-Ottawa scale., Results: Six studies (4 case control, 2 cohort) with patient recruitment between 1993 and 2012 were included. Metaanalysis using a random-effects model, demonstrated that tetracyclines were associated with a decreased risk of CDI (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.47-0.81; P < .001). There was significant heterogeneity, with an I2 of 53% with no publication bias. Subgroup analysis of studies that evaluated the risk of CDI with doxycycline alone also demonstrated a decreased risk of CDI (OR, 0.55; 95% CI, 0.40-0.75; P < .001)., Conclusions: Metaanalyses of existing studies suggest that tetracyclines may be associated with a decreased risk of CDI compared with other antimicrobials. It may be reasonable to use tetracyclines whenever appropriate to decrease CDI associated with antibiotic use., (© The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Purpose of Review: The rising burden of Clostridium difficile infection (CDI) requires urgent identification of preventable risk factors. Observational studies suggest an association between proton-pump inhibitor (PPI) use and CDI risk., Recent Findings: Key historical literature on PPI and CDI associations is reviewed as a prelude to evaluating the plausibility of a causative association. Impactful literature from the past 18 months is examined in detail and critically appraised through the lens of the Bradford Hill Criteria for determination of causality. The PPI and CDI association has been studied extensively and is valid. Nonetheless, causality is not proven due to extensive and difficult to control confounding in observational studies of CDI patient populations with complex comorbidities., Summary: In the authors' opinion, systematic discontinuation of PPIs in patients at risk for CDI is not warranted based on current evidence. Well controlled prospective human studies are needed. Careful and repeated consideration should be given to all PPI prescriptions to avoid potential adverse effects.

Purpose: Patients receiving intensive chemotherapy regimens are at high risk for infectious complications due to prolonged neutropenia and hospital stay. Fluoroquinolone antibiotics, mainly levofloxacin and ciprofloxacin, are the mainstay of prophylactic therapy for these patients. There is limited data regarding the utilization of other quinolone antibiotics including moxifloxacin in this setting., Methods: A retrospective chart review was completed comparing the use of prophylactic moxifloxacin to that of levofloxacin or ciprofloxacin during periods of prolonged neutropenia. Adult patients admitted to a community teaching hospital while receiving induction or reinduction chemotherapy for acute myeloid leukemia were included., Results: One hundred and forty-one patients were included in this study. The two groups displayed slight heterogeneity: patients receiving moxifloxacin were approximately 10 years younger (54 vs. 64 years, p = 0.01), more likely to receive granulocyte colony stimulating factor (GCSF) (45 vs. 19%, p = 0.001), and neutropenic for a longer duration (23 vs. 19 days, p = 0.009). The incidence of febrile neutropenia (76 vs. 81%, RR 0.93, 95% CI 0.78-1.11, p = 0.42) and of documented infections (27 vs. 33%, RR 0.82, 95% CI 0.49-1.36, p = 0.44) was similar between those receiving moxifloxacin and levofloxacin/ciprofloxacin, respectively. Hospital readmission for an infectious issue within 30 days of hospital discharge (9 vs. 5%, p = 0.39) was also similar between groups as was the incidence of Clostridium difficile (9 vs. 9%, p = 0.96)., Conclusions: Moxifloxacin may be an alternative to levofloxacin or ciprofloxacin in patients with a prolonged risk of febrile neutropenia requiring prophylaxis.

Competing Interests: Interessenkonflikt: Der Autor hat Vortragshonorare und Reisegrants von Astellas erhalten.

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.)

Objective: Provide a systematic review of the primary literature on efforts to reduce Clostridium difficile infection (CDI) occurrence and improve outcomes in older adults., Data Sources, Study Selection, Data Extraction: PubMed and CINAHL databases were searched for research studies using search terms CDI, CDI prevention, reduction, control, management, geriatric, elderly, adults 65 years of age and older. The MeSH categories Aged and Aged, 80 and older, were used. A second search of PubMed, CINAHL, National Guideline Clearinghouse, and TRIP databases was conducted for primary, secondary, and tertiary literature for CDI epidemiology, burden, and management in adults of all ages, and prevention and management guidelines. Of the 2,263 articles located, 105 were selected for full review: 55 primary and 50 secondary, tertiary. Primary literature selected for full review included studies of interventions to prevent, reduce occurrence, control, manage, or improve outcomes in adults 65 years of age and older. Patient settings included the community, assisted living, nursing facility, subacute care, or hospital., Data Synthesis: The main outcome measures for research studies were whether the studied intervention prevented, reduced occurrence, controlled, managed, or improved outcomes. Studies were conducted in acute or long-term hospitals, with a few in nursing facilities. Interventions that prevented or reduced CDI included antibiotic policy changes, education, procedure changes, infection control, and multi-intervention approaches. There were few management studies for adults 65 years of age and older or for all adults with results stratified by age. Treatments studied included efficacy of fidaxomicin, metronidazole, vancomycin, and fecal microbiota transplant. Though clinical outcomes were slightly less robust in those 65 years of age and older, age was not an independent predictor of success or failure. The current prevention and management guidelines for adults of all ages, as well as special considerations in skilled nursing facilities, extracted from the secondary/tertiary literature selected, are summarized., Conclusion: There are a limited number of studies designed for older adults. Our findings suggest that guideline recommendations for adults are adequate and appropriate for older adults. Exposure to antibiotics and Clostridium difficile remain the two major risk factors for CDI, reinforcing the importance of antibiotic stewardship and infection control.

The gut microbiome, composed of the microflora that inhabit the gastrointestinal tract and their genomes, make up a complex ecosystem that can be disrupted by antibiotic use. The ensuing dysbiosis is conducive to the emergence of opportunistic pathogens such as Clostridium difficile. A novel approach to protect the microbiome from antibiotic-mediated dysbiosis is the use of beta-lactamase enzymes to degrade residual antibiotics in the gastrointestinal tract before the microflora are harmed. Here we present the preclinical development and early clinical studies of the beta-lactamase enzymes, P3A, currently referred to as SYN-004, and its precursor, P1A. Both P1A and SYN-004 were designed as orally-delivered, non-systemically available therapeutics for use with intravenous beta-lactam antibiotics. SYN-004 was engineered from P1A, a beta-lactamase isolated from Bacillus licheniformis, to broaden its antibiotic degradation profile. SYN-004 efficiently hydrolyses penicillins and cephalosporins, the most widely used IV beta-lactam antibiotics. In animal studies, SYN-004 degraded ceftriaxone in the GI tract of dogs and protected the microbiome of pigs from ceftriaxone-induced changes. Phase I clinical studies demonstrated SYN-004 safety and tolerability. Phase 2 studies are in progress to assess the utility of SYN-004 for the prevention of antibiotic-associated diarrhea and Clostridium difficile disease., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Clostridium difficile infection is one of the most frequent among cancer patients. Its diagnosis is complicated by the fact that the symptoms of the infection and the side effects of the anticancer treatments could be similar. Chemotherapy itself might facilitate Clostridium difficile infection. Several risk factors are known but Clostridium difficile infection can develop in the absence of these. Neutreopenia is a risk factor for fatal Clostridium difficile infection and also the side effect of chemotherapy. Therefore, if symptoms of the potential infection develop (eg. diarrhoea more than three times a day, fever above 38.5 °C, colitis, rapid increase of serum creatinin) Clostridium difficile infection should be excluded. If the infection is confirmed it should be managed in the most efficient way. Orv. Hetil., 2016, 157(28), 1110-1116.

Objectives: Clostridium difficile infection (CDI) is a global healthcare problem. Recent evidence suggests that the availability of iron may be important for C. difficile growth. This study evaluated the comparative effects of iron-depleted (1% Fe(3+) saturated) bovine apo-lactoferrin (apo-bLf) and iron-saturated (85% Fe(3+) saturated) bovine holo-lactoferrin (holo-bLf) in a human in vitro gut model that simulates CDI., Methods: Two parallel triple-stage chemostat gut models were inoculated with pooled human faeces and spiked with C. difficile spores (strain 027 210, PCR ribotype 027). Holo- or apo-bLf was instilled (5 mg/mL, once daily) for 35 days. After 7 days, clindamycin was instilled (33.9 mg/L, four times daily) to induce simulated CDI. Indigenous microflora populations, C. difficile total counts and spores, cytotoxin titres, short chain fatty acid concentrations, biometal concentrations, lactoferrin concentration and iron content of lactoferrin were monitored daily., Results: In the apo-bLf model, germination of C. difficile spores occurred 6 days post instillation of clindamycin, followed by rapid vegetative cell proliferation and detectable toxin production. By contrast, in the holo-bLf model, only a modest vegetative cell population was observed until 16 days post antibiotic administration. Notably, no toxin was detected in this model. In separate batch culture experiments, holo-bLf prevented C. difficile vegetative cell growth and toxin production, whereas apo-bLf and iron alone did not., Conclusions: Holo-bLf, but not apo-bLf, delayed C. difficile growth and prevented toxin production in a human gut model of CDI. This inhibitory effect may be iron independent. These observations suggest that bLf in its iron-saturated state could be used as a novel preventative or treatment strategy for CDI., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Clostridium difficile associated diarrhea (CDAD) is increasingly important in primary care, and associated with high cost, significant morbidity and mortality. As the preferred treatment for different groups of patients varies considerably, it is important to stratify CDAD patients into mild versus severe and uncomplicated versus complicated. While treatment with either metronidazole or oral vancomycin cures a majority of patients, and despite improvement in early diagnosis and therapy, recurrence continues to be a significant problem. In appropriately selected patients, fecal bacteriotherapy has emerged as an effective treatment for the patient with multiple recurrences. Addressing CDAD should include antibiotic stewardship, improved hygiene, prompt diagnosis, appropriate treatment, and infection precautions in hospitals and skilled nursing facilities.

Background: Gastrointestinal complications from antibiotic use, including Clostridium difficile infection (CDI), can have significant morbidity, especially among older patients. This descriptive study surveyed dentists to find out how they would respond to a patient with signs indicating potential CDI., Methods: A survey on prescribing medications for older patients was mailed to 1,000 dentists in New Jersey. Questions were asked regarding antibiotic selection, probiotic use, and approach to a patient scenario of diarrhea after antibiotic use., Results: Respondents chose amoxicillin most frequently as an antibiotic, and clindamycin if penicillin allergy. When informed their patients had diarrhea, 64.5% advised them to stop the antibiotic. If the patient continued to have diarrhea on follow-up, 75.5% contacted the patient's physician. Most (61.6%) do not prescribe probiotics prophylactically., Conclusions: Most dentists respond appropriately to antibiotic-associated diarrhea in advising to stop the antibiotic, and seeking physician involvement if no improvement, but there are still many who make recommendations that could delay appropriate care. Dentists may wish to learn more about benefits of probiotics., (© 2015 Special Care Dentistry Association and Wiley Periodicals, Inc.)

Dentists prescribe significant volumes of antimicrobial drugs within primary care settings. There is good evidence that many of the prescriptions are not justified by current clinical guidance and that that there is considerable misuse of these drugs in dentistry. One of the risks associated with antibiotic administration is Clostridium difficile-associated disease (CDAD), an entity of which many healthcare workers, including dentists, have little knowledge or understanding. This review seeks to identify the extent and nature of the problem and provides an up to date summary of current views on CDAD, with particular reference to community acquired disease. As for all healthcare workers, scrupulous attention to standard infection control procedures and reducing inappropriate antibiotic prescribing are essential to reduce the risks of CDAD, prevent emergence of further resistant strains of microorganisms and maintain the value of the arsenal of antibiotics currently available to us.

Infections caused by multidrug resistant (MDR) organisms are becoming more frequently in daily practice and are associated with an increase in duration of treatment and mortality. During the past decades, particular attention in the field of MDR pathogens was paid to methicillin-resistant staphylococcus aureus (MRSA). For the last years, MDR gram-negative organisms, with e.g., "extended-spectrum beta-lactamases" (ESBL), have been gaining a growing significance. Currently, treatment of infections with these organisms displays a greater challenge for the clinician compared to MRSA infections. This review illustrates the emergence of antibiotic resistance, provides information on the most important gram-negative and gram-positive bacteria, Clostridium difficile and measures to prevent their further spread., (Georg Thieme Verlag KG Stuttgart · New York.)

Vancomycin is a preferred antibiotic for treating Clostridium difficile infection (CDI) and has been associated with a rate of recurrence of CDI of as high as 20% in treated patients. Recent studies have suggested that berberine, an alternative medical therapy for gastroenteritis and diarrhea, exhibits several beneficial effects, including induction of anti-inflammatory responses and restoration of the intestinal barrier function. This study investigated the therapeutic effects of berberine on preventing CDI relapse and restoring the gut microbiota in a mouse model. Berberine was administered through gavage to C57BL/6 mice with established CDI-induced intestinal injury and colitis. The disease activity index (DAI), mean relative weight, histopathology scores, and levels of toxins A and B in fecal samples were measured. An Illumina sequencing-based analysis of 16S rRNA genes was used to determine the overall structural change in the microbiota in the mouse ileocecum. Berberine administration significantly promoted the restoration of the intestinal microbiota by inhibiting the expansion of members of the family Enterobacteriaceae and counteracting the side effects of vancomycin treatment. Therapy consisting of vancomycin and berberine combined prevented weight loss, improved the DAI and the histopathology scores, and effectively decreased the mortality rate. Berberine prevented CDIs from relapsing and significantly improved survival in the mouse model of CDI. Our data indicate that a combination of berberine and vancomycin is more effective than vancomycin alone for treating CDI. One of the possible mechanisms by which berberine prevents a CDI relapse is through modulation of the gut microbiota. Although this conclusion was generated in the case of the mouse model, use of the combination of vancomycin and berberine and represent a novel therapeutic approach targeting CDI., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Objective: To determine the potential epidemiologic and economic value of the implementation of a multifaceted Clostridium difficile infection (CDI) control program at US acute care hospitals, Design: Markov model with a 5-year time horizon, Participants: Patients whose data were used in our simulations were limited to hospitalized Medicare beneficiaries ≥65 years old., Background: CDI is an important public health problem with substantial associated morbidity, mortality, and cost. Multifaceted national prevention efforts in the United Kingdom, including antimicrobial stewardship, patient isolation, hand hygiene, environmental cleaning and disinfection, and audit, resulted in a 59% reduction in CDI cases reported from 2008 to 2012., Methods: Our analysis was conducted from the federal perspective. The intervention we modeled included the following components: antimicrobial stewardship utilizing the Antimicrobial Use and Resistance module of the National Healthcare Safety Network (NHSN), use of contact precautions, and enhanced environmental cleaning. We parameterized our model using data from CDC surveillance systems, the AHRQ Healthcare Cost and Utilization Project, and literature reviews. To address uncertainty in our parameter estimates, we conducted sensitivity analyses for intervention effectiveness and cost, expenditures by other federal partners, and discount rate. Each simulation represented a cohort of 1,000 hospitalized patients over 1,000 trials. RESULTS In our base case scenario with 50% intervention effectiveness, we estimated that 509,000 CDI cases and 82,000 CDI-attributable deaths would be prevented over a 5-year time horizon. Nationally, the cost savings across all hospitalizations would be $2.5 billion (95% credible interval: $1.2 billion to $4.0 billion)., Conclusions: The potential benefits of a multifaceted national CDI prevention program are sizeable from the federal perspective.

Objective: To predict the likelihood of hospital-onset Clostridium difficile infection (HO-CDI) based on patient clinical presentations at admission, Design: Retrospective data analysis, Setting: Six US acute care hospitals, Patients: Adult inpatients, Methods: We used clinical data collected at the time of admission in electronic health record (EHR) systems to develop and validate a HO-CDI predictive model. The outcome measure was HO-CDI cases identified by a nonduplicate positive C. difficile toxin assay result with stool specimens collected >48 hours after inpatient admission. We fit a logistic regression model to predict the risk of HO-CDI. We validated the model using 1,000 bootstrap simulations., Results: Among 78,080 adult admissions, 323 HO-CDI cases were identified (ie, a rate of 4.1 per 1,000 admissions). The logistic regression model yielded 14 independent predictors, including hospital community onset CDI pressure, patient age ≥65, previous healthcare exposures, CDI in previous admission, admission to the intensive care unit, albumin ≤3 g/dL, creatinine >2.0 mg/dL, bands >32%, platelets ≤150 or >420 109/L, and white blood cell count >11,000 mm3. The model had a c-statistic of 0.78 (95% confidence interval [CI], 0.76-0.81) with good calibration. Among 79% of patients with risk scores of 0-7, 19 HO-CDIs occurred per 10,000 admissions; for patients with risk scores >20, 623 HO-CDIs occurred per 10,000 admissions (P<.0001)., Conclusion: Using clinical parameters available at the time of admission, this HO-CDI model demonstrated good predictive ability, and it may have utility as an early risk identification tool for HO-CDI preventive interventions and outcome comparisons.

Purpose: Recent meta-analyses showed that antibiotic prophylaxis in patients with neutropenia after chemotherapy reduced the incidence of fever and mortality rate. Fluoroquinolones appear to be most effective and well tolerated. Thus, in April 2008, we changed our antibiotic prophylaxis regimen from cotrimoxazole/colistin (COT/COL) to the fluoroquinolone ciprofloxacin (CIP) in patients with acute myeloid leukemia (AML). The aim of this retrospective study was to compare efficacy and development of bacterial resistance with two different prophylaxis regimens over a time period of more than 4 years., Methods: Induction chemotherapy courses given for AML during the antibiotic prophylaxis period with COT/COL (01/2006-04/2008) and CIP (04/2008-06/2010) were retrospectively analyzed with a standard questionnaire., Results: Eighty-five courses in the COT/COL group and 105 in the CIP group were analyzed. The incidence of fever was not significantly different (COT/COL 80 % vs CIP 77 %; p = 0.724). Also, the rate of microbiologically documented infections was nearly the same (29 vs 26 %; p = 0.625). In addition, there was no significant difference in the incidence of clinically documented infections (11 vs 19 %; p = 0.155) or in the rates of detected gram-positive and gram-negative bacteria. Of note, there was no increase in resistance rates or cases with Clostridium difficile-associated diarrhea in the CIP group., Conclusion: The antibiotic prophylaxis with CIP compared to COT/COL in AML was similarly effective with no increase in bacterial resistance. COT/COL may have the advantages of providing additional prophylaxis against Pneumocystis jirovecii pneumonia and leaving fluoroquinolones as an additional option for treatment of febrile neutropenia.

Background and Aims: Probiotics, including Saccharomyces boulardii, have been advocated for the prevention of Clostridium difficile infection. The aim of this project was to evaluate the effects of the removal of S. boulardii from an automatic antibiotic order set and hospital formulary on hospital onset C. difficile infection rates., Design: A retrospective chart review was performed on all patients with hospital onset C. difficile infection during the 13 months prior (control group) and the 13 months after (study group) removal of an automatic order set linking S. boulardii capsules to certain broad spectrum antibiotics., Setting: A large 800+ bed tertiary hospital., Results: Among all hospitalized patients, the rate of hospital onset C. difficile infection was 0.99 per 1000 patient days while the S. boulardii protocol was active compared with 1.04 per 1000 patient days (p=0.10) after S. boulardii was removed from the formulary. No difference in the rate of hospital onset C. difficile infection was detected in patients receiving the linked broad spectrum antibiotics during and after the removal of the protocol (1.25% vs. 1.51%, respectively; p=0.70)., Conclusions: Removal of S. boulardii administration to patients receiving broad spectrum antibiotics and the hospital formulary did not impact the rate of hospital onset C. difficile infection in either the hospital population or patients receiving broad spectrum antibiotics.

Probiotics use has increased tremendously over the past ten years. This was coupled with a surge of data relating their importance in clinical practice. Antibiotic-associated diarrhea, whose frequency has risen recently, was one of the earliest targets with data published more than ten years ago. Unfortunately, available trials suffer from severe discrepancies associated with variability and heterogeneity of several factors. Most published randomized controlled trials and subsequent meta-analyses suggest benefit for probiotics in the prevention of antibiotic-associated diarrhea. The same seems to also apply when the data is examined for Clostridium difficile-associated colitis. However, the largest randomized double-blind placebo-controlled trial to date examining the use of a certain preparation of probiotics in antibiotic-associated diarrhea showed disappointing results, but it was flawed with several drawbacks. The commonest species of probiotics studied across most trials is Lactobacillus; however, other types have also shown similar benefit. Probiotics have enjoyed an impeccable safety reputation. Despite a few reports of severe infections sometimes leading to septicemia, most of the available trials confirm their harmless behavior and show similar adverse events compared to placebo. Since a consensus dictating its use is still lacking, it would be advisable at this point to suggest prophylactic use of probiotics to certain patients at risk for antibiotic-associated diarrhea or to those who suffered previous episodes.

Objective: To determine whether controlling the prescription of targeted antibiotics would translate to a measurable reduction in hospital-onset Clostridium difficile infection (CDI) rates., Design: A multicenter before-and-after intervention comparative study., Setting/participants: Ten medical centers in the greater New York region. Intervention group comprised of 6 facilities with early antimicrobial stewardship programs (ASPs). The 4 facilities without ASPs made up the nonintervention group., Interventions/methods: Intervention facilities identified target antibiotics using case-control studies and implemented ASP-based strategies to control their use. Pre- and postintervention hospital-onset CDI rates and antibiotic consumption were compared for a 20-month period from June 2010 to January 2012. Antibiotic usage was compared using defined daily dose, days of therapy, and number of courses prescribed. Comparisons used bivariate and regression techniques., Results: Intervention facilities identified piperacillin/tazobactam, fluoroquinolones, or cefepime (odds ratio, 2.0-9.8 in CDI case patients compared with those without CDI) as intervention targets and selected several interventions (all included a component of audit and feedback). Varying degrees of success were observed in reducing antibiotic consumption over time. Total target antibiotic use significantly decreased (P < .05) when measured by days of therapy and number of courses but not by defined daily dose. Intravenous moxifloxacin and oral ciprofloxacin use showed significant reduction when measured by defined daily dose and days of therapy (P ≤ .01). Number of courses with all forms of these antibiotics was reduced (P < .005). Intervention hospitals reported fewer hospital-onset CDI cases (2.8 rate point difference) compared with nonintervention hospitals; however, we were unable to show statistically significant decreases in aggregate hospital-onset CDI either between intervention and nonintervention groups or within the intervention group over time., Conclusions: Although decreases in target antibiotic consumption did not translate into reductions of hospital-onset CDI in this study, many valuable lessons (including implementation strategies and antibiotic consumption measures) were learned. The findings can inform potential policy decisions regarding incorporating control of CDI and ASP as healthcare quality measures.

Clostridium difficile infection (CDI) is an important health care-associated infection that leads to increased morbidity and mortality. Antibacterial medications used in hospitals serve as targets for antibacterial stewardship programs to reduce C difficile. The objective was to create a benchmark strategy targeting high-risk antibacterials for C difficile. This was a retrospective cross-sectional study using claims data from 58 hospitals. The Data Envelopment Analysis Technique was used to identify best-practice hospitals in terms of less use of 5 classes of antibacterials and fewer CDIs. Of 58 hospitals, 17 (29%) were identified as best-practice hospitals. Antibacterial classes requiring the greatest percentage reduction in use in non-best-practice hospitals versus best-practice hospitals were clindamycin (31%), β-lactam/β-lactamase combinations (30%), and carbapenems (29%). This study suggests that there are areas of improvement in high-risk antibacterial use that could lead to decreased CDIs., (© 2013 by the American College of Medical Quality.)

Objective: To review the chemistry, pharmacology, microbiology, pharmacodynamics, pharmacokinetics, clinical efficacy, tolerability, drug interactions, dosing, and administration of fidaxomicin (FDX)., Data Sources: A search of PubMed using the terms "fidaxomicin," "OPT-80," "PAR-101," "OP-1118," "difimicin," "tiacumicin," and "lipiarmycin" was performed. All English-language articles from 1983 to November 2013 were reviewed for relevance. Bibliographies of all articles were reviewed as well as the manufacturer's Web site to further identify relevant information., Study Selection: All English-language articles from 1983 to November 2013 appearing in these searches were reviewed for relevance to this paper. In addition, their bibliographies were reviewed to identify any articles not identified in the searches., Data Synthesis: FDX is the first macrolide antibiotic with a narrow spectrum of activity targeted against Clostridium difficile. It is administered orally without regard to food. The primary route of elimination is fecal excretion. Advanced age, hepatic dysfunction, or renal impairment do not alter its disposition. Phase III clinical trials have demonstrated that FDX 200 mg twice daily for 10 days is noninferior to vancomycin 125 mg four times daily for 10 days in the treatment of adults with C. difficile infection and is associated with lower recurrence rates. FDX has a favorable side effect profile and a low potential for drug interactions., Conclusion: FDX has been shown to be safe and effective in the treatment of adults with C. difficile infection. Further research and pharmacoeconomic studies are needed to clarify and refine its role in the treatment of patients at high risk for recurrence.

A high consumption of clindamycin was noted in an orthopedics ward with high rates of Clostridium difficile infection (CDI). We restricted clindamycin for the entire ward. A reduction of 88% in CDI (1.07 to 0.12 × 1,000 patients-days, P = .056) and 84% for all-cause diarrhea (2.40 to 0.38 × 1,000 patients-days, P = .021) was achieved. Clindamycin was reduced 92.61% without an increase in other antibiotics. We identified high consumption of clindamycin as a risk factor for CDI., (Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)

Background: Antibiotic-associated diarrhoea (AAD) occurs most commonly in older people admitted to hospital and within 12 weeks of exposure to broad-spectrum antibiotics. Although usually a mild and self-limiting illness, the 15-39% of cases caused by Clostridium difficile infection [C. difficile diarrhoea (CDD)] may result in severe diarrhoea and death. Previous research has shown that probiotics, live microbial organisms that, when administered in adequate numbers, are beneficial to health, may be effective in preventing AAD and CDD., Objectives: To determine the clinical effectiveness and cost-effectiveness of a high-dose, multistrain probiotic in the prevention of AAD and CDD in older people admitted to hospital., Design: A multicentre, randomised, double-blind, placebo-controlled, parallel-arm trial., Setting: Medical, surgical and elderly care inpatient wards in five NHS hospitals in the UK., Participants: Eligible patients were aged ≥ 65 years, were exposed to one or more oral or parenteral antibiotics and were without pre-existing diarrhoeal disorders, recent CDD or at risk of probiotic adverse effects. Out of 17,420 patients screened, 2981 (17.1%) were recruited. Participants were allocated sequentially according to a computer-generated random allocation sequence; 1493 (50.1%) were allocated to the probiotic and 1488 (49.9%) to the placebo arm., Interventions: Vegetarian capsules containing two strains of lactobacilli and two strains of bifidobacteria (a total of 6 × 10(10) organisms per day) were taken daily for 21 days. The placebo was inert maltodextrin powder in identical capsules., Main Outcome Measures: The occurrence of AAD within 8 weeks and CDD within 12 weeks of recruitment was determined by participant follow-up and checking hospital laboratory records by research nurses who were blind to arm allocation., Results: Analysis based on the treatment allocated included 2941 (98.7%) participants. Potential risk factors for AAD at baseline were similar in the two study arms. Frequency of AAD (including CDD) was similar in the probiotic (159/1470, 10.8%) and placebo arms [153/1471, 10.4%; relative risk (RR) 1.04; 95% confidence interval (CI) 0.84 to 1.28; p = 0.71]. CDD was an uncommon cause of AAD and occurred in 12/1470 (0.8%) participants in the probiotic and 17/1471 (1.2%) in the placebo arm (RR 0.71; 95% CI 0.34 to 1.47; p = 0.35). Duration and severity of diarrhoea, common gastrointestinal symptoms, serious adverse events and quality of life measures were also similar in the two arms. Total health-care costs per patient did not differ significantly between the probiotic (£8020; 95% CI £7620 to £8420) and placebo (£8010; 95% CI £7600 to £8420) arms., Conclusion: We found no evidence that probiotic administration was effective in preventing AAD. Although there was a trend towards reduced CDD in the probiotic arm, on balance, the administration of this probiotic seems unlikely to benefit older patients exposed to antibiotics. A better understanding of the pathogenesis of AAD and CDD and the strain-specific effects of probiotics is needed before further clinical trials of specific microbial preparations are undertaken. Evaluation of the effectiveness of other probiotics will be difficult where other measures, such as antibiotic stewardship, have reduced CDD rates., Trial Registration: This trial is registered as ISRCTN70017204., Funding: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 57. See the NIHR Journals Library website for further project information.

Background: Antibiotic-associated diarrhoea (AAD) occurs most frequently in older (≥65 years) inpatients exposed to broad-spectrum antibiotics. When caused by Clostridium difficile, AAD can result in life-threatening illness. Although underlying disease mechanisms are not well understood, microbial preparations have been assessed in the prevention of AAD. However, studies have been mostly small single-centre trials with varying quality, providing insufficient data to reliably assess effectiveness. We aimed to do a pragmatic efficacy trial in older inpatients who would be representative of those admitted to National Health Service (NHS) and similar secondary care institutions and to recruit a sufficient number of patients to generate a definitive result., Methods: We did a multicentre, randomised, double-blind, placebo-controlled, pragmatic, efficacy trial of inpatients aged 65 years and older and exposed to one or more oral or parenteral antibiotics. A computer-generated randomisation scheme was used to allocate participants (in a 1:1 ratio) to receive either a multistrain preparation of lactobacilli and bifidobacteria, with a total of 6 × 10(10) organisms, one per day for 21 days, or an identical placebo. Patients, study staff, and specimen and data analysts were masked to assignment. The primary outcomes were occurrence of AAD within 8 weeks and C difficile diarrhoea (CDD) within 12 weeks of recruitment. Analysis was by modified intention-to-treat. This trial is registered, number ISRCTN70017204., Findings: Of 17,420 patients screened, 1493 were randomly assigned to the microbial preparation group and 1488 to the placebo group. 1470 and 1471, respectively, were included in the analyses of the primary endpoints. AAD (including CDD) occurred in 159 (10·8%) participants in the microbial preparation group and 153 (10·4%) participants in the placebo group (relative risk [RR] 1·04; 95% CI 0·84-1·28; p=0·71). CDD was an uncommon cause of AAD and occurred in 12 (0·8%) participants in the microbial preparation group and 17 (1·2%) participants in the placebo group (RR 0·71; 95% CI 0·34-1·47; p=0·35). 578 (19·7%) participants had one or more serious adverse event; the frequency of serious adverse events was much the same in the two study groups and none was attributed to participation in the trial., Interpretation: We identified no evidence that a multistrain preparation of lactobacilli and bifidobacteria was effective in prevention of AAD or CDD. An improved understanding of the pathophysiology of AAD is needed to guide future studies., Funding: Health Technology Assessment programme; National Institute for Health Research, UK., (Copyright © 2013 Allen et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved.)

Clostridium difficile is currently considered a significant cause of nosocomial infection. The probability of a colonisation of hospitalised patients rises with the length of their stay in hospital and depends on the local epidemiologic situation. Interdisciplinary collaboration is the foundation of the effort to limit the development of this very serious, often fatal disease. The basic element is a rational antibiotic therapy which builds on the knowledge that the administration of antibiotics, even though based on a correct indication, may be fatal in an environment which is massively contaminated by spores of Clostridium difficile. Consequently, the high risk antibiotics (such as aminopenicillins, fluoroquinolones or cefalosporins) should be administered only in such cases where they cannot be substituted by antibiotics with a lower risk of CDI.

Objective: The incidence of hospital-acquired Clostridium difficile infection (CDI) has increased rapidly over the past decade; patients undergoing major surgery, including coronary artery bypass grafting (CABG), are at particular risk. Intravenous vancomycin exposure has been identified as an independent risk factor for CDI, but this is controversial. It is not known whether vancomycin administered for surgical site infection prophylaxis increases the risk of CDI., Methods: Using data from the Premier Perspective Comparative Database, we assembled a cohort of 69,807 patients undergoing CABG surgery between 2004 and 2010 who received either a cephalosporin alone (65.1%) or a cephalosporin plus vancomycin (34.9%) on the day of surgery. Patients were observed for CDI until discharge from the index hospitalization. In these groups, we evaluated the comparative rate of postoperative CDI with Cox models; confounding was addressed using propensity scores., Results: In all, 77 (0.32%) of the 24,393 patients receiving a cephalosporin plus vancomycin and 179 (0.39%) of the 45,414 patients receiving a cephalosporin alone had postoperative CDI (unadjusted hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.56-0.95). After adjusting for confounding variables with either propensity score matching or stratification, there was no meaningful association between adjuvant vancomycin exposure and postoperative CDI (HR, 0.85; 95% CI, 0.61-1.19; and HR, 0.85; 95% CI, 0.63-1.15, respectively). Results of multiple sensitivity analyses were similar to the main findings., Conclusions: After adjustment for patient and surgical characteristics, a short course of prophylactic vancomycin was not associated with an increased risk of CDI among patients undergoing CABG surgery., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: Clostridium difficile is the most common health care-associated infection and a major cause of death and increased morbidity. It is vital that patients and the public are provided with the right information and communication to assist them to understand their role in preventative measures. Successful implementation of communication and management strategies hinges on individuals' risk perceptions., Methods: We performed a structured literature review to examine the evidence regarding public and patients' risk perceptions and responses toward Clostridium difficile and other health care-associated infections. Fourteen studies were included., Results: Only 1 study was specific to Clostridium difficile, and 7 were related to other health care-associated infections. Many reported limited understanding of the technical issues of the infection, concerns of transmission to family and friends, inadequate information available, and distrust. The media were one of the main sources of information. Both emotional and physical responses highlighted the level of confusion, fear, anxiety, and anger., Conclusion: Empirical research of risk perceptions toward Clostridium difficile is limited. Without well-researched studies examining risk perceptions and responses, there is a danger of developing and implementing communication and management strategies that do not meet the needs of our patients or the public., (Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)