Including Clostridium Difficile Infection Research Articles

Current insights into microbiome-based therapy. Review

Current insights into microbiome-based therapy. Review

Antibiotics: the triumph of civilization and its other side

The synthesis of antibacterial drugs and their subsequent use in clinical practice contributed to saving a huge number of people’s lives in the global space. At the same time, they can cause significant harm, including Clostridium difficile infections, in the formation of antibiotic resistance and changes in the human microbiome, the consequences of which have yet to be assessed. Antibiotic management programs are becoming more and more commonplace in modern clinical practice, requiring extensive knowledge based on clinical, genomic and laboratory data. Increasing evidence suggests a role for antibiotics in the manifestation of allergic, inflammatory, metabolic, and functional diseases. On the other hand, there is more and more data on the role of antimicrobial drugs in cancer prevention and treatment of viral diseases.

Lactobacillus rhamnosus GG cell-free supernatant as a novel anti-cancer adjuvant

BackgroundGut microbiota modulation has been demonstrated to be effective in protecting patients against detrimental effects of anti-cancer therapies, as well as to improve the efficacy of certain anti-cancer treatments. Among the most characterized probiotics, Lactobacillus rhamnosus GG (LGG) is currently utilized in clinics to alleviate diarrhea, mucositis or intestinal damage which might be associated with several triggers, including Clostridium difficile infections, inflammatory gut diseases, antibiotic consumption, chemotherapy or radiation therapy. Here, we investigate whether LGG cell-free supernatant (LGG-SN) might exert anti-proliferative activity toward colon cancer and metastatic melanoma cells. Moreover, we assess the potential adjuvant effect of LGG-SN in combination with anti-cancer drugs.MethodsLGG-SN alone or in combination with either 5-Fuorouracil and Irinotecan was used to treat human colon and human melanoma cancer cell lines. Dimethylimidazol-diphenyl tetrazolium bromide assay was employed to detect cellular viability. Trypan blue staining, anti-cleaved caspase-3 and anti-total versus anti-cleaved PARP western blots, and annexin V/propidium iodide flow cytometry analyses were used to assess cell death. Flow cytometry measurement of cellular DNA content (with propidium iodide staining) together with qPCR analysis of cyclins expression were used to assess cell cycle.ResultsWe demonstrate that LGG-SN is able to selectively reduce the viability of cancer cells in a concentration-dependent way. While LGG-SN does not exert any anti-proliferative activity on control fibroblasts. In cancer cells, the reduction in viability is not associated with apoptosis induction, but with a mitotic arrest in the G2/M phase of cell cycle. Additionally, LGG-SN sensitizes cancer cells to both 5-Fluorouracil and Irinotecan, thereby showing a positive synergistic action.ConclusionOverall, our results suggest that LGG-SN may contain one or more bioactive molecules with anti-cancer activity which sensitize cancer cells to chemotherapeutic drugs. Thus, LGG could be proposed as an ideal candidate for ground-breaking integrated approaches to be employed in oncology, to reduce chemotherapy-related side effects and overcome resistance or relapse issues, thus ameliorating the therapeutic response in cancer patients.

Fecal microbiota transplantation in childhood: past, present, and future.

Fecal microbiota transplantation (FMT) has been well described in the treatment of pediatric diseases; however, the latest updates regarding its use in children are unclear and the concepts involved need to be revisited. We performed advanced searches in the MEDLINE, EMBASE, and Cochrane databases using the keywords "Fecal microbiota transplantation OR Fecal microbiota transfer" in the [Title/Abstract] to identify relevant articles published in English within the last five years. To identify additional studies, reference lists of review articles and included studies were manually searched. Retrieved manuscripts (case reports, reviews, and abstracts) were assessed by the authors. Among the articles, studies were based on the mechanism (n = 28), sample preparation (n = 9), delivery approaches (n = 23), safety (n = 26), and indications (n = 67), including Clostridium difficile infection (CDI) and recurrent C. difficile infection (rCDI; n = 21), non-alcoholic fatty liver disease (NAFLD; n = 10), irritable bowel syndrome (IBS; n = 5), inflammatory bowel disease (IBD; n = 15), diabetes (n = 5), functional constipation (FC; n = 4), and autism spectrum disorder (ASD; n = 7). Concepts of FMT in pediatric diseases have been updated with respect to underlying mechanisms, methodology, indications, and safety. Evidence-based clinical trials for the use of FMT in pediatric diseases should be introduced to resolve the challenges of dosage, duration, initiation, and the end point of treatment.

A Comprehensive Review on Amoxicilin and Clavulanic Acid as Potential Antibacterial Agent

Suspensions comprise finely divided medication particles (the suspensoid) spread uniformly in a vehicle with or without stabilisers and other ingredients. Conventional oral suspension is ready-to-use and does not require reconstitution. Dry syrup is more bioavailable than tablets and capsules because it dissolves in water outside the mouth and enters the GI tract. GIT absorbs suspension quickly: Amoxicillin and clavulanic acid have been used since the 1970s. Despite having the same half-life as amoxicillin, clavulanic acid is protein-bound and heat unstable. It causes gastrointestinal side effects, including Clostridium difficile infection, and restricts amoxicillin oral combination doses. Due to clavulanic acid's b-lactamase tendency, the first amoxicillineclavulanic acid ratio was 4:1; currently it's 2:1, 7:1, 14:1, and 16:1. Few ratio comparisons exist. Amoxicillineclavulanic acid is often used as empiric therapy for WHO's Priority Infectious Syndromes in adults and children, resulting in large consumption. Some of these syndromes may be handled with a delayed antibiotic prescription approach or amoxicillin alone.

Use of Proton Pump Inhibitors With Dexamethasone in Patients With COVID-19 Pneumonia: Contributions to Long-Term Polypharmacy.

Introduction Proton pump inhibitors have been used in conjunction with dexamethasone to treat patients with COVID-19. This is given prophylactically to anticipate possible complications while on steroids, including abdominal pain, gastric ulcers, or gastrointestinal bleeding. Proton pump inhibitors have complications, including Clostridium difficile infection, pneumonia, osteoporosis, and vitamin deficiency. The goal of the following project is to assess if there are any subjective and objective benefits to be treated with this regimen instead of dexamethasone on its own. Another inquiry that will be investigated is if this combination results in more patients being prescribed a proton pump inhibitor on discharge. Materials and methodsThe following is a retrospective study involving two groups, the first group taking the aforementioned regimen and the second group on dexamethasone only. Objective findings that will be compared include the change in hemoglobin, blood urea nitrogen, and creatinine levels from admission to discharge between the two groups. Subjective findings include complaints of abdominal pain and reported bloody bowel movements. Medication reconciliation on discharge will also be assessed to observe if patients were discharged with a proton pump inhibitor and how long were they taking this medication as an outpatient. ResultsThe difference between hemoglobin, blood urea nitrogen, and creatinine between the two groups was not significant as the p-values were .14, .43. and .10, respectively. Therefore, the null hypothesis was accepted that there was no difference in these objective findings between the two populations. In addition, neither set had complaints of abdominal pain. For the investigated population on a proton pump inhibitor, it was found that 53% of these patients were discharged with this medication. This subset was on this medication for an average of three months, with the maximum duration being seven months for one patient. The data supported the hypothesis that there was no subjective or objective benefit to being on this drug combination, and consequentially, most patients continue to take this medication for months after discharge. ConclusionThe data affirms the hypothesis that most patients can tolerate dexamethasone without the need for a proton pump inhibitor. This study was limited to patients without any history of gastritis, peptic ulcer disease, or gastrointestinal bleeding; a separate study would need to be done to investigate the need for prophylaxis for patients with these comorbidities. The concerning finding was that patients are being discharged with a medication that they do not need, some patients are taking proton pump inhibitors for more than half the year. There should be further screening to determine if a patient needs to be on a proton pump inhibitor other than steroids.

Rabeprazole

Rabeprazole is a proton pump inhibitor that suppresses gastric acid production in the stomach. Available under different brand name products as well as in a variety of combination products, rabeprazole has several medical uses concerning the management of problems of pathological gastric acid. Rabeprazole's adverse effects tend to be mild but can be serious, including deficiencies in essential nutrients, rare incidences of liver damage, and immune-mediated reactions. As a class effect, rabeprazole can increase the risk for osteoporosis, serious infections (including Clostridium difficile infections), and kidney damage. Rabeprazole can theoretically contribute to numerous drug interactions, mediated both through its metabolic properties and its direct effect on acid in the stomach, though its potential for clinically meaningful drug interactions is low. Like other medications in the proton pump inhibitor class, rabeprazole's mechanism of action involves the irreversible inhibition of proton pumps in the stomach, which are responsible for gastric acid production. Rabeprazole has a number of chemical metabolites, though it is primarily degraded by non-enzymatic metabolism and excreted in the urine. Genetic differences in a person's drug-metabolizing enzymes may theoretically affect individual responses to rabeprazole therapy, though the clinical significance of this interaction is unlikely in comparison to other proton pump inhibitors. The purpose of this review is to provide an up-to-date monograph on rabeprazole.

Effect of lactobacillus casei shirota in preventing antibiotic associated diarrhoea including clostridium difficile infection in patients with spinal cord injuries: a multicentre randomised, double-blinded, placebo-controlled trial

Rationale: Antibiotic associated diarrhoea (AAD) and Clostridium difficile infection (CDI) are of major clinical concern in spinal cord injury (SCI) rehabilitation. Neurogenic bladder dysfunction as a result of SCI often leads to enhanced risk of urinary tract infections.1 Use of invasive devices such as urinary catheters further increases the need for antibiotics and the risks of AAD and CDI.2 A previous open-labelled study found that SCI patient taking a probiotic containing at least 6.5x109 live Lactobacillus casei Shirota (LcS) could prevent AAD.3 In order to confirm this effects and fully demonstrate the extent of LcS effectiveness in preventing AAD/CDI, a double-blinded, placebo-controlled study is indicated.

Faecal microbiota transplantation and the patient experience: A systematic review.

To review and synthesise the literature examining the patients' experience of faecal microbiota transplantation. Faecal microbiota transplantation is a common treatment for many conditions, including Clostridium Difficile infections. Patients' experience of treatments is an important influence on clinical decision-making and treatment adherence. The PRISMA guidelines guided this systematic review. The review was registered with PROSPERO [CRD42020140446]. A search of Cumulative Index of Nursing and Allied Health Literature, Medline and Embase was conducted for studies published in English and French up to June 2020. Risk of bias was examined using Critical Appraisal Skills Program tools, and quality appraisal was performed independently by three reviewers. Primary outcome of interest was the patient experience of faecal microbiota transplantation. Data were synthesised using a narrative approach. The search identified 3316 citations, and 12 studies were included. Methodological quality of studies was moderate to low quality. Few studies have accurately explored the patients' experience of faecal microbiota transplantation: most focus on clinical outcomes or hypothetical scenarios regarding the patients' perspectives of faecal microbiota transplantation. Only one study was identified where the sole focus was the patients' experience of faecal microbiota transplantation. Patient's experience of faecal microbiota transplantation was diverse and complex with physiological and psychological components dependent on the patient's medical condition, the administration method and the efficacy. Patients did not find faecal microbiota transplantation unappealing; however, patients equally reported the procedural experience was unpleasant. Limited results and low quality evidence suggest that further evaluation of the patient experience of faecal microbiota transplantation would be beneficial. Identifying the patients' experience of faecal microbiota transplantation may inform recommendations regarding alternate treatment therapies and enable opportunities to provide quality care for patients that require faecal microbiota transplantation.

Gastrointestinal Complications After Cardiac Surgery: Highly Morbid but Improving Over Time

BackgroundGastrointestinal complications after cardiac surgery are associated with high morbidity and mortality. We sought to determine the granular impact of individual gastrointestinal complications after cardiac surgery and assess contemporary outcomes. Materials and methodsPatients undergoing cardiac surgery from 2010 to 2017 (6070 patients) were identified from an institutional Society of Thoracic Surgeons database. Records were paired with institutional data assessing gastrointestinal complications and cost. Patients were stratified by early (2010-2013) and current (2014-2017) eras. ResultsA total of 280 (4.6%) patients experienced gastrointestinal complications including Clostridiumdifficile infection (94, 33.6%), gastrointestinal bleed (86, 30.7%), hepatic failure (66, 23.6%), prolonged ileus (59, 21.1%), mesenteric ischemia (47, 16.8%), acute cholecystitis (17, 6.0%), and pancreatitis (14, 5.0%). Gastrointestinal complications were associated with higher rates of early postoperative major morbidity [206 (73.6%) versus 773 (13.4%), P < 0.0001], mortality [78 (27.9%) versus 161 (2.8%), P < 0.0001], length of stay (23 versus 6 d, P < 0.0001), and discharge to a facility [115 (41.1%) versus 1395 (24.1%), P < 0.0001]. Patients suffering gastrointestinal complications had worse risk-adjusted long-term survival (hazard ratio: 3.0, P < 0.0001) and higher adjusted cost ($9,173, P = 0.05). Between eras, there was no difference in incidence of gastrointestinal complications [139 (4.4%) versus 141 (4.8%), P = 0.51] or rate of specific complications (all P > 0.05). However, long-term survival increased in modern era (P < 0.0001). ConclusionsAlthough incidence of gastrointestinal complications after cardiac surgery has not changed over time, long-term survival has improved. Gastrointestinal complications remain associated with high resource utilization and major morbidity, but patients are now more likely to recover, highlighting the benefit of quality improvement efforts.

Comparative risk of Clostridium difficile infection between proton pump inhibitors and histamine-2 receptor antagonists: A 15-year hospital cohort study using a common data model.

There are potential concerns regarding infectious complications including Clostridium difficile infections (CDIs) among patients taking gastric acid suppressants. Furthermore, it is speculated that the stronger acid suppression by proton pump inhibitors (PPIs) potentially enhance infectious complications. This study aimed to compare the risk of CDI between PPIs and histamine-2 receptor antagonists (H2RAs). Using the long-term database of the Kangdong Sacred Heart Hospital, converted to the Observational Medical Outcomes Partnership Common Data Model, we identified outpatients treated with PPIs and H2RAs for ≥7days from January 1, 2004 through December 31, 2018. We conducted Cox regression analysis to examine the hazard ratio (HR) of CDI after propensity score matching. During a median follow-up period of 1.2years (interquartile range, 0.2-3.2years), the initial CDI occurrence differed significantly between matched cohorts of patients taking PPIs and H2RAs [PPIs vs H2RAs, 88/31095 person years vs 47/32836 person years; HR, 2.22; 95% confidence interval (CI) 1.29-3.96; P=0.005]. Almost 50% of all events occurred within 1year of drug exposure. The risk of CDIs was significantly greater among groups receiving PPIs or H2RAs than in matched controls (PPIs vs control: HR, 2.65; 95% CI 1.28-5.79; P=0.011; and H2RAs vs control: HR 2.43; 95% CI 1.09-5.68; P=0.034]. In long-term hospital cohort, outpatient-based PPIs were associated with greater risk of CDI than H2RAs. It is necessary to be cautioned about complication of CDI in patients taking long-term PPI therapy.

Effects of diverse materials-based methods on DNA extraction for Clostridium difficle from stool samples

Nosocomial infections, including Clostridium difficile infection (CDI), and their fatality rates have increased in the past few decades. Despite emerging molecular diagnostic technologies with rapid, accurate outcomes, nucleic acid extraction from stool samples remains the first limiting step before downstream applications. Commercial nucleic acid extraction kits greatly decrease labor and time requirements, and also provide nucleic acid preparations with higher quality and purity for enzyme digestion analysis or genotyping. The magnetic bead based technique is a novel method compared with the conventional spin-column method, and currently has widespread use in nucleic acid extraction. We evaluated five DNA extraction kits with magnetic beads using materials with various properties (particle size, concentration of magnetic beads, grinding beads) and reagents (proteinase K, lysozyme, isopropanol, and absolute ethanol) to determine the cost, hands-on time, number of essential operations, and quality and purity of the DNA preparations, compared with those obtained using the QIAamp Fast DNA Stool Mini Kit. The six DNA extraction kits yielded A260/280 ratios ranging from 0.85 to 1.9 (average 1.57), and concentrations from 3.70 to 108.09 ng/μL (average 34.64 ng/μL). All the DNA samples had acceptable downstream application effects, except for those obtained using the TIANGEN Magnetic Soil and Stool DNA Kit. However, gel electrophoresis analysis of the DNA samples resulted in a light strip on the gel, indicating that the proteinaceous contaminant may not have been removed completely. A rapid and accurate molecular diagnostic technique could allow for more suitable treatment and prognosis outcomes for inpatients, depending, in large part, on the quality and purity of DNA preparations, which are frequently neglected. Our study focused on the quality of commercial kits with a primary focus on the treatment of stool samples and molecular diagnostic applications.

Antimicrobial Stewardship: Analysis of Provider Management of Drug-Bug Mismatch in Multi-Drug Resistant Organisms in a Large Medical Group

BACKGROUND The Centers for Disease Control and Prevention (CDC) estimates that 50% of antibiotics used in the outpatient setting are ordered inappropriately. Inappropriate antibiotics can lead to adverse patient outcomes, including clostridium difficile infection and antibiotic-resistant organisms. The purpose of this study is to review inappropriate antibiotic selection, drug-bug mismatch, in a large medical group. METHODS In a large multi-specialty medical group, encompassing 450 sites of care, multi-drug resistant organisms (MDROs) were identified by the microbiology department. Culture results included all MDROs identified from June 1 to August 31, 2018. The infection prevention department, upon receipt of the MDRO surveillance data, reviewed the electronic health record (EHR) for potential drug-bug mismatch. Providers were given 24 hours to address the drug-bug mismatch before infection prevention intervention. RESULTS A total of 179 MRDO cases were reviewed. 47 of the cases (26%) had a drug-bug mismatch. In 41 out of the 47 cases (87%), the provider recognized the drug-bug mismatch before the 24 hour timeframe and changed to effective antimicrobial therapy. 6 out of the 47 cases (13%) required infection prevention intervention. Of the 47 drug-bug mismatches identified, 30 (64%) were Methicillin-resistant Staphylococcus aureus (MRSA) in various wound cultures. 17 (36%) were Escherichia coli or Klebsiella pneumoniae Extended Spectrum Beta-Lactamases (ESBL) producing organisms. CONCLUSIONS This review identifies that providers in a large medical group most often manage drug-bug mismatches appropriately. This model of infection prevention intervention identifies 6 patients (13%) that benefited from early identification of inappropriate antimicrobial selection. The Centers for Disease Control and Prevention (CDC) estimates that 50% of antibiotics used in the outpatient setting are ordered inappropriately. Inappropriate antibiotics can lead to adverse patient outcomes, including clostridium difficile infection and antibiotic-resistant organisms. The purpose of this study is to review inappropriate antibiotic selection, drug-bug mismatch, in a large medical group. In a large multi-specialty medical group, encompassing 450 sites of care, multi-drug resistant organisms (MDROs) were identified by the microbiology department. Culture results included all MDROs identified from June 1 to August 31, 2018. The infection prevention department, upon receipt of the MDRO surveillance data, reviewed the electronic health record (EHR) for potential drug-bug mismatch. Providers were given 24 hours to address the drug-bug mismatch before infection prevention intervention. A total of 179 MRDO cases were reviewed. 47 of the cases (26%) had a drug-bug mismatch. In 41 out of the 47 cases (87%), the provider recognized the drug-bug mismatch before the 24 hour timeframe and changed to effective antimicrobial therapy. 6 out of the 47 cases (13%) required infection prevention intervention. Of the 47 drug-bug mismatches identified, 30 (64%) were Methicillin-resistant Staphylococcus aureus (MRSA) in various wound cultures. 17 (36%) were Escherichia coli or Klebsiella pneumoniae Extended Spectrum Beta-Lactamases (ESBL) producing organisms. This review identifies that providers in a large medical group most often manage drug-bug mismatches appropriately. This model of infection prevention intervention identifies 6 patients (13%) that benefited from early identification of inappropriate antimicrobial selection.

614. Modeling Changes in Gastrointestinal and Respiratory Tract Bacterial Community Diversity Attributable to Common Antibiotic Exposures During Long-Term Acute Care

BackgroundReduced gastrointestinal tract bacterial community diversity has been associated with increased risk for healthcare-associated infections, including Clostridium difficile infection. We sought to develop a model for concomitant change in bacterial community diversity at gastrointestinal and respiratory tract sites, drawing upon a recently completed cohort study of 92 subjects recruited from a long-term acute care hospital (LTACH) for dense longitudinal oral, endotracheal aspirate (ET), and stool specimen collection.MethodsWe evaluated the first 30 subjects enrolled from the LTACH cohort, for whom complete antibiotic administration data and 16S rRNA gene (V1–V2 amplicon) sequencing data were available. Sequencing was performed via the Illumina HiSeq platform; operational taxonomic units (OTUs) were formed and taxonomy assigned (GreenGenes 13.8) via the QIIME 1.9.1 pipeline. Generalized linear mixed effects models were fit using R (3.5.0), Stan (2.1.7), via the “rstan” and “rethinking” packages.ResultsWe evaluated 472 subject-days of study enrollment across the 30 subjects (median 15 days/subject). ET specimens were available for all subject-days; oral and stool for 357 and 177 subject-days, respectively. We modeled daily change in Shannon diversity across oral, ET, and stool specimens, parameterized with daily exposure to cefepime, piperacillin–tazobactam, meropenem, IV vancomycin, and oral vancomycin. All parameters fit with Rhat value lower than 1.1. Absent antibiotic exposure on the previous day, the daily change in Shannon diversity at all sites was near zero. The largest observed effect was oral vancomycin on stool (daily delta Shannon: −0.6, 95% CI: −1.38 to 0.09). All estimated effects for intravenous antibiotics on the stool, and for all antibiotics at other sites were smaller.ConclusionSmall daily changes in bacterial community diversity were attributable to individual antibiotics, but all 95% certainty intervals crossed zero in this pilot study. Further work will focus on modeling specific taxonomic changes attributable to individual antibiotics and antibiotic interactions.Disclosures All authors: No reported disclosures.

Antibiotic Use in Hand Surgery: Surgeon Decision Making and Adherence to Available Evidence.

Background: There are no clearly defined guidelines from hand surgical societies regarding preoperative antibiotic prophylaxis. Many hand surgeons continue to routinely use preoperative prophylaxis with limited supporting evidence. This study aimed to determine for which scenarios surgeons give antibiotics, the reasons for administration, and whether these decisions are evidence-based. Methods: An anonymous 25-question survey was e-mailed to the 921-member American Society for Surgery of the Hand listserv. We collected demographic information; participants were asked whether they would administer antibiotics in a number of surgical scenarios and for what reasons. Respondents were broken into 3 groups based on when they said they would administer antibiotics: Group 1 (40 respondents) would give antibiotics in the case of short cases, healthy patients, without hardware; group 2 (9 respondents) would not give antibiotics in any scenario; and group 3 (129 respondents) would give antibiotics situationally. The Fisher exact test compared demographic variables, frequency of use, and indications of antibiotic prophylaxis. Results: Of the 921 recipients, 178 (19%) responded. Demographic variables did not correlate with the antibiotic use group. Operative case time >60 minutes, medical comorbidity, and pinning each increased antibiotic use. Group 1 respondents were more likely to admit that their practice was not evidence-based (74.4%) and that they gave antibiotics for medical-legal concern (75%). Twenty-two percent of respondents reported seeing a complication from routine prophylaxis, including Clostridium difficile infection. Conclusions: Antibiotics are still given unnecessarily before hand surgery, most often for medical-legal concern. Clear guidelines for preoperative antibiotic use may help reduce excessive and potentially inappropriate treatment and provide medical-legal support.

Standardized Preparation for Fecal Microbiota Transplantation in Pigs.

The intestine of pigs harbors a mass of microorganisms which are essential for intestinal homeostasis and host health. Intestinal microbial disorders induce enteric inflammation and metabolic dysfunction, thereby causing adverse effects on the growth and health of pigs. In the human medicine, fecal microbiota transplantation (FMT), which engrafts the fecal microbiota from a healthy donor into a patient recipient, has shown efficacy in intestinal microbiota restoration. In addition, it has been used widely in therapy for human gastrointestinal diseases, including Clostridium difficile infection, inflammatory bowel diseases, and irritable bowel syndrome. Given that pigs share many similarities with humans, in terms of anatomy, nutritional physiology, and intestinal microbial compositions, FMT may also be used to restore the normal intestinal microbiota of pigs. However, feasible procedures for performing FMT in pigs remains unclear. Here, we summarize a standardized preparation for FMT in pigs by combining the standard methodology for human FMT with pig production. The key issues include the donor selection, fecal material preparation, fecal material transfer, stool bank establishment, and the safety for porcine FMT. Optimal donors should be selected to ensure the efficacy of porcine FMT and reduce the risks of transmitting infectious diseases to recipients during FMT. Preparing for fresh fecal material is highly recommended. Alternatively, frozen fecal suspension can also be prepared as an optimal choice because it is convenient and has similar efficacy. Oral administration of fecal suspension could be an optimal method for porcine fecal material transfer. Furthermore, the dilution ratio of fecal materials and the frequency of fecal material transfer could be adjusted according to practical situations in the pig industry. To meet the potential large-scale requirement in the pig industry, it is important to establish a stool bank to make porcine FMT readily available. Future studies should also focus on providing more robust safety data on FMT to improve the safety and tolerability of the recipient pigs. This standardized preparation for porcine FMT can facilitate the development of microbial targeted therapies and improve the intestinal health of pigs.

Opportunities for Antimicrobial Stewardship in Skilled Nursing Facilities

Overuse of antibiotics in the inpatient, outpatient, and skilled nursing facility (SNF) settings has accelerated the emergence of resistant bacteria. Multidrug resistant organisms (MDROs) are becoming common, with over 35% of SNF residents colonized or infected with MDROs in some studies. The emergence of antimicrobial stewardship programs (ASPs) in acute care hospitals has led to decreased antibiotic resistance, improved patient outcomes, reduced adverse events (including Clostridium difficile infections), and lower costs. In September 2016, the Centers for Medicare and Medicaid Services finalized a rule requiring ASPs in every SNF.

The influence of long-term use of proton pump inhibitors on the gut microbiota: an age-sex-matched case-control study.

Proton pump inhibitors (PPIs) are widely used to treat gastro-esophageal reflux and prevent gastric ulcers, and have been considered as low risk. However, recent studies have identified possible associations between PPI use and gut microbiota, suggesting that PPIs use increases the risk of enteric infections, including Clostridium difficile infection. To investigate gut microbiota in Japanese PPIs users, we conducted 16S metagenomics analysis of fecal samples collected from PPI users and healthy adults. In total, 36 PPI users and 36 PPI non-users (as control subjects) matched by age and sex were recruited and fecal samples were obtained to analyze the gut microbiome using 16S rRNA gene sequencing. There were significant differences in the microbial structure between PPI non-users and PPI users. In contrast, the analysis of α-diversity revealed no significant differences between PPI non-users and PPI users. When comparing in genus level between these two groups, the genera Streptococcus was significantly abundant and the genera Faecalibacterium was significantly decreased in PPI users. Our findings indicate a probable association between PPI use and the alternation of microbiota. These alterations might provide a mechanism by which PPIs predispose enteric infection such as Clostridium difficile infection.

Fecal Microbiota Transplantation: Therapeutic Potential for a Multitude of Diseases beyond Clostridium difficile.

The human intestinal tract contains trillions of bacteria, collectively called the gut microbiota. Recent insights have linked the gut microbiota to a plethora of diseases, including Clostridium difficile infection (CDI), inflammatory bowel disease (IBD), and metabolic diseases such as obesity, type 2 diabetes (T2D), and nonalcoholic steatohepatitis (NASH). Fecal microbiota transplantation (FMT) is currently tested as a therapeutic option in various diseases and can also help to dissect association from causality with respect to gut microbiota and disease. In CDI, FMT has been shown to be superior to antibiotic treatment. For IBD, T2D, and NASH, several placebo-controlled randomized controlled trials are under way. Moreover, techniques and standardization are developing. With the extension of FMT as a treatment modality in diseases other than CDI, a whole new treatment option may be emerging. Moreover, correlating alterations in specific strains to disease outcome may prove pivotal in finding new bacterial targets. Thus, although causality of the gut microbiota in various diseases still needs to be proven, FMT may prove to be a powerful tool providing us with diagnostic and therapeutic leads.

Effect of a Health Care System Respiratory Fluoroquinolone Restriction Program To Alter Utilization and Impact Rates of Clostridium difficile Infection.

Fluoroquinolones are one of the most commonly prescribed antibiotic classes in the United States despite their association with adverse consequences, including Clostridium difficile infection (CDI). We sought to evaluate the impact of a health care system antimicrobial stewardship-initiated respiratory fluoroquinolone restriction program on utilization, appropriateness of quinolone-based therapy based on institutional guidelines, and CDI rates. After implementation, respiratory fluoroquinolone utilization decreased from a monthly mean and standard deviation (SD) of 41.0 (SD = 4.4) days of therapy (DOT) per 1,000 patient days (PD) preintervention to 21.5 (SD = 6.4) DOT/1,000 PD and 4.8 (SD = 3.6) DOT/1,000 PD posteducation and postrestriction, respectively. Using segmented regression analysis, both education (14.5 DOT/1,000 PD per month decrease; P = 0.023) and restriction (24.5 DOT/1,000 PD per month decrease; P < 0.0001) were associated with decreased utilization. In addition, the CDI rates decreased significantly (P = 0.044) from preintervention using education (3.43 cases/10,000 PD) and restriction (2.2 cases/10,000 PD). Mean monthly CDI cases/10,000 PD decreased from 4.0 (SD = 2.1) preintervention to 2.2 (SD = 1.35) postrestriction. A significant increase in appropriate respiratory fluoroquinolone use occurred postrestriction versus preintervention in patients administered at least one dose (74/130 [57%] versus 74/232 [32%]; P < 0.001), as well as in those receiving two or more doses (47/65 [72%] versus 67/191 [35%]; P < 0.001). A significant reduction in the annual acquisition cost of moxifloxacin, the formulary respiratory fluoroquinolone, was observed postrestriction compared to preintervention within the health care system ($123,882 versus $12,273; P = 0.002). Implementation of a stewardship-initiated respiratory fluoroquinolone restriction program can increase appropriate use while reducing overall utilization, acquisition cost, and CDI rates within a health care system.