Efficacy Assessment of the Co-Administration of Vancomycin and Metronidazole in Clostridioides difficile-Infected Mice Based on Changes in Intestinal Ecology.

Vancomycin (VAN) and metronidazole (MTR) remain the current drugs of choice for the treatment of non-severe Clostridioides difficile infection (CDI); however, while their co-administration has appeared in clinical treatment, the efficacy varies greatly and the mechanism is unknown. In this study, a CDI mouse model was constructed to evaluate the therapeutic effects of VAN and MTR alone or in combination. For a perspective on the intestinal ecology, 16S rRNA amplicon sequencing and non-targeted metabolomics techniques were used to investigate changes in the fecal microbiota and metabolome of mice under the co-administration treatment. As a result, the survival rate of mice under co-administration was not dramatically different compared to that of single antibiotics, and the former caused intestinal tissue hyperplasia and edema. Co-administration also significantly enhanced the activity of amino acid metabolic pathways represented by phenylalanine, arginine, proline, and histidine, decreased the level of deoxycholic acid (DCA), and downregulated the abundance of beneficial microbes, such as Bifidobacterium and Akkermansia. VAN plays a dominant role in microbiota regulation in co-administration. In addition, co-administration reduced or increased the relative abundance of antibiotic-sensitive bacteria, including beneficial and harmful microbes, without a difference. Taken together, there are some risks associated with the co-administration of VAN and MTR, and this combination mode should be used with caution in CDI treatment.

Clostridioides difficile infection (CDI): A pan-European multi-center cost and resource utilization study, results from the Combatting Bacterial Resistance in Europe CDI (COMBACTE-CDI).

OBJECTIVES: Clostridioides difficile infection (CDI) is one of the leading nosocomial infections worldwide, resulting in a significantly increasing burden on the healthcare systems. However, Pan-European data about cost and resource utilization of CDI treatment do not exist. METHODS: A retrospective analysis within the Combatting Bacterial Resistance in Europe CDI project was conducted based on resource costs for inpatient treatment and productivity costs. Country-specific cost values were converted to EURO referred to 1 January, 2019 values. Differences in price levels for healthcare services among the participating countries were adjusted by using an international approach of the Organisation for Economic Co-operation and Development. As the study focused on patients with recurrent CDI, the observed study population was categorized into (a) patients with CDI but without CDI recurrence (case group), (b) patients with CDI recurrence (recurrence group), and (c) patients without CDI (control group). RESULTS: Overall, 430 hospitalized patients from 12 European countries were included into the analysis between July 2018 and November 2018. Distribution of mean hospital length of stay and mean overall costs per patient between the case group, recurrence group, and control group were as follows: 22 days (95% CI 17-27 days) vs. 55 days (95% CI 17-94 days) vs. 26 days (95% CI 22-31 days; p 0.008) and € 15 242 (95% CI 10 593-19 891) vs. € 52 024 (95% CI 715-103 334) vs. € 21 759 (95% CI 16 484-27 035; p 0.010), respectively. The CDI recurrence rate during the observational period was 18%. Change escalation in CDI medication (OR 3.735) and treatment in an intensive care unit (OR 5.454) were found to be the most important variables associated with increased overall costs of patients with CDI. CONCLUSIONS: Treatment of patients with recurrent CDI results in a significant burden. Prevention of CDI recurrences should be in focus of daily patient care to identify the most cost-effective treatment strategy.

Assessment of Immune Response and Efficacy of Essential Oils Application on Controlling Necrotic Enteritis Induced by Clostridium perfringens in Broiler Chickens.

Necrotic enteritis (NE) caused by Clostridium perfringens is one of the most important enteric diseases in poultry. The antibacterial activity of two different essential oil (EO) blends against C. perfringens was investigated both in vitro and in vivo. Additionally, the immunological response to EO treatment was assessed. In the in vitro study, the antibacterial activity of EO formulas and commonly used antibiotics was evaluated against C. perfringens using disk diffusion assay, minimum inhibitory concentration (MIC) assay, and minimum bactericidal concentration (MBC) assay. In the in vivo study, NE experimental infection was performed on 440 Ross broiler chicks at 19 days of age for 4 continuous days. The chicks were treated with either EOs or amoxicillin at 22 days of age for 5 continuous days. One day after the end of treatment, the birds' performance was evaluated by calculating the feed conversion ratio. Serum samples from 120 birds were collected to measure the levels of IL-1ß, IFN-γ, IL-8, IL-10, and IL-17. After that, all birds were slaughtered, and their small intestines were subjected to gross and histopathological evaluation. In addition, bacterial counts in the small intestines were evaluated. In the in vitro study, EOs showed higher antimicrobial activities in comparison with antibiotics against C. perfringens. In the in vivo study, birds treated with EOs showed a significant decrease in bacterial counts, a significant decrease in intestinal lesions, and a significant improvement in performance compared with untreated birds (p < 0.05). Moreover, treating birds with EOs directed the immune system toward an anti-inflammatory pathway. None of the treated birds died due to NE compared with the 10% mortality rate in untreated birds. In conclusion, EOs might be an effective and safe alternative to antibiotics in the treatment of chicken NE.

A cost of illness comparison for toxigenic Clostridioides difficile diagnosis algorithms in developing countries.

BACKGROUND: Availability of several commercial tests with different Clostridioides difficile targets contributes to uncertainty and controversies around the optimal diagnostic algorithm. While numerous studies have estimated the financial impact of C. difficile infection, models to guide testing strategies decisions in developing countries, where economic value significantly impacts clinical practice, are currently not available. AIM: To determine the cost of illness of different C. difficile infection (CDI) diagnostic strategies in developing countries. METHODS: Cost-comparison analysis was performed to compare eleven different algorithms of CDI diagnosis. The basis of calculation was a hypothetical cohort of 1000 adult inpatients suspected of CDI. We analyzed turnaround time of test results (i.e., time from taking sample to results emission), test performance (i.e., sensitivity and specificity) and testing costs. Patients were divided in true positive, false positive, true negative and false negative in order to integrate test performance and economics effects. Additional medical costs were calculated: costs of hygiene, medication, length of stay and intensive care unit costs, based on a Brazilian University Hospital costs. CDI prevalence was considered 22.64%. FINDINGS: From laboratory-assisted tests, simultaneous glutamate dehydrogenase (GDH) and toxin A/B rapid immunoassay arbitrated by nucleic acid amplification test (NAAT) presented the lowest cost of illness (450,038.70 USD), whereas standalone NAAT had the highest (523,709.55 USD). Empirical diagnosis only presented the highest overall cost (809,605.44 USD). CONCLUSION: The two-step algorithm with simultaneous GDH and toxin A/B rapid immunoassay arbitrated by NAAT seems to be the best strategy for CDI diagnosis in developing countries.

The prevalence of Clostridioides difficile on farms, in abattoirs and in retail foods in Ireland.

An increasing proportion of Clostridioides difficile infections (CDI) are community acquired. This study tested farm, abattoir and retail food samples for C. difficile, using peer reviewed culture and molecular methods. The contamination rate on beef, sheep and broiler farms ranged from 2/30 (7%) to 25/30 (83%) in faeces, soil and water samples, while concentrations ranged from 2.9 log10 cfu/ml to 8.4 log10 cfu/g. The prevalence and associated counts were much lower in abattoir samples. Although 26/60 were C. difficile positive by enrichment and PCR, only 6 samples yielded counts by direct plating (1.1 log10 cfu/cm2 to 5.1 log10 cfu/g). At retail, 9/240 samples were C. difficile positive, including corned beef (1), spinach leaves (2), iceberg lettuce, little gem lettuce, wild rocket, coleslaw, whole milk yogurt and cottage cheese (1 sample each), with counts of up to 6.8 log10 cfu/g. The tcdA, tcdB, cdtA, cdtB, tcdC and tcdR genes were detected in 41%, 99.2%, 33.6%, 32%, 46.7% and 31.1%, respectively, of the 122 C. difficile isolates obtained. It was concluded that although the prevalence of C. difficile decreased along the food chain, retail foods were still heavily contaminated. This pathogen may therefore be foodborne, perhaps necessitating dietary advice for potentially vulnerable patients.

Impacts of Microbial based Therapy on Growth Performance, Intestinal Health, Carcass Traits and Economic Efficiency of Clostridium perfringens-Infected Cobb and Arbor Acres Broilers.

The poultry farms need a safe and effective alternative for antibiotics that can counteract the negative impacts of necrotic enteritis (NE), which causes severe mortalities and economic losses. The current study was aimed to examine the influence of antibiotic (Flagymox) and the microbial-based administration on carcass traits in Clostridium (C.) perfringens-infected Cobb and Arbor Acres broilers. A total number of 360 Cobb and Arbor Acres broiler chicks (180 numbers per breed) were allocated to four groups; negative control group (without any treatments); positive control group (administration of C. perfringens at the rate of 1 × 109 cfu/bird via crop gavage twice daily from day 16 to 18 post-hatch); C. perfringens challenge plus antibiotic (Flagymox® ) group, and Clostridium perfringens challenge plus microbial-based treatment (Big-lactoα® ) group. The results indicated that the Flagymox and Big-lactoα treated Cobb breed group achieved a significant increase in their body weight (BW) than the positive control group at the third week post-infection. Also, the Arbor Acres breed gained significantly higher weight compared to the Cobb breed at the third week. Total weight gain (TWG) from 0 to the fifth week in the Cobb and Arbor Acres breeds were higher in the groups treated with Flagymox and Big-lactoα compared to the birds challenged with C. perfringens without any treatment, thus, increasing the total return (TR) in the treated groups. Economic efficiency showed no significant differences (p < .05) between the treatment groups of both the breeds. Although the treatment cost of Flagymox is higher than the microbial-based treatment (0.86 versus 0.35 LE), there were no mortalities reported in the microbial-based groups in both the breeds resulting in significantly low losses compared to the Flagymox treated groups. The groups treated with the microbial-based products in both breeds were superior in dressing percentage (75.16 and 77.06% for Cobb and Arbor Acres, respectively) compared to that of the other groups. In conclusion, microbial-based therapy improved the growth rate, carcass traits, survival rate, and economic efficiency in necrotic enteritis induced in Cobb and Arbor Acres broilers.

Neighborhood disadvantage and 30-day readmission risk following Clostridioides difficile infection hospitalization.

BACKGROUND: Clostridioides difficile infection (CDI) is commonly associated with outcomes like recurrence and readmission. The effect of social determinants of health, such as 'neighborhood' socioeconomic disadvantage, on a CDI patient's health outcomes is unclear. Living in a disadvantaged neighborhood could interfere with a CDI patient's ability to follow post-discharge care recommendations and the success probability of these recommendations, thereby increasing risk of readmission. We hypothesized that neighborhood disadvantage was associated with 30-day readmission risk in Medicare patients with CDI. METHODS: In this retrospective cohort study, odds of 30-day readmission for CDI patients are evaluated controlling for patient sociodemographics, comorbidities, and hospital and stay-level variables. The cohort was created from a random 20% national sample of Medicare patients during the first 11 months of 2014. RESULTS: From the cohort of 19,490 patients (39% male; 80% white; 83% 65 years or older), 22% were readmitted within 30 days of an index stay. Unadjusted analyses showed that patients from the most disadvantaged neighborhoods were readmitted at a higher rate than those from less disadvantaged neighborhoods (26% vs. 21% rate: unadjusted OR = 1.32 [1.20, 1.45]). This relationship held in adjusted analyses, in which residence in the most disadvantaged neighborhoods was associated with 16% increased odds of readmission (adjusted OR = 1.16 [1.04, 1.28]). CONCLUSIONS: Residence in disadvantaged neighborhoods poses a significantly increased risk of readmission in CDI patients. Further research should focus on in-depth assessments of this population to better understand the mechanisms underlying these risks and if these findings apply to other infectious diseases.

One Health approach to Clostridioides difficile in Japan.

Clostridioides difficile infections (CDIs) are predominantly a healthcare-associated illness in developed countries, with the majority of cases being elderly and hospitalize patients who used antibiotic therapy. Recently, the incidence of community-associated CDIs (CA-CDIs) in younger patients without a previous history of hospitalization or antibiotic treatment has been increasing globally. C. difficile is sometimes found in the intestine of many animals, such as pigs, calves, and dogs. Food products such as retail meat products and vegetables sometimes contain C. difficile. C. difficile has also been isolated from several environments such as compost manure, rivers, and soils. Yet, direct transmission of C. difficile from animals, food products, and environments to humans has not been proven, although these strains have similar molecular characteristics. Therefore, it has been suggested that there is a relationship between CA-CDIs and C. difficile from animals, food products, and the environment. To clarify the importance of the presence of C. difficile in several sources, characterization of C. difficile in these sources is required. However, the epidemiology of C. difficile in animals, food products, and the environment is not well studied in Japan. This review summarizes recent trends of CDIs and compares the molecular characteristics of C. difficile in Japanese animals, food products, and the environment. The prevalence trends of C. difficile in Japan are similar to those in the rest of the world. Therefore, I recommend using a One Health approach to CDI surveillance, monitoring, and control.

The molecular characters and antibiotic resistance of Clostridioides difficile from economic animals in China.

BACKGROUND: It has been performed worldwidely to explore the potential of animals that might be a reservoir for community associated human infections of Clostridioides difficile. Several genetically undistinguished PCR ribotypes of C. difficile from animals and human have been reported, illustrating potential transmission of C. difficile between them. Pig and calf were considered as the main origins of C. difficile with predominant RT078 and RT033, respectively. As more investigations involved, great diversity of molecular types from pig and calf were reported in Europe, North American and Australia. However, there were quite limited research on C. difficile isolates from meat animals in China, leading to non-comprehensive understanding of molecular epidemiology of C. difficile in China. RESULTS: A total of 55 C. difficile were isolated from 953 animal stool samples, within which 51 strains were from newborn dairy calf less than 7 days in Shandong Province. These isolates were divided into 3 STs and 6 RTs, of which ST11/RT126 was predominant type, and responsible for majority antibiotic resistance isolates. All the isolates were resistant to at least one tested antibiotics, however, only two multidrug resistant (MDR) isolates were identified. Furthermore, erythromycin (ERY) and clindamycin (CLI) were the two main resistant antibiotics. None of the isolates were resistant to vancomycin (VAN), metronidazole (MTZ), tetracycline (TET), and rifampin (RIF). CONCLUSIONS: In this study, we analyzed the prevalence, molecular characters and antibiotic resistance of C. difficile from calf, sheep, chicken, and pig in China. Some unique features were found here: first, RT126 not RT078 were the dominant type from baby calf, and none isolates were got from pig; second, on the whole, isolates from animals display relative lower resistant rate to these 11 tested antibiotics, compared with isolates from human in China in our previous report. Our study helps to deep understanding the situation of C. difficile from economic animals in China, and to further study the potential transmission of C. difficile between meat animals and human.

Incidence and economic burden of Clostridioides difficile infection in Ontario: a retrospective population-based study.

BACKGROUND: Understanding the impact of prevention programs on Clostridioides difficile infection rates is important, and decisions on future program changes, including how to use vaccines currently in development, requires a detailed understanding of the epidemiologic features of C. difficile infection. We analyzed Ontario health administrative data to determine incidence rates and medical costs of C. difficile infection, based on whether acquisition and onset occurred in acute care hospitals (ACHs), long-term care facilities or the community. METHODS: We performed a retrospective analysis using individual-level data from Ontario health databases from Apr. 1, 2005, to Mar. 31, 2015, identifying rates of C. difficile infection requiring hospital admission per 100 000 person-years in adults aged 18 years or more for categories of acquisition and onset. We estimated health care system costs of infection 180 and 365 days after admission by matching patients with C. difficile infection with control patients with similar characteristics. RESULTS: Over the study period, 33 909 people in Ontario were admitted to hospital with C. difficile infection; 17 272 cases (50.9%) were associated with ACHs. The number of cases per 100 000 person-years ranged from 27.7 in 2009/10 to 37.0 in 2012/13. Annually, the highest incidence of infection was for ACH-associated/ACH-onset. Community-associated infection became more prevalent over time, rising from 19.4% of cases in 2005/06 to 29.2% in 2014/15. Infection costs were mostly due to hospital admission within 180 days after hospital discharge. Infection associated with ACHs had the highest total costs and the largest cost attributable to C. difficile infection (median $38 953 for infected patients v. $13 542 for control patients). Median costs attributable to C. difficile infection were $1051 for that associated with long-term care facilities, $13 249 for community-associated infection and $11 917 for ACH-associated/community-onset infection. INTERPRETATION: Community-associated C. difficile infection had similar health care cost implications as hospital-associated infection. With rates of community-associated C. difficile infection on the rise, family physicians should be supported to prevent this infection in their patients.

Healthcare associated Clostridioides difficile infection in adult surgical and medical patients hospitalized in tertiary hospital in Belgrade, Serbia: a seven years prospective cohort study.

Introduction: Clostridioides difficile (C. difficile) infection (CDI) is one of the most common healthcare-associated (HA) infections in contemporary medicine. The risk factors (RFs) for HA CDI in medical and surgical patients are poorly investigated in countries with a limited resource healthcare system. Therefore, the aim of the study was to investigate differences in patients' characteristics, factors related to healthcare and outcomes associated with HA CDI in surgical and medical patients in tertiary healthcare centre in Serbia.Materials and Methods: A prospective cohort study was conducted including adult patients diagnosed with initial episode of HA CDI, first recurrence of disease, readmission to hospital, while deaths within 30 days of CDI diagnosis and in-hospital mortality were also recorded. Patients hospitalized for any non-surgical illness, who developed initial HA CDI were assigned to medical group, whereas those who developed initial HA CDI after surgical procedures were in surgical group. The data on patients' characteristics and factors related to healthcare were collected, too.Results: During 7-year period, from 553 patients undergoing in-hospital treatment and diagnosed with CDI, 268 (48.5%) and 285 (51.5%) were surgical and medical patients, respectively. Age ≥ 65 years, use of proton pump inhibitors, chemotherapy and fluoroquinolones were positively associated with being in medical group, whereas admission to intensive care unit and use of second- and third-generation cephalosporins were positively associated with being in surgical group.Conclusions: Based on obtained results, including significant differences in 30-day mortality and in-hospital mortality, it can be concluded that medical patient were more endangered with HA CDI than surgical ones.

Spatial clusters of Clostridium difficile infection and an association with neighbourhood socio-economic disadvantage in the Australian Capital Territory, 2004-2014.

BACKGROUND: In Australia, rates of Clostridium difficile infection (CDI) in all States and Territories have increased significantly since mid-2011, with rates of infection increasing faster in the community setting than within hospitals. Knowledge about the risk factors for CDI is essential to determine the risk of community outbreaks of CDI and to design interventions that reduce those risks. METHODS: We examine the role of neighbourhood socio-economic disadvantage, demography and testing practices on spatial patterns in CDI incidence in the Australian Capital Territory (ACT). Data on all tests conducted for CDI, including postcode of residence, were obtained from January 2004-December 2014. Distribution of age groups and the neighbourhood Index of Relative Socio-economic Advantage Disadvantage (IRSAD) were obtained from the Australian Bureau of Statistics 2011 National Census data. A Bayesian spatial conditional autoregressive model was fitted at the postcode level to quantify the relationship between CDI and socio-demographic factors. To identify CDI hotspots, exceedance probabilities were set at a threshold of twice the estimated relative risk. RESULTS: After controlling for spatial patterns in testing practices, area-level socio-economic advantage (IRSAD) (RR = 0.74, 95% CI 0.57, 0.94) was inversely associated with CDI. Three postcodes had a high probability (0.8-1.0) of excess risk of diagnosed CDI. CONCLUSION: We demonstrate geographic variations in CDI in the ACT with a positive association of CDI with neighbourhood socioeconomic disadvantage and identify areas with a high probability of elevated risk compared with surrounding communities. These findings provide further evidence to inform a targeted response to reduce CDI risk.

Burden of community-associated Clostridioides difficile infection in southeastern United States: a population-based study.

OBJECTIVES: This cross-sectional population-based study aims to determine overall incidence rate of Clostridioides difficile infection (CDI) in the State of South Carolina and provide an estimated cost of hospitalization due to community-associated CDI (CA-CDI). METHODS: All CDI cases in South Carolina were identified through National Healthcare Safety Network (NHSN) and the South Carolina Infectious Disease and Outbreak Network (SCION) from January 1, 2015 to June 30, 2016, excluding infants < 1 year of age. RESULTS: During the 18-month study period, 10,254 CDI events were identified in South Carolina residents with an overall incidence rate of 139/100,000 person-years. Over one-half of CDI cases were CA-CDI (5192; 51%) with an incidence rate of 71/100,000 person-years. Among patients with CA-CDI, 2127 (41%) required hospitalization with a median length of stay of 5 days. The annual burden of CA-CDI in South Carolina was estimated to be 9282 hospital days and $16,217,295 in hospitalization costs. CONCLUSION: The incidence rate of CA-CDI in South Carolina has surpassed both community-onset healthcare facility associated and hospital-onset CDI combined. The heavy burden of CA-CDI justifies dedication of public health resources to combat CDI in ambulatory settings, through antimicrobial stewardship initiatives.

Application of a new methodology and R package reveals a high burden of healthcare-associated infections (HAI) in Germany compared to the average in the European Union/European Economic Area, 2011 to 2012.

BackgroundHealthcare-associated infections (HAIs) pose a major challenge to health systems. Burden of disease estimations in disability-adjusted life years (DALYs) are useful for comparing and ranking HAIs.AimTo estimate the number of five common HAIs, their attributable number of deaths and burden for Germany.MethodsWe developed a new method and R package that builds on the approach used by the Burden of Communicable Diseases in Europe (BCoDE) project to estimate the burden of HAIs for individual countries. We used data on healthcare-associated Clostridioides difficile infection, healthcare-associated pneumonia, healthcare-associated primary bloodstream infection, healthcare-associated urinary tract infection and surgical-site infection, which were collected during the point prevalence survey of HAIs in European acute-care hospitals between 2011 and 2012.ResultsWe estimated 478,222 (95% uncertainty interval (UI): 421,350-537,787) cases for Germany, resulting in 16,245 (95% UI: 10,863-22,756) attributable deaths and 248,920 (95% UI: 178,693-336,239) DALYs. Despite the fact that Germany has a relatively low hospital prevalence of HAIs compared with the European Union/European Economic Area (EU/EEA) average, the burden of HAIs in Germany (308.2 DALYs/100,000 population; 95% UI: 221.2-416.3) was higher than the EU/EEA average (290.0 DALYs/100,000 population; 95% UI: 214.9-376.9). Our methodology is applicable to other countries in or outside of the EU/EEA. An R package is available from https://CRAN.R-project.org/package=BHAI.ConclusionThis is the first study to estimate the burden of HAIs in DALYs for Germany. The large number of hospital beds may be a contributing factor for a relatively high burden of HAIs in Germany. Further focus on infection prevention control, paired with reduction of avoidable hospital stays, is needed to reduce the burden of HAIs in Germany.

Clostridioides difficile on Ohio swine farms (2015): A comparison of swine and human environments and assessment of on-farm risk factors.

Swine are known reservoirs for Clostridioides difficile, formerly known as Clostridium difficile, and transmission from swine to human farm workers is strongly suggested by previous studies. This cross-sectional study evaluated the potential role of farm environmental surfaces, including those in worker breakrooms and swine housing areas, in the possible transmission of C. difficile from swine to farm workers. Environmental surfaces and piglet faeces at 13 Ohio swine farms were sampled in 2015. Typical culturing techniques were performed to isolate C. difficile from samples, and amplification of toxin genes (tcdA, tcdB and cdtB) and PCR-ribotyping were used to genetically characterize recovered isolates. In addition, sequencing of toxin regulatory gene, tcdC, was done to identify the length of identified deletions in some isolates. A survey collected farm-level management risk factor information. Clostridioides difficile was recovered from all farms, with 42% (188/445) of samples testing positive for C. difficile. Samples collected from all on-farm locations recovered C. difficile, including farrowing rooms (60%, 107/178), breakrooms (50%, 69/138) and nursery rooms (9%, 12/129). Three ribotypes recovered from both swine and human environments (078, 412 and 005) have been previously implicated in human disease. Samples taken from farrowing rooms and breakrooms were found to have greater odds of C. difficile recovery than those taken from nursery rooms (OR = 40.5, OR = 35.6, p < .001 respectively). Farms that weaned ≥23,500 pigs per year had lower odds of C. difficile recovery as compared to farms that weaned fewer pigs (OR = 0.4, p = .01) and weekly or more frequent cleaning of breakroom counters was associated with higher odds of C. difficile recovery (OR = 11.7, p < .001). This study provides important insights into the presence and characterization of C. difficile found in human environments on swine farms and highlights how these areas may be involved in transmission of C. difficile to swine farm workers and throughout the facility.

Developing an antimicrobial stewardship program across a rural health system: The Avera Health experience.

PURPOSE: The stages of development of a health system-wide antimicrobial stewardship program (ASP) using existing personnel and technology are described. SUMMARY: Small hospitals with limited resources may struggle to meet ASP requirements, particularly facilities without onsite infectious disease physicians and/or experienced infectious disease pharmacists. Strategies for ASP development employed by Avera Health, a 33-hospital health system in the Midwest, included identifying relevant drug utilization and resistance patterns, education and pathway development, and implementation of Web-based conferencing to provide pharmacists throughout the system with access to infectious disease expertise on a daily basis. These efforts resulted in an evolving single-system ASP that has leveraged existing resources to overcome some system barriers. Program outcomes to date include a reduction in the use of a targeted agent, improved pathogen susceptibility trends, and rates of hospital-associated Clostridium difficile infection below national benchmarks. CONCLUSION: The Avera Health ASP grew from a collaborative project targeting levofloxacin overuse and resistance among key bacteria to a formal, health system-wide ASP in a rural setting. This program used existing personnel to provide standardized processes, educational campaigns, and antimicrobial expertise through the use of technology. This ASP program may provide helpful examples of ASP strategies for other rural health systems with similar resources.

[Pharmaceutical system of fecal microbiota transplantation: Heterogeneous practices]. / Circuit pharmaceutique, transplantation de microbiote fécal : Des pratiques hétérogènes.

OBJECTIVE: To describe current pharmaceutical practice in French hospitals regarding fecal microbiota transplantation in terms of prescription, preparation and compounding, as well as local legislation. MATERIAL AND METHODS: A national survey was conducted at 28 French university hospital centers followed by the sending of a GoogleForm® questionnaire from June to August 2018 in the 16 respondent centers either performing or subcontracting fecal microbiota transplant. RESULTS: All hospitals performing or subcontracting fecal transplant (n=16,%57) report prescription indication of recurrent Clostridium difficile infection treatment, and 6 of them also as part of a clinical trial protocol. In hospitals performing fecal transplant themselves (n=11), the number of pre-donation consultations with donors varies from one (n=6) to two (n=5). Fecal sample is collected at the donor's home in 45% of cases. Route of administration for transplant is either naso-gastric administration (n=4), rectal (n=4) or both (n=5). Fecal samples for transplant are compounded either in the hospital pharmacy (n=73%) or in the laboratory (27%). Thawing methods include refrigeration between 2-8°C (50%), room temperature (25%) and water bath (25%). Billing system and reporting to health authorities are highly heterogeneous from one hospital to another. CONCLUSION: This survey shows significant pharmaceutical practice heterogeneity within French hospitals regarding fecal microbiota transplantation despite the existence of national and European recommendations.

Estimating the Attributable Disease Burden and Effects of Interhospital Patient Sharing on Clostridium difficile Infections.

OBJECTIVE: To estimate the burden of Clostridium difficile infections (CDIs) due to interfacility patient sharing at regional and hospital levels. DESIGN: Retrospective observational study. METHODS: We used data from the Healthcare Cost and Utilization Project California State Inpatient Database (2005-2011) to identify 26,878,498 admissions and 532,925 patient transfers. We constructed a weighted, directed network among the hospitals by defining an edge between 2 hospitals to be the monthly average number of patients discharged from one hospital and admitted to another on the same day. We then used a network autocorrelation model to study the effect of the patient sharing network on the monthly average number of CDI cases per hospital, and we estimated the proportion of CDI cases attributable to the network. RESULTS: We found that 13% (95% confidence interval [CI], 7.6%-18%) of CDI cases were due to diffusion through the patient-sharing network. The network autocorrelation parameter was estimated at 5.0 (95% CI, 3.0-6.9). An increase in the number of patients transferred into and/or an increased CDI rate at the hospitals from which those patients originated led to an increase in the number of CDIs in the receiving hospital. CONCLUSIONS: A minority but substantial burden of CDI infections are attributable to hospital transfers. A hospital's infection control may thus be nontrivially influenced by its neighboring hospitals. This work adds to the growing body of evidence that intervention strategies designed to minimize HAIs should be done at the regional rather than local level.