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Background: Nursing home residents have increased rates of intestinal colonisation with multidrug-resistant organisms (MDROs). We assessed the colonisation and spread of MDROs among this population, determined clinical risk factors for MDRO colonisation and investigated the role of the gut microbiota in providing colonisation resistance against MDROs., Methods: We conducted a prospective cohort study in a Dutch nursing home. Demographical, epidemiological and clinical data were collected at four time points with 2-month intervals (October 2016-April 2017). To obtain longitudinal data, faecal samples from residents were collected for at least two time points. Ultimately, twenty-seven residents were included in the study and 93 faecal samples were analysed, of which 27 (29.0%) were MDRO-positive. Twelve residents (44.4%) were colonised with an MDRO at at least one time point throughout the 6-month study., Results: Univariable generalised estimating equation logistic regression indicated that antibiotic use in the previous 2 months and hospital admittance in the previous year were associated with MDRO colonisation. Characterisation of MDRO isolates through whole-genome sequencing revealed Escherichia coli sequence type (ST)131 to be the most prevalent MDRO and ward-specific clusters of E. coli ST131 were identified. Microbiota analysis by 16S rRNA gene amplicon sequencing revealed no differences in alpha or beta diversity between MDRO-positive and negative samples, nor between residents who were ever or never colonised. Three bacterial taxa (Dorea, Atopobiaceae and Lachnospiraceae ND3007 group) were more abundant in residents never colonised with an MDRO throughout the 6-month study. An unexpectedly high abundance of Bifidobacterium was observed in several residents. Further investigation of a subset of samples with metagenomics showed that various Bifidobacterium species were highly abundant, of which B. longum strains remained identical within residents over time, but were different between residents., Conclusions: Our study provides new evidence for the role of the gut microbiota in colonisation resistance against MDROs in the elderly living in a nursing home setting. Dorea, Atopobiaceae and Lachnospiraceae ND3007 group may be associated with protection against MDRO colonisation. Furthermore, we report a uniquely high abundance of several Bifidobacterium species in multiple residents and excluded the possibility that this was due to probiotic supplementation.

Clostridium (Clostridioides) difficile infections (CDIs) are among the most frequent healthcare-associated infections in Serbia. In 2013, Serbia participated in the European Clostridium difficile Infection Surveillance Network (ECDIS-Net) who launched a pilot study to enhance laboratory capacity and standardize surveillance for CDI. Two clinics of Clinical Center of Serbia [Clinic for Infectious and Tropical Diseases (CITD) and Clinic of Orthopedic Surgery and Traumatology (COT)] from Belgrade and one general hospital from another metropolitan area of Serbia, Užice, participated. During a period of 3 months in 2013, all patients with diagnosed CDI were included. The CDI incidence rates in CITD, COT, and General Hospital Užice were 19.0, 12.2, and 3.9 per 10,000 patient-days, respectively. In total, 49 patients were enrolled in the study with average age of 72 years. A complicated course of CDI was found in 14.3% of all patients. Six (12.2%) of 49 patients died, but not attributable to CDI. Of 39 C. difficile isolates, available for ribotyping, 78.9% belonged to ribotype 027; other PCR ribotypes were 001, 015, 002, 005, 010, 014, and 276. Antimicrobial susceptibility testing revealed low levels of MIC50 and MIC90 for metronidazole (0.5 μg/ml both) and vancomycin (0.25 and 0.5 μg/ml), while 28 strains of ribotype 027 were resistant to moxifloxacin with MIC ≥4 μg/ml. National surveillance is important to obtain more insight in the epidemiology of CDI and to compare the results with other European countries. This study by ECDIS-Net gives bases for a national surveillance of CDI in Serbia.

A prevalence study in two nursing homes (one each in the Netherlands and Ireland) found four (11%) Dutch and six (9%) Irish residents colonized with 11 extended-spectrum beta-lactamase-producing Escherichia coli, 10 of which contained CTX-M-15. Four Dutch isolates, from three residents of the same ward, belonged to E. coli O25:H4, sequence type (ST) 131 and were part of the same cluster type by whole-genome sequencing. Four Irish residents on three different wards were colonized with an identical E. coli O89:H9, ST131, complex type 1478. Cross-transmission between three Irish wards may reflect differences in nursing home infrastructure, specifically communal areas and multi-bedded resident rooms., (Copyright © 2019 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Objectives: Clostridium difficile infections (CDI) account for 1.5% of diarrhoeic episodes in patients attending a general practitioner in the Netherlands, but its sources are unknown. We searched for community clusters to recognize localized point sources of CDI., Methods: Between October 2010 and February 2012, a community-based prospective nested case-control study was performed in three laboratories in the Netherlands with a study population of 2 810 830 people. Bernoulli spatial scan and space-time permutation models were used to detect spatial and/or temporal clusters of CDI. In addition, a multivariate conditional logistic regression model was constructed to test livestock exposure as a supposed risk factor in CDI patients without hospital admission within the previous 12 weeks (community-acquired (CA) CDI)., Results: In laboratories A, B and C, 1.3%, 1.8% and 2.1% of patients with diarrhoea tested positive for CDI, respectively. The mean age of CA-CDI patients (n = 124) was 49 years (standard deviation, 22.6); 64.5% were female. No spatial or temporal clusters of CDI cases were detected compared to C. difficile-negative diarrhoeic controls. Except for one false-positive signal, no spatiotemporal interaction amongst CDI cases was found. Livestock exposure was not related to CA-CDI (odds ratio, 0.99; 95% confidence interval, 0.44-2.24). Ten percent of CA-CDIs was caused by PCR ribotype 078, spatially dispersed throughout the study area., Conclusions: The absence of clusters of CDI cases in a community cohort of diarrhoeic patients suggests a lack of localized point sources of CDI in the living environment of these patients., (Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: To investigate an unusual outbreak of five patients with a total of eight episodes of a Clostridium difficile infection on a gastrointestinal surgical ward of a Dutch tertiary-care, university-affiliated hospital., Methods: Clinical case investigations and laboratory analyses were performed. Laboratory analyses included PCR ribotyping, multiple-locus variable-number tandem repeat analysis typing, toxin typing, antimicrobial susceptibility testing and whole genome sequencing., Results: The outbreak was associated with recurrent and severe disease in two of five patients. All episodes were due to a unique ribotype that was not recognized in the collection of an international network of reference laboratories and was assigned PCR ribotype 826. PCR ribotype 826 is a toxin A-, toxin B- and binary toxin-positive ribotype which according to molecular typing belongs to clade 5 and resembles the so-called hypervirulent ribotype 078. The presence of a clonal outbreak was confirmed by whole genome sequencing, yet the source of this newly identified ribotype remained unclear., Conclusions: This newly identified C. difficile PCR ribotype 826 is part of clade 5 and might also have increased virulence. The recognition of this outbreak highlights the need for ongoing C. difficile infection surveillance to monitor new circulating ribotypes with assumed increased virulence., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: It has been suggested that the high incidence of ribotype 078 Clostridium difficile infections (CDI) in the Netherlands is related to pig farming., Methods: We used data of hospitalised CDI patients (>2yrs of age) diagnosed between May 2009 and May 2015 in 26 hospitals participating in a national sentinel surveillance. We compared clinical and geographical characteristics of 078 CDI to other CDI. We investigated the association between 078 CDI incidence and four indicators of pig farming (piglet, pig, piglet farm and pig farm density) by mixed-effects Poisson regression. We used a space-time permutation model to search for community-onset 078 CDI clusters (using SaTScan)., Results: A total of 4,691 CDI were identified. Ribotype 078 was isolated in 493 of 3,756 patients (13.1%) including a typing result. These patients had slightly higher community-onset disease and a 35% increase of 30-day mortality compared to non-078 CDI patients. The pooled overall and 078 incidence rates were 2.82 (95% CI, 2.42-3.29) and 0.26 (95% CI, 0.21-0.31) CDI per 10,000 patients-days respectively. Hospital 078 CDI incidence was not associated with provincial pig (IRR, 0.98; 95% CI, 0.89-1.08), piglet (IRR, 0.95; 95% CI, 0.75-1.19), pig farm (IRR, 1.08; 95% CI, 0.84-1.39), or piglet farm density (IRR, 1.00; 95% CI, 0.56-1.79). No clusters of community-onset ribotype 078 CDI were found., Conclusions: Our results do not indicate that the ribotype 078 CDI incidence in hospitals is related to pig (farm) or piglet (farm) density. However, transmission beyond provincial borders or in non-hospitalised patients cannot be excluded.

In 2011-2012, a survey was performed in three regional hospitals in the Czech Republic to determine the incidence of Clostridium difficile infections (CDIs) and to characterize bacterial isolates. C. difficile isolates were characterized by PCR ribotyping, toxin genes detection, multiple-locus variable-number tandem-repeat analysis (MLVA), and antimicrobial susceptibility testing to fidaxomicin, vancomycin, metronidazole, clindamycin, LFF571, and moxifloxacin using agar dilution method. The incidence of CDI in three studied hospitals was 145, 146, and 24 cases per 100,000 inhabitants in 2011 and 177, 258, and 67 cases per 100,000 inhabitants in 2012. A total of 64 isolates of C. difficile was available for molecular typing and antimicrobial susceptibility testing. 60.9% of the isolates were classified as ribotype 176. All 41 isolates of ribotypes 176 and 078 were positive for the presence of binary toxin genes. Ribotype 176 also carried 18-bp deletion in the regulatory gene tcdC. Tested isolates of C. difficile were fully susceptible to vancomycin and metronidazole, whereas 65.1% of the isolates were resistant to moxifloxacin. MLVA results indicated that isolates from three different hospitals were genetically related, suggesting transmission between healthcare facilities.

Background: Little is known about pediatric Clostridium difficile infection (CDI) epidemiology. We describe the clinical and microbiological characteristics of CDI among hospitalized children in the Netherlands., Methods: Between May 2009 and May 2015, 26 hospitals registered characteristics of pediatric (aged 2-18 years) and adult (aged 18 years) CDI in a national sentinel surveillance study. Routine polymerase chain reaction (PCR) ribotyping and multiple-locus variable-number tandem-repeat analysis (MLVA) of selected strains was performed. Pediatric and adult results were compared using proportion and 95% confidence interval (CI). Time trend of pediatric CDI was evaluated using a mixed-effect Poisson model., Results: Pediatric CDIs were reported in 17 of the 26 participating hospitals (n = 135; 3% of all CDIs); the monthly number was constant over time. The median age of pediatric cases was 10 years (interquartile range, 4.7-14.5 years). Fifty-five percent of the children had community onset and 31% had severe CDI. Compared with adults (n = 4,556), complication and mortality rates were lower. Clostridium difficile PCR ribotype 265 (toxin A negative, B positive) was most prevalent in children (15%; 95% CI, 8.8%-24.0%) but rarely found in adults (1%; 95% CI, 0.9%-1.6%). This strain was rarely found in other countries, except for Belgium. MLVA showed genetic relatedness between three-fourths of pediatric and adult ribotype 265 strains, without a clear epidemiological link., Conclusions: Pediatric CDI in hospitals has remained stable over the last 6 years and resulted in fewer complications than for adult CDI. Further studies are needed to elucidate the source and epidemiology of PCR ribotype 265, primarily found in children., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Clostridium difficile infection (CDI) remains poorly controlled in many European countries, of which several have not yet implemented national CDI surveillance. In 2013, experts from the European CDI Surveillance Network project and from the European Centre for Disease Prevention and Control developed a protocol with three options of CDI surveillance for acute care hospitals: a 'minimal' option (aggregated hospital data), a 'light' option (including patient data for CDI cases) and an 'enhanced' option (including microbiological data on the first 10 CDI episodes per hospital). A total of 37 hospitals in 14 European countries tested these options for a three-month period (between 13 May and 1 November 2013). All 37 hospitals successfully completed the minimal surveillance option (for 1,152 patients). Clinical data were submitted for 94% (1,078/1,152) of the patients in the light option; information on CDI origin and outcome was complete for 94% (1,016/1,078) and 98% (294/300) of the patients in the light and enhanced options, respectively. The workload of the options was 1.1, 2.0 and 3.0 person-days per 10,000 hospital discharges, respectively. Enhanced surveillance was tested and was successful in 32 of the hospitals, showing that C. difficile PCR ribotype 027 was predominant (30% (79/267)). This study showed that standardised multicountry surveillance, with the option of integrating clinical and molecular data, is a feasible strategy for monitoring CDI in Europe., (This article is copyright of The Authors, 2016.)

Suboptimal laboratory diagnostics for Clostridium difficile infection (CDI) impedes its surveillance and control across Europe. We evaluated changes in local laboratory CDI diagnostics and changes in national diagnostic and typing capacity for CDI during the European C. difficile Infection Surveillance Network (ECDIS-Net) project, through cross-sectional surveys in 33 European countries in 2011 and 2014. In 2011, 126 (61%) of a convenience sample of 206 laboratories in 31 countries completed a survey on local diagnostics. In 2014, 84 (67%) of these 126 laboratories in 26 countries completed a follow-up survey. Among laboratories that participated in both surveys, use of CDI diagnostics deemed 'optimal' or 'acceptable' increased from 19% to 46% and from 10% to 15%, respectively (p  < 0.001). The survey of national capacity was completed by national coordinators of 31 and 32 countries in 2011 and 2014, respectively. Capacity for any C. difficile typing method increased from 22/31 countries in 2011 to 26/32 countries in 2014; for PCR ribotyping from 20/31 countries to 23/32 countries, and specifically for capillary PCR ribotyping from 7/31 countries to 16/32 countries. While our study indicates improved diagnostic capability and national capacity for capillary PCR ribotyping across European laboratories between 2011 and 2014, increased use of 'optimal' diagnostics should be promoted., (This article is copyright of The Authors, 2016.)

As part of the European Clostridium difficile infections (CDI) surveillance Network (ECDIS-Net), which aims to build capacity for CDI surveillance in Europe, we constructed a new network of hospital-based laboratories in Poland. We performed a survey in 13 randomly selected hospital-laboratories in different sites of the country to determine their annual CDI incidence rates from 2011 to 2013. Information on C. difficile laboratory diagnostic testing and indications for testing was also collected. Moreover, for 2012 and 2013 respectively, participating hospital-laboratories sent all consecutive isolates from CDI patients between February and March to the Anaerobe Laboratory in Warsaw for further molecular characterisation, including the detection of toxin-encoding genes and polymerase chain reaction (PCR)-ribotyping. Within the network, the mean annual hospital CDI incidence rates were 6.1, 8.6 and 9.6 CDI per 10,000 patient-days in 2011, 2012, and 2013 respectively. Six of the 13 laboratories tested specimens only on the request of a physician, five tested samples of antibiotic-associated diarrhoea or samples from patients who developed diarrhoea more than two days after admission (nosocomial diarrhoea), while two tested all submitted diarrhoeal faecal samples. Most laboratories (9/13) used tests to detect glutamate dehydrogenase and toxin A/B either separately or in combination. In the two periods of molecular surveillance, a total of 166 strains were characterised. Of these, 159 were toxigenic and the majority belonged to two PCR-ribotypes: 027 (n=99; 62%) and the closely related ribotype 176 (n=22; 14%). The annual frequency of PCR-ribotype 027 was not significantly different during the surveillance periods (62.9% in 2012; 61.8% in 2013). Our results indicate that CDIs caused by PCR-ribotype 027 predominate in Polish hospitals participating in the surveillance, with the closely related 176 ribotype being the second most common agent of infection.

Farm animals are a potential reservoir for human Clostridium difficile infection (CDI), particularly PCR ribotype 078 which is frequently found in animals and humans. Here, whole genome single-nucleotide polymorphism (SNP) analysis was used to study the evolutionary relatedness of C. difficile 078 isolated from humans and animals on Dutch pig farms. All sequenced genomes were surveyed for potential antimicrobial resistance determinants and linked to an antimicrobial resistance phenotype. We sequenced the whole genome of 65 C. difficile 078 isolates collected between 2002 and 2011 from pigs (n = 19), asymptomatic farmers (n = 15) and hospitalised patients (n = 31) in the Netherlands. The collection included 12 pairs of human and pig isolates from 2011 collected at 12 different pig farms. A mutation rate of 1.1 SNPs per genome per year was determined for C. difficile 078. Importantly, we demonstrate that farmers and pigs were colonised with identical (no SNP differences) and nearly identical (less than two SNP differences) C. difficile clones. Identical tetracycline and streptomycin resistance determinants were present in human and animal C. difficile 078 isolates. Our observation that farmers and pigs share identical C. difficile strains suggests transmission between these populations, although we cannot exclude the possibility of transmission from a common environmental source.