A pilot study in Serbia by European Clostridium difficile Infection Surveillance Network.

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, Uzice, 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 Uzice 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.

Clinical and Microbiological Characteristics of Clostridium difficile Infection Among Hospitalized Children in the Netherlands.

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.

Survey of diagnostic and typing capacity for Clostridium difficile infection in Europe, 2011 and 2014.

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.

Standardised surveillance of Clostridium difficile infection in European acute care hospitals: a pilot study, 2013.

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.

Hospital-based Clostridium difficile infection surveillance reveals high proportions of PCR ribotypes 027 and 176 in different areas of Poland, 2011 to 2013.

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.

Microbiota-associated risk factors for asymptomatic gut colonisation with multi-drug-resistant organisms in a Dutch nursing home.

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.

Ribotype 078 Clostridium difficile infection incidence in Dutch hospitals is not associated with provincial pig farming: Results from a national sentinel surveillance, 2009-2015.

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.