Sentinel surveillance and epidemiology of Clostridioides difficile in Denmark, 2016 to 2019.

BackgroundSince 2008, Danish national surveillance of Clostridioides difficile has focused on binary toxin-positive strains in order to monitor epidemic types such as PCR ribotype (RT) 027 and 078. Additional surveillance is needed to provide a more unbiased representation of all strains from the clinical reservoir.AimSetting up a new sentinel surveillance scheme for an improved understanding of type distribution relative to time, geography and epidemiology, here presenting data from 2016 to 2019.MethodsFor 2─4 weeks in spring and autumn each year between 2016 and 2019, all 10 Danish Departments of Clinical Microbiology collected faecal samples containing toxigenic C. difficile. Isolates were typed at the national reference laboratory at Statens Serum Institut. The typing method in 2016-17 used tandem-repeat-sequence typing, while the typing method in 2018-19 was whole genome sequencing.ResultsDuring the study period, the sentinel surveillance scheme included ca 14-15% of all Danish cases of C. difficile infections. Binary toxin-negative strains accounted for 75% and 16 of the 20 most prevalent types. The most common sequence types (ST) were ST2/13 (RT014/020) (19.5%), ST1 (RT027) (10.8%), ST11 (RT078) (6.7%), ST8 (RT002) (6.6%) and ST6 (RT005/117) (5.1%). The data also highlighted geographical differences, mostly related to ST1 and temporal decline of ST1 (p = 0.0008) and the increase of ST103 (p = 0.002), ST17 (p = 0.004) and ST37 (p = 0.003), the latter three binary toxin-negative.ConclusionSentinel surveillance allowed nationwide monitoring of geographical differences and temporal changes in C. difficile infections in Denmark, including emerging types, regardless of binary toxin status.

Electronic reporting of diagnostic laboratory test results from all healthcare sectors is a cornerstone of national preparedness and control of COVID-19 in Denmark.

The COVID-19 pandemic has led to an unprecedented demand for real-time surveillance data in order to inform critical decision makers regarding the management of the pandemic. The aim of this review was to describe how the Danish national microbiology database, MiBa, served as a cornerstone for providing data to the real-time surveillance system by linkage to other nationwide health registries. The surveillance system was established on an existing IT health infrastructure and a close network between clinical microbiologists, information technology experts, and public health officials. In 2020, testing capacity for SARS-CoV-2 was ramped up from none to over 10,000 weekly PCR tests per 100,000 population. The crude incidence data mirrored this increase in testing. Real-time access to denominator data and patient registries enabled adjustments for fluctuations testing activity, providing robust data on crude SARS-CoV-2 incidence during the changing diagnostic and management strategies. The use of the same data for different purposes, for example, final laboratory reports, information to the public, contact tracing, public health, and science, has been a critical asset for the pandemic response. It has also raised issues concerning data protection and critical capacity of the underlying technical systems and key resources. However, even with these limitations, the setup has enabled decision makers to adopt timely interventions. The experiences from COVID-19 may motivate a transformation from traditional indicator-based public health surveillance to an all-encompassing information system based on access to a comprehensive set of data sources, including diagnostic and reference microbiology.

Extended-spectrum ß-lactamase-producing Escherichia coli in human-derived and foodchain-derived samples from England, Wales, and Scotland: an epidemiological surveillance and typing study.

BACKGROUND: Extended-spectrum ß-lactamase-producing Escherichia coli isolates (ESBL-E coli) cause more than 5000 cases of bacteraemias annually in the UK. The contribution of the food chain to these infections is debated. We aimed to identify the most important reservoirs of ESBL-E coli that colonise and infect humans to identify strategic intervention points. METHODS: Sampling for ESBL-E coli was done between Aug 1, 2013, and Dec 15, 2014. We used selective media to seek ESBL-E coli in routinely submitted samples from human faeces, and prospectively collected samples from sewage, farm slurry, and retail foodstuffs in London, East Anglia, northwest England, Scotland, and Wales. We sequenced recovered isolates and compared these isolates with 293 bloodstream and 83 veterinary surveillance ESBL-E coli isolates from the same regions. FINDINGS: 2157 (11%) of 20 243 human faeces samples contained ESBL-E coli, including 678 (17%) of 3995 in London. ESBL-E coli also were frequent in sewage and retail chicken (104 [65%] of 159 meat samples), but were rare in other meats and absent from plant-based foods (0 of 400 fruit and vegetable samples). Sequence type (ST) 131 dominated among ESBL-E coli from human blood (188 [64%] of 293 isolates), faeces (128 [36%] of 360), and sewage (14 [22%] of 65) with STs 38 and 648 also widespread; CTX-M-15 was the predominant ESBL in these lineages (319 [77%] of 416). By contrast, STs 602, 23, and 117-mostly with CTX-M-1 ESBL-dominated among food and veterinary isolates (68 [31%] of 218), with only two ST131 organisms recovered. ST10 occurred in both animals and humans, being frequent in surveillance bovines (11 [22%] of 51 cattle) and representing 15 (4%) of 360 human faecal isolates (but only three [1%] of 293 from bacteraemias); however, both human and animal ST10 isolates were diverse in serotype. INTERPRETATION: Most human bacteraemias with ESBL-E coli in the UK involve internationally prevalent human-associated STs, particularly ST131; non-human reservoirs made little contribution to invasive human disease. Any interventions that seek to target food or livestock can affect the numbers of human infections caused by ESBL-E coli; prevention of the spread of resistant lineages among humans is more vital. FUNDING: NIHR Policy Research.

Global burden of Clostridium difficile infections: a systematic review and meta-analysis.

BACKGROUND: Clostridium difficile is a leading cause of morbidity and mortality in several countries. However, there are limited evidence characterizing its role as a global public health problem. We conducted a systematic review to provide a comprehensive overview of C. difficile infections (CDI) rates. METHODS: Seven databases were searched (January 2016) to identify studies and surveillance reports published between 2005 and 2015 reporting CDI incidence rates. CDI incidence rates for health care facility-associated (HCF), hospital onset-health care facility-associated, medical or general intensive care unit (ICU), internal medicine (IM), long-term care facility (LTCF), and community-associated (CA) were extracted and standardized. Meta-analysis was conducted using a random effects model. RESULTS: 229 publications, with data from 41 countries, were included. The overall rate of HCF-CDI was 2.24 (95% confidence interval CI = 1.66-3.03) per 1000 admissions/y and 3.54 (95%CI = 3.19-3.92) per 10 000 patient-days/y. Estimated rates for CDI with onset in ICU or IM wards were 11.08 (95%CI = 7.19-17.08) and 10.80 (95%CI = 3.15-37.06) per 1000 admission/y, respectively. Rates for CA-CDI were lower: 0.55 (95%CI = 0.13-2.37) per 1000 admissions/y. CDI rates were generally higher in North America and among the elderly but similar rates were identified in other regions and age groups. CONCLUSIONS: Our review highlights the widespread burden of disease of C. difficile, evidence gaps, and the need for sustainable surveillance of CDI in the health care setting and the community.

OXA-1 ß-lactamase and non-susceptibility to penicillin/ß-lactamase inhibitor combinations among ESBL-producing Escherichia coli.

Background: ESBL-producing Escherichia coli have expanded globally since the turn of the century and present a major public health issue. Their in vitro susceptibility to penicillin/inhibitor combinations is variable, and clinical use of these combinations against ESBL producers remains controversial. We hypothesized that this variability related to co-production of OXA-1 penicillinase. Methods: During a national study we collected 293 ESBL-producing E. coli from bacteraemias, determined MICs by BSAC agar dilution, and undertook genomic sequencing with Illumina methodology. Results: The collection was dominated by ST131 (n = 188 isolates, 64.2%) and blaCTX-M-15 (present in 229 isolates, 78.2%); over half the isolates (159/293, 54.3%) were ST131 with blaCTX-M-15. blaOXA-1 was found in 149 ESBL producers (50.9%) and blaTEM-1/191 in 137 (46.8%). Irrespective of whether all isolates were considered, or ST131 alone, there were strong associations (P < 0.001) between co-carriage of blaOXA-1 and reduced susceptibility to penicillin/inhibitor combinations, whereas there was no significant association with co-carriage of blaTEM-1/191. For piperacillin/tazobactam the modal MIC rose from 2 mg/L in the absence of blaOXA-1 to 8 or 16 mg/L in its presence; for co-amoxiclav the shift was smaller, from 4 or 8 to 16 mg/L, but crossed the breakpoint. blaOXA-1 was strongly associated with co-carriage also of aac(6')-Ib-cr, which compromises amikacin and tobramycin. Conclusions: Co-carriage of OXA-1, a penicillinase with weak affinity for inhibitors, is a major correlate of resistance to piperacillin/tazobactam and co-amoxiclav in E. coli and is commonly associated with co-carriage of aac(6')-Ib-cr, which narrows aminoglycoside options.

The Need for European Surveillance of CDI.

Since the turn of the millennium, the epidemiology of Clostridium difficile infection (CDI) has continued to challenge. Over the last decade there has been a growing awareness that improvements to surveillance are needed. The increasing rate of CDI and emergence of ribotype 027 precipitated the implementation of mandatory national surveillance of CDI in the UK. Changes in clinical presentation, severity of disease, descriptions of new risk factors and the occurrence of outbreaks all emphasised the importance of early diagnosis and surveillance.However a lack of consensus on case definitions, clinical guidelines and optimal laboratory diagnostics across Europe has lead to the underestimation of CDI and impeded comparison between countries. These inconsistencies have prevented the true burden of disease from being appreciated.Acceptance that a multi-country surveillance programme and optimised diagnostic strategies are required not only to detect and control CDI in Europe, but for a better understanding of the epidemiology, has built the foundations for a more robust, unified surveillance. The concerted efforts of the European Centre for Disease Prevention and Control (ECDC) CDI networks, has lead to the development of an over-arching long-term CDI surveillance strategy for 2014-2020. Fulfilment of the ECDC priorities and targets will no doubt be challenging and will require significant investment however the hope is that both a national and Europe-wide picture of CDI will finally be realised.

Risk factors for resistance and MDR in community urine isolates: population-level analysis using the NHS Scotland Infection Intelligence Platform.

BACKGROUND: Urinary tract infections (UTIs) are common. Antibiotic treatment is usually empirical, with the risk of under-treatment of resistant infections. OBJECTIVES: To characterize risk factors for antibiotic-resistant community urine isolates using routine record-linked health data. METHODS: Within the NHS Scotland Infection Intelligence Platform, national surveillance patient-level data on community urine isolates (January 2012-June 2015) were linked to hospital activity and community prescribing data. Associations between age, gender, comorbidity, care home residence, previous hospitalizations, antibiotic exposure and resistant (any antibiotic) or MDR (≥1 antibiotic from ≥3 categories) urinary isolates were quantified using multivariable logistic regression. RESULTS: Of 40984 isolates, 28% were susceptible, 45% were resistant and 27% were MDR. Exposure to ≥ 4 different antibiotics in the prior 6 months increased MDR risk (OR 6.81, 95% CI 5.73-8.11). MDR was associated with ≥29 DDD cumulative exposure, in the prior 6 months, for any antibiotic (OR 6.54, 95% CI 5.88-7.27), nitrofurantoin (OR 8.56, 95% CI 6.56-11.18) and trimethoprim (OR 14.61, 95% CI 10.53-20.27). Associations persisted for 10-12 months for nitrofurantoin (OR 2.31, 95% CI 1.93-2.76) and trimethoprim (OR 1.81, 95% CI 1.57-2.09). Increasing age, comorbidity, previous hospitalization and care home residence were independently associated with MDR. For resistant isolates the factors were the same, but with weaker associations. CONCLUSIONS: To our knowledge, we have demonstrated, using national capability at scale, the risk of MDR in community urine isolates for the first time and quantified the cumulative and sustained impact of antibiotic exposure. These data will inform the development of decision support tools for UTI treatment.

Cumulative and temporal associations between antimicrobial prescribing and community-associated Clostridium difficile infection: population-based case-control study using administrative data.

Background: Community-associated Clostridium difficile infection (CA-CDI; defined as cases without prior hospitalization in the previous 12 weeks who were either tested outside of hospital or tested within 2 days of admission to hospital) is a major public health problem. This study estimates the magnitude of the association between temporal and cumulative prescribing of antimicrobials in primary care and CA-CDI. Methods: Three national patient-level datasets, covering CDI cases, community prescriptions and hospitalizations, were linked by the NHS Scotland unique patient identifier, the Community Health Index (CHI). All validated cases of CDI from August 2010 to July 2013 were extracted and up to six population-based controls were matched to each case from the CHI register for Scotland. Statistical analysis used conditional logistic regression. Results: The 1446 unique cases of CA-CDI were linked with 7964 age-, sex- and location-matched controls. Cumulative exposure to any antimicrobial in the previous 6 months has a monotonic dose-response association with CA-CDI. Individuals with more than 28 DDDs to any antimicrobial (19.9% of cases) had an OR of 4.4 (95% CI 3.4-5.6) compared with those unexposed. Individuals exposed to 29+ DDDs of high-risk antimicrobials (cephalosporins, clindamycin, co-amoxiclav or fluoroquinolones) had an OR of 17.9 (95% CI 7.6-42.2). Elevated CA-CDI risk following high-risk antimicrobial exposure was greatest in the first month (OR = 12.5, 95% CI 8.9-17.4), but was still present 4-6 months later (OR = 2.6, 95% CI 1.7-3.9). Cases exposed to 29+ DDDs had prescription patterns more consistent with repeated therapeutic courses, using different antimicrobials, than long-term prophylactic use. Conclusions: This analysis demonstrated temporal and dose-response associations between CA-CDI risk and antimicrobials, with an impact of exposure to high-risk antimicrobials remaining 4-6 months later.

Carbapenemase-producing Enterobacteriaceae in the UK: a national study (EuSCAPE-UK) on prevalence, incidence, laboratory detection methods and infection control measures.

OBJECTIVES: To estimate UK prevalence and incidence of clinically significant carbapenemase-producing Enterobacteriaceae (CPE), and to determine epidemiological characteristics, laboratory methods and infection prevention and control (IPC) measures in acute care facilities. METHODS: A 6 month survey was undertaken in November 2013-April 2014 in 21 sentinel UK laboratories as part of the European Survey on Carbapenemase-Producing Enterobacteriaceae (EuSCAPE) project. Up to 10 consecutive, non-duplicate, clinically significant and carbapenem-non-susceptible isolates of Escherichia coli or Klebsiella pneumoniae were submitted to a reference laboratory. Participants answered a questionnaire on relevant laboratory methods and IPC measures. RESULTS: Of 102 isolates submitted, 89 (87%) were non-susceptible to ≥1 carbapenem, and 32 (36%) were confirmed as CPE. CPE were resistant to most antibiotics, except colistin (94% susceptible), gentamicin (63%), tigecycline (56%) and amikacin (53%). The prevalence of CPE was 0.02% (95% CI = 0.01%-0.03%). The incidence of CPE was 0.007 per 1000 patient-days (95% CI = 0.005-0.010), with north-west England the most affected region at 0.033 per 1000 patient-days (95% CI = 0.012-0.072). Recommended IPC measures were not universally followed, notably screening high-risk patients on admission (applied by 86%), using a CPE 'flag' on patients' records (70%) and alerting neighbouring hospitals when transferring affected patients (only 30%). Most sites (86%) had a laboratory protocol for CPE screening, most frequently using chromogenic agar (52%) or MacConkey/CLED agars with carbapenem discs (38%). CONCLUSIONS: The UK prevalence and incidence of clinically significant CPE is currently low, but these MDR bacteria affect most UK regions. Improved IPC measures, vigilance and monitoring are required.

Infection prevention and control of Clostridium difficile: a global review of guidelines, strategies, and recommendations.

BACKGROUND: Clostridium difficile is the leading cause of health care-associated infections. Given the high incidence of C. difficile infection (CDI) and the lack of primary prevention through immunization, health care professionals should be aware of the most current guidance, as well as strengths and limitations of the evidence base underpinning this guidance. METHODS: We identified publicly available national or organizational guidelines related to CDI infection and prevention control (IPC) published between 2000 and 2015 and for any health care setting through an internet search using the Google search engine. We reviewed CDI-targeted IPC recommendations and describe the assessment of evidence in available guidelines. RESULTS: We identified documents from 28 countries/territories, mainly from acute care hospitals in North America, the Western Pacific, and Europe (18 countries). We identified only a few specific recommendations for long-term care facilities (LTCFs) and from countries in South America (Uruguay and Chile), South East Asia (Thailand), and none for Africa or Eastern Mediterranean. Of 10 IPC areas, antimicrobial stewardship was universally recognized as essential and supported by high quality evidence. Five other widely reported "strong" recommendations were: effective environment cleaning (including medical equipment), case isolation, use of personal protective equipment, surveillance, and education. Several unresolved and emerging issues were documented and currently available evidence was classified mainly as of mixed quality. CONCLUSION: Our review underlines the need for targeted CDI IPC guidelines in several countries and for LTCFs. International harmonisation on the assessment of the evidence for best practices is needed as well as more robust evidence to support targeted recommendations.

Survey of Clostridium difficile infection surveillance systems in Europe, 2011.

To develop a European surveillance protocol for Clostridium difficile infection (CDI), existing national CDI surveillance systems were assessed in 2011. A web-based electronic form was provided for all national coordinators of the European CDI Surveillance Network (ECDIS-Net). Of 35 national coordinators approached, 33 from 31 European countries replied. Surveillance of CDI was in place in 14 of the 31 countries, comprising 18 different nationwide systems. Three of 14 countries with CDI surveillance used public health notification of cases as the route of reporting, and in another three, reporting was limited to public health notification of cases of severe CDI. The CDI definitions published by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the European Centre for Disease Prevention and Control (ECDC) were widely used, but there were differing definitions to distinguish between community- and healthcare-associated cases. All CDI surveillance systems except one reported annual national CDI rates (calculated as number of cases per patient-days). Only four surveillance systems regularly integrated microbiological data (typing and susceptibility testing results). Surveillance methods varied considerably between countries, which emphasises the need for a harmonised European protocol to allow consistent monitoring of the CDI epidemiology at European level. The results of this survey were used to develop a harmonised EU-wide hospital-based CDI surveillance protocol.

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.

KPC enzymes in the UK: an analysis of the first 160 cases outside the North-West region.

OBJECTIVES: Klebsiella pneumoniae carbapenemases (KPCs) have been increasingly reported in the UK since 2003. We analysed patient and isolate data for KPC-positive bacteria confirmed by the national reference laboratory from UK laboratories from August 2003 to August 2014, excluding North-West England, where the epidemiology has previously been studied. METHODS: MICs were determined by BSAC agar dilution. Carbapenem-resistant isolates lacking imipenem/EDTA synergy were tested by PCR for blaKPC. MLST and blaKPC sequencing were performed on a subset of isolates. Plasmid analysis was performed by transformation, PCR-based replicon typing and, in some cases, whole-plasmid sequencing. Patient data provided by the sending laboratories were reviewed. RESULTS: Two hundred and ten isolates with KPC enzymes were submitted from 71 UK laboratories outside North-West England, representing 160 patients. All were Enterobacteriaceae, predominantly K. pneumoniae (82%; 173/210), and most (91%; 191/210) were from hospitalized patients. Analysis of 100 isolates identified blaKPC-2 (62%), blaKPC-3 (30%) and blaKPC-4 (8%). Clonal group (CG) 258 was dominant among K. pneumoniae (64%; 54/84), but 21 unrelated STs were also identified. Plasmid analysis identified a diverse range of plasmids representing >11 different replicon types and found in multiple STs and species. Most (34/35) plasmids with IncFIB/FIIK replicons exhibited >99% sequence identity to pKpQIL. CONCLUSIONS: KPC enzymes are increasingly detected in Enterobacteriaceae in the UK, albeit without the major outbreaks seen in North-West England. K. pneumoniae CG258 are the dominant hosts, but plasmid spread plays a major role in KPC dissemination between other K. pneumoniae STs and enterobacterial species.

Non-susceptibility of Escherichia coli, Klebsiella spp., Pseudomonas spp., Streptococcus pneumoniae and Staphylococcus aureus in the UK: temporal trends in England, Northern Ireland, Scotland and Wales.

OBJECTIVES: To monitor and compare trends in the non-susceptibility of bloodstream isolates of pathogens to key antibiotics in the constituent countries of the UK between 2010 and 2014. METHODS: Routinely generated antibiotic susceptibility test results for bloodstream isolates of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Pseudomonas spp., Streptococcus pneumoniae and Staphylococcus aureus were collected from hospital microbiology laboratories in each country. RESULTS: With the exception of a decrease in the proportion of S. aureus that were MRSA, non-susceptibility to key antibiotics among the pathogens studied remained largely unchanged over the 5 year study period, with any increases in non-susceptibility being small. Although some intercountry variation in the proportions of non-susceptible isolates was seen, apart from MRSA, the differences were generally small (<5%) and fluctuated from year to year, with no country showing consistently higher or lower rates of resistance. CONCLUSIONS: Collaboration between the constituent countries of the UK allows an integrated approach to nationwide surveillance of antibiotic resistance.

Sentinel community Clostridium difficile infection (CDI) surveillance in Scotland, April 2013 to March 2014.

Surveillance of Clostridium difficile infection (CDI) in Scotland does not currently distinguish between CDI cases from hospitals and the community. Therefore, the incidence of CDI in the community is unknown, and the burden of disease and the relationship with the hospital/healthcare setting is not well understood. A one-year sentinel community surveillance programme was initiated in collaboration with five Scottish health boards in 2013 (representing 36% of all CDI cases reported in Scotland). Inclusion criteria were all cases aged ≥15 years with a CDI diagnosis in the community or within 48 h following admission to hospital. CDI cases were categorised according to definitions used by the European Centre for Disease Prevention and Control. 256 CDI cases met the inclusion criteria, of which 158 (62%) were community-associated cases (CA-CDI). This represented 26% of all cases reported during the surveillance period by the participating health boards (n = 614). The overall CA-CDI incidence rate was 9.9 per 100 000 population per year. CA-CDI cases were more likely to be female and younger, compared to hospital acquired cases (HA-CDI). The total proportion of cases that had onset in the community was 27%. Ribotypes 015, 002, 078 and 005 were the most common types isolated from both CA-CDI and HA-CDI cases. There were no statistically significant differences between the proportion of types that were either CA-CDI or HA-CDI. Of the CA-CDI cases, 37% had not received antibiotics in the 12 weeks preceding CDI diagnosis, 4% were resident in care homes, and the case-fatality rate for CA-CDI cases was 5.6% (with a 30-day mortality rate for CA-CDI of 0.44 per 100 000 population per year). This study has shown that a substantial proportion of CDI cases reported in Scotland are community associated and that there are close links between the community and healthcare settings. It is therefore essential to monitor the trends in CDI in the community at a national level. The study also provides evidence for the need to examine the feasibility for development of interventions to reduce the burden in the community in addition to hospitals.

Control of Clostridium difficile infection in the hospital setting.

Clostridium difficile infection (CDI) has emerged as a leading challenge in the control of healthcare-associated infection (HCAI). The epidemiology of CDI has changed dramatically, this is associated with emergence of 'hypervirulent' strains, particularly PCR ribotype 027. Despite the epidemic spread of these strains, there are recent reports of decreasing incidence from healthcare facilities where multi-facetted targeted control programs have been implemented. We consider these changes in epidemiology and reflect on the tools available to control CDI in the hospital setting. The precise repertoire of measures adopted and emphasis on different interventions will vary, not only between healthcare systems, but also within different institutions within the same healthcare system. Finally, we consider both the sustainability of reductions already achieved, and the potential to reduce CDI further. This takes account of newly emerging data on more recent changes in the epidemiology of CDI, and the potential of novel interventions to decrease the burden of disease.

Community-associated Clostridium difficile infection among older people in Tayside, Scotland, is associated with antibiotic exposure and care home residence: cohort study with nested case-control.

OBJECTIVES: To estimate the risks of community-associated Clostridium difficile infection (CA-CDI) among the population aged ≥ 65 years associated with antibiotic exposure and care home residence. POPULATION AND METHODS: We linked cases from a prospective study in Tayside, Scotland from 1 November 2008 to 31 October 2009 to population datasets to conduct a cohort study and a nested, matched (1 : 10 by age and gender) case-control study. RESULTS: There were 79,039 eligible residents. CA-CDI incidence was 20.3/10,000 person years. In the cohort study, after adjustment, we found a significantly increasing risk of CA-CDI with increasing age and comorbidity, prior hospital admission, care home residence [hazard ratio (HR) 1.96, 95% CI 1.14-3.34] and baseline antibiotic exposure (1.94, 1.35-2.77). In separate adjusted models, '4C' antibiotics (clindamycin, co-amoxiclav, cephalosporins, ciprofloxacin; 2.75, 1.78-4.26) and fluoroquinolones (3.33, 1.95-5.67) had higher associated risks. We matched 62 CA-CDI cases without recent (prior 3 months) hospital admission to 620 controls. In adjusted logistic regression models, exposure to any antibiotics increased the risk of CA-CDI (OR 6.04, 95% CI 3.19-11.43). Exposure to 4C antibiotics or fluoroquinolones had higher associated risks: adjusted OR 11.60 (95% CI 5.57-24.15) and 13.04 (4.91-34.64), respectively. Risk of CA-CDI increased with cumulative antibiotic exposure. Subgroup analysis of 42 cases with C. difficile cultured and 420 controls amplified all associations between antibiotic exposure and CA-CDI. Care home residence independently increased the risk of CA-CDI in all models. CONCLUSIONS: Our results have two important implications. First, they validate the classification of 4C antibiotics and fluoroquinolones in primary care as high risk for CA-CDI. Second, they demonstrate the importance of prior antibiotic exposure and place of residence for risk assessment by primary care prescribers.

Scottish Antimicrobial Prescribing Group (SAPG): development and impact of the Scottish National Antimicrobial Stewardship Programme.

In 2008, the Scottish Management of Antimicrobial Resistance Action Plan (ScotMARAP) was published by the Scottish Government. One of the key actions was initiation of the Scottish Antimicrobial Prescribing Group (SAPG), hosted within the Scottish Medicines Consortium, to take forward national implementation of the key recommendations of this action plan. The primary objective of SAPG is to co-ordinate and deliver a national framework or programme of work for antimicrobial stewardship. This programme, led by SAPG, is delivered by NHS National Services Scotland (Health Protection Scotland and Information Services Division), NHS Quality Improvement Scotland, and NHS National Education Scotland as well as NHS board Antimicrobial Management Teams. Between 2008 and 2010, SAPG has achieved a number of early successes, which are the subject of this review: (i) through measures to optimise prescribing in hospital and primary care, combined with infection prevention measures, SAPG has contributed significantly to reducing Clostridium difficile infection rates in Scotland; (ii) there has been engagement of all key stakeholders at local and national levels to ensure an integrated approach to antimicrobial stewardship within the wider healthcare-associated infection agenda; (iii) development and implementation of data management systems to support quality improvement; (iv) development of training materials on antimicrobial stewardship for healthcare professionals; and (v) improving clinical management of infections (e.g. community-acquired pneumonia) through quality improvement methodology. The early successes achieved by SAPG demonstrate that this delivery model is effective and provides the leadership and focus required to implement antimicrobial stewardship to improve antimicrobial prescribing and infection management across NHS Scotland.

The epidemiology of Clostridium difficile in Scotland.

The objective of this study was to characterise the epidemiology of Clostridium difficile in Scotland by determining the distribution of PCR ribotypes and antimicrobial susceptibility in 1613 isolates collected from all healthboard areas of Scotland in the period November 2007-December 2009. Three PCR ribotypes predominated amongst the Scottish isolates of C. difficile; ribotype 106 (29.4%), ribotype 001 (22%) and ribotype 027 (12.6%) followed by the less prevalent ribotypes including 002, 015, 014, 078, 005, 023 and 020. The distribution of ribotypes varied between healthboard areas. Ribotype 106 or 001 was the predominant ribotype in 10 healthboard areas, while ribotype 027 was the predominant type in two neighbouring areas. Antimicrobial susceptibility testing of C. difficile isolates showed high frequencies of resistance to moxifloxacin, levofloxacin, erythromycin and cefotaxime in the epidemic C. difficile ribotypes 001, 027 and 106 compared to other less common ribotypes. Furthermore, reduced susceptibility to metronidazole was found only in the epidemic strains. These findings are compatible with the hypothesis that fluoroquinolones, macrolides and cephalosporins may play a role in the spread of C. difficile in Scotland (while the role of metronidazole needs further investigations), and highlights the role of antimicrobial stewardship in preventing and controlling C. difficile infection (CDI).