European Practice for CDI Treatment.

Clostridioides difficile infection (CDI) remains a significant cause of morbidity and mortality worldwide. Historically, two antibiotics (metronidazole and vancomycin) and a recent third (fidaxomicin) have been used for CDI treatment; convincing data are now available showing that metronidazole is the least efficacious agent. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) management guidance for CDI were updated in 2021. This guidance document outlines the treatment options for a variety of CDI clinical scenarios and for non-antimicrobial management (e.g., faecal microbiota transplantation, FMT). One of the main changes is that metronidazole is no longer recommended as first-line CDI treatment. Rather, fidaxomicin is preferred on the basis of reduced recurrence rates with vancomycin as an acceptable alternative. Recommended options for recurrent CDI now include bezlotoxumab as well as FMT.A 2017 survey of 20 European countries highlighted variation internationally in CDI management strategies. A variety of restrictions were in place in 65% countries prior to use of new anti-CDI treatments, including committee/infection specialist approval or economic review/restrictions. This survey was repeated in November 2022 to assess the current landscape of CDI management practices in Europe. Of 64 respondents from 17 countries, national CDI guidelines existed in 14 countries, and 11 have already/plan to incorporate the ESCMID 2021 CDI guidance, though implementation has not been surveyed in 6. Vancomycin is the most commonly used first-line agent for the treatment of CDI (n = 42, 66%), followed by fidaxomicin (n = 30, 47%). Six (9%) respondents use metronidazole as first-line agent for CDI treatment, whereas 22 (34%) only in selected low-risk patient groups. Fidaxomicin is more likely to be used in high-risk patient groups. Availability of anti-CDI therapy influenced prescribing in six respondents (9%). Approval pre-prescription was required before vancomycin (n = 3, 5%), fidaxomicin (n = 10, 6%), bezlotoxumab (n = 11, 17%) and FMT (n = 10, 6%). Implementation of CDI guidelines is rarely audited.Novel anti-CDI agents are being evaluated; it is not yet clear what will be the roles of these agents. The treatment of recurrent CDI is particularly troublesome, and several different live biotherapeutics are being developed, in addition to FMT.

Rethinking Clostridioides difficile infection (CDI) surveillance definitions based on changing healthcare utilisation and a more realistic incubation period: reviewing data from a tertiary-referral hospital, Ireland, 2012 to 2021.

BackgroundCommunity-associated Clostridioides difficile infections (CA-CDI) have increased worldwide. Patients with CDI-related symptoms occurring < 48 hours after hospitalisation and no inpatient stay 12 weeks prior are classified as CA-CDI, regardless of hospital day attendances 3 months before CDI onset. Healthcare-associated (HA) CDIs include those with symptom onset ≥ 48 hours post hospitalisation.AimTo consider an incubation period more reflective of CDI, and changing healthcare utilisation, we measured how varying surveillance specifications to categorise patients according to their CDI origin resulted in changes in patients' distribution among CDI origin categories.MethodsNew CDI cases between 2012-2021 from our hospital were reviewed. For patients with CA-CDI, hospital day attendances in the 3 months prior were recorded. CA-CDI patients with hospital day attendances and recently discharged CDI patients (RD-CDI; CDI onset 4-12 weeks after discharge) were combined into a new 'healthcare-exposure' category (HE-CDI). Time from hospitalisation to disease onset was varied and the midpoint between optimal and balanced cut-offs was used instead of 48 hours to categorise HA-CDI.ResultsOf 1,047 patients, 801 (76%) were HA-CDI, 205 (20%) CA-CDI and 41 (4%) were RD-CDI. Of the CA-CDI cohort, 45 (22%) met recent HE-CDI criteria and, when reassigned, reduced CA-CDI to 15%. Sensitivity analysis indicated a day 4 cut-off for assigning HA-CDI. Applying this led to 46 HA-CDI reassigned as CA-CDI. Applying both HE and day 4 criteria led to 72% HA-CDI, 20% CA-CDI, and 8% HE-CDI (previously RD-CDI).ConclusionCDI surveillance specifications reflecting healthcare exposure and an incubation period more characteristic of C. difficile may improve targeted CDI prevention interventions.

Clostridioides difficile infection in neurosurgical patients in a national centre over 10 years: less common but associated with longer hospital stays.

BACKGROUND: Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated (HA) diarrhoea, contributing to patient morbidity and prolonged length-of-stay (LOS). We retrospectively assessed CDI over a decade in a national neurosurgical centre, with a multi-disciplinary approach to CDI surveillance and antimicrobial stewardship, by comparing CDI patients with other patient groups. METHODS: Data on CDI in neurosurgical inpatients between January 2012 and December 2021 were collated. Disease-specific variables were compared to other inpatients with CDI. Rates per 10,000 bed days used were calculated. Patient-specific differences were compared with neurosurgical patients without CDI. CDI rates by patient group were explored using odds ratio (OR) and χ2 analyses. Negative binomial regression was used to investigate CDI rates over time. RESULTS: Of 50 neurosurgical patients with CDI, all were HA; the average age was 53 years (standard deviation (SD) 16.3 years), 49 were first-episode CDI, and three had severe CDI. The majority (76.7%) had received recent antimicrobials. Compared with non-neurosurgical CDI patients, neurosurgical CDI rates differed significantly (1.9 versus 3.6 per 10,000 bed days used, p < 0.05), neurosurgical patients were younger (p ≤ 0.01), C. difficile testing was more likely to be requested by neurosurgeons (OR 2.4; p ≤ 0.01), and the proportion of severe CDI was higher (6% versus 2%, OR 3.0, p = 0.07, confidence interval (CI) 0.54 to 11.3). Within the neurosurgical cohort, CDI patients had an average LOS four times that of other patients (CI 15.2 to 35.1; p < 0.01) and were older (53.5 versus 47.8 years, CI 0.1 to 11 years; p < 0.05). Only one CDI outbreak was linked to neurosurgical patients. CONCLUSION: CDI in neurosurgery patients differed from the wider hospital, with greater awareness of CDI testing. Longer LOS impacted bed utilisation with limited capacity. Robust surveillance supports proactive antimicrobial stewardship programmes in this vulnerable population.

Candida meningitis/ventriculitis over a decade. Increased morbidity and length of stay a concern.

AIM: The primary aim of this study was to review the diagnosis, management and outcome of Candida meningitis/ventriculitis in our hospital over a ten-year period. MATERIALS AND METHODS: We retrospectively reviewed all culture and 18s rRNA nucleic acid positive CSF specimens processed between 1st January 2010 and 31st December 2020. Patient records were subsequently reviewed to assess the significance of the isolate. RESULTS: Of 851 culture-positive cerebrospinal fluid (CSF) specimens, Candida spp. were isolated from 29 (3.4%), representing infection in 12 patients. One culture-negative specimen was positive for Candida on 18s rRNA testing. Of the 13 patients, eight were male; 61.5% and the median age was 47 years; range: 20-70. The median interval from admission to onset of infection and culture positivity was 24 days (range: 1-63 days). All patients had a central nervous system (CNS) device in situ (external ventricular drain: 11; ventriculoperitoneal shunt: 1; lumbar drain: 1). Four were colonised with Candida spp. before meningitis/ventriculitis diagnosis, from wounds (n = 3), respiratory (n = 3), and urine (n = 1) specimens. On culture, the most common species was Candida albicans (n = 8), followed by C. parapsilosis (n = 2), C. tropicalis (n = 1), and C. dubliniensis (n = 1). The median number of follow-up CSFs per patient was nine (range; 3-22), with a median of 6 days to CSF sterility (range 3-10 days). Treatment included; liposomal amphotericin B (n = 5), fluconazole (n = 2), liposomal amphotericin B, and flucytosine (n = 2), liposomal amphotericin B, fluconazole and flucytosine (n = 3), and intra-ventricular amphotericin B (n = 1). Median treatment duration was 25 days (range 11-76) and CNS device removal occurred in 12 patients. The median length-of-stay (LOS) was 58 days (range 24-406). On discharge, moderate to severe disability (Modified Rankin Scale [mRS] 3-5) was evident in eight patients. Two patients died and one was lost to follow-up. CONCLUSION: Meningitis/ventriculitis due to Candida spp. is an uncommon but challenging infection, usually associated with a device, increased morbidity, LOS, and necessitating prolonged treatment. Neurosurgeons need to be aware of these issues in managing and in communicating with such complex patients.

Surveillance of common infections in the early period after renal transplantation in a national center: 2014-2017.

BACKGROUND: Infection prevention and timely and effective treatment are among the major aims of care in kidney transplant recipients. Pre-transplant vaccination and pre-transplant viral screening have been extensively studied and are now considered standard practice. Early post-operative infection surveillance is mandatory in other vulnerable cohorts, but has not been extensively studied in this population. We hypothesized that surveillance of the most common bacterial infection types in the post-transplant setting would be beneficial and identify key areas for improvement. METHODS: All adult kidney transplant recipients whose surgeries were performed in the Irish national kidney transplant unit over a 1-year period had prospective early post-transplant (first 30 days) infection surveillance in 2014 for surgical site infection, urinary tract infection, and secondary bloodstream infections (Group T0). Several key changes were implemented following scrutiny of infection patterns and clinical practice. Subsequently, infection surveillance was undertaken for 2016 and 2017 (Group T1) to assess the impact of these changes. RESULTS: Between 2014 and 2017, the number of kidney transplants increased by 32%. The following aspects of clinical practice were the focus of change following analysis of Group T0 data: timing of surgical antimicrobial prophylaxis (SAP) administration, choice of SAP antimicrobial agent, and routine microbiological testing in the peri-operative period. Following implementation of these changes, the timing of SAP administration was greatly improved (45%-100% of cases appropriately timed). The infection rate decreased from 8.9% to 7.4% in 2016, with a further decrease to 4% in 2017 (OR 0.42 (95% CI: 0.16-1.10); P = .08). Compliance with pre-operative microbiological screening improved in Group T1. CONCLUSIONS: Simple clinical practice changes, implemented upon analysis of common bacterial infection surveillance data in the first 30 days after kidney transplantation resulted in more effective SAP administration and improved compliance with routine microbiological testing in the peri-operative period. These interventions have potentially contributed to reduced early post-operative infection rates, despite increased transplant activity in the unit. Infection surveillance is an important and under-utilized way of reducing infections in this vulnerable patient cohort.

Financial Impact of Colorectal Cancer and Its Consequences: Associations Between Cancer-Related Financial Stress and Strain and Health-Related Quality of Life.

BACKGROUND: The financial impact and consequences of cancer on the lives of survivors remain poorly understood. This is especially true for colorectal cancer. OBJECTIVE: We investigated objective cancer-related financial stress, subjective cancer-related financial strain, and their association with health-related quality of life in colorectal cancer survivors. DESIGN: This was a cross-sectional postal survey. SETTINGS: The study was conducted in Ireland, which has a mixed public-private healthcare system. PATIENTS: Colorectal cancer survivors, diagnosed 6 to 37 months prior, were identified from the population-based National Cancer Registry. MAIN OUTCOME MEASURES: Cancer-related financial stress was assessed as impact of cancer on household ability to make ends meet and cancer-related financial strain by feelings about household financial situation since cancer diagnosis. Health-related quality of life was based on European Organisation for Research and Treatment of Cancer QLQ-C30 global health status. Logistic regression was used to identify associations between financial stress and strain and low health-related quality of life (lowest quartile, score ≤50). RESULTS: A total of 493 survivors participated. Overall, 41% reported cancer-related financial stress and 39% cancer-related financial strain; 32% reported both financial stress and financial strain. After adjustment for sociodemographic and clinical variables, the odds of low health-related quality of life were significantly higher in those who reported cancer-related financial stress postdiagnosis compared with those who reported no change in financial stress postcancer (OR = 2.54 (95% CI, 1.62-3.99)). The odds of low health-related quality of life were also significantly higher in those with worse financial strain postdiagnosis (OR =1.73 (95% CI, 1.09-2.72)). The OR for those with both cancer-related financial stress and financial strain was 2.59 (95% CI, 1.59-4.22). LIMITATIONS: Survey responders were younger, on average, than nonresponders. Responders and nonresponders may have differed in cancer-related financial stress and strain or health-related quality of life. CONCLUSIONS: Four in 10 colorectal cancer survivors reported an adverse financial impact of cancer. Cancer-related financial stress and strain were significantly associated with low health-related quality of life. To inform support strategies, additional research is needed to better understand how both objective and subjective financial distress influence survivors' health-related quality of life. See Video Abstract http://links.lww.com/DCR/A447.

European Practice for CDI Treatment.

Clostridium difficile infection (CDI) remains a significant cause of morbidity and mortality worldwide. Historically, two antibiotics (metronidazole and vancomycin) and a recent third (fidaxomicin) have been used routinely for CDI treatment; convincing data are now available showing that metronidazole is the least efficacious agent. The European Society of Clinical Microbiology and Infectious Diseases CDI treatment guidelines outline the treatment options for a variety of CDI clinical scenarios, including use of the more traditional anti-CDI therapies (e.g., metronidazole, vancomycin), the role of newer anti-CDI agents (e.g., fidaxomicin), indications for surgical intervention and for non-antimicrobial management (e.g., faecal microbiota transplantation, FMT). A 2017 survey of 20 European countries found that while the majority (n = 14) have national CDI guidelines that provide a variety of recommendations for CDI treatment, only five have audited guideline implementation. A variety of restrictions are in place in 13 (65%) countries prior to use of new anti-CDI treatments, including committee/infection specialist approval or economic review/restrictions. Novel anti-CDI agents are being evaluated in Phase III trials; it is not yet clear what will be the roles of these agents. Prophylaxis is an optimum approach to reduce the impact of CDI especially in high-risk populations; monoclonal antibodies, antibiotic blocking approaches and multiple vaccines are currently in advanced clinical trials. The treatment of recurrent CDI is particularly troublesome, and several different live bio therapeutics are being developed, in addition to FMT.

The epidemiology of Clostridium difficile infection in a national kidney transplant center.

BACKGROUND: We aimed to describe the epidemiology and outcomes of CDI in a national kidney transplant center from 2008 to 2015. METHODS: Adult kidney and kidney-pancreas transplant recipients were included for analysis if they met the surveillance CDI case definition. Rates of new healthcare-associated CDI (HA-CDI) were expressed per 10 000 KTR/KTPR bed days used (BDU) to facilitate comparisons. RESULTS: Fifty-two cases of CDI were identified in 42 KTRs and KPTRs. This corresponded to an average annual rate of 9.6 per 10 000 BDU, higher than that seen among general hospital inpatients locally, nationally, and internationally. Of the 45 cases (87%) that were considered HA-CDI, nine (20%) had symptom onset in the community. Recent proton-pump inhibitor (PPI) and broad-spectrum antimicrobial exposure preceded the majority of cases. KTRs and KPTRs with CDI had a longer mean length of hospital stay (35 days) than those KTR and KPTRs admitted during the same period that did not have CDI (8 days). CONCLUSIONS: Education regarding CDI must be extended to transplant recipients and their general practitioners. Other targets for future CDI rate reduction must include stringent antimicrobial stewardship (both in hospital and in the community) and judicious PPI prescribing.

Counting the cost of cancer: out-of-pocket payments made by colorectal cancer survivors.

PURPOSE: Cancer places a significant cost burden on health services. There is increasing recognition that cancer also imposes a financial and economic burden on patients but this has rarely been quantified outside North America. We investigate out-of-pocket costs (OOPCs) incurred by colorectal (CRC) survivors in Ireland. METHODS: CRC survivors (ICD10 C18-20) diagnosed 6-30 months previously were identified from the National Cancer Registry Ireland and invited to complete a postal questionnaire. Cancer-related OOPC for tests, procedures, drugs, allied medications and household management in approximately the year following diagnosis were calculated. Robust regression was used to identify predictors of OOPC; this was done for all survivors combined and stratified by age (<70 and ≥70 years) and employment status (working and not working) at diagnosis. RESULTS: Four hundred ninety-seven CRC survivors completed questionnaires (response rate = 39%). Almost all (90%) respondents reported some cancer-related OOPC. The average total OOPC was €1589. Stage III at diagnosis was associated with significantly higher OOPCs than other stages in the all-survivor model, in those not working in the employment model and in those under 70 years in the age-stratified model. In all-survivor model, those under 70 also had higher OOPCs, as did those in employment. Having one or more children was associated with significantly lower OOPCs in those under 70 years. CONCLUSIONS: Almost all CRC survivors incur cancer-related OOPCs; for some, these are not insignificant. Greater attention should be paid to the development of services to help survivors manage the financial and economic burden of cancer.

Invasive MRSA infections in neurosurgical patients - a decade of progress.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of bloodstream infection (BSI), which is declining in many countries, including Ireland. However, it also causes other invasive infections, such as meningitis in neurosurgical patients. It is unclear whether the decline in MRSA BSI is reflected in other invasive infections and in specialist units. AIM: To investigate trends in the incidence of MRSA invasive infection in a national neurosurgical centre over a 10-year period. METHODS: A retrospective review of neurosurgical patients with MRSA recovered from sterile sites and indicating invasive infection, according to internationally agreed definitions was conducted between January 2006 and December 2015. Rates per 10,000 bed days used (BDU) and neurosurgical bed days used (NBDU) were calculated and trends were analysed. RESULTS: Forty-four cases of invasive MRSA infection were identified over the study period. The majority were BSI (26, 59%) followed by ventriculitis (8, 18%). Invasive MRSA infections declined significantly from 0.52 per 10,000 BDU (or 4.65 per 10,000 NBU) in 2006 to 0.22 per 10,000 BDU (or 2.04 per 10,000 NBDU) in 2015, p < .01, despite an increase in neurosurgical clinical activity. Half of the infections occurred in patients with no previous history of MRSA colonisation/infection. The mean length-of-stay for neurosurgical patients with invasive MRSA infections was 67 days (median 32.5 days), significantly greater for other neurosurgical patients (p < .01). CONCLUSION: There has been a significant decrease in invasive MRSA infections in neurosurgical patients, reflecting national and international trends for MRSA BSI. This indicates that infection prevention and control measures have been effective in reducing invasive MRSA infections overall, thus contributing to improved patient care.

Direct costs of radiotherapy for rectal cancer: a microcosting study.

BACKGROUND: Radiotherapy provides significant benefits in terms of reducing risk of local recurrence and death from rectal cancer. Despite this, up-to-date cost estimates for radiotherapy are lacking, potentially inhibiting policy and decision-making. Our objective was to generate an up-to-date estimate of the cost of traditional radiotherapy for rectal cancer and model the impact of a range of potential efficiency improvements. METHODS: Microcosting methods were used to estimate total direct radiotherapy costs for long- (assumed at 45-50 Gy in 25 daily fractions over a 5 week period) and short-courses (assumed at 25 Gy in 5 daily fractions over a one week period). Following interviews and on-site visits to radiotherapy departments in two designated cancer centers, a radiotherapy care pathway for a typical rectal cancer patient was developed. Total direct costs were derived by applying fixed and variable unit costs to resource use within each care phase. Costs included labor, capital, consumables and overheads. Sensitivity analyses were performed. RESULTS: Radiotherapy treatment was estimated to cost between €2,080 (5-fraction course) and €3,609 (25-fraction course) for an average patient in 2012. Costs were highest in the treatment planning phase for the short-course (€1,217; 58% of total costs), but highest in the radiation treatment phase for the long-course (€1,974: 60% of total costs). By simultaneously varying treatment time, capacity utilization rates and linear accelerator staff numbers, the base cost fell by 20% for 5-fractions: (€1,660) and 35% for 25-fractions: (€2,354). CONCLUSIONS: Traditional radiotherapy for rectal cancer is relatively inexpensive. Moreover, significant savings may be achievable through service organization and provision changes. These results suggest that a strong economic argument can be made for expanding the use of radiotherapy in rectal cancer treatment.

Cost comparisons and methodological heterogeneity in cost-of-illness studies: the example of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide with over 1 million new cases diagnosed each year. Advances in treatment and survival are likely to have increased lifetime costs of managing the disease. Cost-of-illness (COI) studies are key building blocks in economic evaluations of interventions and comparative effectiveness research. We systematically reviewed and critiqued the COI literature on CRC. METHODS: We searched several databases for CRC COI studies published in English, between January 2000 and February 2011. Information was abstracted on: setting, patient population, top-down/bottom-up costing, incident/prevalent approach, payer perspective, time horizon, costs included, cost source, and per-person costs. We developed a framework to compare study methodologies and assess homogeneity/heterogeneity. RESULTS: A total of 26 papers met the inclusion criteria. There was extensive methodological heterogeneity. Studies included case-control studies based on claims/reimbursement data (10), examinations of patient charts (5), and analysis of claims data (4). Epidemiological approaches varied (prevalent, 6; incident, 8; mixed, 10; unclear, 4). Time horizons ranged from 1 year postdiagnosis to lifetime. Seventeen studies used top-down costing. Twenty-five studies included healthcare-payer direct medical costs; 2 included indirect costs; 1 considered patient costs. There was broad agreement in how studies accounted for time, but few studies described costs in sufficient detail to allow replication. In general, costs were not comparable between studies. CONCLUSIONS: Methodological heterogeneity and lack of transparency made it almost impossible to compare CRC costs between studies or over time. For COI studies to be more useful and robust there is need for clear and rigorous guidelines around methodological and reporting "best practice."

How much does it cost to care for survivors of colorectal cancer? Caregiver's time, travel and out-of-pocket costs.

PURPOSE: Cancer treatment is increasingly delivered in an outpatient setting. This may entail a considerable economic burden for family members and friends who support patients/survivors. We estimated financial and time costs associated with informal care for colorectal cancer. METHODS: Two hundred twenty-eight carers of colorectal cancer survivors diagnosed on October 2007-September 2009 were sent a questionnaire. Informal care costs included hospital- and domestic-based foregone caregiver time, travel expenses and out-of-pocket (OOP) costs during two phases: diagnosis and treatment and ongoing care (previous 30 days). Multiple regression was used to determine cost predictors. RESULTS: One hundred fifty-four completed questionnaires were received (response rate = 68%). In the diagnosis and treatment phase, weekly informal care costs per person were: hospital-based costs, incurred by 99% of carers, mean = €393 (interquartile range (IQR), €131-€541); domestic-based time costs, incurred by 85%, mean = €609 (IQR, €170-€976); and domestic-based OOP costs, incurred by 68%, mean = €69 (IQR, €0-€110). Ongoing costs included domestic-based time costs incurred by 66% (mean = €66; IQR, €0-€594) and domestic-based OOP costs incurred by 52% (mean = €52; IQR, €0-€64). The approximate average first year informal care cost was €29,842, of which 85 % was time costs, 13% OOP costs and 2% travel costs. Significant cost predictors included carer age, disease stage, and survivor age. CONCLUSION: Informal caregiving associated with colorectal cancer entails considerable time and OOP costs. This burden is largely unrecognised by policymakers, service providers and society in general. These types of studies may facilitate health decision-makers in better assessing the consequences of changes in cancer care organisation and delivery.

Cost-effectiveness of computed tomography colonography in colorectal cancer screening: a systematic review.

OBJECTIVES: The European Code Against Cancer recommends individuals aged ≥ 50 should participate in colorectal cancer screening. CT-colonography (CTC) is one of several screening tests available. We systematically reviewed evidence on, and identified key factors influencing, cost-effectiveness of CTC screening. METHODS: PubMed, Medline, and the Cochrane library were searched for cost-effectiveness or cost-utility analyses of CTC-based screening, published in English, January 1999 to July 2010. Data was abstracted on setting, model type and horizon, screening scenario(s), comparator(s), participants, uptake, CTC performance and cost, effectiveness, ICERs, and whether extra-colonic findings and medical complications were considered. RESULTS: Sixteen studies were identified from the United States (n = 11), Canada (n = 2), and France, Italy, and the United Kingdom (1 each). Markov state-transition (n = 14) or microsimulation (n = 2) models were used. Eleven considered direct medical costs only; five included indirect costs. Fourteen compared CTC with no screening; fourteen compared CTC with colonoscopy-based screening; fewer compared CTC with sigmoidoscopy (8) or fecal tests (4). Outcomes assessed were life-years gained/saved (13), QALYs (2), or both (1). Three considered extra-colonic findings; seven considered complications. CTC appeared cost-effective versus no screening and, in general, flexible sigmoidoscopy and fecal occult blood testing. Results were mixed comparing CTC to colonoscopy. Parameters most influencing cost-effectiveness included: CTC costs, screening uptake, threshold for polyp referral, and extra-colonic findings. CONCLUSION: Evidence on cost-effectiveness of CTC screening is heterogeneous, due largely to between-study differences in comparators and parameter values. Future studies should: compare CTC with currently favored tests, especially fecal immunochemical tests; consider extra-colonic findings; and conduct comprehensive sensitivity analyses.

Clinical impact of antimicrobial resistance in European hospitals: excess mortality and length of hospital stay related to methicillin-resistant Staphylococcus aureus bloodstream infections.

Antimicrobial resistance is threatening the successful management of nosocomial infections worldwide. Despite the therapeutic limitations imposed by methicillin-resistant Staphylococcus aureus (MRSA), its clinical impact is still debated. The objective of this study was to estimate the excess mortality and length of hospital stay (LOS) associated with MRSA bloodstream infections (BSI) in European hospitals. Between July 2007 and June 2008, a multicenter, prospective, parallel matched-cohort study was carried out in 13 tertiary care hospitals in as many European countries. Cohort I consisted of patients with MRSA BSI and cohort II of patients with methicillin-susceptible S. aureus (MSSA) BSI. The patients in both cohorts were matched for LOS prior to the onset of BSI with patients free of the respective BSI. Cohort I consisted of 248 MRSA patients and 453 controls and cohort II of 618 MSSA patients and 1,170 controls. Compared to the controls, MRSA patients had higher 30-day mortality (adjusted odds ratio [aOR] = 4.4) and higher hospital mortality (adjusted hazard ratio [aHR] = 3.5). Their excess LOS was 9.2 days. MSSA patients also had higher 30-day (aOR = 2.4) and hospital (aHR = 3.1) mortality and an excess LOS of 8.6 days. When the outcomes from the two cohorts were compared, an effect attributable to methicillin resistance was found for 30-day mortality (OR = 1.8; P = 0.04), but not for hospital mortality (HR = 1.1; P = 0.63) or LOS (difference = 0.6 days; P = 0.96). Irrespective of methicillin susceptibility, S. aureus BSI has a significant impact on morbidity and mortality. In addition, MRSA BSI leads to a fatal outcome more frequently than MSSA BSI. Infection control efforts in hospitals should aim to contain infections caused by both resistant and susceptible S. aureus.

PCR ribotype prevalence and molecular basis of macrolide-lincosamide-streptogramin B (MLSB) and fluoroquinolone resistance in Irish clinical Clostridium difficile isolates.

BACKGROUND: Antimicrobial use is recognized as a risk factor for Clostridium difficile infection (CDI) and outbreaks. We studied the relationship between PCR ribotype, antimicrobial susceptibility and the genetic basis of resistance in response to exposure to antimicrobial agents. METHODS: C. difficile isolates were cultured from 133 CDI patients for whom recent antimicrobial drug exposure had been recorded. Isolates were ribotyped by PCR and assessed for their susceptibility to the macrolide-lincosamide-streptogramin B (MLS(B)) group of compounds (erythromycin and clindamycin) and fluoroquinolone antimicrobials (ciprofloxacin, levofloxacin and moxifloxacin). Where relevant, the genetic basis of resistance was determined. RESULTS: Prevalent ribotypes (including 027, 001 and 106) exhibited significantly greater antimicrobial resistance compared with ribotypes 078 and 014, among others. Clindamycin-resistant ribotype 078 was detected for the first time. Ribotypes 027 and 001 were more likely to exhibit MLS(B) resistance, a feature that was associated with the erm(B) gene. Exposure to MLS(B) or fluoroquinolone antimicrobial compounds in the 8 weeks prior to the onset of infection was not associated with specific genetic markers of resistance. Single amino acid substitutions in the A and B subunits of DNA gyrase were noted and were ribotype specific and linked to resistance to moxifloxacin. CONCLUSIONS: Resistance to MLS(B) and fluoroquinolone antimicrobial compounds is common among prevalent ribotypes of C. difficile. The genetic basis for antimicrobial resistance appears to be ribotype specific and conserved in the absence of recent antimicrobial selection pressure.

Sepsis in surgical inpatients: under-recognised but with significant consequences.

BACKGROUND: The true incidence of sepsis in surgical cohorts in Ireland remains unclear. According to inpatient audits, patients in surgical diagnostic groups (DRG) who developed sepsis had a longer length of stay and higher mortality rate compared with medical DRG patients who developed sepsis. AIMS: We investigated sepsis incidence on a general surgical ward to identify risk factors and strategies to improve management. METHODS: Demographics, admission and discharge details, infection risk factors, infection, and sepsis were studied prospectively on a surgical ward in July 2018. RESULTS: The mean age of 164 patients was 60.5 years (range 18-93 years), 107 (65.2%) were admitted electively, 16 (9.8%) were colonised with a multidrug-resistant organism (MDRO), and 30 (18.3%) were classified as frail on admission. Twelve (7.3%) developed sepsis (ward sepsis rate 118.2/10,000 bed days used). 'Sepsis' was documented in six cases and the national sepsis screening form used in four patients. Patients with sepsis were three times as likely to be MDRO-colonised (OR 3.56; 95% CI = 0.86-14.82; p = 0.065) or frail (OR 3.63; 95% CI = 1.07-12.35; p = 0.03), four times as likely to be an inpatient at the end of the study (OR 4.22, 96% CI 1.23-14.49; p = 0.01), and three times as likely to be readmitted (OR 3.46, 95% CI 1.02-11.76; p = 0.03). CONCLUSION: Sepsis was under-documented, and barriers exist with use of the national sepsis screening form. Frailty, which is a sepsis risk factor, should be assessed pre-operatively to maximise prevention.

Vancomycin-Resistant Enterococci (VRE) in The Intensive Care Unit in a Nonoutbreak Setting: Identification of Potential Reservoirs and Epidemiological Associations Between Patient and Environmental VRE.

OBJECTIVE Among nosocomial bloodstream infections caused by enterococcal species, Ireland has the highest proportion caused by vancomycin-resistant enterococci (VRE) in Europe at 45.8%. The contribution of the near-patient environment to VRE transmission outside of outbreaks was investigated. DESIGN A prospective observational study was conducted during 7 sampling periods. METHODS Recovery of VRE isolates by swabbing the near-patient environment and patients in the intensive care unit (ICU) was conducted to identify reservoirs, clinical and molecular epidemiological associations, and the success of active surveillance cultures (ASCs). RESULTS Of 289 sampling occasions involving 157 patients and their bed spaces, VRE isolates were recovered from patient bed spaces, clinical samples, or both on 114 of 289 sampling occasions (39.4%). The patient and their bed space were positive for VRE on 34 of 114 VRE-associated sampling occasions (29.8%). Of 1,647 environment samples, 107 sites (6.5%) were VRE positive, with significantly greater VRE recovery from isolation rooms than from the open-plan area (9.1% vs 4.1%; P < .0001). The most frequently VRE-contaminated sites were the drip stand, bed control panel, and chart holders, which together accounted for 61% of contaminated sites. The use of ASCs resulted in a 172% increase in identification of VRE-colonized patients. Molecular typing revealed 2 environmental clusters, 1 cluster involving 3 patients and generally greater heterogeneity of patient isolates compared to environmental isolates. CONCLUSION Even outside of outbreaks, near-patient ICU environmental contamination with VRE is common. Better infection control policies that limit environmental transmission of VRE in the ICU and that are supported by molecular epidemiological studies, in real time, are needed. Infect Control Hosp Epidemiol 2018;39:40-45.