High Risk For Clostridium Difficile Infection Research Articles

The prevalence and clinical characteristics of Clostridium difficile infection in Saudi patients admitted with inflammatory bowel disease: A case-control study.

Inflammatory bowel disease (IBD) patients are at increased risk of Clostridium difficile infection (CDI), causing significant morbidity and mortality. This study examined CDI's prevalence, predisposing factors, and clinical outcomes in Saudi hospitalized IBD patients. : A retrospective case-control study was conducted at a tertiary medical city in Riyadh, Saudi Arabia. All Saudi adult patients with IBD, admitted over the preceding four years were identified from the hospital's database. Eligible patients were divided into those with CDI and those without CDI. Binary logistic regression was used to determine the predisposing factors for CDI among admitted IBD patients. During the study period, 95 patients were admitted with IBD. Crohn's disease (CD) was the predominant type (71.6%), whereas 28.4% of the patients were with ulcerative colitis (UC). Only 16 (16.8%) patients had positive CDI. CDI-positive patients tend to have hypertension and previous use of steroids. Patients with UC tend to have a higher risk of CDI than those with CD. Most patients recovered from the CDI (81.3%) with a median time to CDI clearance of 14 days. Three patients (18.8%) had recurrent CDI; among them, one died. The prevalence of CDI in Saudi IBD patients is similar to that reported elsewhere. UC, steroid treatment, and hypertension are risk factors for CDI in IBD patients. Recurrence of CDI in IBD patients is common and associated with a poor prognosis.

Prospective assessment of Clostridioides (formerly Clostridium) difficile colonization and acquisition in hematopoietic stem cell transplant patients.

Patients undergoing hematopoietic stem cell transplant (HSCT) possess numerous risk factors for Clostridioides (formerly Clostridium) difficile infection (CDI) and experience a high rate of diarrhea. Colonization rates of Clostridiumdifficile vary greatly among subgroup analyses with recent studies demonstrating colonization rates in the blood and marrow transplant units up to nine times that of the general population. The primary objectives of this study were to identify the rate of Cdifficile colonization and acquisition in HSCT patients admitted to the blood and marrow transplant unit. This was a prospective study that included all adult patients admitted for hematopoietic stem cell transplantation. Stool specimens were routinely collected on admission and weekly thereafter for a maximum of six samples per patient. Forty-two patients met inclusion criteria and had baseline samples available for analysis. The rate of Cdifficile colonization on admission was 24%, and an additional 9% of patients acquired the organism during admission. Twelve percent of patients developed CDI that was diagnosed clinically. Univariate analysis showed an increased risk of colonization for patients with three or more prior chemotherapy cycles. Given high colonization rates coupled with high risk of CDI in this population, providers must be judicious when testing for CDI and interpreting test results for HSCT patients.

1522-P: High Incidence of Hospital-Onset Clostridium Difficile Infection in Diabetic Foot Syndrome Patients: Data from a Single Tertiary Diabetes Care Clinic in Poland

Diabetic Foot Syndrome (DFS) commonly occurs with infected ulceration and is associated with a high rate of amputation and excessive mortality. Antibiotic therapy increases the risk of Clostridium difficile infection (CDI). The mean CDI rate in European hospitals is 7.0 cases (country range 0.7-28.7) per 10 000 patient-bed days (PBD). The risk of hospital-acquired CDI (HA-CDI) among patients with diabetes mellitus (DM) and DFS may be much higher than in the general hospitalized population. The aim of the study is to define the incidence of HA-CDI in patients with DM and DFS. We performed a retrospective analysis using 2018 data from a tertiary diabetes care hospital which provides medical care mostly to patients with diabetes, including those admitted from the emergency department. We included patients with CDI confirmed by positive test result for toxins A/B. In 2018, CDI occurred in 22 cases, including 9 in patients with DFS. Overall, the CDI incidence rate was 21.6 cases per 10 000 PBD. The rate was much higher among patients with DFS than among patients department-wide (IRR: 3.73, 95% CI: 1.59-8.71). Prior to testing for toxins A/B, antibiotics were used in all DM patients with DFS who developed HA-CDI (9/9) and in 83.8% (109/130) DFS cases not complicated by CDI. Patients with DFS and CDI were characterized by lower mean BMI (28.3±0.4 vs. 30.3±0.6 kg/m2, p=0.01) than patients with DFS and without CDI. Between these two groups, no statistically significant differences were found in sex (male: 96/130 vs. 6/9, p=0.70), median age at hospitalization (65.0 (57.0-70.0) vs. 62.0 (52.0-67.0) yrs., p=0.30), HbA1c (68.3 (42.1-80.3) vs. 60.7 (49.7-78.1) mmol/mol, p=0.93) and eGFR (78.0 (62.0-93.0) vs. 84.5 (54.0-97.0) ml/min/1,73m2, p=0.91). Our results showed that DM patients with DFS had a higher risk of CDI than patients department-wide. Disclosure J. Hohendorff: None. M. Serafin: None. P.W. Witek: None. S. Borys: None. B. Katra: None. M. Malecki: None.

206 Oral Vancomycin Prophylaxis for the Primary and Secondary Prevention of Clostridium difficile Infection: A Systematic Review and Meta-Analysis

INTRODUCTION: Clostridium difficile infection (CDI) is the leading cause of infectious healthcare-associated diarrhea. It is a major cause of in-hospital morbidity and increased healthcare costs. Past research has identified populations at high risk of CDI. However, there is no current consensus on CDI prophylaxis. Oral vancomycin prophylaxis (OVP) has been suggested for the primary and secondary prevention of CDI. Therefore, we have conducted a comprehensive systematic review and meta-analysis to investigate the role of OVP in CDI prevention in published literature. METHODS: A computerized search of MEDLINE, EMBASE and Cochrane databases from inception to March 2019 for publications investigating OVP for CDI prevention. Results were screened for relevance and eligibility criteria. Relevant data was extracted and analyzed using Comprehensive Meta Analysis software. Publication bias was assessed for using Egger's test. P < 0.05 was considered significant. RESULTS: Six retrospective cohort studies with total of 1263 patients published between 2016–2019 were included. OVP use was associated with lower CDI (OR 0.175, CI 0.06–0.52) with considerable heterogeneity (I2 67%). OVP use was associated with lower CDI in immunocompromised (OR 0.072 CI 0.01–0.92) (I2 30.8%) as well as immunocompetent (OR 0.22, CI 0.07–0.69) (I2 71%) patients. The reduction in CDI was noted when OVP was used for primary (OR 0.04, CI 0.01–0.27) (I2 0%) as well as secondary (OR 0.27, CI 0.10–0.76) (I2 64%) prevention. Meta regression analysis showed that total daily dose of OVP was correlated to OR of CDI and was able to explain 100% of heterogeneity noted between studies. Only two studies evaluated the risk of VRE emergence in treated populations and found no significant increase. No publication bias was found using Egger's test. CONCLUSION: Our results suggest that the use of OVP was associated with lower CDI rates in at-risk populations. Higher daily doses of OVP were associated with higher rates of CDI suggesting that a lower OVP dose might be more effective for CDI prevention. While it might be prudent for physicians to prescribe OVP for high risk patients, the total daily dose, duration of treatment and long term side-effects are yet to be determined. These questions should be further evaluated with randomized controlled trials.

1002 Clostridioides difficile Infection in Liver Transplant Recipients

INTRODUCTION: Clostridium Difficile Infection (CDI) has been increasing in prevalence within the United States. The CDC estimates that approximately half a million people are infected every year. Patients with liver transplantation tend to require more hospitalizations with increased frequency of antibiotics and higher risk for CDI. We sought to evaluate outcomes of patients with liver transplantation developing CDI. METHODS: The study population was derived from the HCUP-National Inpatient Sampling (NIS) database for the years 2010 to the third quarter of 2015. ICD-9 codes were used to identify patients with history of liver transplant and CDI. In-hospital all-cause mortality, total cost of hospitalization, mean length of stay and outcomes rates were assessed. Propensity score matching was used to adjust for baseline confounders. RESULTS: A total of 8,567 individuals had a history of liver transplantation and co-existing CDI. Age and race were similar between the two groups; 43.7% of the CDI cohort were female. Patient’s in the control group had higher baseline clinical risk (Table 1). All-cause mortality (3.2% vs 1.7%, P < 0.0001), length of stay (10.4 ± 15.4 vs 5.5 ± 7.4, P < 0.0001), cost of hospitalization ($88,866 ± 166,834 vs $50,724 ± 94,482, P < 0.0001) and blood transfusion rates (13.6% vs 19%, P < 0.001) were higher in the CDI and liver transplant population. Colonoscopy and bowel resection were also performed significantly more frequently in the CDI and liver transplantation cohort (7.1% vs 2.9%, P < 0.0001 and 0.8% vs 1.1%, P = 0.012, respectively) (Table 2). After propensity score matching analysis, these statistically significant differences remained; bowel resection rates were similar between the two groups (1.3% vs 1.1%, P = 0.324). (Table 3). CONCLUSION: CDI in liver transplant recipients is associated with significantly higher rates of in-hospital mortality, blood transfusions, length of stay and total cost of hospitalization. Colonoscopy is used more frequently in the management of this population.

Clostridium Difficile infections in patients with AML or MDS undergoing allogeneic hematopoietic stem cell transplantation identify high risk for adverse outcome.

Clostridium difficile (CD) infection is the main cause of nosocomial enterocolitis in western countries and in patients undergoing allogeneic hematopoietic stem cell transplantation (alloHCT). Recipients of alloHCT are at high risk for CD infection but large studies in this population are rare and conflicting results have been reported. We analyzed 727 patients with AML or MDS undergoing alloHCT in our center from 2004 to 2015. Ninety-six patients (13%) had CD infection and 103 patients (14%) were identified as asymptomatic carriers by screening at admission and once a week during aplasia. Patients with CD infection had a shorter median overall survival of 8 months (95% CI, 6-36 months) compared with 25 months (95% CI, 17-35 months) for patients without CD infection, (HR 1.4, p = 0.04). CD positive patients were less likely to develop acute graft-versus-host disease (aGvHD; HR 0.6, p = 0.004) compared with CD-negative patients, but did not show differences in gastrointestinal aGvHD (HR 0.9, p = 0.5). Symptomatic patients developed gastrointestinal aGvHD (HR 2.5, p = 0.02) more often compared with asymptomatic CD positive patients. This analysis demonstrates a high prevalence for CD infection in patients undergoing alloHCT. A significant lower overall survival for patients with CD infection could be demonstrated.

Evaluation of a risk score to predict future Clostridium difficile disease using UK primary care and hospital data in Clinical Practice Research Datalink

ABSTRACT We evaluated the applicability of a Clostridium difficile infection (CDI) risk index developed for patients at hospital discharge to identify persons at high-risk of CDI in a primary care population. This retrospective observational study used data from the UK Clinical Practice Research Datalink, linked with Hospital Episodes Statistics. The risk index was based on the following patient characteristics: age, previous hospitalizations, days in hospital, and prior antibiotics use. Individual risk scores were calculated by summing points assigned to pre-defined categories for each characteristic. We assessed the association of risk factors with CDI by multivariate logistic regression. The estimated CDI incidence rate was 4/10,000 and 2/10,000 person-years in 2008 and 2012, respectively. On an index with a maximal risk of 19, a cut-off for high risk of ≥7 had sensitivity, specificity and positive predictive values of 80%, 87% and 12%, respectively. A high-risk person had a ~ 35% higher risk of CDI than a low-risk person. Multivariate risk factor analysis indicated a need to reconsider the relative risk scores. The CDI risk index can be applied to the UK primary care population and help identify study populations for vaccine development studies. Reassessing the relative weights assigned to risk factors could improve the index performance in this setting.

493. Development of a Simple Clostridium difficile Infection Clinical Risk Prediction Tool for Medical Inpatients

BackgroundPrevention of Clostridium difficile infection (CDI) remains a significant healthcare challenge. Risk prediction tools can potentially identify high-risk patients and allow for early prophylactic interventions. Various tools have been studied but none have been widely adopted. Our objective was to develop a simple risk prediction tool to identify medicine inpatients at high risk for developing primary CDI.MethodsWe conducted a retrospective, single-centre case–control study including patients admitted to the internal medicine service at our institution with a positive C. difficile polymerase chain reaction assay in loose stool. Controls were randomly selected from the same population. Risk factors for CDI were identified using univariate and multivariate logistic regression analyses. A model was created using variables that minimized Akaike Information Criterion and yielded higher area under the curve values.ResultsA total of 314 patients were included (157 with CDI and 157 controls). Variables included in the final 5-point, 3-variable risk prediction tool were age, modified Horn’s index and antibiotic use within 3 months. The tool demonstrated good discrimination with a C statistic of 0.79 and model optimism of 0.04 based on a bootstrap sample of 2,000 replicates.ConclusionOur simple 3-variable risk prediction tool based on age, disease severity and recent antibiotic use facilitates rapid bedside assessment by clinicians to identify medicine patients at high risk of CDI on admission. Further research is needed to determine whether this tool can reduce primary CDI incidence and healthcare costs.Table 1.Five-Point CDI Clinical Risk Tool and Predicted Risk.Figure 1.Receiver operating characteristic (ROC) curve for CDI risk prediction modelFigure 2.CDI risk prediction model calibration plot. Clostridium difficile infection risk prediction model calibration plot showing agreement between observed and predicted risks. Dashed line shows perfect agreement; lines above the dashed line indicate the predicted risks are lower than the actual risk.Disclosures All authors: No reported disclosures.

514. The Effect of Probiotics on the Incidence of Clostridium difficile

BackgroundCurrently there is conflicting evidence regarding probiotics affecting the incidence and/or severity of Clostridium difficile infection (CDI). According to the IDSA guidelines, there are insufficient data to support the use of probiotics as primary prophylaxis of CDI. The primary objective of this study was to evaluate whether the administration of probiotics is efficacious for CDI prophylaxis in patients who are on antibiotics making them at increased risk for contracting CDI.MethodsThe study is an Institutional Review Board approved retrospective cohort study looking at patients who were admitted to NYU Winthrop University Hospital and received at least one dose of antibiotics considered high-risk of inducing CDI. Patients were grouped according to concurrent probiotic use and the association between probiotic use and incident CDI was examined. A model for incident CDI adjusting for number of concurrent antibiotics, patient age, proton pump inhibitors, histamine receptor antagonists, presence of colitis, and chemotherapy was also estimated. Microbiology reports were analyzed for up to 12 weeks post initial administration of antibiotics to determine whether patient acquired CDI. If no CDI occurred during the admission or post discharge, data was censored at 12 weeks.ResultsOf 2,208 patients, 1,502 (68%) were included in the interim analysis. Ninety-six out of 1,502 patients (6.39%) had CDI within 12 weeks of antibiotics initiation. One hundred thirty-five (9%) were on probiotics during antibiotic use and 1,367 (91%) were not. Of those taking probiotics, 11.1% had an incident of CDI and of those not taking probiotics, 5.9% had an incident of CDI with a relative risk of 1.88 (1.11, 3.16) and a P = 0.02. After adjustment, although a positive association between probiotics and CDI was still observed, it was not statistically significant (P = 0.24)ConclusionBased on the interim analysis, probiotics were associated with a higher risk of CDI in univariate analysis, however, when adjusted for several confounding factors this association, while still positive, was no longer statistically significant.Further data collection is ongoing to corroborate these results. Disclosures All authors: No reported disclosures.

Efficacy of Fecal Microbiota Transplantation for Clostridium difficile Infection in Immunocompromised Patients: A Systematic Review and Meta-Analysis

Introduction: Fecal microbiota transplantation (FMT) is a safe and effective therapy for recurrent Clostridium difficile infection (CDI). Although immunocompromised patients are at high risk of CDI, the use of FMT may be limited owing to safety concerns. Since most FMT clinical trials exclude these patients, data on efficacy and safety of FMT in these patients are limited. We report results from a systematicreview and meta-analysis to evaluate the efficacy and safety of FMT in immunocompromised patients. Methods: A systematic search of MEDLINE, Embase and Web of Science was performed up to April 2018, followed by manual search of identified studies. We included case series, case-control or cohort studies, and clinical trials of FMT for CDI in immunocompromised patients with prevention of recurrent CDI as the primary outcome. Our primary analysis focused on calculating weighted pooled cure rate after one or more FMT. Results: A total of 18 studies were included. Among these, 566 immunocompromised patients underwent FMT for recurrent CDI. The various reason for immunosuppression included inflammatory bowel diseases, solid organ transplant (SOT), cancer, human immunodeficiency virus infection, graft versus host disease and hematopoietic stem cell transplants. Of the 566 patients, 430 had clinical cure of CDI with a pooled resolution rate after one FMT of 77.4% (95% CI, 71.6%-83.2%, I2= 57%).The pooled resolution rate increased to 91.5% (95% CI, 87.6%-95.4%, I2=21%) with multiple FMTs. No serious adverse events attributed to FMT were reported in any of the studies. On separating the 9 studies with immunosuppressed IBD patients, resolution after 1 FMT was reported in 328/412 patients, the pooled resolution rate 80.7% (95% CI, 76.6%-84.8%). In three studies with 103 SOT patients, FMT cured 58, with pooled cure rate of 50.2% (95% CI, 29.7%-70.6%). Conclusion: FMT appears to be safe and effective therapy for preventing recurrent CDI in immunocompromised patients. However, efficacy is lower in these patients compared to reported rates in immunocompetent patients. Efficacy improves with multiple FMTs. Although data were not available, repeat non-CDI antibiotic exposure in this population could potentially explain these findings. Studies are needed to explore best treatment practices in these patients including predictors of failed FMT which may identify patients who would benefit from early pre-emptive repeat FMT to prevent recurrent CDI

Effect of CMV on Outcomes Among Hospitalized Patients With Crohnʼs Disease

Introduction: Cytomegalovirus (CMV) is an opportunistic infection that can affect patients with severe Crohn's disease. Few studies have identified CMV as a risk factor for increased mortality and morbidity in Crohn's disease, but there are limited large database studies to understand the prevalence and affect of CMV in patients with Crohn's disease. We analyzed the national inpatient database (NIS) to understand the impact of CMV among hospitalized patients with Crohn's disease. Methods: We used the 2008-2012 NIS to identify patients aged ≥18 years with the diagnosis of Crohn's disease (international classification of diseases 9th revision, clinical modification [ICD-9-CM] diagnosis code 555.0-555.9) who were admitted to the hospital. Patients with concomitant CMV infection were identified using the ICD-9-CM diagnosis code 078.5. Multivariable regression analyses were used to determine the effect of CMV on outcomes including risk of clostridium difficile infection (CDI), colectomy, hospital length of stay (LOS), and in-hospital death. Results: A total of 932,048 patients were admitted to the hospital with either a primary or secondary diagnosis of Crohn's disease. Majority of the patients (75.4%) were aged 18-65 years, 59.5% of the patients were females, 70.8% of the patients were whites, and 41% of the patients had private insurance as their primary expected payer. Thirty two percent of patients had Crohn's disease as their primary diagnosis. A total of 964 patients (0.1%) had a concomitant diagnosis of CMV. In multivariable analyses, the presence of CMV infection showed a trend towards increased risk of CDI (odds ratio [OR] 2.1, 0.94-4.7, p=0.07), and was significantly associated with increased risk of colectomy (OR 7.6, 3.5-16.4, p <0.001), hospital LOS (OR 9.5, 7.1-12.0, p<0.001), and in-hospital death (OR 5.1, 2.6-9.8, p <0.001). In a secondary analysis only patients with primary diagnosis of Crohn's disease were included and the presence of CMV remained significantly associated with higher risk of CDI, colectomy, LOS and in-hospital death after adjusting for other confounding variables. Conclusion: Around 0.1% of the hospitalized patients with Crohn's disease are affected with CMV. Presence of CMV infection is associated with higher rates of CDI, colectomy, hospital LOS and in-hospital death. Risk adjustment is necessary while evaluating patients with Crohn's disease with concomitant CMV infection.

A Retrospective Study Analyzing the Appropriateness of Initial Treatment of Clostridium difficile in Patients with Active Malignancy.

Background Clostridium difficile infection (CDI) is the leading cause of hospital-associated gastrointestinal illness. Previous studies reported that patients with active malignancy are at high risk for CDIs, and yet they are still classified as nonsevere CDI and initially treated with metronidazole. Our aim is to investigate the need for the escalation of antibiotic therapy in patients with CDI and active cancer treated with oral metronidazole versus oral vancomycin. Methods This is a retrospective study of adult patients admitted with CDI and any underlying active malignancy at Beaumont Hospital, Royal Oak, Michigan, from January 2008 to December 2014. Inclusion criteria included age > 18 years old, polymerase chain reaction- (PCR-) proven CDI, and active malignancy. Results 197 patients were included in the final analysis. 44.8% of the metronidazole group required escalation of therapy compared to 15.2% in the vancomycin group (p value = 0.001). 29.8% of the combination group (metronidazole and vancomycin) underwent deescalation of antibiotics, which was significantly higher compared to 2.2% of patients in the vancomycin group (p value < 0.001). Discussion Our results support the initial use of vancomycin or a combination (metronidazole and vancomycin) versus metronidazole in patients with CDI and active malignancy.

Actoxumab + bezlotoxumab combination: what promise for Clostridium difficile treatment?

ABSTRACTIntroduction: Clostridium difficile infection (CDI) is the most common healthcare-associated infection worldwide. As standard CDI antibiotic therapies can result in unacceptably high recurrence rates, novel therapeutic strategies for CDI are necessary. A recently emerged immunological therapy is a monoclonal antibody against C. difficile toxin B.Areas covered: In this review, the authors summarize the available pharmacological, preclinical, and clinical data for the CDI treatment based on anti-toxin A (actoxumab) and anti-toxin B (bezlotoxumab) human monoclonal antibodies (HuMabs), and discuss about the potentiality of a therapy that includes HuMab combined administration for CDI.Expert opinion: Although only bezlotoxumab is indicated to reduce recurrence of CDI, experimental studies using a combination of HuMabs actoxumab and bezlotoxumab have shown that bolstering the host immune response against both the C. difficile toxins may be effective in primary and secondary CDI prevention. Besides neutralizing both the key virulence factors, combination of two HuMabs could potentially offer an advantage for a yet to emerge C. difficile strain, which is a steady threat for patients at high risk of CDI. However, as actoxumab development was halted, passive immunotherapy with actoxumab/bezlotoxumab is actually impracticable. Future research will be needed to assess HuMab combination as a therapeutic strategy in clinical and microbiological cure of CDI.

Association between omeprazole use and Clostridium difficile infection among hospitalized patients: A case-control study of the Saudi population.

Background: While few international studies have assessed the association between omeprazole use and the risk of Clostridium difficile infection (CDI), research into this is lacking in Saudi Arabia and the Middle East region. The aim of this study was to determine whether exposure to omeprazole is associated with the risk of Clostridium difficile infection in a sample of hospitalized Saudi patients. Methodology: A retrospective matched case–control study was conducted at the King Abdulaziz Medical City in Riyadh, Saudi Arabia, from 1 August 2010 through 31 July 2015. The analysis included a total of 200 patients: 100 CDI cases and 100 matched controls. Results: The majority (60%, 120 out of 200) of patients had received proton pump inhibitors (PPIs), and a minority (18.5%, 37 out of 200) had received omeprazole. The PPI use was insignificantly higher in CDI cases than in controls. However, the use of omeprazole was significantly higher in CDI cases compared with controls. Specifically, patients receiving omeprazole were two times more likely to develop CDI compared with controls (aOR = 2.1, 95% confidence interval (CI) = (1.007–4.437)). After adjusting for potential predictors of CDI, watery diarrhea (aOR = 59.1, 95% CI = 19.831–175.974) and abdominal pain (aOR = 7.5, 95% CI = 2.184–25.445) were found to be independent predictors of CDI. Conclusions: The data suggests that PPIs were commonly used in patients admitted to King Abdulaziz Medical City in Riyadh: six out of ten patients received PPIs. The findings support a possible association between the use of omeprazole and a high risk of CDI. To confirm causality, the link between omeprazole and CDI should be assessed in a large interventional study.

Investigating Orthopaedic Surgical Prophylaxis Changes and Post-operative Acute Kidney Injury (AKI) in NHS Grampian – a Test Case for NHS Scotland

ABSTRACT&#x0D; ObjectivesTo support reduction of Clostridium difficile infection (CDI), in 2008 the Scottish Antimicrobial Prescribing Group recommended that all NHS boards in Scotland restrict the use of antibiotics associated with a high risk of CDI. In NHS Grampian the policy for antibiotic prophylaxis in orthopaedic surgery was changed in June 2010. Trauma patients undergoing internal fixation or arthroplasty received flucloxacillin or co-amoxiclav before the policy change and flucloxacillin and gentamicin after the policy change. Previous studies have found similar policy changes resulted in an increase in post-operative acute kidney injury (AKI) and this study examined rates of post-operative AKI before and after this policy change in the NHS Grampian region of Scotland. Patients undergoing elective arthroplasty received either flucloxacillin or co-amoxiclav or cefuroxime before the policy change and cefuroxime afterwards.&#x0D; ApproachAll NHS Grampian patients who underwent an orthopaedic surgical procedure with prophylaxis during the period 01 June 2008 to 31 May 2012 were selected. Cases were linked to local creatinine data to detect post-operative AKI. Cases were further linked to national coverage data: (i) hospital discharge data to create the Charlson score for comorbidity, (ii) patient-level community prescribing data to identify previous exposure to any medicines which predispose to renal impairment, (iii) patient-level infection data to identify any post-operative CDI and (iv) Scottish Renal Registry data for case exclusion purposes. Segmented regression analyses of interrupted time series were used to evaluate changes in level and trend associated with the intervention and estimate effect sizes.&#x0D; Results3,870 trauma cases and 5,475 elective cases were examined. There was a significant increase in AKI rate following the policy change (β=0.28; 95%CI, 0.03 to 0.53; p=0.028) in trauma patients, equating to an increase of 0.28 cases of AKI per 100 procedures per month and a relative intervention effect at 24 months of 150% (95% CI 25% to 250%) There was no significant change in AKI rate among elective patients.&#x0D; ConclusionWe found that a change in orthopaedic antibiotic prophylaxis policy in NHS Grampian to flucloxacillin plus gentamcin was associated with an increase in post-operative AKI. This is consistent with observations in other boards and supports the new recommendation away from this policy made by SAPG in 2012. In cohort of trauma patients we found the change in policy was associated with an increase in post-operative AKI rate.

Use of tigecycline for the management of Clostridium difficile colitis in oncology patients and case series of breakthrough infections

Clostridium difficile infection (CDI) is the most frequent cause of nosocomial diarrhoea in adults. Cancer patients, in particular, are at a higher risk for CDI. Limited clinical data exist regarding the use of tigecycline for the treatment of CDI, especially in patients with oncologic and haematologic malignancies. To characterize the use of tigecycline for treatment of CDI in oncology patients at an academic cancer centre. This was a retrospective, single-centre, single-arm, chart review evaluating the use of tigecycline for the management of CDI in oncology patients at an academic cancer centre. The median age of CDI diagnosis in this patient group (N=66) was 65 years (range: 16-84) and the majority of patients had solid tumour malignancies. Fifty-six percent of patients had severe CDI, 70.3% of which were classified as having severe complicated disease. The median time to initiation of tigecycline therapy was 2 days (mean: 3.83) and the median number of tigecycline doses was 13 (range: 1-50). Twelve non-CDI breakthrough infections were observed, and four patients developed CDI while receiving tigecycline for non-CDI indications. The rate of death was 18% and the recurrence rate was 15.2%. Tigecycline did not lead to overt benefits in outcomes of oncology patients with CDI when compared to historical data. In addition, several breakthrough CDIs were observed in patients who received the drug for a non-CDI indication. Further prospective research is needed to validate the use of tigecycline for management of CDI.

The tipping point: patients predisposed to Clostridium difficile infection and a hospital antimicrobial stewardship programme

The incidence and severity of Clostridium difficile infection (CDI) have increased in recent years. Predictive models may help to identify at-risk patients before the onset of infection. Early identification of high-risk patients could help antimicrobial stewardship (AMS) programmes and other initiatives to better prevent C.difficile in these patients. To develop a predictive model that identifies patients at high risk for CDI at the time of hospitalization. This approach to early identification was evaluated to determine if it could improve upon a pre-existing AMS programme. Logistic regression and receiver operating characteristic (ROC) curve analyses were used to develop an analytic model to predict risk for CDI at the time of hospitalization in a retrospective cohort of inpatients. The model was validated in a prospective cohort. Concurrence between the model's risk predictions and a pre-existing AMS programme was assessed. The model identified 55% of patients who later tested positive as being at high risk for CDI at the time of admission. One in every 32 high-risk patients with potentially modifiable antimicrobial risk factors tested positive for CDI. Half (53%) tested positive before meeting the risk criteria for the hospital's AMS programme. Analytic models can identify most patients prospectively at the time of admission who later test positive for C.difficile. This approach to early identification may help AMS programmes to pursue susceptibility testing and modifications to antimicrobial therapies at an earlier stage in order to better prevent CDI.

Predicting the Risk of Clostridium difficile Infection upon Admission: A Score to Identify Patients for Antimicrobial Stewardship Efforts.

Increasing morbidity and health care costs related to Clostridium difficile infection (CDI) have heightened interest in methods to identify patients who would most benefit from interventions to mitigate the likelihood of CDI. To develop a risk score that can be calculated upon hospital admission and used by antimicrobial stewards, including pharmacists and clinicians, to identify patients at risk for CDI who would benefit from enhanced antibiotic review and patient education. We assembled a cohort of Kaiser Permanente Northwest patients with a hospital admission from July 1, 2005, through December 30, 2012, and identified CDI in the six months following hospital admission. Using Cox regression, we constructed a score to identify patients at high risk for CDI on the basis of preadmission characteristics. We calculated and plotted the observed six-month CDI risk for each decile of predicted risk. We identified 721 CDIs following 54,186 hospital admissions-a 6-month incidence of 13.3 CDIs/1000 patient admissions. Patients with the highest predicted risk of CDI had an observed incidence of 53 CDIs/1000 patient admissions. The score differentiated between patients who do and do not develop CDI, with values for the extended C-statistic of 0.75. Predicted risk for CDI agreed closely with observed risk. Our risk score accurately predicted six-month risk for CDI using preadmission characteristics. Accurate predictions among the highest-risk patient subgroups allow for the identification of patients who could be targeted for and who would likely benefit from review of inpatient antibiotic use or enhanced educational efforts at the time of discharge planning.

Outcomes of Clostridium difficile infection in pediatric solid organ transplant recipients.

The incidence of Clostridium difficile infection (CDI) is increasing in the pediatric population. Pediatric recipients of solid organ transplantation (SOT) may be at a higher risk for CDI in part because of chemotherapy and prolonged hospitalization. We utilized data from the Healthcare Cost and Utilization Project Kids' Inpatient Database to study the incidence and outcomes related to CDI as a complicating factor in pediatric recipients of SOT. Our results demonstrate that hospitalized children with SOT have increased rates of infection, with the greatest risk for younger children with additional comorbidities and severe illness. The type of transplanted organ affects the risk for CDI, with the lowest incidence observed in renal transplant patients. The occurrence of CDI in the pediatric SOT population contributes to a greater length of stay and higher hospital charges. However, CDI is not an independent predictor of increased in- hospital mortality in these patients.

Clostridium difficile Infection in Pediatric Solid Organ Transplant Recipients: Presidential Poster

Introduction: The incidence of Clostridium difficile infection (CDI) is increasing in the pediatric population. Pediatric recipients of solid organ transplantation (SOT) may be at a higher risk for CDI in part due to chemotherapy and prolonged hospitalization. Methods: We utilized data from the Healthcare Cost and Utilization Project Kids' Inpatient Database (HCUP-KID) to study the incidence and outcomes related to CDI as a complicating factor in pediatric recipients of SOT. Results: In 2012 there were an estimated total of 1,580,200 U.S. hospital discharges for children 1-17 years of age. Of these, 12,797 patients had an ICD-9-CM code that identified their hospital stay with a diagnosis relating to one or more of the 6 organ transplants assessed in this study, which were liver, kidney, lung, heart, intestinal and pancreas. In a contemporaneous time period and age group, there were a total of 9,180 hospital discharges with a diagnosis of CDI. The highest incidence was in children with pancreas (7.7%) and intestinal (5.2%) transplantation while the lowest incidence was in children with renal transplantation (2.3%). The rate of CDI infection in children without SOT was 0.6% and was substantially greater (3.6%) in children with SOT (OR 6.6; 95% CI 6.0-7.3; p < 0.05). The rate of CMV infection was higher in the SOT+CDI group compared to children in the SOT-only group (3.7% versus 1.9%; p < 0.05). Similarly, the incidence of GVHD was also higher in SOT patients with CDI (1.50% versus 0.6%; p < 0.05). However, the rate of PTLD, which was approximately 4.0%, did not differ between the two groups (p=0.87). The greatest risk of CDI infection was noted for younger children with additional comorbidities and severe illness. The presence of CDI as a complicating factor in SOT was not independently associated with a higher risk of mortality (aOR 1.5; 95% CI 0.6-4.0). However, CDI did result in a greater-than-median length of stay (aOR 1.7; 95% CI 1.3-2.2) and higher-than-median hospitalization charges (aOR 1.3; 95% CI 1.1-1.7). Conclusion: To our knowledge, this is the first pediatric study utilizing multi-institutional national data to examine the relationship of CDI as a complicating factor in SOT patients. The occurrence of CDI in the pediatric SOT population contributes to a greater length of stay and higher hospital charges. However CDI is not an independent predictor of increased in hospital mortality in these patients.Figure 1Figure 2