Burden Of Clostridioides Difficile Infection Research Articles

Costs Attributable to Clostridioides difficile Infection Based on the Setting of Onset.

Although hospital-onset Clostridioides difficile infection (CDI) is associated with significant healthcare costs, the economic burden of CDI with onset in other facilities or the community has not been well studied. Incident CDI cases were identified using 2011-2017 Medicare fee-for-service data. Controls were randomly selected in a 4:1 ratio matching to the CDI case surveillance definition. Inverse probability of exposure weights were used to balance on measured confounders. One-, 3-, and 5-year cumulative costs attributable to CDI were computed using a 3-part estimator (parametric survival model and pair of 2-part models predicting costs separately in intervals where death did and did not occur). A total of 60 492 CDI cases were frequency-matched to 241 968 controls. One-, 3-, and 5-year adjusted attributable costs were highest for hospital-onset CDI at $14 257, $18 953, and $21 792, respectively, compared with hospitalized controls and lowest for community-associated CDI compared with community controls at $1013, $3161, and $6454, respectively. Adjusted 1-, 3-, and 5-year costs attributable to community-onset healthcare facility-associated CDI were $8222, $13 066, and $16 329 and for other healthcare facility-onset CDI were $5345, $6764, and $7125, respectively. Economic costs attributable to CDI in elderly persons were highest for hospital-onset and community-onset healthcare facility-associated CDI. Although lower, attributable costs due to CDI were significantly higher in cases with CDI onset in the community or other healthcare facility than for comparable persons without CDI. Additional strategies to prevent CDI in the elderly are needed to reduce morbidity and healthcare expenditures.

Prevalence and trends of Clostridioides difficile infection among persons requiring maintenance hemodialysis: A systematic review and meta-analysis.

Clostridioides difficile infection (CDI) is among the most common cause of healthcare-associated infections. Persons requiring maintenance hemodialysis (MHD) are at increased risk of CDI and associated mortality compared to persons not requiring MHD. Given the clinical impact of CDI among persons requiring MHD, we aimed to quantify the burden of CDI and trends over time in this patient population. A systematic review and meta-analysis of studies reporting rates of CDI among persons requiring MHD in MEDLINE, Embase, Web of Science Core Collection, CINAHL, and Cochrane Central Register of Controlled Trials were performed. Searches were conducted on May 17, 2021, and March 4, 2022. In total, 2,408 titles and abstracts were identified; 240 underwent full text review. Among them, 15 studies provided data on rates of CDI among persons requiring MHD, and 8 of these also provided rates among persons not requiring MHD. The pooled prevalence of CDI among persons requiring MHD was 19.14%, compared to 5.16% among persons not requiring MHD (odds ratio [OR], 4.35; 95% confidence interval [CI], 2.07-9.16; P = .47). The linear increase in CDI over time was significant, increasing an average of 31.97% annually between 1993 and 2017 (OR, 1.32; 95% CI, 1.1-1.58; P < .01). The linear annual increase was similar among persons requiring and not requiring MHD (OR, 1.28; 95% CI, 1.13-1.45; P = .11). Persons requiring MHD have a 4-fold higher risk of CDI compared to persons not requiring MHD, and rates of CDI are increasing over time in both groups.

Trends in the incidence of Clostridioides difficile infection in adults and the elderly insured by Medicaid compared to commercial insurance or Medicare only.

Few data are available to quantify the Clostridioides difficile infection (CDI) burden in US adults depending on Medicaid insurance status; thus, we sought to contribute to this body of information. Retrospective cohort study to identify adults with codes for CDI from 2011 to 2017 in MarketScan commercial and Medicaid databases (for those aged 25-64 years) and the CMS Medicare database (for those aged ≥65 years). CDI was categorized as healthcare-facility-associated (HCA-CDI) and community-associated CDI (CA-CDI). CDI incidence rates were compared by year, insurer, and age group. The overall CDI incidence in the elderly was 3.1-fold higher in persons insured by Medicare plus Medicaid than in those insured by Medicare only (1,935 vs 618 per 100,000 person years (PY)), and the CDI incidence was 2.7-fold higher in younger adults with Medicaid compared to commercial insurance (195 vs 73 per 100,000 PY). From 2011 to 2017, HCA-CDI rates declined in the younger Medicaid population (124.0 to 95.2 per 100,000 PY; P < .001) but were stable in those commercially insured (25.9 to 24.8 per 100,000 PY; P = .33). In the elderly HCA-CDI rates declined from 2011 to 2017 in the Medicare-only population (403 to 318 per 100,000 PY; P < .001) and the Medicare plus Medicaid population (1,770 to 1,163 per 100,000 PY; P < .002). Persons with chronic medical conditions and those with immunocompromising conditions insured by Medicaid had 2.8- and 2.7-fold higher CDI incidence compared to the commercially insured population, respectively. The incidence of CDI was lowest in Medicaid and commercially insured younger adults without chronic medical or immunosuppressive conditions (67.5 and 45.6 per 100,000 PY, respectively). Although HCA-CDI incidence decreased from 2011 to 2017 in elderly and younger adults insured by Medicaid, the burden of CDI remains much higher in low-income adults insured by Medicaid.

Characteristics of antibiotic exposures for surgical procedures prior to Clostridioides difficile diagnosis—Minnesota, 2018

Background:Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated diarrhea. Significant risk factors for CDI include antibiotic use and healthcare exposure. Antibiotics are often administered before, during and/or after surgery to prevent postsurgical infection. The contribution of surgery-related antibiotics to the overall CDI burden has not been well described, and assessment of the appropriateness of surgical antibiotic use is complicated by complex clinical guidelines. We have described surgical antibiotic prophylaxis history among adult with CDI in Minnesota in 2018. Method: The Minnesota Department of Health (MDH) performs 5-county active population- and laboratory-based CDI surveillance as a CDC Emerging Infections Program site. Incident CDI was defined as stool positive for C. difficile by toxin or molecular assay from a person aged ≥18 years with no positive test in the preceding 8 weeks. History of CDI was defined as having had a previous CDI episode in the 2009–2018 surveillance data set. Medical records were reviewed for 12 weeks prior to incident CDI test date to identify antibiotic prescriptions. Antibiotics with documented indication for surgical-site infection prevention or surgical prophylaxis were classified as “surgical antibiotic prophylaxis” (SPPX). SPPX type (eg, intraoperative, postoperative), appropriateness of SPPX, and clinical guideline adherence were not assessed. Results: During 2018, 812 incident CDIs were reported to MDH among 736 patients. SPPX preceded 84 (10.3%) cases, non-SPPX antibiotic use preceded 465 cases (57.3%), and 263 cases (32.4%) had no documented prior antibiotic use. The median age of incident CDIs with preceding SPPX was 68 years (IQR, 54–79.5). In 25 incident CDI cases with preceding SPPX (29.8%), there were no other antibiotic exposures. Among incident CDIs with preceding SPPX, 11 (13.1%) had &gt;1 surgery event with SPPX. Prior CDI was identified for 13 (15.7%) with SPPX. Among 99 procedures with preceding SPPX, orthopedic surgeries (n = 27, 27.3%), gastrointestinal surgeries (n = 26, 26.3%), and cardiovascular surgeries (n = 22, 22.2%) were most common. In total 18 SPPX prescriptions (18.2%) originated in outpatient settings. SPPX drugs included cefazolin (n = 67, 67.7%), ceftriaxone (n = 7, 7.1%), ertapenem (n = 6, 6.1%), and clindamycin (n = 6, 6.1%). Median SPPX duration was 1 day (IQR, 1–2), and the median number days between surgery and specimen collection date was 19 (IQR, 7–49). Conclusions: Antibiotic stewardship programs should assess surgical prescribing, including in outpatient centers. Even short antibiotic duration for surgery could put patients at risk for CDI. More data are needed to evaluate the appropriateness of SPPX prescribing and to describe the impact of SPPX on CDI.Funding: NoneDisclosures: None

Epidemiology of Clostridioides difficile Infection in Portugal: A Retrospective, Observational Study of Hospitalized Patients.

Clostridioides difficile is the main cause of healthcare-associated diarrhea in Europe and North America. The aim of this study was to characterize the epidemiology and clinical burden of Clostridioides difficile infection among hospitalized patients in Portugal. Retrospective study conducted in six public hospital centers in Portugal. All primary Clostridioides difficile infection episodes and related recurrences occurring in 2017, as well as episodes developing two to eight weeks after the last episode diagnosed in that year, were documented. The National Reference Laboratory (National Institute of Health Dr. Ricardo Jorge) provided national surveillance data on Clostridioides difficile infection. A total of 385 inpatients with at least one primary episode diagnosed in 2017 were included. Most patients were aged over 70 years-old (73.2%). The included patients developed 451 episodes during the observation period. Approximately 44% of primary episodes were community-associated. Most episodes (94.9%) occurred in patients with one or more risk factors, with recent antibiotic exposure being particularly common (86.0%). All-cause in-hospital mortality was 19.5%, being significantly higher in patients aged over 65 years-old versus those aged 18 to 64 years-old (22.4% vs 7.8%, respectively). Over 50 different ribotypes were observed among 206 Clostridioides difficile strains received by the National Reference Laboratory. In Portugal, hospitalized patients with Clostridioides difficile infection are mostly older patients presenting risk factors for the development of this infection, particularly recent antibiotic exposure. Mortality is disproportionately high among the older population. Community-associated Clostridioides difficile infection is common among inpatients with this infection.

The Incidence and Impact of Clostridioides Difficile Infection (CDI) on Outcomes after Allogeneic Hematopoietic Cell Transplant (alloHCT) - a CIBMTR Study

Introduction: CDI is common after alloHCT mainly due to the frequent use of antibiotics before and during transplant. CDI is reported in 13 to 18% of recipients after alloHCT and in 6 to 8% after autologous HCT, mainly in the first-month post HCT. The determination of incidence and impact of CDI on HCT outcomes will help further our understanding towards the prevention and management of CDI post HCT.Methods: Using the CIBMTR dataset, we examined all patients aged two years and older who received first alloHCT for acute myeloid leukemia (AML), Acute Lymphocytic leukemia (ALL), or myelodysplastic syndrome (MDS) from related or unrelated donors between 2013 and 2018 at US centers. Stem cell sources included HLA-matched marrow, peripheral blood (PBSC), and umbilical cord blood (UCB) (4/6 or higher). The objective was to study the impact of CDI by day 100 on transplant outcomes by one year compared to the control cohort (without documented CDI from the same centers). Multivariable analyses were performed using Cox proportional hazard model for overall survival (OS), disease-free survival (DFS), Transplant related mortality (TRM), Infection-related mortality (IRM), chronic GVHD, and relapse. Both aGVHD preceding CDI and CDI preceding aGVHD were analyzed. Due to overlap in the onset of CDI and aGVHD, an interaction of these time-dependent events in some models were noted necessitating incorporation of a composite variable (CV - CDI+aGVHD) for OS, TRM, IRM, and cGVHD models.Results: A total of 826 patients with CDI and 6723 controls from 127 centers were analyzed. The cumulative incidence of CDI by day 100 following alloHCT was 18.7% (99% CI: 15% - 22.7%) and 10.2% (99% CI: 9.2% - 11.1%) in pediatric and adult patients, respectively [Figure 1]. The median time to diagnosis of CDI was 13 days (0 - 100). Recurrent CDI by 1 year occurred in 15% of patients. Myeloablative conditioning with total body irradiation (compared to Reduced-intensity/non-myeloablative (RIC/NMA) conditioning) and lower gastrointestinal GVHD preceding the diagnosis of CDI were risk factors for CDI. A diagnosis of MDS was associated with a lower risk of CDI. There was significant overlap in the onset of aGVHD and CDI [Figure 2] such that for patients with both CDI and aGVHD [n=378], 115 (30%) had aGVHD prior to CDI, and 70% were diagnosed with CDI first.CV - CDI + aGVHD was associated with a statistically significant increase in IRM and TRM and a decrease in OS. Specifically, CDI was associated with a 2.58-fold [99% CI: 1.43 - 4.66; p<0.001] increase in IRM which increased to >4 fold when CV-CDI + aGVHD was considered, irrespective of whether aGVHD preceded CDI or vice versa [CDI first: 4.88 (99% CI: 2.38 - 9.97), p<0.001; aGVHD first 4.15 (99% CI: 1.46 - 11.80), p = 0.0005]. CDI alone was not associated with increased risk of cGVHD [0.85 (99%CI: 0.66-1.09), p=0.0921], and the CV - CDI+aGVHD had similar risk of cGVHD as aGVHD without CDI. CDI had no impact on relapse or DFS.Conclusion: CDI tightly overlaps with aGVHD. Not surprisingly, the combination of CDI and aGVHD is associated with decreased overall survival and increased TRM. More concerning is that patients having both aGVHD and CDI had a >4-fold increased risk of death due to any infection. Our results highlight the burden and impact of CDI after alloHCT and the critical need to develop new/improved strategies for prevention in alloHCT recipients. [Display omitted] DisclosuresChemaly: Other: Other: Compensation: I am a consultant and advisor on companies who are developing new agents such as Merck, Ansun, and Janssen. Dandoy: Omeros: Other: Consulted and received Honorarium. Perales: Bristol-Myers Squibb: Honoraria; Sellas Life Sciences: Honoraria; Celgene: Honoraria; Cidara: Honoraria; Equilium: Honoraria; Incyte: Honoraria, Other; Karyopharm: Honoraria; Kite/Gilead: Honoraria, Other; Medigene: Honoraria; Merck: Honoraria; Miltenyi Biotec: Honoraria, Other; MorphoSys: Honoraria; Nektar Therapeutics: Honoraria, Other; NexImmune: Honoraria; Novartis: Honoraria, Other; Omeros: Honoraria; Servier: Honoraria; Takeda: Honoraria. Riches: BioIntelect: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Other: Payment; ATARA Biotherapeutics: Other: Payment. Ustun: novartis: Honoraria; Blueprint: Honoraria.

Clostridioides difficile Diarrhea: An Emerging Problem in a South Indian Tertiary Care Hospital.

ContextClostridioides difficile infection (CDI) is one of the most common infectious causes of hospital-acquired diarrhea. The actual burden of the disease is underestimated in India due to inadequate diagnostic methods and limited studies conducted. Aims The aim of this study was to determine the burden and risk factors of CDI among patients with hospital-acquired diarrhea. Methods and Materials Stool specimen of patients (age > 1 year) with hospital-acquired diarrhea were screened for glutamate dehydrogenase antigen and toxin using an enzyme immunoassay. If both antigen and toxin were present, it was reported as positive for toxigenic CDI. Samples positive for antigen and negative for toxin were further tested with Cepheid GeneXpert assay for detecting the toxin producing gene. Results Of 75 patients (mean age 36.07 ± 20.79, 64% males), 14 (18.67%) patients were positive for toxigenic Clostridioides difficile ( C. difficile ) and 3 (4%) patients were nontoxigenic C. difficile . Addition of GeneXpert to the testing algorithm increased the yield of toxin detection in 5/14 patients who were negative by toxin assay. On analysis of risk factors, prolonged hospital stay was found to have significant association ( p -value = 0.022). Patients with factors like intensive care unit stay, presence of diabetes mellitus as a comorbidity, and exposure to antibiotics like carbapenems and glycopeptides have been found to have a higher prevalence of CDI. Conclusions The prevalence of CDI in our population was 18.67% and the major risk factor associated was prolonged hospital stay. The addition of GeneXpert for the detection of toxin gene increased the yield from 12 to 18.68%.

Risks and Preventive Strategies for Clostridioides difficile Transmission to Household or Community Contacts during Transition in Healthcare Settings.

The burden of Clostridioides difficile infection (CDI) has greatly increased. We evaluated the risks for CDI transmission to community members after hospitalized patients are discharged. We conducted a systematic literature review in MEDLINE/PubMed, EMBASE, CINAHL plus EBSCO, Web of Science, Cochrane Library, and gray literature during January 2000‒February 2019 and identified 4,798 citations were identified. We eliminated 4,554 citations through title and abstract screening; 217 additional citations did not meet full criteria. We reviewed texts for the 27 remaining articles qualitatively for internal/external validity. A few identified studies describing risks to community members lacked accurate risk measurement or preventative strategies. Primary data are needed to assess efficacy of and inform current expertise-driven CDI prevention practices. Raising awareness among providers and researchers, conducting clinical and health services research, linking up integrated monitoring and evaluation processes at hospitals and outpatient settings, and developing and integrating CDI surveillance systems are warranted.

Burden of Clostridioides difficile infection (CDI) - a systematic review of the epidemiology of primary and recurrent CDI

BackgroundClostridioides difficile is a Gram-positive anaerobic bacterium, which causes Clostridioides difficile infection (CDI). It has been recognised as a leading cause of healthcare-associated infections and a considerable threat to public health globally. This systematic literature review (SLR) summarises the current evidence on the epidemiology and clinical burden of CDI.MethodsA SLR was conducted to identify CDI and recurrent CDI (rCDI) epidemiology studies, to evaluate patient and disease characteristics, incidence rates, epidemiological findings and risk factors. Embase, MEDLINE and the Cochrane Library databases were searched for English articles from 2009 to 2019. Included territories were the United Kingdom, France, Germany, Italy, Spain, Poland, US, Canada, Australia, Japan and China.ResultsOf 11,243 studies identified, 165 fulfilled the selection criteria. An additional 20 studies were identified through targeted review of grey literature. The most widely reported findings were incidence and risk factors for CDI and rCDI.Among key studies reporting both healthcare-associated (HA-CDI) and community-associated CDI (CA-CDI) incidence rates for each country of interest, incidence rates per 10,000 patient days in the US were 8.00 and 2.00 for HA-CDI and CA-CDI, respectively. The highest incidence in Europe was reported in Poland (HA-CDI: 6.18 per 10,000 patient days, CA-CDI: 1.4 per 10,000 patient days), the lowest from the UK, at 1.99 per 10,000 patient days and 0.56 per 10,000 patient days for HA-CDI and CA-CDI, respectively.No clear trend for incidence over time emerged, with most countries reporting stable rates but some either a decrease or increase.Rates of recurrent CDI varied based on geographical setting. The rate of recurrence was lower in community-associated disease compared to healthcare-associated disease.Independent CDI risk factors identified common to both initial CDI and recurrent CDI included increasing age, antibiotic use, recent hospitalisation, and proton pump inhibitor (PPI) use. In addition, leukocyte count, length of hospital stays, and Charlson comorbidity index score featured as statistically significant risk factors for recurrent CDI, but these are not reported among the most common statistically significant risk factors for initial CDI.ConclusionsDespite considerable heterogeneity, evidence suggests substantial incidence of recurrent and primary CDI, even after considerable efforts in the last decade.

Establishment of a French surveillance system of Clostridiodes difficile infection: Comparison of patient’s characteristics with other national and European data

IntroductionThe magnitude and scope of Clostridioides difficile infection (CDI) has changed with an increase in incidence and severity. The epidemiology of CDI is not well known in France due to difficulties to conduct large continuous surveillance. The objectives were to compare the characteristics of patients with CDI collected through repeated point prevalence survey via DIFTEC™, a free electronic tool, with those from previous French or European studies. MethodsDIFTEC™ was developed to evaluate epidemiological burden, diagnostic strategies and management of CDI in France. National and European guidelines were used for definitions.A literature review of studies conducted in Western Europe on CDI and published between January 2008 and May 2018 was done to compare their data with those included in the DIFTEC™ database. ResultsFrom January 2016, to December 2017, 455 CDI episodes from 22 French hospitals were included. Most of CDI cases were health-care associated (HCA) (78%).The comparison between included patients and French literature data showed that the rates of previous antibiotics exposure, crude mortality and recurrence were not statistically different. However HCA-CDI was significantly more frequent in the DIFTEC™ study.Gender distribution, recurrence and crude mortality rates were not statistically different compared to European data. HCA-CDI was more frequent in the DIFTEC™ study whereas previous treatment with proton pump inhibitors and antibiotics were significantly higher in European studies. DiscussionThese results illustrated the added value of a new tool for increasing the reliable knowledge of CDI in France based on epidemiological surveillance implemented in health-care settings.

The Burden of Clostridioides Difficile Infection during the COVID-19 Pandemic: A Retrospective Case-Control Study in Italian Hospitals (CloVid)

Data on the burden of Clostridioides difficile infection (CDI) in Coronavirus Disease 2019 (COVID-19) patients are scant. We conducted an observational, retrospective, multicenter, 1:3 case (COVID-19 patients with CDI)-control (COVID-19 patients without CDI) study in Italy to assess incidence and outcomes, and to identify risk factors for CDI in COVID-19 patients. From February through July 2020, 8402 COVID-19 patients were admitted to eight Italian hospitals; 38 CDI cases were identified, including 32 hospital-onset-CDI (HO-CDI) and 6 community-onset, healthcare-associated-CDI (CO-HCA-CDI). HO-CDI incidence was 4.4 × 10,000 patient-days. The percentage of cases recovering without complications at discharge (i.e., pressure ulcers, chronic heart decompensation) was lower than among controls (p = 0.01); in-hospital stays was longer among cases, 35.0 versus 19.4 days (p = 0.0007). The presence of a previous hospitalisation (p = 0.001), previous steroid administration (p = 0.008) and the administration of antibiotics during the stay (p = 0.004) were risk factors associated with CDI. In conclusions, CDI complicates COVID-19, mainly in patients with co-morbidities and previous healthcare exposures. Its association with antibiotic usage and hospital acquired bacterial infections should lead to strengthen antimicrobial stewardship programmes and infection prevention and control activities.

Outcomes of Fecal Microbiota Transplantation in Patients With Inflammatory Bowel Diseases and Recurrent Clostridioides difficile Infection

Outcomes of Fecal Microbiota Transplantation in Patients With Inflammatory Bowel Diseases and Recurrent Clostridioides difficile Infection

Cost burden of Clostridioides difficile infection to the health service: A retrospective cohort study in Scotland

Clostridioides difficile infection (CDI) is associated with high healthcare demands and related costs. To evaluate the healthcare and economic burden of CDI in hospitalized patients with community- (HOCA-CDI) or hospital-associated CDI (HOHA-CDI) in the National Health Service in Scotland. A retrospective cohort study was conducted, examining data between August 2010 and July 2013 from four patient-level Scottish datasets, linked to death data. Data examined included prior antimicrobial prescriptions in the community, hospitalizations, length of stay and mortality. Each CDI case was matched to three hospital-based controls on the basis of age, gender, hospital and date of admission. Descriptive economic evaluations were based on bed-day costs for different types of wards. Overall, 3304 CDI cases were included in the study. CDI was associated with additional median lengths of stay of 7.2 days for HOCA-CDI and 12.0 days for HOHA-CDI compared with their respective, matched controls. The 30-day mortality rate was 6.8% for HOCA-CDI and 12.4% for HOHA-CDI. Overall, recurrence within 90 days of the first CDI episode occurred in 373/2740 (13.6%) survivors. The median additional expenditure for each initial CDI case compared with matched controls was £1713. In the 6 months after the index hospitalization, the cost associated with a CDI case was £5126 higher than for controls. Using routinely collected national data, we demonstrated the substantial burden of CDI on healthcare services, including lengthy hospital stays and readmissions, which increased the costs of managing patients with CDI compared with matched controls.

The burden of Clostridioides difficile infection in patients with history of liver transplant and during index admission.

Liver transplant recipients have an increased risk of Clostridioides difficile infection (CDI) which associated with higher morbidity and mortality. CDI in liver transplant has been argued to increase hospital costs, charges, and length of stay (LOS) in small studies. However, no recent nationwide analysis determines these outcomes. This is a retrospective cohort study using the National Inpatient Sample 2016. All patients with ICD10CM diagnostic codes for CDI were included. The cohort was stratified for the history of liver transplant and liver transplant index admission. The primary outcome was the odds of CDI in both patient cohorts to patients without liver transplant. Secondary outcomes were inpatient morbidity, mortality, resource utilization, colectomy rates, LOS, and total hospital costs and charges. A total of 360 364 patients with CDI were identified, 1665 had a history of liver transplant and 155 had liver transplant during that admission. Patients with a history of liver transplant had increased odds of CDI compared to patients with no history of liver transplant (adjusted odds ratio 2.78; 95% confidence interval, 2.44-3.16). Patients with CDI had greater odds of shock, acute kidney injury, ICU stay, organ failure and significantly higher costs, charges and LOS. Patients with a history of liver transplant increased odds of CDI. CDI with history of liver transplant and the index admission for liver transplant had higher odds of morbidity and resource utilization. Clinicians must maintain a high index of suspicion for CDI for early diagnosis and appropriate initiation of treatment.

Modeling inpatient and outpatient antibiotic stewardship interventions to reduce the burden of Clostridioides difficile infection in a regional healthcare network.

Antibiotic exposure can lead to unintended outcomes, including drug-drug interactions, adverse drug events, and healthcare-associated infections like Clostridioides difficile infection (CDI). Improving antibiotic use is critical to reduce an individual’s CDI risk. Antibiotic stewardship initiatives can reduce inappropriate antibiotic prescribing (e.g., unnecessary antibiotic prescribing, inappropriate antibiotic selection), impacting both hospital (healthcare)-onset (HO)-CDI and community-associated (CA)-CDI. Previous computational and mathematical modeling studies have demonstrated a reduction in CDI incidence associated with antibiotic stewardship initiatives in hospital settings. Although the impact of antibiotic stewardship initiatives in long-term care facilities (LTCFs), including nursing homes, and in outpatient settings have been documented, the effects of specific interventions on CDI incidence are not well understood. We examined the relative effectiveness of antibiotic stewardship interventions on CDI incidence using a geospatially explicit agent-based model of a regional healthcare network in North Carolina. We simulated reductions in unnecessary antibiotic prescribing and inappropriate antibiotic selection with intervention scenarios at individual and network healthcare facilities, including short-term acute care hospitals (STACHs), nursing homes, and outpatient locations. Modeled antibiotic prescription rates were calculated using patient-level data on antibiotic length of therapy for the 10 modeled network STACHs. By simulating a 30% reduction in antibiotics prescribed across all inpatient and outpatient locations, we found the greatest reductions on network CDI incidence among tested scenarios, namely a 17% decrease in HO-CDI incidence and 7% decrease in CA-CDI. Among intervention scenarios of reducing inappropriate antibiotic selection, we found a greater impact on network CDI incidence when modeling this reduction in nursing homes alone compared to the same intervention in STACHs alone. These results support the potential importance of LTCF and outpatient antibiotic stewardship efforts on network CDI burden and add to the evidence that a coordinated approach to antibiotic stewardship across multiple facilities, including inpatient and outpatient settings, within a regional healthcare network could be an effective strategy to reduce network CDI burden.

Clostridioides difficile infection after pneumonia in elderly patients: which antibiotic is at lower risk?

Clostridioides difficile infection (CDI) is a frequent and severe complication of antibiotic treatment in older patients hospitalized for acute pneumonia (AP). We aimed to assess the burden and risk factors of CDI and to determine which of the usual antibiotics regimens is at lower risk for post-AP CDI incidence. Among patients aged >75y hospitalized for AP in all departments of a university hospital between 2007 and 2017, all the 92 patients developing a CDI were compared with 213 patients without CDI. Factors associated with 1) in-hospital and one-year mortality, 2) CDI incidence were assessed using logistic regression models. In patients with and without CDI after AP, mortality rates were respectively at 34% vs 20% in hospital and 63% vs 42% at one-year. After adjustment for confounders, CDI was associated with a two-fold risk of in-hospital and one-year mortality after pneumonia (Respective Odds Ratio (95% Confidence Interval), OR (95%CI): 1.95 (1.06-3.58) and 2.02 (1.43-7.31)). High number of antibiotics (Per antibiotic, OR (95%CI): 1.89 (1.18-3.06)), rather than antibiotics duration (Per day, OR 95%CI): 1.04 (0.96-1.11)) was associated with a higher risk of CDI. Compared with other antibiotics, use of penicillin + beta-lactamase inhibitors was associated with a lower risk of CDI (OR (95%CI): 0.43 (0.19 -0.99)) CONCLUSION: In older inpatients, CDI highly increase the burden of AP at both short and long term. If confirmed, these results suggest the preferential use of penicillin + beta-lactamase inhibitors for a lower incidence of CDI in older inpatients with AP.

PGI16 BREAKDOWN OF COSTS ATTRIBUTABLE TO CLOSTRIDIOIDES DIFFICILE INFECTION IN THE US: RESULTS FROM A SYSTEMATIC LITERATURE REVIEW

A previous systematic literature review (SLR) of Clostridioides difficile infection (CDI) global economic burden, conducted up to 2014, showed considerable costs of CDI. This SLR summarizes CDI-attributable economic burden literature in the United States (US) published since 2014. An SLR using terms for CDI, costs, and/or healthcare resource use was conducted across relevant databases from 1 January 2014 to 15 August 2018 without language or geographical restrictions, and supplemented by conference and HTA website searches. Costs attributed to CDI by study authors and differences in regression-adjusted or matched costs between CDI and non-CDI cohorts were extracted, including components of total costs (e.g., inpatient-, outpatient- and indirect costs, etc.) where available. Of 2,342 sources screened, 7 articles included CDI-attributable costs for US patients. Overall CDI-attributable cost ranged from 1.2-3.3 times that of non-CDI patients (incremental $1,700-$80,178), although study methods varied. Three studies presented detailed breakdown of direct costs; none included indirect costs. Two were retrospective database studies with one using insurance claims data. One study in primary CDI patients reported that 87% ($21,096) of the $24,205 overall CDI-attributable costs over 6 months was due to inpatient services, followed by outpatient ($1,520) and emergency services ($555). Another study found inpatient costs represented 91% ($73,045) of total CDI-attributable costs ($80,178). The third study, conducted in nursing homes over two months of follow-up, also found inpatient services were the predominant driver (55% [$8,243]) of total CDI-attributable costs ($14,977), with skilled nursing facility ($3,487) the next largest cost component. Consistent with the prior SLR, recent US studies demonstrate substantial direct medical costs attributable to CDI, with inpatient costs representing the largest proportion (55%-91%). However, non-inpatient services still account for $555-$7,133 in CDI-attributable costs. Future research should incorporate CDI-attributable indirect costs to more completely describe the economic burden of CDI.

Trends in U.S. Burden of Clostridioides difficile Infection and Outcomes

BackgroundEfforts to prevent Clostridioides difficile infection continue to expand across the health care spectrum in the United States. Whether these efforts are reducing the national burden of C. difficile infection is unclear.MethodsThe Emerging Infections Program identified cases of C. difficile infection (stool specimens positive for C. difficile in a person ≥1 year of age with no positive test in the previous 8 weeks) in 10 U.S. sites. We used case and census sampling weights to estimate the national burden of C. difficile infection, first recurrences, hospitalizations, and in-hospital deaths from 2011 through 2017. Health care–associated infections were defined as those with onset in a health care facility or associated with recent admission to a health care facility; all others were classified as community-associated infections. For trend analyses, we used weighted random-intercept models with negative binomial distribution and logistic-regression models to adjust for the higher sensitivity of nucleic acid amplification tests (NAATs) as compared with other test types.ResultsThe number of cases of C. difficile infection in the 10 U.S. sites was 15,461 in 2011 (10,177 health care–associated and 5284 community-associated cases) and 15,512 in 2017 (7973 health care–associated and 7539 community-associated cases). The estimated national burden of C. difficile infection was 476,400 cases (95% confidence interval [CI], 419,900 to 532,900) in 2011 and 462,100 cases (95% CI, 428,600 to 495,600) in 2017. With accounting for NAAT use, the adjusted estimate of the total burden of C. difficile infection decreased by 24% (95% CI, 6 to 36) from 2011 through 2017; the adjusted estimate of the national burden of health care–associated C. difficile infection decreased by 36% (95% CI, 24 to 54), whereas the adjusted estimate of the national burden of community-associated C. difficile infection was unchanged. The adjusted estimate of the burden of hospitalizations for C. difficile infection decreased by 24% (95% CI, 0 to 48), whereas the adjusted estimates of the burden of first recurrences and in-hospital deaths did not change significantly.ConclusionsThe estimated national burden of C. difficile infection and associated hospitalizations decreased from 2011 through 2017, owing to a decline in health care–associated infections. (Funded by the Centers for Disease Control and Prevention.)

Modeling inpatient and outpatient antibiotic stewardship interventions to reduce the burden of Clostridioides difficile infection in a regional healthcare network

Modeling inpatient and outpatient antibiotic stewardship interventions to reduce the burden of Clostridioides difficile infection in a regional healthcare network

The Clinical Burden of Clostridioides difficile in Ontario, Canada.

BackgroundTo understand the clinical burden of Clostridioides difficile infection (CDI), we analyzed health outcome data from Ontario, Canada for CDI associated with and manifested in acute care hospitals (ACH), long-term care facilities (LTCF), the community, or ACH-associated with community-onset.MethodsWe performed a retrospective analysis using individual-level data from Ontario databases (April 1, 2005 to March 31, 2015), identifying CDI cases ≥18 years requiring hospitalization, and stratifying into cohorts based on association and onset location. Cohort members were matched to controls on demographics and medical conditions at onset, for outcomes including 30- and 180-day all-cause mortality and rehospitalization.ResultsWe stratified 22 617 individuals hospitalized with CDI during the study period: 13 152 (58.1%) ACH-associated/ACH-onset, 7116 (31.5%) community-associated/community-onset, 1847 (8.2%) ACH-associated/community-onset, and 502 (2.2%) LTCF-associated/LTCF-onset. Compared with controls, unadjusted 30-day rehospitalization rates were significantly higher (P < .0001) for ACH-associated/ACH-onset CDI (9.5% vs 0.4%), LTCF-associated/LTCF-onset (7.2% vs 1.1%), community-associated/community-onset (7.8% vs 0.8%), and ACH-associated/community-onset (10.9% vs 0.7%). One hundred eighty-day mortality rates were higher in the community-associated/community-onset and the LTCF-associated/LTCF-onset cohorts than controls: 66.3% vs 12.3% (P < .0001) and 30.9% vs 3.1% (P < .0001), respectively. All differences remained significant after adjusting for patient factors.Conclusions Clostridioides difficile infection is associated with higher rates of 30-day rehospitalization compared with controls. In addition, mortality rates within 180-days of hospital discharge are significantly higher for community-associated/community-onset and LTCF-associated/LTCF-onset CDI cohorts than controls. Clostridioides difficile infection warrants increased prevention and monitoring efforts.