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The Clinical Burden of Clostridioides difficile in Ontario, Canada.

ABSTRACT: Background:To 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. Methods:We 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. Results:We 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.

SUBMITTER: Pereira JA

PROVIDER: S-EPMC6993863 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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The Clinical Burden of <i>Clostridioides difficile</i> in Ontario, Canada.

Pereira Jennifer A JA McGeer Allison A Tomovici Antigona A Selmani Alex A Chit Ayman A

Open forum infectious diseases 20191214 2

<h4>Background</h4>To understand the clinical burden of <i>Clostridioides difficile</i> 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.<h4>Methods</h4>We performed a retrospective analysis using individual-level data from Ontario databases (April 1, 2005 to March 31, 2015), identifying CDI cases ≥18 years requiring ho ...[more]

PMID: 32025524

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Project description:BACKGROUND:Understanding the impact of prevention programs on Clostridioides difficile infection rates is important, and decisions on future program changes, including how to use vaccines currently in development, requires a detailed understanding of the epidemiologic features of C. difficile infection. We analyzed Ontario health administrative data to determine incidence rates and medical costs of C. difficile infection, based on whether acquisition and onset occurred in acute care hospitals (ACHs), long-term care facilities or the community. METHODS:We performed a retrospective analysis using individual-level data from Ontario health databases from Apr. 1, 2005, to Mar. 31, 2015, identifying rates of C. difficile infection requiring hospital admission per 100 000 person-years in adults aged 18 years or more for categories of acquisition and onset. We estimated health care system costs of infection 180 and 365 days after admission by matching patients with C. difficile infection with control patients with similar characteristics. RESULTS:Over the study period, 33 909 people in Ontario were admitted to hospital with C. difficile infection; 17 272 cases (50.9%) were associated with ACHs. The number of cases per 100 000 person-years ranged from 27.7 in 2009/10 to 37.0 in 2012/13. Annually, the highest incidence of infection was for ACH-associated/ACH-onset. Community-associated infection became more prevalent over time, rising from 19.4% of cases in 2005/06 to 29.2% in 2014/15. Infection costs were mostly due to hospital admission within 180 days after hospital discharge. Infection associated with ACHs had the highest total costs and the largest cost attributable to C. difficile infection (median $38 953 for infected patients v. $13 542 for control patients). Median costs attributable to C. difficile infection were $1051 for that associated with long-term care facilities, $13 249 for community-associated infection and $11 917 for ACH-associated/community-onset infection. INTERPRETATION:Community-associated C. difficile infection had similar health care cost implications as hospital-associated infection. With rates of community-associated C. difficile infection on the rise, family physicians should be supported to prevent this infection in their patients.

Project description:BackgroundThis real-world study assessed the epidemiology and clinical complications of Clostridioides difficile infections (CDIs) and recurrences (rCDIs) in hospital and community settings in Germany from 2015 - 2019.MethodsAn observational retrospective cohort study was conducted among adult patients diagnosed with CDI in hospital and community settings using statutory health insurance claims data from the BKK database. A cross-sectional approach was used to estimate the annual incidence rate of CDI and rCDI episodes per 100,000 insurants. Patients' demographic and clinical characteristics were described at the time of first CDI episode. Kaplan-Meier method was used to estimate the time to rCDIs and time to complications (colonic perforation, colectomy, loop ileostomy, toxic megacolon, ulcerative colitis, peritonitis, and sepsis). A Cox model was used to assess the risk of developing complications, with the number of rCDIs as a time-dependent covariate.ResultsA total of 15,402 CDI episodes were recorded among 11,884 patients. The overall incidence of CDI episodes declined by 38% from 2015 to 2019. Most patients (77%) were aged ≥ 65 years. Around 19% of CDI patients experienced at least one rCDI. The median time between index CDI episode to a rCDI was 20 days. The most frequent complication within 12-months of follow-up after the index CDI episode was sepsis (7.57%), followed by colectomy (3.20%). The rate of complications increased with the number of rCDIs. The risk of any complication increased by 31% with each subsequent rCDI (adjusted hazard ratio [HR]: 1.31, 95% confidence interval: 1.17;1.46).ConclusionsCDI remains a public health concern in Germany despite a decline in the incidence over recent years. A substantial proportion of CDI patients experience rCDIs, which increase the risk of severe clinical complications. The results highlight an increasing need of improved therapeutic management of CDI, particularly efforts to prevent rCDI.

Project description: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.).

Project description:The response to iron limitation of several bacteria is regulated by the ferric uptake regulator (Fur). The Fur-regulated transcriptional, translational and metabolic networks of the Gram-positive, pathogen Clostridioides difficile were investigated by a combined RNA sequencing, proteomic, metabolomic and electron microscopy approach. At high iron conditions (760 g/l) the C. difficile fur mutant displayed a growth deficiency compared to wild type C. difficile cells. Several iron transporters were found induced by Fur regulation during low iron (11 g/l) conditions. The major adaptation to low iron conditions was observed for the central energy metabolism. Most ferredoxin-dependent amino acid fermentations were found significantly down regulated (had, etf, acd, grd, trx, bdc, hbd). The substrates of these pathways phenylalanine, leucine, glycine and some initial intermediates (phenylpyruvate, oxo-isocaproate, 3-hydroxy-butanoyl-CoA, crotonyl-CoA) were found accumulated, while some end product like isocaproate and butanoate were found reduced. Flavodoxin (fldX) formation and riboflavin biosynthesis (rib) were found enhanced, most likely to replace the missing ferredoxins. Proline reductase (prd), the corresponding ion pumping RNF complex (rnf) and the reaction product 5-aminovalerate were significantly enhanced. An ATP forming ATPase (atpCDGAHFEB,) of the F0F1-type was found induced while the formation of a V-type, mostly proton-pumping, ATP-consuming ATPase (atpDBAFCEKI, was decreased. The [Fe-S] enzyme-dependent pyruvate formate lyase (pfl), formate dehydrogenase (fdh) and hydrogenase (hyd) branch of glucose utilization and glycogen biosynthesis (glg) were significantly reduced, leading to an accumulation of glucose and pyruvate. The formation of [Fe-S] enzyme carbon monoxide dehydrogenase (coo) was inhibited. An intensive remodeling of the cell wall was observed most likely to increase antibiotic resistance. Polyamine biosynthesis (spe) was found induced leading to an accumulation of spermine, spermidine and putrescine. The fur mutant lost most of its flagella. Finally, the CRISPR/Cas and a prophage encoding operon were downregulated. Fur binding sites were found upstream of 20 of the regulated genes. Overall, adaptation to low iron conditions in C. difficile focused on an increase of iron import, significant decrease in metabolic iron utilization and protection during the complex transition.

Dataset Information

The Clinical Burden of Clostridioides difficile in Ontario, Canada.

Publications

The Clinical Burden of <i>Clostridioides difficile</i> in Ontario, Canada.

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