Host and Pathogen Factors for<i>Clostridium difficile</i>Infection and Colonization

Loo, Vivian G.; Bourgault, Anne–Marie; Poirier, Lionel A.; Lamothe, F; Michaud, Sophie; Turgeon, Nathalie; Toye, Baldwin; Beaudoin, Axelle; Frost, Éric; Gilca, Rodica; Brassard, Paul; Dendukuri, Nandini; Béliveau, Claire; Oughton, Matthew; Brukner, Ivan; Dascal, André

doi:10.1056/nejmoa1012413

Cited by 727 publications

(612 citation statements)

References 32 publications

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“…30 However, emerging data suggest that this may no longer be the case. 6,31 Of note, if asymptomatic carriage of C. difficile does maintain a protective effect against CDI and fewer than 50% of HO-CDI cases are from patients colonized on admission, the efficacy of testing should be even greater than found in this study. Given the prevalence of patient colonization at admission, these patients represent an important source of HO-CDI, and approaches to prevent disease in patients who are already colonized at admission are necessary.…”

Section: Discussionmentioning

confidence: 80%

“…5 The increase in C. difficile infection rates is attributed partially to the emergence of the epidemic NAP1/B1/027 strain, which has high levels of toxin A and B production and carries the binary toxin. [6][7][8] Despite the burden and threat posed by C. difficile, CDI prevention has changed little in recent decades. Current control strategies rely on limiting the spread of C. difficile from symptomatic patients.…”

mentioning

confidence: 99%

“…11 Consequently, CDI might be more effectively controlled by targeting additional sources of C. difficile transmission beyond clinical cases. Asymptomatic colonization prevalence for C. difficile among admitted patients has been reported to be up to 20%, 6,13,14 and admitted colonized patients may play an important role in sustaining C. difficile transmission in acute healthcare facilities. Therefore, preventing secondary infection transmission from asymptomatic colonized patients can be an additional control point to decrease CDI burden in hospitals.…”

mentioning

confidence: 99%

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Effectiveness of Screening Hospital Admissions to Detect Asymptomatic Carriers of Clostridium difficile: A Modeling Evaluation

Lanzas

Dubberke

2014

Infect. Control Hosp. Epidemiol.

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ObjectiveBoth asymptomatic and symptomatic Clostridium difficile carriers contribute to new colonizations and infections within a hospital, but current control strategies focus only on preventing transmission from symptomatic carriers. Our objective was to evaluate the potential effectiveness of methods targeting asymptomatic carriers to control C. difficile colonization and infection (CDI) rates in a hospital ward: screening patients at admission to detect asymptomatic C. difficile carriers and placing positive patients into contact precautions.MethodsWe developed an agent-based transmission model for C. difficile that incorporates screening and contact precautions for asymptomatic carriers in a hospital ward. We simulated scenarios that vary according to screening test characteristics, colonization prevalence, and type of strain present at admission.ResultsIn our baseline scenario, on average, 42% of CDI cases were community-onset cases. Within the hospital-onset (HO) cases, approximately half were patients admitted as asymptomatic carriers who became symptomatic in the ward. On average, testing for asymptomatic carriers reduced the number of new colonizations and HO-CDI cases by 40%–50% and 10%–25%, respectively, compared with the baseline scenario. Test sensitivity, turnaround time, colonization prevalence at admission, and strain type had significant effects on testing efficacy.ConclusionsTesting for asymptomatic carriers at admission may reduce both the number of new colonizations and HO-CDI cases. Additional reductions could be achieved by preventing disease in patients who are admitted as asymptomatic carriers and developed CDI during the hospital stay.

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Section: Discussionmentioning

confidence: 80%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Effectiveness of Screening Hospital Admissions to Detect Asymptomatic Carriers of Clostridium difficile: A Modeling Evaluation

Lanzas

Dubberke

2014

Infect. Control Hosp. Epidemiol.

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“…RNAi | nuclear translocation T he leading cause of diarrhea in hospitalized patients is Clostridium difficile infection due to antibiotic use (1). Toxin A (TxA) produced by C. difficile activates nuclear factor κB (NF-κB) and induces transcription of proinflammatory cytokines, including TNF-α and IL-8 (2).…”

mentioning

confidence: 99%

Local injection of dsRNA targeting calcitonin receptor-like receptor (CLR) ameliorates Clostridium difficile toxin A-induced ileitis

Bhargava¹,

Clifton²,

Mhaske³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Enteritis caused by Clostridium difficile toxin (Tx) is a nosocomial disease of increasing clinical concern, but the local mediators of C. difficile TxA inflammation are unknown. The potent vasodilator calcitonin gene-related peptide mediates neurogenic inflammation via the calcitonin receptor-like receptor (CLR). Here we examined the ileum-specific effects of reducing CLR on TxA ileitis by local preinjection of double-stranded RNAs. Treatment with CLR dsRNA for 7 d decreased CLR immunoreactivity, whereas treatment with non-CLR dsRNA did not. Subsequent injection of TxA in the same location increased CLR in rats treated with non-CLR dsRNA but not in rats treated with CLR dsRNA, documenting that local injection of dsRNA is effective in preventing the increase in CLR immunoreactivity in response to local TxA. After non-CLR dsRNA pretreatment, TxA induced robust intestinal secretion, myeloperoxidase activity, and histopathologic indications of inflammation including epithelial damage, congestion, neutrophil infiltration, loss of mucin from goblet cells, and increase in mast cell numbers. After CLR dsRNA pretreatment, TxA-induced changes in intestinal secretion and histopathologic inflammation were improved, including normal mucin staining and fewer resident mast cells. Loss of CLR prevented TxA-mediated activation of NF-κB and concomitant increases in pERK1/2 and TNF-α mRNA. Locally produced CLR plays a proinflammatory role in TxA ileitis via MAPK signaling and TNF-α. The results reported here strongly suggest that a local injection of dsRNA targeting CLR could be an effective local therapeutic approach at the inflammation site in the treatment of a growing, clinically relevant hospital-acquired disease, C. difficile infection.

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“…There is currently no accepted systematic method to determine or stratify the risk of development of RCDI, but there is an abundance of retrospective and surveillance literature citing several factors associated with the development of both an initial episode of CDI and RCDI. Factors shown to repeatedly correlate with RCDI were increasing age (≥ 65 years old), antibiotic therapy, and concomitant use of acid-suppressing medications (proton-pump inhibitors most frequently studied) (5)(6)(7)(12)(13)(14)(15)(16). While these factors were the most commonly cited, there are many other factors individually studied and found to be independently associated with CDI/RCDI including obesity, intraabdominal or gastrointestinal surgery, tube feedings or nasogastric tubes, inflammatory bowel disease (IBD), and immunocompromising disease states or medications (1,4,(17)(18)(19)(20)(21).…”

Section: Clostridium Difficile Infection (Cdi) Occurs Whenmentioning

confidence: 99%

Identification of Factors Impacting Recurrent Clostridium difficile Infection and Development of a Risk Evaluation Tool

et al. 2016

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-Purpose. Recurrent Clostridium difficile infection (RCDI) is a growing concern, yet limited data exists to clarify which patients are at highest risk. Identification of these patients may better inform decisions of those who may benefit from prophylactic intervention. The purpose of this study was to determine which factors are associated with the recurrence of Clostridium difficile infection (CDI) and to develop a risk stratification tool. Methods. Patients readmitted within 10 weeks of positive C. difficile polymerase chain reaction (PCR) with symptoms were included in this retrospective case control study. The primary outcome was analyzed via univariate regression analyses of the independent factors including age, gender, number of CDI episodes, administration of acid blocking agents, antibiotics or chemotherapy, Charlson Comorbidity Index, gastrointestinal conditions, and exposure to healthcare facilities. Results. Recurrent CDI was identified in 44 of 220 included patients. In the univariate analysis, factors associated with development of RCDI included antibiotic exposure (OR 2.51, 95% CI 1.14-5.54; p 0.02) and inflammatory bowel disease (OR 5.77, 95% CI 1.24-26.79; p 0.03). An evaluation tool was created from a well-fit model. Additional factors included in the tool were chosen based on evaluation of findings from existing literature. Conclusions. Antibiotic therapy and inflammatory bowel disease were found to be associated with RCDI. Although a statistically significant association with RCDI was not found for other factors, this is likely related to small sample size. The creation of an evaluation tool using specific patient factors can help determine the risk of RCDI, while future studies may validate this tool.

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Host and Pathogen Factors forClostridium difficileInfection and Colonization

Cited by 727 publications

References 32 publications

Effectiveness of Screening Hospital Admissions to Detect Asymptomatic Carriers of Clostridium difficile: A Modeling Evaluation

Effectiveness of Screening Hospital Admissions to Detect Asymptomatic Carriers of Clostridium difficile: A Modeling Evaluation

Local injection of dsRNA targeting calcitonin receptor-like receptor (CLR) ameliorates Clostridium difficile toxin A-induced ileitis

Identification of Factors Impacting Recurrent Clostridium difficile Infection and Development of a Risk Evaluation Tool

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