Development and Validation of a Prediction Model for Mortality and Adverse Outcomes Among Patients With Peripheral Eosinopenia on Admission for <i>Clostridium difficile</i> Infection

Kulaylat, Audrey S.; Buonomo, Erica L.; Scully, Kenneth W.; Hollenbeak, Christopher S.; Cook, Heather; Petri, William A.; Stewart, David B.

doi:10.1001/jamasurg.2018.3174

Cited by 51 publications

(73 citation statements)

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“…While C. difficile toxins drive epithelial disruption and disease during CDI, recently, many groups have demonstrated that the type of host immune response generated against C. difficile also dictates the severity of symptoms during infection, independent of bacterial factors [26][27][28][29][30]. The host immune system has a multifaceted role during CDI with some level of inflammation required to clear the infection.…”

Section: Microbiota-elicited Immunity and Its Importance In Combatingmentioning

confidence: 99%

Considering the Immune System during Fecal Microbiota Transplantation for Clostridioides difficile Infection

Frisbee

Petri

2020

Trends in Molecular Medicine

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Our understanding and utilization of fecal microbiota transplantation (FMT) has jump-started over the past two decades. Recent technological advancements in sequencing and metabolomics have allowed for better characterization of our intestinal microbial counterparts, triggering a surge of excitement in the fields of mucosal immunology and microbiology. This excitement is well founded, as demonstrated by 90% relapse-free cure rates in FMT treatment for recurrent Clostridioides difficile infections. Growing evidence suggests that in addition to bacterial factors, the host immune response during C. difficile infection greatly influences disease severity. In this review, we discuss recent advancements in understanding the interplay between immune cells and the microbiota and how they may relate to recovery from C. difficile through FMT therapy.

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Section: Microbiota-elicited Immunity and Its Importance In Combatingmentioning

confidence: 99%

Considering the Immune System during Fecal Microbiota Transplantation for Clostridioides difficile Infection

Frisbee

Petri

2020

Trends in Molecular Medicine

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“…While we detected robust eosinophil infiltration in the cecum of young mice, we did not observe this in the colon of young or aged animals. Another group found that peripheral loss of eosinophils in patients with C. difficile infection was predictive of severe disease (4). We report that young mice had significantly increased numbers of intestinal eosinophils during C. difficile infection, compared to mock-infected young controls, while aged mice did not have intestinal eosinophil infiltration and significantly worse CDI disease, compared to young mice.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, peripheral eosinophil counts were found to be predictive of CDI disease severity and mortality in patients (4), and eosinophils were shown to potentially be protective in mouse models of CDI (5, 6). Eosinophils are innate immune cells that predominantly reside in close proximity to microbes that colonize mucosal surfaces under non-inflammatory homeostasis (7).…”

Section: Introductionmentioning

confidence: 99%

“…There is now growing evidence supporting a previously under-appreciated role for eosinophils as important mediators of intestinal immune responses (10), and the expression of a broad range of pattern-recognition receptors in eosinophils suggest a potential role in bacterial infection (11). Recent efforts by multiple research groups have indicated a role for eosinophils in CDI disease (4–6). However, the specific role for eosinophils in CDI disease severity has yet to be completely elucidated, and few studies characterize the innate immune responses to C. difficile strains with a range of virulence potential in animals of advanced age.…”

Section: Introductionmentioning

confidence: 99%

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Aging dampens the intestinal innate immune response duringClostridioides difficileinfection and is associated with altered intestinal eosinophil mobilization

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et al. 2020

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16 17 Clostridioides (formerly Clostridium) difficile is the most common cause of hospital-18 acquired infection, and advanced age is a risk factor for C. difficile infection. Disruption of the 19 intestinal microbiota and immune responses contribute to host susceptibility and severity of C. 20 difficile infection. However, the impact of aging on the cellular immune response associated with 21 C. difficile infection in the setting of advanced age remains to be well described. This study 22 explores the effect of age on cellular immune responses in C. difficile infection as well as 23 disease severity. Young adult mice (2-3 months old) and aged mice (22-28 months old) were 24 rendered susceptible to C. difficile infection with cefoperazone and then infected with C. difficile 25 strains of varying disease-causing potential. Aged mice infected with C. difficile develop more 26 severe clinical disease, compared to young mice. Tissue-specific CD45+ immune cell 27 responses occurred at the time of peak disease severity in the cecum and colon of all mice 28 infected with a high-virulence strain of C. difficile; however, significant deficits in intestinal 29 neutrophils and eosinophils were detected in aged mice. Interestingly, while C. difficile infection 30 in young mice was associated with a robust increase in cecal and colonic eosinophils, there was 31 a complete lack of an intestinal eosinophil response in aged counterparts accompanied by a 32 simultaneous increase in blood eosinophils with severe disease. These findings demonstrate 33 that age-related alterations in immune responses are associated with significantly worse C. 34 difficile infection and support a key role for intestinal eosinophils in mitigating C. difficile-35 mediated disease severity. 55CDI disease (4-6). However, the specific role for eosinophils in CDI disease severity has yet to 56 be completely elucidated, and few studies characterize the innate immune responses to C. 57 difficile strains with a range of virulence potential in animals of advanced age. 58CDI disease severity depends on host factors and virulence of the C. difficile strain (12). 59Aging is known to cause immune dysfunction and negatively impacts patients in the setting of 60 infectious diseases in the intestine (13). While immunosenescence likely plays a role in 61 modulating CDI outcomes (14, 15), dysregulation of particular immune cell subsets may 62 differentially contribute to CDI disease severity. In the present study, we characterize the effect 63 of C. difficile strain virulence and host age on the cellular immune response using a murine 64 model of CDI utilizing C. difficile strain VPI 10463 (high-virulence) and strain 630 (low-65 virulence), as well as a young cohort and an aged cohort of adult mice reared in the same 66 animal facility. 67 68 69 MATERIALS AND METHODS 70 71 Mice. Male and female specific pathogen-free (SPF) C57BL/6 wild-type adult mice that were 72 young (2-3 months old) or aged (22-28 months old) were used in these studies. These mice 73 were from a br...

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“…In contrast, Kulaylat et al developed a model based on findings translated from a mouse model. 2 They hypothesized that admission eosinopenia, defined as a peripheral eosinophil level of 0 k/µl, is associated with worsened outcomes. Using both a training and a validation cohort, they determined that eosinopenia is an independent predictor of inpatient mortality (OR 2.01, 95% CI 1.08–3.73).…”

mentioning

confidence: 99%

Eosinopenia and Adverse Outcomes After Clostridium difficile Infections

Wei

Kao

2018

JAMA Surg

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Development and Validation of a Prediction Model for Mortality and Adverse Outcomes Among Patients With Peripheral Eosinopenia on Admission for Clostridium difficile Infection

Abstract: This study describes a simple, widely available, inexpensive model predicting CDI severity and mortality to identify at-risk patients at the time of admission.

Cited by 51 publications

References 24 publications

Considering the Immune System during Fecal Microbiota Transplantation for Clostridioides difficile Infection

Considering the Immune System during Fecal Microbiota Transplantation for Clostridioides difficile Infection

Aging dampens the intestinal innate immune response duringClostridioides difficileinfection and is associated with altered intestinal eosinophil mobilization

Eosinopenia and Adverse Outcomes After Clostridium difficile Infections

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