Prospective Multicenter Study Evaluating Fecal Calprotectin in Adult Acute Bacterial Diarrhea

Shastri, Yogesh M.; Bergis, Dominik; Povse, Nada; Schäfer, Volker; Shastri, Sarika; Weindel, Martin; Ackermann, H.; Stein, Jürgen M.

doi:10.1016/j.amjmed.2008.06.034

Cited by 93 publications

(79 citation statements)

References 35 publications

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“…Our data show that 88% and 80% of the CDI-positive stools had average lactoferrin and calprotectin concentrations higher than the average concentrations in the stools of the hospitalized patients without diarrhea, respectively. These results agree with those of Shastri et al (28), in which 85.1% and 82.8% of CDI patient stool samples had higher levels of lactoferrin and calprotectin, respectively, than stool samples from healthy adults. Lactoferrin and calprotectin serve as part of the innate inflammatory response, and so their overexpression during CDI may provide insight into the extent of inflammation associated with this infection.…”

Section: Discussionsupporting

confidence: 83%

Colonic Immunopathogenesis of Clostridium difficile Infections

Darkoh

Turnwald

Koo

et al. 2014

Clin Vaccine Immunol

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f There are major gaps in our understanding of the immunopathogenesis of Clostridium difficile infections (CDIs). In this study, 36 different biomarkers were examined in the stools of CDI and non-CDI patients using the Proteome Profiler human cytokine array assay and quantitative enzyme-linked immunosorbent assay. Diarrheal stools from patients with CDI (CDI-positive diarrheal stools) showed higher relative amounts of the following inflammatory markers than the diarrheal stools from CDI-negative patients (CDI-negative diarrheal stools): C5a, CD40L, granulocyte colony-stimulating factor, I-309, interleukin-13 (IL-13), IL-16, IL-27, monocyte chemoattractant protein 1, tumor necrosis factor alpha, and IL-8. IL-8 and IL-23 were present in a larger number of CDI-positive diarrheal stools than CDI-negative diarrheal stools. Th1 and Th2 cytokines were not significantly different between the CDI-positive and CDI-negative diarrheal stools. Lactoferrin and calprotectin concentrations were also higher in the CDI-positive diarrheal stools. Our results demonstrate that CDI elicits a proinflammatory host response, and we report for the first time that IL-23 is a major marker in CDI-positive diarrheal stools. IL-23 may explain the lack of a robust immunological response exhibited by a proportion of CDI patients and may relate to recurrence; the IL-23 levels induced during CDI in these patients may be inadequate to sustain the cellular immunity conferred by this cytokine in promoting the induction and proliferation of effector memory T cells.

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Section: Discussionsupporting

confidence: 83%

Colonic Immunopathogenesis of Clostridium difficile Infections

Darkoh

Turnwald

Koo

et al. 2014

Clin Vaccine Immunol

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“…Our results are similar to those obtained in prior studies in which fCPT levels were found to correlate with the presence of C. difficile (4)(5)(6). In one study, fCPT concentrations were found to be higher in CDI cases diagnosed by a toxin assay than those detected by PCR for the toxin gene (4), supporting the hypothesis that some proportion of CD-PCR ϩ samples represent colonization only (7,8).…”

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confidence: 81%

Usefulness of Adjunctive Fecal Calprotectin and Serum Procalcitonin in Individuals Positive for Clostridium difficile Toxin Gene by PCR Assay

et al. 2015

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In 54/64 subjects with nosocomial diarrhea, fecal calprotectin levels correlated with the results of stool samples tested for Clostridium difficile toxin gene by PCR. Fecal calprotectin levels can be used as an adjunctive measure to PCR to support the diagnosis of C. difficile infection. Fecal calprotectin (fCPT), found predominantly in neutrophils, is a marker of inflammation in inflammatory bowel disease (IBD) (1) due to neutrophilic infiltration of the gut and shedding into the gut lumen and can therefore be quantified in feces. Serum procalcitonin (sPCT), a biomarker of bacterial infection, has been validated for use in monitoring responses to antibiotic therapy and as a prognosticator of sepsis in critically ill patients (2).We performed a prospective exploratory observational study to assess whether fCPT and sPCT could aid in the diagnosis of Clostridium difficile infection (CDI) in the context of a positive PCR for C. difficile toxin gene (CD-PCR).This study was undertaken at a single tertiary 637-bed university teaching hospital and was approved by the institutional research ethics committee. Inpatients whose stool samples were received for CD-PCR underwent testing for fCPT, as assessed by the two Quantum Blue calprotectin lateral flow rapid tests (Bühl-mann, Basel, Switzerland), according to the manufacturer's instructions. Briefly, a 1:150 dilution of sample with the buffer was centrifuged, and 80 l of the supernatant was loaded onto the test cartridge and placed in the dedicated reader. The assay selectively measures calprotectin by a sandwich immunoassay using monoclonal antibodies. The lower-range assay (LR-fCPT) (range, 30 to 300 g/g) was developed as a screen for IBD, and the higher-range assay (HR-fCPT) (range, 100 to 1,800 g/g) is used to follow IBD therapy and for predicting relapses. As per the manufacturer's recommendations for interpretation with IBD, HR-fCPT values of Ͻ100 g/g represent a mild or noninflammatory state of the gut, whereas values of Ͼ200 g/g indicate active organic disease with inflammation. sPCT levels were measured using the Vidas B.R.A.H.M.S PCT assay (bioMérieux, Marcy l'Etoile, France) on leftover serum from subject samples collected within 48 h prior to the date on which the stool sample was collected for CD-PCR. Written informed consent was obtained from all patients for serum and stool testing and for medical chart review.Chi-square and Fisher exact tests were used to compare categorical variables, and a Student t test was used for continuous variables. Quantitative variables were compared by the nonparametric Mann-Whitney U test and Kruskal-Wallis test. P values of Ͻ0.05 were considered statistically significant. IBM SPSS software (version 22) was used for statistical analysis.Between January and September 2013, 64 subjects (44 CD-PCR positive and 20 CD-PCR negative) were enrolled. There were no significant differences in gender (53% male) and age distribution between the 2 groups; 47 (73%) individuals were Ն60 years old. CD-PCR ϩ cases had a higher mean white cell c...

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“…There was an overlap of fecal calprotectin levels between the pathogen-positive patients and the control group (0 to 994 mg/liter and 0.1 to 204.7 mg/liter, respectively). Compared to the other tests, the fecal calprotectin specificity and positive and negative likelihood ratios were statistically better in predicting patients with infectious diarrhea (165). Fecal calprotectin levels were highest for the 87 patients with C. difficile diarrhea compared to patients with other infectious causes of diarrhea (165).…”

Section: Evolution Of Testing Methodsmentioning

confidence: 98%

“…Compared to the other tests, the fecal calprotectin specificity and positive and negative likelihood ratios were statistically better in predicting patients with infectious diarrhea (165). Fecal calprotectin levels were highest for the 87 patients with C. difficile diarrhea compared to patients with other infectious causes of diarrhea (165). In this group, the sensitivity of the test with a cutoff value of Ͼ15 mg/liter was 82.8% (165); however, this value is below the level of acceptability to be used alone as a screening test.…”

Section: Evolution Of Testing Methodsmentioning

confidence: 99%

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Diagnosis of Clostridium difficile Infection: an Ongoing Conundrum for Clinicians and for Clinical Laboratories

2013

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SUMMARY Clostridium difficile is a formidable nosocomial and community-acquired pathogen, causing clinical presentations ranging from asymptomatic colonization to self-limiting diarrhea to toxic megacolon and fulminant colitis. Since the early 2000s, the incidence of C. difficile disease has increased dramatically, and this is thought to be due to the emergence of new strain types. For many years, the mainstay of C. difficile disease diagnosis was enzyme immunoassays for detection of the C. difficile toxin(s), although it is now generally accepted that these assays lack sensitivity. A number of molecular assays are commercially available for the detection of C. difficile . This review covers the history and biology of C. difficile and provides an in-depth discussion of the laboratory methods used for the diagnosis of C. difficile infection (CDI). In addition, strain typing methods for C. difficile and the evolving epidemiology of colonization and infection with this organism are discussed. Finally, considerations for diagnosing C. difficile disease in special patient populations, such as children, oncology patients, transplant patients, and patients with inflammatory bowel disease, are described. As detection of C. difficile in clinical specimens does not always equate with disease, the diagnosis of C. difficile infection continues to be a challenge for both laboratories and clinicians.

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Prospective Multicenter Study Evaluating Fecal Calprotectin in Adult Acute Bacterial Diarrhea

Cited by 93 publications

References 35 publications

Colonic Immunopathogenesis of Clostridium difficile Infections

Colonic Immunopathogenesis of Clostridium difficile Infections

Usefulness of Adjunctive Fecal Calprotectin and Serum Procalcitonin in Individuals Positive for Clostridium difficile Toxin Gene by PCR Assay

Diagnosis of Clostridium difficile Infection: an Ongoing Conundrum for Clinicians and for Clinical Laboratories

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