Clostridium difficile: its disease and toxins.

Lyerly, Davidm .; Krivan, Howard C.; Wilkins, Tracy D.

doi:10.1128/cmr.1.1.1-18.1988

Cited by 115 publications

(185 citation statements)

References 156 publications

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“…A hallmark of this disease is neutrophil accumulation in the pseudomembranes and between them and the intestinal mucosa, suggesting that neutrophils play an important role in this pathology. 61 TxA-induced modification in neutrophil morphology and function has been demonstrated and may be involved in the pathogenesis of this colitis. 62 Thus, the demonstration that Gln restitution is important to control neutrophil migration induced by TxA may be meaningful in the treatment of this condition.…”

Section: Discussionmentioning

confidence: 92%

Glutamine depletion potentiates leucocyte‐dependent inflammatory events induced by carrageenan or Clostridium difficile toxin A in rats

Nascimento¹,

Sousa²,

Martins³

et al. 2005

Immunology

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SummaryThis research investigated the effect of glutamine (Gln) depletion on leucocyte-dependent inflammatory events. Rats were treated intraperitoneally, 16 hr prior to the peak of every parameter evaluated, with either 0Á9% NaCl, methionine-sulphoximine (MSO, an inhibitor of endogenous Gln synthesis, 25 mg/kg) or with MSO + Gln (MSO as above plus Gln 3 g/kg in three doses). MSO-induced Gln depletion increased paw oedema induced both by carrageenan (Cg) and by Clostridium difficile toxin A (TxA) (66Á2% and 45Á5%, respectively; P < 0Á05). In dextran-injected animals, oedema and myeloperoxidase (MPO) activity were not modified by Gln depletion. In Cg-treated paws, Gln depletion increased MPO activity by 44% (P < 0Á05), interleukin-1b (IL-1b) and tumour necrosis factor-a (TNF-a) concentrations by 47% and 52%, respectively (P < 0Á05), and immunostaining for TNF-a in paw tissue. In TxA-injected paws, Gln depletion increased MPO activity (46%; P < 0Á05). Gln depletion increased Cg-and TxA-induced neutrophil migration to subcutaneous air pouches by 56% and 77% (P < 0Á05), respectively, but did not affect migration induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP). Gln infusions reversed all the effects of MSO. Leucocyte counts did not differ between groups. Gln depletion potentiates acute inflammation, possibly by increasing neutrophil migration through resident cell activation and production of IL-1b and TNF-a. Gln supplementation reverses these effects and may be useful during inflammatory catabolic stress.

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Section: Discussionmentioning

confidence: 92%

Glutamine depletion potentiates leucocyte‐dependent inflammatory events induced by carrageenan or Clostridium difficile toxin A in rats

Nascimento¹,

Sousa²,

Martins³

et al. 2005

Immunology

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“…Considering that an ideal diagnostic test must be highly sensitive and specific, easy and quick to perform (Lyerly et al, 1988), none of the methods evaluated in this study has the appropriateness to be used alone in CDAD diagnosis. EIA presented low sensitivity, while PCR and culture did not detect the presence of the active toxin in biologically samples.…”

Section: Discussionmentioning

confidence: 99%

Discrepancies among three laboratory methods forClostridium difficiledetection and a proposal for their optimal use

Monteiro

Pires

Baethgen

et al. 2013

FEMS Microbiol Lett

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Clostridium difficile is the major cause of nosocomial diarrhoea. Several detection methods are available for the laboratory diagnosis of C. difficile, but these vary in terms of sensitivity and specificity. In this study, we compared the performance of three following laboratory tests to detect C. difficile: in-house real-time PCR aiming for toxin B gene (tcdB), EIA for detection of toxins A and B (Premier Toxins A & B) and C. difficile culture in selective medium (bioMerieux). Our results were grouped into three categories as follows: (1) C. difficile-associated diarrhoea (CDAD); (2) asymptomatic carriers; and (3) negative results. Among the 113 patients included in the study, 9 (8.0%) were classified as CDAD, 19 (16.8%) were asymptomatic carriers, 76 (67.2%) had negative results and 9 (8.0%) could not be categorized (positive test for C. difficile toxins only). PCR was found to be the most sensitive diagnostic test in our study, with the potential to be used as a screening method for C. difficile colonization/CDAD. Diagnosis of CDAD would be better performed by a combination of PCR and EIA tests.

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“…However, the following limitations of the test should be considered. False-negative tests may reflect undetectable quantities of cytotoxin in patients with early and mild disease, the production of toxins not identified by the assay, inactivation of toxin during transport, 32 and decreased toxin sensitivity of certain cell lines. 33 Positive tests in the absence of disease may occur in up to 5% of healthy adults and hospital control patients.…”

Section: Discussionmentioning

confidence: 99%

Predicting Clostridium difficile Stool Cytotoxin Results in Hospitalized Patients with Diarrhea

et al. 1997

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OBJECTIVE: To validate a model for the prediction of Clostridium difficile cytotoxin assay results, and to identify a subgroup of patients with a very low likelihood of C. difficile -associated disease in whom the yield of routine cytotoxin testing is low. DESIGN:Prospective cohort study. Relevant clinical symptoms, signs, and antibiotic exposure were recorded before reporting of assay results. Each predictor was assigned a score based on regression coefficients, and patients were stratified according to their total score. SETTING:Two urban, tertiary care, university hospitals. PATIENTS:A total of 609 consecutive adult inpatients who received testing for C. difficile cytotoxin during a 3-month period in 1994. MEASUREMENTS AND MAIN RESULTS:The prevalence of positive cytotoxin assays was 8% in the validation set, compared with 14% in the derivation set. Defining patients without both prior antibiotic use and at least one symptom predictor (significant diarrhea or abdominal pain) as a low-risk subgroup, the misclassification rate was 2.8% (5/177) for assay results; of the five misclassified cases patients, only one was judged to have C. difficile -associated disease. Use of this rule to identify low-risk patients could have potentially averted 29% of all cytotoxin assays. lostridium difficile accounts for substantial morbidity in hospitalized patients and has been recognized to be the most common cause of antibiotic-associated colitis. 1 Disease associated with C. difficile is also costly. In one study, C. difficile colitis during hospitalization accounted for $2,000 in additional charges per patient. 2 Testing for C. difficile accounted for nearly 68% of total hospital charges associated with the laboratory evaluation of diarrhea in another study. 3 The most widely used method for diagnosis of C. difficile -associated disease is based on detecting a cytotoxin produced by C. difficile by means of a tissue culture assay. 4,5 The yield of C. difficile toxin testing in hospitalized patients with diarrhea has been reported to be approximately 20% in patients hospitalized longer than 3 days. [6][7][8][9] Other investigators, however, have suggested that approximately 40% of testing for C. difficile could be eliminated by using selective criteria. 10 Moreover, the yield of serial (repeated) tests for C. difficile toxin has been reported to be low. 11 In a retrospective study of consecutive patients who underwent first-time testing for C. difficile cytotoxin at a university medical center, where the overall prevalence of positive cytotoxin assays was 14%, Katz et al. developed a simple three-variable decision rule. 5 This rule identified a clinical subgroup at low risk of positive cytotoxin assay results (patients without the combination of antibiotic use within 30 days prior to testing and either a significant diarrhea or abdominal pain). This subgroup accounted for 37% of all cytotoxin assays performed. CONCLUSIONS:Although the subjects of this earlier study had a broad range of symptoms and exposure histories, they wer...

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Clostridium difficile: its disease and toxins.

Cited by 115 publications

References 156 publications

Glutamine depletion potentiates leucocyte‐dependent inflammatory events induced by carrageenan or Clostridium difficile toxin A in rats

Glutamine depletion potentiates leucocyte‐dependent inflammatory events induced by carrageenan or Clostridium difficile toxin A in rats

Discrepancies among three laboratory methods forClostridium difficiledetection and a proposal for their optimal use

Predicting Clostridium difficile Stool Cytotoxin Results in Hospitalized Patients with Diarrhea

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