Predicting Clostridium difficile Stool Cytotoxin Results in Hospitalized Patients with Diarrhea

Abstract

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...

Underlying Disease Severity as a Major Risk Factor for Nosocomial Clostridium difficile Diarrhea

“…Numerous studies identifying risk factors for C. difficile diarrhea have been published and clinical prediction rules to optimize cytotoxin testing for C. difficile in hospitalized patients with diarrhea have previously been developed and validated. 1023 ' 24 We are unaware of any previous study designed to allow stratification of antibiotic recipients at the time of hospital admission according to their risk for C. difficile diarrhea. Because of the prospective design of this study, all cases of C. difficile diarrhea in the study population were identified.…”

Predicting Clostridium difficile Stool Cytotoxin Results in Hospitalized Patients with Diarrhea

“…In the derivation set, 5 both maximum temperature (on the index date) and comorbidity score were nearly equivalent for testpositive and test-negative subjects, and thus were not assessed in the current study. Although some hospital units had episodic clusters of cytotoxin-positive cases, utilization of the cytotoxin assay remained relatively constant throughout medical and surgical units of both hospitals.…”

“…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.…”

“…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.…”

Pseudomembranous Colitis: An Update

“…A recent pro-spective analysis of factors predicting a positive C difficile toxin in the stool indicated usefulness of the following predictive parameters: cephalosporin use, prolonged hospital stay, onset of diarrhea six or more days after receiving antibiotics, fecal leucocytes in the stool and presence of semiformed stool (6). A study to identify patients with a very low likelihood of C difficile-associated diarrhea found that patients without a history of antibiotic use or significant diarrhea or abdominal pain were unlikely to have a positive C difficile toxin assay (9). Stool tests: A good review of diagnostic tests has been published recently by Brazier (10).…”