Clinical study
Clinical prediction rules to optimize cytotoxin testing for Clostridium difficile in hospitalized patients with diarrhea

https://doi.org/10.1016/S0002-9343(95)00016-XGet rights and content

Background

Although routine testing of hospitalized patients with diarrhea for Clostridium difficile cytotoxin has been advocated as a high-yield procedure, the rationale for this practice has been questioned. To target a low-yield subgroup for whom routine testing could be deferred, we derived a clinical decision rule for predicting results of the C difficile cytotoxin assay in hospitalized adults with diarrhea.

Methods

We hypothesized a priori that two variables, antibiotic use (within 30 days prior to testing) and history of significant diarrhea (new onset of >3 partially formed or watery stools per 24 hour period), would be highly predictive of cytotoxin results, and obtained these data on 480 consecutive patients who underwent diagnostic testing for C difficile at a university hospital and affiliated Veterans Affairs medical center. For more detailed modelling, we recorded symptoms, signs, comorbidity, and other potential causes of diarrhea for 68 test positive patients (cases) and 265 randomly selected test negative patients (controls) within the study cohort.

Results

The overall prevalence of positive cytotoxin assays was 14%. Prior antibiotic therapy (OR = 9.0, 95% CI 2.1-38.4), significant diarrhea (OR = 2.2, 95% CI 1.1-4.7), and abdominal pain (OR = 1.9, 95% CI 0.96-3.7) were independent predictors of cytotoxin assay results. The model discriminated patients with positive and negative assays with a receiver operating characteristic (ROC) area of 0.68; observed and predicted probabilities of a positive cytotoxin assay were well correlated over the entire range of observed probabilities (r2 = 0.86). A decision rule (defined as positive if prior antibiotic use and either significant diarrhea or abdominal pain are present) demonstrated sensitivity and specificity of 86 and 45%. When applied to the entire dataset (N = 480), a simplified a priori rule, defined as positive if both prior antibiotic use and history of significant diarrhea are present, demonstrated sensitivity, specificity, positive and negative predictive value of 80, 45, 18 and 94%, respectively (6% of those predicted to be cytotoxin-negative actually tested positive). Use of this rule would have averted 39% of cytotoxin assays in our study population.

Conclusions

Patients without prior antibiotic use and either significant diarrhea or abdominal pain are unlikely to have positive C difficile cytotoxin assay results, and may not routinely require cytotoxin testing.

References (50)

  • ArningM et al.

    A lethal course in pseudomembranous enterocolitis during the parenteral administration of vancomycin and imipenem

    Deutsche Medizinische Wochenschrift

    (1992)
  • BiddleW et al.

    Evaluation of antibiotic-associated diarrhea with a latex agglutination test and cell culture cytotoxicity assay for Clostridium difficile

    Am J Gastroenterol

    (1989)
  • ChangT et al.

    Cytotoxicity assay in antibiotic) associated colitis

    J Infect Dis

    (1979)
  • GeorgeW et al.

    Clostridium difficile and its cytotoxin in feces of patients with antimicrobial agent-associated diarrhea and miscellaneous conditions

    J Clin Microbiol

    (1982)
  • McFarlandL et al.

    Risk factors of Clostridium difficile carriage C. difficile-associated diarrhea in a cohort of hospitalized patients

    J Infect Dis

    (1990)
  • KatoN et al.

    Detection of toxigenic Clostridium difficile in stool specimens by the polymerase chain reaction

    J Infect Dis

    (1993)
  • BartlettJ

    Antibiotic-associated diarrhea

    Practical Gastroenterology

    (1992)
  • KellyC et al.

    Clostridium difficile colitis (letter)

    NEJM

    (1994)
  • NolteF

    Practical considerations in the laboratory diagnosis of bacterial enteric infections

    Am J Clin Pathol

    (1994)
  • SiegelD et al.

    Inappropriate testing for diarrheal diseases in the hospital

    JAMA

    (1990)
  • FanK et al.

    Application of refection criteria for stool cultures for bacterial enteric pathogens

    J Clin Microbiol

    (1993)
  • CucharalG et al.

    Cost-effectiveness of strategies for the management of suspected Clostridium difficile associated diarrhea

    Clinical Research

    (1983)
  • Renshaw A, Stelling J, Doolittle M. The value of repeated Clostridium difficile cytotoxicity assays. Arch Pathol Lab...
  • SackR et al.

    Laboratory diagnosis of bacterial diarrhea

    • Cited by (48)

    • A systematic review of tools for predicting complications in patients with acute infectious diarrhea

      2023, American Journal of Emergency Medicine
      Citation Excerpt :

      Risk stratification tools may help predict the need for investigation or treatment and thereby optimize the use of healthcare resources. A large number of these tools have been shown to improve cost-effectiveness while minimizing unnecessary diagnostic imaging, treatment complications, and unnecessary admissions [5-9]. Most of these tools have been developed as decision aids for physicians, and few are intended to help patients and caregivers identify the most appropriate care pathway for the condition [10,11].

    • Lack of improvement in antimicrobial prescribing after a diagnosis of Clostridium difficile and impact on recurrence

      2018, American Journal of Infection Control
      Citation Excerpt :

      Patient demographics including age, sex, site of initial diagnosis (inpatient or outpatient), primary service (medicine-primary care or surgery), CDI risk factors (recent hospitalization, intensive care unit [ICU] admission, proton-pump inhibitor [PPI] use, and type 2 histamine receptor [H2R] blocker use), immunocompromised state (HIV, hematologic malignancy, chemotherapy, biologic anti-inflammatory, and chronic high-dose steroids), and tube feed use were also reviewed. Retrospective review of each case was performed to ensure that subjects met the clinical definition of CDI, which was defined as watery diarrhea with colitis (≥3 loose bowel movements per 24 hours or liquid colostomy output of ≥1,300 mL/d over 2 days) or unexplained lower abdominal pain, ileus, fever, and leukocytosis, in the setting of positive C difficile testing.1,25 Recurrence was defined as resolution of symptoms after completing appropriate therapy for iCDI, as defined by Infectious Diseases Society of America guidelines,1,3 followed by subsequent recurrence of symptoms associated with positive repeat toxin testing.21,26,27

    • Integration of technology into clinical practice

      2013, Clinics in Laboratory Medicine
      Citation Excerpt :

      By age 3, carriage rates are similar to that of nonhospitalized adults (less than 3%).58,59 However, carriage rates in hospitalized patients may be 10% or more.60 Given these high rates of asymptomatic carriage, it is likely that indiscriminant testing for C. difficile will result in a high number of misleading positive results and clinical confusion.

    • Peripartum Clostridium difficile infection: case series and review of the literature

      2008, American Journal of Obstetrics and Gynecology
      Citation Excerpt :

      Each patient's stool sample was tested for the presence of C difficile toxin B by the cytotoxin assay in the hospital diagnostic microbiology laboratory.7 Anaerobic culture was performed on all C difficile toxin B–positive stool specimens by plating specimens onto cycloserine-cefoxitin-fructose agar media (CCFA-VA formulation; Remel, Lenexa, KS).8,9 Plates were incubated anaerobically with the Anaero Pouch System (Remel) at 35°C for up to 5 days before a final interpretation of a negative result was determined.

    • Laboratory diagnosis of Clostridium difficile-associated disease in the Republic of Ireland: a survey of Irish microbiology laboratories

      2008, Journal of Hospital Infection
      Citation Excerpt :

      With regard to which patients to test, in one study prior antibiotic therapy, significant diarrhoea (defined as new onset of more than three partially formed or watery stools per 24 h period) and abdominal pain were independent predictors of a positive cytotoxin assay result. A decision rule (defined as positive if prior antibiotic use and either significant diarrhoea or abdominal pain are present) that was applied to specimens before testing demonstrated sensitivity and specificity of 86 and 45%, leading the authors to conclude that patients without prior antibiotic use and either significant diarrhoea or abdominal pain may not routinely require cytotoxin testing.17 One of the main disadvantages of this approach is the reliance on accurate clinical data being recorded on sample submission to the laboratory, which in practice may be an unattainable goal.

    • Reducing Clostridium difficile Colitis Rates Via Cost-Saving Diagnostic Stewardship

      2018, Infection Control and Hospital Epidemiology
    View all citing articles on Scopus
    1

    Dr. Katz was supported by a Veterans Administration fellowship in ambulatory care at the time of this work. An earlier version of this work was previously presented at the Society of Medical Decision Making Annual Meeting, Research Triangle Park, NC, October 24–27, 1993.

    2

    Dr. Littenberg's current address: Washington University School of Medicine, Campus Box 8005, 660 South Euclid Avenue, St. Louis, Missouri 63110.

    View full text
    Copyright © 1996 Published by Excerpta Medica Inc.