1217. Outcomes in Clostridium difficile Patients with Negative Toxin Immunoassay Results
Session: Oral Abstract Session: New Insights into C. difficile Transmission and Reporting
Saturday, October 5, 2013: 9:30 AM
Room: The Moscone Center: 200-212
Background: Toxins mediate Clostridum difficile disease but 40-60% of patients with diarrhea and C. difficile antigens or DNA lack detectable toxins making it unclear if they need to be treated.  We studied 1431 hospitalized adults with diarrhea to compare clinical and laboratory characteristics and outcomes between toxin+ and toxin- patients with C. difficile and patients with non-C. difficile diarrhea.

Methods: Adult patients with a diarrheal sample submitted for a C. difficile test ≥72 hours after admission had symptoms verified and a toxin immunoassay (toxin EIA), C. difficile PCR and toxigenic culture performed in real time.  Only the toxin EIA results were reported to clinicians.   Additional toxin tests and lactoferrin, a marker of neutrophilic inflammation, were performed on frozen stool.  Additional patient data were collected from medical records. 

Results: There were 303 (21.2%) patients with toxigenic C. difficile and 1084 (75.8%) negative patients.  Of the C. difficile+ patients, 132 (43.6%) had a positive toxin EIA result reported clinically; 48 (15.8%) had a negative result reported but toxins detected by cell cytotoxicity; 123 (40.6%) had a negative result reported and no toxins by cell cytotoxicity.  Fecal lactoferrin levels correlated with fecal C. difficile DNA and toxin concentration and peripheral white blood cell counts (P≤0.001 all comparisons).  Toxin EIA negative samples with C. difficile had less C. difficile DNA, fewer toxins and less lactoferrin than positive samples (P<0.001 all comparisons).  Clinically, toxin EIA negative patients with C. difficile were less likely to be symptomatic at the time of testing than positive patients (P=0.01) and had a duration of diarrhea similar to patients with non-C. difficile diarrhea.  Among toxin EIA negative patients with C. difficile who died in the hospital, none of the deaths was attributable to C. difficile infection. 

Conclusion: Most toxin EIA negative patients with C. difficile have a lower level of infection with fewer toxins, less inflammation, and outcomes that are comparable to patients with non-C. difficile diarrhea.  Exclusive reliance on non-toxin tests for C. difficile diagnosis without tests for toxins or host response is likely to result in overdiagnosis and overtreatment.

Christopher Polage, MD1, Clare Gyorke1, Michael Kennedy1, Jhansi Leslie, BS2, David Chin1, Susan Wang1, Hien H. Nguyen, MD, MAS3, Bin Huang, MD, PhD4, Yi-Wei Tang, MD PhD4, Ed Panacek, MD MPH1, Parker Goodell1, Jay Solnick, MD, PhD5 and Stuart Cohen, MD, FIDSA, FSHEA6, (1)University of California, Davis Medical Center, Sacramento, CA, (2)University of California, Davis, Sacramento, CA, (3)Internal Medicine, University of California, Davis Medical Center, Sacramento, CA, (4)Memorial Sloan Kettering Cancer Center, New York City, NY, (5)Medicine and Microbiology, University of California, Davis, CA, (6)Division Of Infectious Diseases, University of California At Davis Medical Center, Sacramento, CA

Disclosures:

C. Polage, Cepheid: Reagent and Materials Only, Research support
TechLab: Reagent and Materials Only, Research support
Meridian: Reagent and Materials Only, Research support
Alere: Reagent and Materials Only, Research support

C. Gyorke, None

M. Kennedy, None

J. Leslie, None

D. Chin, None

S. Wang, None

H. H. Nguyen, None

B. Huang, None

Y. W. Tang, None

E. Panacek, None

P. Goodell, None

J. Solnick, None

S. Cohen, None

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