Predictive Value and Clinical Significance of Extreme Leukocytosis on Incidence of Clostridium Difficile Infection and Other Conditions in Critically-ill Patients - Analysis of 8,505 Critically-Ill Adults
CCCF ePoster library. Teja B. Nov 9, 2018; 233326; 118
Dr. Bijan Teja
Dr. Bijan Teja
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Introduction: In critically ill patients, extreme leukocytosis (peak white blood cell (WBC) count ≥ 40,000 cells/mm3) often signals the presence of a significant infectious process, with Clostridium difficile (C. difficile), other gram positive sepsis and pulmonary infection being among the processes classically associated with this finding.1 While the incidence of C. difficile infection in hospitalized patients is well documented,1-3 its incidence in critically ill patients with WBC count ≥ 40,000 has yet to be evaluated. Furthermore, the clinical significance of extreme leukocytosis on the incidence of other conditions and their associated mortality rates in these patients has not been elucidated.


Objective: We sought to evaluate the predictive value and clinical significance of extreme leukocytosis on the incidence of C. difficile and other conditions among ICU patients without myeloproliferative disease.


Methods: We conducted a retrospective cohort study of patients in the Medical Information Mart for Intensive Care III (MIMIC-III) database4 who were tested for C. difficile for the first time using C. difficile toxin assay. Patients with ICD-9 codes consistent with myeloproliferative disorders such as leukemia or lymphoma were excluded. In our secondary analyses, we evaluated patients undergoing repeat testing for C. difficile who had not previously tested positive, and also categorized patients with extreme leukocytosis by quintile based on peak WBC count, to assess whether elevations in peak WBC count beyond 40,000 were associated with higher likelihood of C. difficile infection. Additionally, we grouped disease processes using ICD-9 codes to assess disease subgroup incidence and mortality according to peak WBC level.


Results: There were 8,505 patients who met inclusion criteria for the pre-specified primary analysis (Table 1). Although extreme leukocytosis within seven days prior to C. difficile testing had high specificity for C. difficile (98%; 95% CI, 97.5-98.1%), the low prevalence of disease resulted in a relatively low positive predictive value (14%; 95% CI, 13.6-19.2%). Within 14 days after C. difficile testing, the positive predictive value of extreme leukocytosis rose slightly (19%; 95% CI, 13.9-24.3%) (Table 2). Results were similar in the repeat testing cohort (n=2,470), and elevations in peak WBC count beyond 40,000 were not associated with higher incidence of C. difficile. In patients with extreme leukocytosis who tested negative for C. difficile, the most common diagnoses were intra-abdominal process other than C. difficile (48%), pneumonia/pneumonitis (47%) and urinary tract infection (25%). Extreme leukocytosis was associated with significantly higher mortality across diagnostic categories, with mortality ranging from approximately 25-55% (Figure 1).


Conclusion: Extreme leukocytosis in the absence of myeloproliferative disorder is highly specific for C. difficile infection; however, the positive predictive value is relatively low because of the low disease prevalence. Extreme leukocytosis is also associated with significantly higher mortality regardless of diagnosis, and is most commonly associated with intra-abdominal processes other than C. difficile, pneumonia and urinary tract infection in the critically ill. These findings may help guide initiation or withholding of empiric treatment for C. difficile, initiation of isolation precautions, as well as prognostication and consideration of alternative diagnoses.

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