1. Correlation of Leukocyte Count with Clinical Outcomes in Hospitalized Patients with Community-Acquired Pneumonia: Results from Rapid Empiric Treatment with Oseltamivir Study (RETOS) Srinivas Uppatla, MD, 1 Sridivya Peddapalli, MD, 1 Cynthia Meza Ortiz, MD, 1 Kelly Carrico, BS, 1 Timothy Wiemken, PhD, 1 Forest Arnold, DO, MSc. 1 Division of Infectious Diseases. 1 ABSTRACT Introduction: Community-acquired pneumonia (CAP) continues to be a major health problem worldwide. Leukocytes are an important host response factor against invading pathogens causing CAP. Patients with elevated leukocyte count (leukocytosis) are expected to have better clinical outcomes in comparison to patients with normal or low leukocyte count (leukopenia). However, there is limited information about leukocyte count and its correlation with clinical outcomes in hospitalized patients with CAP. The objective of this study was to correlate leukocyte count on admission with clinical outcomes in hospitalized patients with CAP. Methods: This was a secondary analysis of the RETOS database, an on-going, randomized, prospective clinical trial to evaluate the impact of rapid empiric treatment with oseltamivir on the outcomes of hospitalized patients with lower respiratory tract infections (LRTIs). All patients admitted to eight hospitals in Louisville, Kentucky from December 2010 to March 2012 with a diagnosis of LRTI were invited to participate in the study. Patients diagnosed with CAP were divided into 2 groups based on their leukocyte count: 1. Leukocyte count >10,000 and 2. Leukocyte count < 10,000. Logistic regression was used to determine the effect of leukocyte count on 30-day mortality while adjusting for the Pneumonia Severity Index. Results: A total of 476 CAP patients were evaluated. Out of these, 315 (66%) patients had leukocytosis, and 161 (34%) patients had no leukocytosis on admission. The results of the multivariable analysis indicated a significant increase in mortality for patients with leukopenia. Conclusions: This study indicates that CAP patients with leukopenia have higher 30-day mortality when compared to patients with normal leukocyte count and leukocytosis. The finding of leukopenia in a hospitalized patient with CAP should prompt an aggressive management approach since these patients are at a higher risk for mortality. Therapeutic interventions to increase white blood cell count may need to be studied. INTRODUCTION REFERENCES RESULTS -This study indicates that CAP patients with leukopenia trend towards higher 30-day mortality when compared to patients with normal leukocyte count and leukocytosis. -The finding of leukopenia in a hospitalized patient with CAP should prompt an aggressive management approach since these patients are at a higher risk for mortality. -Therapeutic interventions to increase white blood cell count may need to be studied. -In our study, we also found a significant number of CAP patients who did not have leukocytosis on admission. Hence, absence of leukocytosis on admission should not deter physicians from fully evaluating patients with a chest radiograph and ordering appropriate microbiologic tests when patients present with signs and symptoms consistent with pneumonia. CONCLUSIONS Table 1: Demographic characteristics of CAP patients in the study Figure 1: Graph depicting correlation of Percent mortality at 30 Days in CAP patients and WBC count Study design and study population This was a secondary analysis of the RETOS database, an ongoing, randomized, prospective clinical trial to evaluate the impact of rapid empiric treatment with oseltamivir on the outcomes of hospitalized patients with LRTIs. All patients admitted to eight hospitals in Louisville, Kentucky from December 2010 to March 2012 with a diagnosis of LRTI were invited to participate in the study. Although the database was created to evaluate patients’ response to oseltamivir, it contains basic laboratory values from which meaningful information can be derived. Study definition: CAP was defined as the presence of new pulmonary infiltrate on the chest radiograph at the time of hospitalization that was associated with at least one of the following: - New or increased cough - An abnormal temperature ( 37°C) - Leukocytosis (leukocyte count >10,500 cells/ µL), leukopenia (leukocyte count 5% immature neutrophils). Patients diagnosed with CAP were divided into two groups based on their leukocyte count:  Leukocyte count >10,000 cells/ µL  Leukocyte count <10,000 cells/ µL Statistical analysis: Baseline patient characteristics and clinical outcomes were compared between patients with leukocytosis and no leukocytosis using the Chi squared test for categorical variables and the Mann-Whitney U-test for continuous variables. To evaluate the adjusted effect of leukocyte count on 30-day mortality, a logistic regression model was constructed. This model considered the continuous leukocyte count as the primary predictor variable, 30-day mortality as the outcome, and the pneumonia severity index as a confounding variable. P-values of ≤0.05 were considered statistically significant. SAS v9.2 and R v2.14.0 were used for all analyses.. Community-acquired pneumonia (CAP) continues to be a major health problem worldwide. The annual incidence of CAP cases is 5.6 million in the United States, and 1.2 million patients get hospitalized each year. The inpatient mortality rate for hospitalized patients with CAP has been documented to be as high as 5.8 %. 1 Due to its high mortality rate, early diagnosis of CAP is important for initiation of appropriate therapy. Leukocyte count on admission is an important factor that is used in the evaluation of CAP patients. Leukocyte count is routinely used in the evaluation of patients with lower respiratory tract infections (LRTIs) including CAP to help guide the diagnosis and management. 2 Leukocytes are an important host response factor against invading pathogens causing CAP. MATERIALS AND METHODS A total of 476 CAP patients were evaluated. Out of these, 315 (66%) patients had leukocytosis, and 161 (34%) patients had no leukocytosis on admission. Baseline characteristics and clinical outcomes of patients with CAP are shown in Table 1. Results of the multivariable analysis are shown in Figure 1. The trend, although clinically significant for patients with leukopenia did not reach statistical significance overall (P=0.75). This analysis indicated that patients with leukopenia were at a higher risk for mortality than patients with a normal leukocyte count or leukocytosis. 1. Bartlett JG, Dowell SF, Mandell LA, et al. Practice guidelines for the management of community-acquired pneumonia in adults. Infectious Diseases Society of America. Clin Infect Dis 2000; 31:347-82 2. Furer V, Raveh D, Picard E, Goldberg S, Izbicki G. Absence of leukocytosis in bacteraemic pneumococcal pneumonia. Prim Care Respir J 2011; 20(3):276-281 3. Ahkee S, Srinath L, Ramirez J. Community-acquired pneumonia in the elderly: association of mortality with lack of fever and leukocytosis. South Med J 1997; 90:296–298 Variable Leukocyte count >10000 n=315 (66%) Leukocyte count <10000 n=161 (34 %) P-value Age, Median (Range)62 (18-91)61 (22-99)0.542 Female Gender120 (38)62 (39)0.999 Nursing Home Resident25 (8)6 (4)0.115 COPD141 (45)75 (47)0.770 CHF82 (26)48 (30)0.386 Cerebrovascular accident 29 (9)20 (12)0.270 Liver Disease21 (7)14 (9)0.459 Renal Disease60 (19)29 (18)0.805 Diabetes104 (33)63 (39)0.189 Altered Mental Status25 (8)12 (7)0.999 ICU Admission54 (17)22 (14)0.357 Multilobar Infiltrates107 (34)46 (29)0.255 Clinical Outcomes Time to Clinical Stability3 (0-8)2.5 (0-8)0.056 Length of Stay4 (0-36)4 (0-29)0.339 In-Hospital Mortality9 (3)7 (4)0.425 Mortality at 30 Days18 (6)10 (7)0.835 Patients with an elevated leukocyte count (leukocytosis) are expected to have better clinical outcomes in comparison to patients with normal or low leukocyte count (leukopenia). Lack of leukocytosis can be a manifestation of lack of systemic inflammatory response, and may indicate abnormal immune function and has been shown to predict mortality in CAP patients. 3 However, there is limited information about leukocyte count and its correlation with clinical outcomes in hospitalized patients with CAP. The objective of this study was to correlate leukocyte count on admission with clinical outcomes in hospitalized patients with CAP INTRODUCTION (Cont’d) RESULTS (Cont’d)