ABSTRACT METHODS

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INTRODUCTION

CONCLUSIONS

RESULTS

Trends in in-hospital mortality in hospitalized patients with community-acquired pneumonia from 2000-2014

Eman Abbas, Veronica Corcino, Muntadher Khaleefah, Joannis Baez Gonzalez, Laura Binford, Julio Ramirez, Paula Peyrani, Francisco Fernandez, Timothy Wiemken

University of Louisville, School of Medicine, Division of Infectious Diseases

Introduction: Community-acquired pneumonia (CAP) is one of the leadingcauses of death due to infection worldwide. National and internationalorganizations have developed guidelines for the management of CAP with thegoal to improve management and decrease mortality. We hypothesize that,over time, with implementation of these guidelines, we will observe a decreasein mortality in hospitalized patients with CAP.Objective: The objective of this study was to evaluate trends in mortality ratesin hospitalized patients with CAP over time.Methods: This was a secondary data analysis of the Community-AcquiredPneumonia Organization (CAPO) International Cohort Study database. Threetime periods were compared with respect to mortality rates, 2002-2005, 2006-2010, and 2011-2014. The Chi-squared test was used to determine statisticaldifferences in mortality rates.Results: A total of 7,948 patients were included in the study. Mortality rateswere: 8.4%, 9.9%, and 6.1% for each of the three time periods, respectively,(P<0.001).Conclusions: This study documented a significant decrease in mortality forhospitalized patients with CAP in 2011-2014 compared to prior time periods.The development and implementation of guidelines for the management ofhospitalized patients with CAP are the likely explanation for this decrease inmortality.

Community-acquired pneumonia (CAP) is one of the leading causes of deathdue to infection worldwide.1 National and international organizations havedeveloped guidelines for the management of CAP with the goal to improvemanagement and decrease mortality.2

Previous studies suggest that the rates of hospitalization for CAP may beincreasing among US adults, particularly among the older population (patientsaged ≥ 65 years) as well as the number of comorbidities among thesepatients.1 Factors that increase the risk for pneumonia include the presence ofunderlying medical conditions, advanced age, functional disability andresidency in long-term care facilities. We hypothesize that, over time, with theimplementation of guidelines for management of pneumonia we will observe adecrease in mortality in hospitalized patients with CAP.

The primary objective of this study was to evaluate trends in mortality rates inhospitalized patients with CAP over time. The secondary objective was toevaluate time to clinical stability and length of stay in the hospital over time.

Study definitionsCAP: Diagnosis of CAP required the presence of criterion A, B, and C:A. New pulmonary infiltrate on imaging (CT scan or chest x-ray) at the time ofadmission to the hospital.B. Signs and Symptoms of CAP (at least one of the following)

1. New or increased cough (per the patient)2. Fever >37.8°C (100.0°F) or hypothermia <35.6°C (96.0°F).3. Changes in WBC (leukocytosis >11,000 cells/mm3, left shift> 10% band forms/microliter, or leukopenia < 4,000 cells/mm3

C. Working diagnosis of CAP at the time of hospital admission with antimicrobialtherapy given within 24 hours of admission.

Study outcomesIn-hospital mortality: defined as death by any cause during hospitalization.Time to clinical stability (TCS): A patient was defined as clinically stable the daythat the following four criteria were met: a) improved cough and shortness ofbreath, b) lack of fever for at least 8 hours, c) improving leukocytosis (decreasedat least 10% from the previous day), and d) tolerating oral intake with adequategastrointestinal absorption. Patients were evaluated daily within the first 7 daysof hospitalization to determine the day when clinical stability was reached.Length of stay (LOS): defined in days and calculated for each patient as the dayof discharge minus the day of admission. Patients hospitalized for more than 14days were censored at 15 days in an effort to capture LOS data related only tobacterial CAP.

STATISICAL ANALYSISThree time periods were compared with respect to mortality rates, 2002-2005,2006-2010, and 2011-2014.Baseline categorical explanatory variables were summarized as frequenciesand percentages and differences between both groups of patients wereanalyzed using a chi-square test or Fisher’s exact test when appropriate andwarranted. Continuous variables were summarized as frequencies andinterquartile range and differences between groups were analyzed by Mann-Whitney U test. The Chi-squared test was used to determine statisticaldifferences in mortality rates. Kruskal-Wallis one way ANOVA was used todetermine statistical differences in TCS and LOS. P-values ≤ 0.05 wereconsidered statistically significant.

Variable In-Hospital Mortality Alive at Discharge p-valuen=685 n=7255

DemographicsAge , Median (IQR) 78 (24) 68 (28) <0.001Sex, n (%) 391 (57) 4337 (60) 0.179Nursing home resident, n (%) 106 (16) 313 (4) <0.001Comorbid ConditionsCongestive Heart Failure, n (%) 184 (28) 1137 (16) <0.001COPD, n (%) 181 (27) 1664 (23) 0.036Diabetes, n (%) 138 (21) 1233 (18) 0.104HIV, n (%) 43 (6) 428 (6) 0.867Renal Disease, n (%) 125 (19) 664 (9) <0.001Liver Disease, n (%) 47 (7) 370 (5) 0.048Neoplastic Disease, n (%) 130 (19) 654 (9) <0.001Physical ExamAltered mental status on admission, n (%) 249 (38) 767 (11) <0.001Respiratory Rate, Median (IQR) 28 (13) 22 (9) <0.001Systolic blood pressure, Median (IQR) 114 (32) 125 (30) <0.001Temperature (degrees Celsius), Median (IQR) 37.2 (1.8) 37.8 (1.6) <0.001Heart rate, Median (IQR) 104 (30) 98 (26) <0.001Lab/RadiographypH, Median (IQR) 7.4 (0.1) 7.5 (0.1) 0.013PaO2, Median (IQR) 57 (21.8) 63 (20) <0.001Blood Urea Nitrogen, Median (IQR) 47 (56.7) 30 (30) <0.001Serum sodium, Median (IQR) 137 (10) 137 (5) 0.118Serum glucose, Median (IQR) 128.5 (71.2) 119 (50) 0.003Hematocrit, Median (IQR) 36 (10.9) 38 (7.7) 0.002Pleural effusion, n (%) 203 (30) 1678 (23) <0.001Severity of DiseaseICU admission, n (%) 166 (25) 640 (9) <0.001Pneumonia Severity Index, Median (IQR) 125 (52) 96 (49) <0.001

Table 1: Patients’ Characteristics of the study population

Figure 1: Mortality Rates for the three study periods

• This study documented a significant decrease in mortality for hospitalizedpatients with CAP in 2011-2014 compared to prior time periods.

• The development and implementation of guidelines for the management ofhospitalized patients with CAP are the likely explanation for this decrease inmortality.

• Improvements in critical care have likely affected pneumonia outcomes. 5,6

• Improvement in antibiotic therapies such as the use of combination therapymay have also decreased mortality.

• We didn’t document any clinically significant decrease in time to clinicalstability or length of stay during the study period.

• Our data emphasizes the importance of developing national guidelines andthe need of educating and implementing the guidelines at the local hospitallevel.

1.Fry AM, Shay DK, Holman RC, et al. Trends in hospitalizations for pneumonia amongpersons aged 65 years or older in the United States, 1988–2002. JAMA.2005;294:2712–2719.2.Mandell, L. A., Wunderink, R. G., Anzueto, A., Bartlett, J. G., Campbell, G. D., Dean, N.C., ... & Whitney, C. G. (2007). Infectious Diseases Society of America/AmericanThoracic Society consensus guidelines on the management of community-acquiredpneumonia in adults. Clinical infectious diseases,44(Supplement 2), S27-S72.3.Bordón, J., Peyrani, P., Brock, G. N., Blasi, F., Rello, J., File, T., & Ramirez, J. (2008).The presence of pneumococcal bacteremia does not influence clinical outcomes inpatients with community-acquired pneumonia: results from the Community-AcquiredPneumonia Organization (CAPO) International Cohort study. CHEST Journal, 133(3),618-624.4.Hartl WH, Wolf H, Schneider CP, et al. Secular trends in mortality associated with newtherapeutic strategies in surgical critical illness. Am J Surg. 2007;194:535–541.5.Girou E, Brun-Buisson C, Taille S, et al. Secular trends in nosocomial infections andmortality associated with noninvasive ventilation in patients with exacerbation of COPDand pulmonary edema. JAMA.2003;290:2985–2991.6.Mortensen EM, Restrepo M, Anzueto A, et al. Effects of guideline-concordantantimicrobial therapy on mortality among patients with community-acquired pneumonia.Am J Med. 2004;117:726–731.

Figure 2: Time to Clinical Stability for the three study periods

RESULTS

METHODSStudy designThis was a secondary data analysis of the Community-Acquired PneumoniaOrganization (CAPO) International Cohort Study database. Data were collectedbetween 2002 and 2014. In each participating center, non-consecutive medicalrecords of hospitalized patients with the diagnosis of CAP were reviewed. Asample of the data collection form is available at the study website(www.caposite.com). Validation of data quality was performed at the studycenter before the case was entered in to the CAPO database. InstitutionalReview Board approval was obtained by each participating center.

RESULTS• A total of 7,948 patients were included in the study.• Patients’ characteristics are shown in Table 1. • Mortality rates were: 8.4%, 9.9%, 6.1% for each of the three periods,

respectively, (P<0.001). This is shown in Figure 1.• Time to Clinical Stability for the three study periods is shown in Figure 2.• Length Of Stay in the hospital for the three study periods is shown in

Figure 3.

Figure 3: Length of Stay for the three study periods