Characteristics and Clinical Outcomes of Hospitalized Patients with Community-Acquired Pneumonia who are Active Intravenous Drug Users

Background: Intravenous drug users (IVDU) have a 10-fold increased risk of community-acquired pneumonia (CAP) compared to the general population. There is scarce data available evaluating the clinical outcomes of IVDU hospitalized patients with CAP and that data mostly focuses on mortality. The objective of this study was to evaluate the clinical characteristics, incidence and outcomes of hospitalized patients with CAP in active intravenous drug users in Louisville, Kentucky. Methods: This was a secondary data analysis of the University of Louisville Pneumonia study. IVDU patients were propensity score matched to a non-IVDU group. Study outcomes were time to clinical stability (TCS), length of stay (LOS), mortality at discharge, and mortality at 1 year. Stratified Cox proportional hazard regression was performed to evaluate TCS and LOS. Conditional logistic regression was performed to evaluate mortality. Statistical significance was defined as p ≤ 0.05. Results: From a total of 8,284 hospitalized patients with CAP reviewed, 113 patients were matched per group. Median (IQR) age for the IVDU was 33 (28-43) versus 36 (28-48) for the matched nonIVDU group (p<0.001). Analysis showed no association with TCS (stratified hazard ratio (sHR): 0.81; 95% CI: 0.58-1.14; p=0.227), LOS (sHR: 0.71; 95% CI: 0.50-1.01; p=0.053), mortality at discharge (conditional odds ratio (cOR): 1.67; 95% CI: 0.40-6.97; p=0.484) and mortality at 1 year (cOR: 1.125; 95% CI: 0.43-2.92; p=0.808). Conclusions: This study shows that active IVDU hospitalized patients with CAP do not have worse outcomes when compared with non-IVDU hospitalized patients with CAP. Patients in the IVDU group were significantly younger. Since severity scores commonly used are heavily influenced by age, these will not likely be useful tools to assist the physicians with the site for care and management. DOI: 10.18297/jri/vol2/iss2/3 Received Date: February 22, 2018 Accepted Date: July 24, 2018 Website: https://ir.library.louisville.edu/jri Copyright: ©2018 the author(s). This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Affiliations: 1University of Louisville Division of Infectious Diseases, Louisville, KY 40202 2Pfizer, Inc., Collegeville, PA *Correspondence To: Vidyulata Salunkhe Work Address: University of Louisville, Division of Infectious Diseases 501 E. Broadway, Louisville, KY 40202 Work Email: vidyulata.salunkhe@louisville.edu 7 ULJRI Vol 2, (2) 2018 ORIGINAL RESEARCH population-based cohort study of all hospitalized adults with CAP who were residents in the city of Louisville, Kentucky, from June 1st, 2014 to May 31st, 2016 [13]. Inclusion Criteria 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 of admission to the hospital. B. Signs and Symptoms of CAP (at least one of the following): • New or increased cough • Fever >37.8°C (100.0°F) or hypothermia <35.6°C (96.0°F) • 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 antimicrobial therapy given within 24 hours of admission. Study Groups Cases (group 1): Hospitalized patients with CAP with active IVDU documented in the medical record. Controls (group 2): Hospitalized adults with CAP who did not have documentation of actively using intravenous drugs. IVDU cases were matched 1:1 to control cases by age, race, and history of obesity (body mass index >30), current smoker, active alcohol use, chronic obstructive pulmonary disease, congestive heart failure, stroke, diabetes mellitus, HIV, renal disease, and liver disease. Study Variables • Patients’ characteristics: demographics, medical and social history, physical, and laboratory findings were collected if documented in the medical records. • Severity of disease: assessed by the following variables – acute altered mental status on admission, need of intensive care, ventilatory support, or vasopressor on the day of admission, pneumonia severity index risk class IV or V. • Complications: defined as the presence of persistent bacteremia and/or endocarditis. Study Outcomes • Time to clinical stability (TCS): A patient was defined as clinically stable the day that the following four criteria were met: 1. Improvement in cough and shortness of breath 2. Lack of fever for at least 8 hours 3. Improving leukocytosis (decreased at least 10% from the previous day) 4. Tolerating oral intake with adequate gastrointestinal absorption Patients were evaluated daily within the first 7 days of hospitalization to determine the day when clinical stability was reached. • Length of hospital stay (LOS): defined in days and calculated for each patient as the day of discharge minus the day of admission. Patients hospitalized for >14 days and patients who died prior to 14 days were censored at 14 days. • Mortality: defined as death by any cause 1) during hospitalization and 2) at one year after discharge. 8 ULJRI Vol 2, (2) 2018 Table 1 Patients’ characteristics for both study groups Variable IV Drug Users Non IV Drug Users Pvalue Total Population n=113 n=113

population-based cohort study of all hospitalized adults with CAP who were residents in the city of Louisville, Kentucky, from June 1st, 2014 to May 31st, 2016 [13].

Inclusion Criteria
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 of admission to the hospital. B. Signs and Symptoms of CAP (at least one of the following): • • Mortality: defined as death by any cause 1) during hospitalization and 2) at one year after discharge.

Discussion
This study shows that IVDU is not associated with poor outcomes in hospitalized patients with CAP. The more aggressive management that these patients may receive upon admission may be the reason for similar outcomes in both groups despite differences found in the severity of the disease. To our knowledge, this is the first study evaluating clinical outcomes in IVDU hospitalized with CAP.
Active IVDU presented with more severe CAP as evidenced by their higher rates of admission to the intensive care unit and altered mental status. The higher rates of altered mental status could be explained by drug overdose and consequent aspiration. Our findings are in concordance with published data indicating that active substance abuse is a predictor of more severe pneumonia and the need for more intensive management.
Considering that IVDU patients tend to be younger, as shown in our study, scores are heavily influenced by age are those commonly used to assess severity at presentation to the hospital. These may not be useful tools to assist physicians in care and management of IVDU CAP patients.
It has been reported that IVDU patients develop more complications. In a study evaluating risk factors for complicated parapneumonic effusion and empyema, IVDU was independently associated with the development of these complications [11]. However, in our study, a lower number of IVDU presented with pleural effusions/empyema. This could be related to a higher percentage of patients with congestive heart failure in the non-IVDU group who may have developed effusions secondary to this baseline comorbidity and not the pneumonia. IVDU commonly developed persistent bacteremia and endocarditis, particularly in the tricuspid valve with the subsequent septic emboli to the lungs [14][15][16]. Our study also showed higher rates of persistent bacteremia and pulmonary embolism, both independently associated with poor outcomes. There was a higher percentage of patients with chest images compatible with septic emboli. This could indicate that the pneumonia is actually a consequence of infective endocarditis bringing the relevance of obtaining blood cultures on admission to the hospitals and allowing an early identification of this population.  In conclusion, our study shows that IVDU is not associated with poor outcomes among hospitalized CAP patients. IVDU patients were significantly younger and presented with more severe CAP as evidenced by higher rates of admission to the intensive care unit and altered mental status. These patients also developed significantly higher complications like persistent bacteremia, pulmonary emboli and endocarditis. A more aggressive management may be needed in this young population in order to achieve good outcomes and prevent further complications. ULJRI Vol 2, (2) 2018