This a retrospective cohort study of patients hospitalized with pneumonia at 2 academic tertiary care hospitals in San Antonio, Texas. Both hospitals are teaching affiliates of the University of Texas Health Science Center at San Antonio. The Institutional Review Board of the University Health Science Center at San Antonio approved the research protocol with exempt status.
Study Sites/Inclusion and Exclusion Criteria
We identified all patients admitted to the study hospitals between January 1, 1999 and December 1, 2002 with a primary discharge diagnosis of pneumonia (ICD-9 codes 480.0–483.99 or 485–487.0) or secondary discharge diagnosis of pneumonia with a primary diagnosis of respiratory failure (518.81) or sepsis (038.xx). Subjects were included if they were 1) greater than 18 years of age, 2) had an admission diagnosis of pneumonia, and 3) had a radiographically confirmed infiltrate or other finding consistent with pneumonia on chest x-ray or CT obtained within 24 hours of admission.
Exclusion criteria included 1) having been discharged from an acute care facility within 14 days of admission, 2) transfer after being admitted to another acute care hospital, 3) being a resident of a skilled nursing facility prior to admission, and 4) being comfort measures only on this admission. If a subject was admitted more than once during the study period, only the first hospitalization was abstracted.
Data Abstraction
Chart review data included: demographics, comorbid conditions, physical examination findings, laboratory data, and chest radiograph reports. In addition, data on important processes of care measures for patients hospitalized with pneumonia were also abstracted: time to first dose of antibiotics, collection of blood cultures prior to antibiotic administration, and obtaining blood cultures and oxygen saturation measurement within 24 hours of presentation [8]. Antimicrobial therapy was considered guideline-concordant if it agreed with either the 2000 Infectious Diseases Society of America or 2001 American Thoracic Society guidelines [9, 10], which are similar to the recommendations from the 2007 joint guidelines from these societies [11]. Information on all outpatient medications that were either 1) reported as currently being taken by the patient at presentation, or 2) listed in the electronic medical record, were recorded. Patients were defined as having prior antibiotic use if they had received a prescription within the 30-days prior to hospital presentation.
Diagnostic criteria
Microbiologic data results were reviewed, and a microbiologic cause was assigned independently by two of the investigators (MIR and EMM). The cause of pneumonia was stratified as definitive or presumptive. The diagnosis was considered definitive if one of the following conditions were met: (1) positive blood cultures for bacterial or fungal pathogens were obtained (in the absence of extra-pulmonary source of infection); (2) pleural fluid cultures yielded a bacterial pathogen; (3) endotracheal aspirates with moderate or heavy growth of bacterial pathogens were observed; (4) significant quantitative culture growth from bronchoscopic respiratory samples were observed (protected specimen brush cultures of at least 103 cfu/mL, and in bronchoalveolar lavage of at least 104 cfu/mL). A presumptive diagnosis was made if a qualitative valid sputum sample yielded one or more predominant bacterial pathogens. Definitive and presumptive causes were combined for reporting purposes. When two or more microbiologic causes were present, the patient was considered to have a polymicrobial infection. A patient was considered to have pneumonia of unknown cause if microbiologic studies were not performed or were inconclusive.
Risk Adjustment
The pneumonia severity index was used to assess severity of illness at presentation [4]. The pneumonia severity index is a validated prediction rule for 30-day mortality in patients with community-acquired pneumonia. This rule is based on three demographic characteristics, five comorbid illnesses, five physical examination findings, and seven laboratory and radiographic findings from the time of presentation. Patients are classified into five risk classes with 30-day mortality ranging from 0.1% for class I to 27% for class V for patients enrolled in the PORT cohort study [4].
Outcome
We used 30-day mortality as the outcome for this study. Previous research has demonstrated that 30-day mortality is primarily due to the pneumonia rather than other co-existing co-morbid conditions.[12, 13] Mortality was assessed using information from the Texas Department of Health and Department of Veteran Affairs clinical database. Mortality status was assessed through December 2002.
Statistical Analyses
In a post-hoc power calculation, assuming an alpha of 0.05 and beta of 0.2, we were able to detect a 1.7× difference in mortality between the 2 groups.
Univariate statistics were used to test the association of sociodemographic and clinical characteristics with all-cause 30-day mortality. Categorical variables were analyzed using the Chi-square test and continuous variables were analyzed using Student's t-test. A multivariable logistic regression model was derived with 30-day mortality as the dependent variable, and the pneumonia severity index, process of care measures (initial antibiotics within 8 hours and whether antimicrobial therapy was guideline concordant), and prior receipt of antibiotics within the 30-days prior to presentation as independent variables. All analyses were performed using STATA version 9 (Stata Corporation, College Station, Texas).