Outpatient Care Compared with Hospitalization for Community-Acquired Pneumonia

Context Physicians are sometimes unsure about managing a low-risk patient with community-acquired pneumonia at home. Contribution In this trial, 224 immunocompetent patients with community-acquired pneumonia and no respiratory failure, complicated pleural effusions, or unstable comorbid illnesses were randomly assigned to outpatient care with oral levofloxacin or hospitalization with initial intravenous levofloxacin therapy. About 80% of patients in both groups had successful outcomes without any complications. Treatment length and frequency of adverse drug events and subsequent hospital admissions were similar. Outpatients reported greater satisfaction with care than did inpatients. Implications Outpatient treatment appears effective for low-risk patients with community-acquired pneumonia. The Editors Community-acquired pneumonia continues to be a major health problem worldwide. In the United States, about 600000 of the 4 million patients who develop community-acquired pneumonia each year are hospitalized, accounting for an annual cost of approximately $23 billion (1). Selection of the initial site of care, whether outpatient or in-hospital, is one of the most important clinical decisions made in the treatment of community-acquired pneumonia and directly affects the intensity of laboratory testing, microbiological evaluation, and antibiotic therapy (2, 3). Nevertheless, investigators have reported considerable variations in hospital admission rates for patients with community-acquired pneumonia, suggesting that physicians do not use a uniform strategy for determining admission and tend to overestimate the likelihood of death from pneumonia (4). On the other hand, most low-risk patients with community-acquired pneumonia prefer to be cared for at home rather than in the hospital when given the choice (5). The prognosis of patients with community-acquired pneumonia varies greatly (6). The Pneumonia Outcomes Research Team has developed a prediction rule based on the Pneumonia Severity Index (PSI) (7), which is calculated from data that are commonly available at presentation. The PSI accurately stratifies patients into 5 risk classes with 30-day mortality rates ranging from 0.1% in class I to 27.0% in class V (7). This index is viewed as an objective measure of risk stratification to help determine the initial site of care for community-acquired pneumonia (8, 9). Experts currently agree that patients in high-risk classes must be hospitalized, but the most appropriate site of care for patients in risk classes II or III, who account for 30% to 50% of hospitalizations, is still controversial. We designed this randomized trial to test the hypothesis that outpatient care of these low-risk patients with community-acquired pneumonia would be as safe and effective as hospitalization. Methods Study Design and Setting This randomized trial was conducted between 1 October 2000 and 31 October 2002 in Barcelona, Spain, at 2 tertiary care hospitals: the IDIBELL-Hospital Universitari de Bellvitge, a 900-bed university public hospital, and the SCIAS-Hospital de Barcelona, a 300-bed private hospital. The ethical committees of both institutions approved the study. Patient Eligibility and Recruitment Process All immunocompetent patients who were at least 18 years of age and had received a diagnosis of community-acquired pneumonia in the emergency department (24 hours per day, 7 days per week) were screened for potential eligibility. Patients who had neutropenia, HIV infection, transplantation, or splenectomy or who were taking immunosuppressive drugs were not eligible. Community-acquired pneumonia was defined as the presence of a new infiltrate on chest radiography plus at least 1 of the following: fever (temperature 38.0 C) or hypothermia (temperature <35.0 C), new cough with or without sputum production, pleuritic chest pain, dyspnea, or altered breath sounds on auscultation. The chest radiograph was interpreted by the infectious disease consultant, not specifically by a radiologist. Patients with community-acquired pneumonia were stratified into risk classes by using the validated prediction rule calculated according to the PSI scores, as described elsewhere (7). Patients in risk classes I, IV, and V were excluded. Patients in risk classes II and III were considered for randomization but were excluded if they met 1 or more of the following criteria: pregnancy or breastfeeding, allergy to quinolones, receipt of quinolones in the preceding 3 months, respiratory failure (Pao 2 < 60 mm Hg, saturation of 90% using pulse oximetry, or both), concomitant unstable comorbid conditions necessitating hospitalization for treatment, complicated pleural effusion, shock, lung abscess, metastatic infection, severe social problems precluding adequate outpatient treatment, cognitive or psychiatric impairment, or inability to maintain oral intake. Patients in risk class II or III (PSI scores 90 points) without any of these exclusion criteria were randomly assigned. We assessed 998 consecutive patients for eligibility and excluded 571 who presented in risk class I, IV, or V (Figure). Of 427 patients in risk classes II and III, 158 met exclusion criteria and 45 declined to participate. The most common reason for exclusion was respiratory failure in 114 patients, 51 (44.7%) in class II and 63 (55.3%) in class III. Ten patients were excluded because of concomitant unstable comorbid conditions; 3 had new-onset atrial fibrillation, 2 had an exacerbation of congestive heart failure, 2 had angina pectoris, 1 had diabetic ketoacidosis, 1 had severe acute renal failure, and 1 patient with liver disease had ascites. Eight patients were excluded because of social problems; 3 were homeless, and 5 with severe alcohol abuse lacked home care support. Forty-five patients (mean age, 62 years) declined to participate; 26 (57.8%) were men. Of these patients, 35 (77.8%) were in class II and 10 (22.2%) were in class III. Figure. Study profile. Randomization Randomization was performed by using a computer-generated random code with a block size of 10. Randomization was stratified by hospital site, and the random code was held centrally, in a sealed envelope, by the clinical epidemiologist. In the emergency department, the infectious disease consultant (in most cases not a study investigator) opened sealed, sequentially numbered opaque envelopes to randomly assign patients who had provided written informed consent and met the study criteria. Patients were randomly assigned to receive outpatient care or hospitalization. Outpatients were given oral levofloxacin (500 mg/d), and hospitalized patients received sequential intravenous and oral levofloxacin (500 mg/d). All patients received detailed written information about their pneumonia diagnosis and their treatment plan, as well as emergency contact telephone numbers for a nurse or investigator physician. Study End Points The primary end point of the trial was the percentage of patients with an overall successful outcome, defined as meeting all of 7 predefined criteria: cure of pneumonia (as defined later), absence of adverse drug reactions, absence of medical complications during treatment, no need for additional visits, no changes in initial treatment with levofloxacin, absence of subsequent hospital admission in the 30 days after randomization, and absence of death from any cause in the 30 days after randomization. Secondary end points included patients' health-related quality of life and satisfaction with the care received for pneumonia. Follow-up and Outcomes Assessment Patients assigned to outpatient care were visited at home by a nurse 48 hours after emergency department discharge. The visit included assessment of vital signs and measurement of oxygen saturation by pulse oximetry. If the nurse thought that a patient's condition was not improving (worsening of baseline vital signs, oxygen saturation, or both), one of the investigators made an additional visit. The nurse was involved only in outcome assessment. Patients assigned to hospitalization were seen daily during their hospital stay by attending physicians and by at least 1 of the investigators. Criteria for early switching from intravenous to oral levofloxacin were a respiratory rate of 24 breaths/min or less, a pulse rate of 100 beats/min or less, a temperature of 37.8 C or lower on 2 occasions at least 8 hours apart, and maintenance of adequate oral intake. Physicians were advised to discharge patients after their clinical condition stabilized, in accordance with previously recommended criteria (10). All patients were seen at the outpatient clinic at days 7 and 30 after pneumonia diagnosis. Pneumonia was considered cured when all baseline signs (fever, hypothermia, altered breath sounds) and symptoms (cough, chest pain, dyspnea) resolved and when infiltrates on chest radiograph disappeared, according to assessment at the final 30-day visit by at least 2 investigators who were not blinded to the treatment strategy. The investigators also assessed all the remaining variables used as criteria for the primary end point at days 7 and 30 after randomization. All assessments were made by using a standard protocol with a checklist of items. The Short Form-36 (SF-36) health survey questionnaire (11) was used to measure health-related quality of life. This instrument has been previously validated in patients with community-acquired pneumonia (12). The SF-36 includes 1 multi-item scale that assesses 8 health concepts: physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role, and mental health. Scores range from 0 to 100; higher scores indicate better quality of life. The SF-36 was administered at days 7 and 30 after randomization, using the 1-week recall period. The results of the questionnaire at 30 days were compared with data available for people of a similar age distribution in the general Spanish population (13).