Causes and factors associated with early failure in hospitalized patients with community-acquired pneumonia

Background: Early failure is a matter of great concern in the treatment of community-acquired pneumonia. However, information on its causes and risk factors is lacking. Methods: Observational analysis of a prospective series of 1383 nonimmunosuppressed hospitalized adults with community-acquired pneumonia. Early failure was defined as lack of response or worsening of clinical or radiologic status at 48 to 72 hours requiring changes in antibiotic therapy or invasive procedure's. Concordance of antimicrobial therapy was examined for cases with an etiologic diagnosis. Results: At 48 to 72 hours, 238 patients (18%) remained febrile, but most of them responded without further changes in antibiotic therapy. Eighty-one patients (6%) had early failure. The main causes of early failure were progressive pneumonia (n=54), pleural empyema (n=18), lack of response (n=13), and uncontrolled sepsis (n=9). Independent factors associated with early failure were older age (>65 years) (odds ratio [OR], 0.35), multilobar pneumonia (OR, 1.81), Pneumonia Severity Index score greater than 90 (OR, 2.75), Legionella pneumonia (OR, 2.71), gram-negative pneumonia (OR, 4.34), and discordant antimicrobial therapy (OR, 2.51). Compared with treatment responders, early failures had significantly higher rates of complications (58% vs 24%) and overall mortality (27% vs 4%) (P<.001 for both). Conclusions: Early failure is infrequent but is associated with high morbidity and mortality rates. Its detection and management require careful clinical assessment. Most cases occur because of inadequate host-pathogen responses. Discordant therapy is a less frequent cause of failure, which may be preventable by rational application of the current antibiotic guidelines.