The emergence of antimicrobial drug resistance among isolates of S. pneumoniae threatens to have a major impact on the management of patients with community-acquired pneumonia (CAP). S. pneumoniae is the most common cause of CAP and adequate pneumococcal coverage is at the center of empirical guidelines for the management of this disease. Yet, risk factors for infection with drug-resistant vs. drug-susceptible S. pneumoniae are controversial and the clinical impact of in vitro levels of resistance is poorly understood. This study will focus on resistance to penicillin because penicillin and related ,8-lactam antimicrobials are a major component of current empirical treatment options for patients with CAP. Thus, understanding the risk factors for penicillin resistance can make a major contribution to the empirical management of these patients. The primary aim of this study is to identify risk factors for penicillin drug resistance in patients with bacteremic pneumococcal pneumonia. The primary study hypothesis is that both individual and community risk factors independently predict infection with penicillin resistant S. pneumoniae in patients with bacteremic pneumococcal pneumonia. A secondary hypothesis is that the duration of prior antibiotic use is a strong independent predictor of penicillin resistance in these patients. The secondary aims of this study are (1) to develop a prediction rule for penicillin resistance in patients with bacteremic pneumococcal pneumonia and (2) to measure the impact of different levels of penicillin resistance on medical outcomes in these patients. The hypotheses for these secondary aims are that (1) a prediction rule can be developed which accurately categorizes patients into high and low risk groups in order to improve the empirical selection of antimicrobial therapy for patients with CAP and (2) the in vitro level of penicillin resistance, alone, is a poor predictor of medical outcomes, but categorization of the adequacy of antimicrobial drug coverage, based on drug susceptibility profiles and pharmacodynamic drug considerations, will be a strong predictor of medical outcomes. This study is a population-based, case-control study, enrolling all hospitalized patients diagnosed with bacteremic pneumococcal pneumonia within the Pennsylvania Delaware Valley. Risk factors will be identified through patient interview and outpatient and inpatient medical record review. Pneumococcal drug resistance will be categorized at our microbiology laboratory with standardized susceptibility testing of all pneumococcal blood isolates. Finally, a cohort study will be completed within the study design, by examining outcomes for all patients, stratifying by pneumococcal drug susceptibility and adequacy of antimicrobial drug coverage.
