Reducing Antimicrobial Overuse Through Targeted Therapy for Patients with Community-Acquired Pneumonia

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Project Summary/Abstract Community-acquired pneumonia (CAP) is a leading cause of hospitalizations and inpatient morbidity and mortality in the United States. However, the etiological diagnosis of CAP is challenging as >75% of cultures are negative and a causative pathogen cannot be identified. The ATS/IDSA guidelines recommend that extended spectrum empiric antimicrobial therapy be limited to adult patients with risk factors for resistant pathogens. However, in the face of negative cultures and diagnostic uncertainty, clinicians are often uncomfortable de- escalating therapy, because narrowing treatment could result in inadequate coverage. The prolongation of empiric treatment hampers antimicrobial stewardship efforts and encourages the development of antimicrobial resistance. Our overall goal is to improve antimicrobial prescribing for patients with CAP by emphasizing pathogen-directed therapy. An accurate pathogenic diagnosis could contribute to antimicrobial stewardship in 2 ways: 1) by allowing for initial narrow-spectrum therapy and 2) by providing confidence when de-escalating therapy following negative cultures. Rapid diagnostic assays have the potential to provide accurate results within hours and thereby reduce the duration of exposure to extended spectrum empiric therapy. Multiple observational studies have demonstrated that use of molecular diagnostic assays is associated with favorable outcomes including a reduction in the total duration of antimicrobial use and length of stay in the hospital. The most recent antimicrobial stewardship implementation guidelines recommend the use of rapid viral testing for respiratory pathogens as a means to reduce the use of inappropriate antibiotics. However, these recommendations are based on low quality evidence and it is unknown whether more widespread early diagnostic testing could reduce the use of broad-spectrum antibiotics and/or prompt initiation of antiviral therapy. De-escalation following negative bacterial cultures is another antimicrobial stewardship target. While most de-escalation follows identification of a susceptible pathogen, the ATS/IDSA guidelines also recommend de-escalation at 48 hours if cultures are negative. However, these recommendations are also based on observational studies. We propose a large, multicenter 2 X 2 factorial cluster randomized controlled trial to test both approaches to reducing the use of broad-spectrum antibiotics in patients with CAP: a) routine use of rapid diagnostic testing at the time of admission and b) pharmacist-led de-escalation after 48 hours for clinically stable patients with negative cultures. Our study will be the largest randomized trial to determine the impact of rapid diagnostic testing on antimicrobial stewardship and patient outcomes. Our randomized trial design will allow us to establish causality and determine whether broad spectrum antibiotics can be safely de-escalated in stable patients. Findings from our proposed trials will generate important new knowledge about pathogen targeted therapy and antimicrobial de-escalation in patients with CAP. Specifically, knowledge gained from this proposal will allow physicians to limit the use of broad-spectrum antimicrobials and initiate targeted therapy.