Relationship between Time to Clinical Response and Outcomes among PORT III and IV Hospitalized Patients with Community-Acquired Pneumonia who Received Ceftriaxone and Azithromycin.
Antimicrob Agents Chemother. 2014 Apr 21;
Authors: Zasowski E, Butterfield JM, McNutt LA, Cohen J, Cosler L, Pai MP, Gottwald J, Chen WZ, Lodise TP
Recent FDA guidance endorses use of an early clinical response endpoint as the primary outcome for community-acquired bacterial pneumonia (CABP) trials. While antibiotics will be approved now for CABP, they will be primarily used to treat patients with community-acquired pneumonia (CAP) in practice. It is unclear how achievement of the new FDA CABP early response endpoint translates into clinically applicable "real-world" outcomes for patients with CAP. To address this, a retrospective cohort study was conducted among adult patients who received ceftriaxone and azithromycin for CAP of Pneumonia Outcomes Research Team (PORT) risk class III and IV at an academic medical center. Clinical response was defined as clinical stability for 24 hours with improvement in at least one pneumonia symptom and none worsening. Classification and regression tree (CART) was used to determine the delay in response time, measured in days, associated with the greatest risk of a prolonged hospital length of stay (LOS) and adverse outcomes (in-hospital mortality or 30-day CAP-related readmission). A total of 250 patients were included. On average, patients were discharged two days following the achievement of clinical response. In the CART analysis, adverse clinical outcomes were higher among day 5 non-responders relative to those who responded by day 5 (22.4% versus 6.9%, P=0.001). The findings from this study indicate that time to clinical response, as defined by the recent FDA guidance, is a reasonable prognostic indictor of "real-world" effectiveness outcomes among hospitalized PORT risk class III and IV patients with CAP who received ceftriaxone and azithromycin.
PMID: 24752270 [PubMed - as supplied by publisher]