title: Relationship between time to clinical response and outcomes among Pneumonia Outcomes Research Team (PORT) risk class III and IV hospitalized patients with community-acquired pneumonia who received ceftriaxone and azithromycin.
abstract: Recent Food and Drug Administration (FDA) guidance endorses the use of an early clinical response endpoint as the primary outcome for community-acquired bacterial pneumonia (CABP) trials. While antibiotics will now be approved for CABP, in practice they will primarily be used to treat patients with community-acquired pneumonia (CAP). More importantly, 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. The clinical response was defined as clinical stability for 24 h with improvement in at least one pneumonia symptom and with no symptom worsening. A 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 2 days following the achievement of a clinical response. In the CART analysis, adverse clinical outcomes were higher among day 5 nonresponders than 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 indicator of real-world effectiveness outcomes among hospitalized PORT risk class III and IV patients with CAP who received ceftriaxone and azithromycin.
authors.affiliation: Albany College of Pharmacy and Health Sciences, Albany, New York, USA.
authors.forename: Evan
authors.initials: E
authors.lastname: Zasowski
authors.affiliation: Albany College of Pharmacy and Health Sciences, Albany, New York, USA.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Butterfield
authors.affiliation: State University of New York at Albany, Albany, New York, USA.
authors.forename: Louise-Ann
authors.initials: LA
authors.lastname: McNutt
authors.affiliation: Albany Medical Center, Albany, New York, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Cohen
authors.affiliation: Albany College of Pharmacy and Health Sciences, Albany, New York, USA.
authors.forename: Leon
authors.initials: L
authors.lastname: Cosler
authors.affiliation: Albany College of Pharmacy and Health Sciences, Albany, New York, USA Amit.Pai@acphs.edu Thomas.Lodise@acphs.edu.
authors.forename: Manjunath P
authors.initials: MP
authors.lastname: Pai
authors.affiliation: Albany College of Pharmacy and Health Sciences, Albany, New York, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Gottwald
authors.affiliation: Albany College of Pharmacy and Health Sciences, Albany, New York, USA.
authors.forename: Wen Zhen
authors.initials: WZ
authors.lastname: Chen
authors.affiliation: Albany College of Pharmacy and Health Sciences, Albany, New York, USA Amit.Pai@acphs.edu Thomas.Lodise@acphs.edu.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Lodise
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017963:Azithromycin / Q000627:therapeutic use*; D002443:Ceftriaxone / Q000627:therapeutic use*; D015331:Cohort Studies; D017714:Community-Acquired Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D023381:Endpoint Determination; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009518:New York / Q000453:epidemiology; D010359:Patient Readmission; D011014:Pneumonia / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D012189:Retrospective Studies; D018570:Risk Assessment; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D002443:Ceftriaxone; D017963:Azithromycin
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