Severe community-acquired pneumonia as a cause of severe... : Critical Care Medicine (original) (raw)

Continuing Medical Education Article

Severe community-acquired pneumonia as a cause of severe sepsis: Data from the PROWESS study*

Laterre, Pierre-Francois MD; Garber, Gary MD, FRCPC, FACP; Levy, Howard MD, PhD; Wunderink, Richard MD; Kinasewitz, Gary T. MD; Sollet, Jean-Pierre MD; Maki, Dennis G. MD; Bates, Becky MS; Yan, Sau Chi Betty PhD; Dhainaut, Jean-Francois MD, PhD for the PROWESS Clinical Evaluation Committee

Professor in Medicine, Head of Intensive Care Unit, Cliniques Universitaires Saint-Luc Service des Urgences et des Soins Intensifs, UCL, Brussels, Belgium (P-FL); Professor of Medicine, University of Ottawa, Head, Division of Infectious Diseases, The Ottawa Hospital-General Campus, Ottawa, Ontario, Canada (GG); Medical Director, Acute Care, US Medical Division, Eli Lilly and Co., Albuquerque, NM (HL); Professor of Medicine, the Division of Pulmonary and Critical Care Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL (RW); Professor and Chief, Pulmonary and Critical Care Medicine, University of Oklahoma Health Science Center, Oklahoma City, OK (GTK); Specialist in Intensive Care Medicine, Practicien Hospitalier, Victor Dupouy Hospital, Argenteuil, France (J-PS); Ovid O. Meyer Professor of Medicine, Head, Section of Infectious Diseases, Attending Physician, Center for Trauma and Life Support, University of Wisconsin Hospital and Clinics, Madison, WI (DGM); Associate Senior Statistician (BB), Research Fellow (SCBY), Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN; President of the Paris V University, Chairman of the Intensive Care Department, Cochin Port-Royal Hospital-Universitaire, Paris, France (J-FD).

Research supported, in part, by Eli Lilly & Company.

Abstract

Objective:

To investigate community-acquired pneumonia (CAP) as a cause of severe sepsis in the PROWESS (Recombinant Human Activated _Pro_tein C _W_orldwide _E_valuation in _S_evere _S_epsis) trial and to evaluate the effect of drotrecogin alfa (activated) (DrotAA) in this subgroup.

Design:

Retrospective analysis of the severe CAP subgroup in the PROWESS trial.

Setting:

Tertiary care institutions in 11 countries.

Interventions:

DrotAA (n = 850), 24 μg·kg−1·hr−1 for 96 hrs, or placebo (n = 840).

Participants:

The 1,690 patients with severe sepsis enrolled in the PROWESS trial.

Measurements and Main Results:

Patients were classified as having CAP if lung was the primary site of infection and if they were enrolled directly from home (private residence) with ≤4 days in the hospital before receipt of study drug in the PROWESS trial. Survival at 28 days, hospital discharge, and 90 days was compared in DrotAA and placebo groups in the CAP subgroup of PROWESS and CAP subgroups based on disease severity. Of the 1,690 PROWESS patients, 35.6% (DrotAA, n = 324; placebo, n = 278) were classified as severe CAP. Of these severe CAP patients, 26.1% had Streptococcus pneumoniae infections. Within CAP, 79.1% were enrolled by the end of the second calendar day in the hospital, and approximately 90% of CAP patients were at high risk of death according to the Pneumonia Severity Index category. Based on their dependence on vasopressors, 59% of CAP patients were judged at high risk of death. Biomarkers of coagulation and inflammation were markedly abnormal in severe CAP patients. In severe CAP patients treated with DrotAA, a relative risk reduction in mortality of 28% was observed at 28 days, with a relative risk reduction in mortality of 14% observed at 90 days from the start of study drug infusion. The survival benefit was most pronounced in severe CAP patients with S. pneumoniae and in severe CAP patients at high risk of death as indicated by Acute Physiology and Chronic Health Evaluation II score of ≥25, Pneumonia Severity Index score of ≥4, or CURB-65 (confusion, urea, respiratory rate, blood pressure, age) score of ≥3.

Conclusions:

CAP associated with a high Pneumonia Severity Index score, bacteremia, or an intense coagulation and inflammatory response requiring intensive care unit care were indicators of a high risk of death from severe sepsis. In patients with severe sepsis resulting from CAP, a readily identifiable disease, DrotAA, improved survival compared with placebo.