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Early Antibiotic Treatment for Severe Acute Necrotizing Pancreatitis: A Randomized, Double-Blind, Placebo-Controlled Study

Dellinger, E Patchen MD*; Tellado, Jose M. MD†; Soto, Norberto E. MD‡; Ashley, Stanley W. MD§; Barie, Philip S. MD, MBA∥; Dugernier, Thierry MD, PhD¶; Imrie, Clement W. FRCS#; Johnson, Colin D. MChir, FRCS**; Knaebel, Hanns-Peter MD, MBA††; Laterre, Pierre-Francois MD‡‡; Maravi-Poma, Enrique MD, PhD§§; Kissler, Jorge J. Olsina MD, PhD∥∥; Sanchez-Garcia, Miguel MD, PhD¶¶; Utzolino, Stefan MD##

doi: 10.1097/01.sla.0000250414.09255.84
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Background & Aims: In patients with severe, necrotizing pancreatitis, it is common to administer early, broad-spectrum antibiotics, often a carbapenem, in the hope of reducing the incidence of pancreatic and peripancreatic infections, although the benefits of doing so have not been proved.

Methods: A multicenter, prospective, double-blind, placebo-controlled randomized study set in 32 centers within North America and Europe. Participants: One hundred patients with clinically severe, confirmed necrotizing pancreatitis: 50 received meropenem and 50 received placebo. Interventions: Meropenem (1 g intravenously every 8 hours) or placebo within 5 days of the onset of symptoms for 7 to 21 days. Main Outcome Measures: Primary endpoint: development of pancreatic or peripancreatic infection within 42 days following randomization. Other endpoints: time between onset of pancreatitis and the development of pancreatic or peripancreatic infection; all-cause mortality; requirement for surgical intervention; development of nonpancreatic infections within 42 days following randomization.

Results: Pancreatic or peripancreatic infections developed in 18% (9 of 50) of patients in the meropenem group compared with 12% (6 of 50) in the placebo group (P = 0.401). Overall mortality rate was 20% (10 of 50) in the meropenem group and 18% (9 of 50) in the placebo group (P = 0.799). Surgical intervention was required in 26% (13 of 50) and 20% (10 of 50) of the meropenem and placebo groups, respectively (P = 0.476).

Conclusions: This study demonstrated no statistically significant difference between the treatment groups for pancreatic or peripancreatic infection, mortality, or requirement for surgical intervention, and did not support early prophylactic antimicrobial use in patients with severe acute necrotizing pancreatitis.

A double-blind randomized trial of early meropenem versus placebo for patients with necrotizing pancreatitis failed to find any reduction in infectious complications or mortality in the treated group.

From the *Division of General Surgery, University of Washington, Seattle, WA; †Department of Surgery CGI, Hospital Universitario Gregorio Marañon, Madrid, Spain; ‡AstraZeneca, Wilmington, DE; §Department of Surgery, Brigham and Women's Hospital, Boston, MA; ∥Department of Surgery, Weill Medical College of Cornell University, New York, NY; ¶Intensive Care Department, Clinique Saint Pierre, Ottignies, Belgium; #Lister Department of Surgery, Glasgow Royal Infirmary, Scotland, United Kingdom; **University Surgery, Southampton General Hospital, Hampshire, United Kingdom; ††Department of General Surgery, University of Heidelberg, Heidelberg, Germany; ‡‡Department of Intensive Care, St. Luc University Hospital, Brussels, Belgium; §§Intensive Care Unit, Hospital Virgen del Camino, Pamplona, Spain; ∥∥Department of Surgery, Hospital General de la Vall D'Hebron, Barcelona, Spain; ¶¶Hospital Universitario Principe de Asturias, Alcala de Henares, Madrid, Spain; and ##Department of General and Visceral Surgery, Albert-Ludwigs University of Freiburg, Freiburg, Germany.

Presented in part at the Interscience Congress of Antimicrobial Agents and Chemotherapy, Washington, DC [Abstract No. K-1374, December 18, 2005].

Supported by a grant from AstraZeneca Pharmaceuticals.

Reprints: E. Patchen Dellinger, MD, Division of General Surgery, University of Washington, Box 356410, Room BB 428, 1959 NE Pacific Street, Seattle, WA 98195-6410. E-mail: patch@u.washington.edu.

© 2007 Lippincott Williams & Wilkins, Inc.