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n e w e ng l a n d j o u r na l
of
m e dic i n e
Original Article
A BS T R AC T
BACKGROUND
The authors full names, academic degrees, and affiliations are listed in the
Appendix. Address reprint requests to
Dr. Sawyer at the Department of Surgery,
University of Virginia Health System, Box
800709, Charlottesville, VA 22908-0709,
or at r ws2k@virginia.edu.
*Deceased.
N Engl J Med 2015;372:1996-2005.
DOI: 10.1056/NEJMoa1411162
Copyright 2015 Massachusetts Medical Society.
The successful treatment of intraabdominal infection requires a combination of anatomical source control and antibiotics. The appropriate duration of antimicrobial
therapy remains unclear.
METHODS
In patients with intraabdominal infections who had undergone an adequate sourcecontrol procedure, the outcomes after fixed-duration antibiotic therapy (approximately 4 days) were similar to those after a longer course of antibiotics (approximately 8 days) that extended until after the resolution of physiological
abnormalities. (Funded by the National Institutes of Health; STOP-IT ClinicalTrials
.gov number, NCT00657566.)
1996
Me thods
Study Population
A Quick Take
summary is
available at
NEJM.org
1997
The
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The mean APACHE II score for the index infection was 10.10.3 (range, 0 to 29), the most common origin of the infection was the colon or rectum, and one third of the infections were treated
with a percutaneous procedure (Table1). Complete demographic data are provided in Table S1
in the Supplementary Appendix, available at NEJM
.org. There were no differences between the two
study groups, at a significance level of less than
0.05, with respect to any demographic variable.
Adherence to the Protocol
1999
The
n e w e ng l a n d j o u r na l
Variable
Age yr
Experimental
Group
(N=258)
52.21.0
52.21.0
145 (55.8)
144 (55.8)
White
208 (80.0)
196 (76.0)
Black
43 (16.5)
51 (19.8)
Asian
5 (1.9)
6 (2.3)
2 (0.8)
1 (0.4)
20 (7.7)
15 (5.8)
2 (0.8)
4 (1.6)
mm3
9.90.4
10.30.4
15,6000.4
17,1000.7
37.80.1
37.70.1
80 (30.8)
97 (37.6)
Appendix
34 (13.1)
39 (15.1)
Small bowel
31 (11.9)
42 (16.3)
Percutaneous drainage
86 (33.1)
86 (33.3)
69 (26.5)
64 (24.8)
55 (21.2)
54 (20.9)
27 (10.4)
37 (14.3)
Simple closure
20 (7.7)
12 (4.7)
3 (1.2)
4 (1.6)
* Plusminus values are means SE. There were no significant differences between the groups (P<0.05).
Race and ethnic groups were reported by the patient or surrogate.
Acute Physiology and Chronic Health Evaluation (APACHE) II scores range
from 0 to 71, with higher scores indicating an increased risk of death.
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Experimental
Group
(N=257)
P Value
58 (22.3)
56 (21.8)
0.92
Surgical-site infection
23 (8.8)
17 (6.6)
0.43
36 (13.8)
40 (15.6)
0.67
2 (0.8)
3 (1.2)
0.99
Variable
Death
Time to event no. of days after index source-control procedure
Diagnosis of surgical-site infection
15.10.6
8.80.4
<0.001
15.10.5
10.80.4
<0.001
Death
19.01.0
18.50.5
0.66
9 (3.5)
6 (2.3)
0.62
Any site
13 (5.0)
23 (8.9)
0.11
Urine
10 (3.8)
13 (5.1)
0.65
Secondary outcome
Surgical-site infection or recurrent intraabdominal infection with
resistant pathogen no. (%)
Site of extraabdominal infection no. (%)
Blood
3 (1.2)
5 (1.9)
0.71
Lung
3 (1.2)
3 (1.2)
0.99
1 (0.4)
4 (1.6)
0.36
Vascular catheter
0 (0)
2 (0.8)
0.47
3 (1.2)
5 (1.9)
0.71
6 (2.3)
2 (0.8)
0.29
510
45
<0.001
Median
Interquartile range
Antimicrobial-free days at 30 days
<0.001
Median
Interquartile range
21
25
1825
2126
411
411
0.48
Median
Interquartile range
Hospital-free days at 30 days
0.22
Median
Interquartile range
23
22
1826
1626
2001
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1.0
Probability of No Events
0.9
Control group
0.8
Experimental group
0.7
0.6
0.5
0.4
0.3
0.2
P=0.96 by log-rank test
0.1
0.0
10
15
20
25
30
260
255
243
228
219
210
205
258
253
227
214
208
203
202
Discussion
In this randomized study involving patients with
complicated intraabdominal infections, a fixed
duration of 4 days of antibiotic treatment resulted in outcomes that were similar to those of
a traditional, longer course that was based on
resolution of physiological abnormalities, and
the shorter course was associated with significantly fewer days of antibiotic exposure. These
data provide support for the concept that after
an adequate source-control procedure, the beneficial effects of systemic antimicrobial therapy
are limited to the first few days after intervention. In addition, it might be argued that the
delay in manifestation of infectious complications in the control group was itself an adverse
outcome, since the time to recognition of these
events and, therefore, the overall time to resolution of all infections was prolonged.
2002
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Subgroup
No. of
Patients
Days of Antibiotic
Therapy
median
(interquartile range)
Adhered to protocol
Control
Experimental
Did not adhere to protocol
Control
Experimental
APACHE II score 10
Control
Experimental
Health careassociated infection
Control
Experimental
Percutaneous drainage
Control
Experimental
Surgical drainage
Control
Experimental
Appendiceal source
Control
Experimental
Non-appendiceal source
Control
Experimental
189
211
7 (510)
4 (45)
71
47
11 (717)
11 (819)
120
122
8 (510)
4 (45)
94
102
8 (510)
4 (45)
86
86
8 (510)
4 (45)
174
171
8 (510)
4 (45)
34
39
8 (510)
5 (46)
226
218
8 (510)
4 (45)
0.0
0.1
0.2
0.3
0.4
0.5
2003
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Appendix
The authors full names and academic degrees are as follows: RobertG. Sawyer, M.D., JeffreyA. Claridge, M.D., AveryB. Nathens,
M.D., OriD. Rotstein, M.D., ThereseM. Duane, M.D., HeatherL. Evans, M.D., CharlesH. Cook, M.D., PatrickJ. ONeill, M.D., Ph.D.,
JohnE. Mazuski, M.D., Ph.D., Reza Askari, M.D., MarkA. Wilson, M.D., LenaM. Napolitano, M.D., Nicholas Namias, M.D., PrestonR.
Miller, M.D., E.Patchen Dellinger, M.D., ChristopherM. Watson, M.D., Raul Coimbra, M.D., DanielL. Dent, M.D., StephenF. Lowry,
M.D., ChristineS. Cocanour, M.D., MichaelaA. West, M.D., Ph.D., KaysieL. Banton, M.D., WilliamG. Cheadle, M.D., PamelaA.
Lipsett, M.D., ChristopherA. Guidry, M.D., and Kimberley Popovsky, B.S.N.
The authors affiliations are as follows: the Department of Surgery, University of Virginia Health System, Charlottesville (R.G.S.,
C.A.G., K.P.); the Department of Surgery, Virginia Commonwealth University, Richmond (T.M.D.); the Department of Surgery, Case
Western Reserve University, Cleveland (J.A.C.); the Department of Surgery, University of Toronto, Toronto (A.B.N., O.D.R.); the Department of Surgery, University of Washington, Seattle (H.L.E., E.P.D.); the Department of Surgery, Beth Israel Deaconess Medical Center
(C.H.C.), and the Department of Surgery, Brigham and Womens Hospital (R.A.) both in Boston; the Department of Surgery, Maricopa Integrated Health System, Phoenix, AZ (P.J.O.); the Department of Surgery, Washington University, St. Louis (J.E.M.); the Department of Surgery, VA Pittsburgh Healthcare System, Pittsburgh (M.A. Wilson); the Department of Surgery, University of Michigan, Ann
Arbor (L.M.N.); the Department of Surgery, University of Miami Miller School of Medicine, Miami (N.N.); the Department of Surgery,
Wake Forest School of Medicine, Winston-Salem, NC (P.R.M.); the Department of Surgery, University of South Carolina, Columbia
(C.M.W.); University of California, San Diego, San Diego (R.C.), the Department of Surgery, UC Davis Medical Center, Sacramento
(C.S.C.), and the Department of Surgery, University of California, San Francisco, San Francisco (M.A. West) all in California; the
Department of Surgery, University of Texas Health Science Center at San Antonio, San Antonio (D.L.D.); the Department of Surgery,
University of Medicine and Dentistry of New Jersey, Newark (S.F.L.); the Department of Surgery, University of Minnesota Medical
School, Minneapolis (K.L.B.); the Department of Surgery, University of Louisville School of Medicine, Louisville, KY (W.G.C.); and the
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore (P.A.L.).
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