ANNALS OF SURGERY

Vol. 218, No. 2,111-119

1993 J. B. Lippincott Company
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The Gastrointestinal Tract

The "Undrained Abscess" of Multiple
Organ Failure
John C. Marshall, M.D., F.R.C.S.C., F.A.C.S.,*
Nicolas V. Christou, M.D., Ph.D., F.R.C.S.C., F.A.C.S.,t
and Jonathan L. Meakins, M.D., D.Sc., F.R.C.S.C., F.A.C.S.t

From the Departments of Surgery, University of Toronto, Toronto, Ontario,*

and McGill University, Montreal, Quebec,t Canada

Objective
This study determined the association between proximal gastrointestinal (GI) colonization and the
development of intensive care unit (ICU)-acquired infection and multiple organ failure (MOF) in
a population of critically ill surgical patients.

Summary Background Data

ICU-acquired infection in association with progressive organ system dysfunction is an important
cause of morbidity and mortality in critical surgical illness. Oropharyngeal and gastric
colonization with the characteristic infecting species is common, but its association with ICU
morbidity is poorly defined.

Methods
A prospective cohort study of 41 surgical ICU patients was undertaken. Specimens of gastric
and upper small bowel fluid were obtained for quantitative culture; the severity of organ
dysfunction was quantitated by a numeric score.

Results
One or more episodes of ICU-acquired infection developed in 33 patients and involved at least
one organism concomitantly cultured from the upper GI tract in all but 3. The most common
organisms causing ICU-acquired infection-Candida, Streptococcus faecalis, Pseudomonas,
and coagulase-negative Staphylococci-were also the most common species colonizing the
proximal GI tract. Gut colonization correlated with the development of invasive infection within 1
week of culture for Pseudomonas (90% vs. 13% in noncolonized patients, p < 0.0001) or
Staphylococcus epidermidis (80% vs. 6%, p < 0.0001); a weaker association was seen for
colonization with Candida. Infections associated with GI colonization included pneumonia (16
patients), wound infection (12 patients), urinary tract infection (11 patients), recurrent (tertiary)
peritonitis (1 1 patients), and bacteremia (10 patients). ICU mortality was greater for patients
colonized with Pseudomonas (70% vs. 26%, p = 0.03); organ dysfunction was most marked in
patients colonized with one or more of the following: Candida, Pseudomonas, or S. epidermidis.

Conclusions
The upper GI tract is an important reservoir of the organisms causing ICU-acquired infection.
Pathologic GI colonization is associated with the development of MOF in the critically ill surgical
patient.

111

112

Marshall, Christou, and Meakins

Ann. Surg. * August 1993

Nosocomial infection acquired within the intensive

care unit (ICU) commonly complicates the course ofcritical surgical illness. Infections develop during as many as
and are
one third of all admissions to a surgical
associated with increased mortality and a significant pro-

extends those observations to assess the association of

proximal gut colonization with the development of ICUacquired infection and MOF.

ICU,`

longation of ICU stay.4

ICU-acquired infections differ clinically and epidemiologically from the life-threatening surgical infections that
precipitate ICU admission. An important factor in their
development is impairment oflocal host defenses by surgery and the presence of invasive monitoring devices,3'5
the use of broad spectrum antibiotics with disruption of
the endogenous flora,5'6 and the prolonged absence of
enteral feeding.7 Moreover, they arise in the setting of
transient but profound abnormalities of intrinsic host
defenses,8 and their prevalence is highest in patients with
the most marked degrees of organ dysfunction.9
The microbiology of ICU-acquired infection is also
strikingly different from that of community-acquired infection. The most common isolates from episodes of
ICU-acquired infection are endogenous organisms of
low intrinsic virulence including coagulase-negative
Staphylococci, Candida, and enterococci, in addition to
gram-negative aerobes with a predilection for the compromised host, in particular, Pseudomonas, Enterobacter, and Acinetobacter.3 4'9"'l The reservoirs of these
organisms are incompletely defined. Although infection
transmission by ICU staff or other patients,'2 or by contaminated devices6 has been documented, most ICU-acquired infections are caused by the patient's own flora,
after pathologic colonization of endogenous reservoirs.
Earlier reports focused on the role of oropharyngeal colonization in the pathogenesis of nosocomial infection.'3
More recently, it has been appreciated that the stomach
and small bowel also become colonized with the organisms responsible for a significant number of nosocomial
infections in critically ill patients,'147 and it has been
hypothesized that the pathologic colonization of the
gastrointestinal (GI) tract may be a critical prelude to
the development of the syndrome of multiple organ
failure (MOF). 18-20
We previously reported that the most common causes
of nosocomial infection in patients with MOF-Staphylococcus epidermidis, Pseudomonas, and Candida-are
also the most frequent isolates from the upper GI tract of
critically ill surgical ICU patients.9 The current report
Presented in part at the Surgical Forum, American College of Surgeons,
October 1987, and at the 33rd World Congress of Surgery, September 1989, Toronto, Ontario, Canada.
Supported by grants from the Medical Research Council of Canada
and the Dalhousie Medical Research Foundation.
Address reprint requests to John Marshall, M.D., F.R.C.S.C., F.A.C.S.,
Eaton North 9-234, Toronto General Hospital, 200 Elizabeth
Street, Toronto, Ontario M5G 2C4, Canada.

METHODS
Study Subjects
Forty-one patients admitted to the Surgical Intensive
Care Unit of the Royal Victoria Hospital, Montreal,
Quebec, Canada, were studied. All patients had pre-existing access to the upper GI tract through one or more
indwelling nasogastric or nasoenteral tubes, or a surgical
gastrostomy or jejunostomy, and were considered on
clinical grounds to be at high risk for the development of
ICU-acquired infections. The protocol was approved by
the Human Ethics Committee ofthe Royal Victoria Hospital, and informed consent was obtained from the patient or a relative.

Definitions
Infection was diagnosed according to microbiologic
and radiographic criteria as described previously.9 The
diagnosis of pneumonia required the presence of a heavy
growth of an organism in two consecutive sputum specimens, in conjunction with purulent sputum and a chest
roentgenogram revealing a new or changing pulmonary
infiltrate. Urinary tract infection was defined as the presence of an organism at a concentration of greater than
105 colony-forming units (CFU) per milliliter of urine.
Bacteremia was said to be present when an organism was
isolated from a single blood culture specimen, or in the
case of S. epidermidis, from two simultaneous specimens or a single specimen and an intravenous catheter
tip. The diagnosis of wound infection required the demonstration of organisms from a wound that drained pus,
or the persistent presence of organisms in an open
wound that failed to show formation of granulation tissue. The diagnosis of recurrent (tertiary) peritonitis was
based on the isolation of an organism from a specimen of
peritoneal fluid obtained at surgical laparotomy, zipper
laparostomy, or percutaneous catheter drainage.
Infections that were present at the time of ICU admission or that developed subsequently as a direct consequence of a surgical procedure were termed primary infections. An infection was considered to be ICU-acquired if it developed at least 48 hours after ICU
admission and involved either a different anatomic site
or micro-organisms different from those cultured from a
primary infection.

Upper GI Flora and ICU-Acquired Infection

Vol. 218 No. 2

-

113

MOF Scores

Statistics

The severity of organ dysfunction over the course of

the ICU admission was quantitated using an organ failure score as previously described.9 Abnormalities in the
function of eight separate organ systems (respiratory,
renal, hepatic, cardiovascular, neurologic, metabolic, hematologic, and immunologic), each graded from 0 (minimal or no dysfunction) to 2 (severe dysfunction), are
summed to produce the MOF score.

Results are presented as the mean standard deviation. The Student's t test and one-way analysis of variance were used to compare means of normally distributed continuous data. Group frequencies were compared using the chi square statistic with Yates'
continuity correction, or the Fisher exact test. Results
were considered to be significant for values of p < 0.05.

Quantitative Proximal GI Cultures

RESULTS
Demographic Data

Upper GI fluid for quantitative culture was obtained

from indwelling gastric and enteric tubes, a method previously shown to yield reliable and reproducible results
when compared with results obtained by direct sampling
at laparotomy.2' After discarding the initial 3 to 5 mL of
fluid in the tubing, between 5 and 15 mL ofGI fluid were
aspirated into a sterile syringe and immediately transported to the laboratory for processing. The pH of an
aliquot of each specimen was determined using indicator
papers, then serial tenfold dilutions in sterile saline were
performed. One hundred microliters of each dilution
was plated on selective media (blood agar and MacConkey agar for aerobes, blood agar, and phenylethyl alcohol
agar for anaerobes). Aerobic plates were incubated for 24
hours at 37 C and anerobic plates for 48 hours at 37 C.
Colonies were then enumerated and species were identified using the API 20E system (API Laboratory Products) for identification of gram-negatives and standard
techniques for gram-positives. Candida organisms were
identified by growth on blood agar and morphology in
wet preparation and were further divided into albicans
and non-albicans species on the basis of germ tube formation after incubation for 2 hours in horse serum. The
culture technique permitted detection of organisms present at a density of as low as 100 CFU/mL of sample; the
upper limit of detection was 108 CFU/mL. Results are
expressed as log10 CFU/mL of GI fluid.

Demographic data for the 41 patients enrolled into the

study are summarized in Table 1. The ICU mortality
rate was 36.6% (15 patients); one or more episodes of
ICU-acquired infection developed in 33 patients (80.5%
of the study population).

Assessment of Culture Technique

The 83 samples obtained for quantitative culture
yielded a mean of 1.8 1.1 different organisms per sample (range, 0 to 5). Four specimens were sterile, while
bacterial concentrations exceeded the upper limit of detection (2 x 108 CFU/mL) in four cases. Aerobes or facultative aerobes were the predominant isolates; strict
anaerobes were isolated from only four specimens.
Simultaneous gastric (by gastrostomy) and jejunal (by
feeding jejunostomy) cultures were performed in two patients. In both cases, cultures from the two separate sites
yielded similar results: five of six organisms isolated were
present in both sites at a comparable concentration.
Nine patients had two or more specimens taken over a
period of more than 7 days. In 8 of 9 cases, at least 1
organism initially present persisted for more than 1
week, and of 19 organisms initially present in these 9
patients, 10 were present in a subsequent specimen
taken more than 1 week later.

Microbiology of Proximal GI Colonization

No. of patients
Mean age ( SD)
Sex
Male
Female
Admission APACHE II ( SD)
Infection
Primary

ICU-acquired
Median length of stay
MOF score ( SD)
ICU mortality

41

64.5 12.8 yr
21
20
18.4 7.3

18/41 (44%)
33/41 (81%)
23 days (range, 1-219 days)
7.8 4.6

15/41 (36%)

The most common colonizing species are summarized

in Table 2. Candida, the enterococcus, S. epidermidis,
and Pseudomonas were the most frequent isolates.
Patterns of proximal gut colonization were strongly
influenced by the pH of the specimen. Gram-negative
organisms were only cultured when the pH was greater
than 4, while viable Candida could be cultured from
gastric fluid at a pH as low as 1 (Fig. 1).

ICU-Acquired Infection
ICU-acquired infection was a common complication,
developing during more than 80% of ICU admissions.

114

Marshall, Christou, and Meakins

Ann. Surg. - August 1993

Peritonitis
12

Empyema
2

Bacteremia
19

...

Log10
No. of
Patients Colonized (CFU/mL SD)

Organism
Candida
Streptococcus faecalis
Pseudomonas
Staphylococcus epidermidis
Non group D Streptococci
Escherichia coli
Enterobacter
Serratia
Klebsiella
Staphylococcus aureus
Citrobacter
Bacteroides

4.3 1.6
6.8 0.8
6.9 1.1
5.7 1.6
6.9 1.2
6.2 1.6
6.7 1.4
6.5 0.8
5.6 1.7
5.6 2.0
6.2 1.1
7.0 0.9

19
12
10
10
7
7
5
5
5
5
4
3

The sites of these infections are summarized in Figure 2

and their microbiology is presented in Table 3. Most
patients had infection at more than one site, often with
more than one organism at a given site monitored over
time; recurrent infection at a given site was common.
The data on the prevalence of infections, therefore, reflect the development of at least one episode ofinfection
at that site, while the microbiologic data indicate the isolation of the particular organism from at least one site
during the ICU stay.

Correlation of Proximal GI Colonization

with ICU-Acquired Infection
The most common isolates from the upper GI tract of
the study population closely paralleled the most prevaMean pH
9

7.1
0

4.7

7.0

6.1

*000

0*

000*
*0

7
6
pH 5

Pneumonia
22

x.'..'-...'.'~............
......Wound
17

Urinary Tract
22
Figure 2. Sites of ICU-acquired infection in the 34 patients who had at
least one episode of ICU-acquired infection. Numbers refer to the number
of patients having at least one episode of infection at the site indicated.

lent isolates in cases of ICU-acquired infection. Of the 33

patients with ICU-acquired infection, all but 3 had at
least 1 episode of infection with 1 or more organisms
present in the proximal GI tract. Because serial cultures
were not performed in a systematic fashion, it is not possible to determine the temporal relationship of colonization to infection; colonization preceded, coincided with,
and followed infection in approximately similar percentages of cases.
Patients whose upper GI tract was colonized with
Candida, Pseudomonas, or S. epidermidis were significantly more likely to have one or more episodes of invasive infection with that organism over the course of the
ICU stay than patients who were not colonized. The association was strongest for patients colonized with Pseudomonas (9 of 10 colonized patients had one or more episodes of Pseudomonas infection compared with 6 of 31
patients not colonized, p = 0.0003), but it was also evident for S. epidermidis (8 of 10 infections in colonized
patients vs. 10 of 31 in patients not colonized, p = 0.02)
and Candida (15 of 19 infections in colonized patients
vs. 9 of 22 in patients not colonized, p = 0.03, Yates'

0
.

*0

pm>

;.

l
.

Organism

-I

Candida
Figure 1. The pH of upper GI fluid specimens that yielded Pseudomonas
was consistently above 4.0, while Candida could be grown from specimens with a pH as low as 1. Mean pH values of specimens growing
Candida are significantly lower than those growing Pseudomonas (p <
Pseudomonas

0.001).

-148 U
.

S. epidermidis

Enterococcus

Candida
Streptococcus faecalis
Staphylococcus epidermidis
Pseudomonas
Escherichia coli

Staphylococcus aureus
Enterobacter
Klebsiella, Serratia

ej Se

. ........................~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
=
...........

No. of Patients
24
22
20
16
15
12
10
7 each

Upper Gl Flora and ICU-Acquired Infection

Vol. 218 -No. 2

verticular bleed. Gastric cultures performed within the

first 24 hours of ICU admission grew Pseudomonas aeruginosa. Pseudomonas pneumonia and bacteremia were
diagnosed 6 days later; she died 2 days later.

No. of Patients with Invasive

Infection with Same Organism*

Wound Infection

Organism

GI Colonization

No GI
Colonization

Pt

Pseudomonas
Staphylococcus
epidermidis
Candida
Streptococcus faecalis

9/10 (90%)

4/31 (13%)

<0.0001

8/10 (80%)
11/19 (58%)
7/12 (58%)

2/31 (6%)
8/22 (36%)
8/29 (28%)

<0.0001
NS
NS

Indicates the number of patients experencing invasive systemic infection within 1

week of the time of positive GI culture whose upper GI tract was colonized (GI
colonization) or was not colonized (no GI colonization) with the organism in question.
t Chi square test with Yates' continuity correction.
*

corrected chi square). No such correlation between gut

colonization and infection was found for the other common causes of proximal GI colonization-S. faecalis
and Escherichia coli.
Prolonged ICU stays were the rule for many of the
patients studied; therefore, we also analyzed the correlation of upper GI colonization with the development of
invasive infection during a period of 1 week before and
up to 1 week after the GI culture was performed. When
this was done, the association between gut colonization
and coincident invasive infection was even stronger for
Pseudomonas and S. epidermidis, but not for Candida
or S. faecalis (Table 4).

Site-Specific Infections with Upper GI

Organisms
As summarized in Table 5, of those patients having
ICU-acquired infections, colonization of the proximal
GI tract with at least one of the responsible organisms
was common, occurring in from 50% of patients with
urinary tract infections to 92% of patients with tertiary
peritonitis. Representative clinical vignettes illustrate
typical cases.
Pneumonia
One or more episodes of ICU-acquired pneumonia
with an organism isolated from the proximal GI tract
occurred in 16 patients; the mortality rate was 50%. The
microbiology of these infections included the spectrum
of organisms classically associated with ICU-acquired
pneumonia-Pseudomonas (6 patients), Serratia (3 patients), Enterobacter (3 patients), and Staphylococcus
aureus (3 patients).
A 69-year-old woman with chronic lung disease underwent an emergency sigmoid resection for a significant di-

Twelve patients had wound infections with an organism present in the upper GI tract; 7 patients ultimately
died. The infecting organisms included Candida (five patients), S. epidermidis (four patients), Pseudomonas
(four patients), S. faecalis (four patients), and Serratia
(two patients).
Urinary Tract Infection
Eleven patients had

one or more

episodes of urinary

tract infection with an organism that was also present in

the upper GI tract. Candida was the most common isolate, present in nine patients, while Pseudomonas was
the infecting organism in two patients; E. coli and S.
faecalis were responsible for urinary tract infections in
one

patient each.

A 39-year-old woman sustained a cervical spine fracture

and small bowel and colonic perforations in a motor vehicle accident. Gastric cultures taken 4 days after ICU admission grew Candida. Urine cultures were persistently
positive for Candida, although the organism was grown at
no other site.

Recurrent (Tertiary) Peritonitis

Recurrent or tertiary peritonitis (defined as the persistence or recurrence of culture-positive intraperitoneal

infection at least 72 hours after apparently adequate therapy for an episode of primary or secondary peritonitis)
occurred in 11 patients, 8 of whom died. Four of these
patients had direct communication between the upper
GI tract and the peritoneal cavity as a result of either a
perforation (two patients) or an anastomotic leak (two
patients); in the remaining seven, the upper GI tract was
anatomically intact. The infecting species were S. faecalis (five patients), Pseudomonas (five patients), S. epidermidis (four patients), and Candida (two patients).

..

Site
Pneumonia
Wound
Urinary tract
Tertiary peritonitis
Bacteremia

Empyema

:: :: ..:.
::..

~~~~~~~~~
~~~~

~_....

No. of Patients
Infected

No. of Colonized Patients

22
17
22
12
19
2

16 (73%)
12 (71%)
11 (50%)

Experiencing Infection

11 (92%)

10 (53%)
1 (50%)

116

Marshall, Christou, and Meakins

Ann. Surg. * August 1993

A 69-year-old man underwent surgical exploration for

infected pancreatic necrosis; cultures grew Candida. He
was managed with repeat laparostomies using a mesh and
zipper approach. S. epidermnidis was isolated from both
the stomach and necrotic peripancreatic tissue 1 week
after his initial procedure.

Bacteremia
Bacteremia or fungemia, the sine quia non of invasive
infection, occurred with an organism from the upper GI
tract in ten patients (Table 5). Pseudornonas was isolated
in four patients, Candida in three, and S. epidermnidis, E.
coli, and S. facca/is in one.
A 30-year-old man sustained multiple injuries including a pelvic fracture in a fall. Gastric cultures performed 3
The same
days later yielded a heavy growth of S.
organism was isolated from the blood 4 days later, and at
the same time in insignificant numbers in the urine.

'/iwcalis.

An additional patient had a primary infection in association with proximal GI colonization:

A 54-year-old woman on home total parenteral nutrition (TPN) was admitted in septic shock. Blood cultures

grew Klebsiellai pneumoniae; the same organism was

grown from her proximal jejunostomy effluent at a concentration of 105 CFU/mL.

14-1
120

10-

Co

8-

T T T T
*

IL

6-

4.
2-

S. epidermidis

Candida

Pseudomonas

S. fecalis

Others

Colonizing Microorganism
Figure 3. Organ failure (MOF) scores for patients colonized with Candida (19 patients), Pseudomonas (10 patients), S. epidermidis (10 patients), or S. faecalis (12 patients) were significantly higher than the scores
for the 7 patients who were not colonized with any of these 4 organisms (p
0.02, one-way analysis of variance). MOF scores were calculated as
previously described.9 Results are mean SD.

seven patients in whom none of these organisms was

isolated from upper GI fluid had significantly lower
MOF scores (p = 0.02. one-way analysis of variance).

Empyema

Of two patients in whom empyemas were diagnosed

during the ICU stay, one patient had the same organism
isolated from the upper GI tract:
A 35-year-old woman sustained traumatic hemiplegia
in a fall from a height and underwent surgical stabilization
of the spine by an anterior approach. Jejunal cultures ob-

tained 13 days after injury grew S. epidermidis: S. epidermidIs and S. tiecalis were cultured from the chest tube
drainage 3 days later.

Correlation of Proximal GI Colonization

with ICU Mortality
ICU mortality rates for patients having GI colonization with Pseuidoinonas were significantly elevated over
those of patients who did not have colonization (70% vs.
26(7X, p = 0.03, Yates' corrected chi square). ICU mortality rates were also elevated for patients colonized with S.
eIidcrlfelidis (60%) or the enterococcus (58%); however,
the differences did not attain statistical significance.

Correlation of Proximal GI Colonization

with MOF Scores
GI colonization with Candida, iyeudoinonas, or S.
epidc1rinidis was associated with the greatest degree of
organ dysfunction, while MOF scores for patients colonized with S. /Ieccalis were marginally lower (Fig. 3). The

DISCUSSION
In health, the stomach and proximal GI tract are sterile, or sparsely populated with a relatively avirulent flora
including Lactobaci/li and Strepto()co((i.21'22 As this and
previous studiesi4-7 demonstrate, critical illness is associated with significant proximal gut overgrowth with typical ICU pathogens. Both descriptive and interventional
studies suggest that this pathologic colonization contributes significantly to the development of ICU-acquired
infection.
In the current study, more than 90% of the 33 patients
with ICU-acquired infection had at least one episode of
infection with an organism that was simultaneously present in the upper GI tract. Moreover, colonization with
either Pseuidomonas or S. epidermnidis was strongly associated with concomitant infection, while colonization
with C'andida was significantly associated with invasive
fungal infection at some time during the ICU admission.
A purely descriptive study such as this cannot establish causality. It can be argued that gut colonization is a
consequence of infection and a manifestation of microbial dissemination from the initial focus of infection;
however, this interpretation appears less tenable. Despite
the fact that GI cultures were performed at disparate and
arbitrary timepoints while diagnostic cultures were performed regularly on the basis of clinical evidence of infection, gut colonization equally preceded, coincided
with, and followed the development of invasive infec-

Vol. 218 No. 2

-

tion. ICU-acquired infections rarely showed evidence of

widespread dissemination with multiple positive sites
and bacteremia; indeed, bacteremias most commonly
appeared to arise as a result of contaminated intravascular catheters. The interpretation that gut colonization
sets the stage for the development of invasive infection is
supported by published reports demonstrating a reduction in rates of ICU-acquired infection as a result of selective decontamination of the digestive tract'6'23'24 or
the use of cytoprotective agents for stress ulcer prophylaxis,25'26 although the efficacy of both of these strategies
has been questioned.27'28
The relative sterility of the upper GI tract is maintained through the interaction of a number of influences,
including gastric acidity,29 normal intestinal motility,30
and, to a lesser extent, bile salts,3' IgA,32 and defensins
from Paneth cells.33 Enteral feeding is a potent stimulus
to the activation of normal proximal gut antimicrobial
defenses, stimulating gastric acid release, bile flow, and
small intestinal motility; cholecystokinin and secretin
release, in turn, augment IgA production by the small
bowel mucosa.34 Critical illness is associated with profound disruption of these normal defenses. Acid-reducing measures to reduce the risk of stress ulceration result
in gastric gram-negative overgrowth,'4'15"17'25 a phenomenon clearly evident in the current study. Few of the patients in this report were fed enterally because of co-existing ileus; randomized trials have clearly demonstrated
a reduction in rates of nosocomial infection when enteral nutrition is instituted early.7
The indigenous GI flora exerts an important influence
in rendering the gut resistant to colonization with exogenous pathogens; this phenomenon, attributable to the
anerobic flora, has been termed "colonization resistance."35 Disruption of the normal flora by antibiotics
can reduce colonization resistance, and in experimental
models has been shown to promote pathologic colonization by two of the most common isolates seen in this
study-Candida36 and Pseudomonas.37 Whether antibiotic use affected patterns of colonization in the patients
reported here is impossible to determine because all but
5 of the 41 patients had received broad spectrum antibiotics before the performance of the quantitative GI cultures.

Subclinical aspiration of contaminated gastric secretions causing nosocomial ICU-acquired pneumonia is a

well-documented phenomenon,'4'25 believed by many to
be the most important cause of pneumonia in the ICU.38
Pneumonia with an organism simultaneously cultured
from the upper GI tract was documented in 39% of the
patients in this study, the infecting species being the
common isolates in cases of ICU-acquired pneumonia.38
All of our patients had indwelling access to the upper GI
tract, usually in the form of a nasogastric tube; subclinical aspiration in conjunction with nasogastric tubes has

Upper GI Flora and ICU-Acquired Infection

been shown to be a risk factor for the development of

ICU-acquired pneumonia.39
In addition to the 16 documented cases of pneumonia,
however, we also observed remote invasive infection
with organisms colonizing the upper GI tract. Concomitant colonization of an infected wound and the upper GI
tract in our 12 cases may simply reflect a process of generalized epithelial colonization, unrelated to the development of systemic infection. Some of the cases of tertiary
peritonitis may have been secondary to bacterial passage
through anatomic defects in the gut, although only 4 of
the 11 patients with this complication had a macroscopic
communication between the gut lumen and the peritoneal cavity. The organisms isolated from these cases-coagulase-negative Staphylococci, Candida, Pseudomonas,
and the enterococcus-are the organisms typically seen
in recurrent or tertiary peritonitis.40 There were 11 cases
each of urinary tract infection and bacteremia (1 primary) with organisms simultaneously present in the gut,
suggesting that bacterial translocation may be a factor of
importance in the pathogenesis of ICU-acquired infection. The most common causes of gut colonization in
this study-Candida,4' Pseudomonas,42 S. epidermidis,
and the enterococcus43-have all been shown in animal
models to be capable of translocation across an anatomically intact GI tract. Moreover, factors known to promote translocation, including trauma, endotoxemia, parenteral feeding, cholestasis, and use of broad spectrum
antibiotics, are commonly present in the critically ill surgical patient."
It has been suggested that ICU-acquired infection is a
manifestation of organ system dysfunction rather than
its cause,9'45 and studies of attributable mortality of nosocomial infection support this interpretation.46'47 Thus,
the more pronounced degrees of organ dysfunction seen
in patients colonized with Candida, Pseudomonas, or S.
epidermidis may reflect the fact that these organisms
more readily colonize the sickest patients. Gram-negative and fungal intestinal overgrowth alone has been
shown in animal models to induce changes in intermediary metabolism48 and systemic immune responsiveness49'50 characteristic of those developing in the critically ill patient, and it is possible that the adverse sequelae of gut colonization are less related to the
development of invasive infection than to noninfectious
influences on systemic homeostasis.
Whether the relationship between gut colonization
and systemic infection reflects cause and effect or simply
association, it is apparent that the microbial milieu of the
critically ill patient is well-reflected in the patterns of gut
colonization that evolve during the ICU stay. Moreover,
whether ICU-acquired infection is a cause or a manifestation of morbidity, the strong correlation between
pathologic proximal gut colonization, ICU-acquired infection, and the evolution of the clinical syndrome of

118

Marshall, Christou, and Meakins

Ann. Surg. * August 1993

MOF justifies the conceptual characterization of the GI

tract as the "undrained abscess" of MOF. The clinical
challenge, and the proof or refutation of the gut hypothesis, lies in finding an effective method of drainage.

17.

18.

Acknowledgments
The authors thank Dr. Ruth Horn for supervising the microbial cultures and specimen identification, Ms. Betty Giannias for performing
the quantitative bacterial cultures, Lise Laporte, RN, and Mary de
Santis, RN, for collecting clinical data, and Ms. Elaine Caon for assisting with the preparation of the manuscript.

20.
21.
22.

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1. Daschner FD, Frey P, Wolff G, et al. Nosocomial infections in
intensive care wards: a multicenter prospective study. Intensive
Care Med 1982; 8:5-9.
2. Chandrasekar PH, Kruse JA, Mathews MF. Nosocomial infection
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