(Chest. 2000;117:855-869.)
© 2000
American College of Chest Physicians
Fever in the ICU*
Paul E. Marik, MD, FCCP
*
From the Department of Internal Medicine, Section of Critical Care, Washington Hospital Center, Washington, DC.
Correspondence to: Paul E. Marik, MD, Department of Internal Medicine, Washington Hospital Center, 110 Irving St NW, Washington, DC 20010-2975; e-mail: pem4{at}mhg.edu
 |
Abstract
|
|---|
Fever is a common problem in ICU patients. The presence of fever
frequently results in the performance of diagnostic tests and
procedures that significantly increase medical costs and expose the
patient to unnecessary invasive diagnostic procedures and the
inappropriate use of antibiotics. ICU patients frequently have multiple
infectious and noninfectious causes of fever, necessitating a
systematic and comprehensive diagnostic approach. Pneumonia, sinusitis,
and blood stream infection are the most common infectious causes of
fever. The urinary tract is unimportant in most ICU patients as a
primary source of infection. Fever is a basic evolutionary response to
infection, is an important host defense mechanism and, in the majority
of patients, does not require treatment in itself. This article reviews
the common infectious and noninfectious causes of fever in ICU patients
and outlines a rational approach to the management of this
problem.
Key Words: cytokines • fever • ICU • sinusitis • urinary tract infection • ventilator-associated pneumonia
|
Introduction
|
|---|
Fever
is a common problem in ICU patients. The presence of fever frequently
results in the performance of diagnostic tests and procedures that
significantly increase medical costs and expose the patient to
unnecessary invasive diagnostic procedures and the inappropriate use of
antibiotics. The main diagnostic dilemma is to exclude noninfectious
causes of fever and then to determine the site and likely pathogens of those with infections. ICU patients frequently
have multiple infectious and noninfectious causes of
fever,1
necessitating a systematic and comprehensive
diagnostic approach. This article reviews the common infectious and
noninfectious causes of fever in ICU patients and outlines a rational
approach to the management of these patients.
|
Pathogenesis of Fever
|
|---|
Cytokines released by monocytic cells play a central role in the
genesis of fever. The cytokines primarily involved in the development
of fever include interleukin (IL) 1, IL-6, and tumor necrosis factor
(TNF)-
.2
3
4
5
6
7
8
9
10
11
12
13
The interaction between these cytokines is
complex, with each being able to up-regulate and down-regulate their
own expression as well as that of the other cytokines. These cytokines
bind to their own specific receptors located in close proximity to the
preoptic region of the anterior hypothalamus.2
3
Here, the
cytokine receptor interaction activates phospholipase
A2, resulting in the liberation of plasma
membrane arachidonic acid as substrate for the cyclo-oxygenase pathway.
Some cytokines appear to increase cyclo-oxygenase expression directly,
leading to liberation of prostaglandin E2. This
small lipid mediator diffuses across the blood brain barrier, where it
acts to decrease the rate of firing of preoptic warm-sensitive neurons,
leading to activation of responses designed to decrease heat loss and
increase heat production.2
14
In a small proportion of
hospitalized patients, hyperthermia may result from increased
sympathetic activity with increased heat production.
|
Significance of Fever
|
|---|
Fever appears to be a preserved evolutionary response
within the animal kingdom.15
16
17
18
19
20
With few exceptions,
reptiles, amphibians, and fish, as well as several invertebrate
species, have been shown to manifest fever in response to challenge
with microorganism.15
16
17
18
19
Increased body temperature has
been shown to enhance the resistance of animals to
infection.21
22
Although fever has some harmful effects,
fever appears to be an adaptive response that has evolved to help rid
the host of invading pathogens. Temperature elevation has been shown to
enhance several parameters of immune function, including antibody
production, T-cell activation, production of cytokines, and enhanced
neutrophil and macrophage function.23
24
25
26
Furthermore,
some pathogens such as Streptococcus pneumoniae are
inhibited by febrile temperatures.27
It has long been known that increasing body temperature is
associated with improved outcome from infectious diseases. The
preantibiotic era provides abundant, although uncontrolled data, on the
deliberate use of elevated body temperature to treat infections. The
beneficial effects of hot baths and malarial fevers in syphilis were
noted as early as the 15th century.28
In mammalian models,
increasing body temperature results in enhanced resistance to
infection.29
30
31
32
In a retrospective analysis of 218
patients with Gram-negative bacteremia, Bryant and
colleagues33
reported a positive correlation between
maximum temperature on the day of bacteremia and survival. Similarly,
Weinstein and colleagues34
reported that a temperature
> 38°C increased survival in patients with spontaneous bacterial
peritonitis. Dorn and colleagues35
reported that children
with chickenpox who were treated with acetaminophen had a longer time
to crusting of lesions than when treated with placebo.
An elevated body temperature may, however, also be associated
with a number of deleterious effects, most notably an increase in
cardiac output, oxygen consumption, carbon dioxide production, and
energy expenditure.36
Oxygen consumption increases by
approximately 10% per degree Celsius.36
These changes may
be poorly tolerated in patients with limited cardiorespiratory reserve.
In patients who have suffered a cerebrovascular accident or traumatic
head injury, moderate elevations of brain temperature may markedly
worsen the resulting injury.37
Maternal fever has been
suggested to be a cause of fetal malformations or spontaneous
abortions.38
39
However, this association has not been
rigorously tested.
|
Definitions and Measurement of Fever
|
|---|
Accurate and reproducible measurement of body temperature is
important in detecting disease and in monitoring patients with an
elevated temperature. A variety of methods are used to measure body
temperature, combining different sites, instruments, and techniques.
The mixed venous blood in the pulmonary artery is considered the
optimal site for core temperature measurement; however, this method
requires placement of a pulmonary artery catheter.40
41
42
Infrared ear thermometry has been demonstrated to provide values that
are a few tenths of a degree below temperatures in the pulmonary artery
and brain.43
44
45
46
Rectal temperatures obtained with a
mercury thermometer or electronic probe are often a few tenths of a
degree higher than core temperature.40
41
42
Rectal
temperatures are perceived by patients as unpleasant and intrusive.
Furthermore, access to the rectum may be limited by patient position,
with an associated risk of rectal trauma. Oral measurements are
influenced by events such as eating and drinking and the presence of
respiratory devices delivering warmed gases.43
Axillary
measurements substantially underestimate core temperature and lack
reproducibility.43
Body temperature is therefore most
accurately measured by an intravascular thermistor, but measurement by
infrared ear thermometry or with an electronic probe in the rectum is
an acceptable alternative.47
Normal body temperature is
generally considered to be 37.0°C (98.6°F) with a circadian
variation of between 0.5 to 1.0°C.2
14
The definition of
fever is arbitrary and depends on the purpose for which it is defined.
The Society of Critical Care Medicine practice parameters define fever
in the ICU as a temperature > 38.3°C (
101°F).47
Unless the patient has other features of an infectious process, only a
temperature > 38.3°C ( 101°F) warrants further investigation.
|
Fever Patterns
|
|---|
Attempts to derive reliable and consistent clues from evaluation
of a patient’s fever pattern is fraught with uncertainly and not
likely to be helpful diagnostically.2
14
48
Most patients
have remittent or intermittent fever that, when due to infection,
usually follow a diurnal variation.48
Sustained fevers
have been reported in patients with Gram-negative pneumonia or CNS
damage.48
The appearance of fever at different time points
in the course of a patient’s illness may however provide some
diagnostic clues. Fevers that arise > 48 h after institution of
mechanical ventilation may be secondary to a developing
pneumonia.49
50
Fevers that arise 5 to 7 days
postoperatively may be related to abscess formation.51
Fevers that arise 10 to 14 days postinstitution antibiotics for
intra-abdominal abscess may be due to fungal
infections.52
53
54
|
Causes of Fever in the ICU
|
|---|
As outlined above, any disease process that results in the release
of the proinflammatory cytokines IL-1, IL-6, and TNF- will result in
the development of fever. While infections are the commonest cause of
fever in ICU patients, many noninfectious inflammatory conditions cause
the release of the proinflammatory cytokines with a febrile
response.55
56
57
58
59
60
61
Similarly, it is important to appreciate
that not all patients with infections are febrile. Approximately 10%
of septic patients are hypothermic and 35% are normothermic at
presentation. Septic patients who fail to develop a temperature have a
significantly higher mortality than febrile septic
patients.62
63
64
The reason that patients with established
infections fail to develop a febrile response is unclear; however,
preliminary evidence suggests that this aberrant response is not due to
diminished cytokine production.65
The presence of fever in an ICU patient frequently triggers a battery
of diagnostic tests that are costly, expose the patient to unnecessary
risks, and often produce misleading or inconclusive results. It is
therefore important that fever in ICU patient be evaluated in a
systematic, prudent, clinically appropriate, and cost-effective manner.
|
Noninfectious Causes of Fever in the ICU
|
|---|
A large number of noninfectious disorders result in tissue injury
with inflammation and a febrile reaction. Those noninfectious disorders
that should be considered in ICU patients are listed in Table 1
.1
55
66
67
68
For reasons that are not entirely clear, most
noninfectious disorders usually do not lead to a fever > 38.9°C
(102°F); therefore, if the temperature increases above this
threshold, the patient should be considered to have an infectious
etiology as the cause of the fever.67
However, patients
with drug fever may have a temperature > 102°F.69
70
71
Similarly, fever secondary to blood transfusion may be
> 102°F.72
73
Most of those clinical conditions listed in Table 1
are clinically
obvious and do not require additional diagnostic tests to confirm their
presence. However, a few of these disorders require special
consideration. Although drug-induced fever is commonly cited as a cause
of fever,74
< 300 cases of this condition have been
reported in the literature.70
Furthermore, only a single
case of drug fever has been reported in an ICU patient
population.1
However, on the basis of the number of
medications administered to patients in the ICU, one would expect drug
fever to be a relatively common event. Although the true incidence of
this disorder is unknown, drug fever should be considered in patients
with an otherwise unexplained fever, particularly if they are receiving
ß-lactam antibiotics, procainamide, or
diphenylhydantoin.70
Drug fever is usually characterized
by high spiking temperatures and shaking chills.70
It may
be associated with a with leukocytosis and eosinophilia. Relative
bradycardia, although commonly cited, is uncommon.67
70
74
Atelectasis is commonly implicated as a cause of fever. Standard ICU
texts list atelectasis as a cause of fever, although they provide no
primary source.51
75
Indeed a major surgery text states
that "fever is almost always present [in patients with
atelectasis]."51
However, Engeron76
studied 100 postoperative cardiac surgery patients and was unable to
demonstrate a relationship between atelectasis and fever. Furthermore,
when atelectasis is induced in experimental animals by ligation of a
mainstem bronchus, fever does not occur.77
78
However,
Kisala and coworkers79
demonstrated that IL-1 and TNF-
levels of macrophage cultures from atelectatic lungs were significantly
increased compared with the control lungs. The role of atelectasis as a
cause of fever is unclear; however, atelectasis probably does not cause
fever in the absence of pulmonary infection.
Febrile reactions complicate about 0.5% of blood transfusions, but may
be more common following platelet transfusion.72
80
81
Antibodies against membrane antigens of transfused leukocytes and/or
platelets are responsible for most febrile reactions to cellular blood
components.72
Febrile reactions usually begin within 30
min to 2 h after a blood-product transfusion is begun. The fever
generally lasts between 2 h and 24 h and may be preceded by
chills.73
An acute leucocytosis lasting up to 12 h
commonly occurs following a blood transfusion.82
Patients with the ARDS may progress to a "chronic" stage
characterized by pulmonary fibroproliferation and fevers. Meduri and
coworkers1
83
have demonstrated that fever and
leukocytosis may result from the inflammatory-fibrotic process present
in the airspace of patients with late ARDS in the absence of pulmonary
infection. Corticosteroids appear to be associated with an improvement
in lung injury and reduced mortality.83
84
Some authors
recommend an open lung biopsy prior to commencing corticosteroid
therapy, in order to obtain histologic evidence of the
fibroproliferative phase of ARDS and to exclude infection.
Acalculous cholecystis occurs in approximately 1.5% of critically ill
patients.85
86
While relatively uncommon, acalculous
cholecystitis is an important "noninfectious" cause of fever in
critically ill patients, as it is frequently unrecognized and therefore
potentially life threatening.85
86
The pathophysiology of
acalculous cholecystitis is related to the complex interplay of a
number of pathogenetic mechanisms, including gallbladder ischemia, bile
stasis with inpissation in the absence of stimuli for emptying of the
gallbladder, positive-end expiratory pressure, and parenteral
nutrition.87
88
89
90
91
92
Bacterial invasion of the gallbladder
appears to be a secondary phenomenon.89
The diagnosis of acalculous cholecystitis is often exceedingly
difficult and requires a high index of suspicion. Pain in the right
upper quadrant is the finding that most often leads the clinician to
the correct diagnosis, but it may frequently be
absent.85
86
89
Nausea, vomiting, and fever are other
associated clinical features. The clinical findings and laboratory
workup in patients with acalculous cholecystitis are, however, often
nonspecific. The most difficult patients are those recovering from
abdominal sepsis who deteriorate again, misleadingly suggesting a
flare-up of the original infection. Rapid diagnosis is essential
because ischemia may progress rapidly to gangrene and perforation, with
attendant increase in the already high morbidity and
mortality.89
The diagnosis should therefore be considered
in every critically ill patient who has clinical findings of sepsis
with no obvious source.
Radiologic investigations are required for a presumptive diagnosis of
acalculous cholecystitis. Ultrasound is the most common radiologic
investigation used in the diagnosis of acalculous cholecystitis;
features include increased wall thickness, intramural lucencies,
gallbladder distension, pericholecystic fluid, and intramural
sludge.93
94
Wall thickness 3 mm is reported to be the
most important diagnostic feature on ultrasound examination, with a
specificity of 90% and a sensitivity of 100%.93
94
In
ICU patients, hepatobiliary scintigraphy has a high false-positive rate
(> 50%), limiting the value of this test.95
However, a
normal scan virtually excluded acalculous cholecystitis. CT scanning
has been reported to have a high sensitivity and specificity; however,
no prospective studies have been performed comparing ultrasonography
with CT scanning in the diagnosis of acalculous
cholecystitis.96
The management of acalculous cholecystitis is somewhat
controversial.85
89
97
However, with the development of
more advanced radiologic imaging techniques, percutaneous
cholecystostomy may be the procedure of choice. Kiviniemi and
coworker98
demonstrated diminution of pain in 94% of
patients, with normalization of fever in 90% and leukocyte count in
84% of patients treated by percutaneous cholecystostomy. The procedure
is associated with few complications and is the definitive therapy in
most patients.99
Open cholecystectomy is, however,
recommended should the abdominal signs, fever, and leucocytosis not
improve within 48 h of percutaneous
cholecystostomy.85
89
97
While fever may occur in patients with deep venous thrombosis, in
patients suspected of deep venous thrombosis, the predictive value of
fever is poor.100
Furthermore, in critically ill ICU
patients, fever without other features of ileofemoral thrombosis is
uncommon and does not warrant routine venography as part of the initial
diagnostic workup of pyrexia in ICU patients.1
101
|
Infectious Causes of Fever
|
|---|
The prevalence of nosocomial infection in ICUs has been reported
to vary from 3 to 31%.102
103
104
105
106
107
108
Data from the National
Nosocomial Infection Surveillance system database from 1986 to 1990
documented nosocomial infection in 10% of the 164,034 patients, with a
strong correlation between ICU length of stay and the development of
infection.103
In a point prevalence study conducted in
1992, The EPIC Study Investigators104
reported on the
prevalence of nosocomial infections in 10,038 patients hospitalized in
1,417 European ICUs. In this study, 20.6% of patients had an
ICU-acquired infection, with pneumonia being the most common (46.9%),
followed by urinary tract infection (17.6%) and blood stream infection
(12%). This data must, however, be interpreted with some caution. The
presence and type of infection in these studies was documented
according to the "standard definitions" of the Centers for Disease
Control and Prevention (CDC).109
110
The definitions of
nosocomial infection published by the CDC may, however, not be
applicable to ICU patients.109
110
For example, according
to the most recent definitions published in 1988, the presence of rales
and purulent sputum or the presence of new chest radiographic findings
and change in sputum character were used to diagnose
pneumonia.110
In patients receiving mechanical
ventilation, less than a third of patients with these features would be
considered to have pneumonia using invasive diagnostic
methods.111
112
113
114
Similarly, fever and a urine culture of
105 colony-forming units (CFU)/mL was
considered diagnostic of urinary tract infection. As is discussed
below, the presence of these two finding in catheterized critically ill
ICU patients does not represent infection of the urinary tract.
The most common infections reported in ICU patients are
pneumonia, followed by sinusitis, blood stream infection, and
catheter-related infection.1
102
103
104
105
106
107
108
Table 2
lists the most important sites of infection in ICU patients. As is
discussed below, urinary tract infection is probably unimportant in
most ICU patients.
|
Ventilator-Associated Pneumonia
|
|---|
Ventilator-associated pneumonia (VAP) occurs in approximately 25%
of patients undergoing mechanical ventilation.49
115
116
117
118
The impact of VAP on patient outcome has been much
debated117
119
120
; however, Fagon and
colleagues121
reported an attributable mortality of 27%.
The optimal management of patients with suspected VAP requires
confirmation of the diagnosis and identification of the responsible
pathogen(s) in order to provide appropriate antimicrobial therapy. The
diagnosis of VAP remains one of the most difficult clinical dilemmas in
critically ill patients receiving mechanical
ventilation.49
Clinical criteria alone have been shown to
be unreliable in the diagnosis of this
condition.113
115
122
A number of invasive and minimally
invasive techniques have been reported to aid in the diagnosis of VAP.
The number of methods currently available attest to the fact that no
single method is ideal.49
112
120
123
124
125
126
127
128
129
130
131
132
The
optimal technique(s) for diagnosis of VAP remains unclear as a
uniformly agreed on "gold standard," for the diagnosis is
lacking.111
118
124
133
134
135
The impact that diagnostic
tests for VAP have on patient outcome is controversial. Using a
decision analysis method, Sterling and coauthors136
demonstrated that invasive or semi-invasive microbiological diagnostic
techniques improved the outcome of patients with suspected VAP.
However, Luna and colleagues137
and Rello and
coworkers138
have demonstrated that the most important
factor affecting outcome in patients with VAP is the early initiation
of appropriate antibiotic therapy. In the study by Luna et
al,137
the mortality of patients who were changed from
inadequate antibiotic therapy to appropriate therapy based on the
results of the BAL was comparable to the mortality of those patients
who continued to receive inadequate therapy. Kollef and
Ward,139
using noninvasive mini-BAL to diagnose VAP,
confirmed these findings. It should however be noted that patients who
have clinical features of VAP and in whom VAP is "excluded" based
on quantitative culture of lower respiratory tract secretions and in
whom antibiotics are stopped have a significantly lower mortality than
those patient who are culture positive.121
139
Invasive or
noninvasive sampling of lower respiratory tract sections with
quantitative culture therefore allows for the safe discontinuation of
antibiotics in the "culture negative"
patients.123
125
140
141
142
143
144
145
Furthermore, as the initial
empiric antibiotic regimen must be broad and cover both Gram-positive
and negative organisms, these techniques allow for narrowing of the
spectrum once a pathogen has been isolated in those patients with
confirmed pneumonia. This approach to suspected VAP will result
in significant cost savings and reduce the selection of resistant
organisms.113
|
Sinusitis
|
|---|
Because paranasal sinusitis is usually clinically silent in
intubated patients, it is not widely appreciated that nosocomial
sinusitis is an important source of infection and fever in critically
ill patients. Furthermore, many ear, nose, and throat surgeons
are of the belief that paranasal sinusitis in intubated patients
receiving mechanical ventilation does not cause fever or systemic signs
of infection. Nosocomial sinusitis is particularly common following
nasal intubation, with an incidence of up to 85% after a week of
intubation.146
147
148
149
150
151
The incidence of nosocomial sinusitis
appears to be lower in patients in whom both the endotracheal and
gastric tubes are placed orally.146
147
148
149
150
151
The diagnosis of
sinusitis requires a CT scan and cannot be accurately assessed using
standard radiography or echography.152
Sinusitis is
diagnosed by total opacification or the presence of an air fluid level
within any of the paranasal sinuses. The maxillary sinus is most
commonly involved; however, most patients with radiologic maxillary
sinusitis have abnormalities of the ethmoid and sphenoid
sinuses.148
Since radiologic abnormalities of the
paranasal sinuses do not necessarily imply infection, diagnosis of
infectious maxillary sinusitis requires transnasal puncture following
appropriate disinfection of the nares.146
148
150
153
When
the ethmoid or sphenoid sinuses only are involved, bacteriologic
specimens can be obtained by an open
ethmoidectomy/sphenoidotomy.146
Sinus infection is
diagnosed by the presence of pus associated with high quantitative
cultures of implicated pathogens. Rouby and colleagues148
reported that only 38% of patients with radiologic maxillary sinusitis
had true infectious sinusitis. In the series reported by Rouby et
al,148
there was normalization of the core temperature and
WBC count following removal of all nasal tubes, followed by transnasal
puncture and drainage in the patients with infectious maxillary
sinusitis. These authors did not use IV antibiotics. Similarly,
in the series reported by Grindlinger and colleagues146
and by Deutschman and coworkers,147
resolution of
sinusitis was associated with normalization of the temperature and WBC
count. Paranasal sinusitis is best treated by removal of all nasal
tubes together with drainage of the maxillary sinuses. Broad-spectrum
antibiotics are generally recommended.146
147
|
Catheter-Associated Sepsis
|
|---|
Catheter-associated sepsis is defined as blood stream infection
due to an organism that has colonized a vascular catheter.
Approximately 5% of patients with indwelling vascular catheters
(uncoated) will develop blood stream infection (
10
infections/1,000 catheter days).154
155
156
157
158
The incidence of
catheter-associated sepsis increases with the length of time the
catheter is in situ, the number of ports, and increases with
the number of manipulations. Approximately 25% of central venous
catheters become colonized (> 15 CFU), and approximately 20 to 30%
of colonized catheters will result in catheter
sepsis.154
155
156
157
158
Staphylocuccus aureus and
coagulase-negative staphylococci are the most common infecting (and
colonizing) organisms, followed by enterococci, Gram-negative
bacteria, and Candida species.154
155
156
157
158
A number of methods of reducing catheter colonization and blood stream
infection have been studied, including topical antibiotics,
antimicrobial flush solutions, subcutaneous tunneling of catheters, and
silver-impregnated subcutaneous cuffs.156
159
160
161
162
These
studies have generally shown poor or inconsistent results. It has been
suggested that antimicrobial bonding of central venous catheters may be
the most effective method of reducing the rate of catheter colonization
and catheter-related sepsis.163
164
Several types of
antiseptic or antimicrobial coatings have been developed, including
catheters coated with chlorhexidine gluconate and silver sulfadiazine,
as well as with minocycline and rifampin. While a number of studies
have demonstrated the incidence of catheter-related sepsis to be lower
with chlorhexidine/sulfadiazine-coated catheters,165
166
167
not all studies have duplicated these findings.168
169
170
Furthermore, Darouiche and colleagues154
have demonstrated
that central venous catheters impregnated with minocycline and rifampin
are associated with a significantly lower rate of catheter colonization
and blood stream infection than catheters coated with chlorhexidine and
silver sulfadiazine.
Central venous catheterization via the femoral and internal jugular
veins are reported to have a similar infection rates, which are higher
than that for catheters inserted via the subclavian
approach.154
163
165
171
Replacement of a colonized
catheter over a guidewire is associated with rapid recolonization of
the replacement catheter.172
If catheter sepsis is
suspected, the catheter should be changed to a new site, with culture
(quantitative or semiquantitative) of the catheter
tip.154
172
173
174
175
176
In patients with limited venous access or
in patients in whom catheter sepsis is less likely, the catheter can be
changed over a guidewire; however, withdrawal blood cultures and
culture of the catheter tip should be performed and the catheter
removed if the cultures are positive.
|
Urinary Tract Infection
|
|---|
Urinary tract infections (UTIs) have been reported to be common in
ICU patients, where they are reported to account for between 25 to 50%
of all infections.102
103
104
105
106
107
108
However, it is likely that most
of these patients had "asymptomatic bacteriuria" rather than true
infections of the urinary tract. The use of antibiotics in patients
with asymptomatic bacteriuria is based on a single study performed in
the early 1980s that may not be applicable today.177
Platt
and colleagues177
demonstrated that in hospitalized
patients bacteriuria with 105 CFUs of
bacteria per milliliter of urine during bladder catheterization was
associated with a 2.8-fold increase in mortality. Based on this study,
thousands of ICU patients with urinary tract colonization have been
treated with antibiotics.
Most ICU patients require an indwelling urinary catheter for monitoring
fluid balance and renal function. The patients’ colonic flora rapidly
colonizes the urinary tract in these patients.178
Stark
and Maki179
have demonstrated that in catheterized
patients, bacteria in the urinary system rapidly proliferate to exceed
105 CFU/mL over a short period of time.
Bacteriuria, defined as a quantitative culture of
105 CFU/mL, has been reported in up to 30%
of catheterized hospitalized patients.180
The
terms "bacteriuria" and "UTI" are generally although
incorrectly used as synonyms. Indeed, most studies in ICU patients have
used bacteriuria to diagnose a UTI. Bacteriuria implies colonization of
the urinary tract without bacterial invasion and an acute inflammatory
response.181
UTI implies an infection of the urinary
tract.181
Criteria have not been developed for
differentiating asymptomatic colonization of the urinary tract from
symptomatic infection. Furthermore, the presence of white cells in the
urine is not useful for differentiating colonization from infection, as
most catheter-associated bacteriurias have accompanying
pyuria.182
It is therefore unclear how many catheterized
patients with > 105 CFU/mL actually have UTI.
While catheter-associated bacteruria is common in ICU patients, data
for the early 1980s indicates that < 3% of catheter-associated
bacteriuric patients will develop bacteremia caused by organisms in the
urine.183
Therefore, the surveillance for and treatment of
isolated bacteruria in most ICU patients is currently not
recommended.184
Bacteriuria should, however, be treated
following urinary tract manipulation or surgery, in patients with
kidney stones, and in patients with urinary tract obstruction.
|
Clostridia Difficile Colitis
|
|---|
C difficile, the agent that causes pseudomembranous
colitis and antibiotic-associated diarrhea, has become a common
nosocomial pathogen.185
186
187
Approximately 20% of all
hospitalized patients become "infected" with C
difficile, of whom only about a third develop
diarrhea.185
186
187
The majority of hospital inpatients
infected with C difficile are
asymptomatic.188
189
C difficile infection
commonly presents with mild to moderate diarrhea, sometimes
accompanied by lower abdominal cramping. Symptoms usually begin during
or shortly after antibiotic therapy but are occasionally delayed for
several weeks. Severe colitis without pseudomembrane formation may
occur with profuse, debilitating diarrhea, abdominal pain, and
distension. Common systemic manifestations include fever, nausea,
anorexia, and malaise. A neutrophilia and increased numbers of fecal
leukocytes are common.188
189
Pseudomembranous colitis is
the most dramatic manifestation of C difficile infection;
these patients have marked abdominal and systemic signs and symptoms
and may develop a fulminant and life-threatening colitis.
Stool assay for toxins A or B are the main clinical tests used to
diagnose C difficile infection.190
191
192
The
"gold standard" test is the tissue culture cytotoxicity assay. This
test has a high sensitivity (94 to 100%) and specificity (99%). The
major disadvantages of this test are its high expense and the time
needed to complete the assay (2 to 3 days). For these reasons, this
test is no longer routinely performed. Toxin enzyme-linked
immunosorbent assay (ELISA) tests are less sensitive (70 to 90%) than
the cytotoxicity test, but demonstrate excellent specificity (99%) and
can be rapidly processed, and have largely replaced the cytotoxicity
assay.190
191
192
It is suggested that two stool specimens be
examined for leukocytes and toxin ELISA test.190
Should
the ELISA be negative and a high index of suspicion for C
difficile exist, the following are recommended: (1) sigmoidoscopy,
and/or (2) cytotoxicity assay, and/or (3) CT scan of abdomen looking
for thickened colonic wall.
|
Candida Infections
|
|---|
Candida species are important opportunistic pathogens in the ICU.
The CDC National Nosocomial Infection Study reported that 7% of all
nosocomial infections were due to candidal species.193
In
the EPIC study,104
17% of nosocomial ICU infections were
due to fungi. Candida infections should be considered in febrile ICU
patients who have been in the ICU for > 10 days and have received
multiple courses of antibiotics.53
Candida species are
particularly important pathogens in patients with ongoing
peritonitis.52
53
54
It is important to realize that Candida
species are constituents of the normal flora in about 30% of all
healthy people. Antibiotic therapy increases the incidence of
colonization by up to 70%.53
It is probable that most ICU
patients become colonized with Candida species soon after admission.
Not all patients colonized with Candida will become infected with
Candida. Nonneutropenic patients with isolation of Candida species from
pulmonary samples (tracheal aspirates, bronchoscopic or blind sampling
methods), even in high concentrations, are unlikely to have invasive
candidiasis.194
195
Indication for initiation of
antifungal therapy in these patients should be based on histologic
evidence or identification from sterile specimens. Similarly, isolation
of Candida species from the urine in ICU patients with indwelling
catheters usually represents colonization rather than infection.
Although candiduria may be observed in up to 80% of patients with
systemic candidiasis, candidemia from a urinary tract source is
extremely rare.54
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Other Infections
|
|---|
Nosocomial meningitis is exceedingly uncommon in hospitalized
patients who have not undergone a neurosurgical
procedure.196
197
Lumbar puncture, therefore, need not be
performed routinely in ICU patients (nonneurosurgical) who develop a
fever unless they have meningeal signs or contiguous
infection.196
197
In patients who have undergone abdominal
surgery and develop a fever, intra-abdominal infection must always be
excluded. CT scanning of the abdomen is indicated in these patients.
Similarly, in patients who have undergone other operative procedures,
wound infection must be excluded.
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Diagnostic Evaluation
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Abstract
Introduction
