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86. Fichtenbaum CJ, Ritchie DJ, Powderly WG. Use of paromomycin for
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89. Rossignol JF, Ayoub A, Ayers MS. Treatment of diarrhea caused
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90. Rossignol JF, Hidalgo H, Feregrino M, et al. A double-‘blind’ placebocontrolled study of nitazoxanide in the treatment of cryptosporidial diarrhoea in AIDS patients in Mexico. Trans R Soc Trop Med Hyg. 1998;92(6):
663–666.
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CHAPTER 113 ■ CATHETER-ASSOCIATED
URINARY TRACT INFECTIONS IN THE ICU:
IMPLICATIONS FOR CLINICAL PRACTICE
MARC LEONE r CLAUDE MARTIN
OBJECTIVE
DEFINITIONS
Intensive care units (ICUs) represent a meeting point between
the most seriously ill patients receiving aggressive therapy
and the most resistant pathogens that are selected by the
use of broad-spectrum antimicrobial therapy. Most patients
who are hospitalized in ICUs receive an indwelling urinary
catheter to monitor urine output. Urinary tract infection (UTI)
remains a leading cause of nosocomial infections with significant morbidity, mortality, and, hence, additional hospital
costs (1).
Although UTI represents 30% to 40% of nosocomial infections (1,2), its prevalence in patients admitted to the ICU is
approximately 20% (3). In a large European survey, UTI was
the third most common cause of nosocomial infections in the
ICU (3). Another study suggests that the incidence of urosepsis, defined as an inflammation of the upper urinary tract that
causes sepsis, occurs in approximately 16% of the ICU patient
population (4). The aim of this chapter is to focus on the prevention and management of UTI in patients hospitalized in the
ICU.
The Centers for Disease Control and Prevention (CDC) definitions of symptomatic UTIs and asymptomatic UTIs are collected in Tables 113.1, 113.2, and 113.3 (5). In the ICU, UTI is
the consequence of placement of an indwelling catheter. This results in the concept of catheter-associated UTI, the definition of
which is restricted to the presence of bacteria in the bladder of a
patient with an indwelling catheter. Bacteriuria is defined as the
detection of greater than or equal to 105 micro-organisms/mL
of urine with no more than two species of organisms (5). It is
of interest to note that, contrary to non–ICU-acquired urinary
tract infections, this definition does not take into account the
clinical symptoms.
PATHOPHYSIOLOGY
With the exception of the distal urethra, the urinary tract is
normally sterile. Resistance to UTI is influenced by exposure to
uropathogenic bacteria, age, hormonal status, and urine flow
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TA B L E 1 1 3 . 1
DEFINITIONS FOR SYMPTOMATIC URINARY TRACT INFECTIONS
At least one of the following criteria:
CRITERION 1
Patient has at least one of the following signs or symptoms with no other recognized cause : fever (>38◦ C), urgency, frequency,
dysuria, or suprapubic tenderness and patient has a positive urine culture with ≥105 micro-organisms/mL of urine with no more
than two species of micro-organisms.
CRITERION 2
Patient has at least one of the following signs or symptoms with no other recognized cause: fever (>38◦ C), urgency, frequency, dysuria,
or suprapubic tenderness and at least one of the following: (a) positive dipstick for leukocyte esterase and/or nitrate; (b) pyuria
(urine specimen with 10 white blood cells (WBC)/μL or ≥3 WBC/high-power field of unspun urine); (c) organisms seen on Gram
stain of unspun urine; (d) at least two urine cultures with repeated isolation of the same uropathogen (Gram-negative bacteria or
Staphylococcus saprophyticus) with ≥102 colonies/mL in nonvoided specimens; (e) ≤105 colonies/mL of a single uropathogen
(Gram-negative bacteria or S. saprophyticus) in a patient being treated with an effective antimicrobial agent for a urinary tract
infection; (f) physician diagnosis of a urinary tract infection; or (g) physician institutes appropriate therapy for a urinary tract
infection.
CRITERION 3
Patient ≤1 year of age with at least one of the following signs or symptoms with no other recognized cause: fever (>38◦ C),
hypothermia (<37◦ C), apnea, bradycardia, dysuria, lethargy, or vomiting and positive urine culture with ≥105 micro-organisms/mL
of urine with no more than two species of micro-organisms.
CRITERION 4
Patient ≤1 year of age with at least one of the following signs or symptoms with no other recognized cause: fever (>38◦ C),
hypothermia (<37◦ C), apnea, bradycardia, dysuria, lethargy, or vomiting and (a) positive dipstick for leukocyte esterase and/or
nitrate; (b) pyuria (urine specimen with 10 WBC/μL or ≥3 WBC/high-power field of unspun urine); (c) organisms seen on Gram
stain of unspun urine; (d) at least two urine cultures with repeated isolation of the same uropathogen (Gram-negative bacteria or S.
saprophyticus) with ≥102 colonies/mL in nonvoided specimens; (e) ≤105 colonies/mL of a single uropathogen (Gram-negative
bacteria or S. saprophyticus) in a patient being treated with an effective antimicrobial agent for a urinary tract infection; (f)
physician diagnosis of a urinary tract infection; or (g) physician institutes appropriate therapy for a urinary tract infection.
From Garner JS, Jarvis WR, Emori TG, et al. CDC definitions for nosocomial infections, 1988. Am J Infect Control. 1988;16:128.
(6). Insertion of a catheter allows organisms to gain access
to the bladder. The catheter induces an inflammation of the
urethra, allowing bacteria to ascend into the bladder in the
space between the urethral mucosa and the catheter. Catheterassociated UTI usually follows the formation of biofilm, which
consists of adherent micro-organisms, their extracellular products, and host components deposited on both the internal and
external catheter surfaces. The biofilm protects the organisms
from both antimicrobials and the host immune response (7).
The ascending route of infection is predominant in women, owing to their short urethra and contamination with anal flora.
An internal route of contamination (i.e., through the lumen of
the catheter) is less frequent and related to reflux of pathogens
from the drainage system into the bladder. This contamination
occurs when the drainage system fails to close or contamination
of urine in the collection bag.
TA B L E 1 1 3 . 2
DEFINITIONS FOR ASYMPTOMATIC URINARY TRACT INFECTIONS
One of the following criteria:
CRITERION 1
Patient has had an indwelling urinary catheter within 7 d before the culture and patient has a positive urine culture with ≥105
micro-organisms/mL of urine with no more than two species of micro-organisms and patient has no fever (>38◦ C), urgency,
frequency, dysuria, or suprapubic tenderness.
CRITERION 2
Patient has not had an indwelling urinary catheter within 7 d before the first positive culture and patient has had at least two positive
urine cultures with ≥105 micro-organisms/mL with repeated isolation of the same micro-organism and no more than two species of
micro-organisms and patient has no fever (>38◦ C), urgency, frequency, dysuria, or suprapubic tenderness.
From Garner JS, Jarvis WR, Emori TG, et al. CDC definitions for nosocomial infections, 1988. Am J Infect Control. 1988;16:128.
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TA B L E 1 1 3 . 3
OTHER URINARY TRACT INFECTIONS
One of the following criteria:
CRITERION 1
Patient has organisms isolated from culture of fluid (other than urine) or tissue from affected site.
CRITERION 2
Patient has an abscess or other evidence of infection seen on direct examination, during surgical operation, or during a histopathologic
examination.
CRITERION 3
Patient has at least two of the following signs or symptoms with no other recognized cause: fever (>38◦ C), localized pain, or tenderness
at the involved site and at least one of the following: (a) purulent drainage from affected site; (b) organisms cultured from blood that
are compatible with suspected site of infection; (c) radiographic evidence of infection (e.g., abnormal ultrasound, computed
tomography [CT] scan, magnetic resonance imaging [MRI], or radiolabel scan); (d) physician diagnosis of infection of the kidney,
ureter, bladder, urethra, or tissues surrounding the retroperitoneal or perinephric space; or (e) physician institutes appropriate
therapy for an infection of the kidney, ureter, bladder, urethra, or tissues surrounding the retroperitoneal or perinephric space.
CRITERION 4
Patient ≤1 year of age with at least one of the following signs or symptoms with no other recognized cause: fever (>38◦ C),
hypothermia (<37◦ C), apnea, bradycardia, dysuria, lethargy, or vomiting and at least one of the following: (a) purulent drainage
from affected site; (b) organisms cultured from blood that are compatible with suspected site of infection; (c) radiographic evidence
of infection (e.g., abnormal ultrasound, CT scan, MRI, or radiolabel scan); (d) physician diagnosis of infection of the kidney, ureter,
bladder, urethra, or tissues surrounding the retroperitoneal or perinephric space; or (e) physician institutes appropriate therapy for
an infection of the kidney, ureter, bladder, urethra, or tissues surrounding the retroperitoneal or perinephric space.
From Garner JS, Jarvis WR, Emori TG, et al. CDC definitions for nosocomial infections, 1988. Am J Infect Control. 1988;16:128.
MICROBIOLOGY
The isolated pathogens in ICU patients with bacteriuria are essentially relatively few: Escherichia coli, Pseudomonas aeruginosa, and Enterococcus species (Table 113.4) (8–10). Polymicrobial infections represent a relatively small percentage—5%
to 12% (2,8,9)—of total infections. In a large report investigating nosocomial infections in ICU patients, Gram-negative
bacteria caused 71% of UTIs, with stability over a 17-year period of surveillance (10). Resistance to antimicrobials increased
during this period, with rates of resistance to third-generation
cephalosporins up to 20% for E. coli (10,11). Although its role
is demonstrated in a urologic ward, cross-transmission probably plays a much greater role than suggested up to the present
(12).
RISK FACTORS
As stated, in ICU patients, UTIs are associated with the presence of indwelling catheters. The first step of prevention is to
highlight the risk factors of catheter-associated UTI in this specific population. In a study assessing risk factors for bacteriuria
in 553 patients with a urinary catheter for more than 48 hours
and hospitalized in an ICU (8), female sex, length of ICU stay,
prior use of antibiotics, severity score on admission, and duration of catheterization were independently associated with an
increased risk of catheter-associated bacteriuria; these results
mirrored those from a previous clinical study (13). Such results emphasize that reducing the duration of catheterization
appears to be the most important clinical step that can be iden-
tified for prevention. One notable study showed that in 21%
of 202 patients, the initial indication for the placement of a urinary catheter was unjustified. In a medical intensive care unit,
excessive duration of urinary catheter use for monitoring urine
output resulted in 64% of the total of unjustified patient-days
(14).
IMPACT OF URINARY TRACT
INFECTIONS IN THE INTENSIVE
CARE UNIT
Although adverse consequences of asymptomatic UTIs have
been described during pregnancy or in nursing home patients
(15), the real impact of ICU-acquired UTIs on outcome remains unclear. In a general hospital population, Platt et al.
showed that nosocomial UTIs were associated with significant
attributable mortality (16). The picture is probably different
in a specific ICU population. Indeed, even after controlling for
many risk factors, UTIs have a higher incidence in ICUs as
compared to other wards (17), although the urinary tract is
the source of sepsis in only 10% to 14% of the cases, which
is far less than the lung (Table 113.5) (18,19). Development
of ICU-acquired UTIs is associated with both an increase in
the length of ICU stay and the crude rate of mortality (8,9).
However, adequately powered studies demonstrate that UTIs
are not dependent factors for mortality (9,17).
Urosepsis is defined as an inflammation of the upper urinary tract that causes seeding of the blood with bacteria, resulting in local and distant destruction of tissue. A retrospective
study evaluated 126 trauma patients with a urinary catheter for
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TA B L E 1 1 3 . 4
PERCENTAGE OF PATHOGENS ASSOCIATED WITH NOSOCOMIAL URINARY
TRACT INFECTIONS
Percentage of isolates
Pathogens
Leone et al.a
(n = 53)
Laupland et al.b
(n = 290)
Gaynes et al.c
(n = 4,109)
Gram negative
Escherichia coli
Pseudomonas aeruginosa
Enterobacter species
Acinetobacter acinus
Proteus species
Klebsiella species
Citrobacter species
39
22
15
11
11
11
2
23
10
3
—
5
5
1
26
16.3
6.9
1.6
—
9.8
4
2
2
15
1
5
17.4
3.6
4.9
2
20
8
—
—
Gram positive
Enterococcus species
Staphylococcus aureus
Coagulase-negative Staphylococcus
Yeast
Candida albicans
Candida non-albicans
a
Leone M, Albanese J, Garnier F, et al. Risk factors of nosocomial catheter-associated urinary tract
infection in a polyvalent intensive care unit. Intensive Care Med. 2003;29:1077.
b
Laupland KB, Bagshaw SM, Gregson DB, et al. Intensive care unit-acquired urinary tract infections in a
regional critical care system. Crit Care. 2005;9:R60.
c
Gaynes R, Edwards JR, National Nosocomial Infections Surveillance System. Overview of nosocomial
infections caused by gram-negative bacilli. Clin Infect Dis. 2005;41:848.
sepsis. Twenty (16%) were diagnosed with urosepsis, which
was correlated with age older than 60 years, extended length
of stay in the ICU and/or hospital, and duration of catheterization. The mortality rates (15%) of the patients without urosepsis and with urosepsis did not differ (4). Similarly, in a prospective study, 6 out of 60 (10%) catheterized patients with asymptomatic bacteriuria developed urosepsis (20). Another prospective, cohort study of 235 catheter-acquired infections among
1,497 patients, 90% of whom were asymptomatic, reported
only one (0.42%) secondary bloodstream infection (21).
TA B L E 1 1 3 . 5
RATES OF SEPSIS ACCORDING TO EACH SITE
Percentages of patients
Sites
Lung
Abdomen
Blood
Urine
a
Vincent et al.a
(n = 1,177)
Angus et al.b
(n = 192,980)
68%
22%
20%
14%
44.0%
8.6%
17.3%
9.1%
Vincent JL, Sakr Y, Sprung CL, et al. Sepsis in European intensive
care units: results of the SOAP study. Crit Care Med. 2006;34:344.
b
Angus DC, Linde-Zwirble WT, Lidicker J, et al. Epidemiology of
severe sepsis in the United States: analysis of incidence, outcome, and
associated costs of care. Crit Care Med. 2001;29:1303.
Finally, UTIs can incur significant additional cost. An
episode of symptomatic nosocomial UTI in a hospitalized patient is expected to result in an average of $676 in additional
cost (22). Interestingly, however, a Turkish study calculated the
daily antibiotic costs per infected ICU patient. Among the sites
of nosocomial infections, urinary tract infections had the lowest daily antibiotic cost per infected patient ($52) (23).
DIAGNOSTIC TOOLS IN THE
INTENSIVE CARE UNIT
Urosepsis should be suspected any time a patient has a febrile
episode. Because of the prevalence of bacteriuria in patients
with urinary catheters, some have advocated daily monitoring of urine in catheterized patients. Routine daily bacteriologic monitoring of the urine from all catheterized patients is
not an effective way to decrease the incidence of symptomatic,
catheter-associated UTI, and is not recommended (24).
Three clinical trials have assessed the effectiveness of urinary dipsticks (leukocyte esterase and nitrite) for screening patients instead of quantitative urine culture in the ICU (Table
113.6) (25–27). Leukocyte esterase activity is an indicator of
pyuria, and urinary nitrite production is an indicator of bacteriuria. In the medical ICU, it has been demonstrated that the
urinary dipstick strategy is a rapid and cost-effective test with
which to screen asymptomatic catheterized patients. This effectiveness is observed only for a positive quantitative urine
culture level of 105 micro-organisms/mL. The urinary dipstick
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TA B L E 1 1 3 . 6
ASSESSING URINARY REAGENT STRIPS IN THE
INTENSIVE CARE UNIT
Prevalence (%)
Sensitivity (%)
Specificity (%)
Positive predictive
value (%)
Negative predictive
value (%)
Tissot
et al.a
Mimoz
et al.b
Legras
et al.c
31
87
61
31
38
84
41
46
42
90
65
61
96
81
91
a
Tissot E, Woronoff-Lemsi MC, Cornette C, et al. Cost-effectiveness
of urinary dipsticks to screen asymptomatic catheter-associated
urinary infections in an intensive care unit. Intensive Care Med.
2001;27:1842.
b
Mimoz O, Bouchet E, Edouard A, et al. Limited usefulness of
urinary dipsticks to screen out catheter-associated bacteriuria in ICU
patients. Anaesth Intens Care. 1995;23:706.
c
Legras A, Cattier B, Perrotin D. Dépistage des infections urinaires
dans un service de rintérêt des bandelettes réactives. Med Mal Infect.
1993;23:34.
1687
tive urine culture—cannot be recommended for symptomatic
UTIs in ICU patients. The Infectious Disease Society of America (IDSA) guidelines recommend that asymptomatic bacteriuria or funguria not be screened in patients with an indwelling
urethral catheter (28). Hence, in symptomatic patients, quantitative urine culture with Gram stain examination is recommended to obtain rapid identification of the pathogen.
PREVENTION
The best prevention of ICU-acquired UTIs is to simply reduce
the use of indwelling urethral catheters. In a medical ICU, an
independent observer determined that 64% of the total unjustified patient-days with urethral catheter resulted from its
prolonged use for monitoring urine output (14). Hence, each
member of the critical care medicine team should attempt to reduce the length of urethral catheterization and, whenever possible, this evaluation should occur during daily rounds. Other
measures, described below, can be useful only in units with a
restrictive policy of catheterization (Table 113.7).
Urinary Drainage System
strategy decreases the cost of diagnosis of nosocomial infection
and the daily workload in the microbiology laboratory (25).
One limitation of this study is that the incidence of asymptomatic bacteriuria was 31%, as compared with 6% to 9% in
other studies (8,9).
In a prior study, analysis of 102 urine samples determined
a positive predictive value of 81%. Those authors did not recommend the use of urinary dipsticks (27). Our best sense of
these data is that the use of dipsticks—instead of quantita-
In order to prevent infection, the maintenance of a closed sterile
drainage system is recommended as the most successful method
(29). A closed drainage system was described for the first time
in 1928 (30), and its benefit has been subsequently re-enforced
(16). A subgroup analysis of a randomized study, in which analyzed patients did not receive antibiotic treatment, showed a
reduction in mortality in the group using the closed system (16).
Historically, “open systems” were large, uncapped glass bottles. The drainage catheters were inserted into the glass bottles,
TA B L E 1 1 3 . 7
COMPARATIVE STUDIES PERFORMED IN THE INTENSIVE CARE UNIT ON THE PREVENTION OF
CATHETER-ASSOCIATED URINARY TRACT INFECTION
Leone et al.a
Leone et al.b
Thibon et al.c
Bologna et al.d
Method (number of
patients)
Prospective
Not randomized
(311)
Prospective
Randomized
(224)
Rate of bacteriuria
(%)
8
12
Prospective
Randomized
Multicenter
(199)
11
Prospective
Not randomized
Multicenter
(108)
8.1 vs. 4.9
Study group
Two-chamber simple
closed drainage
system
Two-chamber simple
closed drainage
system
Catheter coated with
hydrogel and silver
salts
Hydrogel latex
Foley catheter with
silver metal
Control group
Complex closed
system
Complex closed
system
Standard catheter
Standard catheter
Conclusion
No difference
No difference
No difference
No difference
a
Leone M, Garnier F, Dubuc M, et al. Prevention of nosocomial urinary tract infection in ICU patients. Comparison of effectiveness of two urinary
drainage systems. Chest. 2001;120:220.
Leone M, Garnier F, Antonini F, et al. Comparison of effectiveness of two urinary drainage systems in intensive care unit: a prospective, randomized
clinical trial. Intensive Care Med. 2003;29:410.
c
Thibon P, Le Coutour X, Leroyer R, et al. Randomized multi-centre trial of the effects of a catheter coated with hydrogel and silver salts on the
incidence of hospital-acquired urinary tract infections. J Hosp Infect. 2000;45:117.
d
Bologna RA, Tu LM, Polansky M, et al. Hydrogel/silver ion-coated urinary catheter reduces nosocomial urinary tract infection rates in intensive care
unit patients: a multicenter study. Urology. 1999;54:982.
b
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often below the level of urine. Urine was stagnant, and bacteria could easily grow and ascend through the drainage catheter.
The introduction of closed drainage systems was a major improvement, and their use has greatly reduced the rate of bacteriuria. However, in the modern era, several studies have failed to
confirm the benefit of complex closed systems compared with
simple devices (31–33).
There are only two studies in the literature specifically focused on ICU patients (34,35) and comparing a two-chamber,
open drainage system with a complex closed drainage system.
Both of them, which were performed by the same team of investigators, found similar results, although one of these studies was not randomized (34). In the randomized and prospective trial, 311 patients requiring an indwelling urinary catheter
for longer than 48 hours were assigned to the two-chamber
drainage system group or to the complex closed drainage system group to compare the rates of bacteriuria. The rates of
UTIs were 12.1 and 12.8 episodes per 1,000 days of catheterization, respectively (35). The data extracted from the recent
literature do not support the use of complex closed drainage
systems in ICU patients in view of the increased cost.
Owing to the lack of specific ICU studies, the guidelines
for the management of drainage systems should be viewed as
recommendations at best.
The following are reasonable suggestions:
1. Only people who know the proper technique of aseptic
insertion and maintenance of the catheter should handle
catheters.
2. Hospital personnel should be given periodic in-service training stressing the proper techniques and potential complications of urinary catheterization.
3. Hand washing should be performed immediately before and
after any manipulation of the catheter site or apparatus.
4. If small volumes of fresh urine are needed for examination,
the distal end of the catheter, or preferably the sampling port
if present, should be cleansed with a disinfectant, and urine
then aspirated with a sterile needle and syringe.
5. Larger volumes of urine for special analyses should be obtained aseptically from the drainage bag.
6. Unobstructed flow should be maintained.
7. In order to achieve free flow of urine, (a) the catheter and collection tube should be kept from kinking; (b) the collection
bag should be emptied regularly using a separate collecting
container for each patient (the draining spigot and nonsterile collection container should never come into contact); (c)
poorly functioning or obstructed catheters should be irrigated or, if necessary, replaced; (d) collection bags should
always be kept below the level of the bladder; and (e) indwelling catheters should not be changed at arbitrary fixed
intervals (36).
Types of Urethral Catheters
There are a large number of articles in the literature that stress
the efficacy of antiseptic-impregnated catheters, including silver
oxide or silver alloy, and antibiotic-impregnated catheters in
hospitalized patients (37–39). The results of two meta-analyses
clarify some points (38,39) related to these devices.
Silver oxide catheters are not associated with a reduction
in bacteriuria in short-term catheterized adults, whereas silver
alloy catheters reduce the incidence of asymptomatic bacteriuria and the risk of symptomatic UTI in catheterized adults.
Further, economic evaluation is required to confirm that the
reduction of infection compensates for their increased cost.
Catheters coated with a combination of minocycline and rifampin or nitrofurazone may also be beneficial in reducing bacteriuria in hospitalized men catheterized less than 1 week, but
this requires further testing (38,39). No trials directly compare
nitrofurazone-coated and silver alloy–coated catheters.
In a specific ICU patient population, a randomized, prospective, double-blind multicenter trial compared catheters coated
with hydrogel and silver salt with classic urinary tract catheters
in 199 patients requiring urethral catheterization for more
than 3 days (40). The cumulative incidence of UTIs associated
with catheterization was 11.1% overall, 11.9% for the control
group, and 10% for the coated catheter group. The odds ratio
was 0.82 (95% confidence interval [CI] 0.3–2.2). The differences between the two groups were not significant, although
the power of the study was more than 90% (40). A prior trial,
which included five hospitals selected to participate in a blinded
prospective study, exchanged the standard latex Foley catheter
for a hydrogel latex Foley catheter with a monolayer of silver
metal applied to the inner and outer surfaces of the device. The
adjusted catheter-associated infection rate during the baseline
and intervention periods was 8.1 and 4.9 infections per 1,000
catheter-days (p = 0.13), respectively (41).
Meatal Care
Twice-daily cleansing of the urethral meatus with povidoneiodine solution and daily cleansing with soap and water have
failed to reduce catheter-associated UTIs. Thus, at this time,
daily meatal care with either of these two regimens cannot be
endorsed.
A randomized, controlled, prospective clinical trial involving 696 patients hospitalized in medical and surgical units was
undertaken to determine the effectiveness of 1% silver sulfadiazine cream applied twice daily to the urethral meatus in preventing transurethral catheter-associated bacteriuria. The overall incidence of bacteriuria was approximately 13% in both
groups (p = 0.56) (42). In the absence of data from an ICUspecific patient population, the current guidelines should be
followed.
There are no data available on the level of sterility required
to insert a urinary catheter. Experts recommend that catheters
should be inserted using an aseptic technique and sterile equipment, including gloves, drapes, and sponges. However, in a
prospective study conducted in the operating room, 156 patients underwent preoperative urethral catheterization, randomly allocated to “sterile” or “clean/nonsterile” technique
groups. There was no statistical difference between the two
groups with respect to the incidence of UTI, but the cost differed considerably between the two groups (43).
Vesical Irrigation and Antiseptic
in the Drainage System
The objective of antibiotic irrigation is to clear bacteria from
the urinary tract. A randomized study compared 89 patients receiving a neomycin-polymyxin irrigation administered through
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a closed urinary catheter to 98 patients not so irrigated. Although the number of ICU patients was not specified in this
clinical study, 19 of the 98 (18%) patients not irrigated became
infected as compared with 14 out of the 89 (16%) of those who
were irrigated; the organisms from the irrigated patients were
more resistant (44). Another study was conducted in 264 urology patients, evaluating the effect of povidone-iodine bladder
irrigation prior to catheter removal on subsequent bacteriuria.
Of 264 patients, 138 received irrigation and 126 were controls.
Urine cultures were positive in 22% in the control group and
18% in the study group (45). Thus, irrigation methods failed
to demonstrate efficacy in surgical patients, and its use is not
recommended in ICU patients.
The addition of antimicrobial agents to the drainage device
has not been studied in the ICU. The largest reported clinical
trial evaluating the effect of H2 O2 insertion into the drainage
device of 353 patients, and comparing this to 315 control patients, failed to show a benefit in the treatment group. It is
of interest to note that 68% of these patients required an indwelling catheter for hemodynamic monitoring, with antimicrobial therapy prescribed in 75% of the patients, suggesting
that these results may apply to ICU patients (46). Expert opinion recommends that we not use irrigation unless obstruction
is anticipated, as might occur with bleeding after prostatic or
bladder surgery.
Alternatives to a Urinary Catheter
For selected patients, other methods of urinary drainage, such
as condom catheters, suprapubic catheterization, and intermittent urethral catheterization, should be considered as alternatives to indwelling urethral catheterization. There are limited
ICU data available to assess these alternative devices. There is
evidence, however, that suprapubic catheterization is advantageous, as compared to indwelling catheters, with respect to
bacteriuria, recatheterization, and discomfort (47,48). The use
of a condom connected to a collection bag has been evaluated in a study comparing 167 patients over two periods of
6 months. The occurrence of bacteriuria was significantly decreased for the period using the condom catheters (26.7 vs.
2.4%) (49). However, this issue merits further study to determine whether or not this alternative method may actually reduce bacteriuria rates. The use of intermittent catheterization is
also associated with a lower risk of bacteriuria than indwelling
urethral catheter, although such a procedure has never been
investigated in ICU patients (48,50,51).
Miscellaneous Measures
While there is a low risk of bacteremia during urinary catheterization (52), the administration of antimicrobial therapy at the
time the device is placed leads to a reduction in bacteriuria
(53–55). The efficacy of antibiotic treatment has been assessed
as optimal for catheterization lasting less than 14 days (54).
However, the prophylactic use of antibiotic in the ICU can
be detrimental to the bacterial ecology by increasing the pressure for antimicrobial resistance among bacteria. The practice
of administration of prophylactic antimicrobials in this manner must be discouraged in our ICUs. It should be noted that
in most ICU studies, 75% of the patients with an indwelling
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catheter require antibiotics for reasons unrelated to the urinary
catheter (8). Further, all measures aimed at reducing the burden
of nosocomial infections can reduce the rate of UTIs (56–58).
TREATMENT AND MANAGEMENT
The management of catheter-associated UTI has not been evaluated in ICU patients. Several nonspecific measures, including
hydration, have been advocated in the therapy of UTI. Adequate hydration would appear to be important, although there
is no evidence that it improves the effectiveness of an appropriate antimicrobial therapy (59). The management of complicated UTIs in the ICU may include mechanical intervention.
Consequently, appropriate diagnostic tests and urologic consultation should be included in the algorithm of the management of these patients (Fig. 113.1).
Management of Asymptomatic Bacteriuria
According to leaders in our field, asymptomatic catheterassociated UTI does not require treatment (28). However, antimicrobial treatment may be considered for asymptomatic
women with a catheter-acquired UTI that persists 48 hours
after catheter removal (60). In a specific ICU patient population, 60 patients with an indwelling urethral catheter for longer
than 48 hours who developed an asymptomatic positive urine
culture were randomized to receive either a 3-day course of
antibiotics associated with the replacement of the indwelling
urethral catheter 4 hours after the first antibiotic administration or no antibiotics and no catheter replacement. Six patients
equally distributed in the two groups developed urosepsis. The
profile of bacterial resistance was similar in the two groups.
Hence, treating a positive urine culture in an asymptomatic
patient with an indwelling urethral catheter does not reduce
the occurrence of urosepsis (20).
Management of Symptomatic Urinary
Tract Infections
Choice of Antimicrobial Agents
The optimal characteristics of agents to treat urinary tract infection must include activity against the major pathogens involved in these infections, good tissue penetration, and minimal
side effects. High urinary levels should be present for an adequate period to eliminate the organisms, since disappearance
of bacteriuria correlates with the sensitivity of the pathogen
to the concentration of the antimicrobial agent achieved in the
urine (61). Inhibitory urinary concentrations are achieved after administration of essentially all commonly used antibiotics.
However, an antibiotic that achieves active concentrations in
the renal tissue is required for infection of the renal tissue. The
antibiotic concentration in the serum or plasma can be used as
surrogate markers for the antibiotic concentrations in the renal
tissue (62). For drugs with concentration-dependent time-kill
activity such as the aminoglycosides or the fluoroquinolones,
the peak antibiotic concentration is the most important parameter for the in vivo effect. Experimentally, gentamicin and
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Bacteriuria in patient with an indwelling urethral catheter
Urosepsis
No symptoms
Do not consider
CT scan or ultrasound: Renal injury
Yes
No
Shock
No
Fluoroquinolones
(oral)
OR
third-generation
cephalosporin (IV)
14 days
Shock
Yes
No
Third-generation
cephalosporin*
(parenteral)
+ aminoglycoside
OR
fluoroquinolone#
21 days
Third-generation
cephalosporin
(parenteral)
7 days
fluoroquinolone treatment are both more effective than the βlactam antibiotics in rapid bacterial killing (62).
Most clinical studies have shown that the renal concentrations of the cephalosporins remained higher than the minimal
inhibitory concentration for the most common bacteria during
the time interval between the administration of two doses (63–
65). By contrast, β-lactam antibiotics, which have a low pKa
and poor lipid solubility, penetrate poorly into the prostate,
except for some cephalosporins. Good to excellent penetration
into the prostatic tissue has been demonstrated with many antimicrobial agents, such as aminoglycosides, fluoroquinolones,
sulfonamides, and nitrofurantoin (66).
In ICU patients, the side effects of treatment should be minimized at both the individual and the community level. Many
patients develop renal failure, associated with the inability to
concentrate antimicrobial agents in the urine. Additionally, administration of drugs with potential renal toxicity may worsen
renal insufficiency. This may be an important limiting factor
for using aminoglycosides in patients with renal failure. Otherwise, antimicrobial treatment must produce a minimal effect
on the bacterial flora of the community (67). From this standpoint, there is significant literature demonstrating that the use
of fluoroquinolone is associated with the emergence of resistant pathogens (68–70). This implies that an indication for
antibacterial therapy should be weighed thoroughly and fluoroquinolones should be used in accordance with sensitivity testing (70). Hence, it is of importance to stress that UTI should
not be treated before the results of sensitivity testing, except
in patients with pyelonephritis and those with severe sepsis or
septic shock who require empirical antimicrobial therapy.
Cystitis
As acute uncomplicated cystitis is infrequent in ICU patients,
most recommendations focus on the treatment of nonhospi-
Yes
Third-generation
cephalosporin*
(parenteral)
+ aminoglycoside
OR
fluoroquinolone#
7 days
FIGURE 113.1. Suggested algorithm for the management of urinary tract infections related to an indwelling
catheter in the intensive care unit. CT, computed tomography. *Discuss the need for antipseudomonal coverage according to the duration of hospitalization, prior
medical history, and local ecology. # Discuss if renal failure.
talized women, which makes their relevance in ICU patients
questionable; E. coli is the evident target pathogen. The 1999
IDSA guidelines recommend treatment with trimethoprimsulfamethoxazole for 3 days as standard therapy for acute
uncomplicated cystitis. Single-dose therapy is less effective in
eradicating initial bacteriuria than longer durations of treatment with trimethoprim-sulfamethoxazole, trimethoprim, norfloxacin, ciprofloxacin, fleroxacin, and, as a group, β-lactam
antibiotics (71). In contrast, a meta-analysis determined that 3
days of antibiotic therapy is similar to 5 to 10 days in achieving symptomatic cure during uncomplicated UTI treatment,
while the longer treatment is more effective in obtaining bacteriologic cure. Consequently, such durations should be considered for treatment of women in whom eradication is critical
(72). Quinolones are recommended for acute cystitis in regions
where the level of resistance to trimethoprim-sulfamethoxazole
is high. There were no significant differences in clinical or microbiologic efficacy between quinolones. The rate of adverse
events causing antimicrobial withdrawal tends to be lower with
norfloxacin and ciprofloxacin than with other quinolones (73).
Antibiotic treatment of UTI depends on the ability of the
antibiotic to inhibit the growth or kill the bacteria present in the
urinary tract. This is related to the concentration of antibiotics
at the site of infection. Very high concentrations of antibiotics
with renal clearance are obtained in urine. Consequently, even
in the presence of pathogens exhibiting in vitro resistance, the
high concentrations of antibiotics in urine inhibit the growth
of pathogens, rendering them effective to treat a UTI.
Prostatitis
For outpatients, bacterial prostatitis is a common diagnosis and
a frequent indication for antibiotics. Although urethral instrumentation and prostatic surgery are known causes of prostatitis, the incidence of prostatitis among ICU patients has never
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been assessed, and there is only a weak relation between acute
and chronic prostatitis.
Acute prostatitis is an acute infection producing local heat,
tenderness, and fever, with the presence of IgA and IgG
bacteria-specific immunoglobulins in the prostatic secretions.
Few symptoms, usually perineal discomfort, are exhibited with
prostatitis. Most patients with chronic prostatitis have no history of positive urine or urethral cultures (74).
In ICU patients, acute bacterial prostatitis is probably a
common infection. The patient presents septic, but without an
evident source of infection. There may be a history of urine
retention due to bladder outlet obstruction. Rectal examination, a crucial step in the diagnosis, reveals a warm, swollen,
and tender prostate. The prostatic fluid contains leukocytes
and the pathogen responsible for the infection. However, massage of the prostate is proscribed to avoid bacteremia. Fluoroquinolones are the drugs of choice to treat acute prostatitis because of their excellent penetration in the tissue and excretions
(75,76). The targeted pathogens are E. coli, Proteus sp., Klebsiella sp., Enterococcus sp., Staphylococcus aureus, Neisseria
gonorrhoeae, and Chlamydia trachomatis. For acute prostatitis
occurring without bacteremia, antimicrobial treatment consists
of oral ofloxacin 200 mg twice per day for 28 days; ceftriaxone
2 g/day has good prostatic tissue penetration and represents an
alternative to ofloxacin (77). Gentamicin 3 mg/kg/day is added
in the presence of positive blood cultures (Table 113.8). Of
importance, urethral instrumentation should be discouraged,
and if acute retention occurs, suprapubic drainage of urine is
required. Treatment of chronic prostatitis is based on the oral
administration of ofloxacin 200 mg twice per day, or trimethoprim 160 mg–sulfamethoxazole 800 mg twice per day for at
1691
least 28 days. The indications for this treatment should be discussed with specialists.
Acute Pyelonephritis
There are no specific data available in the literature on the management of acute pyelonephritis in the ICU. The urine of all
patients with suspicion of complicated pyelonephritis should
be cultured and a Gram stain of the spun urine performed.
Blood cultures, which are positive in 36% of women not admitted to the ICU, are also required (78). All patients with acute
pyelonephritis should have an ultrasound examination or a renal computed tomography scan to evaluate for obstruction and
stones.
For uncomplicated acute pyelonephritis, the IDSA, in 1999,
derived two conclusions from the analysis of randomized clinical trials. The first is that trimethoprim-sulfamethoxazole is
preferred over ampicillin. Indeed, there is a relatively high
prevalence of organisms causing acute pyelonephritis that are
resistant to ampicillin, and even for susceptible organisms,
there is a significantly increased recurrence rate in patients
given ampicillin compared with those given trimethoprimsulfamethiazole. The second conclusion is that 10 to 14 days
of therapy appears to be adequate for the majority of women
(71). There has been little additional information since the
publication of these recommendations. However, 255 outpatients were randomized to oral ciprofloxacin, 500 mg twice
per day for 7 days, followed by placebo for 7 days versus
trimethoprim-sulfamethoxazole, 160/800 mg twice per day
for 14 days. In this study, a 7-day ciprofloxacin regimen was
associated with greater bacteriologic and clinical cure rates
than a 14-day trimethoprim-sulfamethoxazole regimen (79)
TA B L E 1 1 3 . 8
ANTIMICROBIAL TREATMENT OF URINARY TRACT INFECTIONSa
Source of infection
Pathogens
Treatment
Duration
Acute prostatitis (without
bacteremia)
Escherichia coli, Proteus sp., Klebsiella
sp., Enterococcus sp., Staphylococcus
aureus, Neisseria gonorrhoeae,
Chlamydia trachomatis
Ofloxacin 200 mg twice daily (oral)
28 d
Acute prostatitis (with
bacteremia)
E. coli, Proteus sp., Klebsiella sp.,
Enterococcus sp., S. aureus, N.
gonorrhoeae, C. trachomatis
Ofloxacin 200 mg twice daily (oral)
or
Ceftriaxone 2 g/d
and
gentamicin 3 mg/kg/d IV
28 d
3d
Chronic bacterial
prostatitis
E. coli, Proteus sp., Klebsiella sp.,
Enterococcus sp., S. aureus, N.
gonorrhoeae, C. trachomatis
Ofloxacin 200 mg twice daily (oral)
or
Trimethoprim 160 mg/sulfamethoxazole
800 mg twice daily (oral)
28 d
Acute pyelonephritis
(uncomplicated)
Enterobacteriaceae, E. coli, Proteus sp.,
Enterococcus sp.
Ciprofloxacin 500 mg twice daily (oral)
If oral route not possible: Ceftriaxone 2
g/d IV
14 d
Acute pyelonephritis
(complicated)
Enterobacteriaceae, E. coli, Proteus sp.,
Enterococcus sp.
Ciprofloxacin 500 mg twice daily (oral)
or
Ceftriaxone 2 g/d IV
AND
Gentamicin 3 mg/kg/d
14–21 d
Each empirical treatment must be adapted to the susceptibility testing results.
3d
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(Table 113.8). Gatifloxacin appears to be equivalent to
ciprofloxacin for this indication (80).
Patients with complicated acute pyelonephritis should be
hospitalized and initial administration of broad-spectrum intravenous antibiotics begun. The targeted bacteria are Enterobacter sp., E. coli, Proteus sp., and Enterococcus sp.
Ciprofloxacin, 500 mg twice daily, is administered orally for 14
to 21 days. Gentamicin, 3 mg/kg/day intravenously, is added
during the first 3 days. Interestingly, oral ciprofloxacin is as effective as the intravenous regimen in the initial empirical management of complicated pyelonephritis (81), and gatifloxacin
is as effective as ciprofloxacin (80). If needed, ceftriaxone, 2
g/day intravenously, is an alternative choice to ciprofloxacin.
Further, the success rates are similar in patients given ceftriaxone or ertapenem (82).
The drainage of urine must be urgently performed using
bladder catheterization, percutaneous nephrostomy drainage,
or definitive surgery. Antimicrobial treatment is administered
after urine and blood specimen collection. The antibiotic selection is based on the result of the Gram stain of the urine and
the knowledge of the local ecology. Antimicrobial treatment
should be adapted to the susceptibility testing results as soon
as possible, and de-escalation should be performed in favor of
a narrow-spectrum antibiotic.
Specificities of Complicated Urinary Tract
Infections in the Intensive Care Unit
Although there is little in the literature on the treatment of
UTIs in the ICU, one presumes the need for intravenous antibiotics for these patients because of the possibility of bacteremia
or sepsis. The guidelines from the Surviving Sepsis Campaign
state that (a) antibiotic therapy should be started within the first
hour of recognition of severe sepsis, after appropriate cultures
have been obtained; (b) initial empirical anti-infective therapy
should include one or more drugs that have activity against
the likely pathogens and that penetrate the presumed source of
sepsis; and (c) monotherapy is as effective as combination therapy with a β-lactam and an aminoglycoside as empiric therapy
of patients with severe sepsis or septic shock (83). Hence, empirical antimicrobial therapy should include drugs with good
penetration in the urinary tract, and the choice is guided by
the susceptibility patterns of micro-organisms in the hospital.
For the septic shock patients whose presumed source is urine,
we recommend, empirically, a combination of a β-lactam antibiotic with antipseudomonal activity and a fluoroquinolone.
This broad-spectrum treatment is narrowed as soon as the results of the susceptibility testing are known. The durations of
treatment should be tailored to the source of infection.
Management of Candiduria
Candiduria represents from 3% to 15% of catheter-associated
UTI in the ICU (8,9,13). Candida albicans and Candida (Torulopsis) glabrata are found in 46% and 31% of cases, respectively (84). According to the International Conference for the
Development of a Consensus on the Management and Prevention of Severe Candidal Infections, colonized patients without
evidence of infection do not require treatment, but the contributing cause should be addressed, such as changing or removing the indwelling catheter and discontinuing inappropriate antibiotic therapy. Fluconazole may be the best option for
treating a candiduria (85), but only if the species is C. albi-
cans. Voriconazole may be more effective against non-albicans
species.
Clinician reaction to isolating Candida organisms in urine
was assessed in a retrospective review of 133 consecutive patients. The average patient age was 68.8 years old, most (78%)
had an indwelling catheter, and many (35%) were in the ICU. In
response to culture results, clinicians initiated antifungal therapy in 80 instances (60%). Treatment was often based on a
single culture result without evidence of infection (66%) and
in the absence of risk of invasive disease. Removal of the indwelling catheter was never attempted and antibiotics were
rarely discontinued or modified (1.3%). Fluconazole was most
frequently utilized (52%), followed by amphotericin B bladder irrigation (32%) and combined fluconazole/amphotericin
B bladder irrigation (15%). Therapy was more frequently initiated in ICU cases (77 vs. 56%; p = 0.02) (86). These results
show the poor adherence to guidelines.
A prospective, randomized trial compared fungal eradication rates among 316 hospitalized patients with candiduria
treated with fluconazole (200 mg) or placebo daily for 14 days.
Candiduria cleared by day 14 in 50% of the patients receiving
fluconazole and 29% of those receiving placebo, with higher
eradication rates among patients completing 14 days of therapy. Fluconazole initially produced high eradication rates, but
cultures at 2 weeks revealed similar candiduria rates among
treated and untreated patients. In 41% of the catheterized subjects, candiduria was resolved as the result of catheter removal
only. The outcomes of patients were not provided in the results
(87).
Bladder irrigation using amphotericin B has been proposed
as an alternative technique to clear Candida from the urine.
A comparative and randomized study of 109 elderly patients
showed that funguria was eradicated in 96% of the patients
treated with amphotericin B and 73% of those treated with
fluconazole (p <0.05). One month after study enrollment, the
mortality rate associated with all causes was greater among patients who were treated with amphotericin B bladder irrigation
than among those who received oral fluconazole therapy (41%
vs. 22%, respectively; p <0.05). This finding suggests that irrigation therapy could be associated with poorer survival (88).
There has only been one study performed in ICU patients
developing candiduria, which reached the same conclusions;
unfortunately, methodologic issues restrict the interest of this
study. The authors retrospectively compared three means to
manage candiduria in ICU patients: successful bladder irrigation with amphotericin B (10 of 27 patients), failure of bladder
irrigation requiring the use of parenteral amphotericin B (17
of 27), and patients treated with parenteral fluconazole (n =
20). Severity score on admission day was significantly lower
in the first group than in the two others. However, the mortality rate was 53% and 5% in patients experiencing a failure
of bladder irrigation and in patients receiving fluconazole, respectively (89). These results must be considered with caution
because of serious methodologic limitations. However, these
data indicate that bladder irrigation of critically ill patients has
a negative survival advantage.
SUMMARY
Bacteria in the bladder constitute a reservoir for the development of multiresistant bacterial strains, and the rate of bacteriuria may be used as a marker of the level of care in the
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ICU. Prevention of UTIs in the ICU is not improved by the
use of expensive devices, but can reflect the level of general
unit hygiene. While management of UTIs in the ICU is poorly
described in the literature, it is reasonably clear that there is
no need to treat asymptomatic bacteriuria. However, although
infrequent, severe sepsis with a urine source requires empirical broad-spectrum antimicrobial treatment based on the local
bacterial ecology. Treatment is de-escalated after identification
of the pathogen and reporting of the susceptibility testing.
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October 24, 2008
Section XI: Infectious Disease
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CHAPTER 114 ■ FUNGAL AND VIRAL
INFECTIONS
MINH-LY NGUYEN r MINH-HONG NGUYEN r KEVIN J. FARRELL r CORNELIUS J. CLANCY
FUNGAL INFECTIONS
Fungal Pathogens
Medically relevant fungi are classically considered as one of
three types of organism: yeasts, molds, or dimorphic agents.
The yeasts grow as smooth colonies on culture plates. Microscopically, they are oval or spherical, and they reproduce
by budding. The two most common human yeast pathogens
are Candida spp. and Cryptococcus spp.; the molds appear
as fuzzy colonies on agar plates. Microscopically, they have
hyphae, which are tubular or filamentous morphologies that
grow by branching and longitudinal extension. Hyphae can
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