International Journal of Antimicrobial Agents 17 (2001) 299– 303

www.ischemo.org

Catheter-associated urinary tract infections

John W. Warren *
Di6ision of Infectious Diseases, Uni6ersity of Maryland School of Medicine, 10 S. Pine Street, Room 9 -00, Baltimore, MD 21201, USA

Abstract

Nosocomial urinary tract infection (UTI) is the most common infection acquired in both hospitals and nursing homes and is
usually associated with catheterization. This infection would be even more common but for the use of the closed catheter system.
Most modifications have not improved on the closed catheter itself. Even with meticulous care, this system will not prevent
bacteriuria. After bacteriuria develops, the ability to limit its complications is minimal. Once a catheter is put in place, the clinician
must keep two concepts in mind: keep the catheter system closed in order to postpone the onset of bacteriuria, and remove the
catheter as soon as possible. If the catheter can be removed before bacteriuria develops, postponement becomes prevention.
© 2001 Elsevier Science B.V. and International Society of Chemotherapy. All rights reserved.

Keywords: Nosocomial UTI; Catheter-associated UTI; Prevention of catheter-associated UTI; Bacteremia

1. Introduction 2. Pathogenesis

The urethral catheter is one of the most venerable of
medical devices, having been used for urine retention
on an intermittent or indwelling basis for centuries. In
the 1920s, Foley introduced a catheter which could be
held in place with an intra-bladder balloon. In the first
several decades of use, Foley catheters were attached to
collecting tubes which drained into buckets placed on
the floor beside the bed, the so-called ‘open-catheter
system’. Bacteriuria occurred by the end of 4 days. The
1950s saw the progressive development of ‘closed’
catheter systems. Plastic collection bags fused to the
distal end of the tubes began to be used in the 1960s.
This arrangement allows drainage through a tube into a
receptacle so that the urine is always contained within a
lumen protected from the contaminated environment.
The onset of bacteriuria is now more than 30 days in
closed catheter systems. Although no well-designed
controlled trials comparing open with closed catheters
have been performed, reports have been sufficiently
positive so that the closed system has become the
standard for patients requiring indwelling urethral
catheters.
* Fax: + 1-410-7068700.
Insertion of a catheter may carry urethral organisms
into the bladder. The catheter may be disconnected
from the collection tube and bacteriuria has been asso-
ciated with such interruptions. The drainage tube of the
collection bag must be opened periodically to drain
accumulated urine. If the lumen of the drainage tube is
contaminated with bacteria, organisms may enter the
drainage bag and ascend the collection tube and
catheter. Even with meticulous attention to mainte-
nance of the closed system, the space between the
external catheter and the urethral mucosa offers oppor-
tunity for bacterial entry directly into the bladder and
this is the most common route of entry for bacteria [1].
In marked contrast to the non-catheterized urinary
tract where small numbers of organisms introduced in
the bladder are eliminated efficiently, most bacterial
strains that enter the catheterized urinary tract are able
to multiply to high concentrations within a day [2].
Biofilm, which covers and secures bacteria against a
catheter or mucosal surface, has been demonstrated on
drainage bags, catheters, and the uroepithelium. Organ-
isms contained within the biofilm appear to be well-pro-
tected from the mechanical flow of urine, host defenses,
and even antibiotics. The biofilm may allow the con-
tained sessile organisms to establish a microenviron-
ment from which some may move into the urine; these

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300 J.W. Warren / International Journal of Antimicrobial Agents 17 (2001) 299–303
planktonic microbes are those that are voided and
enumerated as bacteriuria by the diagnostic microbiol-
ogy laboratory. Additionally, the catheter may mechan-
ically damage urinary epithelium and the
glycosaminoglycan layer. As a foreign body, the
catheter may disrupt adequate anti-bacterial polymor-
phonuclear leukocyte function. Finally, catheter
drainage is often imperfect and volumes of urine may
remain in the bladder, thus allowing some stability to
the residence of bacteria.
The duration of catheterization is the most important
risk factor for the development of catheter-associated
bacteriuria [3] and is a result of the indications for
urethral catheterization:
1. Surgery,
2. Urine output measurement,
3. Urine retention, and
4. Urinary incontinence.
Once a urethral catheter is in place, in patients in a
hospital or a nursing home, the daily increase in preva-
lence of bacteriuria is 3 – 10% [4]. The great majority of
catheterized patients will be bacteriuric by the end of 30
days, a convenient dividing line between short-term and
long-term catheterization.
2.1. Short-term catheterization
Between 15 and 25% of patients in general hospitals
may have a catheter in place sometime during their
stay. Most are in place for only a short time, up to
one-third for less than a day; both the mean and
median durations are between 2 and 4 days. In short-
term catheterization, common bacteriuric species such
as Escherichia coli are isolated. Other common organ-
isms are Pseudomonas aeruginosa, Klebsiella pneumo-
niae, Proteus mirabilis, Staphylococcus epidermidis,
enterococci, and Candida species. Most bacteriuria in
short-term catheterization is of single organisms.
Most episodes of short-term catheter-associated bac-
teriuria are asymptomatic [5]. Less than 5% of catheter-
associated bacteriuric patients will be identified with
bacteremia, but because of the large number of
catheterized patients, these bacteremias comprise up to
15% of nosocomial blood stream infections [6]. The
contribution of catheter-associated UTI to mortality is
unclear. At autopsy, patients with catheter-associated
bacteriuria dying in a hospital may have acute
pyelonephritis, urinary stones, or perinephric abscesses.
However, in prospective or case-controlled studies,
catheter-associated urinary tract infections (UTIs) are
often not found to be associated with excess mortality.
One study, however, has suggested an increased risk of
death associated with catheter-associated bacteriuria
[7]. Minimal estimates are that catheter-associated bac-
teriuria add 1 day of hospitalization for the bacteriuric
patient. The significance of this is magnified by the
large number of catheters in use and the high incidence
of infection in the US. Catheter-associated bacteriuria
is estimated to cause 900 000 additional hospital days
per year. Nosocomial UTIs directly cause almost 1000
deaths and contribute to an additional 6500 deaths per
year in the US [8].
2.2. Long-term catheterization
Although the magnitude of long-term urethral
catheter use has not been directly measured, several
studies suggest that at any given time, more than
100 000 patients in American nursing homes have ure-
thral catheters in place [9]. Many of these patients have
been catheterized for months or years. The two most
frequent indications are urinary incontinence and blad-
der outlet obstruction.
Even with excellent care, all patients will become
bacteriuric if catheterized long enough. This ‘universal’
prevalence of bacteriuria is a function of two related
phenomena. The first is the incidence of new episodes
of bacteriuria similar to that seen in short-term
catheterized patients, although caused by a wide variety
of gram-negative and gram-positive bacterial species
[10]. The second is the ability of some of these strains to
persist for weeks in the catheterized urinary tract. At
least two types of bacteria inhabit the long-term
catheterized urinary tract. The first comprises common
uropathogens such as E. coli which have adhered to
uroepithelium just as they would in the noncatheterized
urinary tract. The second is of other organisms such as
Pro6idencia stuartii which are rarely found outside the
catheterized urinary tract and may use the catheter
itself as a niche. These phenomena result in polymicro-
bial bacteriuria in up to 95% of urine specimens from
long-term catheterized patients. Such specimens com-
monly have two to four bacterial species, each at
concentrations of 105 cfu/ml or more; some may even
have up to six to eight species at similar concentrations
[10].
Complications of long-term catheter-associated bac-
teriuria fall into two categories. The first includes symp-
tomatic UTIs such as seen with short-term
catheterization, i.e. fever, bacteremia, and acute
pyelonephritis [11 –14]. Some of these episodes may end
in death. The second group is more often associated
with long-term catheterization: obstruction, urinary
tract stones [15,16], local periurinary infections, chronic
pyelonephritis [17,18] and with prolonged use, bladder
cancer [19].
Although two-thirds of febrile episodes in aged long-
term catheterized patients may arise from the urinary
tract, the incidence is low, about one episode per 100
days of catheterization. Most women presents with
low-grade fever, lasting for 1 day or less, and resolve
without antibiotic therapy or catheter change [11].
 J.W. Warren / International Journal of Antimicrobial Agents 17 (2001) 299–303
UTIs are the most common source of bacteremias in
nursing homes [12] and the indwelling urethral catheter
is the leading risk factor for bacteremia. Patients with
catheters in place are about 60 times more likely to be
bacteremic over a 1-year period than patients without
catheters [13]. Although E. coli is significantly more
likely than other bacteriuric organisms to cause bac-
teremia, others, even ‘non-uropathogens’ such as P.
stuartii or Morganella morganii, can do so as well.
Acute pyelonephritis is undoubtedly the source of many
of these febrile episodes. Moreover, autopsies have
revealed acute pyelonephritis in more than one third of
patients dying with long-term catheters in place [14].
Bacteriuria caused by P. mirabilis is associated with
catheter obstruction, probably because of its potent
urease, which hydrolyses urea to ammonia, increasing
urine pH and causing crystallization of struvite and
apatite in the catheter lumen [15,16]. A similar process
may occur in the urinary tract itself resulting in ‘infec-
tion stones’, a common problem in long-term catheter-
ized patients. Such stones in the bladder, often crusting
around the catheter balloon and tip, are relatively
benign. However, renal stones may be more serious and
are associated with chronic pyelonephritis and renal
dysfunction [17,18].
3. Prevention
3.1. Pre6ention of catheterization
The last several decades have seen major advances in
understanding complications of catheterization which
prompted attention to the use of alternatives such as
patient training, biofeedback, medications, surgery, and
using special clothes and bed-clothes. Additionally, sev-
eral devices have been explored as options to the ure-
thral catheter.
For men with urinary incontinence, condoms applied
about the penis that empty through a collection tube
into a drainage bag have been widely used. Although
these avoid problems of having a tube in the urinary
tract, urine within these condom catheters may develop
high concentrations of organisms, the urethra and skin
may be colonized with uropathogens, and bladder bac-
teriuria may develop [20]. Although no properly-de-
signed controlled trials have been performed, parallel
studies of condom catheters and urethral catheters in
the same institution suggest a substantially lower inci-
dence of bacteriuria with condom catheters [21,22].
Following its re-introduction in the 1940s, intermit-
tent catheterization by the 1970s had become the stan-
dard of care for spinal injured patients. Insertion of a
catheter every 3–6 h by caregivers or the patient,
drainage of urine, and immediate removal of the
catheter provide periodic bladder emptying. The inci-
301
dence of bacteriuria is about 1–3% per catheterization
[23]. A randomized study comparing clean versus sterile
catheters showed no difference in symptomatic UTI but
did show that clean catheterization was associated with
reduced costs [24]. Oral antibiotics and methenamine
compounds as well as instillations of povidone iodine
and chlorhexidine preparations have been used to post-
pone bacteriuria for short periods in intermittently
catheterized patients; whether such practices would be
beneficial over months and years has not been shown.
Bacteriuria is usually asymptomatic and, although no
well-designed comparisons have been performed, inter-
mittent catheterization may be an improvement over
indwelling catheterization in regard to local periurethral
infections, febrile episodes, bacteremia, bladder and
renal stones, and deterioration of renal function.
Suprapubic catheterization has been increasingly
used in several types of surgery. Studies have randomly
assigned patients to suprapubic or urethral catheteriza-
tion and some have shown significant benefits of supra-
pubic catheterization in terms of lowering the
incidences of bacteriuria, urethral strictures, or pain
[25].
3.2. Pre6ention of bacteriuria
Once a urethral catheter is in place, only two princi-
ples are universally recommended for prevention of
bacteriuria: keep the closed catheter system closed and
remove the catheter as soon as possible. Urine speci-
mens should be obtained without opening the catheter-
collection tube junction. The only point at which the
system must be opened is the bag drainage tube and
personnel must avoid touching the end of the drainage
tube to possibly contaminated containers. If the
catheter can be removed before bacteriuria develops,
postponement becomes prevention. More than a third
of days late in catheterization courses may be unneces-
sary [5]. A reasonable management tool would be a
daily review of the necessity to continue catheterization
in any given patient.
Although many logical modifications have been at-
tempted, most have not markedly improved upon the
ability of the closed system to postpone bacteriuria.
Irrigation of the catheter and bladder with antibacterial
solutions has not curtailed bacteriuria. Additionally,
antimicrobials in the collection bag have generally been
ineffective. Given that the potential space between the
urethra and the external catheter surface is probably
the most common route of entry for organisms, numer-
ous investigators have attempted to block this pathway
by applying topical antibacterial agents. However, stud-
ies have shown little if any, postponement of bacteri-
uria with such techniques. Indeed, several studies
revealed that patients receiving such agents actually
tended to have an increased incidence of bacteriuria, a
302 J.W. Warren / International Journal of Antimicrobial Agents 17 (2001) 299–303
finding attributed to physical manipulation of the ure-
thra allowing easier ingress of urethral and periurethral
bacteria.
Another modification has been to manipulate the
composition of the catheter material [26,27].
Most studies of using systemic antibiotics, retrospec-
tive or prospective, have demonstrated effectiveness in
initially diminishing the incidence of bacteriuria in
catheterized patients. In hospitals, up to 80% of
catheterized patients are administered antibiotics during
but not usually because of catheterization. Neverthe-
less, those studies which followed patients long enough,
revealed that antibiotics were effective for the first
several days before resistant organisms began to appear
in the urine. Most authorities feel that the use of
antibiotics to postpone bacteriuria is not indicated be-
cause of side effects, cost, and emergence of resistant
bacteria in the patient and in the medical unit. There
may be exceptions to this generalization. For instance,
patients at high risk for complications of catheter-asso-
ciated bacteriuria, e.g. renal transplant and granulocy-
topenic patients, might benefit from antibiotic use
during short-term catheterization.
3.3. Pre6ention of complications of bacteriuria
Treatment with antibiotics of asymptomatic bacteri-
uria in catheterized patients may seem a logical preven-
tive measure for the complications of fever, urinary
symptoms, acute pyelonephritis, and bacteremia. How-
ever, the data available suggest that this approach is
not particularly useful. Garibaldi et al. noted that in
hospitalized patients, symptomatic catheter-associated
UTIs tended to occur on the first day of bacteriuria
[28]. These patients would be precluded from effective
prevention with antibiotics. Furthermore, even if antibi-
otics prescribed for asymptomatic bacteriuria were
100% effective in preventing the delayed symptomatic
UTIs, for each one prevented, 250 urine cultures would
be required to identify the asymptomatic bacteriuria’s
precipitating treatment. In long-term catheterized pa-
tients, the hypothesis that antibiotic treatment of
catheter-associated bacteriuria will prevent symp-
tomatic UTIs has been tested in a prospective trial. In
the study, cephalexin was administered whenever a
susceptible organism appeared in the urine. There was
no effect upon the incidence of new bacteriuria, number
of bacterial strains per urine specimen, or most impor-
tantly, incidence of febrile episodes [29]. The only
change was a marked increase in antibiotic-resistant
organisms.
These investigations suggest that asymptomatic bac-
teriuria need not be treated as long as the catheter,
short-term or long-term, remains in place. There are
exceptions. One is if such a therapy is part of a plan to
control a cluster of infections by a particular organism
in a medical unit. Another is for patients who may be
at high risk of serious complications (e.g. granulocy-
topenic patients, solid organ transplant patients, and
pregnant women). A third exception includes patients
undergoing urologic surgery. The final possible group is
of patients undergoing other types of surgery, particu-
larly those in whom prostheses may be left in place.
Some patients undergoing long-term catheterization
have recurrent obstructions of the catheter, which are
mostly associated with infections by P. mirabilis and
subsequent encrustation with struvite and apatite crys-
tals. Unfortunately, daily catheter irrigation with nor-
mal saline appears to be ineffective in reducing
obstructions [30]. Interestingly, methenamine prepara-
tions may reduce the incidence of obstruction, possibly
because of biochemical alteration of salt solubility [31].
4. Treatment of complications
For the patient who develops fever and/or signs of
bacteremia, the clinician should rule out sources outside
the urinary tract, catheter obstruction, and, especially
among men, periurethral infection. Urine and blood
cultures should be performed. Many clinicians would
empirically treat such patients with parenteral antibi-
otics to treat possible bacteremia from a bacteriuric
species. Because of the likelihood of bacteria se-
questered in a biofilm on the catheter surface, a reason-
able decision may be to replace or remove the catheter
during therapy of symptomatic catheter-associated bac-
teriuria, a move apparently supported by recent data
[32]. For patients with increasing renal dysfunction or
recalcitrant or recurring bacteremia or fever, a search
for urinary stones may be helpful.
Candiduria may develop in catheterized patients and
its incidence is directly related to the duration of
catheterization and hospitalization and to antibiotic
use. Catheter-associated candiduria is generally asymp-
tomatic and, because its natural history is not well-un-
derstood, its management is unclear. Removal of the
catheter results in the disappearance of candiduria in
up to 40% of patients; simply changing the catheter
results in 20% clearance of candiduria. For asymp-
tomatic patients whose candiduria persists or who must
remain catheterized, appropriate management is a
problem. A randomized trial of using fluconazole ver-
sus irrigation of the bladder with amphotericin B re-
vealed similar eradication rates [33]. A group of
investigators of candidal diseases reached consensus
that, if possible, catheters should be removed from the
urinary tracts of patients with candiduria and such
patients should be treated before undergoing a geni-
tourinary tract operative procedure. Furthermore, if
non-krusei candidal cystitis were to be treated, oral
fluconazole should be the choice [34]. Complications of
 J.W. Warren / International Journal of Antimicrobial Agents 17 (2001) 299–303
candiduria can develop and include fever, renal and
perirenal abscesses, fungus balls, and in patients with
genitourinary abnormalities, disseminated candidiasis.
In these situations, systemic therapy with amphotericin
B or fluconazole and appropriate surgical procedures
are indicated.
References
[1] Daifuku R, Stamm W. Association of rectal and urethral colo-
nization with urinary tract infection in patients with indwelling
catheters. J Am Med Assoc 1984;252:2028–30.
[2] Stark RP, Maki DG. Bacteriuria in the catheterized patient.
What quantitative level of bacteriuria is relevant? N Engl J Med
1984;311:560– 4.
[3] Platt R, Polk BF, Murdock B, et al. Risk factors for nosocomial
urinary tract infection. Am J Epidemiol 1986;124:977–85.
[4] Warren JW, Platt R, Thomas RJ, et al. Antibiotic irrigation and
catheter-associated urinary-tract infections. N Engl J Med
1978;299:570.
[5] Hartstein AI, Garber SB, Ward TT, et al. Nosocomial urinary
tract infection: a prospective evaluation of 108 catheterized
patients. Infect Control 1981;2:380–6.
[6] Bryan C, Reynolds K. Hospital-acquired bacteremic urinary
tract infection: epidemiology and outcome. J Urol
1984;132:494– 8.
[7] Platt R, Polk BF, Murdock B, et al. Mortality associated with
nosocomial urinary tract infection. N Engl J Med 1982;307:637.
[8] Stamm WE. Catheter-associated urinary tract infections: epi-
demiology, pathogenesis, and prevention. Am J Med
1991;91(Suppl 3B):65S–71.
[9] Warren JW, Steinberg L, Hebel JR, et al. The prevalence of
urethral catheterization in Maryland nursing homes: estimates
for the United States. Arch Intern Med 1989;149:1535–7.
[10] Warren JW, Tenney JH, Hoopes JM, et al. A prospective
microbiologic study of bacteriuria in patients with chronic in-
dwelling urethral catheters. J Infect Dis 1982;146:719–23.
[11] Warren JW, Damron D, Tenney JH, et al. Fever, bacteremia,
and death as complications of bacteriuria in women with long-
term urethral catheters. J Infect Dis 1987;155:1151–8.
[12] Muder R, Brennen C, Wagener M, et al. Bacteremia in a
long-term care facility: a five year prospective study of 163
consecutive episodes. CID 1992;14:647–54.
[13] Rudman D, Hontanosas A, Cohen Z, et al. Clinical correlates of
bacteremia in a Veterans Administration extended care facility. J
Am Geriatr Soc 1988;36:726–32.
[14] Warren JW, Muncie HL, Jr, Hall-Craggs M. Acute
pyelonephritis associated with the bacteriuria of long-term
catheterization: a prospective clinico-pathological study. J Infect
Dis 1988;158:1341– 6.
[15] Mobley HLT, Warren JW. Urease-positive bacteriuria and ob-
struction of long-term urinary catheters. J Clin Microbiol
1987;25:2216– 7.
[16] Mobley HLT, Hausinger RP. Microbial ureases: significance,
regulation, and molecular characterization. Microbiol Rev
1989;53:85– 108.
303
[17] Warren JW, Muncie HL, Jr, Hebel JR, et al. Long-term urethral
catheterization increases risk of chronic pyelonephritis and renal
inflammation. J Am Geriatr Soc 1994;42:1286– 90.
[18] Tribe CR, Silver JR. Renal Failure in Paraplegia. London:
Pitman Medical Publishing, 1969.
[19] Locke JR, Hill DE, Walzer Y. Incidence of squamous cell
carcinoma in patients with long-term catheter drainage. J Urol
1985;133:1034– 5.
[20] Nicolle LE, Harding GKM, Kennedy J, et al. Urine specimen
collection with external devices for diagnosis of bacteriuria in
elderly incontinent men. J Clin Microbiol 1988;26:1115–9.
[21] Ouslander JG, Greengold B, Chen S. Complications of chronic
indwelling urinary catheters among male nursing home patients:
a prospective study. J Urol 1987;138:1191– 5.
[22] Ouslander J, Greengold B, Chen S. External catheter use and
urinary tract infections among incontinent male nursing home
patients. J Am Geriatr Soc 1987;35:1063– 70.
[23] King RB, Carlson CE, Mervine J, et al. Clean and sterile
intermittent catheterization methods in hospitalized patients with
spinal cord injury. Arch Phys Med Rehabil 1992;73:798–802.
[24] Duffy LM, Cleary J, Ahern S, et al. Clean intermittent catheter-
ization: safe, cost-effective bladder management for male resi-
dents of VA nursing homes. J Am Geriatr Soc 1995;43:865–70.
[25] Andersen JT, Heisterberg L, Hebjorn S, et al. Suprapubic versus
transurethral bladder drainage after coloposuspension/vaginal
repair. Acta Obstet Gynecol Scand 1985;64:139– 43.
[26] Johnson JR, Roberts PL, Olsen RJ, et al. Prevention of catheter-
associated urinary tract infection with a silver oxide-coated
urinary catheter: clinical and microbiologic correlates. J Infect
Dis 1990;162:1145– 50.
[27] Riley D, Classen D, Stevens L, et al. A large randomized clinical
trial of a silver-impregnated urinary catheter: lack of efficacy and
staphylococcal superinfection. Am J Med 1995;98:349–56.
[28] Garibaldi RA, Mooney BR, Epstein BJ, et al. An evaluation of
daily bacteriologic monitoring to identify preventable episodes of
catheter-associated urinary tract infection. Infect Control
1982;3:466– 70.
[29] Warren JW, Anthony WC, Hoopes JM, et al. Cephalexin for
susceptible bacteriuria in afebrile, long-term catheterized pa-
tients. J Am Med Assoc 1982;248:454– 8.
[30] Hoopes J, Muncie H, Warren J, et al. Once-daily irrigation of
long-term urethral catheters with normal saline. Lack of benefit.
Arch Intern Med 1989;149:441– 3.
[31] Norberg A, Norberg B, Parkhede U, et al. Randomized double-
blind study of prophylactic methenamine hippurate treatment of
patients with indwelling catheters. Eur J Clin Pharmacol
1980;18:497– 500.
[32] Raz R, Schiller D, Nicolle LE. Replacement of catheter im-
proves the outcome of patients with permanent urinary catheter
and symptomatic bacteriuria. 1998; Abstracts of the 38th Annual
ICAAC p. 532
[33] Jacobs L, Skidmore E, Freeman K, et al. Oral fluconazole
compared with bladder irrigation with amphotericin B for treat-
ment of fungal urinary tract infections in elderly patients. CID
1996;22:30– 5.
[34] Edwards JE, Jr, Bodey GP, Bowden RA, et al. International
conference for the development of a consensus on the manage-
ment and prevention of severe candidal infections. Clin Infect
Dis 1997;25:43– 59.