COMMENTARY
Bacteriuria in Individuals Who Become Delirious
Urinary tract infection is considered a common cause of
delirium in the elderly. In long-term care facilities, altered
mental status is the most common indication for ordering
a urine culture,1 and a urinary tract infection is the most
common reason for prescribing antibiotics.2 We hypothesize
that asymptomatic bacteriuria, by which we mean significant
bacteriuria without local urinary tract symptoms or evidence
of systemic infection, does not cause delirium and should
not be treated with antibiotics. Stated differently, delirium is
not a symptom of asymptomatic bacteriuria. The widespread
belief that asymptomatic bacteriuria causes delirium is
harmful. We propose strategies to mitigate this harm until
better evidence is developed. Catheterized patients are not
considered here.
RANDOMIZED CONTROLLED TRIALS
Randomized controlled trials of antibiotic treatment for
asymptomatic bacteriuria show benefit in only 2 groups:
pregnant women and patients soon to undergo invasive
urologic procedures. No benefit is seen in young non-
pregnant women, diabetic women, persons with spinal cord
injury, and persons with indwelling catheters.3 Likewise, 5
randomized controlled trials3 conducted with community-
dwelling and institutionalized elders show no benefit in
mortality, infectious morbidity, or incontinence when
asymptomatic bacteriuria is treated with antibiotics. The
4 trials that describe subjects’ baseline cognition report
a high prevalence of impairment described as follows:
“confusion” (74%), “confusion (42%) or dementia (35%),”
“impaired mental status” (31%), or an average Mini-Mental
State Examination score of only 12 of 30. Although none uses
the term, these trials undoubtedly include many subjects with
delirium.
Partly on the basis of these studies, an expert consensus
conference devised criteria to reduce overtreatment of uri-
nary tract infections in long-term care facilities. The criteria,
endorsed by the Society for Healthcare Epidemiology of
Funding: None.
Conflict of Interest: None.
Authorship: All authors had access to the data and played a role in
writing this manuscript.
Requests for reprints should be addressed to Robin McKenzie, MD,
Division of Infectious Diseases, Johns Hopkins University, Johns Hopkins
Bayview Medical Center, 5200 Eastern Ave, MFL Center Tower, 3rd Floor,
Baltimore, MD 21224.
E-mail address: rmckenz@jhmi.edu
0002-9343/$ -see front matter Ó 2014 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.amjmed.2013.10.016
America (SHEA), do not include delirium as a reason to
treat suspected urinary tract infections in noncatheterized
residents. In a large trial, long-term care facilities were
randomized to use of the SHEA criteria or to standard
care. Use of the criteria was safe: rates of hospitalization or
death did not differ. Antibiotic treatment for urinary tract
infections was significantly reduced in facilities that used
the SHEA criteria, although overall antibiotic use was not.4
Randomized controlled trials also suggest that in some
instances asymptomatic bacteriuria may be protective and
antibiotic treatment may be harmful. Patients with spinal
cord injury who were randomized to bladder instillation of a
nonvirulent Escherichia coli strain had fewer symptomatic
urinary tract infections during the subsequent year than
those randomized to saline instillation.5 Young women with
asymptomatic bacteriuria and previous symptomatic in-
fections were randomized to antibiotic treatment or placebo.
Treated women had more symptomatic recurrences during
1 year’s follow-up.6
EXPERT OPINION
SHEA and the Infectious Diseases Society of America both
recommend against treating asymptomatic bacteriuria in
the elderly (except before invasive urologic procedures).3
One of 5 recommendations of the American Geriatrics
Society’s Choosing Wisely campaign is “Don’t use anti-
microbials to treat bacteriuria in older adults unless specific
urinary tract symptoms are present.” Only SHEA directly
addresses delirium: treatment of asymptomatic bacteriuria
in delirious patients is not recommended unless a urinary
catheter is present.
EVIDENCE SUPPORTING ANTIBIOTIC
TREATMENT OF ASYMPTOMATIC BACTERIURIA
Anecdotal evidence is influential. Many elderly patients
with delirium and abnormal urinalyses are treated with
antibiotics for suspected urinary tract infection and improve
promptly. However, for some who improve promptly urine
cultures subsequently demonstrate mixed urogenital flora,
organisms resistant to the antibiotic given, or sterile urine. In
these cases, improvement is likely due to the brief self-
limited course of some delirium episodes. For example,
careful daily evaluation of 432 hospitalized elderly patients
identified delirium in 64; of these, 44 (69%) had resolu-
tion in 1 day.7 (Such episodes are one extreme in the
256
heterogeneous syndrome of delirium, which also can lead to
lasting impairment.)
To date, studies that suggest a causal relationship
between urinary tract infection and delirium are observa-
tional and lack prospective design, clear definition and
ascertainment of urinary tract infection and delirium, ade-
quate sample size, demonstration of a chronologic link,
adjustment for comorbidities, evaluation for other causes of
delirium, outcomes data after antibiotic treatment, or some
combination of these. We found no studies showing that
antibiotic treatment of asymptomatic bacteriuria is associ-
ated with better delirium outcomes.
INCIDENTAL BACTERIURIA AND INCIDENT
DELIRIUM
Prevalence of asymptomatic bacteriuria in the elderly is
high, with community rates ranging from 11% to 16%
among women and 4% to 19% among men. In long-term
care facilities, the corresponding rates are more than twice
as high: 25% to 50% and 15% to 40%, respectively.3 The
majority do not become delirious. Patients with delirium
from a completely unrelated cause will have asymptomatic
bacteriuria at these rates by chance alone. Rates may be
even higher because factors such as advanced age, dementia,
functional disability, medical illness, and institutional
residence are associated with both syndromes.
WHAT DATA ARE NEEDED?
No data show that delirium-related outcomes improve when
patients with asymptomatic bacteriuria are treated with
antibiotics. Rigorous observational trials would likely be
burdensome and inconclusive. Surveillance for incident
bacteriuria, for example, would require repeated bladder
catheterization of many elderly women. Randomized con-
trolled trials are essential. Such trials would also provide an
opportunity to investigate interactions between host and
bacteria via study of urine and serum biomarkers.
If antibiotic treatment of delirious patients with asymp-
tomatic bacteriuria is shown to be ineffective, 2 difficult and
important treatment questions would follow. First, are
antibiotics necessary for all delirious patients who do have
lower urinary tract symptoms? In the elderly, urinary
symptoms are prevalent and nonspecific.8 Further, ran-
domized controlled trials in young women with lower uri-
nary tract symptoms suggest that delaying or withholding
antibiotic treatment is safe.9 Similar studies in the elderly
would require careful planning and execution. Second, how
should bacteriuria and delirium be managed in patients who
are so impaired that they can neither confirm nor deny
symptoms? Prevalence rates of asymptomatic bacteriuria are
high in these individuals, who are susceptible to mental
status change with slight perturbation. Severely demented
patients are frequently treated with antibiotics and conse-
quently harbor highly resistant bacteria.10 These bacteria
pose an individual and public health threat. Gauging the
The American Journal of Medicine, Vol 127, No 4, April 2014
benefits and harms of antibiotic treatment will require
meticulously cautious study.
CONCLUSIONS
Delirium and urinary tract infection are each complex,
incompletely defined, and poorly understood syndromes.
No evidence beyond anecdote suggests that delirious pati-
ents who have asymptomatic bacteriuria do better with
antibiotic treatment. For these patients, we believe clinicians
should not ask whether there is a “real urinary tract infec-
tion,” but whether the patient is safer with antibiotic treat-
ment or without it. Accepting asymptomatic bacteriuria as
the cause of delirium, dubbing it “urinary tract infection,”
and then giving antibiotics is dangerously complacent.
Until better evidence is developed, we suggest the
following for delirious patients with asymptomatic
bacteriuria as we define it. (1) Use the term “bacteriuria”
or “asymptomatic bacteriuria” rather than “urinary tract
infection.” This nomenclature will encourage continuing
diagnostic evaluation for other causes of delirium and
may moderate the impulse to give antibiotics. (2) Consider
careful monitoring rather than antibiotic administration.
For those with recent Clostridium difficile infection, for
example, the balance surely tips toward careful observa-
tion. (In contrast, patients with features of the systemic
inflammatory response syndrome are excluded from our
definition of asymptomatic bacteriuria and often require
prompt empiric antibiotic treatment.) (3) If the decision is
made to treat with antibiotics, obtain a urine culture be-
forehand and stop treatment if the culture is negative. If
the culture is positive, causality is not established. Whether
the patient has improved, stabilized, or worsened, the
benefits and burdens of continued antibiotic treatment
require ongoing evaluation. Short-course therapy is often
the best course.
Randomized controlled trials will require careful
evaluation and follow-up of many vulnerable subjects. The
goals—to ensure proper evaluation of delirium in the many
patients with incidental bacteriuria, to protect these often
frail individuals from the dangers of unnecessary antibiotic
treatment, and to curtail the enormous costs and society-wide
harms from antibiotic resistance—fully justify this effort.
Robin McKenzie, MDa
Miriam T. Stewart, MDb
Michele F. Bellantoni, MDc
Thomas E. Finucane, MDc
a
Division of Infectious Diseases
Johns Hopkins University
Baltimore, Md
b
Johns Hopkins School of Medicine
Baltimore, Md
(current affiliation: The Children’s Hospital of Philadelphia,
Philadelphia, Pa)
c
Division of Geriatrics
Johns Hopkins University
Baltimore, Md
McKenzie et al Bacteriuria and Delirium
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