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MEDICAL MICROBIOLOGY INVITED ARTICLE

L. Barth Reller and Melvin P. Weinstein, Section Editors

Laboratory Diagnosis of Urinary Tract Infections


in Adult Patients
Michael L. Wilson1,2 and Loretta Gaido1,2
1
Department of Pathology and Laboratory Services, Denver Health Medical Center, and 2Department of Pathology, University of Colorado School of Medicine,
Denver, Colorado

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Urinary tract infections (UTIs) are among the most common bacterial infections and account for a significant part of the
workload in clinical microbiology laboratories. Enteric bacteria (in particular, Escherichia coli) remain the most frequent
cause of UTIs, although the distribution of pathogens that cause UTIs is changing. More important is the increase in resistance
to some antimicrobial agents, particularly the resistance to trimethoprim-sulfamethoxazole seen in E. coli. Physicians dis-
tinguish UTIs from other diseases that have similar clinical presentations with use of a small number of tests, none of which,
if used individually, have adequate sensitivity and specificity. Among the diagnostic tests, urinalysis is useful mainly for
excluding bacteriuria. Urine culture may not be necessary as part of the evaluation of outpatients with uncomplicated UTIs,
but it is necessary for outpatients who have recurrent UTIs, experience treatment failures, or have complicated UTIs, as well
as for inpatients who develop UTIs.

Urinary tract infections (UTIs) are among the most common ferent diagnostic criteria than those used for the general patient
bacterial infections. It has been estimated that symptomatic population. Because of these factors, physicians frequently rely
UTIs result in as many as 7 million visits to outpatient clinics, on a small number of imperfect laboratory tests to augment
1 million visits to emergency departments, and 100,000 hos- clinical impressions; even when clinical diagnoses are un-
pitalizations annually [1]. UTIs have become the most common equivocal, physicians may order laboratory tests to identify the
hospital-acquired infection, accounting for as many as 35% of cause of the infection and/or to provide isolates for anti-
nosocomial infections, and they are the second most common microbial susceptibility testing. It therefore comes as no sur-
cause of bacteremia in hospitalized patients [2, 3]. The annual prise that the laboratory examination of urine specimens ac-
cost to the health care system of the United States attributable counts for a large part of the workload in many hospital-based
to community-acquired UTI alone is estimated to be approx- laboratories. In fact, in many clinical laboratories, urine cultures
imately $1.6 billion [4]. are the most common type of culture, accounting for 24%–
UTIs are challenging, not only because of the large number 40% of submitted cultures; as many as 80% of these urine
of infections that occur each year, but also because the diagnosis cultures are submitted from the outpatient setting.
of UTI is not always straightforward. Physicians must distin- The purpose of this review is to summarize the laboratory
guish UTI from other diseases that have a similar clinical pre- diagnosis of routine UTI using current diagnostic methods. The
sentation, some UTIs are asymptomatic or present with atypical review will not cover the diagnosis of UTI in special patient
signs and symptoms, and the diagnosis of UTIs in neutropenic populations, a topic that merits a separate review.
patients (who do not typically have pyuria) may require dif-

Received 15 January 2003; accepted 3 December 2003; electronically published 6 April


CAUSES OF UTIs
2004.
The etiological agents of community-acquired and hospital-
Reprints or correspondence: Dr. Michael L. Wilson, Dept. of Pathology and Laboratory
Services, Denver Health Medical Center, Mail Code 0224, 777 Bannock St., Denver, CO 80204- acquired UTIs differ (table 1) [5–14]. Only a limited amount
4507 (michael.wilson@dhha.org). of data has been published regarding changes in the frequency
Clinical Infectious Diseases 2004; 38:1150–8
 2004 by the Infectious Diseases Society of America. All rights reserved.
of causative agents among outpatients. Enteric bacteria (in par-
1058-4838/2004/3808-0019$15.00 ticular, Escherichia coli) have been and remain the most frequent

1150 • CID 2004:38 (15 April) • MEDICAL MICROBIOLOGY


cause of UTI, although there is some evidence that the per- suggests that the cleansing procedures may not decrease urine
centage of UTIs caused by E. coli is decreasing [6, 15]. In contamination rates significantly and, therefore, may be un-
contrast, significant changes in the causes of nosocomial UTI necessary as a routine [18–23]. There may be difficulties with
have been reported since 1980. Bronsema et al. [13] reported proper collection of samples from elderly patients, as well as
that, from 1980 through 1991, the percentage of UTIs caused from those patients who have physical or other types of im-
by E. coli, Proteus species, and Pseudomonas species decreased, pairments, which adds to the importance of collecting speci-
whereas the percentage of UTIs caused by yeasts, group B strep- mens properly to avoid contamination.
tococci, and Klebsiella pneumoniae increased. Weber et al. [6] As discussed below, correct processing and handling of urine
reported different changes in the causative agents of UTI, with specimens, as well as correct interpretation of test results, is
a decrease in the percentage of UTIs caused by Enterobacter dependent on the method used to collect the specimen. It is,
species, but with an increase in the percentage of UTIs caused therefore, of obvious importance for clinicians to specify the
by Acinetobacter species and Pseudomonas aeruginosa. Candida method of collection on the test requisition slip. Other infor-
albicans is the most common cause of funguria, followed by mation that should be included on the test requisition slip
Candida glabrata, Candida tropicalis, Candida parapsilosis, Can- includes the date and time of specimen collection, patient dem-

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dida krusei, and other yeasts [16]. ographic information, and any clinically relevant information
(e.g., whether the patient was treated with antimicrobial agents
or whether anatomic abnormalities, stones, or an indwelling
SPECIMEN COLLECTION, TRANSPORTATION, urinary catheter were present).
AND PROCESSING Specimen transportation. Several studies have demon-
Specimen collection. Suprapubic aspiration is the best strated the adverse effect of delays in transportation or pro-
method to avoid contamination of specimens with bacteria in cessing of urine specimens on their quality [24–26]. In each
the distal urethra. This collection method is used infrequently study, urine specimens were plated within 2 h after collection
because it is not indicated clinically (except in rare circum- and then were plated again after delays of up to 24 h; results
stances), it is invasive and uncomfortable, and it requires too were compared to determine whether delays in plating resulted
much time and too many resources to be practical. Collection in an increase in colony counts. In each of the studies, some
of urine by use of a single catheter (straight catheter technique) of the cultures that were delayed showed increases in the num-
is the next-best technique for obtaining urine specimens with ber of colony forming units (cfu) per mL to 1105 cfu/mL,
minimal contamination, but, again, it is not indicated clinically thereby leading to false-positive results. It should be noted that
for most patients because it is too labor intensive and costly these 3 studies were performed before the publication of current
for routine use and it is invasive. It has added disadvantages, criteria for interpreting quantitative urine cultures and that the
because the process of inserting a catheter through the urethra effect on interpretation would have been even greater if colony
can introduce bacteria into the bladder (and thereby cause counts of 102 or 103 cfu/mL were used to define probable in-
UTI), and rare complications have been reported. fection in specific patients [15]. On the basis of the results of
Most urine specimens are obtained from adult patients via these and other similar studies, it is currently recommended
the clean-catch midstream technique. This technique has the that urine specimens be plated within 2 h after collection unless
following advantages: it is neither invasive nor uncomfortable, specimens have been refrigerated or kept in a preservative [17].
it is simple and inexpensive, it can be performed in almost any Specimen processing. Routine urine cultures should be
clinical setting, there is no risk of introducing bacteria into the plated using calibrated loops for the semiquantitative method.
bladder by catheterization, and there is no risk of complications. This method has the advantage of providing information re-
Colony counts from urine specimens collected by this method garding the number of cfu/mL, as well as providing isolated
correlate reasonably well with those of specimens collected via colonies for identification and susceptibility testing. The types
suprapubic aspiration or straight catheterization [15]. The ob- of media used for routine cultures should be limited to blood
vious disadvantage of this technique is that the urine sample agar and MacConkey’s agar. For urine specimens obtained from
passes through the distal urethra and can become contaminated outpatients, it is not necessary to routinely inoculate a medium
with commensal bacteria. Simple procedures that have been that is selective for gram-positive bacteria, because nearly all
developed to decrease the contamination rate include cleans- UTIs in outpatients are caused by aerobic and facultative gram-
ing of skin and mucous membranes adjacent to the urethral negative bacteria (table 1) [27, 28]. Even in patient populations
orifice before micturition, allowing the first part of the urine in which Staphylococcus saprophyticus is a common cause of
stream to pass into the toilet, and collecting urine for culture UTIs, it is not necessary to use selective media. In contrast,
from the midstream [17]. Although the clean-catch midstream urine specimens obtained from hospitalized patients are likely
method is accepted and used widely, the available evidence to contain enterococci, which have emerged as the second most

MEDICAL MICROBIOLOGY • CID 2004:38 (15 April) • 1151


Table 1. Percentage distribution of etiologic agents of urinary tract infections among outpatients
and inpatients, by pathogen.

Outpatients Inpatients
Percentage Percentage
Pathogen with pathogen Reference(s) with pathogen Reference(s)
Escherichia coli 53–72 [5–9] 17.5–56.7 [5, 6, 8–14]
Coagulase-negative staphylococci 2–7.5 [5, 7] 2.1–12.5 [5, 8–14]
Klebsiella species 6–12 [5–7] 6.2–15.0 [5, 6, 8–14]
Proteus species 4–6 [5–7] 3.8–8.2 [5, 6, 8–13]
Enterobacter species 0.6–5.8 [5–7] 0.9–6.5 [5, 6, 8–14]
Morganella morganii 3.1–4.4 [6] 4.7–6.0 [6]
Citrobacter species 0.1 [5] 0.2–3 [5, 8, 9, 11–13]
Enterococcus species 1.7–12 [5–7] 6.5–15.8 [5, 6, 8–14]

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Staphylococcus aureus 2 [5, 7] 1.6–3.5 [5, 8–12,14]
Staphylococcus saprophyticus 0.2–2 [5, 7] 0.4 [5]
Pseudomonas species 0.1–4 [5–7] 1.3–11 [5, 6, 8–14]
Candida species … … 9.4–15.8 [8, 9, 14]
Other 3–8 [5–7] 1.8–26.3 [5, 6, 8, 10–14]

common cause of nosocomial infections. Laboratories may Gram stain of uncentrifuged urine specimens is a simple
want to consider inoculating urine specimens obtained from method. A volume of urine is applied to a glass microscope
hospitalized patients, or from patients in whom gram-positive slide, allowed to air dry, stained with Gram stain, and examined
bacterial infection is suspected but not documented, to a me- microscopically. The performance characteristics of the test are
dium that is selective for gram-positive cocci. A medium such not well-defined, because different criteria have been used to
as phenylethyl alcohol suppresses the growth of swarming Pro- define a positive test result. In one study, the test was found
teus species and other gram-negative bacilli that can overgrow to be sensitive for the detection of ⭓105 cfu/mL but insensitive
gram-positive cocci in the specimen. Urine cultures should be for the detection of lower numbers of bacteria (table 2) [28].
incubated overnight at 35C–37C in ambient air before being Other investigators have found the test to be of low sensitivity
read. There is no added benefit to incubating routine urine for the detection of UTI [33–42].
cultures for 48 h, provided that specimens are incubated for a The urine Gram stain test has the important advantage of
full 24 h and that urine specimens containing !104 uropath- providing immediate information as to the nature of the in-
ogens or specimens from patients with suspected funguria are fecting bacterium or yeast (rarely infectious agents such as mi-
incubated for 48 h [29–31]. crosporidia) and thereby guiding the physician in selecting em-
Most pathogenic yeasts grow well on blood agar plates, so piric antimicrobial therapy. This is of importance in some
it is unnecessary to use selective fungal media for urine cul- settings, but the Gram stain test has 3 disadvantages that limit
tures, even for samples obtained from patients with suspected its usefulness in most clinical settings. First, it is an insensitive
funguria. Selective fungal media can be used in those rare test, being reliably positive only if the concentration of bacteria
instances in which there is a high clinical probability that a in the urine is ⭓105 cfu/mL; infections with bacterial concen-
UTI is caused by a more fastidious yeast or mold. Urine trations of 102–103 cfu/mL may not be detected by this test.
specimens obtained from patients with suspected mycobac- Second, the test is too labor intensive for it to be practical for
terial UTIs should be processed and plated to the appropriate most clinical microbiology laboratories to offer it on more than
mycobacterial media [32]. a select basis. Last, because it may not detect bacteria at con-
centrations of 102–103 cfu/mL, it should not be used in the
outpatient setting for patients with uncomplicated UTIs. Be-
NONCULTURE METHODS FOR THE
cause of these limitations, its use should be limited to patients
LABORATORY DIAGNOSIS OF UTI
with cases of acute pyelonephritis, patients with invasive UTIs,
Detection of bacteriuria by urine microscopy. Bacteriuria or other patients for whom it is important to have immediate
can be detected microscopically using Gram staining of un- information as to the nature of the infecting pathogen.
centrifuged urine specimens, Gram staining of centrifuged Detection of bacteriuria by nitrite test. Bacteriuria can be
specimens, or direct observation of bacteria in urine specimens. detected chemically when bacteria produce nitrite from nitrate.

1152 • CID 2004:38 (15 April) • MEDICAL MICROBIOLOGY


Table 2. Performance characteristics of Gram staining for detection of bacteriuria.

Performance characteristics, %
Predictive value
Specimen, colony count Sensitivity Specificity Positive Negative Reference(s)
Uncentrifuged urine
NDa 96 95 54 100 [33]
b
ND 91 99 93 99 [33]
⭓10 cfu/mL
5
81–97 71–96 31–90 92–100 [34–36, 38]
⭓104 cfu/mL 86–96 75–99 59–98 80–99 [28, 40]
Centrifuged urine
⭓105 cfu/mL 92–100 8–94 7–77 98–100 [37, 39, 41]
⭓10 cfu/mL
4
74 86 78 84 [39]
⭓103 cfu/mL 63 91 89 69 [39]

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NOTE. The criteria used to assess the clinical importance of isolates and the laboratory methods
used varied between studies; the data are presented only as an overview of reported performance
characteristics of the test. All numbers are rounded to the nearest whole number. ND, not done.
a
⭓1 bacterium per oil immersion field.
b
⭓5 bacteria per oil immersion field.

The biochemical reaction that is detected by the nitrite test is correlates with a urinary leukocyte excretion rate of ⭓400,000
associated with members of the family Enterobacteriaceae (the leukocytes/h [43]. Moreover, the correlation of hemocytometer
pathogens most commonly responsible for UTIs), but the use- counts with urine colony counts has shown that patients with
fulness of the test is limited because nitrite production is not symptomatic UTIs and bacterial concentrations of 1105 cfu/
associated with urinary-tract pathogens such as S. saprophyticus, mL have urine leukocyte counts of ⭓10 leukocytes/mm3 [43].
Pseudomonas species, or enterococci [43]. Another limitation The correlation of hemocytometer cell counts for patients with
to the test is that it requires testing a specimen of the first urine bacterial concentrations of !105 cfu/mL was studied by Stamm
produced in the morning, as ⭓4 h are required for bacteria to et al. [15], who found that urine leukocyte counts of ⭓8 cells/
convert nitrate to nitrite at levels that are reliably detectable. mm3 correlated with bacterial concentrations of !105 cfu/mL
Detection of pyuria by urine microscopy. Pyuria can be in specimens obtained by suprapubic aspiration or straight
detected and quantified microscopically by measuring the uri- catheterization from acutely dysuric female subjects. Although
nary leukocyte excretion rate, counting leukocytes with a hem- using a hemocytometer to count leukocytes is easier than mea-
ocytometer, counting leukocytes in urine specimens using suring urinary leukocyte excretion rates, it is impractical for
Gram staining, or counting leukocytes in a centrifuged speci- clinical laboratories to use a hemocytometer to count leukocytes
men. The advantages to urine microscopy are that leukocytes, on a routine basis. The most practical microscopic method
leukocyte casts, and other cellular elements are observed di- involves counting the number of leukocytes in the sediment of
rectly. One disadvantage to urine microscopy is that leukocytes centrifuged urine specimens. As reviewed by Pappas [43], this
deteriorate quickly in urine that is not fresh or that has not method is inaccurate because of inadequate standardization of
been adequately preserved. In addition, each of these methods the method. For these reasons, and to facilitate the processing
has disadvantages that limit its usefulness as a routine test [28]. of large numbers of specimens, most laboratories use rapid
Because of these disadvantages, urine microscopy should be tests for leukocyte esterase as a surrogate for microscopic leu-
limited to patients in whom pyelonephritis or other more se- kocyte counts.
rious infections are suspected. Detection of pyuria by leukocyte esterase tests. Leukocyte
The most accurate microscopic method for quantitating py- esterase tests are based on the hydrolysis of ester substrates by
uria is to measure the urinary leukocyte excretion rate [43]. proteins with esterolytic activity [44]. Human neutrophils pro-
Patients with symptomatic UTIs have urinary leukocyte excre- duce as many as 10 proteins with esterolytic activity. These
tion rates of ⭓400,000 leukocytes/h [43]. The test is impractical proteins react with ester substrates to produce alcohols and
for clinical use, however, making it necessary for laboratories acids that then react with other chemicals to produce a color
to use other methods. A simple and inexpensive alternative is change that is proportional to the amount of esterase in the
to count urine leukocytes with a hemocytometer. Comparison specimen [44]. These tests have the advantage of detecting both
of hemocytometer counts with urinary leukocyte excretion rates esterases in intact leukocytes and esterases released after cell
has shown that a hemocytomer count of ⭓10 leukocytes/mm3 lysis; therefore, even specimens that have not been preserved

MEDICAL MICROBIOLOGY • CID 2004:38 (15 April) • 1153


properly may yield a positive test result. Leukocyte esterase tests the studies. Nonetheless, the results are sufficiently consistent
can yield false-positive test results when the urine is contam- to allow some conclusions to be made. First, the 2 tests, when
inated with bacteria present in vaginal fluid; when the specimen used together, perform better than either test performs when
contains eosinophils or Trichomonas species, both of which can used alone. Second, the tests have better performance char-
act as sources of esterases; and when oxidizing agents or for- acteristics for detecting bacteriuria at high colony counts than
malin react with the test strips to generate false-positive test at low colony counts [51]. Third, these tests have low sensitivity,
results [44, 45]. Leukocyte esterase tests may show a decrease high specificity, low positive-predictive values, and high neg-
in positive test results when the specimen has an elevated spe- ative-predictive values. Taken together, the performance char-
cific gravity and/or elevated levels of protein and glucose; when acteristics of these tests make them useful as a way to rule out
boric acid preservatives are present; when large amounts of bacteriuria on the basis of a negative test result.
ascorbic or oxalic acid are present; and when the patient has A number of drugs can change the color of urine; abnormal
received antimicrobial agents, such as cephalothin, cephalexin, urine color may affect urine tests that are based on the inter-
or tetracycline [44, 45]. High concentrations of tetracycline may pretation of color changes. In some cases, this can mask color
result in false-negative test results [45]. As shown in table 3, changes, and in others, it may result in false-positive interpre-

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when it is used alone, the leukocyte esterase test has a relatively tations [45].
low sensitivity and specificity and low positive predictive values
as a test for UTIs, with higher negative predictive values [28,
CULTURES AND THE LABORATORY
35, 38, 46–54].
DIAGNOSIS OF UTIs
Simultaneous detection of bacteriuria and pyuria. Com-
mercial urinalysis products include tests for both nitrite and Routine bacterial urine cultures. Urine culture may not be
leukocyte esterase, thus providing tests for both bacteriuria and necessary as part of the evaluation of outpatients with uncom-
pyuria. As shown in table 3, a number of clinical evaluations plicated UTIs [55, 56]. However, urine cultures are necessary
have defined the performance characteristics of these tests. The for outpatients who have recurrent UTIs, experience treatment
evaluations are not directly comparable because the studies failures, or have complicated UTIs. Urine cultures are also nec-
occurred over a 20-year period in a number of different lab- essary for inpatients who develop UTIs. The bacterial culture
oratories and health care settings, there were a multiplicity of remains an important test in the diagnosis of UTI, not only
study designs, and various commercial products were used in because it helps to document infection, but also because it is

Table 3. Performance characteristics of leukocyte esterase and nitrite tests, alone or in combination,
for detection of bacteriuria and/or pyuria.

Performance characteristics
Predictive values
Test, colony count Sensitivity Specificity Positive Negative Reference(s)
Leukocyte esterase
⭓105 cfu/mL 68–98 59–96 19–86 91–97 [35, 48, 49, 53, 54]
⭓104 cfu/mL 64–77 59–83 16–52 89–96 [47, 49, 53]
⭓103 cfu/mL 62–79 55–84 3–81 51–99 [49, 52, 53]
Nitrite
⭓105 cfu/mL 19–45 95–98 50–78 82–89 [48, 49, 53, 54]
⭓104 cfu/mL 8–39 97–98 27–81 85–87 [49, 53]
⭓103 cfu/mL 0–50 48–98 0–82 37–99 [49, 52, 53]
Leukocyte esterase and nitrite
⭓105 cfu/mL 35–84 98–100 84 98 [48, 53]
⭓103 cfu/mL 0–45 62–98 0–66 42–99 [52, 53]
Leukocyte esterase and/or nitrite
⭓105 cfu/mL 67–100 67–98 40–95 84–96 [28, 38, 48–50]
⭓10 cfu/mL
4
74–79 66–82 42–54 91–92 [49, 50]
⭓103 cfu/mL 71–84 41–83 49–81 46–90 [49, 50, 52]

NOTE. The criteria used to assess the clinical importance of isolates and the laboratory methods used varied between
studies; the data are presented only as an overview of reported performance characteristics of the tests. All numbers are
rounded to the nearest whole number. cfu, colony-forming units,

1154 • CID 2004:38 (15 April) • MEDICAL MICROBIOLOGY


Table 4. Interpreting culture results for urine specimens yielding common
urinary tract pathogens.

Probability of
contamination, no. of Quantitation,
microorganisms isolated cfu/mL Interpretation
a
Low probability
1 !102 Probable contaminant
1 ⭓10 2
Significant isolate
2 !102 for each Probable contaminants
2 ⭓102 for each Significant isolates
2 ⭓102 for 1 Significant isolate and contaminant
⭓3 ⭓10 for 1
5
Significant isolate and contaminants
⭓3 ⭓105 for each Probable contaminants
b
High probability

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1 !102 Probable contaminant
1 ⭓10 2
Significant isolate
2 ⭓105 for each Significant isolates
2 ⭓105 for 1 Significant isolate and contaminant
2 !105 for each Probable contaminants
⭓3 ⭓105 for 1 Significant isolate and contaminants
⭓3 ⭓10 for each
5
Probable contaminants

NOTE. cfu, colony-forming units.


a
Urine specimens obtained via aspiration (suprapubic, bladder, ureter, renal pelvis, kidney)
or single (straight) catheterization, specimens obtained in the operating room, and urine spec-
imens obtained from patients receiving antimicrobial therapy.
b
Urine specimens obtained via clean catch technique, from indwelling catheters (urinary
or suprapubic), or from nephrostomy tubes, ureterostomy tubes, or ileal loops.

necessary for determination of the identity of the infecting ingly, the most appropriate diagnostic criterion for urine culture
microorganism(s) and for antimicrobial susceptibility testing. specimens obtained via suprapubic aspirate or catheterization
This is particularly true because of the increased incidence of is a bacterial concentration of ⭓102 cfu/mL [15, 59].
antimicrobial resistance. Routine follow-up cultures for test-of-cure are not recom-
The most commonly used criterion for defining significant mended for patients who have been treated for asymptomatic
bacteriuria is the presence of ⭓105 cfu per milliliter of urine bacteriuria, acute uncomplicated cystitis, or acute uncompli-
[15, 57, 58]. This criterion was established only for women cated pyelonephritis [60] and for whom there is evidence of
with acute pyelonephritis or women who were asymptomatic an appropriate clinical response to therapy [2]. Follow-up cul-
but had multiple urine cultures that yielded this number of tures are, however, recommended for patients with infections
bacteria; however, the criterion is often applied to other patient that do not respond to therapy, patients who have recurrent
populations [15]. Most patients with UTIs, however, do not UTIs, patients who have anatomic or functional abnormalities
fall into either category, and 30%–50% of patients with acute of the urinary tract, or patients who continue to have unex-
urethral syndrome will have colony counts of !105 cfu/mL [15]. plained abnormal urinalysis findings.
For this reason, many laboratories have opted to use lower Anaerobic bacterial urine cultures. The normal flora of
colony counts as a criterion for interpreting and reporting re- the large intestine, vagina, and skin contain large numbers of
sults. One common criterion is a colony count of 104 cfu/mL, anaerobic bacteria. Because anaerobic bacteria cause UTIs only
which would be expected to increase the sensitivity of the test in rare circumstances, however, recovery of anaerobic bacteria
without making the test impractical for clinicians and labo- from urine by culture is of no clinical relevance for most pa-
ratories to use. tients with UTIs. Urine cultures for anaerobic bacteria should
Catheterized patients (who may have low concentrations of be limited to patients with anatomic abnormalities (e.g., en-
bacteria that can progress to higher concentrations) and many terovesicular fistulae) that increase the likelihood of infection
patients with infections of the lower urinary tract have colony with anaerobic bacteria.
counts much lower than 105 cfu/mL if the specimens are ob- Fungal urine cultures. As stated previously, microbiologic
tained via suprapubic aspirate or catheterization [59]. Accord- detection of almost all cases of funguria can be achieved using

MEDICAL MICROBIOLOGY • CID 2004:38 (15 April) • 1155


routine bacterial media. There are limited data regarding the On the other hand, interpretation of urine cultures that yield
use of tests other than culture to detect funguria. Huang et al. mixed flora in varying quantities can be difficult. Although a
[61] reported that pyuria did not correlate with funguria, re- number of algorithms have been developed to guide the in-
gardless of whether patients had concomitant bacteriuria or an terpretation of urine cultures, the large number of potential
indwelling urinary catheter. Kauffman et al. [16] reported that, combinations of microorganisms—in varying quantities—
of 648 patients with funguria whose urine specimens underwent and the need to correlate these results with different types of
urinalysis, 354 (54.6%) had pyuria and 230 (35.5%) had he- UTIs limits the usefulness of any algorithm. One algorithm
maturia. Of the 648 patients, only 410 had urine specimen is presented in table 4.
reports that included a comment as to the presence or absence Irrespective of the algorithm used to guide interpretation,
of yeasts; 247 (60.2%) of these 410 patients had urine specimens laboratories should report culture results with interpretive
that were positive for yeasts [16]. On the basis of these obser- guidelines to help the ordering physician assess the clinical
vations, and because the nitrite test would be of no use in the relevance of the results. Cultures that yield unambiguous cul-
detection of funguria, there appears to be limited value in using ture results should be interpreted and reported as such. Test
urinalysis in the detection of funguria at this time. This con- reports for cultures that yield mixed flora in varying quantities

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clusion may change as further information is published re- should specify the microorganisms that were recovered, the
garding the clinical outcomes of patients with funguria, the quantity of each microorganism, and the probable clinical im-
results of laboratory testing of urine specimens, and the effects portance of each isolate.
of chemotherapy. Antimicrobial susceptibility testing. Each laboratory
Mycobacterial urine cultures. Although it is an uncom- should have guidelines by which pathogens are tested for an-
mon finding in the United States, extrapulmonary tuberculosis timicrobial susceptibility. These guidelines should be developed
may involve the genitourinary tract. The traditional laboratory and antimicrobial susceptibility tests should be performed and
diagnosis of mycobacterial UTI is by use of acid-fast smears reported according to the most recent version of the NCCLS
and mycobacterial cultures [62], but more recent data suggests guidelines. Bacterial or fungal isolates of uncertain clinical im-
that the diagnosis can also be made by use of nucleic acid portance should not be tested for antimicrobial susceptibility
amplification tests [63, 64]. There are, however, only limited for purposes of routine patient care.
data about the use of such assays for the diagnosis of genito-
urinary tuberculosis, and none of these assays have been cleared
or approved by the US Food and Drug Administration for this CONCLUSION
indication. Until better data are available, the authors recom- Most patients with uncomplicated acute cystitis have cases that
mend against the routine use of nucleic acid amplification tests, are clinically straightforward, and they may not require any
particularly with patients for whom there is low clinical sus- laboratory testing beyond urinalysis. For a significant number
picion of genitourinary tuberculosis. of patients, however, the clinical history and physical findings
Because nontuberculous mycobacteria, such as Mycobac- alone may be insufficient to make a definitive diagnosis of UTI.
terium smegmatis, may be present as colonizing flora (and to For those patients and for patients with complicated UTIs,
reduce the number of contaminating bacteria), the external laboratory tests are necessary to make the diagnosis and to
genitalia should be washed before specimens are obtained [64]. provide specific information regarding the identity and the an-
The best specimen for mycobacterial urine cultures is the first timicrobial susceptibility pattern of pathogens. Both the lab-
voided urine. Multiple specimens may be needed, because my- oratory diagnosis and the clinical diagnosis of laboratory test
cobacterial culture results are positive for 25%–95% of patients results must be made in light of the method of collection used;
and smears are positive for 50%–70% of patients with tuber- clinicians should specify the method of collection on test req-
culous genitourinary tract infections [62]. uisition forms. Of the available laboratory tests, urinalysis is
Interpretation of urine culture results. Microbiologists helpful primarily as a means of excluding bacteriuria, but it is
need to interpret the microbiologic relevance of growth on not a surrogate for culture. Although cultures identify patho-
culture plates to determine whether further identification and gens, the accurate interpretation of culture results requires clin-
antimicrobial susceptibility testing are necessary. Most culture ical information that is usually available only to the clinician.
results can be interpreted readily; no growth and gross con- We hope that infectious diseases physicians, in particular, will
tamination are both unambiguous results, as are pure cultures understand both the strengths and the limitations of the lab-
of common pathogens growing in a quantity of 1105 cfu per oratory-based diagnostic studies for UTIs that have been re-
milliliter of urine. The interpretation of cultures that yield viewed in this article, and we hope that they will incorporate
pure growth in lower quantities is also clear for specimens this understanding with current treatment guidelines [65] to
obtained via suprapubic aspiration or straight catheterization. optimize patient care.

1156 • CID 2004:38 (15 April) • MEDICAL MICROBIOLOGY


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