2C_Coverpg_Cumitech_557019 3/2/09 1:37 PM Page 1

2C
Laboratory Diagnosis
of Urinary Tract
Infections
YVETTE S. McCARTER, EILEEN M. BURD,
GERRI S. HALL, AND MARCUS ZERVOS

COORDINATING EDITOR
SUSAN E. SHARP

Cumitech
CUMULATIVE TECHNIQUES AND PROCEDURES IN CLINICAL MICROBIOLOGY
2C_Coverpg_Cumitech_557019 3/2/09 1:37 PM Page 2

Cumitech 1C Blood Cultures IV (2005) Cumitech 31 Verification and Validation of Procedures

Cumitech 2C Laboratory Diagnosis of Urinary Tract in the Clinical Microbiology Laboratory
Infections (2009) (1997)
Cumitech 3B Quality Systems in the Clinical Cumitech 32 Laboratory Diagnosis of Zoonotic
Microbiology Laboratory (2005) Infections: Viral, Rickettsial, and Parasitic
Agents Obtained from Food Animals and
Cumitech 7B Lower Respiratory Tract Infections (2004)
Wildlife (1999)
Cumitech 10A Laboratory Diagnosis of Upper Respiratory
Tract Infections (2006) Cumitech 33 Laboratory Safety, Management, and
Diagnosis of Biological Agents Associated
Cumitech 12A Laboratory Diagnosis of Bacterial Diarrhea with Bioterrorism (2000)
(1992)
Cumitech 34 Laboratory Diagnosis of Mycoplasmal
Cumitech 13A Laboratory Diagnosis of Ocular Infections
Infections (2001)
(1994)
Cumitech 16A Laboratory Diagnosis of the Cumitech 35 Postmortem Microbiology (2001)
Mycobacterioses (1994) Cumitech 36 Biosafety Considerations for Large-Scale
Cumitech 18A Laboratory Diagnosis of Hepatitis Viruses Production of Microorganisms (2002)
(1998) Cumitech 37 Laboratory Diagnosis of Bacterial and
Cumitech 21 Laboratory Diagnosis of Viral Respiratory Fungal Infections Common to Humans,
Disease (1986) Livestock, and Wildlife (2003)
Cumitech 23 Infections of the Skin and Subcutaneous Cumitech 38 Human Cytomegalovirus (2003)
Tissues (1988)
Cumitech 39 Competency Assessment in the Clinical
Cumitech 24 Rapid Detection of Viruses by Microbiology Laboratory (2003)
Immunofluorescence (1988)
Cumitech 40 Packing and Shipping of Diagnostic
Cumitech 26 Laboratory Diagnosis of Viral Infections Specimens and Infectious Substances (2004)
Producing Enteritis (1989)
Cumitech 41 Detection and Prevention of Clinical
Cumitech 27 Laboratory Diagnosis of Zoonotic
Microbiology Laboratory-Associated Errors
Infections: Bacterial Infections
(2004)
Obtained from Companion and Laboratory
Animals (1996) Cumitech 42 Infections in Hemopoietic Stem Cell
Cumitech 28 Laboratory Diagnosis of Zoonotic Transplant Recipients (2005)
Infections: Chlamydial, Fungal, Viral, and Cumitech 43 Cystic Fibrosis Microbiology (2006)
Parasitic Infections Obtained
from Companion and Laboratory Animals Cumitech 44 Nucleic Acid Amplification Tests for
(1996) Detection of Chlamydia trachomatis and
Neisseria gonorrhoeae (2006)
Cumitech 29 Laboratory Safety in Clinical Microbiology
(1996) Cumitech 45 Infections in Solid-Organ Transplant
Recipients (2008)
Cumitech 30A Selection and Use of Laboratory Procedures
for Diagnosis of Parasitic Infections of the Cumitech 46 Laboratory Procedures for Diagnosis of
Gastrointestinal Tract (2003) Blood-Borne Parasitic Diseases (2008)

Cumitechs should be cited as follows, e.g.: McCarter, Y. S., E. M. Burd, G. S. Hall, and M. Zervos. 2009. Cumitech 2C, Laboratory Diagnosis of Urinary
Tract Infections. Coordinating ed., S. E. Sharp. ASM Press, Washington, DC.
Editorial Board for ASM Cumitechs: Alice S. Weissfeld, Chair; Maria D. Appleman, Vickie Baselski, Mitchell l. Burken, Roberta Carey, Lynne Garcia, Larry
Gray, Amy L. Leber, Andrea J. Linscott, Yvette S. McCarter, Michael Saubolle, Susan E. Sharp, James W. Snyder, Allan L. Truant, Punam Verma.
Effective as of January 2000, the purpose of the Cumitech series is to provide consensus recommendations regarding the judicious use of clinical micro-
biology and immunology laboratories and their role in patient care. Each Cumitech is written by a team of clinicians, laboratorians, and other interested
stakeholders to provide a broad overview of various aspects of infectious disease testing. These aspects include a discussion of relevant clinical consid-
erations; collection, transport, processing, and interpretive guidelines; the clinical utility of culture-based and non-culture-based methods and emerging
technologies; and issues surrounding coding, medical necessity, frequency limits, and reimbursement. The recommendations in Cumitechs do not repre-
sent the official views or policies of any third-party payer.
Copyright © 2009 ASM Press Address editorial correspondence to ASM Press,
American Society for Microbiology 1752 N St. NW, Washington, DC 20036-2904, USA
1752 N St. NW E-mail: books@asmusa.org
Washington, DC 20036-2904, USA Send orders to ASM Press, P.O. Box 605, Herndon, VA 20172, USA
ISBN 978-1-55581-517-2 Phone: (800) 546-2416 or (703) 661-1593 • Fax: (703) 661-1501
Online: estore.asm.org
All Rights Reserved
10 9 8 7 6 5 4 3 2 1
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Laboratory Diagnosis of
Urinary Tract Infections

Yvette S. McCarter
Department of Pathology, University of Florida College of
Medicine—Jacksonville, 655 W. 8th St., Jacksonville, FL 32209
Eileen M. Burd
Department of Pathology and Laboratory Medicine, Emory
University Hospital, 1364 Clifton Rd. NE, Atlanta, GA 30322
Gerri S. Hall
Section of Clinical Microbiology, Cleveland Clinic,
9500 Euclid Ave., Cleveland, OH 44195
Marcus Zervos
Division of Infectious Diseases, Henry Ford Health System,
2799 West Grand Blvd., CFP3, Detroit, MI 48202
COORDINATING EDITOR: Susan E. Sharp
Kaiser Permanente, 13705 N.E. Airport Way, Portland, OR 97230

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Clinical Considerations and Clinical Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . 2
Significance of UTIs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Clinical Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Pathogenesis, Microbial Flora, and Antimicrobial Resistance . . . . . . . . . . . . . . . . . . . . . . . 4
Diagnostic Approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Frequency of Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Specimen Collection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
SPA and Straight (in and out) Catheterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Clean-Catch Midstream Specimens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Indwelling Catheters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Bagged and Diaper Specimens from Pediatric Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Ileal Conduits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Other Methods of Specimen Collection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Specimen Transport . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Specimen Handling in the Laboratory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Specimen Workup . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Communication between the Clinician and the Laboratory . . . . . . . . . . . . . . . . . . . . . . . . . 9
Approach to Laboratory Workup . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Guidelines for Specimen Inoculation, Incubation, Workup, and Interpretation
of Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Reimbursement and Coding Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
Reporting Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Antimicrobial Susceptibility Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Rapid Urine Screens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
Microscopic Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
Enzyme Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
Bacteriologic Culture Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Unacceptable Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

1
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2 McCarter et al.
INTRODUCTION
U
rinary tract infection (UTI) is one of the most
commonly encountered infectious diseases.
Urine cultures account for the majority of the
workload in the clinical microbiology laboratory. It
is the responsibility of the clinical microbiologist to
provide relevant, cost-effective information to health
care providers for diagnosis and treatment of this
common infection. In contrast to other community
and hospital-acquired infections, there have been few
new pathogens identified as a cause of UTIs. How-
ever, there have been significant changes in antimi-
crobial resistance patterns and increasing antimicro-
bial resistance among urinary tract pathogens. This
updated Cumitech incorporates expanded clinical in-
formation, including additional sections on diagnos-
tic approaches and frequency of testing. For the lab-
oratorians, the guidelines for culture workup and
interpretation have been updated and include meth-
ods of specimen collection. In addition, new sections
on reimbursement, coding issues, and antimicrobial
susceptibility testing have been added.
CLINICAL CONSIDERATIONS
AND CLINICAL DIAGNOSIS
Significance of UTIs
UTI is one of the more common infections and re-
sults in as many as 8 million office visits per year
(109) and about 1 million hospital admissions (73,
121). The exact frequency of UTI is not known; how-
ever, according to current evidence from office and
hospital surveys, it is estimated that there are ap-
proximately 7 million episodes of cystitis (142) and
250,000 episodes of pyelonephritis (159) annually in
the United States. One prospective study determined
the annual incidence of cystitis to be 0.5 to 0.7% per
person-year (68). Although many cases of uncompli-
cated UTI are transient with mild symptoms, studies
suggest that considerable morbidity, mortality, and
cost are associated with all forms of UTI.
UTI is an illness that can occur from infancy
through old age, in otherwise healthy persons, and in
those who are compromised or debilitated. The preva-
lence of UTI varies greatly with age, race, and gender.
Between 4.1 and 7.5% of serious bacterial infections
in febrile pediatric patients are attributed to UTI,
with the highest prevalence (17%) in white females
(134, 160). The majority of patients with UTI are fe-
male, with a lifetime occurrence rate close to 50%
(117, 137). As both sexes age, the incidence of bac-
teriuria increases from less than 5% in young adult
women and less than 0.1% in young adult men to at
least 20% of women and 10% of men older than age
CUMITECH 2C
65 (69). UTIs in women vastly outnumber those in
men (69). This discrepancy could be related to such
factors as the length of the urethra, distance of the
urogenital meatus from the anus, and the antibacte-
rial properties of prostatic fluid (89). Younger pa-
tients are at low risk for occult genitourinary tract
abnormalities and are less likely to have comorbid
conditions. Certain patient subgroups, however, have
complicating conditions that increase the risk for ac-
quiring invasive or systemic infection that include
occurrence in men, children, and pregnant women,
but complications are particularly common in the
elderly, in immunocompromised patients, and in in-
dividuals with neurological disorders, underlying
structural abnormalities, and infection due to antimi-
crobial-resistant organisms.
Because UTI is such a common problem and urine
specimens are easy to obtain from patients, clinicians
submit urine specimens more frequently than almost
any other type of specimen. As a result, urine cultures
account for a major share of the workload in many
clinical microbiology laboratories. Therefore, it is
important for microbiology laboratory personnel to
have an understanding of the clinical context from
which these specimens originate because clinical con-
siderations often profoundly influence the laboratory
evaluation of urine specimens (73).
Clinical Syndromes
UTI encompasses a wide range of clinical syndromes.
Each syndrome is characterized by the presence of
microorganisms within a normally sterile urinary
tract and usually an acute and symptomatic inflam-
matory response.
UTI syndromes differ with respect to the specific
site or the extent of infection within the urinary tract,
the intensity of the inflammatory response, and the
underlying status of the host. The UTI syndromes
commonly encountered in clinical practice include
asymptomatic bacteriuria, cystitis, pyelonephritis, and
complicated and uncomplicated UTI.
Asymptomatic Bacteriuria
Asymptomatic bacteriuria is defined as the presence
of bacteria within the urinary tract in the absence of
symptoms (72) and is generally not considered clini-
cally significant except in pregnant women (because
of the risk of later development of pyelonephritis),
patients who are to undergo an invasive procedure
involving the urinary tract, and children with vesi-
coureteral reflux.
Cystitis and Pyelonephritis
Cystitis is the term applied to UTI presumed to be
confined to the bladder and characterized by symp-
toms suggesting bladder involvement, such as dys-
uria or urinary frequency. Pyelonephritis is a clinical
2C_Cumitech_557019 3/2/09 1:35 PM Page 3
CUMITECH 2C
diagnosis of infection that involves the kidney and re-
nal pelvis and is often associated with signs of systemic
infection, such as fever and rigors. Other findings in-
clude back pain or tenderness and nausea. Clinical cri-
teria are notoriously inaccurate in localizing the site of
UTI. The differential diagnosis of UTI also includes
vaginitis and urethritis that can produce symptoms
similar to UTI.
UTIs in the Elderly
The majority of patients with UTI present with un-
ambiguous symptoms and signs suggestive of this
disease process; therefore, these patients present few
diagnostic challenges for the clinician. However, a
minority of infections, especially those encountered
in the elderly or immunocompromised individual, can
be more clinically challenging. For example, most cli-
nicians have little difficulty making the diagnosis of
UTI in a young woman presenting with 1 day of dys-
uria and frequency, whereas diagnostic challenges are
likely to surface when UTI causes obtundation in an
elderly male. There are many diagnostic methods
available for diagnostic evaluation, so the practitioner
must determine which laboratory tests and/or imag-
ing methods are appropriate and cost-effective in in-
dividuals presenting with symptoms suggestive of UTI.
The elderly are especially susceptible to acquiring
UTI. In fact, UTIs are the most common group of
acute infections observed in nursing home residents
and are the most frequent cause of bacteremia in
both institutionalized and community-dwelling eld-
ers. The case fatality rate associated with bacteremic
UTI is approximately 10 to 30% in this population
(114). UTIs in the elderly frequently present in an
atypical manner. For example, the classic lower tract
symptoms of frequency, urgency, and dysuria, accom-
panied by upper tract findings of chills, flank pain,
and tenderness, may be altered or absent in the elderly
patient or in those with indwelling catheters. Geri-
atric patients can be afebrile and, in some cases, can
even be hypothermic (16). Although acute pyelo-
nephritis in the elderly typically exhibits a septic syn-
drome with such manifestations as fever, tachycardia,
and altered mental status, UTI in the elderly can pre-
sent with a wide range of chief complaints, which can
include mental status deterioration, nausea, vomit-
ing, abdominal pain, or respiratory distress (1, 113,
127).
In the elderly patient residing in a long-term care
(LTC) or hospitalized setting, bacteremic UTI can
present as confusion, cough, and dyspnea. In one
study, new urinary symptoms were the chief com-
plaints in only 20% of cases (15). In another study,
only one-half of older bacteremic UTI patients were
febrile. However, older patients were no more likely
to be afebrile than were younger bacteremic patients
Laboratory Diagnosis of Urinary Tract Infections 3
(40% of whom had normal temperatures) (128). Be-
cause of the wide range of presenting symptoms, the
misdiagnosis of UTI in the geriatric patient ranges
from approximately 20 to 40% (113, 128).
Complicated versus Uncomplicated UTI
Experts have found it problematic to agree on a pre-
cise definition of complicated UTI (cUTI). However,
in the medical literature, the term cUTI has typically
been used to describe an infection that occurs in a pa-
tient with a structural or functional abnormality im-
peding urine flow or in a host with altered defenses
that predispose the patient to a higher risk of treat-
ment failure and/or complications. From a practical,
clinical perspective, the distinction between cUTI and
uncomplicated UTI is important because, when com-
plicating factors are present, antimicrobial resistance
is more common, the diagnosis can be more difficult,
and the response to therapy is often disappointing,
even with the use of agents active against the causa-
tive microbial pathogen. Severe complications in pa-
tients with cUTI are common and can include uro-
sepsis, renal scarring, or end-stage disease. Some
patients with cUTI are not likely to respond satisfac-
torily to short-term antibiotic treatment (98, 147).
UTIs occurring in the presence of catheterization or
functional or anatomical abnormalities of the urinary
tract are also considered cUTIs (131, 133). The term
cUTI is also used to categorize infections occurring in
a host with compromised immune function, altered
mechanical barriers, and other comorbid conditions.
The natural history of UTI in patients with abnormal
urinary tracts and/or altered host defenses has not
been accurately defined. There are various morpho-
logical and functional changes in the urinary tract
that do not influence the natural history of UTI. On
the other hand, there are numerous other factors be-
side morphological and functional abnormalities that
might result in failure of short-term antimicrobial
therapy.
Despite problems in developing a precise defini-
tion of cUTI with predictable prognostic value, the
distinction between complicated and uncomplicated
infections remains important. The spectrum of uro-
pathogens encountered in uncomplicated UTI and
cUTI is different, with Pseudomonas, Enterococcus,
Proteus, and antimicrobial-resistant Escherichia coli
more likely to be implicated as pathogens in cUTI.
Although UTI is common and its prevalence in-
creases with age (reaching about 7% in women 50
years old or older and 3.6% in men 70 years old or
older) (148), renal scarring leading to end-stage dis-
ease is rare. It seems probable that the presence of
complicating factors is necessary to exacerbate the
natural history of the disease. cUTIs, as defined
above, occur in less than 5% of patients with UTI,
2C_Cumitech_557019 3/2/09 1:35 PM Page 4
4 McCarter et al.
most of whom also have recurrent infections. If one
defines cUTI according to guidelines of the Infectious
Diseases Society of America (133), which include
azotemia due to renal disease as a criterion for cUTI,
this proportion can become somewhat higher.
Special note should be taken of factors that in-
crease the risk of acquiring bacteriuria (such as the
presence of an indwelling catheter), promote an in-
fection, and/or contribute to the persistence of an in-
fection that may lead to more serious consequences,
including the development of renal insufficiency
(112). Infections that involve the prostate and uri-
nary tract in ambulatory or nonambulatory elderly
patients are often considered complicated.
Whereas most UTIs in younger women are un-
complicated, those in older women are often compli-
cated. Although uncomplicated cystitis does occur in
men, it is uncommon. Therefore, UTIs in men are gen-
erally considered complicated (133). Bacterial factors,
such as resistant pathogens of nosocomial origin or
infection following recent antimicrobial therapy, also
have been proposed as possible indicators of cUTI.
These criteria, however, should not be used as singu-
lar factors determining cUTI but rather as an indica-
tion for a thorough search for other complicating
factors interfering with the normal function of the
urinary tract.
Obstruction to urine flow, one of the most consis-
tent elements associated with a cUTI, encompasses
intrinsic and extrinsic disorders of the kidney and re-
nal pelvis (e.g., congenital abnormalities, calculi, neo-
plasms, aberrant vessels, strictures, inflammatory
bowel disease, retroperitoneal hematoma, and fibro-
sis); intrinsic or extrinsic abnormalities of the urethra
(e.g., calculi, tumors, vesicoureteral reflux, radiation
inflammatory sequelae, and retroperitoneal fibrosis);
pathology of the bladder and/or bladder neck (e.g.,
benign prostatic hyperplasia, prostate or bladder can-
cer, bladder neck contraction, and vesical calculi);
neurogenic bladder dysfunction; and disease of the
urethra (e.g., polyps, structure, and valves). cUTIs
also encompass those UTIs experienced by hosts with
altered defenses, namely, diabetics, renal transplant
recipients, persistently granulocytopenic patients, and
patients who receive immunosuppressive therapy,
particularly prednisone (131, 133).
Pathogenesis, Microbial Flora,
and Antimicrobial Resistance
UTI is most commonly caused by bacteria from the
patient’s own intestinal flora that enter the urinary
tract by the ascending route via the urethra (16, 55,
72, 73). In children and adults, the fact that E. coli is
by far the most common etiological agent of UTI re-
flects not only the predominance of E. coli in stool
but also specific virulence factors, such as its ability
CUMITECH 2C
to adhere to uroepithelial cells. Occasionally, UTI de-
velops from the bacteremic route from a distant site
of infection, such as with Staphylococcus aureus.
Staphylococcus saprophyticus accounts for a minor-
ity of UTIs in women and presumably arises from an
ascending route. The reservoir of this organism, how-
ever, has not been determined.
For many years, pathogens associated with un-
complicated UTI remained constant, with E. coli
identified as the etiologic agent in 75 to 90% of in-
fections (69). Five to fifteen percent of uncompli-
cated UTIs are caused by S. saprophyticus (55), with
Klebsiella, Proteus, Enterococcus, and Pseudomonas
species seen in much smaller percentages (57, 75,
173). Whereas in uncomplicated UTI, E. coli is by far
the predominant causative pathogen, in hospital-
acquired and cUTI, gram-negative, aerobic bacilli
other than E. coli (e.g., Enterobacter spp., Klebsiella
spp., Serratia spp., Citrobacter spp., Providencia spp.,
Acinetobacter spp., and Pseudomonas spp.) as well
as gram-positive cocci (e.g., enterococci and staphy-
lococci) also are implicated frequently (104, 141). In
elderly men, E. coli continues to be an important or-
ganism, but Proteus, Klebsiella, Serratia, and Pseu-
domonas species, and enterococci have become in-
creasingly important (104). Enterococci are far more
frequent in cUTIs than in uncomplicated UTIs (104,
130, 163). Group B streptococcus (GBS) infection is
observed in neonates secondary to inoculation from
a colonized mother during delivery through the vagi-
nal canal.
Anaerobic bacteria rarely cause UTI despite their
prevalence in fecal flora. Lactobacillus species,
coagulase-negative staphylococci, and Corynebac-
terium species are not considered clinically signifi-
cant isolates in the urine of healthy children between
the ages of 2 months and 2 years (88, 145). Coryne-
bacterium, Lactobacillus, and Streptococcus species
are identified only rarely; when present, they nearly
always represent contamination of the specimen.
Candida species are being increasingly recognized as
causes of UTI, especially in catheterized patients and
in patients who received previous treatment for en-
terococcal UTI (63).
Antimicrobial resistance in urinary tract patho-
gens is an ever-increasing problem, particularly in
hospitals and extended care facility settings. Emerg-
ing resistance of E. coli species to trimethoprim-
sulfamethoxazole (TMP-SMX) is about 22% nation-
ally, and resistance to ciprofloxacin is up to 20% na-
tionally. In the inpatient setting, however, a recent
evaluation of antimicrobial susceptibility data from
1999 to 2002 reveals increasing resistance to both
ciprofloxacin and levofloxacin among E. coli isolates
derived from the in-hospital environment and LTC
setting (66, 176). European studies have shown E. coli
2C_Cumitech_557019 3/2/09 1:35 PM Page 5
CUMITECH 2C
resistance rates to multiple antibiotics, specifically
TMP-SMX, in as many as one-third of patient iso-
lates (167). In a cross-sectional survey of urine cul-
tures obtained in the emergency departments of urban
tertiary care centers in the United States, microbial
resistance was as high as 48% to ampicillin, 25% to
tetracycline, 14 to 28% to TMP-SMX, and 13% to
nitrofurantoin (56).
Similar susceptibility trends have been identified
in gram-negative isolates from LTC facilities, which
are known to be a source of outbreaks for resistant
bacterial infections and colonization. Although there
have been numerous reports about the resistance pat-
terns of such bacteria as methicillin-resistant Staph-
ylococcus aureus and vancomycin-resistant entero-
cocci in LTC facilities, there are few comprehensive
resistance surveillance studies in this setting. One
study evaluating resistance trends in nursing homes
has shown that 36.5% of E. coli showed complete re-
sistance to ciprofloxacin, whereas 2% were resistant
to ceftriaxone and 0.8% were resistant to cefepime
and piperacillin-tazobactam (136).
Diagnostic Approach
Clinical experience suggests that many uncompli-
cated lower UTIs encountered in the outpatient set-
ting can be diagnosed clinically and without the use
of urine cultures. Patients who present with symp-
toms consistent with cystitis or urethritis should un-
dergo a history, physical exam, and urinalysis. The
use of dipstick urinalysis and/or microscopic urinaly-
sis provides a diagnostic yield that is sufficiently spe-
cific and sensitive to establish the diagnosis of un-
complicated UTI. However, urine culture continues
to be important in patients with recurrent UTI or
treatment failure (171). In view of increasing anti-
microbial resistance in urinary pathogens, culture is
necessary for performing antimicrobial susceptibility
testing.
Urinalysis
Urinalysis continues to be the “workhorse” labora-
tory evaluation for establishing the diagnosis of UTI
in a broad range of patients. The primary utility of a
urinalysis is to examine for and document the pres-
ence of pyuria, hematuria, nitrates, leukocyte ester-
ase, and bacteria. Semiquantitative dipstick and mi-
croscopic urinalysis are widely used (14, 71, 78, 81,
103, 161).
The presence of red or white cells in the urine can
help differentiate the location of the infection. Pyuria
is present in almost all patients with urethritis, cysti-
tis, and pyelonephritis. The laboratory or clinical
definition of pyuria (number of white blood cells
[WBC] per high-power field [HPF]) will affect its sen-
sitivity and specificity for establishing the diagnosis
Laboratory Diagnosis of Urinary Tract Infections 5
of UTI. One group found that the presence of more
than 5 WBC/HPF was 85% sensitive for UTI (157),
whereas other authors have reported that more than
10 WBC/HPF was a more reliable breakpoint for
making the diagnosis (14). The presence or absence
of pyuria should be interpreted within the context of
other findings in the urinalysis. Hematuria can be
present with cystitis and pyelonephritis but is rarely
seen in urethritis. Hematuria can be diagnosed semi-
quantitatively with a urine dipstick or quantitatively
on a microscopic urinalysis. Studies looking at dip-
stick hematuria have found a sensitivity of 44% and
a specificity of 88% (108). Microscopic analysis of
the urine also can demonstrate red cell casts that are
indicative of upper tract disease.
Several unique esterases produced by neutrophils
in the urine form the basis of one of the screening
tests for UTI. Leukocyte esterase can be rapidly de-
tected by using a urine dipstick and appears to pro-
vide a reliable method for detecting pyuria with a
sensitivity of 74 to 96% and a specificity of 94 to
98% (49, 78, 80), although it may not distinguish the
presence of pyuria with this degree of accuracy in the
hands of nonlaboratorians (21, 172).
The nitrite test on a urinalysis dipstick is a rapid
screening test for bacteriuria and has been found to be
39% sensitive and 93% specific for bacteria in the
urine in both prospective and retrospective studies
(14, 20, 161). One investigation combined nitrate re-
sults with the presence of microscopic bacteriuria
and/or pyuria (
10 WBC/HPF) and found a sensitiv-
ity and specificity of 71 to 95% and 54 to 86%, re-
spectively (14). Other studies have found that the ac-
curacy of this test can be affected by a low level of
infection (e.g., organisms producing a small amount
of nitrite) or the type of infecting microorganism (e.g.,
organisms that do not reduce nitrate to nitrite) (65).
Urine Culture
Bacteriuria is considered by most clinicians to be the
definitive marker of UTI. Studies conducted in the
1950s found that 105 CFU per ml of urine were in-
dicative of a UTI (65, 76). However, more recent
studies suggest that this level of bacteriuria can miss
a large group of patients with UTI and support the
concept that lower levels (102 to 104 CFU/ml) should
be considered positive (48, 79, 171). In one provoca-
tive study, patients provided urine samples when a
diagnosis of UTI was suspected, but they were not
treated for 2 days after the onset of symptoms. A re-
peat urine culture was obtained 2 days later, at which
time empiric treatment was started. Interestingly, urine
cultures cleared spontaneously in only 5% of the pa-
tients who had a low colony count initially, while
48% now had a colony count of 105 CFU/ml or more
(11).
2C_Cumitech_557019 3/2/09 1:35 PM Page 6
6 McCarter et al.
Lower levels of bacteriuria have been shown to pre-
dict UTI in a variety of settings. Levels greater than
102 CFU/ml have shown a sensitivity of 95% and a
specificity of 85% for the diagnosis of cystitis in
women (158). Male patients with urine samples grow-
ing greater than 103 CFU/ml are considered positive
for UTI (91). All patients with pyelonephritis have a
higher level of bacteriuria, with cultures almost uni-
formly growing at levels greater than 104 CFU/ml. In
summary, studies suggest that antibiotic therapy
should be considered for any patient with symptoms
of a UTI and a culture positive for a urinary tract
pathogen at 103 CFU/ml or greater. For S. saprophyti-
cus, lower colony counts, even as low as 103 CFU/ml,
may be considered significant.
Frequency of Testing
More than one urine culture may be necessary to es-
tablish a diagnosis of UTI because factors such as
timing of specimen collection, excessive fluid intake,
and contaminated voided midstream urine can affect
culture results. After initiation of treatment with an
antimicrobial agent to which the organism is suscep-
tible, bacteria are eliminated from urine within 48 h
in nearly all patients with uncomplicated UTI (37,
118, 155, 166). Therefore, reculturing for proof of
bacteriologic cure is not recommended (37, 118, 155,
166). If symptoms do not resolve or if symptoms re-
cur, a urine culture should be obtained (155). Fever
beyond 48 h is common in children hospitalized with
UTI in spite of negative follow-up urine cultures (37).
Follow-up cultures are recommended at 1 to 2 weeks
after completion of therapy to detect relapses in preg-
nant women and patients at high risk for renal dam-
age, even if they are asymptomatic (155).
SPECIMEN COLLECTION
Appropriate collection of microbiology urine speci-
mens has an important influence on the usefulness of
culture results. Even the most carefully collected
specimens can easily become contaminated with per-
ineal, vaginal, and periurethral flora. Proper urine
collection techniques are critical, since an unreliable
collection often results in the production of inaccu-
rate data.
SPA and Straight (in and out) Catheterization
Suprapubic aspiration (SPA) is considered the gold
standard for obtaining bladder urine because the
specimen is the least likely to be contaminated. SPA
is relatively easy and safe, and it remains the method
of choice for the diagnosis of UTIs in infants, espe-
cially those who appear septic and require immediate
therapy (19, 53, 86, 146). SPA is not routinely per-
CUMITECH 2C
formed on older children and adults. SPA is per-
formed primarily in the inpatient setting. To perform
the procedure appropriately, the bladder must be full.
Skin overlying the bladder is disinfected and the
bladder is punctured above the symphysis pubis by
using a needle and syringe.
In older children and adults, a more commonly
used method for the collection of an uncontaminated
specimen is straight catheterization, also referred to
as “in and out” catheterization. Straight catheteriza-
tion is performed when patients are unable to pro-
duce a reliable self-collected specimen, e.g., patients
with altered mental status or an inability to void due
to neurologic or urologic complications. It is also
used when results from clean-catch midstream speci-
mens are equivocal and a diagnosis is essential. To
avoid potential contamination, meticulous attention
must be paid to proper skin preparation and catheter-
ization technique. Following insertion of the catheter
into the bladder, the first few milliliters of urine are
discarded and the remaining urine is collected into a
sterile container. The first few milliliters of urine are
discarded to eliminate the risk of false-positive cul-
tures caused by urethral flora that could have col-
lected on the catheter during insertion (86). Although
a properly performed straight catheterization can
yield a specimen free of urethral contaminants,
catheterization does carry a risk of introducing bac-
teria into the bladder and inducing infection in up to
5% of patients (61). For this reason, it should not be
used to obtain urine specimens from pregnant pa-
tients (10).
Clean-Catch Midstream Specimens
Collection of a clean-catch midstream specimen, of-
ten referred to as a clean-catch specimen, is the most
frequently used and preferred method of urine col-
lection because it is noninvasive and avoids the risks
inherent to catheterization (88, 120). The clean-catch
method is often recommended despite the fact that
there is little rigorous scientific research that sup-
ports a clean-catch urine sample as the standard for
urine collection. Despite the effort that goes into in-
struction for a clean-catch urine sample, these sam-
ples are among the most prone to contamination with
perineal, vaginal, and urethral flora. Patient instruc-
tion in appropriate collection has been shown to be
important in reducing potential contamination (24).
In women, the appropriate collection of a clean-
catch sample requires the cleansing of the periurethral
area and perineum with two or three cleansing pads
(usually soap and water) and a front-to-back wiping
motion, followed by rinsing with water-soaked pads
or gauze. While the patient holds the labial folds
apart, the patient should void the first few milliliters
2C_Cumitech_557019 3/2/09 1:35 PM Page 7
CUMITECH 2C
of urine to flush bacteria from the urethra. Without
stopping the stream, the patient should use a wide-
mouthed sterile container to collect the midstream
portion of the urine. The container should have a
tight-fitting lid to prevent leakage, and the lid must
be screwed on tightly to prevent leakage of urine.
In men, it is usually sufficient to clean the urethral
meatus with water just before collection, but cleans-
ing pads may also be used. Care must be taken to re-
tract the foreskin in uncircumcised males to minimize
contamination. Urine is then collected in the same
manner as for women.
It is important to keep in mind that the optimum
specimen for nucleic acid amplification assays for
Chlamydia trachomatis and Neisseria gonorrhoeae is
a first-void specimen that has been collected without
cleansing. Thus, if clean-catch midstream specimens
are required for culture, multiple specimens may
need to be collected.
The necessity of performing the clean-catch mid-
stream technique has been called into question be-
cause the collection of a clean-catch midstream urine
specimen is often difficult to obtain in a standardized
fashion. In women, is it the cleansing, the midstream
collection, or the parting of the labial folds that con-
tributes to minimizing contamination? Numerous
studies have compared the contamination rates of
clean-catch specimens with midstream specimens
(samples collected midstream without cleansing) and
found that there was not a significant difference in
the two collection methods (13, 19, 64, 85, 125).
These studies concluded that there is minimal to no
benefit to cleansing the perineum in women prior to
collection of a midstream specimen. Some studies
have indicated that the procedure that plays the most
important role in decreasing contamination in
women is holding the labia apart during sample col-
lection (12, 13). In addition, studies have shown that
the collection of a clean-catch midstream specimen
does not minimize contamination compared to a
first-void specimen in either men or women (21, 70,
88, 90, 91). These studies were performed primarily
on young to middle-aged men and women in the
ambulatory setting. The collection of clean-catch
midstream urine samples in elderly patients is often
problematic because of issues with coordination, in-
continence, and poor hygiene. Catheterization is of-
ten required to obtain an adequate sample in this
population (113). Some studies have suggested that
reliable samples can be collected by cleaning the vul-
val region with water or an iodine solution prior to
collection and collecting samples in a clean container
placed inside the toilet or bedpan (100, 119). In eld-
erly men, a clean “condom” catheter can be as useful
as bladder catheterization (115).
Laboratory Diagnosis of Urinary Tract Infections 7
Indwelling Catheters
Specimens from patients with indwelling (Foley)
catheters should be collected by using sterile tech-
niques and by collecting urine from the collection
port. The collection port, usually a soft rubber di-
aphragm, should be disinfected prior to specimen
collection with a needle and syringe. The catheter
and collection tubing should not be disconnected
(i.e., a closed system must be maintained) to mini-
mize the risk of infection (36). Urine samples should
never be collected from the collection bag because
bag urine is usually contaminated. Instead, the col-
lection tubing can be clamped for a brief period of
time to allow urine to collect for sampling. Although
relied on for diagnosis, urine obtained through an in-
dwelling catheter might not be representative of
urine in the urinary system, especially in patients
with long-term indwelling catheters (168). Organ-
isms colonizing the catheter usually are associated
with a biofilm and do not always colonize the blad-
der. Thus, it is more useful to collect samples follow-
ing the placement of a new catheter rather than from
an old one (52).
Bagged and Diaper Specimens
from Pediatric Patients
Midstream urine samples from toilet-trained children
and older adolescents are often as reliable as speci-
mens collected from adults. As with adults, there re-
mains a question as to whether cleansing prior to col-
lection is necessary (42, 146). However, in infants,
collection of midstream specimens, while technically
possible, is rarely performed. Adhesive (“tinkle”)
bags are frequently used for specimen collection in
infants, especially in the outpatient primary care set-
ting, because these bags are noninvasive. Obtaining
interpretable results from bag urine is frequently dif-
ficult. Bagged urine specimens often yield unaccept-
ably high false-positive results and poor specificity
(8, 144, 152). Contamination is most frequent in fe-
males and uncircumcised males (143). One study
showed the use of bagged specimens for culture can
result in more adverse clinical outcomes, delays in di-
agnosis and treatment, unnecessary treatment, and
hospitalization and concluded that the risks of cul-
turing bagged specimens outweighed the benefits (5).
Most studies agree that negative cultures obtained
from bagged urine effectively rule out a UTI but that
positive cultures, even those containing a single patho-
gen, should be confirmed by collection of urine by
straight catheterization or SPA (8, 42, 53, 146).
Several studies have also advocated the use of
urine from diapers or urine collection pads for cul-
ture and found a good correlation with samples
2C_Cumitech_557019 3/2/09 1:35 PM Page 8
8 McCarter et al.
collected by catheterization or SPA (35, 149). How-
ever, most studies have determined that urine collec-
tion pads, while comfortable and easy to use, produce
specimens with unacceptably high contamination
rates similar to those of bagged specimens (3, 87, 96,
126).
Despite the frequent contamination of bagged and
diaper specimens, their use is likely to continue be-
cause collection is noninvasive and requires limited
time and expertise. Contamination can be minimized
with bag specimens by properly cleansing and rinsing
the perineum prior to applying the bag and removing
the bag promptly following collection (8).
Ileal Conduits
Ileal conduits are created when urine flow from the
kidneys is diverted through a segment of small bowel
(ileum) to an opening or stoma in the abdominal
wall. Urine is captured in an external appliance, usu-
ally a collection bag. Collection of urine from ileal
conduits is performed by trained health care profes-
sionals. The external bag is removed, and the urine is
discarded. The stoma is appropriately disinfected,
and urine is obtained following insertion of a double-
lumen catheter through the stoma into the conduit.
Culture of urine from the collection bag should not
be performed because the urine is usually contami-
nated. Although the ileum is not heavily colonized
with bacteria, issues with colonization of the conduit
and the stoma make the results of urine cultures col-
lected from this site difficult to interpret.
Other Methods of Specimen Collection
Urine specimens occasionally need to be collected
from specific areas of the urinary tract by invasive
methods. Samples collected via percutaneous neph-
rostomy, a thin catheter which passes through the
skin of the back into the kidney parenchyma and re-
nal collecting system, represent urine from high in
the urinary tract (e.g., kidney). Specimens collected
during cystoscopy following passage of a fiberoptic
cystoscope through the urethra into the bladder are
representative of urine in the lower urinary system
(urethra, bladder, and occasionally, the ureter). These
procedures are performed by surgeons, interven-
tional radiologists, or urologists. Cultures of these
samples can be used to determine the site of infection
in the urinary tract (50).
Multiple samples can be submitted in an effort to
localize the site of infection. This is particularly true
in the diagnosis of prostatitis. The gold standard seg-
mented culture technique, which requires the collec-
tion of multiple urine specimens and prostatic secre-
tions, is rarely used today because it is labor-intensive
and costly. A more commonly used technique involves
the collection of urine directly before and after pro-
CUMITECH 2C
static massage (40). Multiple specimens can also be
collected to distinguish between upper and lower
tract infections when using Fairley’s bladder washout
technique in which a urine sample is collected fol-
lowing insertion of an indwelling catheter. Subse-
quently, sterile saline and antibiotic are instilled into
the bladder. After the bladder is emptied and washed,
urine is collected at 10-min timed intervals. Although
this technique is reliable, it is cumbersome, expen-
sive, and invasive.
SPECIMEN TRANSPORT
Urine specimens should be collected appropriately as
outlined above, and the correct label indicating the
usual patient information should be affixed to the
container. The label should include the method for
collection of the urine, i.e., whether the urine is a
clean-catch, catheter-collected, SPA, or other speci-
men. Because laboratories can have guidelines for
processing urine specimens differently when the spec-
imens come from various types of patients, patient
locations, or clinical services, such critical informa-
tion should be included on the container label. The
exact time of collection, prior or current antibiotic
treatment, and excess fluids that the patient is receiv-
ing are also important pieces of information for the
laboratory to obtain for each patient sample.
Urine should be processed as near to the time of
collection as possible to minimize chances for in-
crease in the actual colony count of any pathogens
and contaminants present. If the urine will not be
processed at the point of collection, transport should
be immediate. If it is not possible to transport the
urine to the lab within 2 h, the urine should be re-
frigerated or preserved during transport; if delays ex-
ceed 24 h, a transport device with preservative (usu-
ally boric acid) should be used (44, 51). Preservative
vials or tubes have been demonstrated to preserve the
colony count in urine for 24 to 48 h. The volume of
urine placed into the preservative tube or container
should be
3 ml to ensure growth of most patho-
gens. Use of lesser amounts of urine can result in or-
ganism inhibition by the boric acid and reduce the
optimal growth of some bacteria, in particular En-
terococcus spp. (111). There are also several culture
media onto which a urine sample can be immediately
cultured at the point of collection to reduce issues
with transport delays.
SPECIMEN HANDLING
IN THE LABORATORY
After the urine specimens are received in the labora-
tory, they should be processed immediately or refrig-
erated. Since the colony count of the urine in culture
2C_Cumitech_557019 3/2/09 1:35 PM Page 9
CUMITECH 2C
is a significant part of the interpretation of whether a
pathogen is truly present, efforts should be made to
preserve the urine as close as possible to what it was
like when it was collected. If specimens arrive and
there is no information included as to the time of col-
lection, the ordering site should be contacted to de-
termine the appropriateness of further processing. If
inappropriately collected or transported urine arrives
in the laboratory, it should never be discarded before
the physician is contacted and a determination of
whether another sample can be collected and submit-
ted is made.
SPECIMEN WORKUP
Communication between the
Clinician and the Laboratory
Continual communication between the clinical mi-
crobiology laboratory and health care providers has
been and will continue to be the primary means for
ensuring that specimens are appropriately collected.
Because voided urine specimens are easily contami-
nated with periurethral and perineal flora, it is the re-
sponsibility of the microbiologist to educate health
care providers on methods of proper specimen col-
lection, preservation, labeling, and transport. Such
education ensures that resulting cultures will yield
the most meaningful and clinically relevant results.
Health care providers should particularly be made
aware that the method of collection plays a significant
role in selection of media and quantitative inoculum
as well as the workup and reporting of results. Health
care providers should inform the laboratory with re-
quests to culture for unusual pathogens or organisms
that can require longer incubation times. Microbiol-
ogists should also be available for consultations from
health care providers regarding the interpretation of
culture and antimicrobial susceptibility results.
Approach to Laboratory Workup
Although UTIs are caused by many species of mi-
croorganisms, the majority of infections are caused
by relatively few species. Many of these organisms
can be found as part of the commensal urethral and
fecal flora. Factors such as host age, underlying con-
ditions (e.g., diabetes and structural abnormalities),
and instrumentation have an impact on the etiology
of UTIs.
The amount of polymicrobial bacteriuria is not
well established. One older study has shown that if
the urine is collected appropriately, less than 5% of
urine samples should contain mixed organism types
(18). Another study examined the incidence and sig-
nificance of mixed cultures and concluded that, in
most cases, the mixed finding was significant and not
Laboratory Diagnosis of Urinary Tract Infections 9
necessarily due to improper collection or inappropri-
ate processing (150). The number of mixed-culture
urine specimens that will occur in a laboratory de-
pends on several factors, the most important of
which are how appropriately the specimen was col-
lected, the type of specimen, the time from collection
to processing, and the means of transport during that
time. If the specimen is collected from an indwelling
catheter or from a patient with conditions that might
increase the chance for contamination, mixed cul-
tures can be expected to be as high as 30 to 80% of
all urine cultures (67, 170).
Common Urinary Pathogens
Gram-negative bacilli account for the majority of
UTIs, specifically E. coli, Proteus mirabilis, Klebsiella
pneumoniae, and Pseudomonas aeruginosa. Among
the gram-positive cocci, Enterococcus spp., S. sapro-
phyticus, and GBS are the major etiologic agents. Al-
though the etiologies of community and hospital-
acquired UTI are different, E. coli remains the single
most common etiologic agent of UTI regardless of
age. E. coli is responsible for up to 90% of cases of
uncomplicated UTI in college-aged women (58), 70%
of community-onset cases of uncomplicated UTI, and
as much as 66% of cases of cUTI or acute pyelone-
phritis (83, 122). K. pneumoniae is often second in
incidence to E. coli in community-onset cases and
has been reported to have increased clinical impor-
tance in the renal transplant population, in which
isolates are often multidrug resistant (4). P. mirabilis
and Morganella spp. are often associated with older
patients and patients with renal calculi or stones. P.
aeruginosa is more commonly found in nosocomial
UTI than in community-onset cases. S. saprophyticus
is the most common species of coagulase-negative
staphylococci to cause UTI. S. saprophyticus causes
UTI in adolescents and young adult women who ex-
perience their first UTI and has been found in up to
11% of UTIs in college-aged women (82). However,
it is a rare cause of UTI in elderly females (129). En-
terococcus spp. have been reported in as many as
10% of all UTI (46) and up to 16% in the subset of
nosocomial UTI (140). Enterococci can be more of-
ten associated with patients with underlying struc-
tural abnormalities or in patients who had prior uro-
logic manipulations (102). S. aureus is much rarer as
a causative agent of UTI and often represents infec-
tion in association with S. aureus bacteremia or in
catheterized patients (106). Isolation of GBS from
urine can be used to determine vaginal carriage in the
pregnant female instead of isolation of GBS from
vaginal-rectal swab specimens. In such cases, the lab-
oratory must be informed by the health care provider
that the patient is pregnant. GBS can cause UTI in
pregnant females and in the nonpregnant population,
2C_Cumitech_557019 3/2/09 1:35 PM Page 10
10 McCarter et al.
especially diabetics, where GBS infection is two to
three times more common than in nondiabetic pa-
tients (45, 129).
Rare or Unusual Urinary Tract Pathogens
Special culture conditions are sometimes indicated
for patients with specific diagnoses, suspected fastid-
ious organisms, or particular patient groups.
Corynebacterium urealyticum
Corynebacterium urealyticum (at one time re-
ferred to as Corynebacterium D-2) is an uncommon
cause of UTIs. The organism can be a catalyst for
struvite stone formation because of its strong urease
activity and has been found associated with alkaline-
encrusted cystitis and pyelitis in children and adults
with urinary tract symptoms and the formation of
calculi (99). In one study, the main risk factors for
these conditions were underlying urinary tract dis-
ease, antibiotic treatment, prolonged hospitalization,
and urological manipulation (110). Renal transplant
patients seem to be at particular risk for severe dis-
ease with C. urealyticum (2). In these patients, it is
highly related to obstructive uropathy (94). C. ure-
alyticum should be looked for either when specifically
requested by the ordering physician or in specific
high-risk populations, such as the renal transplant
patient in which routine cultures are negative or in
which the presence of kidney stones is listed on the
requesting order. C. urealyticum will grow on blood
agar plates (BAP) but not MacConkey agar (MAC).
There is a selective medium that contains heart infu-
sion, cysteine, urea, Tween 80, glucose, polymyxin,
aztreonam, fosfomycin, amphotericin B, and a phe-
nol red indicator that can be used for isolation of
C. urealyticum (94). When this medium was used in
a study of 163 renal transplant patients, urine from
16 patients yielded C. urealyticum. Twenty-two pa-
tients (13.5%) were found to have skin colonization
with the organism (94). A prevalence study in 1994
suggested that because the organism is such an un-
usual cause of UTI, routine cultures are unnecessary;
the organism should be sought only if the following
are noted: crystals, alkaline urine, and red blood cells
and/or leukocytes in the urine (110). Linezolid and
quinupristin-dalfopristin have been found to be uni-
versally effective in treating UTI caused by C. ure-
alyticum (138).
Aerococcus spp.
Members of the Aerococcus genus have emerged as
potentially significant pathogens in UTIs. The colonies
can bear a very close resemblance to Enterococcus
spp. and are not easily recognized when isolated from
urine cultures. Aerococcus spp. are catalase-negative,
gram-positive cocci in tetrads and clusters, rather
than the usual pairs and chains of Enterococcus spp.
CUMITECH 2C
Aerococcus urinae is alpha-hemolytic, pyrrolidonyl
aminopeptidase (PYR) negative, and leucine amino-
peptidase (LAP) positive. Aerococcus viridans, much
less commonly associated with UTIs, is PYR positive
and LAP negative. A rarely isolated species, Aero-
coccus sanguinicola, has been associated with UTIs.
It is usually PYR positive and LAP positive, although
there may be some cross-reaction with other species
of Aerococcus. Gram staining of alpha-hemolytic,
catalase-negative cocci should be performed, and if
the smear resembles staphylococci instead of strepto-
cocci or enterococci, identification as Aerococcus
spp. should be considered. Colonies that are alpha-
hemolytic, catalase negative, PYR negative, and LAP
positive can be presumptively identified as A. urinae.
In one study, most patients found to be infected with
A. urinae were elderly males with predisposing con-
ditions and who presented with UTI (178). In an-
other study of 54 patients in which A. urinae was iso-
lated in urine cultures, only 31% of patients with
UTI and 45% of colonized patients had A. urinae
isolated in pure cultures. Both groups had significant
but similar underlying medical conditions, with uro-
logic conditions being predominant. In this study,
more patients were elderly females and significantly
more patients in the UTI group had urinary catheters
(151). Lack of standardized methods and interpretive
criteria for this group of organisms makes it difficult
to assess susceptibility patterns. Aerococcus spp. are
generally susceptible to penicillin, but resistance to
sulfonamides is common in A. urinae.
Gardnerella vaginalis
There are few published reports describing UTIs
with Gardnerella vaginalis. Two reports written more
than 14 years ago describe the finding of this organ-
ism in urine cultures from men. In one study, G. vagi-
nalis was isolated from 0.1% of male urine samples,
and 10 of 15 (67%) patients were symptomatic or
were also found to have significant neutrophils in the
urine (153). In a study from Spain in 1994, G. vagi-
nalis was isolated in pure or mixed culture from 76
specimens of 1,365 (5.6%) urine specimens exam-
ined (9). In 12 of these 76 urine specimens, G. vagi-
nalis was isolated in pure culture, 8 in females and 4
in males. Six patients had symptoms of a UTI; two
patients were pregnant. Pyuria was only detected in 2
of 12 patients. The authors concluded that isolation of
G. vaginalis from urine does not always imply a UTI.
Certainly in the female patient, where G. vaginalis is
part of the normal vaginal flora, its isolation from
urine could suggest contamination with vaginal flora.
If a laboratory isolates G. vaginalis from a urine cul-
ture without the presence of symptoms and/or the
presence of pyuria or in mixed cultures, care should
be taken before reporting this as a probable patho-
2C_Cumitech_557019 3/2/09 1:35 PM Page 11
CUMITECH 2C
gen. If isolated in pure culture, consultation with the
clinician is suggested before reporting it as a poten-
tial cause of the UTI. Routinely extending culture in-
cubation time specifically to recover G. vaginalis is
discouraged.
Haemophilus influenzae
Rarely is Haemophilus influenzae isolated from a
urine culture, and its true incidence is unknown be-
cause urine specimens are not routinely cultured on
chocolate agar or other media that would support its
growth. However, if it is isolated, perhaps in con-
junction with an organism like staphylococcus that
supplies the NAD it needs for growth on blood agar,
the significance of the isolation could be discussed
with the ordering physician. A recent article looked
at UTI caused by H. influenzae and Haemophilus
parainfluenzae in children (60). Over 24 years, 36
cases of Haemophilus spp. bacteriuria were found in

5,000 episodes of UTI in pediatric patients. All but
one child had a prior urinary tract abnormality, in-
cluding malformation, gross reflux, or bladder dys-
function. H. influenzae was isolated more often from
girls and H. parainfluenzae from boys. With recent
overall decreasing incidence of systemic Haemophi-
lus influenzae infections, one would expect that the
incidence is very rare. It is recommended that, with
the exception of specific requests for Haemophilus
isolation from urine, chocolate agar should not be
added to routine urine cultures.
GBS
Laboratories which serve hospitals or physicians’
offices that include obstetrical practices should pro-
vide cultures of vaginal-rectal specimens to detect the
presence of GBS during the third trimester of all
pregnant females. In addition, urine can be used for
recovery of GBS in the pregnant female. The CDC
currently recommends reporting the presence of any
amount of GBS in the urine of pregnant females (29).
This recommendation is based on studies that used
standard laboratory criteria to define bacteriuria
rather than the presence of any amount of GBS in
urine. Previous studies have shown increased risk
only in those women having symptomatic UTIs (17).
The laboratory should work closely with pediatrics
and obstetrics to determine the best process for im-
plementing urine culture reporting. It is imperative
that urine specimens from pregnant females be la-
beled as being from a pregnant patient to facilitate
laboratory reporting of GBS in these women.
Sterile Pyuria
The finding of WBC (5 to 8 WBC per HPF) in a
urinalysis in the absence of bacteria in concurrent
routine urine culture is referred to as “sterile pyuria.”
Almost any injury to the urinary tract can cause ster-
Laboratory Diagnosis of Urinary Tract Infections 11
ile pyuria. Sterile pyuria is also frequent in catheter-
ized patients. Sterile pyuria can also be associated
with systemic or localized diseases and can be a result
of a variety of infectious and noninfectious causes
(39).
In cases of sterile pyuria, Gram staining is impor-
tant. If organisms are seen on Gram stain but not re-
covered in culture and if clinical symptoms persist, it
is appropriate to culture for anaerobes and more
slowly growing organisms, particularly if the patient
has a chronic UTI or anatomic abnormality. The in-
cidence of anaerobic UTI without the presence of
these specific risk factors is very low. UTIs caused by
anaerobes have also been reported in children (22).
Anaerobes have been involved in cases of peri-
urethral cellulitis or abscess, acute and chronic pro-
statitis, prostatic or scrotal abscesses, and retroperi-
toneal or perinephric abscesses. The organisms most
commonly seen in anaerobic UTIs are similar to
those colonizing the distal urethra. Bacteroides and
Fusobacterium spp. are encountered more frequently.
Other potential anaerobic pathogens include Pep-
tostreptococcus, Clostridium, Eubacterium, and Lac-
tobacillus. If anaerobic infection is suspected, a supra-
pubic bladder aspirate should be submitted rather
than clean-catch or catheterized urine. Culturing of
specimens obtained by other collection methods
should only be performed after consultation with the
ordering physician or when bacteria suggestive of
anaerobes are seen in direct Gram stain but fail to
grow in aerobic culture (23).
Sterile pyuria can also be associated with Chlamy-
dia trachomatis, Ureaplasma urealyticum, Mycobac-
terium tuberculosis, systemic fungal infections, or
Leptospira. The genitourinary tract is the most com-
mon site of extrapulmonary M. tuberculosis. Con-
comitant pulmonary findings are present in only
about 66% of newly diagnosed cases of genitouri-
nary tuberculosis (6). In genitourinary tuberculosis,
urine mycobacteriology cultures grow M. tuberculo-
sis in about 90% of cases. Early diagnosis and treat-
ment are sometimes difficult because these infections
are often clinically silent; however, early diagnosis is
very important to prevent irreversible renal destruc-
tion (6). PCR that detects insertion sequence IS6110
has been shown to provide rapid detection of M. tu-
berculosis in urine (105). Because routine urine cul-
tures will be negative for M. tuberculosis, the labora-
tory must rely on the health care provider to request
mycobacterial culture. In cases of suspected renal
tuberculosis, three consecutive first-morning urine
samples should be submitted for mycobacterial cul-
ture (101). UTIs caused by atypical mycobacteria are
rare. Mycobacterium kansasii has been recovered in
urine from patients with prostatic, epididymal, and
disseminated infection (62, 92).
2C_Cumitech_557019 3/2/09 1:35 PM Page 12
12 McCarter et al.
C. trachomatis urethritis should be considered if
the patient is sexually active with multiple partners.
Ureaplasma urealyticum and Mycoplasma hominis
have been implicated as causes of chronic pyelone-
phritis, although this association remains controver-
sial and culture for these organisms is not generally
justified. Urethritis due to Mycoplasma genitalium or
Mycoplasma fermentans has been described in HIV-
infected individuals (38).
Leptospirosis has a broad spectrum of clinical
manifestations and should be considered in patients
with possible occupational or recreational exposure
or after flooding (175). Leptospira appears in urine
after the first week of illness. Prompt recognition and
appropriate antibiotic treatment can dramatically re-
duce patient morbidity and mortality even with se-
vere multiple-organ damage. Culture for leptospires
is performed in reference laboratories and requires
neutralizing the pH of urine to ensure survival of lep-
tospires during transport of the specimen. Culture
is done on Fletcher’s, Stuart’s, or Ellinghausen-
McCullough-Johnson-Harris semisolid media for up
to 13 weeks of incubation. Molecular methods and
serologic tests are preferred for diagnosis and offer
more rapid diagnosis. These tests are performed by a
few reference laboratories.
Noninfectious conditions of the urogenital tract
that can produce sterile pyuria include vesicoureteral
reflux, interstitial cystitis, polycystic kidney disease,
staghorn calculi and stones of smaller size, anatomic
abnormalities, or contiguous infection or tumor rest-
ing on the ureter or bladder. In addition, the finding
of pyuria does not necessarily indicate infection and
does not add significantly to the diagnostic evaluation
in patients with indwelling urinary catheters (162).
Yeast
Detection of yeast, virtually always Candida spp.,
in urine is uncommon in healthy individuals but is an
increasingly important problem in hospitalized pa-
tients, particularly in intensive care units and LTC in-
stitutions (7, 26, 77). Candida albicans is the yeast
most frequently isolated from urine (77). The primary
risk factors for candiduria include diabetes mellitus,
neoplasms, urinary catheterization, periodic use of
broad-spectrum antibiotics or steroids, surgical pro-
cedures within the preceding month, female sex, in-
creased age, and hospitalization longer than 7 days
(7, 26, 77). Diabetes and previous treatment with an-
tifungals are independent risk factors for isolation of
Candida species other than C. albicans (7, 77). Most
patients with candiduria are asymptomatic, and can-
diduria most likely indicates only colonization of the
urinary bladder, perineum, or indwelling urinary
catheter by endogenous Candida species inhabiting
the genital and perineal areas (77). Pyelonephritis or
CUMITECH 2C
nephritis caused by Candida spp. is thought to be a
result of retrograde migration of endogenous organ-
isms (26, 43). Hematogenous seeding of the kidney
cortex can also occur in the course of disseminated
candidiasis (77).
The main difficulty in interpreting the significance
of Candida in the urine is the inability to distinguish
infection from colonization (77). Studies have not
been able to establish clear quantitative criteria for
urine cultures in UTI due to Candida. The detection
of concurrent pyuria can be helpful but only for pa-
tients without long-term indwelling urinary cathe-
ters. For patients with indwelling urinary catheters,
renal infection has been documented with as few as
104 CFU/ml, and colonization has been associated
with 104 to 105 or more CFU/ml (77). Therefore, any
concentration of Candida in the urine could indicate
renal involvement. The presence of candiduria as an
isolated observation probably does not have much
clinical significance and generally does not indicate
risk of subsequent invasive disease. Candiduria may
be more significant in diabetics and patients with ob-
struction, since unusual complications occur more
often in these patients. In neonates, candiduria is sig-
nificant and usually indicates hematogenous spread
to the kidneys.
It is not necessary to inoculate fungal culture me-
dia when yeast cultures are requested. However, to
recover yeast, it is important to inoculate at least
0.01 ml of urine per plate and hold the cultures for
48 to 72 h to detect yeast that grows more slowly or
is present in low numbers. Since clinical significance
is not associated with quantity, clear guidelines for
workup of yeast in urine cultures are not established.
Antifungal treatment is recommended for infants
with very low birth weight, patients undergoing in-
vasive genitourinary procedures, neutropenic pa-
tients, renal transplant recipients, and symptomatic
patients, and workup may be warranted in these in-
stances (95). Because clinical information is not rou-
tinely available to the laboratory, identification of
C. albicans and Candida glabrata is recommended
when present in quantities considered significant for
bacteria, with others identified on request (124).
Guidelines for Specimen Inoculation,
Incubation, Workup, and Interpretation
of Results
A uniform or standard method of urine processing
for all laboratories does not exist. The amount of
urine cultured, the type of media utilized, and the
length of incubation will vary with the type of labo-
ratory and the patient population the laboratory
services (outpatients versus inpatients, nursing home
patients, or the mix of patients that has special needs
[e.g., infants, transplant patients, patients with spinal
2C_Cumitech_557019 3/3/09 3:57 PM Page 13

CUMITECH 2C Laboratory Diagnosis of Urinary Tract Infections 13

cord injuries, etc.]). In many situations, there will be Selection of Media

a need for guidelines that specifically address the va-
riety of patient types. Every laboratory should de-
velop its own guidelines for the processing of urine
samples for culture.
Table 1 shows a simple, useful, and adaptable
urine processing and culture interpretation scheme
based on method of collection. Specimens that are
easiest to collect, such as clean-catch, indwelling
catheter, and pediatric bag samples, are more likely
to contain colonizing organisms. More invasively
collected specimens, such as straight catheter, SPA,
cystoscopy, and nephrostomy samples, are less likely
to contain contaminating organisms.
It is generally accepted that urine cultures should be
processed on blood agar and a gram-negative selec-
tive medium (MAC or eosin-methylene blue [EMB]
agar). Some laboratories also choose to add colistin-
nalidixic acid agar (CNA) or phenylethyl alcohol
agar to facilitate detection of gram-positive organisms
when overgrowth of gram-negative organisms is an-
ticipated. A variety of chromogenic media are avail-
able for the identification and differentiation of urine
pathogens. These chromogenic media can be used for
all urine specimens or those that might be considered
to be at a higher risk for contamination. There are three
chromogenic media: BBL CHROMagar Orientation

Table 1. Scheme for processing and workup of urine cultures based on method of collection

Processing inoculum Minimum

No. of Colony count Extent of
Type of collection and plating length of
isolates (CFU/ml) workupa
media incubation (h)

Noninvasive: clean- 0.001 ml onto BAP and 16 1 10,000 MMIa

catch voided, MAC (or other suit-
10,000 ID and AST
indwelling able gram-negative (if appropriate)
(Foley) catheter, selective medium);
2 Both 10,000 MMI (both isolates)
pediatric bag CNA or phenylethyl
alcohol agar optional Both
10,000 ID and AST (if appropriate)
(both isolates)
1 isolate 10,000 MMI (10,000 CFU/ml)
1 isolate
10,000 ID and AST
(if appropriate)
(≥10,000 CFU/ml)

3 1 isolate ≥100,000 ID and AST
(if appropriate)
(
100,000 CFU/ml)
2 isolates 10,000 MMI (10,000 CFU/ml)
Any other amt MMI (all isolates): report
with message indicat-
ing presence of multi-
ple bacterial morpho-
types and suggestion
for re-collection
Invasiveb: straight 0.01 ml onto BAP and 48 1 1,000 MMI
catheter, SPA, MAC (or other suit-
1,000 ID and AST
cystoscopy, able gram-negative (if appropriate)
nephrostomy selective medium)
2 Both isolates 1,000 MMI (both isolates)
Both isolates
1,000 ID and AST (if appropri-
ate) (both isolates)
1 isolate 1,000 MMI (1,000 CFU/ml)
1 isolate
1,000 ID and AST (if appro-
priate) (
1,000
CFU/ml)

3 1 isolate
10,000 ID and AST (if appropri-
ate) (
10,000 CFU/ml)
2 isolates 1,000 MMI (1,000 CFU/ml)
Any other amt MMI
a
Minimal morphologic identification (MMI) indicates morphologic identification of organisms based on colony/Gram stain morphology, hemolysis, and rapid
same-day biochemical or serological tests. ID, definitive identification; AST, antimicrobial susceptibility testing.
b
This includes urine specifically cultured for yeast or organisms such as Corynebacterium urealyticum that may require extended incubation.
2C_Cumitech_557019 3/2/09 1:35 PM Page 14
14 McCarter et al.
(BD Diagnostics), CPS ID 3 (bioMérieux), and Spec-
tra UTI chromogenic medium (Remel). Specific or-
ganisms will produce colored colonies depending
upon the enzymes they produce and substrates incor-
porated into the medium. The major advantage of
these media is the ability to quickly detect mixed cul-
tures and to reduce the number of identifications that
need to be performed. Several studies have reported
favorable results with use of chromogenic media as a
complement to the other urine culture media (30, 31,
41, 139).
Specimen Inoculation and Incubation
As indicated in Table 1, culture of noninvasive spec-
imens should include quantitative cultures of the
urine that would allow the detection of 104 to 105
CFU/ml. This detection is usually accomplished by
inoculation of 0.001 ml of the urine onto appropri-
ate media. The urine should be spread across the
solid media using a back and forth streaking method.
For more invasively collected specimens or when de-
tection of a low colony count is requested, 0.01 ml of
the urine along with the routine 0.001 ml sample
should be cultured onto appropriate media. Requests
for detection of low colony counts can be ordered
specifically or can be automatically performed on
certain urine types in which
102 CFU/ml is consid-
ered significant for certain pathogens (e.g., urine
specimens collected from transplant patients, urology
patients, or women in their reproductive years). Plates
should be incubated at 35 to 37°C overnight (mini-
mum of 16 h) before being examined (27, 74, 171).
Examination of plates that have been incubated for
less than 16 h is not recommended; colonies are often
very small and it is difficult to differentiate organisms
in mixed cultures (27). There is literature to support
the practice of some laboratories that incubate plates
for 1 day (24 h) before discarding them as negative
(74, 107). There are some laboratories that routinely
hold urine specimens for up to 48 h, in particular,
cultures from invasively collected specimens and if
asked to isolate pathogens such as C. urealyticum,
Haemophilus spp., or other more fastidious bacteria
or yeasts (84, 135).
All culture methods should routinely be able to
detect the common urinary pathogens, such as the
Enterobacteriaceae, staphylococci, streptococci, En-
terococcus spp., and GBS.
Reimbursement and Coding Issues
The CPT codes used for billing standard bacterial urine
cultures include the following:
87086: Culture, bacterial; quantitative colony count,
urine
87088: Culture, bacterial; with isolation and pre-
sumptive identification of isolates, urine
CUMITECH 2C
87077: Aerobic isolate, additional methods required
for definitive identification, each isolate
87184: Susceptibility studies, antimicrobial agent;
disk method, per plate (12 or fewer agents)
87186: Susceptibility studies, antimicrobial agent;
microdilution or agar dilution (minimum inhibitory
concentration or breakpoint), each multiantimicro-
bial, per plate
The Center for Medicare and Medicaid Services
(CMS) has developed National Coverage Determina-
tions (NCD) for some common laboratory tests, in-
cluding urine cultures. The NCD for urine cultures
became effective on 25 November 2002 and lists the
indications and limitations of coverage (28). The fol-
lowing guidelines may be used for billing for bacte-
rial urine cultures:
• Use CPT 87086 for a quantitative urine culture.
This code may be used only one time per encounter.
If a culture shows no growth, this is the only code
billed.
• For each distinct isolate that is presumptively
identified, add CPT 87088. CPT 87088 was re-
vised in 2007 to permit its use multiple times, since
UTIs may be polymicrobial. There are no colony
count restrictions associated with the use of CPT
87088, since significant counts may vary depend-
ing upon the syndrome or clinical circumstance.
This code is most frequently used when multiple
organism morphotypes are isolated and definitive
identification is not performed.
• For each distinct aerobic isolate that is definitively
identified, add CPT 87077. This code may be used
multiple times, since UTIs may be polymicrobial.
Note that only the most definitive procedure used
should be coded and billed. Therefore, if a pre-
sumptive identification is reported for a potential
pathogen but it is followed up by definitive identi-
fication, only the definitive method should be
coded and billed.
• If identification requires immunologic agglutina-
tion (for Streptococcus, Staphylococcus aureus
etc.), CPT 87147 (immunologic method, other than
immunofluorescence [e.g., agglutination group-
ing], per antiserum) may be used in place of CPT
87077. If other methods are used, the correspon-
ding codes should be reported.
• For anaerobic cultures of suprapubic urine, use
CPT 87075 (any source, except blood, anaerobic
with isolation and presumptive identification of
isolates) or CPT 87076 (anaerobic isolate, addi-
tional methods required for definitive isolation,
each isolate).
• Use CPT 87184 and/or CPT 87186, as appropri-
ate, for susceptibility testing of each isolate.
2C_Cumitech_557019 3/2/09 1:35 PM Page 15
CUMITECH 2C
For bacteriologic culture systems, use the follow-
ing CPT codes:
87081: Culture, presumptive, pathogenic organisms,
screening only
87084: with colony estimation from density chart
NCD does not specify limitations on frequency of
testing for urine cultures. Modifier -59 or -91 should
be used to indicate multiple urine cultures for the
same beneficiary on the same date of service if they
are obtained by a different procedure.
Testing for asymptomatic bacteriuria is generally
not indicated and is considered screening in the ab-
sence of clinical or laboratory evidence of infection
(165). Although it is medically appropriate to screen
pregnant women for asymptomatic bacteriuria using
urine culture at 12 to 16 weeks of gestation, it is also
considered screening and, therefore, not covered by
CMS.
REPORTING RESULTS
Regardless of the algorithm used to guide interpreta-
tion, laboratories should report cultures with inter-
pretations and clinical comments to help the provider
assess the clinical relevance of results. Negative cul-
ture results should not be reported merely as “nega-
tive” or “no growth.” Instead, they should be reported
as “sterile or 100 CFU/ml” or “no growth of 100
CFU/ml” if 0.01 ml was cultured or “sterile or
1,000 CFU/ml” or “no growth of 1,000 CFU/ml”
if 0.001 ml was cultured. Positive cultures should be
reported with the colony count and either minimal
morphologic or definitive identification of each po-
tential pathogen isolated. Guidelines for rapid identi-
fication of many common urinary tract pathogens
are available to facilitate rapid reporting (34, 124).
Cultures that yield mixed species of organisms in
varying quantities should indicate the presence of
mixed flora, the quantity found, and a message sug-
gesting re-collection (124). Unusual positive cultures
should be brought to the attention of the health care
provider.
ANTIMICROBIAL SUSCEPTIBILITY TESTING
Treatment of uncomplicated UTI is usually empiric
(54, 97, 169). Although management of UTI has be-
come more complicated because of increasing resis-
tance to commonly used antibiotics, in general, clini-
cians reserve urine culture and susceptibility testing
for complicated cases, treatment failures, and those
patients with risk factors for resistant isolates (e.g.,
repeated infections, recent hospitalization, or recent
antibiotics) (59, 97, 177). The choice of antibiotic to
be used for empiric treatment can be influenced by
Laboratory Diagnosis of Urinary Tract Infections 15
several factors, including the previous experience of
the practitioner and the patient, practice guidelines,
drug marketing, and data on antibiotic susceptibility
patterns of uropathogens in the geographic area. The
data on cumulative antibiotic susceptibility patterns
are generally reported by organism and not by spec-
imen type; therefore, the data can be biased and in-
correctly estimate the rates of resistance for uro-
pathogens in the community (93). Even if data are
stratified by specimen type, bias may exist relating to
referral patterns (e.g., culture of treatment failures
only) and clinical condition (e.g., complicated versus
uncomplicated UTI). Optimal empiric therapy should
be based on data that distinguish complicated from
uncomplicated UTI and resistance percentages of un-
selected uropathogens (116).
Antibiotic susceptibility testing should be per-
formed on isolates from symptomatic patients with
bacteriuria and colony counts that are clinically sig-
nificant for a particular condition (11, 79, 158). The
laboratory should be willing to accommodate special
requests such as workup of low-count bacteriuria in
patients who may have urethral syndrome, etc. Each
laboratory should decide which antibiotics to test
and report after consultation with the infectious dis-
ease practitioners and pharmacy staff.
Routine susceptibility testing for most antibiotics
is standardized, and interpretation of results is based
on anticipated responses to bloodstream infections.
However, there is poor correlation between the dis-
appearance of bacteria in the urine and levels of an-
tibiotics in blood (156). However, there is good cor-
relation between the disappearance of bacteria from
the urine and the level of antibiotic achieved in the
urine (156). Many antibiotics are concentrated in the
renal tubules and achieve high urine levels that are
inhibitory for susceptible microorganisms. The clini-
cal significance of resistance is not completely known
because susceptibility testing does not usually reflect
urinary concentrations of antibiotic. In one recent
outcomes study, clinical results correlated with or-
ganism susceptibility in that patients with UTI due to
a susceptible organism had a better clinical outcome
than those with a resistant organism (97). In another
study, symptoms resolved without further treatment
in 11 of 18 patients with resistant organisms (54).
The practice of performing direct antimicrobial
susceptibility testing of urine specimens has the ad-
vantage of next-day reporting of antimicrobial sus-
ceptibilities and has been evaluated over many years.
However, the performance of direct susceptibility
testing from urine specimens is not recommended
because it is not as accurate compared to standard
methods (124, 154). By special request, direct sus-
ceptibility testing can be performed if the direct Gram
stain suggests that the infection is monomicrobial. If
2C_Cumitech_557019 3/2/09 1:35 PM Page 16

16 McCarter et al. CUMITECH 2C

performed, results must be interpreted by experi-
enced microbiologists and should be reported with a
disclaimer. Direct susceptibility testing must be fol-
lowed by standard susceptibility testing (32, 33, 124).
RAPID URINE SCREENS
Rapid urine screens are nonautomated procedures
used to detect bacteria and/or leukocytes directly in
urine specimens, and they include microscopic and
nonmicroscopic methods (Table 2). The purpose of
rapid urine screens is to provide evidence of UTI be-
fore culture results are available. Rapid testing can be
used to screen urine specimens prior to culture, to
provide a more rapid turnaround time for reporting
negative urine specimens, and to potentially reduce
the number of cultures that have to be performed. If
screening tests are positive, the urine culture is per-
formed. If negative, the urine culture is usually not
performed, but the urine can be saved for a defined
period of time in case the physician requests culture.
In general, these rapid tests are less sensitive than cul-
ture, and the nonmicroscopic methods are best used
in clinics or physicians’ offices, where there is better
control over how and when samples are collected.
Because of their simplicity, the nonmicroscopic tests
are granted waived status under the Clinical Labora-
tory Improvement Amendments (www.cms.hhs.gov/
CLIA/downloads/waivetbl.pdf).
Microscopic Methods
Microscopy of urine from symptomatic patients can
be helpful in rapidly determining the type and count
of bacteria in urine and should be performed upon
request. Microscopic bacteriuria is found in over
90% of specimens from patients whose infections are
associated with colony counts of at least 105 CFU/ml
and is best assessed with a Gram stain of uncen-
trifuged urine (164). Bacteria cannot usually be de-
tected microscopically in infections which yield
lower colony counts (104 CFU/ml). The detection
of bacteria by urinary microscopy is thus very spe-
cific for infection but not sensitive (the absence of mi-
croscopically detectable bacteria does not exclude
the diagnosis). The urine for the Gram stain is pre-
pared by placing 0.01 ml of well-mixed, uncen-
trifuged urine on a clean glass slide and allowing the
specimen to air dry. Following staining, bacteria are
enumerated per oil immersion field with each bac-
terium corresponding to a count of 105CFU/ml of
urine. Although the Gram stain is not a primary stain
to show cellular morphology, the presence and rela-
tive quantity of cells should also be reported. The
presence of WBC indicates pyuria. The presence of
many squamous epithelial cells and multiple bacte-
rial morphotypes suggests contamination.
Enzyme Methods
Dipstick Urinalysis
The nitrate reduction test is based on the reduction of
nitrate in the urine (from diet) to nitrite by the action
of gram-negative bacteria in the urine. The test is
most accurate on a first-morning urine specimen or
on a sample that has been collected 4 h or more after
the last voiding to allow organisms in the bladder
time to metabolize the nitrate. The test is reasonably
effective in identifying infection due to members of
the family Enterobacteriaceae but fails to identify in-
fection due to gram-positive organisms, Pseudomo-
nas spp., or yeast (171).

Table 2. Microscopic and nonmicroscopic rapid urine screens

Screening system
Configuration Comment(s)
(manufacturer)

Gram stain Microscopic method based on staining Each bacterium seen corresponds to a count of 105
reaction of microorganisms; cells are CFU/ml; the presence of many squamous epithe-
also observed lial cells and multiple bacterial morphotypes sug-
gests contamination

Chemstrip urine test strips Enzyme dipstick for detection of Measures nitrate reductase (gram-negative bacteria)
(Roche Diagnostics Corp., bacteria and WBC and leukocyte esterase; most useful in screening
Indianapolis, IN) symptomatic patients
Multistix (Siemens Medical
Solutions Diagnostics,
Tarrytown, NY)

Uriscreen (Savyon Diagnostics,
Ashdod, Israel, distributed
by J&S Medical Associates,
Framingham, MA)
AccuTest (Jant Pharmacal
Corp., Encino, CA)
Enzyme tube test with dehydrated Measures release of catalase from bacteria, leuko-
reagent cytes, and erythrocytes by the addition of hydro-
gen peroxide to urine; primarily intended for
screening asymptomatic patients
2C_Cumitech_557019 3/2/09 1:35 PM Page 17
CUMITECH 2C
Pyuria is demonstrated in almost all acute bacte-
rial UTI, and its absence should call the diagnosis
into question. The leukocyte esterase test for pyuria
will detect both lysed and intact leukocytes and is
based on the presence of intracellular esterases that
catalyze the hydrolysis of esters, releasing compo-
nents that yield a purple color. The leukocyte esterase
test is less sensitive than microscopy in identifying
pyuria but is a useful alternative when microscopy is
not feasible (69).
In commercially available systems such as Chem-
strip urine test strips (Roche Diagnostics Corp., Indi-
anapolis, IN) and Multistix (Siemens Medical Solu-
tions Diagnostics, Tarrytown, NY), the nitrate test
and a test for leukocyte esterase (along with other
chemical parameters) are present on a single reagent
strip that can be read in less than 2 min. The reagent
strip is dipped into the urine and read by comparing
the reactions to a color chart or in an automated
reagent strip reader. Dipstick tests are most useful in
screening symptomatic patients. Dipstick methods are
very simple to perform and an inexpensive method of
screening. However, in patients who urinate fre-
quently, dilution of the two enzymes may result in re-
duced detection. Ascorbic acid concentrations of 25
mg/dl or greater may cause false-negative results in
specimens containing only small amounts of nitrite.
Other interfering substances include elevated glucose
concentrations, high specific gravity, the presence of
cephalexin or cephalothin, and high concentrations
of oxalic acid or tetracycline.
Catalase
Commercially available tests such as Uriscreen
(Savyon Diagnostics, Ashdod, Israel, distributed by
J&S Medical Associates, Framingham, MA) and
AccuTest (Jant Pharmacal Corp., Encino, CA) meas-
ure the release of catalase from bacteria, leukocytes,
and erythrocytes in urine (123). Urine is added to a
test tube containing reagent powder. Hydrogen per-
oxide is added, and the contents of the tube are
mixed. The formation of foam on the surface of the
liquid within 1 to 2 min indicates a positive reaction.
This test is primarily intended for the screening of
symptomatic patients.
BACTERIOLOGIC CULTURE SYSTEMS
Self-contained culture systems have been developed
to aid physicians’ offices and alternate laboratory
sites in the diagnosis of UTI at the point of care.
These systems allow for semiquantitation, isolation,
and presumptive identification of common bacterial
urinary tract pathogens. The currently available sys-
tems are listed in Table 3. Delays in transport and im-
proper storage of specimens are known to adversely
Laboratory Diagnosis of Urinary Tract Infections 17
affect urine culture results. The use of these systems
permits the direct inoculation of urine onto growth
media, minimizing false-positive cultures. The advan-
tages of these systems include ease of inoculation by
unskilled personnel and minimal requirements for in-
cubator space. The use of chromogenic agar in these
systems (CPS ID 3 and DipStreak) also offers the
added advantage of accurate presumptive identifica-
tion of common urinary tract pathogens and differ-
entiation of mixed cultures (139). Although most
systems claim a detection limit of 103 CFU/ml, the
sensitivities of these systems are highest when only
one pathogen is likely and at concentrations of 105
CFU/ml (25, 124, 174). Other disadvantages include
the use of broad interpretive standards by some sys-
tems rather than exact colony counts and the inabil-
ity of some systems to detect potential pathogens
such as group A streptococcus (47). The disadvan-
tages of the conventional dipslides (e.g., Dip N
Count, Uri-Check, and Uricult) include confluent
growth at high organism concentrations, difficulty in
sampling low volumes of urine, and the possibility of
antimicrobial carryover resulting in false-negative re-
sults (132). The addition of a specimen sampling ap-
paratus in some systems (onSite urine culture device
and DipStreak) has alleviated some of these prob-
lems. Overall, these self-contained culture systems
are simple to use and incorporate many advantages
of conventional culture.
UNACCEPTABLE PROCEDURES
Several procedures sometimes used for the diagnosis
of UTIs are considered unacceptable. These include
the following:
Cultures
• Do not culture urine specimens delayed longer
than 2 h without refrigeration or preservative.
• Do not culture 24-h urine collections.
• Do not culture Foley catheter tips.
• Do not culture urine from the bag of a catheter-
ized patient.
• Do not culture urine from a container that has
leaked.
• Request a repeat specimen or obtain the informa-
tion when the collection time and method of col-
lection have not been provided.
• Consider specimens obtained with the same col-
lection method within 24 h to be duplicate speci-
mens. Reculturing for proof of bacteriologic cure
is not recommended. If symptoms do not respond
by 48 h, or if symptoms recur, new urine for cul-
ture should be obtained.
2C_Cumitech_557019 3/2/09 1:35 PM
Table 3. Summary of bacteriologic culture systems for common urinary tract pathogens
Culture system
(manufacturer)
Bullseye urine plate
(HealthLink Diagnos-
tics, Jacksonville, FL)
CPS ID 3 (bioMérieux
Vitek Inc., Durham, NC)
onSite urine culture de-
vice (Trek Diagnostic
Systems,
Cleveland, OH)
Dip N Count (Starplex
Scientific, Etobicoke,
Ontario, Canada)
Uri-Check,
Uri-Check Plus (Troy
Biologicals, Troy, MI)
Uricult (Orion Diagnostica,
Espoo, Finland, distrib-
uted by LifeSign LLC,
Somerset, NJ)
DipStreak (NovaMed,
Jerusalem, Israel)
a
CLED, cystine lactose electrolyte-deficient agar; TSA, tryptic soy agar; XLD, xylose lysine deoxycholate agar; KESC, Klebsiella/Enterobacter/Serratia/
Citrobacter.
b
UriSelect is a nonselective agar with chromogenic substrates for
-glucosidase and
-glucuronidase and tryptophan for detection of tryptophanase and
tryptophan deaminase activity.
Page 18
Configurationa
Five-chambered plate con-
taining TSA with 5%
sheep blood, EMB, XLD,
and citrate urinary agar
surrounding a central
chamber with Mueller-
Hinton agar (for suscepti-
bility testing)
Chromogenic culture media
containing substrates for

-D-glucosidase and

-D-glucuronidase
Transparent hinged plastic
case containing CLED and
MAC
Dip paddle with MAC-CLED
or EMB-CLED attached to
a screw cap and sus-
pended in a clear plastic
vial
Dip paddle in various
combinations:
CLED-EMB
CLED-polymyxin-EMB
CLED-polymyxin-MAC
Paddle is attached to a
screw cap and suspended
in a clear plastic vial
(“Plus” versions have
larger surface areas)
Dip paddle in various
combinations:
CLED-MAC
CLED-polymyxin-MAC
CLED-EMB
CLED-polymyxin-EMB
Paddle is attached to a
screw cap and suspended
in a clear plastic vial
Plastic paddle with various
media attached back-to-
back:
CLED-MAC
TSA-blood-MAC
Columbia CNA-MAC
CLED-UriSelectb
TSA-blood/UriSelectb
MacConkey/UriSelectb
Inoculation and incubation
Inoculation: disposable cali-
brated inoculating loops
(provided)
Incubation: plate, 18–24 h at
33–37°C; susceptibility test-
ing, 16–18 h at 33–37°C
Inoculation: 10-l loop
Incubation: 18–24 h at 37°C
Inoculation: attached plastic
sampler containing 2 bent
tips; the sampler is dipped
into the urine specimen to
take up a standard volume
of urine and is then pulled
out through the case, simul-
taneously inoculating the
surfaces of the media with
a streaking dilution.
Incubation: 18–24 h at 37°C
Inoculation: paddle is im-
mersed in the urine speci-
men and returned to the
plastic vial
Incubation: 18–24 h at 35°C
Inoculation: paddle is
immersed in the urine
specimen and returned
to the plastic vial
Incubation: 18–24 h at
35–37°C
Inoculation: paddle is
immersed in the urine
specimen and returned to
the plastic vial
Incubation: 18–24 h at
35–37°C
Inoculation: a ring with elon-
gated prongs is attached to
the end of the paddle; the
ends of the prongs are
dipped into the urine
sample; upon reinsertion
into the plastic tube, the
prongs inoculate the agar
surfaces
Incubation: 18–24 h at
35–37°C
18
Comment(s)
Actual colony count or estimated colony
count
Presumptive identification by comparing
growth reactions to reference texts or
identification chart provided
Susceptibility testing can be performed
Estimated colony count
Identifies E. coli, Proteeae, Enterococcus,
and KESC group; identification of
other organisms requires additional
biochemical tests
Presumptive identification of GBS
Estimated colony count
Presumptive identification of E. coli,
K. pneumoniae, P. aeruginosa, P.
mirabilis, Proteus vulgaris, S. aureus,
Staphylococcus epidermidis,
Enterococcus faecalis
Estimated colony count
Presumptive identification of E. coli,
Proteus spp., K. pneumoniae,
Enterobacter spp., P. aeruginosa,
E. faecalis, S. aureus
Estimated colony count
Presumptive identification of E. coli,
Proteus spp., K. pneumoniae,
Enterobacter spp., P. aeruginosa,
E. faecalis, S. aureus
Estimated colony count
Estimated colony count
Presumptive identification of E. coli,
Proteus spp., KESC group, E. faecalis,
S. aureus
2C_Cumitech_557019 3/2/09 1:35 PM Page 19
CUMITECH 2C
• Discourage submission of voided or bagged speci-
mens from infants. A catheterized specimen
should be collected.
• Except for suprapubic bladder aspirates, do not
culture specimens for anaerobic culture except by
special request or when bacteria suggestive of
anaerobes are seen in direct smear but fail to grow
on culture.
• It is not necessary to inoculate fungal culture me-
dia when yeast cultures are requested. However, to
recover yeast, it is important to inoculate at least
0.01 ml per plate and hold the cultures for 48 to
72 h to detect yeast in low numbers or that grow
more slowly.
• Do not perform a urine screen without also cul-
turing screen-positive specimens, except in acute
cystitis in females.
Identification
Always identify organisms to the species level if they
are oxidase positive and indole positive because
gram-negative bacilli such as Vibrio spp. and Aero-
monas spp. are considered pathogens regardless of
count.
Susceptibility Testing
Avoid doing susceptibility testing directly from urine
specimens. By special request, direct susceptibility
testing can be performed if the direct Gram stain sug-
gests that the infection is monomicrobial. Results
must be interpreted by experienced microbiologists
and should be reported with a disclaimer. Direct sus-
ceptibility testing must be followed by standard sus-
ceptibility testing.
Reporting Results
• Low-count bacteriuria with members of the fam-
ily Enterobacteriaceae, even in midstream urine
samples, can indicate the early phase of infection
in symptomatic patients. Avoid reporting results
as “mixed flora.”
• Although a count of fewer than 102 CFU/ml is ev-
idence against UTI, avoid reporting “no growth” if
organisms are present. Instead, use 100 CFU/ml.
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