31.  Screening for Asymptomatic Bacteriuria

RECOMMENDATION

Screening for asymptomatic bacteriuria by urine culture is recommended for all pregnant women

(see Clinical Intervention). There is insufficient evidence to recommend for or against routine

screening for asymptomatic bacteriuria in diabetic or ambulatory elderly women, but

recommendations against such screening may be made on other grounds. Routine screening for

asymptomatic bacteriuria in other persons is not recommended.

Burden of Suffering

Asymptomatic bacteriuria is defined as a significant bacterial count (usually 105 or 106

organisms/mL) present in the urine of a person without symptoms. Asymptomatic bacteriuria

may precede symptomatic urinary tract infection, characterized by dysuria, frequency, pain,

fever, etc., which accounts for over 6 million outpatient visits each year.1 Urinary tract infection

may be associated with renal insufficiency and increased mortality in adults, but these

complications rarely occur among those without underlying structural and functional diseases of

the urinary tract.2 In both institutionalized and noninstitutionalized elderly, urinary tract

infection is the most common cause of bacteremia, which may be associated with a 10-30% case

fatality rate.3,4 Most such bacteremia occurs in residents with indwelling catheters or urinary

tract abnormalities, however. Similarly, most of the 300,000 hospitalizations each year for

urinary tract infections1 involve patients with indwelling urethral catheters.

In children, asymptomatic bacteriuria may be a sign of underlying urinary tract abnormalities.

About 10-35% of infants and children with asymptomatic bacteriuria have vesicoureteral reflux

and 6-37% have renal scarring or other abnormalities (the lower prevalences generally

reflecting more stringent definitions of abnormality),2,5-8 whereas such abnormalities are

uncommon in the general population of children.2,9 Children with major structural

abnormalities, chronic pyelonephritis, or severe vesicoureteral reflux are at increased risk of

renal scarring, obstructive renal atrophy, hypertension, and renal insufficiency.2

Pyelonephritis, reflux nephropathy, and urinary tract malformations may cause as much as one

fifth of cases of renal failure in children.10 In pregnancy, 13-27% of untreated women with

asymptomatic bacteriuria develop pyelonephritis, usually requiring hospitalization for

treatment.11-14 Bacteriuria in pregnant women increases the risk for preterm delivery and low

birth weight about 1.5-2-fold, and may also increase the risk of fetal and perinatal

mortality.15-23

The risk of acquiring bacteriuria varies with age and sex. Asymptomatic bacteriuria in term

infants is more common in males (estimated prevalence of 2.0-2.9% vs. 0.0-1.0% in females),

but it is considerably more common in girls after age 1 (0.7-2.7% in girls vs. 0.0-0.4% in

boys).2,5-8,24 Approximately 5-6% of girls have at least one episode of bacteriuria between

first grade and their graduation from high school, and as many as 80% of these children

experience recurrent infections.2 Asymptomatic bacteriuria in adulthood is more prevalent in

women than men (3-5% vs. <1% in those under 60 years), and its prevalence increases with

age.25-27 Asymptomatic bacteriuria is a common finding in older persons, especially those who

are very old (20% of women and 10% of men >80 years old living in the community) or

institutionalized (30-50% of women and 20-30% of men).3,4 Bacteriuria occurs in 2-7% of

pregnant women; of those who are not bacteriuric at initial screening, 1-2% will develop

bacteriuria later in the pregnancy.28-30 An increased prevalence of asymptomatic bacteriuria

(about 10-20%) has been reported in asymptomatic diabetic women, although several studies

have found no increase when compared to matched nondiabetic controls or to expected age- and

sex-specific population rates.2,31-34

Accuracy of Screening Tests

The most accurate test for bacteriuria is urine culture, but laboratory charges make this test

expensive for routine screening in populations that have a low prevalence of asymptomatic

bacteriuria. The most commonly used tests for detecting bacteriuria in asymptomatic persons are

dipstick urinalysis and direct microscopy. The dipstick test is rapid, inexpensive, and requires

little technical expertise. The dipstick leukocyte esterase (LE) test, which detects esterases

released from degraded white blood cells, is an indirect test for bacteriuria. When compared with

culture (at least 100,000 organisms/mL), it has a sensitivity of 72-97% and a specificity of

64-82%.35-40 The nitrite reduction test, which detects nitrites produced by urinary bacteria

(usually limited to Gram-negative bacteria), has variable sensitivity (35-85%) but good

specificity (92-100%).35-39,41-49 In children, dipstick testing for LE and/or nitrites has

been found to have sensitivity and specificity of around 80% compared to quantitative culture.50-

57 Among pregnant women, a sensitivity of only 50% for dipstick testing compared to culture has

been reported.30 False-positive and false-negative urinalysis results are due to a variety of

factors, including specimen contamination, certain organisms, and the timing of specimen

collection. The sensitivity of this test can be improved by obtaining first-morning specimens,

preferably on consecutive days, instead of performing random collection.41 Many of the studies

assessing the accuracy of dipstick testing in children and adults do not describe the patients

included. A proportion of these patients were undoubtedly symptomatic, possibly leading to bias in

the accuracy estimates. In one study, dipstick sensitivity was significantly lower (56% vs. 92%)

and specificity significantly higher (78% vs. 42%) in patients with few symptoms and a low

prior probability of bacteriuria, compared to patients with a high prior probability of

bacteriuria (i.e., those with dysuria, frequency, etc.).58

Examination of the sediment by microscopic urinalysis to detect bacteria and white blood cells has

also been evaluated as a screening test for bacteriuria. In children (including symptomatic

patients), microscopy performs similarly to dipstick testing for detection of bacteriuria.50 In

pregnant women, microscopic analysis, with either bacteriuria or pyuria indicating a positive

test, had a sensitivity of 83% but a specificity of only 59%.30 In hospitalized adults, only 3% of

urine specimens that were macroscopically (including dipstick) negative had clinically significant

abnormalities detected by routine microscopic examination.59,60 Microscopy has limited value as

a screening test for asymptomatic persons because of the cost, time, and technique required.30

In populations with a low prevalence of urinary tract disorders, most positive screening tests are

falsely positive. Thus, in asymptomatic men, and in asymptomatic women under age 60, a dipstick

test has a positive predictive value for significant bacteriuria of less than 10% (assuming a

sensitivity of 85% and a specificity of 70%).20,25,43 In children, the likelihood of bacteriuria

in the presence of a positive dipstick screening test has been estimated at 0.1% for boys and 4%

for girls.57 In groups at increased risk for urinary tract infection, the positive predictive value

of dipstick tests is higher: 13% in pregnant women, 18% in women over age 60, 33% in diabetic

women, and 44% in institutionalized older persons.20,25,29,32,41,43,61-64 The predictive

value of bacteriuria found on microscopic urinalysis among pregnant women was 4.2-4.5%.30

Urine screening tests are generally performed on a clean-catch specimen. In infants and young

children, collection of a "clean" urine specimen is difficult, and as a result few studies of the

accuracy of screening tests have included infants. Adhesive polyethylene bag specimens are the

most acceptable choice, but these may have a significant contamination rate (false positives).

Compared to suprapubic aspiration, positive results on bag specimens indicate true bacteriuria in

only 7.5% of specimens.65 The collection of confirmatory sterile culture specimens by

suprapubic aspiration or urethral catheterization is too invasive and costly to be considered in a

screening protocol for asymptomatic infants, as is routine screening by urethral catheterization.

Effectiveness of Early Detection

The early detection of asymptomatic bacteriuria may reduce the rate of bacteriuria and prevent

symptomatic infection and its complications. Some observational studies suggest that persons with

untreated asymptomatic bacteriuria are at increased risk of developing symptomatic urinary tract

infection66,67 and other complications (e.g., structural damage, renal insufficiency,

hypertension, or mortality).41,61-64,68-71 Evidence is not conclusive, however, that these

clinical outcomes are caused by bacteriuria (especially in the absence of a structural

abnormality), or that early treatment results in important clinical benefits. A randomized

placebo-controlled trial of conventional treatment for asymptomatic bacteriuria in both young and

middle-aged women (ages 20-65) reported no significant differences in the prevalence of

bacteriuria or incidence of symptomatic urinary tract infection at 1-year follow-up.66 Another

randomized controlled trial (available only in abstract form) among women ages 16-69 years

with asymptomatic bacteriuria reported significant reductions in bacteriuria at 1 and 3 years

with vigorous individualized antimicrobial therapy, but did not report on clinical outcomes.72

Among a cohort of middle-aged women (38-60 years) screened for asymptomatic bacteriuria, the

prevalence of asymptomatic bacteriuria at 6-year follow-up in women identified with

asymptomatic bacteriuria and appropriately treated remained significantly higher than in the

nonbacteriuric group (23% vs. 5%) and 58% of the treated women had recurrent or persistent

infection within 2 years of treatment.25 Studies evaluating the treatment or natural history of

asymptomatic bacteriuria are not available for young or middle-aged men.

Randomized controlled trials in institutionalized elderly women73 and men74 found no decreases

in genitourinary morbidity with treatment of asymptomatic bacteriuria despite a reduced

prevalence of bacteriuria. In both studies, life-table analyses suggested a survival advantage for

the untreated group, but the differences were not statistically significant. In women, treatment

was associated with an increased incidence of adverse antimicrobial drug effects and increased

reinfections.73

Among noninstitutionalized ambulatory elderly women, a randomized controlled trial reported that

treatment significantly reduced the prevalence of bacteriuria at 6-month follow-up.67

Symptomatic urinary tract infection and mortality rates were 16.4% and 4.9%, respectively,

without treatment, compared to 7.9% and 3.2%, respectively, with treatment, but these

differences were not statistically significant; sample size may have been inadequate to detect a

difference, however. In a nonrandomized controlled trial in noninstitutionalized elderly women,

treatment of asymptomatic bacteriuria did not significantly reduce mortality (adjusted relative

risk 0.92, 95% confidence interval, 0.57 to 1.57), although wide confidence intervals do not

exclude the possibility of a substantial benefit.75 A large cohort study from the same center

reported no association between asymptomatic bacteriuria and mortality in ambulatory elderly

women after control for confounding, even though the cure rate with treatment was 83% compared

to a 16% spontaneous remission rate in untreated patients.75 It is not clear whether the possible

but unproven benefits from treatment of such women justify routine screening or the potential

adverse effects of antibiotic therapy, including drug toxicity and the development of resistant

organisms while treating recurrent infections. No controlled trials of therapy for asymptomatic

bacteriuria in noninstitutionalized elderly men have been reported. In a prospective cohort study

of 234 elderly men followed for up to 4.5 years, 29 (12%) had asymptomatic bacteriuria at

initial screening, and 20 (8%) became positive in follow-up.76 Of untreated bacteriuric

subjects, 76% spontaneously cleared. Only five bacteriuric subjects were treated for

symptomatic infection, with prompt recurrence of asymptomatic bacteriuria in three; no adverse

outcomes from symptomatic infection were reported. Cohort and cross-sectional studies that have

included elderly ambulatory men have reported no differences in mortality, chronic geniturinary

symptoms, or systemic symptoms such as anorexia, fatigue, or malaise between those with and

without asymptomatic bacteriuria, after adequate adjustment for confounding variables.77-79

Although some trials of elderly patients may have included persons with diabetes, we found no

controlled clinical trials specifically evaluating the effectiveness of early detection of

asymptomatic bacteriuria in diabetics for improving clinical outcome. Case series suggest

treatment of asymptomatic bacteriuria usually clears bacteriuria and may reduce clinical

symptoms, but bacteriuria recurs in more than two thirds of treated patients.80-83 Continuous

suppressive antibiotic therapy in diabetic patients can prevent re-infection but provides no

posttreatment benefit.80,81 The long-term consequences of asymptomatic bacteriuria in this

population are undefined, although in one series persistent bacteriuria did not appear to

contribute to renal damage.83

The early detection of asymptomatic bacteriuria is of greater potential value for pregnant women,

in whom bacteriuria is an established risk factor for serious complications, including acute

pyelonephritis, preterm delivery, and low birth weight. Randomized controlled trials, cohort

studies, and a meta-analysis of 8 randomized clinical trials have shown that treatment of

asymptomatic bacteriuria during pregnancy can significantly reduce the incidence of symptomatic

urinary tract infection, low birth weight, and preterm delivery.12-14,18,20,28,84 There is

little evidence regarding the optimal periodicity of screening in pregnancy. A urine culture

obtained at 12-16 weeks of pregnancy will identify 80% of women who will ultimately have

asymptomatic bacteriuria in pregnancy,85 with an additional 1-2% identified by repeated

monthly screening.

In children, detection of bacteriuria might lead to the identification of correctable abnormalities of

the urinary tract and the prevention of renal scarring, obstructive atrophy, hypertension, and

renal insufficiency. However, in three randomized controlled trials in girls aged 5-15 years,

treatment of asymptomatic bacteriuria did not significantly reduce emergence of symptoms,

pyelonephritis, renal scarring, or persistence of vesicoureteral reflux.86-88 In two of these

trials,86,87 sample sizes may have been too small to detect important differences, but adverse

outcomes were rare in both groups. Treated and control subjects had similar growth, blood

pressure, renal growth, and concentrating capacity at the end of follow-up, ranging from 12 to 48

months. In longitudinal studies from the Oxford-Cardiff Cohort screening program, girls with

asymptomatic bacteriuria in childhood had an increased prevalence of asymptomatic bacteriuria in

pregnancy, and among those with asymptomatic bacteriuria and renal scarring, increased

preeclampsia, hypertension, and obstetric interventions.89,90 On the other hand, in pregnant

women with a history of symptomatic urinary tract infection in childhood, there were no

differences in preeclampsia or operative delivery, although asymptomatic bacteriuria was again

more common.91 All pregnancies in these studies had satisfactory maternal and fetal outcomes.

Most of the complications from urinary tract abnormalities are thought to occur before children

reach school age,2 and therefore screening might be more effective in younger children. There

have been no studies, however, proving that preschool urinalyses result in lower morbidity from

recurrent infection or in less renal damage.2,92 Several studies have evaluated the natural

history of asymptomatic bacteriuria detected in infancy and followed through the preschool years.

In a Swedish cohort of 3,581 screened newborns, 50 infants were identified with asymptomatic

bacteriuria, of whom 3 (<0.1%) were treated for underlying renal or urologic abnormalities and

2 were treated for pyelonephritis that occurred within 2 weeks of testing.8,93 All 45 infants

with untreated asymptomatic bacteriuria followed for up to 7 years cleared either spontaneously

(80%) or after antibiotic treatment for other conditions (20%). Three subsequently developed

cystitis and 20% had recurrences of asymptomatic bacteriuria, but none had major renal or

urologic abnormalities as measured by concentrating capacity and urography at a median

follow-up of 32 months. Forty infants developed symptomatic urinary tract infection in the first

year of age, but only 2 (5%) had evidence of bacteriuria on previous screening. In another cohort

of 1,617 healthy infants followed for 5 years, screening for asymptomatic bacteriuria detected 5

cases (0.3%) with high-risk lesions (such as obstructive uropathy, vesicoureteral junction

ectopia, etc).94 Whether early detection of bacteriuria improved prognosis was not established by

this study. In 113 infants less than 1 year old undergoing urologic evaluation, the proportion of

abnormal kidneys on dimercaptosuccinic acid (DMSA) scan did not differ between those with and

without urinary tract infection (33% vs. 28%), suggesting that renal scarring from reflux may

occur independently of bacteriuria.95 Renal abnormalities detectable by ultrasound are found in

1.4% of infants who are considered normal,2,96 compared to 6%of infants with asymptomatic

bacteriuria.8 However, these infants might have been detected outside the screening program as

their symptoms developed.

The effectiveness of detecting asymptomatic bacteriuria in patients with indwelling or

intermittent urethral catheterization, of periodic screening in patients with known urologic

structural abnormalities, or of follow-up of symptomatic urinary tract infection with repeat

cultures, is not discussed in this report. These forms of testing are considered within the domain

of diagnostic studies for patients with existing medical or surgical conditions, rather than a part of

routine screening tests for asymptomatic persons.

Recommendations of Other Groups

The American Academy of Family Physicians (AAFP) recommends periodic screening by dipstick

combining leukocyte esterase and nitrite tests to detect bacteriuria in preschool children, those

who are morbidly obese, persons with diabetes or a history of gestational diabetes, and persons

aged 65 years and older.97 The recommendations of the AAFP are currently under review. The

American College of Physicians recommends against routine screening of adults for asymptomatic

bacteriuria with urinalysis or urine culture.98 The Canadian Task Force on the Periodic Health

Examination recommends against routinely screening asymptomatic infants, children, elderly

men, or institutionalized elderly women for bacteriuria, and found insufficient evidence to

recommend for or against screening noninstitutionalized elderly women.99 Bright Futures does

not recommend routine urinalyses in infants, children, or adolescents.100 The  American Academy

of Pediatrics (AAP) recommends routine urinalysis at age 5, and dipstick urinalysis for

leukocytes for all adolescents, preferably at age 15 years.102

The American College of Obstetricians and Gynecologists and the AAP recommend a urinalysis,

including microscopic examination and infection screen, at the first prenatal visit, with the need

for additional laboratory evaluations including urine culture determined by findings obtained from

the history and physical examination.101 The Canadian Task Force recommends a urine culture at

12-16 weeks of pregnancy.99

Discussion

Screening for asymptomatic bacteriuria is important during pregnancy, where there is strong

evidence that treatment is efficacious in improving outcome. Given the benefits of detecting

asymptomatic bacteriuria in pregnancy, prenatal testing should be carried out by urine culture

(rather than by urinalysis) to reduce the risk of false negatives. A specimen obtained at 12-16

weeks will detect most cases of asymptomatic bacteriuria. There are, however, inadequate data to

determine the optimal frequency of subsequent urine testing during pregnancy.

Screening for asymptomatic bacteriuria in school-age girls has been shown to produce little

clinical benefit in controlled trials. The effectiveness of screening school-age boys for

asymptomatic bacteriuria has not been evaluated, but because the prevalence is extremely low in

this population and the specificity of screening tests is only about 80% in children, most positive

tests will be false positives (estimated at 99.9% in one overview57), with the potential for

consequent adverse effects including unnecessary antibiotic therapy and invasive testing.

Screening in infants, toddlers, and preschool children might be beneficial in preventing renal

damage, but its effectiveness has not been established and cohort studies suggest little risk from

untreated asymptomatic bacteriuria. In addition, no accurate and noninvasive screening test is

available for infants or toddlers in diapers. Given an 80% sensitivity and specificity of current

screening methods, and a 1% prevalence of asymptomatic bacteriuria in girls and 0.03% in boys,

screening 100,000 children is estimated to result in 19,897 false-positive tests, or nearly 1 in

5 children screened.57

Trials of routine screening have shown no benefit for institutionalized elderly persons and suggest

the occurrence of adverse consequences such as unintended drug effects and increased reinfection

rates. Screening is therefore not justified in this population. Screening urinalysis might be

appropriate in certain high-risk groups, such as diabetic and noninstitutionalized elderly women,

but firm evidence of benefit is not available. Several trials in ambulatory elderly women have

found no clinical benefit from screening for asymptomatic bacteriuria, but sample sizes were

small and do not exclude the possibility of important benefits. Potential benefits must be balanced

against the high likelihood of reinfection after treatment in these groups and the adverse effects

associated with antibiotic use. Screening is not justified in the general adolescent and adult

population, or in ambulatory elderly men, because unrecognized, serious urinary tract disorders

are uncommon, the positive predictive value of screening urinalysis is low, and the effectiveness

of early detection and treatment is unproven.

CLINICAL INTERVENTION

Screening for asymptomatic bacteriuria with urine culture is recommended for pregnant women

at 12-16 weeks of gestation ("A" recommendation). The optimal frequency for subsequent

periodic urine cultures during pregnancy has not been determined and is left to clinical discretion.

The urine specimen should be obtained in a manner that minimizes contamination. Routine

screening for asymptomatic bacteriuria with leukocyte esterase or nitrite testing in pregnant

women is not recommended because of poor test characteristics compared to urine culture ("D"

recommendation).

There is currently insufficient evidence to recommend for or against routine screening for

asymptomatic bacteriuria with leukocyte esterase or nitrite testing in ambulatory elderly women

or in women with diabetes ("C" recommendation), but recommendations against such screening

may be made on other grounds, including a high likelihood of recurrence and the potential adverse

effects of antibiotic therapy. Routine screening for bacteriuria with leukocyte esterase or nitrite

testing is not recommended for other asymptomatic persons, including school-aged girls ("E"

recommendation), institutionalized elderly ("E" recommendation), and other children,

adolescents, and adults ("D" recommendation). Screening for asymptomatic bacteriuria with

microscopy testing is not recommended ("D" recommendation).

The draft update of this chapter was prepared for the U.S. Preventive Services Task Force by

Carolyn DiGuiseppi, MD, MPH, based in part on materials prepared for the Canadian Task Force on

the Periodic Health Examination by Michael B.H. Smith, MB, BCh, CCFP, FRCPC, and Lindsay E.

Nicolle, MD.

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