Evidence for the U.S. Preventive Services Task Force Reaffirmation Recommendation
Statement
July 2008
Prepared by: Kenneth Lin, MD, and Kevin Fajardo, MD, MPH, MTMH
Corresponding Author: Kenneth Lin, MD, Center for Primary
Care, Prevention, and Clinical Partnerships, Agency for Healthcare Research
and Quality, 540 Gaither Road, Rockville, MD 20850; E-mail,
kenneth.lin@ahrq.hhs.gov.
This report is based on research conducted by staff at the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD. The investigators involved have declared no conflicts of interest with objectively conducting this research. The findings and conclusions in this document are those of the authors, who are responsible for its content, and do not necessarily represent the views of AHRQ. No statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.
The information in this report is intended to help clinicians, employers, policymakers, and others make informed decisions about the provision of health care services. This report is intended as a reference and not as a substitute for clinical judgment.
This report may be used, in whole or in part, as the basis for the development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.
This article was first published in the Annals of Internal Medicine on July 1, 2008 (Ann Intern Med 2008;149:W-20-W-24).
Contents
Abstract
Introduction
Methods
Results
Discussion
References
Abstract
Background: Asymptomatic bacteriuria is common, and screening
for this condition in pregnant women is a well-established, evidence-based standard of current medical practice. Screening other
groups of adults has not been shown to improve outcomes.
Purpose: To review new and substantial evidence on screening for
asymptomatic bacteriuria, to support the work of the U.S. Preventive
Services Task Force.
Data Sources: English-language studies of adults (age >18 years)
indexed in PubMed and the Cochrane Library and published from
1 January 2002 through 30 April 2007.
Study Selection: For benefits of screening or treatment for
screened populations, systematic reviews; meta-analyses; and randomized,
controlled trials were included. For harms of screening,
systematic reviews; meta-analyses; randomized, controlled trials; cohort
studies; case–control studies; and case series of large multisite
databases were included. Two reviewers independently reviewed
titles, abstracts, and full articles for inclusion.
Data Extraction: Two reviewers extracted data from studies on
benefits of screening and treatment (including decreases in the
incidence of adverse maternal and fetal outcomes, symptomatic
urinary tract infections, hypertension, and renal function decline).
Data Synthesis: An updated Cochrane systematic review of 14
randomized, controlled trials of treatment supports screening for
asymptomatic bacteriuria in pregnant women. A randomized, controlled
trial and a prospective cohort study show that screening
nonpregnant women with diabetes for asymptomatic bacteriuria is
unlikely to produce benefits. No new evidence on screening men
for asymptomatic bacteriuria or on harms of screening was found.
Limitation: The focused search strategy may have missed some
smaller studies on the benefits and harms of screening for asymptomatic
bacteriuria.
Conclusion: The available evidence continues to support screening
for asymptomatic bacteriuria in pregnant women, but not in other
groups of adults.
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Introduction
The presence of bacteria in the urine of an individual
without signs or symptoms of a urinary tract infection
is called asymptomatic bacteriuria. This condition is normally
present in 3% to 5% of women younger than age 60
years and is more common in patients with diabetes and
elderly persons. In pregnant women, asymptomatic bacteriuria
has been associated with an increased incidence of
pyelonephritis and low-birthweight offspring.1
In 2004, the U.S. Preventive Services Task Force
(USPSTF) recommended "screening for asymptomatic
bacteriuria with urine culture for pregnant women at 12 to
16 weeks' gestation" (a grade A recommendation) on the
basis of good evidence that treatment for asymptomatic
bacteriuria reduces the incidence of symptomatic urinary
tract infections, low-birthweight children, and preterm delivery.2 Citing a lack of evidence that screening for
asymptomatic bacteriuria improves clinical outcomes in
men and nonpregnant women, the USPSTF recommended
against screening these groups (a grade D recommendation).2
In 2008, the USPSTF reexamined the evidence to reaffirm
its recommendations on screening for asymptomatic
bacteriuria in adults. The USPSTF decided to perform a
reaffirmation update because there is a strong evidence base
for the 2004 recommendations on screening for asymptomatic
bacteriuria, and therefore only contradictory information
from large, high-quality studies could change these
recommendations. The USPSTF performs reaffirmation
updates for recommendation statements that remain USPSTF
priorities and are within the scope of the USPSTF and
for which there is compelling reason for the USPSTF to
have a current recommendation statement. The goal of this
reaffirmation update was to find new, substantial, highquality
evidence regarding the benefits and harms of
screening for asymptomatic bacteriuria in adults.
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Methods
The USPSTF requested that this update address 2 primary
key questions:
- What are the benefits of screening and treatment for
asymptomatic bacteriuria in pregnant women, nonpregnant
women, and men?
- What are the harms of screening for asymptomatic
bacteriuria in pregnant women, nonpregnant women, and
men?
The Task Force determined that this update need not
review new evidence for the harms of antibiotic treatment
for asymptomatic bacteriuria because the adverse effects of
commonly used antibiotic medications are well established.
Data Sources and Searches
We performed literature searches for the benefits of
screening for asymptomatic bacteriuria and the harms of
screening, limited 1 January 2002 through 30 April 2007,
using the search terms asymptomatic bacteriuria, screening,
and urine culture. Initial searches were limited to English-language
articles indexed in the Cochrane Database of Systematic
Reviews and PubMed core clinical journals. Core
journals are a subset of 120 English-language journals defined
by the National Library of Medicine, previously
known as the Abridged Index Medicus. When initial
searches revealed few articles, we expanded searches to include
noncore journals. We supplemented these searches
by reviewing reference lists of recent systematic and narrative
reviews and clinical guidelines.
Study Selection
We searched for studies on the benefits and harms of
screening and the benefits of treatment for asymptomatic
bacteriuria. We included studies of adults 18 years of age
or older from the United States and from other countries
with patient populations generalizable to the United States.
We excluded studies of very high-risk or special patient
populations, including patients with a history of recurrent
urinary tract infections, immunocompromised patients,
and patients with sickle cell disease.
For benefits of screening or treatment of screened
populations, we included randomized, controlled trials
(RCTs); meta-analyses; and systematic reviews. For harms
of screening, we included systematic reviews, meta-analyses,
RCTs, cohort studies, case– control studies, and case
series of large multisite databases. We excluded editorials,
case reports, narrative reviews, and guideline reports.
We evaluated all articles for predetermined exclusion
criteria at each stage of review (title, abstract, and full article).
Articles selected by at least 1 team member advanced
to the next stage of review. At the full article stage, we
resolved differences of opinion by consensus.
Data Extraction
We abstracted information on sample size, entry criteria,
demographic characteristics, comorbid conditions,
study design, treatment group allocation, and clinical outcomes
of interest.
Data Synthesis and Analysis
Data from included studies were synthesized qualitatively
in a narrative format.
Role of the Funding Source
The work of the USPSTF is supported by the Agency
for Healthcare Research and Quality. This review did not
receive separate funding.
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Results
We identified 93 potentially eligible articles and entered
them into a reference database. After sequential application
of exclusion criteria (Figure), 1 systematic review
of treatment for asymptomatic bacteriuria in pregnant
women and 1 RCT of treatment for asymptomatic bacteriuria
in nonpregnant women with diabetes met inclusion
criteria for this update. An additional prospective cohort
study of outcomes of asymptomatic bacteriuria in diabetic
women that did not meet the inclusion criteria is also reviewed
in detail. These 3 new studies are discussed in the
next sections (Table).
1. What Are the Benefits of Screening and Treatment for
Asymptomatic Bacteriuria in Pregnant Women,
Nonpregnant Women, and Men?
Pregnant Women
We identified no new RCTs of screening for asymptomatic
bacteriuria in pregnant women. A 2007 Cochrane
systematic review and meta-analysis of randomized trials
comparing antibiotic treatment with placebo or no treatment
included 14 studies involving 2302 pregnant women.
The review found statistically significant reductions in the
incidence of pyelonephritis (relative risk [RR], 0.23 [95%
CI, 0.13 to 0.41]) and low-birthweight babies (RR, 0.66
[CI, 0.49 to 0.89]).3
Although all of the studies included in the Cochrane
review were published in 1987 or earlier, we considered the
meta-analysis to represent new evidence because it came to
a different conclusion than a previous Cochrane review4
about the effect of antibiotic treatment on the incidence of
preterm delivery. The previous review relied on the standard
definition of preterm delivery from the 1960s, birthweight
less than 2500 g, rather than the currently accepted
definition of birth before a certain gestational age. When
the Cochrane review investigators included only the 3
studies that used a gestational age-based definition of preterm
delivery, antibiotic treatment for asymptomatic bacteriuria
had no effect on rates of preterm delivery (RR,
0.37 [CI, 0.10 to 1.36]).3
Nonpregnant Women
We found 1 good-quality RCT of treatment that compared
antibiotics with placebo in diabetic women with
asymptomatic bacteriuria.5 Endocrinology offices in 2
tertiary care hospitals and community practices in Canada
recruited 105 participants. Eligible patients were nonpregnant
women older than 16 years of age with diabetes, normal
renal function, no symptoms consistent with a urinary
tract infection, and 2 consecutive positive urine cultures
(>105 colony-forming units of an organism per mL of
urine). After randomization, patients received either trimethoprim–sulfamethoxazole (or ciprofloxacin if they
could not use sulfa drugs) or placebo. Four weeks after
treatment, and every 3 months for up to 36 months, investigators
rescreened patients for bacteriuria with urine
cultures. Patients in the experimental group with positive
results received additional antibiotics for progressively
longer periods. Patients in either group who developed
symptomatic urinary infections were also treated with the
study drugs.
After the initial round of therapy, significantly (P <
0.001) more women in the placebo group continued to
have bacteriuria. However, during follow-up, the time to
symptoms consistent with a urinary tract infection was
similar in both groups. The placebo group was no more
likely than the treatment group to have a symptomatic
urinary tract infection (RR, 1.19 [CI, 0.28 to 1.81]), pyelonephritis
(RR, 2.13 [CI, 0.81 to 5.62]), or hospitalization
for a urinary tract infection (RR, 1.93 [CI, 0.47 to
7.89]). Patients in the placebo group averaged 34 days of
antibiotic use per 1000 days of follow-up, compared with
158 days of antibiotic use per 1000 days of follow-up in
the treatment group.
Two additional clinically important outcomes thought
to be related to asymptomatic bacteriuria are renal function
decline and development of hypertension. We identified a
multicenter prospective cohort study of interest that did
not meet inclusion criteria for this review because it was
not a randomized trial.6 We present it here as a good-quality
study that contributed to the USPSTF's understanding
of screening for asymptomatic bacteriuria in
women with diabetes.
A total of 644 women with type 1 and type 2 diabetes,
who were from hospital outpatient diabetic clinics in the
Netherlands, were evaluated for asymptomatic bacteriuria
and monitored for a mean of 6.1 years for changes in
creatinine clearance and blood pressure. A multivariate
analysis, adjusted for patient age, length of follow-up, duration
of diabetes, and presence of microalbuminuria at
study entry, found no association between the presence of
asymptomatic bacteriuria and subsequent changes in creatinine
clearance. Similarly, investigators observed no relationship
between asymptomatic bacteriuria and the development
of hypertension. These findings suggest that screening
and treatment for asymptomatic bacteriuria in women
with diabetes would have no effect on either outcome.
Men
We identified no studies of screening or treatment for
asymptomatic bacteriuria in men.
2. What Are the Harms of Screening for Asymptomatic
Bacteriuria in Pregnant Women, Nonpregnant Women,
and Men?
We identified no new studies of the harms of screening
for asymptomatic bacteriuria in pregnant women, nonpregnant
women, or men.
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Discussion
Although urine culture remains the gold standard for
screening for and diagnosis of asymptomatic bacteriuria in
pregnant women, it is time- and labor-intensive and patients
may have difficulty providing uncontaminated samples
for testing. It would be useful to identify a rapid test
with a high negative predictive value for asymptomatic
bacteriuria that could replace urine culture as a screening
test. Urine cultures would then be performed only on patients
with positive screening results.
The 2004 USPSTF evidence update on screening for
asymptomatic bacteriuria7 highlighted the Uriscreen
(Savyon Diagnostics, Ashdod, Israel) enzymatic screening
test as having good potential because of its reported 100%
sensitivity and negative predictive value in 1 study of 313
consecutive pregnant patients in Israel. However, in a 2005
study of 150 asymptomatic pregnant women in Venezuela,
the test detected only 17 of 28 patients whose catheterized
urine samples showed bacteriuria, yielding a sensitivity of
60.7% and negative predictive value of 90.8% compared
with urine culture.8
Whether pregnant women benefit from additional
screening for asymptomatic bacteriuria after the first trimester
is unknown. A 2005 Canadian study conducted in
outpatient clinics at an urban teaching hospital compared
the diagnostic yield of a single urine culture, 2 urine cultures,
and 3 urine cultures at fewer than 20 weeks', 28
weeks', and 36 weeks' gestation.9 Additional cultures
were performed at routine prenatal visits if a leukocyte
esterase–nitrite test result was positive; the gold standard
for asymptomatic bacteriuria was any single positive urine
culture.
Forty-nine of the 1050 patients in the Canadian study
had asymptomatic bacteriuria. A single urine culture before
20 weeks' gestation (consistent with the USPSTF recommendation)
detected only 40.8% of cases, whereas the
3-urine-culture strategy detected 87.8% of cases. However,
the study did not assess the effect of increased detection on
clinical outcomes.
In summary, we found some new evidence that continues
to support screening for asymptomatic bacteriuria in
pregnant women, as well as evidence that suggests no benefit
from screening other groups of adults. No currently
available screening tests have a high enough sensitivity and
negative predictive value for asymptomatic bacteriuria in pregnant women to replace the urine culture. Future research
is needed to clarify the optimal timing and periodicity
of screening in pregnant women.
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References
1. Screening for asymptomatic bacteriuria. In: U.S. Preventive Services Task
Force. Guide to Clinical Preventive Services, 2nd ed. Rockville, MD: Agency for
Healthcare Research and Quality; 1996:347-59.
2. U.S. Preventive Services Task Force. Screening for Asymptomatic Bacteriuria:
Recommendation Statement. Rockville, MD: Agency for Healthcare Research
and Quality; 2004. Accessed at www.ahrq.gov/clinic/uspstf/uspsbact.htm on 19
March 2008.
3. Smaill F, Vazquez JC. Antibiotics for asymptomatic bacteriuria in pregnancy.
Cochrane Database Syst Rev 2007:CD000490. [PMID: 17443502]
4. Smaill F. Antibiotics for asymptomatic bacteriuria in pregnancy. Cochrane
Database Syst Rev 2001:CD000490. [PMID: 11405965]
5. Harding GK, Zhanel GG, Nicolle LE, Cheang M. Manitoba Diabetes Urinary
Tract Infection Study Group. Antimicrobial treatment in diabetic women
with asymptomatic bacteriuria. N Engl J Med 2002;347:1576-83. [PMID:
12432044]
6. Meiland R, Geerlings SE, Stolk RP, Netten PM, Schneeberger PM, Hoepelman
AI. Asymptomatic bacteriuria in women with diabetes mellitus: effect on
renal function after 6 years of follow-up. Arch Intern Med 2006;166:2222-7.
[PMID: 17101940]
7. Gartlehner G, Kahwati L, Lux L, West S. Screening for Asymptomatic Bacteriuria:
A Brief Evidence Update for the U.S. Preventive Services Task Force.
Rockville, MD: Agency for Healthcare Research and Quality; February 2004.
AHRQ Publication No. 05-0551-B. Accessed at www.ahrq.gov/clinic/3rduspstf/asymbac/asymbacup.pdf on 5 May 2008.
8. Teppa RJ, Roberts JM. The uriscreen test to detect significant asymptomatic
bacteriuria during pregnancy. J Soc Gynecol Investig 2005;12:50-3. [PMID:
15629672]
9. McIsaac W, Carroll JC, Biringer A, Bernstein P, Lyons E, Low DE, et al.
Screening for asymptomatic bacteriuria in pregnancy. J Obstet Gynaecol Can
2005;27:20-4. [PMID: 15937578]
Acknowledgment: The authors thank Marion Torchia, Office of Communications
and Knowledge Transfer, Agency for Healthcare Research
and Quality, for helpful and timely editorial support.
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AHRQ Publication No. 08-05120-EF-3
Current as of July 2008
Internet Citation:
Lin K, Fajardo K. Screening for Asymptomatic Bacteriuria in Adults: Evidence for the U.S. Preventive Services Task Force Reaffirmation Recommendation
Statement. AHRQ Publication No. 08-05120-EF-3, July 2008. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/clinic/uspstf08/asymptbact/asbactart.htm