Targeting Asymptomatic Bacteriuria in Antimicrobial Stewardship: the Role of the Microbiology Laboratory

This minireview focuses on the microbiologic evaluation of patients with asymptomatic bacteriuria, as well as indications for antibiotic treatment. Asymptomatic bacteriuria is defined as two consecutive voided specimens (preferably within 2 weeks) with the same bacterial species, isolated in quantitative counts of ≥10⁵ CFU/ml in women, including pregnant women; a single voided urine specimen with one bacterial species isolated in a quantitative count ≥10⁵ CFU/ml in men; and a single catheterized urine specimen with one or more bacterial species isolated in a quantitative count of ≥10⁵ CFU/ml in either women or men (or ≥10² CFU/ml of a single bacterial species from a single catheterized urine specimen).

ABSTRACT

This minireview focuses on the microbiologic evaluation of patients with asymptomatic bacteriuria, as well as indications for antibiotic treatment. Asymptomatic bacteriuria is defined as two consecutive voided specimens (preferably within 2 weeks) with the same bacterial species, isolated in quantitative counts of ≥10⁵ CFU/ml in women, including pregnant women; a single voided urine specimen with one bacterial species isolated in a quantitative count ≥10⁵ CFU/ml in men; and a single catheterized urine specimen with one or more bacterial species isolated in a quantitative count of ≥10⁵ CFU/ml in either women or men (or ≥10² CFU/ml of a single bacterial species from a single catheterized urine specimen). Any urine specimen with ≥10⁴ CFU/ml group B Streptococcus is significant for asymptomatic bacteriuria in a pregnant woman. Asymptomatic bacteriuria occurs, irrespective of pyuria, in the absence of signs or symptoms of a urinary tract infection. The two groups with the best evidence of adverse outcomes in the setting of untreated asymptomatic bacteriuria include pregnant women and patients who undergo urologic procedures with risk of mucosal injury. Screening and treatment of asymptomatic bacteriuria is not recommended in the following patient populations: pediatric patients, healthy nonpregnant women, older patients in the inpatient or outpatient setting, diabetic patients, patients with an indwelling urethral catheter, patients with impaired voiding following spinal cord injury, patients undergoing nonurologic surgeries, and nonrenal solid-organ transplant recipients. Renal transplant recipients beyond 1 month posttransplant should not undergo screening and treatment for asymptomatic bacteriuria. There is insufficient evidence to recommend for or against screening of renal transplant recipients within 1 month, patients with high-risk neutropenia, or patients with indwelling catheters at the time of catheter removal. Unwarranted antibiotics place patients at increased risk of adverse effects (including Clostridioides difficile diarrhea) and contribute to antibiotic resistance. Methods to reduce unnecessary screening for and treatment of asymptomatic bacteriuria aid in antibiotic stewardship.

INTRODUCTION

Asymptomatic bacteriuria (ASB) is defined as the presence of ≥10⁵ CFU/ml of one or more bacterial species, irrespective of pyuria, in a urine specimen from a patient without signs or symptoms of a urinary tract infection (UTI) (1, 2) (Table 1). In men, one voided urine specimen meeting these criteria defines ASB. For women (including pregnant women), two consecutive voided urine specimens should be obtained, ideally within 2 weeks, with recovery of the same species at levels of ≥10⁵ CFU/ml to meet criteria for ASB (1, 2). The United States Preventive Services Task Force (USPSTF) further adds that >10⁴ CFU/ml is significant if the bacterium is group B Streptococcus in pregnant women (3). In men or women with indwelling catheters, bacteria present in a single catheterized urine specimen at quantities of ≥10⁵ CFU/ml are diagnostic of asymptomatic bacteriuria (1, 2). Bacterial counts as low as ≥10² CFU/ml also may be used for catheterized patients, but the clinical significance of counts this low has not been fully vetted in this population (1, 2). As in symptomatic bacteriuria, urine cultures from asymptomatic patients that yield a mixture of bacteria in quantities of <10⁵ CFU/ml suggest that the specimen is contaminated with organisms that colonize the external genitalia, and recollection is recommended (1).

TABLE 1.

Microbiologic definition of asymptomatic^a bacteriuria^b

Criteria for ASB diagnosis
Two consecutive voided urine specimens (preferably within 2 wk) with the same bacterial species isolated in quantitative count of >105 CFU/ml in women, including pregnant women (1, 2)
A single voided urine specimen with one bacterial species isolated in a quantitative count of >105 CFU/ml in men (1, 2)
A single catheterized urine specimen with one or more bacterial species isolated in a quantitative count of >105 CFU/ml in either women or men (1) or ≥102 CFU/ml of a single bacterial species from a single catheterized urine specimen (2)
Any urine specimen with >104 CFU/ml of group B Streptococcus is significant for ASB in a pregnant woman (3)

^aNo signs or symptoms referable to the urinary tract, e.g., typical urinary tract symptoms include urinary frequency, urinary urgency, lower abdominal pain, pelvic pain, and/or flank pain.

^bPresence of more than one bacterial type indicates contamination with organisms normally found on the skin. The presence of yeast in the urine of asymptomatic patients is almost always the result of external genital tract colonization, and there are no consistent diagnostic criteria to define significant infection (7).

Pyuria, the presence of increased numbers of white blood cells in the urine, is a marker of genitourinary inflammation, and although it is common in patients with ASB, the presence alone is nonspecific and is not sufficient to diagnose bacteriuria (1). Although there are studies that extrapolate ASB from the presence of pyuria in urine specimens, guidelines do not incorporate the detection of pyuria and recommend only quantitative urine culture for diagnosis (1). Similarly, leukocyte esterase and nitrites are not useful tests for detecting ASB (4).

ASB becomes more common with age, from <2% in children to up to 50% in elderly residents of long-term care facilities (1). Although the prevalence of ASB in patients hospitalized in acute care institutions is unknown, 8.5% of patients admitted to a tertiary care center were found to have ASB (5). Patients with long-term indwelling urethral catheter placement have the highest prevalence of ASB, with up to 100% in chronically catheterized patients (1). ASB is largely caused by the same types of bacteria that are associated with symptomatic UTI. The most common bacteria isolated from urine specimens from patients with ASB include Escherichia coli as well as other Enterobacterales, including Klebsiella spp., Enterobacter spp., Proteus spp., and Citrobacter spp. Other organisms isolated include coagulase-negative Staphylococcus, Staphylococcus aureus, Enterococcus species, Streptococcus agalactiae (group B Streptococcus), and other Gram-negative bacilli (Pseudomonas spp., etc.) (6). In patients with ASB and indwelling urethral catheters, 77% of specimens are polymicrobial (6). The presence of yeast in the urine of asymptomatic patients is almost always the result of contamination with colonizing organisms, and there are no consistent diagnostic criteria to define significant infection (7). Asymptomatic candiduria is usually benign, and guidelines do not recommend antifungal therapy unless the patient is at high risk of dissemination, such as severely immunosuppressed or neutropenic patients, infants with very low birth weight (<1,500 g), and patients who will undergo urologic instrumentation (7). The elimination of predisposing risk factors, such as indwelling bladder catheters, whenever feasible, is usually sufficient to clear the candiduria (7). Candiduria may implicate Candida spp. as the causative organism in neonates with signs and symptoms of meningoencephalitis but negative blood cultures or cerebrospinal fluid cultures (7).

Routine screening for and treatment of ASB is not generally recommended. Guidelines for the management of ASB from the Infectious Diseases Society of America (IDSA) are the most comprehensive and were updated in 2019, supported by a revised evidence report and systematic review (1) (Table 2). The IDSA guidelines advise that only two groups, pregnant women and patients undergoing urologic procedures in which mucosal bleeding is anticipated, can benefit from diagnosis and treatment of ASB (1). Not treating ASB has been a longstanding IDSA recommendation, and the updated guidelines consider populations not addressed in previous guidelines. The updated IDSA guidelines make specific recommendations to avoid screening and treatment of ASB in the following populations: pediatric patients, healthy nonpregnant women, older patients (men and women) residing in the community or in long-term care facilities, patients with well-regulated diabetes, patients with short-term (<30 days) or long-term indwelling urethral catheters, patients with impaired voiding after spinal cord injuries, patients with recurrent urinary tract infections, patients undergoing elective, nonurologic surgeries, patients undergoing implantation or living with urologic devices, and patients who have received a nonrenal solid-organ transplant (1). Renal transplant patients who are beyond 1 month of their transplant should not undergo screening for or treatment of ASB. There is insufficient evidence to recommend for or against screening or treatment of ASB within the first month after renal transplantation or for patients with indwelling catheters at the time of catheter removal (1). There are also no recommendations for or against screening neutropenic patients, noting that patients with high-risk neutropenia (<100 cells/mm³, ≥7-day duration following chemotherapy) are frequently on prophylactic antimicrobial therapy, and patients with low-risk neutropenia (>100 cells/mm³, ≤7-day duration following chemotherapy) and ASB are likely not at greater risk of symptomatic UTI than nonneutropenic patients (1).

TABLE 2.

Clinical practice guidelines for screening for asymptomatic bacteriuria

Recommendation	Organization,a evidence gradeb
Screening urine cultures recommended
Pregnancy	IDSA, strong recommendation, moderate-quality evidence
	USPSTF, grade B
	EAU, weak recommendation
	CTFPHC, weak recommendation, low quality evidence
	NICE, no rating
	AAFP, no rating
	Other societies (AAP, ACOG, SOGC, and SIGN) do not make specific recommendations for screening but do have recommendations for treating ASB
Prior to invasive urologic procedures associated with mucosal injury	IDSA, strong recommendation, moderate-quality evidence
	EAU, strong recommendation
Screening urine cultures not recommended
Pediatric patients	IDSA, strong recommendation, low-quality evidence
Healthy nonpregnant women	IDSA, strong recommendation, moderate-quality evidence
	USPSTF, grade D
	EAU, strong recommendation
Older men or women residing in community or long-term care facilities	IDSA, strong recommendation, moderate-quality evidence
	USPSTF, grade D
	EAU, strong recommendation
Older functionally or cognitively impaired patients	IDSA, strong recommendation, low-quality evidence
Well-regulated diabetic patients	IDSA, strong recommendation, moderate-quality evidence
	EAU, strong recommendation
Renal transplant patients >30 days posttransplant	IDSA, strong recommendation, high-quality evidence
	EAU, strong recommendation
Solid organ transplant patients other than renal transplant	IDSA, strong recommendation, moderate-quality evidence
Spinal cord injury with impaired voiding	IDSA, strong recommendation, low-quality evidence
	EAU, strong recommendation
Patients with short-term (<30 days) or long-term indwelling urethral catheter	IDSA, strong recommendation, low-quality evidence)
Patients undergoing elective nonurologic surgery	IDSA, strong recommendation, low-quality evidence
	EAU, strong recommendation (prior to arthroplasty)
Patients undergoing implantation or living with urologic devices (i.e. penile prosthesis, artificial urologic sphincter)	IDSA, weak recommendation, very low-quality evidence
	EAU, strong recommendation (for patients with dysfunctional or reconstructed urinary tract)
Patients with recurrent urinary tract infections	EAU, strong recommendation
No recommendations made for urine cultures
Neutropenic patients	IDSA knowledge gapc
Patients with indwelling urethral catheters at time of catheter removal	IDSA knowledge gap
Renal transplant recipients within one month of transplantation	IDSA knowledge gap

^aIDSA, Infectious Diseases Society of America (1); USPSTF, United States Preventive Services Task Force (8); EAU, European Association of Urology (2); CTFPHC, Canadian Task Force on Preventive Health Care (10); NICE, United Kingdom National Institute for Health and Care Excellence (11); AAFP, American Academy of Family Physicians (8); AAP, American Academy of Pediatrics (8); ACOG, American College of Obstetricians and Gynecologists (8); SOGC, Society of Obstetricians and Gynaecologists of Canada (cited in Moore et al. [10]); SIGN, Scottish Intercollegiate Guidelines Network (12).

^bGrade A, the USPSTF recommends the service. There is high certainty that the net benefit is substantial. Suggestions for practice: offer or provide this service. Grade B, the USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial. Suggestions for practice: offer or provide this service. Grade C, the USPSTF recommends selectively offering or providing this service to individual patients based on professional judgment and patient preferences. There is at least moderate certainty that the net benefit is small. Suggestions for practice: offer or provide this service for selected patients depending on individual circumstances. Grade D, the USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. Suggestions for practice: discourage the use of this service. Grade I, the USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined. Suggestions for practice: read the clinical considerations section of USPSTF recommendations statements; if the service is offered, patients should understand the uncertainty about the balance of benefits and harms.

^cIDSA knowledge gap, insufficient evidence to inform a recommendation for or against.

Multiple other societies, including the United States Preventive Services Task Force (USPSTF), the European Association of Urology (EAU), the American Academy of Family Physicians (AAFP), the Canadian Task Force on Preventive Health Care (CTFPHC), and the United Kingdom National Institute for Health and Care Excellence (NICE), also recommend screening pregnant women for ASB, although in recently updated guidelines, the USPSTF downgraded its recommendation from grade A to grade B (2, 8–11). (For grade A, the USPSTF recommends this service with high certainty that the net benefit is substantial. For grade B, the USPSTF also recommends this service but states that there is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial. For both grade A and grade B, the USPSTF suggestions for practice are to offer or provide the service). Guidelines from the American College of Obstetricians and Gynecologists (ACOG), the American Academy of Pediatrics (AAP), the Society of Obstetricians and Gynaecologists of Canada (SOGC), and the Scottish Intercollegiate Guidelines Network (SIGN) do not make specific recommendations for screening but support treatment for ASB in pregnant women (8, 10, 12). In addition to the IDSA, the EAU also supports screening patients for bacteriuria prior to urologic procedures associated with mucosal trauma (2).

ASB remains a major target for antimicrobial stewardship, because inappropriate screening and antibiotic treatment of patients with ASB can result in worsening antimicrobial resistance patterns of urinary pathogens as well as increased Clostridioides difficile infections, adverse drug effects, and unnecessary costs for medical care (13). This minireview will focus on ASB screening and treatment recommendations in select populations that are at greater risk of developing a symptomatic infection and on the role of addressing ASB in antimicrobial stewardship.

PREGNANCY

Asymptomatic bacteriuria occurs in up to 10% of pregnant women compared to 1% to 5% in healthy premenopausal women (1). Studies dating back to the 1960s report associations of ASB in pregnancy with low birth weight, preterm delivery, stillbirths, and progression to symptomatic UTI, including pyelonephritis (1). The best-documented consequence of untreated ASB in pregnant women is a significant risk of acute pyelonephritis, which can be life-threatening to both the mother and infant. The incidence of pyelonephritis associated with ASB in pregnancy was reported to be as high as 25 to 36% in older studies, and these older studies have informed guidelines, since few recent studies have been published (1, 8).

A more recent multicenter prospective cohort study of over 4,000 pregnant women (age, >18 years) between 16 and 22 weeks of gestation was conducted in the Netherlands (14). ASB screening was done with one point-of-care dipslide (UricultW; Orion Diagnostica, Espoo, Finland) containing cysteine lactose electrolyte-deficient medium and MacConkey medium and was considered positive at ≥10⁵ CFU/ml of a single microorganism or when 2 different colony types were isolated but at least one had a concentration of ≥10⁵ CFU/ml (14). Women with ASB were eligible to participate in the randomized controlled portion of the trial that compared 5 days of treatment with either nitrofurantoin or placebo. The risk of pyelonephritis was low in pregnant women without ASB (0.6%, 24 of 4,035 women), and the presence of untreated or placebo-treated ASB increased the risk to about 2.5% (5 of 208 cases) (adjusted odds ratio, 3.9; 95% confidence intervals, 1.4 to 11.4). This study concluded that ASB was not associated with preterm birth but was significantly associated with pyelonephritis, and the authors questioned routine screening and treatment of ASB in pregnancy given the low absolute risk of pyelonephritis in untreated ASB (14). The population studied was at low risk of preterm birth or complicated UTI, and ASB was defined by one screening urine culture. Whether this is generalizable to pregnant women at higher risk or with variable access to health care requires further study. Given the currently available data, pregnancy remains one of the conditions in which screening and treatment for ASB is recommended by many medical societies to reduce the rate of pyelonephritis and its complications. The IDSA, ACOG, and AAP recommend screening with urine culture early in pregnancy, whereas the USPTF and AAFP recommend screening at 12 to 16 weeks of gestation or at the first prenatal visit if it occurs later than 12 to 16 weeks (1, 8, 9).

There is insufficient evidence to recommend one antibiotic over another for the treatment of pregnant women with ASB (15). Empiric antibiotic selection should be based on local susceptibility patterns and safety of the antibiotic in pregnancy (15). The most commonly used antibiotics in this setting include penicillins, cephalosporins, clindamycin, macrolides, and nitrofurantoin. There is limited data about the use of fosfomycin in pregnancy. Trimethoprim, sulfonamides, and ciprofloxacin are generally avoided when alternatives exist due to the potential for adverse events in pregnancy (1, 15). Final treatment should be adjusted based on culture results as needed (15).

The optimal duration of therapy has not been established and may depend on the antibiotic used. However, guidelines suggest a short course of oral antibiotics, similar to the treatment of symptomatic cystitis in pregnancy. The IDSA recommends a 4- to 7-day course, and the EAU recommends a 2- to 7-day course (1, 2). Current guidelines do not comment on whether repeat urine cultures should be obtained posttreatment of ASB in pregnancy, since there is a lack of direct evidence to support the practice (1). Similarly, there is no evidence to support the use of prophylactic antibiotics for the duration of pregnancy to prevent recurrence (1).

UROLOGIC PROCEDURES

ASB is well established as a risk factor for the development of significant postoperative infections in patients undergoing transurethral resection of the prostate (TURP), as well as other urologic procedures that breach the mucosal lining (e.g., ureteroscopy, including lithotripsy) (1). Screening for and treatment of ASB is recommended before these procedures (1, 2). A urine culture should be obtained prior to the procedure, and in cases of ASB, preoperative treatment is recommended. Targeted, rather than empirical, therapy with a short course (1 or 2 doses) of antibiotic initiated 30 to 60 min before the procedure is favored over a more prolonged course (1). The timing of the culture is not stated, presumably at least several days before therapy, given that 24 to 48 h are needed for results to be available.

Outcome studies have suggested that prosthetic urologic surgery can be done safely without performing preoperative screening urine cultures. Guidelines do not recommend screening for and treatment of ASB for patients undergoing penile prosthesis implantation or artificial urine sphincter placement or in those living with implanted urological devices (1). Studies also note that common skin microbiota likely introduced at the time of surgery are typically the cause of penile prosthesis or artificial urine sphincter infection and not urinary tract pathogens.

Prostate biopsies may occasionally be done through the urethra or perineum, but the most common approach is through the rectum. The transrectal approach presents the possibility of additional infectious complications, e.g., ASB or UTI, prostatitis, bacteremia, and/or sepsis, following the procedure. Infection is caused by bacteria present in the rectum prior to the biopsy procedure that are seeded into the prostate, bladder, and/or bloodstream by the hollow-core biopsy needle that passes through the rectum into the prostate/bladder. Studies suggest that prebiopsy urine culture to screen for ASB is unnecessary, except perhaps in men with a history of UTI or urinary retention (16). Prebiopsy rectal cultures have, however, become accepted practice to detect fluoroquinolone-resistant bacteria, allowing for targeted antibiotic prophylaxis (17).

INTERVENTIONS AND ANTIBIOTIC STEWARDSHIP

Despite the presence of guidelines with strong recommendations to not screen for ASB among nonpregnant adults, inappropriate use of urine cultures and antibiotic treatment of ASB appear to be common in daily practice. Based on several recent studies, the estimated rate of overtreatment of ASB in hospitalized patients is about 30 to 60% (18–22). These studies and others have found that there is no benefit associated with the treatment of ASB in patients who have no clear indication, and there is potential harm, e.g., longer length of hospitalization, C. difficile infection, antibiotic adverse events, and increased costs (20, 22).

Choosing Wisely, an ABIM (American Board of Internal Medicine) Foundation Initiative, is a United States-based educational campaign to reduce unnecessary health care. Choosing Wisely proposals from numerous professional societies in the United States, Canada, and Australia have identified the overdiagnosis and overtreatment of ASB as a problem requiring attention (Table 3). The recommendations from the societies are publicized on Choosing Wisely websites (http://www.choosingwisely.org/clinician-lists/) to raise awareness and provide a call to action for health care providers to initiate interventions at the local institutions where they work.

TABLE 3.

Choosing wisely recommendations for asymptomatic bacteriuria

Society	Recommendation
Choosing Wisely United States (http://www.choosingwisely.org/clinician-lists)
American Academy of Pediatrics	Avoid the use of surveillance cultures for screening and treatment of ASB
American Geriatrics Society (Feb 27, 2014)	Do not use antimicrobials to treat bacteriuria in older adults unless specific urinary tract symptoms are present
The Society for Post-Acute and Long-Term Care Medicine (AMDA) (Mar 20, 2015)	Do not obtain a urine culture unless there are clear signs and symptoms that localize to the urinary tract
Infectious Diseases Society of American (IDSA)	Do not treat ASB with antibiotics
Society for Healthcare Epidemiology of America (SHEA)	Do not perform urinalysis, urine culture, blood culture, or C. difficile testing unless patients have signs or symptoms of infection; tests can be falsely positive, leading to overdiagnosis and overtreatment
American Urological Association (June 11, 2015)	Prescribing antimicrobials to patients using indwelling or intermittent catheterization of the bladder unless there are signs and symptoms of urinary tract infection
Choosing Wisely Canada (https://choosingwiselycanada.org)
Association of Medical Microbiology and Infectious Disease Canada (Feb 1, 2017)	Do not obtain a urine culture from adults who lack symptoms localizing to the urinary tract or fever, unless they are pregnant or undergoing genitourinary instrumentation where mucosal bleeding is expected
Canadian Association of Pathologists (Oct 29, 2014)	Do not obtain urine culture on asymptomatic patients, including elderly patients, patients with diabetes, or as a follow-up to confirm effective treatment
Canadian Geriatrics Society (Apr 2, 2014)	Do not use antimicrobials to treat bacteriuria in older adults unless specific urinary tract symptoms are present
Canadian Nurses Association (Jan 9, 2017)	Do not treat bacteriuria in older adults unless specific urinary tract symptoms are present
Canadian Nurses Association/Infection Prevention and Control Canada (Nov 2017)	Do not do urine dipstick or culture unless urinary tract symptoms are present
Long Term Care Medical Directors Association of Canada (Jan 18, 2017)
Canadian Society of Hospital Medicine (June 2, 2015)	Do not prescribe antibiotics for ASB in nonpregnant patients
Canadian Urological Association (Oct 29, 2014)	Do not treat asymptomatic bacteriuria in elderly patients
Choosing Wisely Australia (www.choosingwisely.org.au)
Australasian Society for Infectious Diseases (Mar 1, 2016)	Do not use antibiotics in asymptomatic bacteriuria
Australian and New Zealand Society for Geriatric Medicine (Aug 9, 2016)	Do not treat bacteriuria in older adults where specific urinary tract symptoms are not present
Royal College of Pathologists of Australasia (Apr 22, 2015)	Do not perform surveillance urine cultures or treat bacteriuria in elderly patients in the absence of symptoms or signs of infection

Several studies have identified a variety of barriers to managing ASB according to guidelines. The strongest factors were linked to the interpretation of laboratory results, and providers tended to treat pyuria or a positive urine culture, particularly with Gram-negative bacteria and higher bacterial counts of >10⁵ CFU/ml, without taking the clinical picture into account (19, 22–24). There are also misperceptions about ASB developing into symptomatic UTI in elderly patients and an anticipated improved physical and mental function with antibiotic treatment (24). As such, older patients, especially women and patients with altered mental status, dementia, or urinary incontinence, are frequently unnecessarily treated (19, 22). Audits to determine familiarity with guidelines have shown that a lack of awareness is also a central barrier to their implementation. Less than half of resident physicians working in an academic hospital were aware of indications for treating ASB in one survey (19). The publication of guidelines does not, on its own, automatically result in their use (19, 24). Therefore, an implementation plan is needed. The plan should take into account what is known about barriers and develop tailored implementation strategies (19, 24).

A variety of strategies have been reported to decrease the inappropriate ordering of urinalysis and urine cultures and to decrease unnecessary treatment. A multifaceted approach that combines some elements of education, audit and feedback, and clinical decision support, along with evaluation and sustainability plans, is probably most effective (19, 20, 23). At the outset, it is essential to create a multidisciplinary team to design and carry out the plan. Members of the team could include infectious disease physicians, nursing leadership, microbiology staff, pharmacists, information technology specialists, and others (23). Existing antibiotic stewardship programs usually have the needed framework to coordinate activities across an institution (23).

Educational efforts directed at ordering providers and nursing staff to raise awareness of guidelines can have a positive impact. Educational interventions could include posters or pocket cards with short, user-friendly versions of the guidelines as well as continuing medical education sessions with small groups that emphasize symptoms, the poor predictive value of abnormal urinalysis, and the evidence supporting not treating ASB in certain populations to dispel erroneous assumptions about anticipated outcomes (22, 23). Groups employing educational interventions have documented decreases in urine culture collection from 2.6 to 0.9/1,000 patient days in one study and a reduction of about 9% in another study (23). Postintervention, fewer patients with ASB were treated with antibiotics (15% versus 47%; P < 0.05), and fewer monthly urine cultures were sent (3,127 versus 3,419; P < 0.001) (23).

Further strategies are workflow focused. Interventions to decrease the ordering of urine cultures when there are no clinical indications would have the most impact, since they would prevent detection and, therefore, subsequent treatment of ASB. Decision support systems are designed to prompt health care providers to manage clinical actions according to current evidence. One decision support strategy is to remove standing orders to facilitate reduction in urine cultures performed in nonindicated populations. An orthopedic center that performs over 3,000 surgeries yearly removed routine urine cultures from their preoperative order set (25). In addition, all cultures received in the microbiology laboratory from that clinic were rejected, with a comment stating that routine preoperative urine cultures are not indicated. The rejection included an option to call the laboratory to have the specimen processed if the patient had symptomatic UTI. Over a 3-year time period, there was a 99% relative reduction in the number of urine cultures processed with no significant increase in prosthetic joint infection as a result of the intervention, and none of the prosthetic joint infections reported during the intervention were caused by urinary pathogens (25).

Other proposed interventions occur at the stage of laboratory reporting. Many microbiology laboratories report a urine culture as positive if there is growth of ≥10⁴ CFU/ml, based on evidence that this threshold is most sensitive for detecting acute cystitis in young outpatient women. Multiple studies have shown that this threshold may not be appropriate for hospitalized patients and that ≥10⁵ CFU/ml is the most sensitive indicator for detecting a clinically significant UTI for inpatients with a urine specimen obtained noninvasively by a clean-catch voided or indwelling catheter. The data also strongly suggest that reporting a culture as positive encourages antibiotic treatment. As part of a 2-year controlled interrupted time series study at an acute care hospital in Toronto, Canada, the threshold for identification and susceptibility testing of potential uropathogens from inpatient urine cultures (excluding those from maternity wards and emergency departments and invasively obtained specimens) was changed from ≥10⁴ CFU/ml to ≥10⁵ CFU/ml (26). Isolates from urine cultures with colony counts between 10⁴ and 10⁵ CFU/ml were not worked up and were reported with a comment stating that cultures with organisms present in this quantity usually represent ASB and could be worked up at telephone request if there was a high clinical suspicion for UTI. The intervention was associated with a significant reduction in antimicrobial treatment among patients with colony counts in the 10⁴- to 10⁵-CFU/ml group compared with the 10⁵-CFU/ml control group, and there was no evidence of adverse events. There were few requests (less than 10%; n = 17) for workup in the 10⁴- to 10⁵-CFU/ml group, and when workup was requested, patients were more likely to have a UTI (6/17 [35%] versus 17/237 [7%]; P < 0.001).

Strategies that use audit and feedback of individual performance in real time can be highly effective but require substantial manual time and effort. Audit and feedback stewardship efforts to reduce overtreatment of ASB and culture-negative pyuria in one study involved the introduction of an electronic reminder after urine culture results were reported (18). Abnormal urine culture results were retrieved from the microbiology laboratory two or three times a week. In the intervention group, an educational reminder of evidence-based guidelines against treating ASB and culture-negative pyuria (which they defined as at least 4 leukocytes per high-power field) was placed on charts of patients receiving antibiotics. This reminder was sent within 48 h of urinalysis or urine culture collection if the following criteria were met: lack of documented UTI-related symptoms, presence of fewer than 10⁵ CFU/ml of a single pathogen on urine culture, and/or lack of pyuria. Compared to a control group, the intervention resulted in a statistically significant 65% reduction in mean unnecessary antimicrobial days with no adverse events noted (18).

The design of studies using multifaceted approaches are varied but generally combine education, audit and feedback, and clinical decision support (23). Prior to intervention at two tertiary care academic medical centers, the microbiology laboratories at each facility added a comment to all positive urine culture reports stating that antibiotic treatment is only indicated for symptomatic patients (27). At one of the centers, residents were given 15-min educational sessions presented by an infectious disease physician once a month before morning rounds. During these sessions, the residents also received verbal feedback on patients that had been identified by the intervention team as being inappropriately managed. In addition, the residents were provided with a UTI treatment algorithm that emphasized nontreatment for ASB. During the baseline period, 160/341 (46.9%) positive urine cultures were collected from asymptomatic patients at the two hospitals, and 94/160 (58.8%) were treated inappropriately with antibiotics. At the end of the intervention, 2/24 (8%) patients with ASB were inappropriately treated at the intervention hospital unit compared to 14/29 (52%) at the control hospital unit. Of note is that there was not a significant reduction of the number of urine cultures ordered until education of nursing staff was instituted in the intervention hospital unit.

A carefully constructed multiyear, multisite intervention project, called “Less is More,” will be launched from the successfully conducted “Kicking CAUTI” campaign at the Veterans Affairs Medical Center in Houston, TX (28). The new project aims to reduce the inappropriate treatment of ASB. The two main intervention strategies are to create an actionable algorithm and case-based audit and feedback to train clinicians to use the algorithm. For the algorithm, providers are asked to consider two questions about symptoms and whether there could be a nonurinary cause before ordering a urine culture or starting antibiotics. Pocket cards with the algorithm will be distributed as teaching materials. The pharmacy champion at each site will audit cases with positive urine cultures for which antibiotics have been prescribed to determine if the case is ASB versus UTI. The pharmacist will deliver feedback to the ordering provider by telephone in real time. Weekly 10-min teaching sessions focusing on the cases from that week will be presented to small groups of providers as part of standing meetings, e.g., rounds and resident teaching conferences. During the intervention, ongoing statistics will be posted on the network shared drive for each site. Outcome measures will be decreases in the number of screening cultures ordered, use of antibiotics, and C. difficile infections without an increase in urinary source bacteremia. The economic benefits associated with the adoption of this program will also be evaluated. The stewardship team recognizes that the success of this program and others like it depends largely on the energy, involvement, and reputation of the team leaders.

CONCLUSIONS

The two settings in which screening for and treatment of ASB are best established are before urological procedures where mucosal bleeding is anticipated (e.g., TURP) and for pregnant women. There are specific recommendations to avoid screening and treatment of ASB in pediatric patients, healthy nonpregnant women, older patients residing in the community or in long-term care facilities, patients with diabetes, patients with indwelling urethral catheters, patients with impaired voiding after spinal cord injuries, neutropenic patients, patients undergoing nonurologic surgeries, and nonrenal solid-organ transplant recipients. The benefits and harms of screening and treating renal transplant patients in the very early (<1 month) posttransplant period remains to be learned. There are also knowledge gaps regarding ASB in patients with high-risk neutropenia and in patients with indwelling catheters at the time of catheter removal (1). Antibiotic use for patients with ASB is unwarranted in many settings and is associated with higher rates of antibiotic resistance for individual patients as well as on a global level. Targeting ASB is an ideal antimicrobial stewardship opportunity for both inpatient and outpatient settings. Microbiology laboratories should facilitate adherence to guidelines and be actively involved in interventions to reduce urine culture ordering in asymptomatic patients in groups for which culture is not recommended.