1. Asymptomatic Bacteriuria: To Treat or Not to Treat
Amy Robertson, PharmD
PGY-1 Pharmacy Resident – UAMS NW

2. Disclosure and Conflict of Interest
I have no relevant financial or nonfinancial relationships or conflicts of interest to disclose.

3. Objectives
Describe appropriate management of asymptomatic bacteriuria in various patient populations
Identify risks associated with inappropriate treatment of asymptomatic bacteriuria
Understand the evidence supporting the recommendation not to treat asymptomatic bacteriuria in certain patient populations

4. Guidelines
“Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of Asymptomatic Bacteriuria in Adults”
Update in progress
Projected publication in Spring 2017

5. Definitions
Asymptomatic bacteriuria (ASB) – isolation of a specified quantitative count of bacteria in appropriately collected urine specimens obtained from a person without symptoms or signs referable to urinary infection
Acute uncomplicated urinary tract infection (UTI) – symptomatic bladder infection characterized by frequency, urgency, dysuria, or suprapubic pain in women with a normal genitourinary (GU) tract
Complicated urinary tract infection – symptomatic urinary infection in individuals with functional or structural abnormalities of the GU tract; may involve either the bladder or kidneys
Acute non-obstructive pyelonephritis – renal infection characterized by costovertebral angle pain and tenderness, often with fever

6. Definitions Continued
Relapse – recurrent UTI after therapy resulting from persistence of the pre-therapy isolate in the urinary tract
Reinfection – recurrent UTI with an organism originating from outside of the urinary tract, either a new bacterial strain or strain previously isolated that persisted in the colonizing flora
Pyuria – presence of increased numbers of polymorphonuclear leukocytes in the urine; evidence of inflammatory response in the urinary tract
ASB or asymptomatic urinary infection
Acute uncomplicated urinary tract infection: symptomatic bladder infection characterized by frequency, urgency, dysuria, or suprapubic pain in a woman with a normal genitourinary (GU) tract
Rarely occurs in men, UTI is usually considered complicated
Acute nonobstructive pyelonephritis: renal infection characterized by costovertebral angle pain and tenderness, often with fever
Occurs in the same population that experiences acute uncomplicated urinary infection

7. Why is this topic relevant?
Lack of understanding of ASB guidelines
Inappropriate ordering of urinalysis and urine cultures
Antibiotics prescribed when not indicated
Overtreatment of ASB
Antimicrobial resistance, adverse events, cost

8. Diagnosis Asymptomatic Women Asymptomatic Men
Two consecutive voided urine specimens with:
Isolation of the same bacterial strain AND ≥105 cfu/mL
Asymptomatic Men
Single voided urine specimen (clean-catch) with:
Isolation of 1 bacterial species AND ≥105 cfu/mL
Catheterized Women or Men
Single voided urine specimen with:
Isolation of 1 bacterial species AND ≥102 cfu/mL
Diagnosis is based on the culture of a urine specimen collected in a manner that minimizes contamination
Pyuria is common in subjects with asymptomatic bacteriuria

9. Urinary Tract Infection
ASB versus UTI
Bacteriuria
Urinary Tract Infection

10. Urinary Tract Infection
ASB versus UTI
Bacteriuria
Symptoms
Urinary Tract Infection
Frequency
Urgency
Dysuria
Suprapubic pain

11. Appropriate Criteria for Sending a Urine Culture2
Population
Criteria
Urinary catheter present (indwelling catheter, condom catheter, or intermittent straight cathetherization)
New onset of fever (>38ºC) or provider report of fever
Rigors
Altered mental status
Acute hematuria
Costovertebral pain or tenderness
Increased spasticity or autonomic dysreflexia (spinal cord injury)
Urinary catheter removed
<48 h prior
Any of the above criteria or
Urgency
Frequency
Dysuria
No history of urinary catheter or removal >48 h prior to development of symptoms
Fever >38ºC
Suprapubic pain
New or worsening incontinence

12. Prevalence of ASB Women Men
Increases with age, sexual activity, and a diagnosis of diabetes
No difference observed between pregnant and non-pregnant women
Men
Increases with age
Rarely seen in healthy, young men
No difference seen with diagnosis of diabetes
Special populations
Patients with impaired urinary voiding or in those with indwelling urinary devices
High prevalence irrespective of sex
Spinal cord injury
Prevalence of >50%
Hemodialysis
Prevalence of 28%
Elderly in long-term care facilities
Women, 25-50%
Men, 14-50%
Long-term indwelling catheter or permanent ureteric stent
Prevalence of 100%

13. ASB Prevalence in Special Populations
Patient Population
Prevalence
Short-term indwelling urethral catheters
2-7% per day
Spinal cord injury
>50%
Hemodialysis
28%
Elderly in long-term care facilities
Women: 25-50%
Men: 14-50%
Long-term indwelling catheter or permanent ureteric stent
100%
Special populations
Many patient groups with chronic disabilities or comorbidities characterized by impaired urinary voiding or with indwelling urinary devices have a very high prevalence of asymptomatic bacteriuria, irrespective of sex.
Patients with impaired urinary voiding or in those with indwelling urinary devices
High prevalence irrespective of sex
Spinal cord injury
Prevalence of >50%
Hemodialysis
Prevalence of 28%
Elderly in long-term care facilities
Women, 25-50%
Men, 14-50%
Long-term indwelling catheter or permanent ureteric stent
Prevalence of 100%

14. Long-term urologic device
Microbiology
Women
Escherichia coli
Other Enterobacteriaceae
Coagulase-negative staphylococci
Enterococcus species
Group B streptococci
Gardnerella vaginalis
Men
Gram-negative bacilli
Proteus mirabilis
Long-term urologic device
Pseudomonas aeruginosa
Providencia stuartii
Morganella morganii
Organisms common in women
E. coli
Single most common organism isolated from bacteriuric women
Less virulence in asymptomatic bacteriuria compared to those isolated from symptomatic infections

15. To Treat or Not to Treat?

16. Treat
Do Not Treat
Pregnant women
Urologic interventions/traumatic genitourinary procedures associated with mucosal bleeding
Premenopausal, non-pregnant women
Diabetic women
Older persons in the community
Elderly institutionalized subjects
Spinal cord injury patients
Long-term catheters
IDSA guidelines
Pyuria is not sufficient, by itself, to diagnose bacteriuria and the presence/absence of it does not differentiate symptomatic from asymptomatic urinary infection; Not an indication for antimicrobial treatment!
*Pyuria is NOT an indication for antimicrobial treatment*

17. Treatment Populations

18. Pregnant Women Why? Screening Treatment
20 to 30-fold increased risk of pyelonephritis
Increased risk of premature delivery of infants with low birth weight
Screening
Urine culture at least once in early pregnancy
Must test for cure once treated for ASB
Periodic screening for recurrent bacteriuria following antibiotic therapy
No recommendation on repeated screening of culture-negative women
Treatment
If urine culture is positive  give antibiotics
Optimal antibiotic duration has not been determined
May consider 3-7 days
Pregnant Women with asymptomatic bacteriuria
20 to 30-fold increased risk of pyelonephritis during pregnancy compared with those without bacteriuria
More likely to have premature delivery and to have infants of low birth weight
Antibiotic treatment:
Decreases the risk of pyelonephritis from 20-35% to 1-4%
Decreases the frequency of low-birth weight infants and preterm delivery
Optimal length of treatment with antibiotics has not been determined
Study compared continuous antibiotic therapy to the end of the pregnancy to 14 days of nitrofurantoin or sulfamethoxazole
If 2 week treatment group again developed bacteriuria they were re-treated based on weekly urine culture screening
Similar outcomes for both groups
A systematic review concluded that there was insufficient evidence to recommend a duration of antimicrobial therapy for pregnant women among singlel-dose, 3-day, 4-day, and 7-day treatment regimens
Optimal duration of antimicrobial therapy has not been determined
Recommendation: the duration of antimicrobial therapy should be 3-7 days
Screening
Pregnant patients should be screened for bacteriuria by urine culture at least once in early pregnancy and should be treated if the results are positive
Periodic screening for recurrent bacteriuria should be undertaken after therapy
No recommendation can be made for or against routine repeated screening of culture negative women in the later phase of pregnancy
Optimal frequency not defined
Pyuria has low sensitivity for identification of bacteriuria in pregnancy (50%)
****A prospective, randomized study of continuous antimicrobial therapy to the end of pregnancy compared with 14 days of nitrofurantoin or sulfamethizole, followed by weekly urine culture screening and re-treatment if bacteriuria recurred, reported similar outcomes for the2 treatment groups
***A recent Cochrane systematic review concluded that there was insufficient evidence to recommend a duration of antimicrobial therapy for pregnant women among single-dose, 3-day, 4-day, and 7-day treatment regimens [66]. Thus, the optimal duration of antimicrobial therapy for treatment of bacteriuria in pregnant women has not been determined.

19. Urologic Interventions
Why?
Higher rate of post-procedure bacteremia and sepsis
Antibiotics prevent complications of bacteriuria
Screening
Prior to transurethral resection of the prostate is recommended
Prior to other urologic procedures for which mucosal bleeding is anticipated
Treatment
Initiate antibiotics shortly before the procedure
Antibiotics should not be continued after the procedure
Exception: indwelling catheter remains in place
Little evidence for other procedures, but any intervention with a high probability of mucosal bleeding should be considered a risk
Pretreatment is not beneficial in all invasive procedures – replacement of a long-term indwelling foley catheter
Associated with low risk of bacteremia and antimicrobial treatment is not beneficial
Appropriate timing for administration of pre-procedure antibiotic not determined
Night before or immediately before the procedure is effective - >72H has been associated with superinfection
Optimal time to obtain a sample for culture before the procedure and the duration of antimicrobial therapy are also not addressed
May continue antibiotics until catheter is removed, but no concrete recommendation on this
If not indwelling catheter – d/c abx right after the procedure

20. Non-treatment Populations

21. Possible Considerations
Benefits
Risks
Adverse events
Antimicrobial resistance
Decreased mortality
Decreased recurrence

22. Premenopausal, non-pregnant women
No difference seen in recurrence rate of symptomatic UTI
Premenopausal, non-pregnant women
No differences in rates of symptomatic UTI, mortality, number of hospitalizations, or progression of diabetic complications
Diabetic Women
No difference in rates of symptomatic UTI, adverse outcomes, or survival
Older Persons in the Community
No difference in rates of symptomatic UTI, survival, or chronic symptoms
Increased rate of ADRs and reinfections with resistant organisms
Elderly Institutionalized Subjects
No difference in rate of occurrence of bacteriuria
Reinfections with resistant organisms
Spinal Cord Injury Patients
No difference in rates of symptomatic UTI or fever
Long-Term Catheters
Healthy, bacteriuric, premenopausal women are at increased risk for symptomatic UT and are more likely to have bacteriuria at follow-up, but it is not associated with long-term adverse outcomes (HTN, CKD, genitourinary cancer, or decreased survival rate) and treatment neither decreases the frequency of symptomatic infection nor prevents further epidsodes of bacteriuria.
The association of asymptomatic bacteriuria with symptomatic urinary infection is likely attributable to host factors that promote both symptomatic and asymptomatic urinary infection, rather than symptomatic infection being attributable to asymptomatic bacteriuria
Long-term catheters: 75% of reinfecting organisms in untreated group remained susceptible to cephalexin (only 36% in treatment group)

23. Actual Considerations
Benefits
Risks
C. difficile infection
Adverse events
Antimicrobial resistance
Length of stay/cost
No difference in:
Recurrence of symptomatic UTI
Survival rates
Hospitalizations
Adverse outcomes
Worsening GU symptoms, progression of disease

24. Evidence Unnecessary urine cultures
According to Hartley et al2, 76% (71/94) of patients with ASB had no guideline- based indication for urine culture
Inappropriate prescribing of antibiotics
20-83% of patients with ASB (positive urine culture) receive antibiotics2,5,7
Hartley et al2 identified 435 days of unnecessary antibiotic use
Increased antibiotic resistance
Cai et al4 revealed E. coli isolates significantly more resistant to antibiotics in patients repeatedly treated for ASB compared to no treatment
Increased recurrence rate
Cai et al4 showed significantly more recurrences in patients treated for ASB
38% (97/257) in non-treated patients versus 70% (204/293) in treated patients

25. Cognitive Biases WBC Altered mental status Pyuria Old age Fever
Organism
Pyuria
WBC
Fever
Old age
Altered mental status
Common cognitive biases that lead to overtreatment of ASB include:
Type of organism
Presence of pyuria/change in character of the urine
Leukocytosis
Fever with alternative source
Old age
Altered mental status

26. What needs to be done?
“Multimodal interventions are needed to improve antimicrobial use”2
Possible mechanisms2 for decreasing inappropriate treatment of ASB include:
Education
Audit and feedback
Computer-based reminders
Antibiotic “timeouts”
Multiple studies have shown improvements in prescribing practices after implementation of various interventions
Grigoryan et al3 administered a pre- and post-intervention survey that revealed:
Significant increase in knowledge scores
Decreased utilization of inaccurate prescribing cues

27. Intervention Results3
Pre-intervention sample
Post-intervention sample
ESBL E. coli
E. Coli
Candida
Mixed GP + enterococcus
Mixed GP
Percent of respondents that withheld antibiotics from patients with ASB

28. What Pharmacists Can Do…
In-service presentations
Notifications posted in the physician offices, conference rooms, and mailboxes
Pocket cards with ASB algorithms and antibiogram
Electronic memorandums to hospitalists for ASB management recommendations
Pharmacists alerted daily to positive urine cultures
Pharmacist participation in daily rounds
Encourage hospitalists to document indication for ordering urine culture, the category of UTI being treated, and anticipated duration of treatment
Implementation of an antimicrobial stewardship educational quality initiative (ASEQI) using in-service presentations on ASB provided to the targeted physician groups and clinical pharmacists; notifications posted in the physician offices, conference rooms, and mailboxes; distribution of pocket cards containing an algorithm on ASB diagnosis and an antibiogram for common uropathogens; electronic memorandums to hospitalists for ASB management recommendations; pharmacist participation in daily rounds with EM and IM teams; daily review of common antibiotics for the treatment of UTI by members of the antimicrobial stewardship program (ASP)
Before-and-after educational initiative analysis assessing ASB management among the emergency medicine, internal medicine, and hospitalist medicine services.

29. Yes No Send urinalysis and urine cultures Do NOT send urine culture
Does the patient have any of the following without alternate explanation?
Urgency, frequency, dysuria
Suprapubic pain/tenderness
Flank pain or tenderness
New onset delirium
Fever >38ºC or rigors
Acute hematuria
Increased spasticity or autonomic dysreflexia in spinal cord injury
≥2 SIRS criteria or shock with concerns for sepsis
Send urinalysis and urine cultures
Document indication
Do NOT send urine culture
Yes No

30. What Pharmacists Can Do…
Multi-modal pharmacist-driven interventions led to a significant decrease in treatment of ASB
Hartley SE et al6 revealed decrease in inappropriate antibiotics from 76.8% (76/99) to 53.3% (49/92)
Hartley SE et al6 revealed decrease in antimicrobial days of therapy per patient from 4.6 (455 days/99 patients) to 3.3 (305 days/92 patients)
Kelley et al7 revealed decrease in empiric antibiotics from 62% (66/107) to 26% (28/107)

31. ASB Resource Nebraska Medicine Antimicrobial Stewardship
Urinary Tract Infection and Asymptomatic Bacteriuria Guidance

32. Which patient should not receive antimicrobial treatment?
28-year-old asymptomatic pregnant female with urine culture revealing bacteriuria
72-year-old male with urine culture revealing >100,000 cfu/mL, new-onset altered mental status, fever, and costovertebral pain
20-year-old female with positive urinalysis, urgency, and dysuria
45-year-old asymptomatic diabetic female with pyuria and urine culture revealing >100,000 cfu/mL
65-year-old male with planned transurethral resection of the prostate found to have asymptomatic bacteriuria
Answer = D

33. Conclusions
There are select patient populations that warrant treatment of ASB
Pregnant women
Urologic interventions
Risks of treating ASB outweigh benefits in other patient populations
Interventions are needed to bridge the gap between recommendations in clinical guidelines and prescribing habits

34. References
1Nicolle LE, Bradley S, Colgan R, et al. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis 2005;40:643–654.
2Hartley S, Valley S, Kuhn L, et al. Overtreatment of Asymptomatic Bacteriuria: Identifying Targets for Improvement. Infect Control Hosp Epidemiol 2015;36(4):470–473. doi: /ice
3Grigoryan L, Naik AD, Horwitz D, et al. Survey find improvement in cognitive biases that drive overtreatment of asymptomatic bacteriuria after a successful antimicrobial stewardship intervention. Am J Infect Control 2016.
4Cai T, Nesi G, Mazzoli S, et al. Asymptomatic Bacteriuria Treatment Is Associated With a Higher Prevalence of Antibiotic Resistant Strains in Women With Urinary Tract Infections. Clin Infect Dis 2015;61(11):1655–61.
5Lee MJ, Kim M, Kim NH, et al. Why is asymptomatic bacteriuria overtreated?: A tertiary care institutional survey of resident physicians. BMC Infect Dis 2015;15:289. doi: /s
6Hartley SE, Kuhn L, Valley S, Washer LL, Gandhi T, Meddings J, Robida M, Sabnis S, Chenoweth C, Malani AN, Saint S, Flanders SA. Evaluating a Hospitalist-Based Intervention to Decrease Unnecessary Antimicrobial Use in Patients with Asymptomatic Bacteriuria. Infect Control Hosp Epidemiol 2016;37:1044–1051.
7Kelley D, Aaronson P, Poon E, McCarter YS, Bato B, Jankowski CA. Evaluation of an Antimicrobial Stewardship Approach to Minimize Overuse of Antibiotics in Patients with Asymptomatic Bacteriuria. Infect Control Hosp Epidemiol 2014;35(2):
8Trautner BW, Grigoryan L, Petersen NJ, et al. Effectiveness of an Antimicrobial Stewardship Approach for Urinary Catheter- Associated Asymptomatic Bacteriuria. JAMA Intern Med 2015;175(7): doi: /jamainternmed
9Irfan N, Brooks A, Mithoowani S, et al. A Controlled Quasi-Experimental Study of an Educational Intervention to Reduce the Unnecessary Use of Antimicrobials For Asymptomatic Bacteriuria. PLoS ONE 10(7):e doi: /journal.pone
10Colgan R, Nicolle LE, McGlone A, Hooton TM. Asymptomatic Bacteriuria in Adults. Am Fam Physician 2006;74:

35. Questions?

36. Asymptomatic Bacteriuria: To Treat or Not to Treat
Amy Robertson, PharmD
PGY-1 Pharmacy Resident – UAMS NW