Asymptomatic Bacteriuria in Hospitalized Patients

1. Asymptomatic Bacteriuria in Hospitalized Patients Mattie M. Follen, PharmD PGY-1 Pharmacy Resident Millcreek Community Hospital October 26, 2019

2. Pharmacist Objectives • At the end of this presentation, pharmacists should be able to: • Distinguish when it is appropriate to treat for a urinary tract infection (UTI) in hospitalized patients • Identify the outcomes associated with antibiotic treatment of hospitalized patients with asymptomatic bacteriuria

3. Technician Objectives • At the end of this presentation, technicians should be able to: • Recognize the correlation between urinary symptoms and the diagnosis of a UTI • Identify consequences of inappropriate antibiotic use

4. Background • Urinary tract infections (UTIs) are the second most common infection among hospitalized patients • Accurate diagnosis requires a combination of relevant signs and symptoms, generally supported by a positive urine culture • Asymptomatic bacteriuria (ASB): bacterial growth in a urine culture without accompanying symptoms • Treatment of ASB with antibiotics does not improve outcomes • Exceptions: pregnancy or patients undergoing invasive urological procedures

5. UTI • Cystitis: infection of the bladder/lower urinary tract • Pyelonephritis: infection of the kidney/upper urinary tract • Risk factors: recent sexual intercourse, history of UTI, comorbidities such as diabetes or structural or functional urinary tract abnormalities • Microbiology: Escherichia coli is the most frequent microbial cause of UTI • Treatment options: nitrofurantoin, fosfomycin, sulfamethoxazole-trimethoprim, cephalosporins

6. Background • Inappropriate use of antibiotics can result in adverse events, increased antibiotic resistance, and Clostridioidesdifficileinfection • Few studies have assessed factors and outcomes associated with antibiotic treatment for ASB in hospitalized patients • Important to identify factors associated with inappropriate treatment of ASB and evaluate the clinical outcomes of antibiotic treatment

7. Diagnostic Approach to UTI • Clinical suspicion and evaluation: UTI should be suspected in patients who have symptoms of dysuria, urinary frequency or urgency, hematuria, and/or suprapubic pain • No additional testing is warranted to make the diagnosis • Urinalysis (UA) is a useful diagnostic tool if symptoms are suggestive of UTI but not clearly diagnostic • Absence of pyuria on UA suggests a diagnosis other than UTI

8. Diagnostic Approach to UTI • Urinalysis (UA) is a useful diagnostic tool if symptoms are suggestive of UTI but not clearly diagnostic • Absence of pyuria on UA suggests a diagnosis other than UTI • Urine culture and susceptibility testing are also generally unnecessary • Exceptions: • Patients who are at risk for infection with a resistant organism • Patients with risk factors for more serious infection • Underlying urologic abnormalities, immunocompromising conditions, poorly controlled diabetes

9. Variables Associated with ASB Treatment • Patient characteristics • Older age, acutely altered mental status, dementia, urinary incontinence • Laboratory results • Positive urinalysis (UA) • Presence of leukocyte esterase or nitrite, or > 5 white blood cells per high-power field • Urine culture with a bacterial colony count greater than 100,000 CFU/mL

10. Risk Factors and Outcomes Associated with Treatment of Asymptomatic Bacteriuria in Hospitalized Patients The Journal of the American Medical Association 2019 Petty LA, Vaughn VM, Flanders SA, Malani AN, Conlon A, Kaye KS, Thyagarajan R, Osterholzer D, Nielsen D, Eschenauer GA, Bloemers S, McLaughlin E, Gandhi TN

11. Importance of Study • Treatment of asymptomatic bacteriuria with antibiotics is a common factor for inappropriate antibiotic use • Risk factors and outcomes associated with treatment of ASB in hospitalized patients are not well defined • Objective: To evaluate factors associated with treatment of ASB among hospitalized patients and the possible association between treatment and clinical outcomes

12. Study Design and Participants • Retrospective cohort study • January 1, 2016 – February 1, 2018 • 46 hospitals in the Michigan Hospital Medicine Safety Consortium • A total of 2733 hospitalized medical patients with ASB, defined as a positive urine culture without any documented signs or symptoms attributable to urinary tract infection, were included in the analysis • Exposures: one or more antibiotic dose for treatment of ASB

13. Main Outcomes and Measures • Estimators of antibiotic treatment of ASB • Secondary outcomes: • 30 day mortality • 30 day hospital readmission • 30 day emergency department visit • Discharge to post-acute cares settings • Clostridioidesdifficile infection at 30 days • Duration of hospitalization after urine testing

14. Results • Of 2733 patients with ASB, 2138 were women (78.2%); median age was 77 years • A total of 2259 patients (82.7%) were treated with antibiotics for a median of 7 days (IQR, 4-9 days) • Treatment of ASB was associated with longer duration of hospitalization after urine testing • 4 vs 3 days; relative risk 1.37; 95% CI 1.28 – 1.47 • No other differences in secondary outcomes were identified

15. Conclusions and Relevance • Hospitalized patients with ASB commonly receive inappropriate antibiotic therapy • Antibiotic treatment did not appear to be associated with improved outcomes • Treatment may be associated with longer duration of hospitalization after urine testing • Reduction of inappropriate antibiotic use: • Stewardship efforts should focus on improving urine testing practices and management strategies for elderly patients with altered mental status

16. Clinical Practice Guidelines for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America Infectious Diseases Society of America 2019 Nicolle, L.E., Kalpana, G., Bradley, S. F., Colgan, R., DeMuri, G. P., Drekonja D., Eckert, L. O., Geerlings S. E., Köves, B., Hooton, T. M., Juthani-Mehta, M., Knight, S. L., Saint, S., Schaeffer, A. J., Trautner, B., Wullt, B, Siemieniuk, R.

17. Background • Studies have shown that antimicrobial treatment does not confer any benefits • Antimicrobials increase the risk of outcomes such as antimicrobial resistance and Clostridioidesdifficile infection (CDI) • Increase the risk of UTI shortly after therapy • For some populations with a high prevalence of ASB, a sterile urine cannot be maintained, despite intense antimicrobial use • Chronic indwelling catheters, older institutionalized populations, patients with spinal cord injury (SCI), and some persons with diabetes

18. Background • Includes new recommendations for populations not previously addressed • Pediatric patients • Solid organ transplant recipients • Patients with neutropenia • Patients undergoing non-urologic surgery • Addresses the interpretation of non-localizing clinical symptoms in populations with a high prevalence of ASB

19. Background • Antimicrobial use drives antimicrobial resistance in the community, as well as in the individual treated • Antimicrobial stewardship programs have identified the treatment of ASB as an important contributor to inappropriate antimicrobial use, which promotes resistance • A positive urine culture often encourages antimicrobial use, irrespective of symptoms • Obtaining urine cultures when not clinically indicatedpromotes inappropriate antimicrobial use

20. Definitions • The definition of ASB in patients without indwelling catheters is ≥105CFU)/mL in a voided urine specimen without signs or symptoms attributable to UTI • Women • 2 consecutive specimens should be obtained, preferably within 2 weeks, to confirm the persistence of bacteriuria. • Men • A single urine specimen meeting these quantitative criteria is sufficient for diagnosis • Patients with indwelling devices often have multiple organisms isolated from the urine • Organisms present in lower quantitative counts likely represent contamination of the urine specimen

21. Pediatric Patients • IDSA recommends against screening for or treating asymptomatic bacteriuria in infants and children

22. Kidney Transplant Recipients • In renal transplant recipients who have had renal transplant surgery >1 month prior, IDSA recommends against screening for or treating ASB • There is insufficient evidence to inform a recommendation for or against screening or treatment of ASB within the first month following renal transplantation

23. Solid Organ Transplant Recipients • IDSA recommends against screening for or treating ASB in non-renal solid organ transplant (SOT) recipients • Limit the growth of antimicrobial-resistant organisms or Clostridioidesdifficile infection in SOT patients, who are at increased risk for these adverse outcomes • Symptomatic UTI is uncommon in non-renal SOT recipients and adverse consequences of symptomatic UTI are extremely rare • The risk of complications from ASB is probably negligible

24. Patients with Neutropenia • Patients with high-risk neutropenia • Absolute neutrophil count <100 cells/mm3, ≥ 7 days’ duration following chemotherapy • There is no recommendation for or against screening for ASB or treatment of ASB

25. Patients with Neutropenia • High-risk neutropenia managed with current standards of care • Including prophylactic antimicrobial therapy and prompt initiation of antimicrobial therapy when febrile illness occurs • It is unclear how frequently ASB occurs and how often it progresses to symptomatic UTI

26. Patients Undergoing Non-urologic Surgery • IDSA recommends against screening for or treating ASB in patients undergoing elective non-urologic surgery

27. When to Screen for and Treat ASB • Pregnant women • Patients undergoing endo-urological procedures

28. Pregnant Women with ASB • ISDA suggests a urine culture collected at 1 of the initial visits early in pregnancy • There is insufficient evidence to inform a recommendation for or against repeat screening during the pregnancy for a woman with an initial negative screening culture or following treatment of an initial episode of ASB.

29. Pregnant Women with ASB • IDSA suggests 4–7 days of antimicrobial treatment rather than a shorter duration • The optimal duration of therapy will vary depending on the antimicrobial given • The shortest effective course should be used

30. When ASB Should Not Be Treated • Pediatric patients • Healthy, non-pregnant women • Functionally impaired older women or men residing in the community • Older residents of long-term care facilities • Older patients with functional and/or cognitive impairment with bacteriuria and without local genitourinary symptoms or other systemic signs of infection • Patients with diabetes

31. When ASB Should Not Be Treated • Patients who have received a kidney transplant • Patients who have received a solid organ transplant • Patients with impaired voiding following spinal cord injury • Patients with an indwelling urethral catheter • Patients undergoing elective nonurologic surgery • Patients undergoing implantation of urologic devices or living with urologic devices

32. Patients with Indwelling Catheters • IDSA makes no recommendation for or against screening for ASB and treating ASB at the time of catheter removal

33. Patients with Indwelling Catheters • Antimicrobial prophylaxis given at the time of catheter removal may confer a benefit for prevention of symptomatic UTI for some patients • It is unclear whether or not the benefit is greater in patients with ASB

34. Conclusions • Asymptomatic bacteriuria is not an indication to treat unless the patient is a pregnant female or undergoing an invasive urological procedure • Antimicrobial stewardship programs should aim to reduce the number of UAs and urine cultures • Treatment of ASB could result in serious adverse consequences

35. References • Hooten, T. M., Gupta, K. (2016). Acute simple cystitis. UpToDate Web site. Accessed October 8, 2019. • Petty LA, Vaughn VM, Flanders SA, Malani AN, Conlon A, Kaye KS, Thyagarajan R, OsterholzerD, Nielsen D, Eschenauer GA, BloemersS, McLaughlin E, Gandhi TN. (2019). Risk factors and outcomes associated with treatment of asymptomatic bacteriuria in hospitalized patients. The Journal of the American Medical Association. Nicolle, L. E., Bradley, S. F., Colgan, R., DeMuri, G. P., Drekonja, D., Eckert, L. O., Geerlings, S. E., Koves, B., Hooten, T. M., Juthanie-Mehta, M., Knight, S. L., Saint, S., Schaeffer, A. J., Trautner, B., Wullt, B., Siemieniuk, R. (2019). Clinical practice guideline for the management of asymptomatic bacteriuria: 2019 update by the infectious diseases society of America., 68(10):1611-1615.