1. TO TREAT OR NOT TO TREAT THAT IS THE QUESTION Dr. Ruth Kandel Director, Infection Control Hebrew SeniorLife

2. Objectives Define whether to screen for or treat asymptomatic bacteriuria in an elderly population Review complications of antibiotic use Define symptomatic urinary tract infections Review challenges of diagnosis in the elderly 2

3. Clinical Infectious Disease 2005;40:643-654 3

4. What is Asymptomatic Bacteriuria?

5. Asymptomatic Bacteriuria (ASB) Laboratory diagnosis Positive urine culture – Colony count significant (> 10⁵ cfu/mL) Absence of symptoms Clinical Infectious Disease 2010;50:625-663 5

6. Pyuria Pyuria (> 10 WBC / high-power field) is evidence of inflammation in the genitourinary tract Pyuria is commonly found with ASB Elderly institutionalized residents 90% (Infect Dis Clin North Am 1997;11:647-62) Short-term (< 30 days) catheters 30-75% (Arch IM 2000;160:673-82) Long-term catheters 50-100% (Am J Infect Control 1985;13:154-60) 6

7. Treatment for ASB Indicated Pregnant women – Increased risk for adverse outcomes Urologic interventions TURP Any urologic procedure with potential mucosal bleeding 7

8. Treatment for ASB Not Indicated Premenopausal, non-pregnant women Diabetic women Older persons living in the community Elderly living in long term care facilities Persons with spinal cord injury Catheterized patients CID2005;40:643-654 8

9. Prevalence of ASB POPULATIONPrevalence % Healthy premenopausal women1-5 Postmenopausal women2.8-8.6 (50 to 70 years of age) 3 3 0.7 to 1.0 Older community-dwelling patients – Women (older than 70 years)10.8-16 – Men3.6-19 Older long-term care residents – Women25-50 – Men15-40 Patients with an indwelling catheter – Short-term9-23 – Long-term100 CID2005;40:643-654 9

10. No Benefit Treating ASB in the Elderly Large long-term studies of ASB in pre and postmenopausal women – NO ADVERSE OUTCOMES in women not treated Randomized studies (treatment vs. no treatment) in elderly LTC residents – NO BENEFIT to treatment – No decreased rate of symptoms – No improved survival CID2005;40:643-654 10

11. Prospective Randomized Studies Treatment vs. No Treatment ASB AuthorsSubjectsInterventionOutcome Nicolle LE, et al. NEJM 1983;309:1420-5 Men, NH, median age 80 Treated 16 Not treated 20 Duration 2 years No difference mortality or infectious morbidity 2 groups Nicolle LE, et al. Am J Med 1987;83:27-33 Women, NH, median age 83 Treated 26 Not treated 24 Duration 1 year No difference mortality/GU morbidity. Increase drug reactions and AB resistance treated group. Abrutyn E, et al. Ann Intern Med 1994;120:827-33 Women, ambulatory and NH Mean age 82 Treated 192 Not treated 166 Duration 8 years No survival benefit from treatment Ouslander JG Ann Intern Med 1995;122:749-54 Women and men NH Mean age 85 Treated 33 Not treated 38 Duration 4 weeks No difference chronic urinary incontinence 11

12. Cohort Studies AuthorsSubjectsObservationOutcome JAGS 1990;38:1209-14 Men, Ambulatory, > 65 years 29 Subjects Duration 1-4.5 years No adverse outcomes attributed to no treatment NEJM 1986;314:1152-6 Population based Swedish men and women Duration 5 yearsNo association between bacteriuria and survival Gerontology 1986;32:167-71 Population based Finnish men and women > 85 years Duration 5 yearsNo association between bacteriuria and survival 12

13. Proportion of Women with Diabetes Who Remained Free of Symptomatic Urinary Tract Infection, According to Whether They Received Antimicrobial Therapy or Placebo at Enrollment. Harding GK et al. N Engl J Med 2002;347:1576-1583. 13

14. IDSA Recommendations Routine screening for and treatment of ASB in older individuals in the community is not recommended. Screening for and treatment of ASB in elderly residents in LTCFs is not recommended. CID2005;40:643-654 14

15. Any Problems Just Treating Anyway?

16. 16

17. CDC Website 17

18. Antibiotic misuse adversely impacts patients - resistance Getting an antibiotic increases a patient’s chance of becoming colonized or infected with a resistant organism.

19. Antibiotic Resistance CDC Website 19

20. Antibiotic Resistance CDC Website 20

21. Antibiotic resistance increases mortality

22. Mortality associated with carbapenem resistant (CR) vs susceptible (CS) Klebsiella pneumoniae (KP) Patel G et al. Infect Control Hosp Epidemiol 2008;29:1099-1106 OR 3.71 (1.97-7.01) OR 4.5 (2.16-9.35) p<0.001

23. Mortality of resistant (MRSA) vs. susceptible (MSSA) S. aureus Mortality risk associated with MRSA bacteremia, relative to MSSA bacteremia: OR: 1.93; p < 0.001. 1 Mortality of MRSA infections was higher than MSSA: relative risk [RR]: 1.7; 95% confidence interval: 1.3–2.4). 2 1. Clin. Infect. Dis.36(1),53–59 (2003). 2. Infect. Control Hosp. Epidemiol.28(3),273–279 (2007).

24. CDC: Get Smart About Antibiotics 24

25. CDC: Get Smart About Antibiotics Antibiotic resistance is one of the world’s most pressing public threats. Antibiotic resistance in long-term care increases risk – Hospitalization – Death – Cost of treatments 25

26. Antibiotic misuse adversely impacts patients- resistance Increasing use of antibiotics increases the prevalence of resistant bacteria in hospitals.

27. Reservoir for Spread of Antibiotic Resistant Pathogens Clinical Infections Colonized (asymptomatic) Patients 27

28. Antibiotic‐Resistant Bacteria Travels Journal of the American Geriatrics Society pages 242-246, 12 JUL 2002 http://onlinelibrary.wiley.com/doi/10.1046/j.1532-5415.50.7s.5.x/full#f1 http://onlinelibrary.wiley.com/doi/10.1046/j.1532-5415.50.7s.5.x/full#f1 28

29. And Another Reason Not To Treat

30. Clostridium Difficile Infection 30

31. Clostridium difficile infection (CDI) cases by location and type of exposures — United States, Emerging Infections Program, 2010 MMWR March 9, 2012 31

32. Rates of Clostridium difficile Infection Among Hospitalized Patients Aged ≥65 Years CDC September 2, 2011 / 60(34);1171 32

33. Heron et al. Natl Vital Stat Rep 2009;57(14). http://www.cdc.gov/nchs/data/nvsr/nvsr57/nvsr57_14.pdf Background: Impact Age-Adjusted Death Rate* for Enterocolitis Due to C. difficile, 1999–2006 *Per 100,000 US standard population 0 0.5 1.0 1.5 2.0 2.5 19992003 Rate 200020042001200520022006 Year Male Female White Black Entire US population 33

34. Deaths from Gastroenteritis Double C. difficile and norovirus are the leading causes Adults over 65 years old accounted for 83 percent of deaths. Clostridium difficile and norovirus most common infectious causes. Clostridium difficile – Accounted for two-thirds of the deaths. – Presumed cause is spread of a hypervirulent, resistant strain of C. difficile. CDC March 14, 2012 Press Release 34

35. Background: Epidemiology Risk Factors Antimicrobial exposure Acquisition of C. difficile Advanced age Underlying illness Immunosuppression Tube feeds Gastric acid suppression FDA Drug Safety Communication: Clostridium difficile infection can be associated with stomach acid drugs known as proton pump inhibitors (PPIs) February 2012 Main modifiable risk factors 35

36. When to Treat Urinary Tract Infections Long Term Care

37. Challenges Comorbid illnesses may result in symptoms similar to UTIs. Cognitive impairment may make reporting of symptoms difficult. Older individuals can have atypical presentations for infections. There is a lack of evidenced based guidelines for symptomatic UTIs. 37

38. Criteria for Surveillance, Diagnosis and Treatment Based on consensus group recommendations Modified by – Recent clinical practice guidelines – Current research 38

39. Criteria for Surveillance, Diagnosis and Treatment Consensus group recommendations McGeer criteria developed for surveillance and outcome assessments – Used by Centers for Medicare and Medicaid Services Loeb criteria recommends minimal set of criteria necessary to initiate antibiotic therapy for UTI – Similar to IDSA Guidelines 39

40. McGeer Criteria No Indwelling Catheter At least three of the following – Fever* or chills – New or increased dysuria, frequency or urgency – New flank or suprapubic pain or tenderness – Change in character of urine – Worsening of mental or functional status Chronic Indwelling Catheter At least two of the following – Fever* or chills – New flank or suprapubic pain or tenderness – Change in character of urine – Worsening of mental or functional status *Fever > 100.4° F Am J Infect Control 1991;19:1-7 40

41. Loeb Minimal Criteria Initiating Antibiotics No Indwelling Catheter Acute dysuria Or Fever* + new or worsening (must have at least one of following) – Urgency – Frequency – Suprapubic pain – Gross hematuria – Costovertebral angle tenderness – Urinary incontinence Chronic Indwelling Catheter Must have at least one of the following Fever* New costovertebral angle tenderness Rigors (shaking chills) New onset delirium *Fever > 100° or 2.4° F above baseline ICHE 2001;22:120-124 41

42. Criteria for Surveillance, Diagnosis and Treatment Clinical Practice Guidelines Infectious Disease Society of America (IDSA) Clinical Practice Guidelines Fever and Infection Long-Term Care Facilities 2008 CID 2009;48:149-171 IDSA Clinical Practice Guidelines Catheter- Associated Urinary Tract Infections Adults 2009 CID 2010;50:625-663 IDSA Guidelines Asymptomatic Bacteriuria CID 2005;40:643-654 42

43. Criteria for Surveillance, Diagnosis and Treatment Current Research Diagnostic algorithm for ordering urine cultures for NH residents in intervention arm Loeb M et al. BMJ 2005;331:669 ©2005 by British Medical Journal Publishing Group 43

44. Treatment algorithm for prescribing antimicrobials to NH residents in intervention arm Loeb M et al. BMJ 2005;331:669 ©2005 by British Medical Journal Publishing Group 44

45. Monthly rates of antimicrobial prescriptions for urinary indications in intervention and usual care nursing homes. Loeb M et al. BMJ 2005;331:669 ©2005 by British Medical Journal Publishing Group 45

46. Collecting Urine Samples Mid-stream or clean catch specimen for cooperative and functionally capable individuals. However, often necessary – For males to use freshly applied, clean condom (external) catheter and monitor bag frequently – For females to perform an in-and-out catheterization Residents with long-term indwelling catheters – Change catheter prior to collection (sterile technique/equip.) Resident with short-term catheterization (< 30 days) – Obtain by sampling through the catheter port using aseptic technique – If port not present may puncture the catheter tubing with a needle and syringe – If catheter in place > 2 weeks at onset of infection, replace CID 2009;48:149-171 CID 2010;50:625-663 46

47. Role of Urine Analysis and Dipstick Testing in the Evaluation of Urinary Tract Infection in Nursing Home Residents Negative urine analysis for WBCs and negative dipsticks tests for leukocyte esterase and nitrites do not support UTI BUT cannot completely rule it out – Leukocyte esterase (LE) Enzyme found in white blood cells (WBCs) – Nitrites Certain bacteria reduce urinary nitrates to nitrites – Pyuria > 10 WBC / high-power field Squamous cells Increased number suggests contamination Infect Control Hosp Epidemiol 2007;28:889-891 Am Fam Phys 2005;71:1153-1162 47

48. Urine Culture A urine culture should always be obtained when evaluating SYMPTOMATIC infections. Urine cultures will assist in appropriate antibiotic selection. A negative urine culture obtained prior to initiation of antibiotics excludes routine bacterial urinary infection 48

49. At least one of the following that are new or increased □ Fever (> 100°F or 2.4°F > baseline) □ Costovertebral angle tenderness □ Rigors (shaking chills) □ Delirium □ Flank pain* or pelvic discomfort* □ Acute hematuria* □ Malaise or lethargy with no other cause* *CID 2010;50:625-663 Acute dysuria alone OR Fever (> 100°F or 2.4°F > baseline) AND at least one of the following that is new or increased □ Urgency □ Frequency □ Suprapubic pain □ Gross hematuria □ Costovertebral angle tenderness □ Urinary incontinence □ Change in mental status* □ Rigors (shaking chills)* If accompanied only by fever, rule out other causes *CID 2012;54:973-978 BMJ 2005;331:669 49

50. Key Points Routine screening for and treatment of ASB is not recommended – In older individuals in the community – In elderly residents in LTCFs Get Smart About Antibiotics – Antibiotic resistance is one of the world’s most pressing public threats. – Clostridium difficile infections are on the rise and are associated with increased mortality especially among the elderly Treat only symptomatic urinary tract infections in the elderly – Refer to clinical guidelines to assist in making a diagnosis 50