Kristin Nierenberg, MD Swedish Family Medicine Residency – First Hill R3 talks: May 9, 2014

1. Urinary Tract InfectionsHow to diagnose and when to treat:Evidence based answers for the primary care physician Kristin Nierenberg, MD Swedish Family Medicine Residency – First Hill R3 talks: May 9, 2014

2. Declarations None.

3. Objectives Review the epidemiology of UTIs Define how to properly diagnose cystitis , pyelonephritis, and asymptomatic bacteriuria Review the evidence behind antibiotic treatment Overview of care of the pregnant woman What to do about recurrent UTI Further areas of investigation

5. Definitions Uncomplicated UTI: acute cystitis or pyelonephritis occurring in healthypremenopausal, nonpregnant women with no history of abnormal urinary tract Complicated UTI: infections in patients with functional, metabolic, or anatomical conditions that may increase risk of infection or treatment failure / serious outcomes Acute Cystitis: Infection of the urinary bladder (lower urinary tract) Acute pyelonephritis: infection of the kidney (upper urinary tract)

6. Epidemiology UTI: Most commonly occurring bacterial infection in the outpatient setting. ~50% of women by age 30 Estimated incidence 10-15% average of 6 days of discomfort, leading to ~ 7 million outpatient visits / year, estimated costs > $1.5 billion! Risk factors: Sexual intercourse, spermicide, new sexual partner in past year, previous UTI, family hx of UTI

7. Acute Cystitis: Diagnosis • History: New onset of frequency and dysuria, with absence of vaginal discharge or irritation: PPV 90% • Physical exam: usually normal. 10-20% suprapubic tenderness. • Labs: urine dip vs. urinalysis with urine microscopy. • Nitrites and LE most accurate indicators of acute uncomplicated cystitis in symptomatic women • Culture recommended only if suspected pyelo, recurrence, atypical symptoms, or complicated infection • Colony count of > 103 CFU / mL is diagnostic > other studies showing use of 102 in women with classic symptoms.

9. Microbiology Main cause isE.Coli(75-95%) Other enterobacteriaceae(proteus, klebsiella) or Staph saprophyticus. Contaminants include lactobacilli, enterococci, GBS, or coagneg staph Resistance rates >20% common for ampicillin Fluoroquinoloneresistance generally < 10% but increasing over past decade Use of TMP-SMX in past 3-6 months or international travel: independent risk factors for bacteria resistance, concern if > 20%

12. Diagnosis of Pyelonephritis • History: variable with similar symptoms of cystitis but may additionally have fever, chills, flankpain, N/V • Physical exam: Fever, tachycardia, CVAT (any signs of sepsis) • Labs: Urinalysis and Urine culture • Urine culture > 104cfu/mL indicates clinically relevant bacteriuria • Imaging not needed generally if clinical response within 72 hours.

13. Treatment of Pyelonephritis • OUTPATIENT tx: Ok for those with mild to moderate illness who can be stabilized with rehydration, and follow up with close supervision. Ciprofloxacin: 500mg BID x 7 daysor 1000mg ER x 7 days or Levofloxacin750mg x 5 days Trimethoprim-sulfamethoxazole DS BID x 14D • INPATIENT tx: severe illness, high fever, pain, inability to hydrate or take oral meds, pregnancy, or concern about compliance. • - initial IV abx (fluoroquinolone, aminoglycoside, extended spectrum cephalosporin or penicillin, or carbapenem. Regimen tailored to susceptibility results. • Treatment response within 48 hours

14. Self-diagnosis and telephone management Studies indicate that if a woman has 2 symptoms of UTI, without vaginal discharge or irritation she has > 90% chance of having UTI Numerous studies have looked at treatment of UTI over the phone. Randomized trial in 2001: similar symptoms and patient satisfaction Retrospective cohort study of > 4,000 women showed that it was safe to treat as outpatient but up to 20% women require office evaluation within 6 weeks.

16. Outcomes of telephone based treatment

17. UTI in men

18. UTI in men • Usually considered complicated because majority occur in infants or elderly associated with urologic abnormalities • Small number occur in men age 15-50. (5-8 / 100,000 men per year) • Labs: Recommended UA and culture. • 104CFU/mlis diagnostic. • Men with recurrent UTI > undergo evaluation for prostatitis • Treatment: • TMP-SMXBID, CiproBID / daily, Levodaily. (7-14 days) • Do not use nitrofurantoinor beta-lactams due to poor tissue concentrations > less effective for occult prostatitis.

19. Asymptomatic Bacteriuria • Diagnosis • >105 CFU/mL in asymptomatic women collected in 2 consecutive voided specimens • 1 clean catch needed for men • Single catheterized specimen > 102 for men or women. • Screening: in pregnant women (more to follow), before urologic procedures • Treatment: 3-7 days. • Prevalence: 2-7% in healthy young pregnant or non-pregnant women.

20. What to do in Pregnancy?

21. Asymptomatic bacteriuria in pregnancy • Increases risk of complications: • 20-30x increased risk of pyelonephritis • More likely for prematuredelivery and low birth weight • Screen: at least once in early pregnancy > treated if positive. • Periodic screening after therapy (per ACOG 3rd trimester) • No recommendation for screening for culture-negative women in later pregnancy (consider in high risk women) • Treatment: • Decreases risk of pyelo from 20-35% > 1-4% • No determined duration of treatment (3-7 days) • Fluoroquinolonescontraindicated • TMP-SMX: avoid during 1st trimester > category C • Nitrofurantoin: 100mg BID x 5 days > category B (50-100mg qhs > suppression) • Amoxicillin: 500mg BID 3-7 days > category B • Augmentin: 500mg BID 3-7 days > category B • Cephalexin: 500mg BID 3-7 days. > category B • Test of cure

22. Cystitis in pregnancy • Diagnosis: Should perform urine culture • 103 CFU/mL • Treatment: • Nitrofurantoin100mg BID x 5 days • Cefpodoxime 100mg BID x 3-7 days • Augmentin 500mg BID x 3-7 days • Fosfomycin 3g x 1 • TMP-SMX DS BID x 3 days (avoid in 1st trimester or term) • Amoxicillin 500mg BID x 7 days • Suppressive therapy: bacteria persists after 2 or more courses, or for recurrent infection • Nitrofurantoin50-100mg qhs • Cephalexin 250-500mg qhs • GBS: treated as GBS carriers and receive prophylactic abx during labor.

23. Pyelonephritis in pregnancy • Pathogenesis: • Pressure on bladder, smooth muscle relaxation, immunosuppression of pregnancy, increased plasma volume • Treatment: • Hospitalization and IV abxuntil afebrile x 48 hours • 3rd generation cephalosporinsfavored over 1st /2nd gen • Avoid aminoglycosides due to ototoxicity • Carbapenems> effective vs ESBL • Complete 10-14 days tx • Recurrence: • Occurs in 6-8% or women > treat with prophylaxis • Nitrofurantoin50-100mg qhs • Cephalexin 250-500mg qhs

24. Recurrent UTI Recurrent UTI: Symptomatic UTI that follows resolution of an earlier episode, usually after appropriate treatment Relapse: Symptomatic recurrent UTI with the same organism < 2 weeks after treatment. Reinfection: Either recurrent UTI with previously isolated bacteria with a negative intervening culture, OR a recurrent UTI caused by a 2nd bacterial isolate. > 2 weeks after treatment. *Most are due to REINFECTION with same organism. • Epidemiology: In college women > 25% will have recurrence within 6 months, ~ 3% will have > 1 recurrence. In all women: ~35-50% recurrence within 1 year. • Diagnosis: Obtain urine culture

25. Recurrent UTI • Treatment: same as for regular UTI > consider test of cure • Prophylaxis: consider if 2UTIs in 6 months or 3 in 1 year. 6-12 motx will reduce rate of relapse. • Postcoital prophylaxis results in less abx use. • Cranberry juice / probiotics: Lacking randomized trials.

26. Recurrent UTI

27. What are the bugs at Swedish?

28. Effect of stewardship intervention on adherence to UTI / pyelo guidelines in ED setting ED chose to use UTI orderset as a quality indicator Feedback given to ED doc by ID and stewardship Primary outcome > adherence to IDSA guideline Secondary outcome > total days of abx, fluoroquinolonesfor cycsitis, diagnositicaccuracy.

29. Outcomes of stewardship interventions Improved adherence to guidelines with minimal resources Decreased unnecessary days of abxuse Reduced overuse of fluoroquinolones No change in UTI diagnostic accuracy

30. Swedish ED smartset… not so smart? • Labs: not possible to obtain UA without culture • No wet mount, GC/CT • Treatment: amoxicillin, cefpodoxime, azithro, doxy, erythro, levo, nitrofurantoin, phenazopyridine, bactrim(no specification re: duration) • No delineation of complicated vs. uncomplicated, cystitis vs. pyelonephritis • Appropriate inpatient supplemental orders

31. Take Home Points Cephalosporinsare NOT first line for UTI treatment Beware of Bactrimresistance > 20% Reserve use of fluoroquinolonesin cystitis If resistance pattern unknown in pyelo > good to treat with 1 dose CTX Antibioticstewardships and ordersets > could be helpful in helping to follow treatment guidelines. Treating over the phone may not cause harm to patient, but could worsen collateral damage!

33. References Gupta K, Hooton T, et al. International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women: A 2010 Update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clinical Infectious Diseases. 2011;52(5):103-120. Coglan R and Williams M. Diagnosis and Treatment of Acute Uncomplicated Cystitis. American Family Physician. 2011;84(7):771-776. Schauberger C, Merkitch K, et al. Acute Cystitis in Women: Experience with a Telephone-Based Algorithm. Wisconsin Medical Journal. 2007;106(6):326-330. Barry HC, Hickner J, et al. A rnadomized control trial of telephone management of suspected urinary tract infection in women. Journal of Family Practice. 2001;50(7):589-594. Vinson D and Queensberry C. The Safety of Telephone Management of presumed cystitis in women. Arch Intern Med. 2004;164(9):1026-1029. Nicolle L, Bradley S, et al. Infectious Diseases Society of America Guidelines for Diagnosis and Treatment of Asymptomatic Bacteriuria in Adults. Clinical Infectious Diseases. 2005;40:643-654. Kodner C and Gubton E. Recurrent Urinary Tract Infections in Women: Diagnosis and Management. American Family Physician. 2010;82(6)638-643.

34. References Cont’d DelzellJ and Lefevre M. Urinary Tract Infections During Pregnancy. American Family Physician. 2000;61(3):713-720 Hooton T, Bradley S, et all. Diagnosis, Prevention, and Treatment of Catheter-Associated Urinary Tract Infection in Adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clinical Infectious Diseases. 2010;50:625-663. BilirF, Akdemir N, et al. Increased serum procalcitonin levels in pregnant patients with asymptomatic bacteriuria. Annals of Clinical Microbiology and Antimicrobials. 2013;12:25-30. Ha Y, Kang C, Wi Y, et al. Diagnostic usefulness of procalcitonin as a marker of bacteremia in patients with acute pyelonephritis. Scandinavian Journal of Clinical and Laboratory Investigation. 2013; 1-5 12. Sugimoto K, Adomi S, et al. Procalcitonin as an indicator of urosepsis. Research and Reports in Urology. 2013:5 77-80. 13. Park J, Wee J, et all. Serum procalcitonin level for the predication of severity in women with acute pyelonephritis in the ED: value of procalcitonin in acute pyelonephritis. The American Journal of Emergency Medicine. 2013;31:1092-1097. 14. Hecker M, Fox C. et al. Effect of a Stewardship Invervention on Adherence to Uncomplicated Cystitis and Pyelonephritis Guidelines in an Emergency Department Setting. Plos One. 2014;9(2):1-8.