1. Urinary Tract Infection Ryan Nall MD Assistant Professor of Medicine Division of General Internal Medicine

2. Objectives Describe the pathogenesis and microbiology of urinary tract infections Explain the difference between complicated and uncomplicated cystitis and how this impacts mgmt Describe the diagnostic tools used to diagnose UTIs and their testing characteristics Understand counseling and mgmt options for recurrent UTIs

3. “UTI” Clinical entities encompassed… asymptomatic bacteriuria acute uncomplicated cystitis recurrent cystitis complicated UTI catheter-associated asymptomatic bacteriuria catheter-associated UTI (CAUTI) prostatitis pyelonephritis

4. CASE Dys Uria is a 23 yo female who presents with pain with urination and increased frequency. She had one similar episode earlier this year which resolved with Sulfa-Trimethoprim and cranberry juice. – What additional history do you want to know about this patient? – What physical exam is needed? – What is your differential diagnosis? – Are additional tests, studies needed? – How would you treat?

6. Epidemiology Most common bacterial infection encountered in ambulatory setting 8.6 million visits in 2007 (84% by women) Self-reported annual incidence in women is 12% By age 32 - 50% of all women have had a UTI In young healthy women with UTI 25% will have a recurrence in 6 months

7. Risk Factors Prior UTI Sexual Intercourse Spermicides: anti-microbial properties of nonoxynol- 9 may alter vaginal flora First Degree Female Relative Case control studies have shown NO relationship with pre/post coital voiding pattern, wiping patterns, tampon use, douching, hot tubs, type of underwear, BMI?????

8. Pathogenesis and Microbiology Urinary pathogens from bowel colonize vaginal introitus and urethral meatus and ascend the urethra (short in women/longer in men) to the bladder, ureter, kidney E. coli causes 75-95% of cases of uncomplicated cystitis Proteus, Enterobacter, Klebsiella pneumoniae Gram positive: Staphylococcus saprophyticus, Enterococcus faecalis, and Streptococcus agalactiae (group B streptococcus)

9. Uncomplicated Complicated Women Premenopausal Healthy, no known anatomic or functional abnormality to the urinary tract Everyone Else? Men, women, or children with functional, metabolic, or anatomical conditions that may increase the risk of treatment failure or serious outcomes Obstruction, stone, pregnancy, male sex, diabetes, neurogenic bladder, renal insufficiency, immunosuppression

11. Poll Women with which constellation of symptoms have the highest probability of cystitis? Fever, dysuria, back pain Dysuria, frequency, hematuria Dysuria, Absence of vaginal Discharge and irritation, Back pain Dysuria, Frequency, Absence of vaginal discharge and irritation

12. Signs and Symptoms DYSURIA Frequency Urgency Suprapubic Pain Hematuria Think PYELONEPHRITIS! Fever Nausea/Vomiting Flank Pain CVA Tenderness

13. Diagnostic Evaluation Urine Dipstick Urine Microscopy Urine Culture Imaging Your test is only as good as your sample! **Pregnancy Test

15. The Dipstick Leukocyte Esterase: Enzyme released by lysed leukocytes Nitrite: Enterobacteriaceae reduce nitrates in urine to nitrites Heme: Originates from intact RBCS, hemoglobin or myoglobin Protein: Microalbuminuria not picked up, NO light chains pH: Range 4.5 to 8. Normal 5.5 to 6.5 Specific Gravity: Normal 1.008 to 1.009, equates to osmolality of 280 mosmol/kg (normal plasma). Beware of high specific gravity! Glucose: Glycosuria when glucose over 180mg/dl Ketones: Dipstick detects acetic acid Bilirubin/Urobilinogen: – Conjugated bilirubin is water soluble and can be secreted in biliary obstruction, viral/alcoholic hepatitis – Urobilinogen is made in the intestine from conjugated bilirubin and indicates hemolysis, hepatocellular disease, bacterial overgrowth

16. Microscopy Evaluation for pyuria (>5 HPF) Confirm presence of RBC Culture Traditionally + if >100,000 CFU/ml single organism, however if symptoms consider positive if less Send if… Pyelonephritis suspected Complicated infection Recurrent infection Recent Antibiotics or history of resistant organisms Imaging If concern for anatomical abnormality, obstruction, stone Infants, young boys Middle age/Elderly men check post void residual, consider renal us, cystoscopy, IVP If continued symptoms despite 3 days of antibiotics for UTI or SICK!

18. Poll What is recommended first line treatment for uncomplicated cystitis? – Nitrofurantoin 100mg twice daily x 5 days – Trimethoprim-Sulfamethoxazole DS twice daily x 3 days – Fosfomycin 3 grams x one – Ciprofloxacin 500mg twice daily x 3 days – A, B, or C – All of the above

19. Treatment Uncomplicated Cystitis

20. * Pregnant

21. Treatment Uncomplicated Pyelonephritis

22. Treatment Complicated Send Culture! Empiric: oral fluoroquinolones 7-10 days, shorter if mild symptoms and rapid improvement May need IV therapy if SICK or unable to take PO

23. Recurrent Cystitis >2 in 6 months, >3 in 1 year Self Diagnosis and Treatment Post-Coital Antibiotics (92% reduction) Daily Antibiotics (95% reduction) – more side effects – trial 6 months then off

25. Special Considerations Asymptomatic Bacteriuria – Screen and Treat: pregnancy, prior to urologic procedure with possible mucosal injury Atrophic Vaginitis – Post menopausal women – Pain with intercourse, vaginal discharge, bleeding – Vaginal dryness, Decreased Pubic hair, Fusion of labia minora – Can cause irritation of the urinary tract leading to frequency, dysuria, hematuria, urethral discomfort

26. UpToDate 2014

27. CASE Ms. Fre Quency is a 77 yo female with history of diabetes, paraplegia and neurogenic bladder with suprapubic tube. She presents to the ED for evaluation of cough, sore throat, rhinorrhea. CXR is negative. Normal CBC with diff. A urinalysis performed shows +leukocyte esterase, +nitrite, -blood. – What questions do you have for the patient? – What is your differential? – What will you look for on exam? – What is your next step in mgmt? Urine culture returns several days later and shows 40,000 E. Coli. – How would you manage the patient?

28. CASE from a different angle Same patient but Ms. Fre Quency also reports spasms in the bladder, increased lower extremity spasticity, foul smelling urine. Dipstick: + leukocyte esterase, +nitrite, +blood. Urine culture E. coli >100,000. – How does your management change? Sensitivities show E. coli to be resistant to bactrim, ciprofloxacin, and extended spectrum beta-lactamase (esbl) producing – How does your management change?

29. Summary UTIs are extremely common in women and most often caused by E. Coli Cystitis in healthy pre-menopausal women should be considered uncomplicated Women with dysuria, frequency and absence of vaginal discharge/irritation have a very high probability of cystitis Sensitivity, Specificity of urine dipstick isn’t fantastic. If high pre-test probability of UTI the dipstick won’t rule out Don’t treat asymptomatic bacteriuria Consider prophylactic antibiotic therapy in women with >3 urinary tract infections each year