$ 2.6 Billion annual costs in U.S. 8.1 Million health care provider visits Peak incidence = years 50-60% of women have UTI at least once in

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Paul Brown
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1 August 8, 2018

2 $ 2.6 Billion annual costs in U.S. 8.1 Million health care provider visits Peak incidence = years 50-60% of women have UTI at least once in lifetime 20-30% have recurrent episode usually within 6 months of the initial infection 10% of women > 50 years, 20% > 65 years 25-40% of acute infections resolve spontaneously

3 Uncomplicated Healthy individuals Complicated At risk for failing therapy and subsequent increased morbidity Pregnancy Urinary tract abnormalities Diabetes Immunosuppression Urinary tract stones Hx urologic surgery Elderly Indwelling catheters Nosocomial infection Spinal cord injury

4 Premenopause Sexual activity- frequent, recent Prior UTIs Spermicides/diaphragm use Parity / Pregnancy Diabetes Obesity Sickle cell anemia Congenital abnormalities Stones

5 Post-menopause Urogenital atrophy Voiding dysfunction (incomplete emptying) Prolapse Previous pelvic floor surgery Poor perineal hygiene

7 Acute bacterial cystitis (bladder infection) Acute bacterial urethritis Pyelonephritis Asymptomatic bacteriuria Recurrent UTI Reinfection Chronic / persistent UTI Relapse of infection

8 Acute bacterial cystitis = Lower urinary tract infection Symptoms = dysuria, frequency, urgency, SP pain, occasionally hematuria, fever, urine odor Urine culture = single bacterial isolate 10⁵ cfu/ml

9 If urinate, it s significant

10 Pyelonephritis = Upper UTI ( pelvicaliceal system) bacteriuria and pyuria Symptoms = FEVER, CVA Tenderness, N/V

11 Recurrent UTI = 3 episodes of UTI / 12mo Or 2 episodes of UTI / 6mo. Relapse = recurrent UTI with same organism after adequate therapy caused by a focus within the urinary tract such as a stone. Reinfection = UTI NG culture UTI w/ same organism or UTI UTI w/ different organism Chronic /persistent UTI = infections same bacterial isolate with no documented negative intervening culture and/or persistent symptoms

12 Asymptomatic bacteriuria = Considerable bacteriuria 10⁵ cfu/ml clean catch voided x 2 or 10² cfu/ml cath x1 in a woman with NO Symptoms

13 CDC - 10⁵ colony forming units (CFU) of one or two bacterial species And one or more symptoms of dysuria, frequency, fever, suprapubic pain, urgency 10² CFU by cath specimen is significant Urinalysis dipstick +leukocyte esterase or +nitrites Hematuria does not occur frequently with UTI (gross or micro)

14 Leukocyte esterase - Detection of pyuria reagent strip w/ acid ester that catalyzes hydrolysis producing acid and aromatic compound in reagent strip diazonium salt to produce purple color (azodye) = diazo reaction neutrophil enzyme -high specificity sensitivity better with more bacteria Protein & Vit. C cause false positives

15 Nitrites (E coli, Klebsiella, Proteus), Pseudomonas, enterococcus, and S. saphrophyticus DO NOT produce nitrites (lack nitrate reductase) Bacterial Nitrate reductase ----Nitrites - nitrate reductase (dietary nitrates to nitrites) high specificity (82-100%) low sensitivity (only 25% of pts with UTI test positive) May be negative due to lack of dietary nitrates, diuretics False negative results are common

16 On dipstick UA

17 NOT HELPFUL (POOR SENSITIVITY)

18 Ascending infection Hematologic and lymphatic spread rare (pyelo from Staph. Aureus)

20 75-90% of UTIs are E. coli Remainder are Enterobacteriaceae #2 Staphylococcus saprophyticus (4.4%) Klebsiella (4.3%) Proteus(3.7%) Enterobacter Serratia Pseudomonas aeruginosa (instrumentation) Providencia Morganella

21 Candida albicans and other fungals Diabetes Indwelling catheters Immunocompromised (renal disease, transplant)

23 NEGATIVE Cultures -FAILED antibiotics Chlamydia Mycoplasma Ureaplasma Nephrolitiasis Interstitial nephritis Malignancy TB

Acidic vaginal ph- lactobacilli Bladder glycosaminoglycans- urothelial integrity Immunoglobulins in urine- block bacterial adherence Dilutional effects of urine- flushing effect?

24 Acidic vaginal ph- lactobacilli Bladder glycosaminoglycans- urothelial integrity Immunoglobulins in urine- block bacterial adherence Dilutional effects of urine- flushing effect? Virulence factors- E coli intracellular bacterial colonies = resistance to antibiotics and cellular phagocytosis Type1 fimbriae bind mannose on urothelium sticky E coli Drug resistance transfer plasmids Elderly- decreased cell mediated immunity, decreased estrogen Pregnancy- decreased peristalsis, stasis, mechanical compression obstruction, increased filtration (less drug exposure) Genetic --- HSPA1B, CXCR1,2, TLR2,4 gene therapy future

25 Hypoestrogenism DECREASED Lactobacilli (protective normal flora) INCREASED ph Atrophy = INCREASED parabasal cells, DECREASED mature squamous cells DECREASED GLYCOGEN

26 Sexual activity New sexual partner Spermicides (alter vaginal ph) Previous UTI Family history (genetic urothelial mucosal factors)

28 NOT shown to be risk factors: Post coital voiding Wiping behaviors Beverage consumption Douching Tampons Type of underwear Hot tubs BMI

29 Urethral diverticulum Stones Significant anterior vaginal prolapse (retention) Foreign body Duplicate / ectopic ureter Papillary necrosis Atrophic pyelonephritis Medullary sponge kidney

30 CT w/ and w/o IV contrast h/o previous upper UTIs h/o childhood UTIs h/o persistent infections by same organism (proteus mirabilis)- associated with stones Suspected fistula (rapid recurrence of infect) Hematuria (painless) with infection Stone history IVP fistulas MRI Urethral diverticula

31 Not useful or indicated in uncomplicated infection May be useful to evaluate recurrent / persistent infection in women with h/o stones or prior pelvic surgery such as synthetic mesh procedures (MUS, prolapse repair), gross hematuria, persistent microhematuria, or suspected fistula

32 1-3 days of antibiotics equally effective to traditional 7 days. Benefits Improved compliance Few side effects / adverse events Lower cost Lower drug resistance Single dose therapy less effective

33 1 st line- TMP/Sulfa, nitrofurantoin, fosfomycin, cephalosporin 2 nd line- fluroquinolones, β lactams

34 TMP-SMX (Bactrim, Septra) First-line, 3 day Most cost effective SEs: Fever, rash, photosensitivity, thrombocytopenia, anorexia, nausea/vomiting, pruritus, urticaria, HA, Stevens-Johnson Synd, toxic epidermal necrosis If local E coli resistance is >20% consider alternative

35 Escherichia coli 45% susceptible 71% susceptible 72% susceptible 92% susceptible Ampicillin TMP/SMZ ciprofloxacin nitrofurantoin

36 Nitrofurantoin (Macrodantin, Macrobid) T 1/2 = 19 min. metabolized in all body tissues Causes no change in gut or vaginal flora No bacterial resistance / 30 yrs. No resistance to E. coli*- use for suppressive rx, 5day dosing Inexpensive QID dosing BID dosing macrocapsules SEs: hypersensitivity, peripheral neuropathy hemolytic anemia in G6PD, pulmonary fibrosis Good for suppressive therapy Avoid in renal disease/ elderly if gfr <40

37 Flouroquinolones Ciprofloxacin Levofloxacin Norfloxacin Use for complicated / high risk infections, recurrent infections, hospital acquired infections Can be used for suppressive therapy SEs: rash, confusion, mental status changes in elderly, seizures, restlessness, HA, hypersensitivity, hypoglycemia, hyperglycemia, Achilles tendon rupture

38 Fosfomycin (Monurol) 1gm single dose packet NO Resistance Less effective, redosing may be required. Useful for Pseudomonas

39 Ampicillin / Tetracycline E. coli resistance, yeast infections, pseudomembranous colitis Cephalexin (Keflex) Good for suppressive therapy

40 Methenamine salts (methenamine hippurate, methenamine mandelate) Bacteriostatic Conversion to formaldehyde in urine UTI prevention for uncomplicated recurrent UTI Do not use in neuropathic bladder or renal tract abnormality

Continuous suppression (prophylaxis) Daily low dose nitrofurantoin / cephalosporin 6-12 months then re-evaluate Self-start (patient initiated therapy) Self test urine with

41 Continuous suppression (prophylaxis) Daily low dose nitrofurantoin / cephalosporin 6-12 months then re-evaluate Self-start (patient initiated therapy) Self test urine with onset of symptom Give pt script w/ refills fluoroquinolone x 3 days Call and come to office if not better after 2 days Peri-coital Macrobid mg or Bactrim DS single dose

Topical Estrogen Cream (Premarin, Estrace)- Most effective in prevention UTI in postmenopausal women Probiotics (lactobacilli) Limited data- promotes normal bact colonization vagina H2O2, decrease ph

43 Topical Estrogen Cream (Premarin, Estrace)- Most effective in prevention UTI in postmenopausal women Probiotics (lactobacilli) Limited data- promotes normal bact colonization vagina H2O2, decrease ph urine, anti-inflam cytokines Intravesicle hyaluronic acid/chondroitin sulfate Reduced time to reinfection and # infec /yr Cranberry Extract /juice Active chemical=proanthocyanidins inhibit P-fimbriae adhesion Weak data to support recommending Urine Acidification - weak data to support recommending Vitamin C Mannose (decreased E coli adherance to urothelium)

44 Bladder analgesic Short term use (few days) Discolored nails icterus Bilirubinemia Methemoglobinemia Renal failure Avoid use if sulfa allergic

45 Common in older women Do not perform routine screening UA (except pregnancy) DO NOT TREAT

46 COMMON CAUSE OF HOSPITAL AQUIRED INFECTION REMOVE Foley catheters ASAP DO NOT SCREEN THE URINE FOR INFECTION DO NOT GIVE PROPHYLACTIC ANTIBIOTICS WHILE CATHETER IS IN AVOID IRRIGATING INTERMITTENT CLEAN SELF CATH IS BETTER for longer term drainage if able

47 1. daily suppressive ciprofloxacin 250mg 2. recommend culture with symptoms and rx accordingly 3. start topical estradiol cream to reduce risk of future infections 4. perform cystocele repair 5. cystoscopy and see if urine the bladder

Your plan is.. 1.Prescribe topical vaginal conjugated equine estrogens to decrease the native lactobacilli concentration and start pericoital suppressive antibiotics. 2.

48 Your plan is.. 1.Prescribe topical vaginal conjugated equine estrogens to decrease the native lactobacilli concentration and start pericoital suppressive antibiotics. 2. Advise patient and her provider to discontinue screening the urine for infection 3. Place a vaginal pessary and start estradiol 1mg po daily and recheck in 6 months 4. Obtain a cath specimen for post void residual and reculture 5. Cranberry extract, topical vaginal estrogen, probiotics, and a self start ciprofloxacin regimen as this is now a complicated case.

49 Asymptomatic bacteriuria -2-10% UTI -20% Pyelonephritis 2-4% Screening for bacteriuria beginning at initial visit and treat asymptomatic bacteriuria Risks

50 ACOG Practice Bulletin-Treatment of Urinary Tract Infections in Nonpregnant Women. Number 91, March 2008 Urogynecology & Female Pelvic Reconstructive Surgery;Siddighi & Hardesty Chapter Ostergard s Urogynecology and Pelvic Floor Dysfunction. Bent, Cundiff, & Swift Chapter 10: Karram & Siddighi; 6 th Ed 2008 UTI Swift Comprehensive Review Course in Female Pelvic Medicine and Reconstructive Surgery Dallas, TX Feb 2013 Urinary Tract Infections Grimes and Lukacz FPMRS Vol 17 number6 Nov Dec 2011 Urinary Tract Infections in Older Women: A clinical review Mody and Juthani-Mehta JAMA 311: 8 Feb 2014 Urinary symptoms and their associations with urinary tract infections in urogyncologic patients Dune, et al Obstet and Gynecol vol130 no 4 Oct 2017

TMP/SMZ DS Ciprofloxacin Norfloxacin Ofloxacin Cefadroxil * 30 Amoxicilin 86* 19 25

TMP/SMZ DS Ciprofloxacin Norfloxacin Ofloxacin Cefadroxil * 30 Amoxicilin 86* 19 25 Evidence-Based Evaluation and Treatment of UTI UTI Prevalence Leslee L. Subak, MD Associate Professor Obstetrics, Gynecology & RS Epidemiology & Biostatistics University of California, San Francisco 50%