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Clinical Concerns Chronic Urinary Tract Infections Getting to the Root of the Problem Magali Robert, MD Presented at the University of Calgary’s Family Practice Update in Calgary, Alberta, on November 21, 2011. Presentation Sarah’s Case Urinary tract infections are diagnosed in symptomatic individuals with positive urine cultures. © Common symptoms include dysuria, urinary frequency, urgency, suprapubic pain, and possiad, o l n w 1 bly hematuria. A cpositive n do urine culture in the ers a s u use asymptomatic d e absence of symptoms nisalcalled ris o o s h r t e u p A y f or ited. bacteriuria le cop and should not be treated. prohib g Sarah is a healthy 48-year-old woman who presents with recurrent UTIs. In the last year, she has had four confirmed UTIs, which have responded well to antibiotics. She has not had UTIs prior to this and worries about why this is occurring now. She is also concerned about the use of antibiotics. t n h o i t g i u r b i y r is t D Cop l a i c er m m o C r o e l a S r Not fUonauthorilsaeyd, vuieswe and print a sin She is in a stable relationship. Sarah has noticed that the infections may have occurred following intercourse. Shedhas ispbeen using a lubricant for vaginal dryness for several years. Sarah has increased her fluids, voided around sexual activity, and is fastidious about perineal hygiene. At least 50 % of women will experience a urinary tract infection (UTI) in their lifetime. Roughly 25% of these women will go on to develop recurrent UTIs. Recurrent, or chronic, UTIs are defined as three or more infections in one year or, less commonly, as two infections in the last six months. The infection is considered a reinfection if there has been a different cultured bacteria, a negative follow-up culture, or a two week asymptomatic period following therapy. A relapse is less commonly seen but occurs if symptoms recur quickly after therapy and the same organism is cultured. This is often a reflection of under treatment. Consider Why You Are Treating On average, bladder symptoms last for three days with treatment and an additional two days without treatment.2 In normal individuals, the risk of pyelonephritis is 0.34% with no treatment, versus 0.15% with treatment.3 This means that to prevent one patient from developing pyelonephritis, 500 individuals with a UTI need to be treated. And 250,000 patients would need to be treated to prevent one case of renal scarring.3 In the elderly population, UTIs have never been shown to cause physical or cognitive decline. Up to 40% of elderly patients in care facilities will have asymptomatic bacteriuria.4 Risk Factors for Recurrence In the premenopausal woman, the greatest risks surround intercourse. New partners and use of The Canadian Journal of Diagnosis / April 2012 65 spermicidal gels further increase the risk. In postmenopausal women, the hypoestrogenic state increases risk. A voiding dysfunction, with an inability to empty, can be seen at any age but is more frequent in elderly women. Structural urogenital abnormalities are infrequently the cause. Host factors (diabetes, immune compromise, etc.) and urophilic bacteria also play a role. Differential Diagnosis The differential diagnosis includes interstitial cystitis/painful bladder syndrome, overactive bladder, and vaginitis. All of these result in negative urine cultures. Empiric treatment with resolution of symptoms does not confirm a UTI, as women with interstitial cystitis will often report initial improvement. Investigations Investigations are usually limited to urine culture and sensitivity and an examination looking for prolapse and estrogen status. The pain, urgency, frequency (PUF) questionnaire screens for painful bladder syndrome.5 A post-void residual should also be done. Cystoscopy should be considered for persistent hematuria, culture of uncommon organisms, and to rule out suspected structural abnormalities. Upper urinary tract screening should be performed if there is suspicion of renal stones. Reflux needs to be investigated in those presenting with a history of childhood UTIs, recurrent pyelonephritis, neurological disease, or previous bladder or ureteric surgery. Decreasing Risks The use of cranberry products can reduce the risk of recurrence with a RR = 0.65 (95%, CI 66 UTI Myths6 UTIs are not caused by: • • • • • • • Direction of cleaning after defecation Use of tampons Bubble baths Tight undergarments Dietary factors (coffee, alcohol) Riding bicycles Not voiding after intercourse 0.46 to 0.90) by 12 months.7 Often, taking one tablet b.i.d. is more palatable then drinking pure juice. Methenamine hippurate 1 g q.i.d. with meals and q.h.s. can decrease the rate of symptomatic UTIs with a RR=0.24 (95%, CI 0.07 to 0.89).8 This dosage can be titrated to lower levels if relief is achieved. This medication is often well tolerated.8 In perimenopausal and menopausal women, vaginal estrogen significantly reduces the risk of UTIs. This is not seen with oral estrogen supplementation.9 If a high post-void residual is identified, initiation of self-catheterization can decrease the risk of recurrent UTIs. Antibiotics The use of prophylactic antibiotics needs to be balanced between benefits and risks (bacterial resistance, Clostridium difficile, adverse reactions). To prevent one recurrence, 1.85 people need to be treated.10 Some studies have shown similar results with methenamine hippurate compared to prophylactic antibiotics. If UTIs are Back to Sarah Sarah has confirmed positive urine cultures. She is perimenopausal and an exam reveals vaginal atrophy with no prolapse. Her post-void residual is less than 100 mL. She is started on vaginal estrogen and cranberry pills b.i.d. Sarah does not have a UTI in the following year. The Canadian Journal of Diagnosis / April 2012 Take-home Messages Table 1 Oral Regimens for Continuous Prophylaxis1 Antibiotic Dosage TMP-SMX 40/200 mg q.d. TMP-SMX 40/200 mg 3x/week TMP 100 mg q.d. Nitrofurantoin, monohydrate/ macrocrystals 50–100 mg q.d. Nitrofurantoin macrocrystal 50–100 mg q.d. Cephalexin 125–250 mg q.d. Cefaclor 250 mg q.d. Ciprofloxacin 125 mg q.d. Cinoxacin 250–500 mg q.d. related to sexual activity, taking one dose following intercourse has similar results to continuous prophylaxis.10 Otherwise, prophylaxis is usually initiated for six to twelve months, with a preference for six months (Table 1). No single antibiotic regimen seems superior to another, and selection is dependent on culture sensitivities. Recurrent UTIs are common in the general population and, rarely, will cause long-term sequelae. Initial efforts should be made to decrease risk before prophylaxis antibiotics are started. Dx • • • • Do not treat asymptomatic bacteruria Consider why you are treating Confirm UTI with urine culture Begin therapy with vaginal estrogen (if appropriate), cranberries, and methanamine • In sexually active women, one dose postcoital antibiotics appear as efficacious as long-term prophylaxis References 1. Epp A, Larochelle A, Lovatsis D, et al: Recurrent Urinary Tract Infection. J Obstet Gynaecol Can 2010; 32(11):1082–1101. 2. Little P, Merriman R, Turner S, et al: Presentation, Pattern, and Natural Course of Severe Symptoms, and Role of Antibiotics and Antibiotic Resistance among Patients Presenting with Suspected Uncomplicated Urinary Tract Infection in Primary Care: Observational Study. BMJ 2010: 340(b5633): n.p. 3. Foxman B: The Epidemiology of Urinary Tract Infections. Nat Rev Urol 2010; 7(12):653–660. 4. Woodford HJ, George J: Diagnosis and Management of Urinary Infections in older people. Clin Med 2011; 11(1):80–83. 5. Parsons CL, Dell J, Stanford EJ, et al: Increased Prevalence of Interstitial Cystitis: Previously Unrecognized Urologic and Gynecologic Cases Identified Using a New Symptom Questionnaire and Intravesical Potassium Sensitivity. Urology 2002; 60(4): 573–578. 6. Franco AV: Recurrent Urinary Tract Infections. Best Pract Res Clin Obstet Gynaecol 2005; 19(6):861–873. 7. Jepson RG, Craig JC: Cranberries for Preventing Urinary Tract Infections. Cochrane Database Syst Rev 2008; (1):CD001321. 8. Lee BB, Simpson JM, Craig JC, et al: Methenamine Hippurate for Preventing Urinary Tract Infections. Cochrane Database Syst Rev 2007;(4):CD003265. 9. Perrotta C, Aznar M, Mejia R,et al: Oestrogens for Preventing Recurrent Urinary Tract Infection in Postmenopausal Women. Cochrane Database Syst Rev 2008; (2):CD005131. 10. Albert X, Huertas I, Pereiró II, et al: Antibiotics for Preventing Recurrent Urinary Tract Infection in Non-pregnant Women. Cochrane Database Syst Rev 2004; (3):CD001209. Dr. Magali Robert is an Associate Professor of Gynecology at the University of Calgary, Calgary, Alberta. The Canadian Journal of Diagnosis / April 2012 67