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ESSENTIALS OF DIAGNOSIS
Dysuria.
Frequency, urgency, or both.
Urine dipstick analysis positive for nitrites or leukocyte esterase.
Positive urine culture (>104 organisms).
No fever or flank pain.
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General Considerations
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Acute, uncomplicated cystitis is most common in women. Approximately one-third of all women have experienced at least one episode of cystitis by the age of 24 years, and nearly half will experience at least one episode during their lifetime. When a young woman presents to a health care provider with one or more symptoms, her probability of UTI is approximately 50%. Young women’s risk factors include sexual activity, use of spermicidal condoms or diaphragm, and genetic factors such as blood type or maternal history of recurrent cystitis. Healthy, noninstitutionalized older women can also experience recurrent cystitis. Risk factors among these women include changes in the perineal epithelium and vaginal microflora after menopause, incontinence, diabetes, and history of cystitis before menopause.
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Although men can also suffer from cystitis, it is rare (annual incidence: <0.01% of men aged 21–50 years) in men aged <35 years who have normal urinary anatomy. Urethritis from sexually transmitted pathogens should always be considered in this age group, and prostatitis should always be ruled out in the older age group by a rectal examination. Any cystitis in a man is complicated, due to the presence of the prostate gland, and should be treated for 10–14 days to prevent a persistent prostatic infection.
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Considering the frequency and morbidity of cystitis among young women, it is hardly surprising that the lay press and medical literature contain a host of ideas about how to prevent recurrent cystitis. These range from the suggestion that cotton underwear is “healthier” to wiping habits, voiding habits, and choice of beverage. Unfortunately, the vast majority of these preventive measures do not hold up to scientific study (Table 23-1).
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Recent studies have shown no effect of back-to-front wiping, precoital voiding, tampon use, underwear fabric choice, or use of noncotton hose or tights. Behaviors that do appear to have an impact on frequency of cystitis in young women include sexual activity (four or more episodes per month in one study), delayed postcoital voiding, use of spermicidal condoms (several studies), use of unlubricated condoms (one study), use of diaphragms or cervical caps, and intake of cranberry juice.
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It can be concluded from Table 23-1 that a few behaviorally oriented strategies can be offered to young women who suffer from recurrent cystitis. Recommending a change in contraception to oral contraceptive pills, intrauterine devices, or nonspermicidal, lubricated condoms may be helpful.
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Cranberry juice and cranberry extract have long been proposed as a possible way to prevent UTIs. Cranberries supposedly contain a substance that changes the surface properties of Escherichia coli and prevents it from adhering to the bladder wall. A recent Cochrane Review identified 10 studies comparing the effects of cranberry products with placebo, juice, or water. There was evidence to show cranberries in the form of juice or capsules could prevent recurrent UTIs in women. A reasonable dose in capsule form is 300–400 mg twice daily. As for juice, 8 oz 3 times daily of unsweetened juice is recommended. It is unclear how long the duration should be.
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Prophylactic antibiotics, either low-dose daily antibiotics or postcoital antibiotics, remain the mainstay of prevention of recurrent UTIs for young women and can reduce recurrence rates by ≤95%.
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B. Postmenopausal Women
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Risk factors for cystitis in older women include urologic factors such as incontinence, cystocele, and postvoid residual; hormonal factors resulting in a lack of protective lactobacillus colonization; and a prior history of cystitis. For the above mentioned risk factors, the most easily administered effective prevention is estrogen.
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There are many possible ways to administer estrogen. These include traditional oral hormone replacement therapy, which is still considered indicative (after thorough discussion with the patient of risks and benefits) for menopausal symptoms, vaginal estrogen rings, or vaginal creams.
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The only form of estrogen that has been proven to decrease recurrent UTIs in postmenopausal women is vaginal. The usual side effects of estrogen can be seen with vaginal use as well as oral. These include breast tenderness, vaginal bleeding, vaginal discharge, and vaginal irritation. Contraindications (as with oral estrogens) include a history of endometrial carcinoma, breast carcinoma, thromboembolic disorders, and liver disease. Patients’ functional and cultural abilities should be considered before prescribing vaginal applications.
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One study compared the effects of cranberry extract (500 mg daily) to trimethoprim for the prevention of recurrent UTIs in older women. There was only a slight advantage of the antibiotic over cranberry extract.
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The only studies focusing on prevention of UTI in young men have investigated infant circumcision; because the risk of UTI is so low in normal men, these studies are prohibitively expensive. In boys with recurrent UTI or high-grade ureteral reflux, the NNTs are 11 and 4, respectively. The complication rate of circumcision is 2–10%, with adverse sequelae ranging from minor transient bleeding (common) to amputation of the penis (extremely rare). It does appear to decrease the chance of UTI in boys and men. The risk of UTI in normal boys hovers around 1% in the first 10 years of life, given that the number needed to treat (NNT) for circumcision is 111.
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D. Future Trends in Prevention
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Several investigations are ongoing in finding ways to prevent recurrent urinary tract infections, given the high prevalence and health burden that they impose. Vaginal vaccines are working their way through clinical trials and are not yet commercially available; whether they will prove to be more efficacious than prophylactic antibiotics is yet to be determined. Currently, a sublingual bacterial vaccine is also in development. This also looks promising, but needs more research.
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A. Symptoms and Signs
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Symptoms include dysuria, ideally felt more internally than externally, and of sudden onset; suprapubic pain; cloudy, smelly urine; frequency; and urgency.
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Physical examination in the afebrile, otherwise healthy patient with a classic history is done essentially to rule out other diagnoses and to ensure that red flags are not present. The examination might range from checking a temperature and percussing the costovertebral angles to a full pelvic examination, depending on where the history leads. There are no pathognomonic signs on physical examination for cystitis.
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B. Laboratory Findings
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Laboratory studies include dipstick test of urine, urinalysis, and urine culture. In some cases laboratory tests are not required to diagnose cystitis with high accuracy; however, they should probably be omitted only in settings where follow-up can be easily arranged in case of failure of treatment, which would, of course, indicate further workup. Figure 23-1 provides a diagnostic algorithm for cystitis.
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1. Urine dipstick testing
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Dipstick findings are positive for leukocyte esterase or nitrite, or both. Several references now support treatment of simple, uncomplicated UTI in the young, nonpregnant woman on the grounds of clinical history alone, if that history leads to high suspicion for cystitis (and low suspicion of STD). For women with an equivocal clinical history, urine dipstick analysis may suffice to reassign the women to high or low suspicion and treat or not treat accordingly.
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Urinalysis will be positive for WBCs, with few or no epithelial cells. It should be noted, however, that urinalysis is more expensive than dipstick analysis and only minimally more accurate.
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The gold standard of diagnosis is a culture growth of 100,000 (105) organisms in a midstream clean-catch sample. However, some patients have classic clinical cases of UTI and only 100 (102) organisms on culture. Few laboratories are equipped to detect anything fewer than 104 organisms. Culture is strongly suggested if a relapsing UTI or pyelonephritis is suspected to ensure sensitivities and eradication (see Figure 23-1).
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Imaging studies are seldom required for patients with simple uncomplicated UTIs.
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These tests are generally required only for failures of treatment, symptoms suggesting a diagnosis other than cystitis, or complicated cystitis (see section on complicated cystitis, later).
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Differential Diagnosis
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There are virtually no complications from repeated uncomplicated cystitis if it is recognized and treated. Delay in treatment may lead to ascending infection and pyelonephritis. In the case of infection with urea-splitting bacteria, “infection stones” of struvite with bacteria trapped in the interstices may be formed. These stones lead to persistent bacteriuria and must be completely removed to clear the infection. Proteus mirabilis, Staphylococcus saprophyticus, and Klebsiella bacteria can all split urea and lead to stones.
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There is ample evidence from randomized clinical trials to support the superiority of 3-day antibiotic therapy to 1-day treatment and, equivalently, of therapy for longer periods of time, with the exception of nitrofurantoin. This is true for treatment of older, noninstitutionalized women as well. Trimethoprim-sulfamethoxazole, in the absence of allergies to sulfa and local resistance rates of >10–20%, should be considered first-line therapy. Risk factors for trimethoprim-sulfamethoxazole resistance include recent antibiotic exposure, recent hospitalization, diabetes mellitus, three or more UTIs in the past year, and possibly use of oral contraceptive pills or estrogen replacement therapy. For patients who are allergic to sulfa drugs, a 5–7-day course of nitrofurantoin or a 3-day course of a fluoroquinolone (eg, ciprofloxacin) can be used. However, because of concern regarding fluoroquinolone resistance and frequency of cystitis, they should be used sparingly. β-Lactam antibiotics are not as effective as other classes of drugs against urinary pathogens and should not be used as first-line agents except in pregnant patients.
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B. Acute Cystitis in the Pregnant Woman
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Treatment with amoxicillin, a cephalosporin, nitrofurantoin, or another pregnancy-safe antibiotic for 7 days remains the standard. Asymptomatic bacteriuria, if found on cultures, is treated in pregnant women with the same antibiotics (see section on asymptomatic bacteriuria, earlier).
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C. Prophylaxis for Recurrent Cystitis
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Low-dose, prophylactic antibiotics have been shown to decrease recurrences by ≤95%. Most recommendations suggest starting prophylaxis after a patient has had more than three documented UTIs in 1 year. Prophylactic antibiotics are usually administered for 6 months to 1 year but can be given for longer periods of time. Antibiotics can be taken daily at bedtime or used postcoitally by women whose infections are associated with intercourse (Table 23-3). Unfortunately, prophylaxis does not change the propensity of these women for recurrent UTIs; when prophylaxis is stopped, approximately 60% of women develop a UTI within 3–4 months. Prophylaxis should not start until cultures have shown no growth after treatment, to rule out bacterial persistence.
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Long-term prognosis in terms of kidney function is excellent; prognosis of arresting recurrent cystitis without permanent prophylaxis is not as good. New preventive treatments are currently being explored, and it is hoped that these will prove beneficial.
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