Managing first-time and recurrent UTIs

With growing resistance due to empiric antibiotic use, what’s first-line therapy? Should asymptomatic women be treated? Our expert has the answers.

One in five women will have a UTI during her lifetime, but even more astonishing is the recurrence rate. As many as 20% of women who have one episode will experience another, and up to 30% of these women will have a third; in the latter group, recurrence rates can approach 80%.1 Thus, management of this common condition can be complicated by high rates of recurrence and by such other factors as ever-changing patterns of resistance to antibiotics and increasing recognition of the need to use antibiotics judiciously.

Older women not immune

UTIs are usually caused by Escherichia coli, which accounts for 85% of community-acquired cases. Other common culprits are Enterococcus faecalis, Staphylococcus saprophyticus, Klebsiella pneumoniae, and Proteus mirabilis, with the latter two pathogens more common in women older than 50 years.2

In young women, sexual activity is the most common cause of uncomplicated UTI.3 Other risk factors in the 18- to 49-year-old age group include incontinence, spermicide use, diaphragm use, a recent UTI, diabetes, and maternal history of UTI.1, 4

Postmenopausal women have a lower likelihood of UTI, but, as in younger women, risk factors include sexual activity, history of UTI, and presence of diabetes mellitus. Other risk factors, such as insulin dependence, higher lifetime number of UTIs, and urinary incontinence, have also been identified in postmenopausal women.5,6

The presence of cystoceles, history of genitourinary surgery, increased residual urine volume after voiding, and increased presence of abnormalities, e.g., bladder diverticuli, are associated with recurrent UTIs in community-dwelling elderly women. A greater variety of organisms are isolated from elderly women than their younger counterparts with acute uncomplicated UTIs.7

In elderly women residing in long-term-care facilities, UTIs are the most common bacterial infection. Factors in this population include chronic comorbidities that can impair bladder voiding and interventions to manage incontinence.7

Clinical features may include painful urination, urinary frequency, urinary urgency, and suprapubic pain.3, 8 In a natural history study of women with uncomplicated UTI, frequency was the most common symptom. Patients waited an average of almost five days before seeking medical attention, and by that time, symptoms had significantly affected their normal activities.2, 9 Bothersome symptoms can also result in absence from work.2

In a woman with a history of UTI, self-diagnosis can be sufficient to initiate treatment. In those without such a history, a urine dipstick result positive for nitrites, leukocyte esterase, or both is highly suggestive of diagnosis. Specimens, preferably first-morning, midstream, and clean-catch, should be collected in clean, dry, disposable containers to minimize contamination.

Combined symptoms of dysuria and frequency in the absence of vaginal discharge or irritation have a high likelihood of being diagnostic for UTI as well.10 In symptomatic women, routine urine cultures are generally not necessary because the causative pathogens can be anticipated, but cultures may be appropriate when patients do not respond to initial treatment3 or if an atypical organism is suspected, as in an immunocompromised patient.

Myths of UTIs in the elderly

The management of UTI in elderly women can be complex. Widespread and incorrect myths surrounding the elderly and UTIs—specifically, that UTIs can cause nonspecific symptoms such as anorexia and malaise, and that treating asymptomatic bacteriuria can improve chronic genitourinary symptoms, such as incontinence—have led to overtreatment.11 At the same time, UTIs in elderly frail women can be associated with significant morbidity and even mortality.2 As in younger women, dysuria, frequency, and urgency are common symptoms, but they require cautious interpretation because they are often present in those without infection.

Frail, elderly women with acute symptomatic UTIs require treatment, but diagnosis should be based on careful clinical evaluation. A urine sample that grows bacteria cannot distinguish between a true UTI and colonization/ contamination.

Thus, clinicians should treat the patient, not the culture results, to avoid antibiotic overuse. Indeed, some recommend using urine cultures in older persons only to confirm antimicrobial susceptibility.11,12

Should asymptomatic bacteriuria be treated? In premenopausal, nonpregnant women, current guidelines from the Infectious Diseases Society of America (IDSA) do not recommend screening and treatment of asymptomatic bacteriuria. Pregnant women should be screened at least once, preferably early in the pregnancy, and treated if results are positive. For older women living in the community and for institutionalized elderly women, IDSA guidelines also do not recommend routine screening and treatment. With the exception of pregnant women or those undergoing selected invasive genitourinary procedures, symptomatic bacteriuria has not been shown to be harmful, and treatment has not been proven to decrease the frequency of symptomatic infection.13 In short, the current guidelines recommend screening and treatment of asymptomatic bacteriuria only in selected populations and urge avoidance of antimicrobial therapy when no benefit has been demonstrated.

Selecting the best treatment

Trimethoprim/sulfamethoxazole (TMP/SMX) remains one the mainstays for uncomplicated UTI, but the growing resistance of E. coli to this therapy makes its use much less automatic than it used to be.14

Low-cost TMP/SMX can be given for three to seven days. The recurrence rate may be higher with the shorter course, but more adverse effects can occur with longer treatment.13 TMP/SMX has an eradication rate >93% for susceptible pathogens—making it the first-line option for empiric treatment. However, E. coli resistance to TMP/SMX is an increasing problem. Based on in vitro surveillance data, approximately 10%-20% of urinary E. coli isolates from female outpatients in the United States are resistant to TMP/SMX.15 In a nationwide analysis of TMP/SMX and E. coli isolates, the western United States had the highest resistance rate (22%). In another study, recent use of TMP/SMX was associated with high rates of infection with TMP/SMX-resistant isolates and its use in women with TMP/SMX-resistant isolates resulted in high rates of treatment failure.16 It is prudent, therefore, to consider local resistance patterns and each patient’s recent antibiotic use before prescribing TMP/SMX for a UTI.

Fosfomycin: In those with mild symptoms, single-dose fosfomycin may be considered. Fosfomycin is bactericidal and concentrates in the urine, thereby blocking growth of pathogens for 24-36 hours. Drawbacks to its use are that it is more expensive than TMP/SMX and less effective.3 IDSA guidelines note that single-dose fosfomycin therapy is much less effective in eradicating initial bacteriuria than longer duration treatment with TMP/SMX, norfloxacin, and ciprofloxacin.13

Nitrofurantoin: Escherichia coli continues to have a low resistance to nitrofurantoin. At its recommended dosing (7-10 days b.i.d.), nitrofurantoin is similar to fosfomycin in efficacy. A comparative trial of single-dose fosfomycin and seven-day nitrofurantoin demonstrated an equivalent overall clinical success rate (cure and improvement) of 80% with each agent. 3,17, 18

Fluoroquinolones: As a group, these agents are highly effective, but they have drawbacks, including cost.14 Fluoroquinolones can be given in three-day regimens and they have the highest cure rates, but resistance, while low, is increasing. In the analysis of antimicrobial susceptibility patterns previously discussed, non-E. coli isolates from women older than 50 years were much less susceptible to fluoroquinolones than isolates from younger women.18 Thus, age may be a consideration when prescribing a quinolone. So, too, may susceptibility patterns. One study has shown that among TMP-SMX-resistant E. coli isolates, nearly 10% were also resistant to ciprofloxacin.15

Because these agents are also highly useful in treating complicated UTIs, clinicians may want to consider prescribing other agents to treat uncomplicated UTIs so as to lessen the risk of increased resistance with widespread use. However, when the pathogen is S. saprophyticus in women of childbearing age, longer therapy with fluoroquinolones in particular may be appropriate.14 Overall, fluoroquinolones may be most appropriate for use in areas with high resistance rates to TMP/SMX (10%-20%) and in women with more bothersome symptoms or with contraindications to the use of other antibiotics.17

Cephalosporins: These are not recommended as first-line agents for UTIs. Their use is limited by increasing rates of resistance and by their broad spectrum of activity, which can increase the risk of vulvovaginal candidiasis.3, 16It has been speculated that their rapid rate of excretion allows little time for significant drug levels to be reached in urine and that their relative inefficacy in eradicating gram-negative rods predisposes patients to recurrence.14

Other therapies: Although cranberry juice is a well-known folk remedy for UTIs, the evidence for its use is mixed. One study showed a significantly decreased rate of UTI recurrence in women who drank cranberry/lingonberry juice compared with those who drank a lactobacillus drink or a control group.19 However, a Cochrane review concluded that the evidence to recommend cranberry juice is insufficient at this time.20 Drinking lots of water, another folk remedy, also lacks scientific support. In fact, patients should be advised not to drink lots of water while taking an antibiotic for a UTI because this may dilute the urinary concentration of the antimicrobial.

Probiotics, which involves lactobacillus instillation into the vagina to avert or halt the ascension of uropathogens into the bladder, are also being investigated. Use of a vaginal suppository containing a strain of Lactobacillus crispatus GAI 98322 significantly reduced the number of UTI recurrences in a small pilot trial in cystitis-prone women.21 Efficacy has been shown for Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri B-54, but they are not available in this country. No probiotic product can be recommended for widespread use to prevent UTI at this time.22 Advise patients that many claims for OTC probiotic products have not been substantiated in controlled clinical trials.

Studies of estrogen have been contradictory. Some have shown an increased risk of UTI in women taking estrogen; in others estrogen was preventive. Currently, topical estrogen preparations can be recommended only in women not taking oral estrogens who are experiencing three or more UTIs each year. In such cases, topic vaginal estrogen may be effective, especially when antimicrobial resistance is an issue.23

A novel approach to prevention of UTIs involves vaccines. Mucosal, parenteral, oral, and vaginal vaccines are being investigated for use against E. coli and other uropathogens. Early results have been promising, but no vaccine is clinically available yet.1

Dr. Sadovsky is associate professor of family medicine at SUNY-Downstate Medical Center, in Brooklyn, N.Y.

References

1. The National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC). Urinary tract infections in adults. Available at kidney.niddk.nih.gov/kudiseases/pubs/utiadult. Accessed April 10, 2007.

2. Griebling TL. Urinary tract infection in women. In: Litwin MS, Saigal CS, eds. Urologic Diseases in America. U.S. Dept. of Health and Human Services, Public Health Service, NIH, NIDDKD. Washington, DC: U.S. Government Printing Office, 2004; NIH publication 04-5512;155-186.

3. Mehnert-Kay SA. Diagnosis and management of uncomplicated urinary tract infections. Am Fam Physician. 2005;72:451-456.

4. Scholes D, Hooton TM, Roberts PL, et al. Risk factors associated with acute pyelonephritis in healthy women. Ann Intern Med. 2005;142:20-27.

5. Jackson SL, Boyko EJ, Scholes D, et al. Predictors of urinary tract infection after menopause: a prospective study. Am J Med. 2004;117:903-911.

6. Hu KK, Boyko EJ, Scholes D, et al. Risk factors for urinary tract infections in postmenopausal women. Arch Intern Med. 2004;164:989-993.

7. Nicolle LE. Urinary tract infection in geriatric and institutionalized patients. Curr Opin Urol. 2002;12:51-55.

8. CDC Coordinating Center for Infectious Diseases/Division of Bacterial and Mycotic Diseases. Urinary tract infections. Available at www.cdc.gov/ncidod/dbmd/diseaseinfo/urinarytractinfections_t.htm. Accessed April 10, 2007.

9. Nickel JC, Lee JC, Grantmyre JE, Polygenis D. Natural history of urinary tract infection in a primary care environment in Canada. Can J Urol. 2005;12:2728-2737.

10. Aubin C. Does this woman have an acute uncomplicated urinary tract infection? Ann Emerg Med. 2007;49:106-108.

11. McMurdo ME, Gillespie ND. Urinary tract infection in old age: over-diagnosed and over-treated. Age Ageing. 2000;29:297-298.

12. Stein GE. Comparison of single-dose fosfomycin and a 7-day course of nitrofurantoin in female patients with uncomplicated urinary tract infection. Clin Ther. 1999;21:1864-1872.

13. Nicolle LE, Bradley S, Colgan R, et al. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis. 2005;40:643-654.

14. Warren JW, Abrutyn E, Hebel JR, et al. Guidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women. Clin Infect Dis. 1999;29:748-758.

15. Karlowsky JA, Thornsberry C, Jones ME, Sahm DF. Susceptibility of antimicrobial-resistant urinary Escherichia coli isolates to fluoroquinolones and nitrofurantoin. Clin Infect Dis. 2003;36:183-187.

16. Brown PD, Freeman A, Foxman B. Prevalence and predictors of trimethoprim-sulfamethoxazole resistance among uropathogenic Escherichia coli isolates in Michigan. Clin Infect Dis. 2002;34:1061-1066.

17. Czaja CA, Hooton TM. Update on acute uncomplicated urinary tract infection in women. Postgrad Med. 2006;119:39-45.

18. Gupta K, Sahm DF, Mayfield D, Stamm WE. Antimicrobial resistance among uropathogens that cause community-acquired urinary tract infections in women: a nationwide analysis. Clin Infect Dis. 2001;33:89-94.

19. Kontiokari T, Sundqvist K, Nuutinen M, et al. Randomised trial of cranberry-lingonberry juice and Lactobacillus GG drink for the prevention of urinary tract infections in women. BMJ. 2001;322:1571.

20. Jepson RG, Mihaljevic L, Craig J. Cranberries for treating urinary tract infections. Cochrane Database Syst Rev. 2000;(2):CD001322.

21. Uehara S, Monden K, Nomoto K, et al. A pilot study evaluating the safety and effectiveness of Lactobacillus vaginal suppositories in patients with recurrent urinary tract infection. Int J Antimicrob Agents. 2006;28(suppl 1):S30-S34.

22. Reid G, Bruce AW. Probiotics to prevent urinary tract infections: the rationale and evidence. World J Urol. 2006;24:28-32.

23. Stamm WE. Estrogens and urinary-tract infection. J Infect Dis. 2007;195:623-624.

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