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UTI And RUTI Management Conundrums

Written by Dr Arthur Tseng, Obstetrician Gynecologist (visit his profile here)

INTRODUCTION TO UTI AND RUTI MANAGEMENT CONUNDRUMS

UTI and RUTI Management Conundrums

The inconvenience, discomfort and incapacitation that women feel when a urinary tract infection (UTI) strikes is all too common to general practitioners and specialists alike. Uropathogenic bacteria originating from the gut system can easily spread to cause infection. The belief that simply giving antibiotics is all that is required is still in force. Unfortunately, with the rampant overuse of antibiotics, bacterial resistance has developed rapidly.

UTIs are especially common in females, requiring over 6 million visits to physicians per year in the United States alone. UTIs are commonly termed cystitis (infection of urethra and bladder) and represent the majority of  renal tract infections. Rarer but more severe infections include pyelonephritis, where there is upper urinary tract involvement by contiguous infective spread. Asymptomatic bacteriuria, which describes bacteria in the urine in an asymptomatic patient is significant in pregnant women for risk of significant urosepsis and pregnancy-related complications.

Unfortunately, one in four (25%) women with acute cystitis will progress to have recurrent UTI (RUTI), which is defined as 2 or more infections in a 6 month period. These infections tend to cluster in time, and are due to colonization in faecal, peri-urethral and bladder reservoirs (1).

WHAT ARE SIGNS AND SYMPTOMS OF UTI AND RUTI MANAGEMENT CONUNDRUMS?

The classic symptoms of a UTI are that of dysuria, urinary  frequency and urgency, suprapubic pain, possible flank and costo-vertebral pain, foul-smelling and/or bloody urine, and voiding difficulties. The addition of fever, chills and rigors are often associated with pyelonephritis.

There is growing appreciation that voiding dysfunction is the earliest symptom to herald a UTI, where there is difficulty initiating urination,  hesitancy and poor stream, from urethral spasm secondary to bacterial irritation. This may be a crucial indicator of when to start treatment for patients prone to RUTI.

UTI AND RUTI MANAGEMENT CONUNDRUMS: PATHOPHYSIOLOGY

Escherichia coli causes the majority (70-95% prevalence) of UTI.  Other pathogens responsible include Staphylococcus saprophyticus, Proteus mirabilis, Klebsiella pneumoniae and Enterococcus faecalis.

The urinary tract is sterile under normal circumstances, due to the regular emptying of stale urine, thus reducing the potential for bacterial multiplication and bladder mucosal invasion (2).

Uropathogenic bacteria cause UTIs by peri-genital spread, with colonization, ascending contiguous spread, and the unique ability to adhere to bladder mucosa, thereafter invading between cells to form bio-films that evade local host immune systems and antibiotic attack.

Thus in women, the shorter urethra predisposes to UTIs. Sexual intercourse, dehydration with urinary volume depletion, obstruction, bladder instrumentation, vesico-ureteric reflux, poor catheter care and drainage are other risk factors for UTIs.

In post-menopausal women, the lack of Lactobacilli species in the vagina prevent competitive inhibition of uropathogens. Pregnancy, pre-existing urinary tract abnormalities and obstruction (from pelvic organ prolapse), Diabetes Mellitus and other immunocompromised states all predispose to complicated UTIs and recurrent infection (3,4).

UTI AND RUTI MANAGEMENT CONUNDRUMS: DIAGNOSTIC TOOLS

Urine Dipstick

With acute UTIs, many doctors rely on dipstick to look for positive leukocyte esterase, and nitrite positive status. "Leukocyte esterase positive" status has only a 57-96% sensitivity, but is 94-98% specific. The wide ranging sensitivity reduces accuracy of diagnosis. Moreover, only 25% of patients with UTI are "nitrite positive".

Hence, for women with a risk of complicated acute and recurrent UTIs, it is useful to do a urine microscopy and culture. More so, if the patient is immunosuppressed in anyway, had recent antibiotic exposure, recent bladder instrumentation, known obstruction, post-menopausal, and is of advanced age (5).

Urine Microscopy

A WBC count greater than 10/mL in a fresh unspun sample is abnormal, and has a sensitivity of 80-95%, but with a specificity of 50-75% only for UTI detection. As such, in symptomatic women with a negative urine dipstick, a urine microscopy should be performed, as levels as low as 2-5 WBC/mL can be significant (6).

Gram staining for presence of bacteria, during urine microscopy is highly sensitive and specific for UTI (90 and 88% respectively).

Urine Culture

The current definitions of UTI, based on culture reporting are (7):

Cystitis – more than 1000 CFU/mL

Pyelonephritis – more than 10,000 CFU/mL

Asymptomatic bacteriuria – more than 100,000 CFU/mL

The reduced CFU numbers for cystitis are in recognition that lower counts in symptomatic patients is significant and ought to be treated. Due to emergent antibiotic resistance, empirical antibiotic treatment should be based on knowledge of local sensitivity and resistance patterns, but the eventual culture sensitivities for particular bacterial strains allows for targeted treatment, with higher symptomatic and bacteriologic cure rates and reduced re-infection rates (8). This however, does predispose to antibiotic resistance in uropathogenic bacteria and adversely affects beneficial gut and vaginal flora (9).

Consequently, it is not just appropriate antibiotic therapy that is required, but other adjunctive treatments that can help reduce symptoms and ultimately prevent recurrence.

In patients with RUTI, further investigations are required, and include investigating for Diabetes Mellitus where there is clinical suspicion. Urine cytology is a useful screen for malignancy. An ultrasound of the renal tract is required to exclude stones, obstruction, or malignancy. Cystoscopy with possible biopsy is required for full assessment of the lower renal tract. CT urography has largely superseded ultrasound in sensitivity and specificity for upper tract abnormalities (10).

UTI AND RUTI MANAGEMENT CONUNDRUMS: TREATMENT

In patients with an uncomplicated acute UTI, Gupta, international guidelines for antibiotics usage are recommended, with first-line antibiotics would included Nitrofurantoin, Fosfomycin, and the beta-lactam antibiotic or cephalosporin group. Bactrim (trimethoprim-sulfamethoxazole) should be less often used as resistance patterns are high in various localities and limited usage will maintain effectiveness for certain serious infections. Fluoroquinolones, as second-line agents, should be reserved for complicated UTIs. Treatment duration should range between 3 to 7 days (11). Fosfomycin, in a single 3 gm  dose, is particularly effective due to minimal resistance patterns and collateral damage to gut and vaginal flora currently, when compared to other antibiotic types and is better tolerated in pregnancy (12).

With such treatment, women can expect symptom relief after the third day of antibiotic use, and complete resolution by one week. There isn't a need to do a "test-of-cure" urine culture in uncomplicated cases; unless patients have risk of recurrence or have a complicated UTI, wherein treatment regimes can be up to 2 weeks with an appropriate antibiotic (13).

Urinary alkalinizers, such as Citravescent or Ural, are used concomitantly to reduce dysuria and burning discomfort and pain.

In patients with RUTI, low-dose suppressive antibiotics are used, on a monthly rotational basis, fora minimum duration of 3 to 6 months to eradicate the bacteria(e) present in the bladder. Rotational antibiotic use again reduces the risk of antibiotic resistance emerging in uropathogenic bacteria(e).

In patients with a risk of recurrent complicated UTI, long-term prophylactic treatment between 6 to 12 months may be attempted with Bactrim (1 tablet), Nitrofurantoin (100mg), Norfloxacin (200mg) or Trimethoprim (100mg) as a nightly dose; with a drug break after extended symptom-free period, as 30% of women will be UTI-free for a prolonged period of time. Long-term suppression has been evaluated to be safe and effective even at 5 years of continuous usage.

An alternative therapeutic mode for RUTI is self-initiated antibiotic therapy. Once a woman suspects herself to have a UTI, she initiates treatment using Ofloxacin 200mg BD or Levofloxacin 250mg OM for 3 days, with a clinical cure rate of 95% efficacy (14).

UTI AND RUTI MANAGEMENT CONUNDRUMS: ADJUNCTIVE MEASURES

Adequate hydration is paramount, with suggested fluid intake of 2.0 to 3.0 L/day to produce a uni-directional flow of dilute urine, thus flushing the bladder regularly.

Patients should avoid holding their bladders beyond three to four hours, as this allows stale urine to become rapidly infected. In patients with voiding dysfunction and RUTI, timed interval voiding reduces infective risk.

In sexually active women, drinking adequate amounts of fluids, cleansing the perineum before intercourse, and voiding after  intercourse reduces the risk of "honeymoon cystitis". The use of single-dose suppressive antibiotics post-coitally is particularly effective in prevent infection. Spermicides should be avoided, as they kill normal vaginal flora that keeps uropathogenic bacteria in check.

The use of cranberry juice (300 mL/day) or extract appears to be useful in preventing RUTI, by reducing bacterial adherence due to the active ingredient type A proanthocyanidins and bactericidal effects of hippuric acid (15,16). Recent meta-analysis has proven cranberry benefits if used twice daily at requisite doses (17).

Probiotic usage to prevent RUTIs has been studied, has found that oral administration restored vaginal lactobacilli flora and reduced colonization of uropathogenic bacteria, as did  intra-vaginal probiotic suppository usage. In both methods, reduction in recurrence was comparable to antibiotic  suppression, with less adverse effects and less resistance build-up in bacteria species.  Currently, evidence is accruing that may support the widespread use of probiotic therapy in pre- and post-menopausal women with RUTIs, as a reasonable alternative for women wishing to avoid long-term antibiotic use and minimize antimicrobial resistance (18,19).

In menopausal women with RUTI, topical oestrogen therapy  bolsters vaginal, peri-urethral and bladder local defenses by restoring lactobacilli that resist uropathogenic infection (20,21).

Perineal hygiene is important in preventing contiguous spread. The action of wiping from front to back, and never reusing soiled tissue paper reduces bacterial spread. Taking showers and avoiding long baths reduces the risk of skin flora from infecting the bladder. The use of tampons during periods reduces menstrual blood contamination of the perineum and infective risk. The use of breathable cotton undergarments to prevent moisture accumulation and perineal skin maceration reduces infective risk.

There is some research suggesting intravesical chondroitin sulphate and hyaluronic acid instillation, compared to prophylactic antibiotics, significantly reduces RUTI recurrence rates, with improved quality of life and urodynamic parameters over a 12 month study period (22).

CONCLUSION ON UTI AND RUTI MANAGEMENT CONUNDRUMS

With the onset of antibiotic resistance, gone are the days where simply throwing any antibiotic at a patient was guaranteed a cure for what was considered a minor, albeit troublesome and unpleasant, infection by most doctors. The need to be aware of local antibiotic sensitivities and resistance patterns makes UTI, RUTI and complicated UTIs more challenging. Hence, the need to educate our patients on good perineal hygiene habits, the possibility of instituting non-antibiotic modalities of treatment, and entertain novel therapeutic methods that are on the horizon. Perhaps, some bright spark ought to study of home-made barley water and the reputed benefits of preventing and treating UTIs?

Article written by Dr Arthur Tseng, Obstretician Gynecologist (visit his profile)

Return to Urbanrehab: Physiotherapy & Rehabilitation Specialist Singapore Home Page from our UTI and RUTI Management Conundrums page

REFERENCES

1. Nosseir SB, et al. Recurrent Uncomplicated Urinary Tract Infections in Women: A Review. J Womens Health (Larchmt). Dec 2 2011.

2. Lane DR, Takhar SS. Diagnosis and management of urinary tract infection and pyelonephritis. Emerg Med Clin North Am. Aug 2011;29(3):539-52.

3. Hooton TM, et al. 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis. Mar 1 2010;50(5):625-63.

4.Tiemstra JD, et al. Genitourinary infections after a routine pelvic exam. J Am Board Fam Med. May-Jun 2011;24(3):296-303.

5. Little P, et al. Dipsticks and diagnostic algorithms in urinary tract infection. Health Technol Assess. Mar 2009;13(19):iii-iv, ix-xi, 1-73.

6. Schaeffer AJ, et al. Infections of the Urinary Tract. In: McDougal WS, et al, eds. Campbell-Walsh Urology. 10th Ed. Philadelphia, PA: Elsevier Saunders; 2012:46-55.

7. Mehnert-Kay SA. Diagnosis and Management of Uncomplicated Urinary Tract Infections. American Family Physician. August 1, 2005;27/No.3:1-9.

8. Falagas ME, et al. Antibiotics versus placebo in the treatment of women with uncomplicated cystitis: a meta-analysis of randomized controlled trials. J Infect. Feb 2009;58(2):91-102.

9. Foxman B. The epidemiology of urinary tract infection. Nat Rev Urol. Dec 2010;7(12):653-60.

10. Nickel JC, et al. Value of urologic investigation in a targeted group of women with recurrent urinary tract infection. Can J. Surg.34(6), 591-594 (1991).

11. Gupta K, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. Mar 2011;52(5):e103-20.

12. Falagas ME, et al. Fosfomycin versus other antibiotics for the treatment of cystitis: a meta-analysis of randomized controlled trials. J Antimicrob Chemother. Sep 2010;65(9):1862-77.

13. Little P, 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. Feb 5 2010;340:b5633.

14. Gupta K, et al. Patient-initiated treatment of uncomplicated recurrent urinary tract infections in young women. Ann Intern Med. Jul 3 2001;135(1):9-16.

15. Jepson RG, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev. Jan 23 2008;CD001321.

16. Tempera G, et al. Inhibitory activity of cranberry extract on the bacterial adhesiveness in the urine of women: an ex-vivo study. Int J Imumunopathol Pharmacol. Apr-Jun 2010;23(2):611-8.

17. Wang CH, et al. Cranberry-containing products for prevention of urinary tract infections in susceptible populations: a systematic review and meta-analysis of randomized controlled trials. Arch Intern Med 2012;172:988–96.

18. Reid G, et al. Oral use of Lactobacillus rhamnosus GR-1 and L.fermentum RC-14 significantly alters vaginal flora: randomized, placebo-controlled trial in 64 healthy women. FEMS Immunol Med Microbiol 2003;35:131–4.

19. Stapleton AE, et al. Randomized, placebo-controlled phase 2 trial of a Lactobacillus crispatus probiotic given intravaginally for prevention of recurrent urinary tract infection. Clin Infect Dis 2011;52:1212–17.

20. Raz R, Stamm WE. A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections. N Engl J Med. Sep 9 1993;329(11):753-6.

21. Perrotta C, Aznar M, Mejia R, et al. Oestrogens for preventing recurrent urinary tract infection in postmenopausal women. Cochrane Database Syst Rev 2008;CD005131.

22. De Vita D, Giordano S. Effectiveness of intravesical hyaluronic acid/chondroitin sulfate in recurrent bacterial cystitis: a randomized study. Int Urogynecol J. Dec 2012;23(12):1707-13.

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