142 CHAPTER 5 Infections and inflammatory conditions

Recurrent urinary tract infection

Recurrent UTI is defined as >2 infections in 6 months, or 3 within 12 months. It may be due to reinfection (i.e., infection by different bacteria) or bacterial persistence (infection by the same organism originating from a focus within the urinary tract).

Bacterial persistence

This implies the presence of bacteria within a site in the urinary tract, the presence of which leads to repeat episodes of infection. Such sites include urolithiasis anywhere in the urinary tract, chronically infected pro-state (chronic bacterial prostatitis), bacteria within an obstructed or atrophic kidney, bacteria gaining access to the urinary tract via a fistula (bowel or vagina), and bacteria within a urethral diverticulum.

Thus, recurrent urinary infection due to bacterial persistence implies a functional or anatomical problem. The recurrent UTIs will not resolve until this underlying problem has been addressed.

Reinfections

Reinfections usually occur after a prolonged interval (months) from the previous infection and are often caused by a different organism than the previous infecting bacterium. Bacterial persistence often leads to frequent recurrence of infection (within days or weeks) and the infecting organism is usually the same organism as that causing the previous infection(s).

Women with reinfection do not usually have an underlying functional or anatomical abnormality. Reinfections in women are associated with increased vaginal mucosal receptivity for uropathogens and ascending colonization from the fecal flora. These women cannot be cured of their predisposition to recurrent UTIs, but they can be managed by a variety of techniques (see below).

Men with reinfection may have underlying BLADDER OUTLET OBSTRUCTION (due to prostate enlargement or urethral stricture), which makes them more likely to develop a repeat infection, but between infections their urine is sterile (i.e., they do not have bacterial persistence between symptomatic UTIs). A urethrogram, flexible cystoscopy, postvoid bladder ultrasound for residual urine volume, and, in some cases, urodynamics may be helpful in establishing the potential causes.

Both men and women with bacterial persistence usually have an underlying functional or anatomical abnormality and they can potentially be cured of their recurrent UTIs if this abnormality is identified and corrected.

Management of women with recurrent UTIs from reinfection

Most urologists will arrange a series of screening tests (KUB radiograph, renal ultrasound, CT scan, flexible cystoscopy) to evaluate for a potential source of bacterial persistence. In the absence of finding an underlying functional or anatomic abnormality, many of these patients cannot be cured of their tendency to recurrent UTI, but they can be managed in one of the following ways.

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Avoidance of spermicides used with the diaphragm or on condoms

Spermicides containing nonoxynol-9 reduce vaginal colonization with lactobacilli and may enhance E. coli adherence to urothelial cells. Recommend an alternative form of contraception.

Estrogen replacement therapy

Lack of estrogen in postmenopausal women causes loss of vaginal lactobacilli and increased colonization by E. coli. In postmenopausal women, estrogen replacement, locally or systemically, has been shown to decrease the rate of recurrent UTI by recolonization of the vagina with lactobacilli and to eliminate colonization with bacterial uropathogens.1

Low-dose antibiotic prophylaxis

Oral antimicrobial therapy with full-dose oral tetracyclines, ampicillin, sulfonamides, amoxicillin, and cephalexin causes resistant strains in the fecal flora and subsequent resistant UTIs. However, trimethoprim, nitrofurantoin, low-dose cephalexin, and the fluoroquinolones appear to have minimal adverse effects on the fecal and vaginal flora.

Efficacy of prophylaxis

Recurrences of UTI may be reduced by as much as 90% when compared with placebo.2 Prophylactic therapy requires only a small dose of an antimicrobial agent, generally given at bedtime for 6 to 12 months.

Symptomatic reinfection during prophylactic therapy is managed with a full therapeutic dose with the same prophylactic antibiotic or another antibiotic. Prophylaxis can then be restarted.

Symptomatic reinfection immediately after cessation of prophylactic therapy is managed by restarting nightly prophylaxis.

Trimethoprim

The gut is a reservoir for organisms that colonize the periurethral area and that may subsequently cause episodes of acute cystitis in young women. Trimethoprim eradicates gram-negative aerobic flora from the gut and vaginal fluid (i.e., it eliminates the pathogens from the infective source). Trimethoprim is also concentrated in bactericidal concentrations in the urine following an oral dose.

Dosage for trimethoprim is 100 mg/day.

Adverse reactions include blood dyscrasias due to bone marrow depression; rarely, Stevens–Johnson syndrome; allergic reactions; and rarely, erythema multiforme, toxic epidermal necrolysis (photosensitivity).

Nitrofurantoin

Nitrofurantoin is completely absorbed and/or degraded or inactivated in the upper intestinal tract and therefore has no effect on gut flora. It is present for brief periods at high concentrations in the urine and leads to repeated elimination of bacteria from the urine. Nitrofurantoin prophylaxis therefore does not lead to a change in vaginal or introital colonization with Enterobacteria.

1 Perrotta C, Aznar M, Mejia R, Albert X, Ng CW (2008). Oestrogens for preventing recurrent urinary tract infection in postmenopausal women. Cochrane Database Syst Rev 16;(2):CD005131. 2 Kaur H, Arunkalaivanan AS (2007). Urethral pain syndrome and its management. Obstet Gynecol Surv. 62(5):348–351

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“Self-start therapy”

Women keep a home supply of an antibiotic (e.g., trimethoprim, nitrofurantoin, a fluoroquinolone) and start treatment when they develop symptoms suggestive of UTI. This program should be limited to those who have been completely evaluated and are knowledgeable in the appropriate use of self-directed therapy.

Management of men and women with recurrent UTIs due to bacterial persistence

Investigations

These are directed at identifying the potential causes of bacterial persistence, outlined above.

•KUB radiograph to detect radio-opaque renal calculi.

•Renal ultrasound to detect hydronephrosis and renal calculi. If hydro-nephrosis is present, but the ureter is not dilated, consider the possibility of a radio-opaque stone obstructing the PUJ (this will

usually be seen as an acoustic shadow on the ultrasound; arrange a CT urogram if no stone is seen) or a PUJO (arrange a MAG3 renogram to

determine the presence or absence of PUJO).

•Determination of post-void residual urine volume by bladder ultrasound

•IVP or CT urogram where a stone is suspected but not identified on plain X-ray or ultrasound

•Flexible cystoscopy to identify possible causes of recurrent UTIs such as bladder stones, an underlying bladder cancer (rare), urethral or bladder neck stricture, or fistula

Treatment

Treatment depends on the functional or anatomical abnormality identified as the cause of the bacterial persistence. If a stone or multiple stones are identified, they should be removed. If there is obstruction (e.g., BPO, PUJO, DSD in spinal injured patients), this should be corrected.

Further reading

Schooff M, Hill K (2005). Antibiotics for recurrent urinary tract infections [review]. Am Fam Physician 1;71(7):1301–1302.