Definitions

• Bacteriuria - this refers to the presence of bacteria in the urine.
• Urinary tract infection (UTI) - this implies the presence of characteristic symptoms and significant bacteriuria from kidneys to bladder. Many laboratories regard 10⁵ colony-forming units per millilitre (cfu/ml) as the threshold for diagnosing significant bacteriuria.
• Lower UTI - this is generally considered to be infection of the bladder (cystitis).
• Upper UTI - this includes pyelitis and pyelonephritis.
• Recurrent UTI - this may be due to relapse or re-infection.The number of recurrences that is regarded as clinically significant depends on age and sex.
• Uncomplicated UTI - this refers to infection of the urinary tract by a usual pathogen in a person with a normal urinary tract and with normal kidney function.
• Complicated UTI - this occurs where anatomical, functional, or pharmacological factors predispose the person to persistent infection, recurrent infection or treatment failure, e.g. abnormal urinary tract.

Between 52% and 90% of men with a UTI have been reported to have prostatic involvement in the infection, which can result in prostatic abscesses or prostatitis.¹

Pathogenesis

Several micro-organisms are known to cause UTI, but the majority of infections will be produced by three organisms:

• Escherichia coli
• Staphylococcus saprophyticus
• Proteus mirabilis

Infection with less common organisms is more likely to occur in patients who have underlying pathology and/or frequent infections, are immunosuppressed, or who are catheterised. Organisms which may produce infection under these circumstances include:

• Klebsiella spp.
• Proteus vulgaris
• Candida albicans
• Pseudomonas spp.

Epidemiology

UTIs are common in general practice, accounting for 1-3% of all consultations. The frequency of acute cystitis in young women is of the order of 0.5-0.7 episodes per person per year, and approximately 25% of these will develop recurrent episodes.²

• UTIs occur much less frequently in men at all ages.
• Patients of either sex are more likely to develop a UTI if there is an abnormality of the renal tract or if there has been recent instrumentation of the renal tract.
• Antibiotic use changes the vaginal flora and promotes colonisation of the genital tract with E. coli, resulting in subsequent increased risk of UTI.
• Other risk factors associated with UTI include:¹
  • Recent sexual activity.
  • New sexual partner.
  • Use of spermicide.³
  • Diabetes.
  • Presence of catheter.
  • Institutionalisation.
  • Pregnancy - possible pregnancy should be sought in women of childbearing age.
• Genetic component to risk - increased incidence of UTI in the immediate female relatives of women with recurrent UTI (also supported by the fact that UTIs are 3-4 times more likely to occur in women with certain blood groups.⁴)

Presentation

A UTI can present with a range of symptoms, or may be totally asymptomatic and diagnosed only on routine dip testing. The presenting symptoms will vary with the age and sex of the patient and also with the severity and site of the infection but may include:

• Urinary frequency.
• Painful frequent passing of only small amounts of urine.
• Dysuria.
• Haematuria.
• Foul-smelling ± cloudy urine.
• Urgency.
• Urinary incontinence.
• Suprapubic or loin pain.
• Rigors.
• Pyrexia.
• Nausea ± vomiting.
• Acute confusional state - particularly elderly patients.

Differential diagnosis

The differential diagnosis will depend on the presenting symptoms:

• Many of the symptoms of a UTI can be seen in women with urethral syndrome who have no bacterial infection or in postmenopausal women with atrophic vaginitis and urethritis.
• Other infections of the genital tract such as with Candida albicans, herpes simplex, Chlamydia trachomatis and Gardnerella spp. may also produce similar symptoms in some women.
• In men, an enlarged or inflamed prostate may also present in a similar manner to a UTI.

Investigations

Investigation of a patient with symptoms suggestive of a UTI may include:

• History - e.g. any previous UTI, sexual history, antibiotic use, any history of renal tract abnormality or diabetes, use of immunosuppressant agents such as steroids, family history of UTI.
• Examination of bladder and kidneys.
• Dipstick analysis of urine - may treat as bacterial if positive results for nitrite and/or leukocytes.
• Urine microscopy - leukocytes indicate presence of infection.
• Urine culture - to exclude the diagnosis or if high-risk, e.g. pregnant, immunosuppressed, renal tract anomaly or if failed to respond to earlier empirical treatment. Urine culture should always be performed in men with a history suggestive of UTI regardless of the results of the dipstick test. Urine culture is not required for symptomatic lower UTI in non-pregnant women.
• Asymptomatic bacteriuria in elderly men should not be investigated or treated.⁵
• An ultrasound evaluation of the upper urinary tract should be performed to rule out urinary obstruction or renal stone disease in acute uncomplicated pyelonephritis in premenopausal, non-pregnant women.⁶

Indications for referral

Further investigations are rarely necessary in otherwise healthy females, as underlying renal tract abnormalities are uncommon even in those patients with recurrent infections.

Referral for imaging or cystoscopy should be considered in patients who:

• Have persistently not responded to treatment.
• Have a history of renal tract disease or anomaly.
• Have haematuria.
• In women with more than three confirmed infections in the last year (two confirmed infections in the case of men).
• In addition to the above criteria, referral should be considered for men who have any suggestion of obstruction along the urinary tract, e.g. enlarged prostate.

Management

General measures

Some women may find it helpful to be made aware of the risk factors for recurrent infection. These include:

• Use of spermicide.
• Frequent sexual intercourse.
• New sexual partner.

There is some evidence to suggest that cranberry juice may be helpful in both the treatment and prevention of UTI.^4,7 However, there is also some contrary evidence.⁸

Pharmacological

• Trimethoprim remains the drug of first choice for the empirical treatment of uncomplicated UTI, although 10-20% of E. coli infections will be resistant to it.⁹ Other antibiotics which may be used as first-line agents in patients who are allergic to trimethoprim include nitrofurantoin and cefalexin.¹⁰ Amoxicillin is not used routinely as 50% of organisms will be resistant to it. Current recommendations suggest that the treatment period should be no longer than three days in women with uncomplicated UTI, although should remain at seven days for the treatment of UTIs in men.^1,6
• First-line therapy in mild cases of uncomplicated pyelonephritis is an oral fluoroquinolone for seven days in areas where the rate of fluoroquinolone-resistant E. coli is still low, i.e. <10%.
• The use of topical oestrogen for a short period of time may be of use in postmenopausal women.
• Prophylactic low-dose antibiotics to prevent recurrent UTI are recommended or post-intercourse prophylaxis for women in whom episodes of infection are associated with sexual intercourse.⁶ However, earlier research has shown that 50% of women will have a further infection within three months of stopping prophylaxis.¹¹ Standard regimes are 50 mg nitrofurantoin/day or 100 mg trimethoprim/day.
• Research is currently evaluating the possible role of probiotics and vaccines in the prevention of recurrent infections.
• Paracetamol and/or non-steroidal anti-inflammatory drugs (NSAIDS) are of use for symptomatic relief. However, recent research suggests that diclofenac may also have the capacity to treat UTI caused by E. coli.¹²

A comparison of different management strategies (e.g. delayed script, dipstick testing or sending MSU) showed all gave similar symptom control.¹³

Complications

Ascending infection can occur leading to:

• Pyelonephritis
• Perinephric and intrarenal abscess
• Hydronephrosis or pyonephrosis
• Renal failure
• Septicaemia

Men with UTI may also have infection of the prostate.

Complications of untreated asymptomatic bacteriuria in pregnancy include:¹⁴

• Pyelonephritis (in up to 40% of women).
• Preterm delivery and low-birthweight infants.
• Anaemia.

Pregnancy-induced hypertension may also be associated with this.

Document references

1. Management of suspected bacterial urinary tract infection in adults, Scottish Intercollegiate Guidelines Network - SIGN (2006)
2. Stapleton A; Prevention of recurrent urinary-tract infections in women. Lancet. 1999 Jan 2;353(9146):7-8.
3. Foxman B, Manning SD, Tallman P, et al; Uropathogenic Escherichia coli are more likely than commensal E. coli to be shared between heterosexual sex partners. Am J Epidemiol. 2002 Dec 15;156(12):1133-40. [abstract]
4. Finer G, Landau D; Pathogenesis of urinary tract infections with normal female anatomy. Lancet Infect Dis. 2004 Oct;4(10):631-5. [abstract]
5. McMurdo ME, Gillespie ND; Urinary tract infection in old age: over-diagnosed and over-treated. Age Ageing. 2000 Jul;29(4):297-8.
6. Guidelines on the Management of Urinary and Male Genital Tract Infections, European Association of Urology (2008)
7. Jepson RG, Craig JC; Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD001321. [abstract]
8. Barbosa-Cesnik C, Brown MB, Buxton M, et al; Cranberry juice fails to prevent recurrent urinary tract infection: results from Clin Infect Dis. 2011 Jan;52(1):23-30. [abstract]
9. Guidelines on Urological Infections, European Association of Urology (2011)
10. Management of Infection - Guidance for Primary Care, Health Protection Agency, various dates; (including diagnosis - quick reference guides)
11. Hooton TM; Recurrent urinary tract infection in women. Int J Antimicrob Agents. 2001 Apr;17(4):259-68. [abstract]
12. Mazumdar K, Dutta NK, Dastidar SG, et al; Diclofenac in the management of E. coli urinary tract infections. In Vivo. 2006 Sep-Oct;20(5):613-9. [abstract]
13. Little P, Moore MV, Turner S, et al; Effectiveness of five different approaches in management of urinary tract BMJ. 2010 Feb 5;340:c199. doi: 10.1136/bmj.c199. [abstract]
14. Foxman B; Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Am J Med. 2002 Jul 8;113 Suppl 1A:5S-13S. [abstract]