Urinary Tract Infection in Adults Causes, Symptoms and Treatment

Definitions^[1]

• Bacteriuria - this refers to the presence of bacteria in the urine. This may be symptomatic or asymptomatic. Asymptomatic bacteriuria is the presence of significant levels of bacteria in the urine in a person without signs or symptoms of UTI.
• Lower UTI - this is generally considered to be infection of the bladder (cystitis).
• Upper UTI - this includes pyelitis and pyelonephritis.
• Recurrent UTI - this is usually defined as two or more episodes of UTI in six months or three or more episodes in one year.
• 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 - eg, abnormal urinary tract.

Urinary tract infection pathogenesis

Several micro-organisms are known to cause UTI but the majority of urinary tract infections will be produced by Escherichia coli. Other causative organisms are:

• Staphylococcus saprophyticus
• Proteus mirabilis
• Enterococci
  

Urine infections with less common organisms are 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.

Urinary tract infection epidemiology^{[1, 2]}

• Around one in three women have had a UTI by the age of 24 and around half of all women report at least one UTI sometime during their lifetime.
• 20-30% of women who have had a UTI will have a recurrence.
• The incidence of UTI in women increases with age. One study reported that it was found to increase from 9.03 to 10.96 in women aged 65-74 years, 11.35 to 14.34 in those aged 75-84 years, and 14.65 to 19.80 in those aged over 85 years.
• Asymptomatic bacteriuria is estimated to occur in:

• 2-10% of pregnant women.
• 1-5% of healthy pre-menopausal women.
• 4-19% of healthy elderly women - this may increase up to 50% in women in long-term care facilities.
• 0.7-27% of people with diabetes.
• 23-89% of patients with spinal cord injuries.

UTIs occur much less frequently in men at all ages. This is thought to be due to the shorter urethra in women.

Risk factors in men include:

• Increasing age (it is rare before the age of 50).
• Coexisting illness.
• Institutional care
• An indwelling urinary catheter.

Prevalence of bacteriuria increases over the age of 65 and does not equate to a diagnosis of a UTI. Alone it is not usually an indication for treatment. In the population aged over 65, bacteriuria may be so high that urine culture ceases to be a diagnostic test.

Risk factors

Apart from age and gender, risk factors associated with UTI include:

• Recent instrumentation of the renal tract.
• Abnormality of the renal tract
• Incomplete bladder emptying - particularly by prostatic obstruction in men.
• Antibiotic use changes the vaginal flora and promotes colonisation of the genital tract with E. coli, resulting in subsequent increased risk of UTI.
• Sexual activity.
• New sexual partner.
• Use of spermicide.
• Diabetes.
• Presence of catheter.
• Institutionalisation.
• Pregnancy.
• Immunocompromise.
• Genetic component to risk - increased incidence of UTI in the immediate female relatives of women with recurrent UTI, and associated genes have been identified^[3].

Urinary tract infection presentation

A urinary tract infection in adults 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 C. albicans, herpes simplex, Chlamydia trachomatis and Gardnerella spp. may also produce similar symptoms in some women.
• In men, an enlarged or inflamed prostate gland may also present in a similar manner to a UTI.

Investigations

Investigation of a patient with symptoms suggestive of a urinary tract in adults may include:

• History - eg, 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 the bladder and kidneys.
• Dipstick analysis of urine - may treat as bacterial if there are positive results for nitrite and/or leukocytes. It is advised that dipstick testing is not used to diagnose UTIs in adults with indwelling urinary catheters^[4].
• Urine microscopy - leukocytes indicate presence of infection.
• Urine culture - to exclude the diagnosis, or if high-risk (eg, 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.
• An ultrasound evaluation of the upper urinary tract should be considered to rule out urinary obstruction or renal stone disease in acute uncomplicated pyelonephritis. Further imaging may be required in those who remain febrile following 72 hours of treatment^[5].

Indications for referral^{[1, 2]}

Further investigations are rarely necessary in otherwise healthy females with lower tract infections, as underlying renal tract abnormalities are uncommon even in those patients with recurrent infections. However, women should be referred urgently if they show signs of serious or systemic illness such as sepsis.

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.
• Are women with recurrent infections who are not responding to preventative measures, or men with two or more episodes in three months

In addition to the above criteria, referral should be considered for men who have any suggestion of obstruction along the urinary tract - eg, enlarged prostate gland, or who have had signs of upper UTI.

Guidelines from the National Institute for Health and Care Excellence (NICE) for suspecting cancer in 2015 advise^[6]:

• Consider a prostate specific antigen (PSA) test and digital rectal examination (DRE) to assess for prostate cancer in men with lower urinary tract symptoms (such as nocturia, urinary frequency, hesitancy, urgency or retention) or visible haematuria.
• Refer under the two-week wait rule if a person aged 45 or over has:
• Unexplained visible haematuria without UTI; or
• Visible haematuria which persists or recurs after successful treatment of UTI.
• Refer under the two-week wait rule if a person aged 60 or over has unexplained non‑visible haematuria and either dysuria or a raised white cell count on a blood test.
• Consider non-urgent referral to exclude bladder cancer in those aged 60 or over with recurrent or persistent unexplained UTI.

Urinary tract infection treatment and management^{[1, 2]}

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

Cranberry juice has been traditionally advised as being helpful in the prevention and treatment of UTI but the evidence base is low and it is not recommended by current guidelines.

Also traditionally, a number of measures have been advised, such as increasing fluid intake and personal hygiene behaviours (for example, avoiding delay in urination, wiping from front to back after defection, avoiding douching), but there is no evidence to support these^[5].

Pharmacological

• A delayed script may be appropriate in non-pregnant women with mild symptoms and no risk factors for complicated infection.
• Trimethoprim or nitrofurantoin remains the drug of first choice for the empirical treatment of uncomplicated UTI. 10-20% of E. coli infections may be resistant. 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. Offer nitrofurantoin 100 mg modified-release twice a day for three days (if eGFR ≥45 ml/minute) or trimethoprim 200 mg twice a day for three days (if low risk of resistance).
• If a second choice is required (eg, if there is no improvement in symptoms when first-choice antibiotic is taken for at least 48 hours or if first choice is unsuitable) consider prescribing:
  • Nitrofurantoin 100 mg modified-release twice a day for three days (if eGFR ≥45 ml/minute and not used as first choice); or
  • Pivmecillinam (a penicillin) 400 mg initial dose, then 200 mg three times a day for a total of three days; or
  • Fosfomycin 3 g single-dose sachet.
• For pregnant women without haematuria prescribe:
• Nitrofurantoin (avoid at term) 100 mg modified-release twice a day for seven days if eGFR ≥45 ml/minute.
• As second choice (no improvement in lower UTI symptoms on first choice taken for at least 48 hours or when first choice not suitable), consider prescribing:
  • Amoxicillin (only if culture results available and susceptible) 500 mg three times a day for seven days.
  • Cefalexin 500 mg twice a day for seven days.
  • For alternative second choices, discuss with local microbiologist.
• For non-pregnant women with a catheter consider:
• First-choice oral antibiotic (for lower UTI symptoms only):
• Nitrofurantoin (if eGFR ≥45 ml/minute) 100 mg modified-release twice a day for seven days.
• Trimethoprim (if low risk of resistance) 200 mg twice a day for seven days.
• Amoxicillin (only if culture results available and susceptible) 500 mg three times a day for seven days.
• Second choice (for lower UTI symptoms only, when first choice unsuitable):
• Pivmecillinam (a penicillin) 400 mg initial dose, then 200 mg three times a day for a total of seven days.
• Be aware that nitrofurantoin and pivmecillinam are only licensed for uncomplicated lower UTIs, and are not suitable for people with upper UTI symptoms or a blocked catheter.
• When prescribing for acute pyelonephritis for women who are not pregnant, men, and people with indwelling catheters, take account of local antimicrobial resistance data, and prescribe either of the following first-line options^[7]:
  • Cefalexin 500 mg twice or three times a day (up to 1-1.5 g three or four times a day for severe infections) for 7-10 days.
  • Co-amoxiclav (only if appropriate in line with culture and sensitivity results) 500/125 mg three times a day for 7-10 days.
  • Trimethoprim (only if appropriate in line with culture and sensitivity results) 200 mg twice a day for 14 days.
  • Ciprofloxacin 500 mg twice a day for seven days.
• For pregnant women who do not require admission, prescribe cefalexin 500 mg twice or three times a day (up to 1-1.5 g three or four times a day for severe infections) for 7-10 days
• Studies suggest the use of topical oestrogen in postmenopausal women reduces recurrence of UTI^[8].
• Prophylactic low-dose antibiotics may be helpful if underlying cause has been investigated and behavioural/personal hygiene measures and vaginal oestrogen (in postmenopausal women) are ineffective or inappropriate. Consider the severity and frequency of symptoms, risk of complications, previous urine culture and susceptibility results, previous antibiotic use and the woman's preference:
• Discuss the risks of long-term antibiotics including resistance and possible adverse effects.
• Ensure that any current UTI has been adequately treated and consider single-dose antibiotic prophylaxis for use when exposed to an identifiable trigger:
• First choice - trimethoprim 200 mg single dose when exposed to a trigger or nitrofurantoin (if eGFR ≥45 ml/ minute) 100 mg single dose when exposed to a trigger.
• Second choice - amoxicillin 500 mg single dose when exposed to a trigger (off label indication) or cefalexin 500 mg single dose when exposed to a trigger.
• If there is no improvement after single-dose antibiotic prophylaxis or no identifiable triggers, ensure that any current UTI has been adequately treated and then consider a trial of daily antibiotic prophylaxis:
• First choice - trimethoprim 100 mg at night or nitrofurantoin (if eGFR ≥45 ml/minute) 50-100 mg at night.
• Second choice - amoxicillin 250 mg at night (off-label indication) or cefalexin 125 mg at night.
• Paracetamol and/or non-steroidal anti-inflammatory drugs (NSAIDS) are of use for symptomatic relief.

Asymptomatic bacteriuria should not be treated in adults with catheters or in non‑pregnant women. Antibiotic prophylaxis is not required to prevent UTI in adults with long‑term indwelling catheters unless there is a history of recurrent or severe UTI^[4].

Urinary tract infection complications

Ascending urinary tract infection in adults can occur leading to:

• Pyelonephritis.
• Perinephric and intrarenal abscess.
• Hydronephrosis or pyonephrosis.
• Acute kidney injury.
• Sepsis.

Men with UTI may also have infection of the prostate gland. Prostatic involvement in the infection can result in prostatic abscesses or prostatitis.

Complications of untreated asymptomatic bacteriuria in pregnancy include^[9]:

• Pyelonephritis (in up to 40% of women).
• Preterm delivery and infants with low birth weight.
• Anaemia.

See also the separate Recurrent Urinary Tract Infection, Urinary Tract Infection in Children, Lower Urinary Tract Symptoms in Men and Lower Urinary Tract Symptoms in Women articles for further information.