Urinary Tract Infection

Introduction

Urinary tract infection is one of the commonest bacterial infections in clinical practice and one of the commonest reasons for an antibiotic prescription in the UK. It describes the presence of a pathogenic organism within the normally sterile urinary tract, together with an inflammatory response.¹

The great majority are ascending infections, in which bowel flora colonise the perineum, ascend the urethra and establish infection in the bladder. Haematogenous seeding of the kidney is uncommon and generally occurs in the context of bacteraemia. Around 50% of women will have at least one UTI in their lifetime, whereas UTI in men is much less common and carries different implications.

Aetiology

Uropathogens are overwhelmingly enteric Gram-negative bacilli derived from the patient's own bowel flora. The mnemonic KEEPS covers those worth knowing, and each of the less common organisms carries a clinical clue.

Host defences

The urinary tract resists infection through the flushing action of regular voiding, the low pH and high urea concentration of urine, the vesicoureteric valve preventing reflux, and urothelial antibacterial secretions including Tamm-Horsfall protein. Almost every risk factor for UTI can be understood as a breach of one of these defences.

Risk factors

• Female sex - a short urethra in close proximity to the anus; the single largest risk factor
• Sexual activity - mechanically introduces perineal flora into the urethra; spermicide and diaphragm use additionally disrupt normal vaginal flora
• Urinary catheterisation - the commonest cause of hospital-acquired UTI; risk rises with every day the catheter remains in place
• Urinary stasis or incomplete bladder emptying - benign prostatic hyperplasia, neurogenic bladder, prolapse, constipation
• Obstruction - stones, strictures, tumours
• Pregnancy - progesterone-mediated smooth muscle relaxation and mechanical compression cause urinary stasis
• Postmenopausal oestrogen deficiency - vaginal atrophy and loss of protective lactobacilli
• Diabetes mellitus - glycosuria, impaired immunity and autonomic bladder dysfunction
• Immunosuppression
• Previous UTI and a family history of recurrent UTI
• Vesicoureteric reflux and other congenital abnormalities - particularly relevant in children
• Renal transplant and other instrumentation of the tract

Clinical features

Lower urinary tract infection (cystitis)

• Dysuria - burning or stinging on passing urine
• Urinary frequency and urgency
• Suprapubic pain or discomfort
• Cloudy, offensive-smelling urine
• Visible (macroscopic) haematuria in a proportion
• Systemically well - the absence of fever, rigors and loin pain is what distinguishes this from pyelonephritis

Features suggesting upper urinary tract infection

Fever, rigors, loin or flank pain, nausea and vomiting, and renal angle tenderness indicate pyelonephritis, which is a systemic illness requiring a longer antibiotic course and, in many patients, admission.

Differential diagnosis

Investigations

In a non-pregnant woman under 65 with classic symptoms of dysuria, frequency and suprapubic pain, UTI can be diagnosed clinically and treated empirically without any test.¹ Investigation is directed at those in whom the diagnosis is uncertain or the infection is complicated.

Urine dipstick

• Nitrites - the more specific marker. Gram-negative organisms reduce dietary nitrate to nitrite, so a positive nitrite strongly supports infection. Note that it may be negative with Gram-positive organisms (which lack the enzyme) or where urine has not been in the bladder long enough to convert
• Leucocyte esterase - indicates pyuria; sensitive but less specific, as it is raised in any inflammation of the tract
• Blood - often positive but non-specific
• Protein - non-specific
• Interpretation: nitrite positive (with or without leucocytes) means treat. Nitrite negative with leucocytes positive is equivocal - send a culture and use clinical judgement. Both negative makes UTI unlikely and should prompt a search for another cause
• Do not use the dipstick to diagnose UTI in patients over 65 or with a urinary catheter - asymptomatic bacteriuria is so common that a positive result carries little meaning, and relying on it leads to missed alternative diagnoses

Urine culture (MSU for microscopy, culture and sensitivity)

A midstream specimen of urine should be sent before starting antibiotics in the following groups:

• All pregnant women, all men, and all children
• Patients over 65 and those with a catheter (where the catheter should ideally be changed and the sample taken from the new one)
• Suspected pyelonephritis or systemic illness
• Recurrent UTI, treatment failure or persistent symptoms after 48 hours, and recent antibiotic use or hospitalisation (resistance risk)
• Visible haematuria or atypical features

Classical significant bacteriuria is more than 10⁵ colony-forming units per mL of a single organism, though lower counts can be significant in a symptomatic patient. Mixed growth usually indicates contamination and should prompt a repeat sample rather than treatment.

Further investigation

• Bloods (FBC, CRP, U&Es, cultures) - if systemically unwell or pyelonephritis is suspected
• Sexual health screen (NAAT for chlamydia and gonorrhoea) - in sexually active patients with dysuria and sterile pyuria
• Bladder scan - to assess post-void residual volume where incomplete emptying or retention is suspected
• Renal tract ultrasound - for recurrent UTI, suspected obstruction, all men with upper UTI, poor response to treatment, and in children per NICE guidance
• CT urogram or cystoscopy - where structural pathology or malignancy is suspected, particularly with persistent haematuria
• Consider tuberculosis in persistent sterile pyuria with negative routine cultures - request early morning urine samples for acid-fast bacilli

Management

Management follows NICE NG109, and the two things examiners look for are the correct drug and the correct duration for that patient group.¹

Supportive measures and safety-netting

• Adequate fluid intake and paracetamol or ibuprofen for pain
• Advise return if symptoms worsen at any time, or fail to improve within 48 hours of starting treatment
• Back-up (delayed) prescription is an option in mild symptoms, with advice to use it if things do not settle within 48 hours
• Send a culture and switch antibiotic according to sensitivities if there is no response

Asymptomatic bacteriuria

Bacteriuria without symptoms should not be treated in non-pregnant adults, older people or catheterised patients - treatment does not improve outcomes and drives resistance and C. difficile infection. The exception is pregnancy, where asymptomatic bacteriuria carries a significant risk of progression to pyelonephritis and is associated with preterm labour and low birth weight; it is screened for routinely at booking and treated with a 7-day course, with a follow-up culture to confirm clearance.

Recurrent UTI

Defined as two or more infections in 6 months, or three or more in 12 months. Management is stepwise:

1. Confirm the diagnosis with cultures - many patients labelled with recurrent UTI have persistently sterile urine and another cause
2. Investigate for an underlying cause - post-void residual volume, renal tract ultrasound, and consideration of stones, obstruction or malignancy
3. Behavioural and self-care measures - adequate fluid intake, not delaying voiding, voiding after intercourse, avoiding spermicide and diaphragms
4. Topical vaginal oestrogen in postmenopausal women - restores lactobacilli and is genuinely effective
5. D-mannose or cranberry products - modest and inconsistent evidence, but low risk and may be discussed
6. Methenamine hippurate - a urinary antiseptic, now supported by trial evidence as an alternative to antibiotic prophylaxis
7. Antibiotic prophylaxis - either single-dose post-coital where infections are clearly related to intercourse, or low-dose nightly prophylaxis, reviewed regularly because of resistance

Complications

• Ascending infection causing pyelonephritis - the commonest significant complication
• Urosepsis and septic shock - the urinary tract is one of the commonest sources of sepsis, particularly in older and catheterised patients
• Renal or perinephric abscess - suspect where fever persists beyond 72 hours of appropriate antibiotics
• Emphysematous pyelonephritis - a rare, gas-forming, necrotising infection occurring almost exclusively in poorly controlled diabetes; a surgical emergency
• Obstructed and infected system (pyonephrosis) - infection above an obstructing stone; requires urgent decompression, not just antibiotics
• Acute kidney injury
• Chronic pyelonephritis and renal scarring - particularly with recurrent childhood infection and vesicoureteric reflux, potentially causing hypertension and CKD in later life
• In pregnancy: preterm labour, low birth weight and pyelonephritis
• Struvite staghorn calculi - from recurrent infection with urease-producing organisms such as Proteus
• Antibiotic-related harm - Clostridioides difficile infection and antimicrobial resistance from repeated courses

Red flags

Prognosis

Uncomplicated lower UTI has an excellent prognosis. Symptoms typically resolve within 2 to 3 days of starting appropriate antibiotics, and a significant proportion of mild cases resolve without antibiotics at all - which is the rationale behind back-up prescribing. Complications are rare in an otherwise healthy non-pregnant woman.

Recurrence is common rather than a sign of failure: around 20-30% of women who have one UTI will have another within 6 months, and this reflects host and behavioural factors more often than treatment inadequacy. Most respond well to the stepwise preventive measures above, and topical oestrogen in postmenopausal women is one of the more effective interventions.

Outcomes are less benign in complicated infection. Pyelonephritis, urosepsis and infection in the presence of obstruction, diabetes, pregnancy or immunosuppression carry meaningful morbidity and mortality, and the prognosis then depends largely on how quickly source control is achieved. In children, the long-term concern is renal scarring from recurrent upper tract infection, which is why prompt diagnosis, treatment and appropriate imaging matter well beyond the acute episode.