Urinary Tract Infections

Core

Introduction

The bladder is normally sterile; urine is the by-product of glomerular filtration and tubular handling, edited along the nephron and stored briefly before voiding. Bacteria can colonise the urinary tract by ascending the urethra (the dominant route in adults) or, much less commonly, by haematogenous seeding (the dominant route in neonates and in unusual organisms such as Mycobacterium tuberculosis and Candida). When bacteria do colonise, the result ranges from asymptomatic bacteriuria, through a self-limiting cystitis, to severe pyelonephritis with sepsis.

UTI is one of the most common reasons for antibiotic prescription in the UK, and consequently a major driver of antibiotic resistance. The principles of antibacterial chemotherapy are covered in Antibiotics and Antibiotics (Infection); the relevant anatomy is in Anatomy of the Kidneys, Bladder and Urethra.

Definitions and Classification

Several overlapping terms are used. The pre-clinical core is:

• Bacteriuria: bacteria in the urine. Significant bacteriuria is conventionally ≥ 10⁵ colony-forming units per mL on a midstream sample, although lower counts can be significant in symptomatic patients or with fastidious organisms.
• Asymptomatic bacteriuria: significant bacteriuria with no urinary symptoms. Most cases require no treatment; the exceptions (pregnancy and pre-urological surgery) are the points worth memorising.
• Lower UTI (cystitis): symptomatic infection limited to the bladder and urethra.
• Upper UTI (pyelonephritis): symptomatic infection of the kidney and renal pelvis.
• Urethritis: isolated infection of the urethra. Most cases of urethritis are sexually transmitted (gonococcal, chlamydial) and are dealt with separately as reproductive tract infections.

The clinically more useful axis is uncomplicated vs complicated:

• Uncomplicated UTI: in a non-pregnant woman with a structurally and functionally normal urinary tract. This group has the most predictable microbiology and the shortest treatment courses.
• Complicated UTI: UTI in any patient with structural or functional abnormality (stones, obstruction, vesico-ureteric reflux, neurogenic bladder, indwelling catheter), in pregnancy, in men, in immunocompromise, or in the presence of significant comorbidity such as diabetes or renal impairment.

UTI in any man is, by convention, treated as complicated, because the longer male urethra and the prostate make UTI in men intrinsically harder to clear.

Epidemiology and Risk Factors

UTI is the most common bacterial infection in adult women. About 50% of women will have at least one UTI in their lifetime, and in the UK around 10% of women have a UTI in any given year. Men are largely protected until older age, when prostatic enlargement and urinary stasis become important.

The major risk factors map closely on to the principles of pathogenesis:

• Female anatomy: short urethra (4 cm vs 18-20 cm), proximity of meatus to the vaginal introitus and anus.
• Sexual intercourse: mechanical introduction of perineal flora; the so-called "honeymoon cystitis".
• Diaphragm with spermicide: alters vaginal flora and predisposes to colonisation by uropathogenic E. coli.
• Pregnancy: smooth-muscle relaxation by progesterone and ureteric compression by the gravid uterus produce stasis.
• Postmenopausal status: oestrogen deficiency thins the vaginal and urethral epithelium and reduces protective lactobacilli.
• Diabetes mellitus: glycosuria provides substrate; autonomic neuropathy reduces complete bladder emptying.
• Urinary tract obstruction: stones, prostatic hypertrophy, strictures, tumours; covered in Urinary Tract Obstruction.
• Indwelling urinary catheter: bacterial biofilm forms on the catheter surface; risk of bacteriuria rises by 3-7% per day of catheterisation.
• Vesico-ureteric reflux: the major risk factor for recurrent pyelonephritis and renal scarring in children.
• Immunocompromise, including pharmacological (steroids, chemotherapy) and disease-related (HIV, post-transplant).

Microbiology and Pathogenesis

The dominant pathogen by a wide margin is Escherichia coli, which causes 70-85% of community UTIs and around 50% of hospital UTIs. The remainder of community cases are mostly:

• Staphylococcus saprophyticus: almost exclusively in young sexually active women; the second commonest community cause.
• Klebsiella pneumoniae.
• Proteus mirabilis: produces urease, which splits urea into ammonia, alkalinising the urine and promoting struvite (magnesium ammonium phosphate) stones. The combination of UTI and a staghorn renal calculus suggests Proteus.
• Enterococci, particularly in older patients or after instrumentation.

In the catheterised, hospitalised or recently antibiotic-treated patient, the spectrum widens to include Pseudomonas aeruginosa, Serratia and resistant Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBL).

The dominant route of infection is ascending: organisms from the perineum reach the bladder through the urethra, sometimes propelled by sexual activity or instrumentation. E. coli strains causing UTI are generally uropathogenic E. coli (UPEC), distinguished from commensal strains by virulence factors:

• P-fimbriae (pili): adhere to glycolipid receptors on uroepithelium; particularly associated with pyelonephritis.
• Type 1 fimbriae: bind mannose-rich receptors and mediate attachment to bladder uroepithelium.
• Haemolysins: damage host tissue.
• Aerobactin: iron-acquisition system to compete with host transferrin.

Host defences include the constant flushing action of urine, the protective mucopolysaccharide GAG layer of the bladder, urinary IgA, low urinary pH, high urea concentration, and tight inter-cell junctions of the urothelium. Failure of any of these (incomplete emptying, oestrogen deficiency, instrumentation) tilts the balance towards infection.

Clinical Features

Lower UTI (Cystitis)

The classical syndrome is frequency, urgency and dysuria, often with suprapubic discomfort and cloudy or malodorous urine. Visible blood in the urine (haematuria) is reported in roughly a third of women and is not, in this context, a sinister sign by itself. Symptoms typically come on over hours.

Cystitis is a clinical diagnosis. In an otherwise healthy non-pregnant woman, the combination of dysuria and frequency without vaginal symptoms has a positive predictive value of around 90%, and empirical treatment without further testing is supported by NICE guidance for typical cases.

Upper UTI (Pyelonephritis)

The hallmark of pyelonephritis is systemic illness on top of urinary tract symptoms:

• Fever, rigors, sweats, malaise.
• Loin (flank) pain, often unilateral, worse on movement, with tenderness elicited at the renal angle (between the 12th rib and the lateral border of erector spinae).
• Nausea and vomiting.
• Tachycardia, hypotension if septic.
• Lower urinary tract symptoms (dysuria, frequency) are usually present but can be absent.

Pyelonephritis can progress to urosepsis; any UTI with features of sepsis requires urgent hospital assessment and intravenous antibiotics. Sepsis is covered separately in Sepsis.

Atypical Presentations

Two groups merit special suspicion because UTI presents atypically:

• Older adults: classical urinary symptoms are less commonly reported. UTI may present as new confusion or delirium, falls, anorexia, generalised malaise or non-specific decompensation. The diagnosis is over-made in this group: a positive urine dipstick alone in an asymptomatic catheterised older adult is not a UTI and antibiotics are not indicated. Treat only when there are clinical features of infection.
• Catheterised patients: bacteriuria is almost universal, dipstick is uninterpretable, and most positive cultures represent colonisation rather than infection. Antibiotics are reserved for symptomatic cases (pain, sepsis, signs of upper-tract involvement).

Investigations

Investigation should be matched to the clinical picture:

• Urine dipstick: tests for nitrites (produced by Gram-negative bacteria reducing dietary nitrate; specific but not sensitive; some organisms such as S. saprophyticus, enterococci and pseudomonas do not produce nitrites) and leukocyte esterase (a surrogate for white cells in the urine, sensitive but not specific). The combination of nitrite-positive and leukocyte-esterase-positive has the strongest predictive value. Dipstick is most useful as a rule-in test in symptomatic non-pregnant women aged 16-65, and is less useful in older adults, catheterised patients, pregnancy and children.
• Midstream urine (MSU) for microscopy, culture and sensitivity: the gold standard for confirming infection and guiding antibiotic choice. Indicated in pregnancy, men, children, treatment failures, complicated UTI, suspected pyelonephritis, recurrent UTI and catheterised patients before treatment.
• Blood tests in pyelonephritis or sepsis: full blood count, C-reactive protein, urea, creatinine, electrolytes, blood cultures, lactate.
• Imaging, usually a renal tract ultrasound in patients with pyelonephritis who fail to respond to 48-72 hours of antibiotics, or who have suspected obstruction or stones. CT KUB is the test of choice for stones; contrast CT for suspected renal or perinephric abscess.

Special Groups

Pregnancy

Bacteriuria in pregnancy is significant even when asymptomatic, because:

• It is associated with preterm labour and low birth weight.
• About 20-30% of untreated pregnant women with asymptomatic bacteriuria develop pyelonephritis.

UK guidance is therefore to screen all pregnant women for asymptomatic bacteriuria at booking and treat positive cultures. Antibiotic choice is constrained by teratogenicity:

• Nitrofurantoin: safe in early pregnancy but avoided at term (last few weeks) because of the risk of haemolytic anaemia in the neonate (G6PD-deficient red cells).
• Trimethoprim: avoided in the first trimester because it is a folate antagonist and is associated with neural-tube defects.
• Cefalexin and amoxicillin are reasonable alternatives once sensitivities are known.

Children

UTI in children is a red flag for underlying urinary tract abnormality, particularly vesico-ureteric reflux (VUR). UK NICE guidance recommends investigation with renal tract ultrasound for any child < 6 months with their first UTI, and additional imaging (e.g. DMSA scan for scarring, MCUG for VUR) in atypical or recurrent cases. Untreated reflux can lead to chronic renal scarring, hypertension and chronic kidney disease.

Catheter-Associated UTI

Indwelling catheters develop a bacterial biofilm within days; bacteriuria rises by approximately 3-7% per day of catheterisation and is near-universal by around a month. The clinical decisions are:

• Do not send routine urine cultures from asymptomatic catheterised patients.
• Treat only when there are signs of infection (fever, suprapubic pain, costovertebral angle tenderness, sepsis).
• Where possible, change or remove the catheter as part of treatment, since the biofilm shelters bacteria from antibiotics.

Recurrent UTI

Recurrent UTI is conventionally defined as two or more infections in 6 months or three or more in 12 months. The first task is to distinguish:

• Relapse: same organism within 2 weeks; suggests inadequate treatment or anatomical reservoir (stone, prostatitis).
• Reinfection: new organism, or same organism > 2 weeks after previous infection; suggests host susceptibility rather than treatment failure.

Investigation in recurrent UTI looks for an anatomical or functional abnormality (post-void residual measurement, ultrasound, sometimes cystoscopy in older patients).

Principles of Management

Antibiotic choice should be guided by local resistance patterns and the most recent NICE / Public Health England guidance. The pre-clinical principles are:

Uncomplicated lower UTI in non-pregnant women. First-line UK options (per NICE NG109) are short-course oral nitrofurantoin or, where local susceptibility supports it, trimethoprim. Nitrofurantoin concentrates in urine, not tissues, and is therefore unsuitable for pyelonephritis; current BNF guidance is to avoid it once eGFR falls below 45 mL/min, with cautious short-course use possible at eGFR 30-44 if alternatives are unsuitable. Trimethoprim has good urinary penetration but rising resistance.

If the first-line agent fails or resistance is high, second-line options include pivmecillinam or fosfomycin guided by sensitivities.

UTI in men. Always treated as complicated. A 7-day course of nitrofurantoin or trimethoprim is the usual starting point. Suspected prostatitis requires longer courses with an antibiotic that penetrates the prostate (such as a quinolone or trimethoprim) because most antibiotics do so poorly.

Pyelonephritis. Per NICE NG111, oral treatment is most often cefalexin (with co-amoxiclav or trimethoprim acceptable only when culture sensitivity supports it). Quinolones such as ciprofloxacin are reserved for cases where first-line options are unsuitable, in line with MHRA fluoroquinolone restrictions. Septic or vomiting patients require intravenous therapy; typically a cephalosporin, an aminoglycoside such as gentamicin, or co-amoxiclav, chosen per local protocol. The pharmacology of these agents is covered in Antibiotics.

Pregnancy. As above, with first-line agents chosen for safety: nitrofurantoin (avoid at term), cefalexin, amoxicillin (per culture). Avoid trimethoprim in the first trimester and avoid quinolones throughout.

Catheter-associated UTI. Treat only symptomatic infection; change the catheter; choose antibiotics by culture; broaden empirical cover if previous resistant organisms have been isolated.

Complications

Pre-clinical students should know the main complications of UTI:

• Urosepsis: pyelonephritis is one of the commonest sources of bacteraemic Gram-negative sepsis in UK hospitals.
• Renal abscess and perinephric abscess: suggested by failure to respond to appropriate antibiotics; require imaging and often percutaneous drainage.
• Emphysematous pyelonephritis: rare necrotising infection with gas-forming organisms, typically in patients with diabetes; carries a substantial mortality.
• Renal scarring and chronic kidney disease, particularly in children with vesico-ureteric reflux and recurrent pyelonephritis. See Chronic Kidney Disease.
• Struvite stones: following Proteus or other urease-producing infection; can grow into staghorn calculi.
• Pregnancy complications: preterm labour, low birth weight, neonatal sepsis.

Prevention

Prevention strategies for women with recurrent UTI are evidence-graded; only some are well-supported.

• Behavioural advice: adequate hydration, voiding after intercourse, wiping front-to-back, avoiding spermicide-coated diaphragms. Evidence is modest but the interventions are cheap and risk-free.
• Topical vaginal oestrogen in postmenopausal women: restores the protective lactobacillus flora and significantly reduces recurrence.
• D-mannose: previously suggested as prophylaxis on the basis that it interferes with type 1 fimbrial adhesion to bladder uroepithelium, but a large UK placebo-controlled randomised trial published in 2024 (the MERIT trial, JAMA Internal Medicine) found no reduction in recurrent UTI. It is no longer recommended as routine prophylaxis.
• Cranberry preparations: long-touted, but the most rigorous trials show inconsistent benefit; current NICE guidance is that the evidence is uncertain and there is no convincing benefit in older women.
• Methenamine hippurate: a urinary antiseptic that releases formaldehyde in acidic urine. Recent UK trials (the ALTAR trial) have shown non-inferiority to long-term low-dose antibiotic prophylaxis in women with recurrent UTI, with the major advantage of avoiding antibiotic resistance.
• Long-term low-dose antibiotic prophylaxis: trimethoprim or nitrofurantoin nightly for 3-6 months remains an option but is increasingly being replaced by methenamine because of resistance concerns.

Summary

• UTI is the symptomatic infection of the urinary tract; asymptomatic bacteriuria is generally not treated, except in pregnancy and before urological surgery.
• The most useful classification is uncomplicated (non-pregnant women, normal tract) versus complicated (everyone else, including all men).
• E. coli is the dominant pathogen, ascending from the perineum. Staph saprophyticus, Klebsiella, Proteus (urease, struvite stones) and Enterococcus account for most of the rest in community settings.
• Cystitis presents with frequency, urgency and dysuria; pyelonephritis adds fever, loin pain and systemic illness. Older adults and catheterised patients present atypically.
• First-line treatment of uncomplicated cystitis in non-pregnant women is short-course nitrofurantoin or trimethoprim. Pyelonephritis requires longer broader-spectrum therapy (oral or IV per NICE NG111) and consideration of imaging if not improving.
• Pregnancy, children, men and catheterised patients all need a different treatment approach. Vesico-ureteric reflux is the major reason to investigate paediatric UTI thoroughly.

Reviewed by: Dr. Marcus Judge

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