Urinary Tract Infections

1. Introduction
2. Definitions and Classification
3. Epidemiology and Risk Factors
4. Microbiology and Pathogenesis
5. Clinical Features
   • Lower UTI (Cystitis)
   • Upper UTI (Pyelonephritis)
   • Atypical Presentations
6. Investigations
7. Special Groups
   • Pregnancy
   • Children
   • Catheter-Associated UTI
   • Recurrent UTI
8. Principles of Management
9. Complications
10. Prevention
11. Summary
12. Quiz

• Urinary tract infection (UTI) is the presence of bacteria multiplying in the urine with associated symptoms or signs of infection. It is one of the most common conditions seen in primary care.
• UTIs are classified in two ways. The anatomical axis separates lower UTI, or cystitis (infection of the bladder and urethra), from upper UTI, or pyelonephritis (infection of the kidney). The clinical axis separates uncomplicated from complicated UTI. The uncomplicated vs complicated distinction matters more for treatment than the lower vs upper one.
• Escherichia coli (a bowel bacterium) is identified in up to 77% of UTIs seen in primary care. It ascends through the urethra from the perineal flora (the bacteria living on the skin between the anus and the genitals). The shorter female urethra explains the marked female predominance, as does the closeness of its opening (the meatus) to the vaginal entrance (the introitus) and the anus.
• Uncomplicated cystitis is treated with a 3-day course of oral antibiotics. Nitrofurantoin is a first choice if kidney function is adequate (eGFR, the estimated glomerular filtration rate, is 45 mL/min or more). Trimethoprim is the other first choice, if there is a low risk of resistance. Pyelonephritis (kidney infection) needs a longer course, most often 7 to 10 days of oral cefalexin. Intravenous antibiotics are reserved for severe or septic cases, per local guidance. The choices include a cephalosporin (a class of antibiotic related to penicillin) or gentamicin, and co-amoxiclav only in combination with another antibiotic or when the culture result shows it will work. Pregnancy, children and catheter-associated infections need special consideration.

Introduction

The bladder is normally sterile. Urine is the by-product of glomerular filtration (the kidney filtering the blood) and tubular handling (reabsorption and secretion along the nephron). It is stored briefly before voiding (passing urine). Bacteria can colonise the urinary tract (live in it, without necessarily causing symptoms) by ascending the urethra. This is the dominant route in adults. Much less commonly, bacteria arrive by haematogenous seeding (spread through the blood). Blood-borne spread is the dominant route in newborn babies (neonates) and for unusual organisms such as Mycobacterium tuberculosis and Candida (a yeast). When bacteria do colonise, the result ranges from asymptomatic bacteriuria (bacteria in the urine without symptoms) to a self-limiting cystitis (one that clears by itself). At the severe end is pyelonephritis (kidney infection) 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 antibiotic treatment (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 (viable bacteria that grow into colonies on a culture plate) on a midstream sample (urine caught mid-flow). Lower counts can be significant in symptomatic patients or with fastidious organisms (organisms that are hard to grow in culture).
• 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 or chlamydial, meaning caused by gonorrhoea or chlamydia) 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 of these situations:
  • a structural or functional abnormality of the urinary tract, such as stones, obstruction, vesico-ureteric reflux (urine flowing backwards from the bladder up the ureter), a neurogenic bladder (a bladder with abnormal nerve control) or an indwelling catheter (one left in place in the bladder);
  • pregnancy;
  • infection in men;
  • a weakened immune system (immunocompromise);
  • any other significant long-term illness (comorbidity), such as diabetes or renal impairment (reduced kidney function).

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 common in women. NICE Clinical Knowledge Summaries (CKS, guidance summaries for primary care) say that acute UTI occurs in up to 50% of women. In an England survey, 37% of women reported at least one UTI in their lifetime, and 11% reported a UTI in the past year. Estimates vary with how UTI is defined. Men are largely protected until older age, when prostatic enlargement and urinary stasis (urine stagnating in the bladder) become important.

The major risk factors map closely on to how infection arises (its pathogenesis):

• Female anatomy: short urethra (about 4 cm in women against 18-20 cm in men), proximity of the urethral opening (meatus) to the vaginal entrance (introitus) and anus.
• Sexual intercourse: mechanical introduction of perineal flora (bacteria from the skin around the anus and genitals); the so-called "honeymoon cystitis".
• Contraceptive diaphragm (a vaginal cap) with spermicide (a sperm-killing contraceptive gel): alters the vaginal flora (the normal bacteria of the vagina) and makes colonisation by uropathogenic E. coli more likely. E. coli is a bowel bacterium, and uropathogenic strains are those able to infect the urinary tract.
• Pregnancy: smooth-muscle relaxation by progesterone and ureteric compression by the pregnant (gravid) uterus produce stasis.
• Postmenopausal status: oestrogen deficiency thins the vaginal and urethral epithelium and reduces protective lactobacilli (the harmless bacteria that normally dominate the vagina).
• Diabetes mellitus: glucose in the urine (glycosuria) provides substrate (food for bacteria); damage to the autonomic nerves (autonomic neuropathy) reduces complete bladder emptying.
• Urinary tract obstruction: stones, prostatic hypertrophy (enlargement of the prostate), narrowings (strictures), tumours; covered in Urinary Tract Obstruction.
• Indwelling urinary catheter: a biofilm (a sticky layer of bacteria) forms on the catheter surface; the incidence of bacteriuria is 3-8% per day of catheterisation (an extra 3 to 8 in every 100 catheterised people each day).
• Vesico-ureteric reflux (urine flowing backwards from the bladder up the ureter): the major risk factor for recurrent pyelonephritis and renal scarring in children.
• Immunocompromise (a weakened immune system) impairs defence against bacteria. It may be caused by drugs (steroids, chemotherapy) or by disease (HIV, or after a transplant).

Microbiology and Pathogenesis

The dominant pathogen by a wide margin is Escherichia coli, which is identified in up to 77% of UTIs seen in primary care (in a 2023 survey of hospital inpatients in England, it made up about 47% of the organisms identified in healthcare-associated UTIs). The remainder of community cases are mostly:

• Staphylococcus saprophyticus: a recognised cause in young sexually active women, in whom it is the second commonest cause of UTI after E. coli.
• Klebsiella pneumoniae.
• Proteus mirabilis: produces urease (an enzyme), which splits urea into ammonia, making the urine more alkaline (alkalinising it) and promoting struvite (magnesium ammonium phosphate) stones. The combination of UTI and a staghorn renal calculus (a large, branching kidney stone) suggests Proteus.
• Enterococci, particularly in older patients or after instrumentation (procedures that put devices into the urinary tract).

In the catheterised, hospitalised or recently antibiotic-treated patient, the spectrum widens to include Pseudomonas aeruginosa and Serratia. Resistant Enterobacteriaceae (a family of bowel bacteria that includes E. coli) also appear. These produce extended-spectrum beta-lactamases (ESBL), which are enzymes that destroy many penicillin-type antibiotics.

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 (harmless residents of the bowel) by virulence factors (features that help bacteria cause disease):

• P-fimbriae (pili): hair-like surface projections that adhere to glycolipid receptors (receptors made of a fat molecule with a sugar attached) on uroepithelium (the epithelium lining the urinary tract); particularly associated with pyelonephritis.
• Type 1 fimbriae: bind mannose-rich receptors (receptors rich in mannose, a sugar) and mediate attachment to bladder uroepithelium.
• Haemolysins: damage host tissue.
• Aerobactin: iron-acquisition system to compete with host transferrin (the blood protein that carries iron).

Host defences include the constant flushing action of urine and the protective mucopolysaccharide layer of the bladder (the glycosaminoglycan or GAG layer, a mucus coat over the bladder lining). They also include urinary IgA (immunoglobulin A, an antibody), low urinary pH, high urea concentration, and tight junctions between the cells of the uroepithelium. 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: needing to pass urine often (frequency) and suddenly (urgency), with painful urination (dysuria). There is often suprapubic discomfort (pain above the pubic bone) and cloudy or foul-smelling (malodorous) urine. Visible blood in the urine (haematuria) is reported in roughly a third of women. It can occur with a simple UTI. NICE CKS advises an urgent 2-week-wait urology referral for a woman aged 45 or over whose visible haematuria persists or recurs after successful treatment of the UTI. Symptoms typically come on over hours.

Cystitis is a clinical diagnosis. In an otherwise healthy non-pregnant woman, dysuria and frequency without vaginal symptoms raise the probability of UTI to more than 90%. That figure is a positive predictive value (the chance that the diagnosis is right when these symptoms are present). NICE CKS lists three key symptoms: dysuria, new nocturia (waking at night to pass urine) and cloudy urine. A woman under 65 with two or three of them and no risk factors for complicated UTI does not need a urine dipstick test (a strip dipped in the urine that changes colour to show nitrite, white cells and blood), because UTI is likely. Empirical treatment (treatment started on the likely cause before test results) can then be considered. With only one key symptom, CKS advises a urine dipstick test.

Upper UTI (Pyelonephritis)

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

• Fever, rigors (shaking chills), sweats, malaise (feeling generally unwell).
• Loin (flank) pain, often unilateral, worse on movement, with tenderness elicited at the renal angle, also called the costovertebral angle (between the 12th rib and the lateral border of erector spinae, the muscle beside the spine).
• Nausea and vomiting.
• Tachycardia (fast heart rate), hypotension (low blood pressure) if septic.
• Lower urinary tract symptoms (dysuria, frequency) are usually present but can be absent.

Pyelonephritis can progress to urosepsis (sepsis arising from the urinary tract); 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 (loss of appetite), generalised malaise or non-specific decompensation (a general decline in how well the person is coping). UTI is over-diagnosed 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 with a long-term catheter. A dipstick is not used to diagnose infection in these patients. Most positive cultures represent colonisation (bacteria present without causing disease) 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 and for leukocyte esterase. Nitrites are produced when Gram-negative bacteria (a bacterial group defined by Gram staining) reduce dietary nitrate. The nitrite test is specific but not sensitive: a positive result is likely to be real, but a negative result does not rule infection out. Some organisms, such as S. saprophyticus, enterococci and Pseudomonas, do not produce nitrites. Leukocyte esterase is a surrogate for white cells in the urine. That test is sensitive but not specific: a negative result helps rule infection out, but a positive result can have other causes. The UK Health Security Agency (UKHSA) cites an English primary care study of 434 women with at least 2 urinary symptoms and no vaginal discharge. In that study, the positive predictive value (the chance that a positive result is a true UTI) was 92% for a positive nitrite together with either blood or leukocyte esterase. NICE CKS advises a dipstick for a woman under 65 with one key symptom of UTI or other urinary symptoms. A dipstick that is positive for nitrite, or for both leukocyte esterase and red blood cells, makes UTI likely. A dipstick that is negative for nitrite, leukocyte esterase and red blood cells makes UTI less likely. CKS advises against using a dipstick to make the diagnosis in women over 65, in pregnancy, or when a catheter is in place. A urine sample is sent for culture instead. In babies and children aged 3 months to 3 years, NICE advises dipstick testing.
• Midstream urine (MSU) for microscopy, culture and sensitivity (looking at the urine under a microscope, growing the bacteria, and testing which antibiotics kill them): the most reliable test (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 who have symptoms. In a catheterised patient the sample is taken from the catheter (through the sampling port if there is one, using an aseptic technique, which keeps outside germs out of the sample), before antibiotics are given. If the catheter has been changed, the sample is taken from the new catheter. If it has been removed, a midstream sample is sent instead.
• Blood tests in pyelonephritis or sepsis: full blood count (to look for a raised white cell count), C-reactive protein (a blood marker of inflammation), urea, creatinine and electrolytes (to check kidney function), blood cultures (to find the organism if bacteria are in the blood) and lactate (a marker of poor blood flow to the tissues, as in septic shock).
• Imaging in patients with pyelonephritis whose symptoms persist despite 48 to 72 hours of appropriate antibiotics. A renal tract ultrasound is the usual first scan, with CT or MRI if obstruction is suspected or symptoms persist. NICE advises reassessing if symptoms worsen at any time, or have not started to improve within 48 hours of starting the antibiotic. Suspected obstruction by a stone is different and must not wait. With signs of infection or sepsis it is an emergency: the person needs immediate hospital admission and urgent drainage of the kidney (decompression). CT KUB (a low-dose CT of the kidneys, ureters and bladder) is the test of choice for stones. NICE advises it within 24 hours for suspected renal colic (severe pain caused by a stone in the urinary tract), with ultrasound instead in pregnancy. Contrast CT (a CT scan done after an injection of dye, which shows up on the scan) is used for suspected renal or perinephric (around the kidney) abscess.

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