Urinary Tract Infections

Urinary tract infection (UTI) is microbial invasion of the urinary tract, from urethra to kidney. It is the commonest bacterial infection in women, and the commonest cause of healthcare-associated infection.

Classification:

• By site: lower tract (urethritis, cystitis, prostatitis) and upper tract (pyelonephritis, renal and perinephric abscess).
• Uncomplicated: acute cystitis or pyelonephritis in healthy, non-pregnant premenopausal women without structural or functional abnormality.
• Complicated: infection in men, pregnant women, children, older adults with comorbidity, or in the presence of obstruction, stones, catheters, neurogenic bladder, diabetes, immunosuppression, renal impairment, recent instrumentation, healthcare association or multidrug-resistant pathogens.
• Recurrent: at least 2 episodes in 6 months or 3 in 12 months (relapse with the same organism within 2 weeks vs reinfection).
• Asymptomatic bacteriuria: isolation of 10^5 CFU/mL or more from two consecutive midstream samples (one in men) in the absence of symptoms.
• Catheter-associated: bacteriuria with symptoms in a catheterised patient (10^3 CFU/mL or more).

Epidemiology:

• About 50 to 60% of women have at least one UTI, 25 to 30% have recurrence within 6 months. In men, incidence is low until age 50, then rises with prostatic disease. Infants: boys under 1 year more commonly (uncircumcised, anomalies).
• Healthcare-associated: catheter-associated UTI accounts for about 40% of nosocomial infections, 1 to 5% daily acquisition of bacteriuria per catheter day.

Pathogens:

• E. coli (75 to 90% of community UTIs), Klebsiella, Proteus mirabilis, Enterococcus faecalis, Staphylococcus saprophyticus (young sexually active women), Pseudomonas, Enterobacter, Citrobacter, Candida (catheters, diabetics, antibiotics), group B streptococci (pregnancy), and Acinetobacter.
• Resistance: ESBL-producing Enterobacterales, fluoroquinolone and trimethoprim-sulfamethoxazole resistance, and carbapenem-resistant organisms.

Pathogenesis: periurethral colonisation by faecal flora, ascent through the urethra, adherence (type 1 fimbriae, P fimbriae), biofilm formation, and host factors (short female urethra, mucosal defences, antimicrobial peptides, blood group secretor status).

Risk factors: female sex, sexual intercourse, spermicides, new partner, menopause (oestrogen deficiency), diabetes, pregnancy, incomplete bladder emptying, obstruction, stones, catheters, reflux, vaginal prolapse, immunosuppression, and genetic predisposition.

Cystitis: dysuria, frequency, urgency, suprapubic discomfort, haematuria, nocturia, and cloudy or malodorous urine. No systemic features. Absence of vaginal symptoms raises probability of UTI above 90%.

Pyelonephritis: fever, rigors, flank pain, nausea, vomiting (see pyelonephritis article).

Prostatitis (acute): fever, perineal pain, voiding symptoms, tender prostate.

Special populations

• Older adults: non-specific presentations (delirium, falls, reduced appetite, functional decline). Positive urine culture without local symptoms is usually asymptomatic bacteriuria and should not be treated.
• Children: fever without a source, irritability, vomiting, poor feeding, jaundice in neonates, abdominal pain, enuresis, dysuria in older children.
• Pregnancy: asymptomatic bacteriuria in 2 to 10%, leading to pyelonephritis in 20 to 30% if untreated.
• Catheterised patients: fever, suprapubic or flank tenderness, rigors, delirium, with or without lower tract symptoms.
• Recurrent UTI: pattern of triggers (postcoital, postmenopausal).

Red flags: fever above 38 degrees with flank pain, sepsis, pregnancy, male sex, obstruction, haematuria persisting after treatment, recurrent infection, immunosuppression, neurological disease, and children under 3 months.

Differential diagnosis: urethritis (chlamydia, gonorrhoea), vaginitis, genitourinary syndrome of menopause, interstitial cystitis, overactive bladder, bladder cancer, stones, radiation cystitis, genital herpes, and prostatitis.

Urinalysis (dipstick):

• Positive nitrite (specific, about 95%, sensitivity 45 to 60%, absent with Enterococcus, Staphylococcus, Pseudomonas) and leukocyte esterase (sensitivity 75 to 96%). Both negative has high negative predictive value (above 95%) in low-risk symptomatic women.
• Microscopy: pyuria (10 or more WBC/µL, or more than 5 per high power field) and bacteriuria.

Culture:

• Midstream clean-catch (or catheter specimen in children and catheterised patients, via suprapubic aspiration in infants if needed). Threshold: 10^3 CFU/mL or more in symptomatic women (uncomplicated cystitis), 10^4 for pyelonephritis, 10^5 for asymptomatic bacteriuria. In men 10^3.
• Indications: pyelonephritis, complicated UTI, pregnancy, treatment failure, recurrent UTI, men, children, catheters, and healthcare-associated infection.
• Do not test or treat asymptomatic bacteriuria except in pregnancy, before urological procedures breaching mucosa, and after renal transplant in the early period (varies).

Further tests:

• Blood tests in systemic illness: CBC, CRP, creatinine, glucose, lactate, blood cultures.
• Imaging (ultrasound, CT, voiding cystourethrogram): in pyelonephritis with complications, men with first UTI, recurrent UTI, haematuria, children (ultrasound after first febrile UTI, DMSA for scarring, VCUG for abnormal ultrasound or recurrence), suspected obstruction or stones, and poor response.
• Cystoscopy: recurrent UTI with suspicion of anatomic cause, persistent haematuria.
• Post-void residual measurement by ultrasound.
• STI testing in sexually active patients with urethritis symptoms or sterile pyuria.

Use local antibiogram, avoid collateral damage, treat the shortest effective duration.

Uncomplicated cystitis (women)

• Nitrofurantoin 100 mg modified release twice daily for 5 days (avoid if eGFR below 30 mL/min, G6PD deficiency, near term).
• Fosfomycin trometamol 3 g single dose.
• Pivmecillinam 400 mg three times daily for 3 to 5 days.
• Trimethoprim 200 mg twice daily for 3 days, or trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days (when resistance below 20%).
• Second-line: cefalexin 500 mg twice daily for 5 to 7 days, amoxicillin-clavulanate 625 mg three times daily for 5 days, and fluoroquinolones (ciprofloxacin 250 to 500 mg twice daily for 3 days) reserved for resistant organisms or pyelonephritis.
• Symptom relief: fluids, paracetamol, ibuprofen 400 mg, potassium citrate. NSAID-only therapy with delayed antibiotics is an option for mild symptoms.

Complicated UTI and men

• Culture-directed therapy: ciprofloxacin 500 mg twice daily (7 days), trimethoprim 200 mg twice daily (7 to 14 days), cefalexin 500 mg four times daily, amoxicillin-clavulanate 625 mg three times daily, or IV therapy (ceftriaxone 1 to 2 g daily, gentamicin 5 mg/kg daily, piperacillin-tazobactam 4.5 g every 6 to 8 hours, meropenem 1 g every 8 hours for ESBL) for severe infection. Duration 7 days (10 to 14 days if delayed response, men 7 to 14 days). Treat prostatitis for 2 to 4 weeks (acute) or 4 to 6 weeks (chronic).
• Correct the underlying anomaly (relieve obstruction, treat stones).

Pregnancy

• Screen at the first antenatal visit and treat asymptomatic bacteriuria for 5 to 7 days: cefalexin 500 mg four times daily or 1 g twice daily, amoxicillin-clavulanate 625 mg three times daily, nitrofurantoin 100 mg twice daily (avoid first trimester and near term), fosfomycin 3 g. Avoid trimethoprim first trimester and fluoroquinolones throughout. Test of cure after treatment, and monthly cultures or prophylaxis in recurrence.

Children

• Febrile UTI: oral (cefalexin 25 mg/kg twice daily, co-amoxiclav 15 mg/kg three times daily) or IV (ceftriaxone 50 to 75 mg/kg daily, gentamicin 5 to 7.5 mg/kg daily) therapy for 7 to 10 days. Neonates and infants under 3 months need IV therapy with cefotaxime and ampicillin and sepsis evaluation.

Catheter-associated UTI

• Treat only symptomatic infection. Replace the catheter (if in place for more than 2 weeks) before starting antibiotics and obtain culture from the new catheter. Treat for 7 days (14 days if delayed response or severe). Remove catheters as soon as possible, use intermittent catheterisation, closed drainage systems, and avoid routine antibiotic prophylaxis or bladder irrigation.

Asymptomatic bacteriuria

• Treat only in pregnancy, before urologic procedures with mucosal bleeding (single dose of culture-directed antibiotic, such as cefazolin 1 to 2 g IV or trimethoprim-sulfamethoxazole), and selected transplant recipients. Do not treat in older adults, diabetics, catheterised patients, or spinal cord injury.

Recurrent UTI prevention

• Non-antimicrobial: hydration, post-coital voiding, avoid spermicides, timed voiding, vaginal oestrogen (estradiol 10 micrograms vaginal insert or estriol cream 0.5 mg) in postmenopausal women, cranberry (36 mg proanthocyanidins daily), D-mannose 2 g daily (limited evidence), methenamine hippurate 1 g twice daily (with vitamin C no longer required), bladder instillations (hyaluronic acid, chondroitin), and OM-89 (Uro-Vaxom) or MV140 immunoprophylaxis.
• Antibiotic prophylaxis for 6 to 12 months: nitrofurantoin 50 to 100 mg at night, trimethoprim 100 mg at night, cefalexin 125 to 250 mg at night, or fosfomycin 3 g every 10 days. Post-coital prophylaxis with a single dose (trimethoprim 100 mg or nitrofurantoin 50 to 100 mg). Self-start therapy for patients who can recognise symptoms and send culture.
• Evaluate for correctable factors (post-void residual, stones, prolapse) and review underlying disease.

Candiduria

• Treat only if symptomatic, in neutropenia, before urological procedures, or in low birth weight infants: fluconazole 200 to 400 mg daily for 7 to 14 days. Remove the catheter.

Follow-up

• Reassess if symptoms persist after 48 to 72 hours or recur within 2 weeks. Test of cure only for pregnancy and some urological conditions. Educate patients about prevention and about early reporting.