Fever with urinary symptoms

Fever with urinary symptoms is a temperature of 38.0 degrees Celsius or over with dysuria, frequency, urgency, suprapubic or flank pain, haematuria, cloudy urine, urinary retention, or genital symptoms. It indicates upper urinary tract or systemic infection until proven otherwise.

Definitions. Uncomplicated cystitis is lower tract infection in a nonpregnant premenopausal woman with a normal urinary tract and no fever. Acute pyelonephritis is infection of the renal pelvis and parenchyma with fever, flank pain and often systemic features.

Complicated urinary tract infection is infection with a structural or functional abnormality (obstruction, stones, catheter, reflux, neurogenic bladder, renal transplant, diabetes, immunosuppression, pregnancy, male sex, or resistant organisms). Men with urinary infection are classed as complicated infection by definition.

Catheter associated infection is symptomatic infection in a patient with a catheter in place for over 48 hours or removed within 48 hours.

Classification

• Lower tract: cystitis, urethritis, prostatitis (acute and chronic bacterial).
• Upper tract: acute pyelonephritis, emphysematous pyelonephritis, renal and perinephric abscess, pyonephrosis (infected obstructed kidney), xanthogranulomatous pyelonephritis.
• Male genital: epididymo-orchitis, prostatic abscess.
• Device related: catheter associated urinary tract infection, nephrostomy and stent infection.
• Specific: urinary tuberculosis, schistosomiasis, candiduria, and sexually transmitted urethritis.
• Systemic infection or noninfectious illness with urinary symptoms: pelvic inflammatory disease, appendicitis, diverticulitis, kidney stones, glomerulonephritis, and vasculitis.

Epidemiology. Urinary tract infection affects about half of women once in their life and is the commonest bacterial infection, with a recurrence rate of about 25% within 6 months. Escherichia coli causes 75% to 90% of community infections, followed by Klebsiella, Proteus, Enterococcus and Staphylococcus saprophyticus.

Catheter infections and hospital infections include Pseudomonas, extended spectrum beta-lactamase producing Enterobacterales, and Candida. Urosepsis accounts for a quarter of sepsis cases. Pregnant women have a 2% to 10% prevalence of bacteriuria, with a 30% risk of pyelonephritis if untreated.

Mechanisms. Ascending infection by periurethral bacteria, facilitated by short urethra, sexual activity, catheters and stasis. Bacteria adhere to uroepithelium by fimbriae. Haematogenous seeding (Staphylococcus aureus, tuberculosis, candida) is less common. Obstruction impairs clearance and allows rapid parenchymal damage.

Key distinctions. Dysuria and frequency without fever or flank pain point to cystitis. Fever, flank pain, vomiting and costovertebral tenderness point to pyelonephritis. Perineal pain, retention, a tender boggy prostate and fever point to acute prostatitis. A swollen painful scrotum points to epididymitis (or testicular torsion, which needs emergency exclusion). A fever with a blocked kidney and stone requires urgent decompression. Sterile pyuria suggests tuberculosis, chlamydia or recent antibiotic use.

History

• Urinary symptoms: dysuria, frequency, urgency, nocturia, haematuria, hesitancy, poor stream, retention, incontinence, suprapubic pain, flank pain radiating to the groin, vomiting, rigors.
• Duration, previous infections and organisms, response to treatment, and recent antibiotics.
• Sexual history: new partners, urethral or vaginal discharge, ulcers, pelvic pain, contraception.
• Risk factors: diabetes, pregnancy, stones, prostate enlargement, catheter, instrumentation, urological surgery, neurogenic bladder, immunosuppression, recent hospital stay, travel to areas with resistant organisms, menopausal atrophy, and kidney transplant.
• Haematuria with weight loss and night sweats (tuberculosis), travel to schistosomiasis areas.
• Drugs: sodium glucose cotransporter 2 inhibitors (genital and urinary infection), immunosuppressants, anticholinergics (retention), nephrotoxins, and allergy history.

Examination

• Vital signs and sepsis screen: temperature, pulse, blood pressure, respiratory rate, oxygen saturation, mental state, and capillary refill.
• Abdomen: suprapubic tenderness, palpable bladder, renal angle tenderness, masses.
• Genital examination: scrotal swelling, tenderness, cord thickening (epididymitis), testicular lie (torsion), urethral discharge, penile lesions, foreskin.
• Digital rectal examination in men with suspected prostatitis (gentle, no massage in acute infection).
• Pelvic examination when discharge or pelvic pain is present.
• Catheter site and drainage, pressure sores, spinal examination in neurogenic bladder.
• Cardiac murmurs when bacteraemia is likely.

Red flags

• Sepsis: hypotension, tachycardia, tachypnoea, confusion, lactate over 2 mmol/L, oliguria.
• Obstruction: anuria, severe colic, known stone, hydronephrosis on ultrasound, or rising creatinine with fever.
• Pregnancy with fever or flank pain.
• Diabetes with poor control, emphysematous infection (gas on imaging).
• Renal transplant or immunosuppression.
• Persistent fever beyond 72 hours of treatment (abscess, obstruction, resistant organism).
• Testicular pain of sudden onset (torsion) or Fournier gangrene (perineal pain, crepitus, rapidly spreading necrosis).
• Gross haematuria with clots or retention.
• Urinary tract infection in an infant or young child.
• Spinal cord injury with autonomic dysreflexia.
• Infection with extended spectrum beta-lactamase, carbapenem resistance, or Pseudomonas.

Special groups

• Pregnancy: screen and treat asymptomatic bacteriuria. Treat pyelonephritis in hospital.
• Children: fever without a source needs urine testing. Infants have nonspecific features. Use paediatric doses and imaging.
• Older adults: confusion, falls or functional decline without urinary symptoms. Do not treat positive urine alone when asymptomatic.
• Men: always complicated. Consider prostatitis, obstruction and stones.
• Catheterised patients: bacteriuria is universal and treatment depends on symptoms.
• Region specific: schistosomiasis, tuberculosis and resistant Gram negative bacteria.

Urinary tract infection

• Cystitis (uncomplicated or complicated).
• Acute pyelonephritis, emphysematous pyelonephritis, pyonephrosis.
• Renal cortical and perinephric abscess.
• Acute bacterial prostatitis and prostatic abscess.
• Epididymo-orchitis.
• Catheter associated urinary tract infection.
• Urinary tuberculosis and schistosomiasis.
• Candiduria and fungal bezoar.

Genital and pelvic infection

• Urethritis from gonorrhoea, chlamydia, Mycoplasma genitalium, trichomonas, and herpes.
• Pelvic inflammatory disease and tubo-ovarian abscess.
• Vulvovaginitis and cervicitis.

Non urinary causes of fever with flank or lower abdominal pain

• Renal colic with infected stone.
• Appendicitis, diverticulitis, cholecystitis and liver abscess.
• Pelvic or ovarian pathology: ectopic pregnancy, ovarian torsion.
• Testicular torsion and strangulated hernia.
• Basal pneumonia and pleurisy.
• Spinal infection (discitis, vertebral osteomyelitis, epidural abscess).

Non infectious

• Glomerulonephritis, interstitial nephritis, and renal infarction.
• Renal cell carcinoma and lymphoma with fever.
• Urothelial cancer and haemorrhagic cystitis (cyclophosphamide, radiation).
• Interstitial cystitis and bladder pain syndrome.
• Vasculitis and systemic lupus erythematosus.

Step 1. Assess for sepsis and obstruction. Record vital signs. Measure lactate and creatinine. Start sepsis treatment if criteria are met. Check for retention and a palpable bladder.

Step 2. First line tests

• Urine dipstick (leucocyte esterase and nitrite; a negative dipstick for both makes infection unlikely in women under 65 years with typical symptoms) and midstream urine microscopy and culture before antibiotics in all patients with fever, pregnant women, men, children, recurrent or failed treatment, and complicated infection.
• Catheter specimen from a newly replaced catheter in catheterised patients.
• Significance: 100,000 colony forming units/mL (10^5) in midstream samples; 1000 colony forming units/mL (10^3) in symptomatic women with typical symptoms or in catheter specimens.
• Two sets of blood cultures in fever, pyelonephritis and sepsis.
• Full blood count, C-reactive protein, urea, creatinine, electrolytes, glucose, lactate, and liver tests.
• Pregnancy test in women of reproductive age.
• Sexually transmitted infection testing (nucleic acid amplification for chlamydia, gonorrhoea, Mycoplasma genitalium; first catch urine or swabs) with consent when risk exists.

Step 3. Imaging

• Renal and bladder ultrasound within 24 hours for severe infection, suspected obstruction, male patients with fever, renal impairment, diabetes, or no response in 48 to 72 hours. Measure post void residual volume when retention is suspected.
• Non contrast CT of the kidney, ureters and bladder for stones, followed by contrast CT for abscess, emphysematous infection, or poor response.
• Doppler ultrasound of the scrotum when torsion cannot be excluded clinically.
• Magnetic resonance imaging of the spine when back pain with neurological signs suggests epidural abscess.
• Voiding cystourethrogram and renal scintigraphy in children after first febrile infection with abnormal ultrasound, recurrent infection, or atypical organisms.

Step 4. Other tests

• Prostate specific antigen is not useful during acute prostatitis.
• Urine acid fast bacilli on three early morning samples and culture for sterile pyuria.
• Urine microscopy for schistosome eggs (terminal urine, midday) in people from endemic areas.
• Cystoscopy and urology review for recurrent infection, haematuria, or abnormal imaging after resolution.

Step 5. Interpretation. Fever with positive urine culture and flank pain establishes pyelonephritis. Asymptomatic bacteriuria in a patient with fever should not stop the search for another source. Positive culture in a catheterised patient without local or systemic signs is colonisation. Negative cultures after antibiotics, or sterile pyuria, need testing for chlamydia, tuberculosis and fastidious organisms. Limits.

Dipstick is less accurate in older adults, pregnancy and catheterised patients. Urine contamination causes false positives. Early antibiotics render cultures negative. Ultrasound can miss early abscess and small stones.

Immediate. Assess for sepsis and treat within 1 hour: intravenous crystalloid 500 mL boluses (30 mL/kg for hypotension or lactate 4 mmol/L or over), oxygen as required, blood cultures, antibiotics, and urine output monitoring. Antipyretic and analgesia with paracetamol 1 g every 6 hours (maximum 4 g daily) and avoid nonsteroidal drugs in acute kidney injury. Obstructed infected system: urgent decompression by nephrostomy or retrograde stent. Catheter retention: insert a urinary catheter and replace long term catheters.

Uncomplicated cystitis in women (no fever)

• Nitrofurantoin modified release 100 mg orally twice daily for 3 days (creatinine clearance 45 mL/min or over; avoid in pregnancy at term and in infants under 3 months).
• Pivmecillinam 400 mg orally as the first dose then 200 mg three times daily for 3 days.
• Trimethoprim 200 mg orally twice daily for 3 days when local resistance is under 20% (avoid in the first trimester of pregnancy and with folate deficiency).
• Fosfomycin 3 g orally as a single dose.
• Symptomatic treatment: fluids and paracetamol. Ibuprofen 400 mg three times daily for 3 days with food can be used without antibiotics for selected mild cases.

Acute pyelonephritis and complicated urinary tract infection (adults)

• Oral treatment for mild to moderate disease in patients who can swallow and are not septic: ciprofloxacin 500 mg twice daily for 7 days (use only if local resistance is under 10% and the patient has no fluoroquinolone risk factors such as age over 60 years, tendon disease, corticosteroid use, aortic aneurysm or seizures), or co-amoxiclav 625 mg three times daily for 7 to 10 days, or cefalexin 500 mg to 1 g three times daily for 7 to 10 days, or trimethoprim 200 mg twice daily for 14 days if the isolate is susceptible.
• Intravenous treatment for severe disease or vomiting: ceftriaxone 1 to 2 g once daily, or gentamicin 5 to 7 mg/kg once daily (adjust to ideal body weight, with levels, and avoid in renal impairment and pregnancy except with specialist advice), or amoxicillin with clavulanic acid 1.2 g every 8 hours. Switch to oral therapy after 48 hours of apyrexia, directed by culture.
• Duration: 7 days for pyelonephritis with a prompt response (14 days for beta-lactams alone in some regimens, 10 to 14 days in men), and 10 to 14 days for complicated infection with delayed response.
• Extended spectrum beta-lactamase producers: meropenem 1 g intravenously every 8 hours (creatinine clearance 26 to 50 mL/min, 1 g every 12 hours; 10 to 25 mL/min, 500 mg every 12 hours; under 10 mL/min, 500 mg every 24 hours), or ertapenem 1 g once daily (500 mg daily at creatinine clearance 30 mL/min or under). Oral options by susceptibility: fosfomycin, nitrofurantoin for lower tract only, and temocillin in some settings.
• Pseudomonas or high risk: piperacillin with tazobactam 4.5 g intravenously every 6 hours (creatinine clearance 20 to 40 mL/min, 4.5 g every 8 hours; under 20 mL/min, 4.5 g every 12 hours), or ceftazidime 2 g every 8 hours, or meropenem 1 g every 8 hours with the renal doses given for extended spectrum beta-lactamase producers.
• Enterococcus: amoxicillin 1 g intravenously every 8 hours.
• Men: infection is complicated by definition; use 7 to 14 days of therapy with agents that penetrate the prostate (ciprofloxacin 500 mg twice daily, trimethoprim 200 mg twice daily, or co-trimoxazole 960 mg twice daily when susceptible).
• Emphysematous pyelonephritis or abscess: broad spectrum antibiotics, percutaneous drainage or nephrectomy by urology.

Prostatitis

• Acute bacterial prostatitis: ciprofloxacin 500 mg twice daily for 14 days (then continue to 28 days total for chronic or relapse risk) or co-trimoxazole 960 mg twice daily for 14 to 28 days. Intravenous ceftriaxone 2 g daily with gentamicin if septic. Alpha blocker (tamsulosin 400 micrograms daily) for retention, and suprapubic catheter instead of urethral catheter if retention. Drain abscess.
• Chronic bacterial prostatitis: ciprofloxacin 500 mg twice daily for 28 days, or doxycycline 100 mg twice daily for 28 days, and urology review.

Epididymo-orchitis

• Age under 35 years or high sexual risk: ceftriaxone 1 g intramuscularly once plus doxycycline 100 mg orally twice daily for 10 to 14 days, and test and treat partners.
• Age over 35 years or enteric organisms: ciprofloxacin 500 mg twice daily or ofloxacin 200 mg twice daily for 10 to 14 days.
• Scrotal support, analgesia, and exclude torsion. Surgical review if abscess or no response.

Catheter associated urinary tract infection

• Treat only symptomatic infection. Replace the catheter before sampling and starting treatment if in place for over 7 days. Use the complicated infection regimens for 7 days (10 to 14 days when delayed response). Remove the catheter as soon as possible. Do not treat asymptomatic bacteriuria.

Asymptomatic bacteriuria

• Treat only in pregnancy (nitrofurantoin 100 mg modified release twice daily for 5 to 7 days, or cefalexin 500 mg twice daily for 7 days, directed by culture) and before urological procedures that breach the mucosa. Do not treat in older adults, diabetes, spinal cord injury or catheterised patients.

Special populations

• Pregnancy: pyelonephritis needs admission. Ceftriaxone 1 to 2 g intravenously once daily or cefuroxime 750 mg every 8 hours, switching to oral cefalexin 500 mg twice or three times daily to complete 10 to 14 days. Then suppressive nitrofurantoin 50 to 100 mg at night or cefalexin 250 mg at night until delivery. Avoid fluoroquinolones, tetracyclines, and gentamicin unless essential.
• Children: febrile infection in infants under 3 months needs admission and intravenous ceftriaxone 50 to 75 mg/kg daily (avoid in neonates with jaundice; use cefotaxime) with ampicillin if Listeria is possible. Older children: cefalexin 25 mg/kg twice daily or co-amoxiclav for 7 to 10 days, and ultrasound.
• Older adults: reduce doses of gentamicin and avoid nitrofurantoin when creatinine clearance is under 45 mL/min.
• Renal and hepatic impairment: adjust doses; avoid nitrofurantoin and nephrotoxins; monitor creatinine and aminoglycoside levels.
• Renal transplant: specialist care, with culture directed therapy.

Prevention of recurrent urinary tract infection

• Behavioural measures (adequate fluids, post coital voiding), topical vaginal oestrogen for postmenopausal women (oestradiol 10 micrograms vaginal tablet daily for 2 weeks then twice weekly), methenamine hippurate 1 g twice daily, cranberry products (modest effect), and treatment of constipation.
• Antibiotic prophylaxis for at least 6 months after 3 or more infections yearly: nitrofurantoin 50 to 100 mg at night, or trimethoprim 100 mg at night, or cefalexin 125 to 250 mg at night, or single dose post coital.
• Investigation of anatomical abnormality and stones.

Monitoring. Vital signs, urine output, temperature, creatinine and electrolytes, C-reactive protein, culture and sensitivity, gentamicin levels at 6 to 14 hours, and imaging if no improvement in 48 to 72 hours.

Referral and escalation. Urology for obstruction, stones, abscess, recurrent infection, haematuria and prostatitis. Nephrology for acute kidney injury and transplant. Infectious diseases for resistant organisms. Obstetric care in pregnancy. Paediatric nephrology for children.

Admission criteria. Sepsis, vomiting or inability to take oral therapy, pregnancy, obstruction, diabetes with poor control, immunosuppression, renal impairment, failure of oral treatment, abscess, and infants and young children.

Discharge and follow up. Complete the antibiotic course, drink fluids, review culture results, repeat urine culture 1 to 2 weeks after treatment in pregnancy, and assess again at 48 to 72 hours. Safety net advice: return for rigors, vomiting, persisting fever over 72 hours, reduced urine output, flank pain, confusion, or testicular pain.