Pyelonephritis

Pyelonephritis is infection of the renal parenchyma and pelvis, usually ascending from the lower urinary tract. It is the commonest serious urinary tract infection and presents as acute pyelonephritis, with sepsis in a significant minority.

Epidemiology:

• Incidence about 15 to 17 per 10,000 women per year and 3 to 4 per 10,000 men. Peak in young women (sexually active), pregnant women (1 to 2% of pregnancies), and older adults.
• Mortality is low in uncomplicated cases but up to 5 to 10% with urosepsis in complicated cases.

Pathogens:

• Escherichia coli (75 to 90% of community-acquired infections, with uropathogenic virulence factors such as P fimbriae).
• Klebsiella, Proteus mirabilis (struvite stones, urease), Enterococcus, Pseudomonas aeruginosa, Staphylococcus saprophyticus, Staphylococcus aureus (haematogenous), Candida (diabetes, catheter, antibiotics).
• Increasing resistance: ESBL-producing Enterobacterales (up to 10 to 30% in some regions), fluoroquinolone resistance, and carbapenem-resistant organisms.

Risk factors:

• Uncomplicated: young non-pregnant women, sexual activity, spermicide use, new partner, previous urinary tract infection.
• Complicated (structural or functional abnormality, immunocompromise or resistant organisms): urinary obstruction (calculi, BPH, tumour, stricture), vesicoureteral reflux, neurogenic bladder, catheters or instrumentation, diabetes (including emphysematous pyelonephritis), pregnancy, male sex, immunosuppression, renal transplant, polycystic kidney disease, healthcare-associated infection, and hospital admission.

Pathophysiology: ascent of bacteria from the bladder via the ureters (facilitated by reflux or stasis), adherence to the urothelium, and renal parenchymal invasion, with inflammation, neutrophil infiltration, oedema and, if severe, abscess or scarring. Haematogenous seeding is uncommon (S. aureus bacteraemia).

Variants and complications:

• Emphysematous pyelonephritis: gas-forming (E. coli, Klebsiella), mainly in diabetics, with high mortality (20 to 40%).
• Xanthogranulomatous pyelonephritis: chronic, with obstructing stone and Proteus, causing a destroyed kidney mimicking tumour.
• Pyonephrosis, renal and perinephric abscess, papillary necrosis (diabetes, sickle cell, analgesic abuse, obstruction).
• Sepsis and septic shock, acute kidney injury, and renal scarring in children.
• Chronic pyelonephritis (scarring from reflux and recurrent infection).

Typical presentation (acute, over 1 to 2 days):

• Fever (above 38 degrees Celsius), chills and rigors, flank or loin pain, costovertebral angle tenderness, nausea and vomiting, malaise.
• Lower tract symptoms in about 70% (dysuria, frequency, urgency), but may be absent.

Atypical presentations:

• Older adults, diabetics and immunosuppressed patients present with confusion, falls, functional decline, abdominal pain or sepsis, with minimal local symptoms.
• Infants and children: fever and irritability, poor feeding, vomiting.

Signs: tachycardia, hypotension (sepsis), loin tenderness, suprapubic tenderness, and abdominal tenderness. Palpable renal mass or bladder suggests obstruction.

Differential diagnosis: acute cystitis (no fever or flank pain), ureteric colic with infection, appendicitis, cholecystitis, diverticulitis, pelvic inflammatory disease, ovarian torsion, pneumonia (lower lobe), herpes zoster, musculoskeletal pain, renal infarction, and renal or perinephric abscess.

Criteria for complicated pyelonephritis (hospital care): sepsis, vomiting preventing oral therapy, pregnancy, obstruction, solitary kidney, transplant, immunosuppression, diabetes with poor control, male sex, healthcare-associated, resistant organism risk, and failure of outpatient therapy.

Red flags: hypotension, altered mental state, rising lactate, lack of improvement after 48 to 72 hours, obstruction, and suspected emphysematous disease.

Laboratory:

• Urinalysis (pyuria, bacteriuria, nitrites, leukocyte esterase, haematuria), white cell casts support the diagnosis.
• Urine culture before antibiotics (10^4 CFU/mL or more significant). Blood cultures in sepsis, hospital admission, or immunocompromise (positive in 15 to 20%).
• CBC (leukocytosis), CRP and procalcitonin, creatinine and electrolytes, glucose, lactate, and pregnancy test.

Imaging (not required routinely for uncomplicated pyelonephritis in young women responding within 72 hours):

• Indications: severe illness or sepsis, suspected obstruction, stones, history of urolithiasis, diabetes, immunosuppression, male patients, poor response to treatment (no improvement in 48 to 72 hours), recurrent infection, pregnant women, and renal impairment.
• Ultrasound (first line, rapid): hydronephrosis, stones, renal enlargement, abscess, residual bladder volume.
• CT with IV contrast (best for complications): wedge-shaped zones of decreased enhancement, striated nephrogram, perinephric stranding, abscess, gas (emphysematous disease), and obstruction (CT KUB non-contrast for stones). Gas pattern defines emphysematous pyelonephritis classes.
• MRI in pregnancy or contrast allergy.
• DMSA scan in children, to detect renal scarring.
• Voiding cystourethrogram in children after first febrile infection with abnormal ultrasound or recurrence.

Additional evaluation: HbA1c, HIV where relevant, genitourinary evaluation in men (prostate examination, PSA avoided in acute infection), and cystoscopy when recurrent.

Outpatient therapy (uncomplicated pyelonephritis in non-pregnant adult women, haemodynamically stable, tolerating oral intake)

• Take cultures first. Empirical choices depend on local resistance (fluoroquinolone resistance above 10% requires an initial IV dose of a long-acting agent):
• Ciprofloxacin 500 mg orally twice daily for 7 days (or 1000 mg extended release daily for 7 days), or levofloxacin 750 mg daily for 5 days (when local resistance is under 10%).
• Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 14 days (only when susceptibility is known or resistance below 20%), with an initial dose of ceftriaxone 1 g IV.
• Oral beta-lactams (cefpodoxime 200 mg twice daily, cefuroxime 500 mg twice daily, amoxicillin-clavulanate 875/125 mg twice daily) for 10 to 14 days, with an initial parenteral dose of ceftriaxone 1 g (less effective).
• Avoid nitrofurantoin and fosfomycin for pyelonephritis (inadequate tissue levels).
• Review at 48 to 72 hours.

Hospital therapy (complicated disease, sepsis, vomiting, pregnancy)

• Parenteral therapy:
• Ceftriaxone 1 to 2 g IV daily, cefepime 1 to 2 g IV every 12 hours, ciprofloxacin 400 mg IV every 12 hours, or gentamicin 5 mg/kg IV daily (single daily dose, renal-adjusted with levels) or amikacin 15 mg/kg daily, piperacillin-tazobactam 4.5 g IV every 6 to 8 hours.
• Suspected ESBL, recent hospital admission, or previous colonisation: meropenem 1 g IV every 8 hours (or ertapenem 1 g daily if no Pseudomonas risk). Avoid carbapenems when not needed. Newer agents (ceftazidime-avibactam 2.5 g IV every 8 hours, ceftolozane-tazobactam 1.5 g every 8 hours, cefiderocol, plazomicin) for carbapenem-resistant organisms.
• Enterococcus suspected: ampicillin 2 g IV every 6 hours, or vancomycin 15 to 20 mg/kg every 8 to 12 hours.
• Candida: fluconazole 200 to 400 mg daily for 14 days.
• Switch to oral therapy when afebrile for 24 to 48 hours and clinically improved, guided by susceptibility. Total duration 7 days for fluoroquinolone-based, 10 to 14 days for beta-lactams, and 14 days for complicated disease or delayed response (7 days may suffice for prompt responders with a fluoroquinolone or even other agents).
• Fluid resuscitation, antipyretics (paracetamol 1 g every 6 hours), antiemetics (ondansetron 4 mg), analgesia, and glucose control. Sepsis bundle in septic shock (30 mL/kg fluids, vasopressors).
• Men: treat for 14 days (prostate involvement), with evaluation for obstruction and prostatitis.

Pregnancy

• Hospital admission, IV ceftriaxone 1 to 2 g daily (or cefazolin 1 g every 8 hours, ampicillin and gentamicin, aztreonam), change to oral cephalexin 500 mg four times daily or amoxicillin-clavulanate when afebrile for 48 hours, total 10 to 14 days. Avoid fluoroquinolones, tetracyclines and trimethoprim in the first trimester.
• Suppressive prophylaxis (nitrofurantoin 50 to 100 mg at night, or cephalexin 250 mg) for the rest of pregnancy. Monitor for preterm labour, ARDS and sepsis.

Source control and complications

• Obstructive pyelonephritis: urgent decompression with ureteral stent or percutaneous nephrostomy (a urological emergency, particularly with pyonephrosis and sepsis), then definitive stone management when the infection has resolved.
• Renal or perinephric abscess: percutaneous drainage (under CT or ultrasound) for abscess over 3 to 5 cm, with antibiotics for 2 to 6 weeks. Surgery for large or multiloculated abscess.
• Emphysematous pyelonephritis: IV antibiotics, glycaemic control, percutaneous drainage with relief of obstruction, and nephrectomy for extensive gas (Class 3 and 4) or non-response (Huang and Tseng classification).
• Xanthogranulomatous pyelonephritis: antibiotics and nephrectomy.
• Catheter-related: replace catheter, and remove if not needed.

Follow-up and prevention

• Repeat urine culture is not needed in uncomplicated cases that resolve, but required in pregnancy (test of cure 1 to 2 weeks after therapy, and monthly cultures).
• Recurrent infection: behavioural measures, hydration, post-coital voiding, vaginal oestrogen in postmenopausal women, cranberry, methenamine hippurate 1 g twice daily, and prophylaxis (nitrofurantoin 50 mg nightly, trimethoprim 100 mg, or cefalexin 125 mg) for 6 to 12 months. Investigate recurrent or complicated infection with imaging for reflux, stones or obstruction.
• Children: renal imaging, prophylaxis in selected high-grade reflux, and long-term follow-up for scarring, hypertension and renal function.