Lucan · Conditions

Acute pyelonephritis

Australian guidance: eTG Antibiotic — Pyelonephritis

1. Definition and epidemiology

Acute pyelonephritis is a bacterial infection of the renal parenchyma and collecting system that arises most commonly via ascending spread from the lower urinary tract. It is one of the most common serious bacterial infections managed in Australian emergency departments and general practice, disproportionately affecting women of reproductive age, pregnant individuals, and older adults of both sexes. In Australia, community-acquired pyelonephritis accounts for a significant proportion of febrile urinary tract infections (UTIs) requiring hospitalisation each year, with Escherichia coli identified as the causative pathogen in 70 to 95% of cases.

2. Pathophysiology

Acute pyelonephritis nearly always originates from ascending colonisation of the urethra and bladder by faecal flora, most commonly uropathogenic E. coli (UPEC). UPEC expresses type 1 and P fimbriae that bind to uroepithelial receptors, facilitating ascent through the ureter to the renal pelvis and parenchyma. Vesicoureteric reflux, obstructive uropathy, or instrumentation accelerates this ascent. Once within the renal medulla, bacteria trigger an acute suppurative inflammatory response: neutrophil infiltration into collecting ducts and interstitium, tubular necrosis, and focal or diffuse abscess formation. The renal medulla is particularly vulnerable because its high osmolality and low blood flow impair leucocyte function and complement activity. Haematogenous seeding of the kidney is uncommon but occurs with Staphylococcus aureus bacteraemia. On gross pathology, the kidney is enlarged with suppurative foci that may coalesce into a cortical abscess or progress to emphysematous pyelonephritis in diabetic patients. (Robbins Ch 20)

3. Clinical presentation and diagnostic criteria

The classic triad is fever, costovertebral angle (CVA) tenderness, and lower urinary tract symptoms (dysuria, frequency, urgency). Systemic features including rigors, nausea, and vomiting distinguish pyelonephritis from uncomplicated cystitis. Examination reveals unilateral or bilateral CVA tenderness on percussion. A diagnosis of pyelonephritis is made clinically in a patient with features of a febrile UTI: temperature above 38 degrees Celsius, CVA or loin tenderness, and a urinalysis or urine microscopy consistent with infection. In older adults, younger children, and immunocompromised patients, the presentation may be atypical, with confusion, non-specific abdominal pain, or absence of localising urinary symptoms. Complicated pyelonephritis is defined by the presence of structural or functional urinary tract abnormality, diabetes, immunocompromise, pregnancy, recent urinary instrumentation, hospital-acquired infection, or inadequate response to initial outpatient therapy.

4. Investigations and AU-specific cutoffs

1. Urine microscopy, culture, and sensitivity (MCS): midstream urine should be collected before commencing antibiotics. Pyuria (greater than 10 white cells per microlitre or greater than 5 per high-power field) and bacteriuria support the diagnosis. A colony count greater than or equal to 10 to the power of 5 colony-forming units per millilitre is the conventional threshold for significant bacteriuria in symptomatic patients; lower counts may be clinically significant in pyelonephritis.

2. Blood cultures: recommended in all patients requiring hospitalisation, given the risk of bacteraemia and the importance of identifying resistant organisms for targeted de-escalation.

3. Full blood count, C-reactive protein (CRP), and renal function: leucocytosis and elevated CRP are expected. Renal impairment occurs in severe cases and guides fluid management and aminoglycoside dosing adjustment.

4. Imaging: renal ultrasound is indicated when there is concern for obstruction, abscess, or nephrolithiasis, particularly in patients who fail to improve within 48 to 72 hours of appropriate antibiotics. Contrast CT of the abdomen and pelvis is the preferred modality when complications such as perinephric abscess or emphysematous pyelonephritis are suspected.

5. Pregnancy testing: a pregnancy test should be performed in all women of childbearing age because pregnancy significantly alters management.

5. Management

The decision between outpatient oral and inpatient intravenous therapy depends on the severity of illness, ability to tolerate oral medication, and the presence of complicating factors. Patients who are systemically unwell, vomiting, pregnant, unable to achieve adequate oral intake, or failing outpatient therapy should be admitted for intravenous antibiotics.

For uncomplicated pyelonephritis in nonpregnant adults who can be managed as outpatients, eTG recommends oral trimethoprim (300 mg at night for 10 to 14 days) as the preferred first-line agent in regions where local E. coli susceptibility exceeds 80 to 85%. Ciprofloxacin (500 mg orally twice daily for 7 days) is an alternative where trimethoprim resistance is a concern or when susceptibility results support its use; however, fluoroquinolone use should be reserved to limit ecological resistance pressure. Cephalexin (500 mg four times daily for 10 to 14 days) is an option where beta-lactam susceptibility is confirmed.

For inpatient intravenous therapy, gentamicin (4 to 7 mg/kg daily as a single dose, adjusted for renal function) is the preferred agent, with dose adjustment guided by therapeutic drug monitoring, trough levels, and renal function. Ceftriaxone (1 g daily intravenously) is an alternative where aminoglycosides are contraindicated or in pregnancy. Empirical therapy should be rationalised to the narrowest effective agent once culture and sensitivity results are available. Transition to oral therapy is appropriate when the patient has been afebrile for at least 24 hours and can tolerate oral medications. Total treatment duration for pyelonephritis is 10 to 14 days, including the oral step-down phase.

In patients with risk factors for multidrug-resistant (MDR) gram-negative bacteria, including extended-spectrum beta-lactamase (ESBL)-producing E. coli, empirical therapy with an aminoglycoside (gentamicin or tobramycin) is preferred for inpatient management, as ESBL-producing organisms are resistant to broad-spectrum cephalosporins such as ceftriaxone. Oral step-down options for confirmed ESBL pyelonephritis include amoxicillin plus clavulanate, trimethoprim plus sulfamethoxazole, or ciprofloxacin if susceptibility is demonstrated.

6. Pharmacology and AU PBS notes

First-line oral agents: - Trimethoprim 300 mg orally at night for 10 to 14 days. Preferred where local resistance rates permit. PBS listed (Streamlined Authority Code applies for complicated UTI in some state formularies). - Ciprofloxacin 500 mg orally twice daily for 7 days. Fluoroquinolone; reserve for documented susceptibility or trimethoprim resistance. PBS listed as an Authority Required item for complicated UTI.

First-line intravenous agents: - Gentamicin 4 to 7 mg/kg intravenously once daily; therapeutic drug monitoring mandatory. Dose-adjust in renal impairment. Aminoglycoside nephrotoxicity and ototoxicity risk with cumulative or prolonged dosing. Trough level must be below 1 mg/L before the next dose. Available as gentamicin sulfate (AU brand: Gentamicin Pfizer, Gentamicin DBL). - Ceftriaxone 1 g intravenously or intramuscularly once daily; preferred in pregnancy or where gentamicin is contraindicated. Third-generation cephalosporin; not effective against ESBL-producing organisms.

Second-line oral agents: - Amoxicillin plus clavulanate 875 mg/125 mg orally twice daily for 10 to 14 days; option when susceptibility confirmed (AU brand: Augmentin Duo Forte). - Cephalexin 500 mg orally four times daily for 10 to 14 days; for susceptible organisms.

Nitrofurantoin is NOT appropriate for pyelonephritis because it does not achieve adequate tissue or blood levels outside the bladder.

7. Complications and monitoring

Key complications include:

• Bacteraemia and urosepsis: occurs in 10 to 30% of hospitalised patients; managed with early intravenous antibiotics and fluid resuscitation per Sepsis 6 principles.
• Perinephric abscess: failure to improve by 72 hours necessitates imaging; percutaneous or surgical drainage is required.
• Emphysematous pyelonephritis: gas-forming infection seen predominantly in patients with diabetes mellitus; CT diagnosis; requires urgent urological and surgical review.
• Renal papillary necrosis: complication of severe pyelonephritis in the context of diabetes, sickle cell disease, or analgesic nephropathy; may cause sloughed papilla in urine and acute kidney injury.
• Chronic pyelonephritis and renal scarring: repeated episodes of acute infection, especially in the context of vesicoureteric reflux or obstruction, cause progressive cortical scarring, hypertension, and chronic kidney disease.

Monitoring: daily clinical review in hospitalised patients for fever resolution, haemodynamic stability, and urine output. Repeat renal function, electrolytes, and gentamicin trough levels at 48 to 72 hours and again at any change in renal status. Urine culture should be repeated at 48 to 72 hours if clinical response is inadequate. A test-of-cure urine MCS is recommended 5 to 7 days after completing antibiotics in pregnant patients and those with complicated pyelonephritis. All patients with recurrent pyelonephritis, men with a first episode, children, and pregnant individuals warrant imaging to exclude structural abnormality.

Written for Australian practice and grounded in the guidance named above. Study material only — not medical advice. Always check against current guidelines.