Pyelonephritis

Pyelonephritis is an infection of the renal pelvis and parenchyma that is usually associated with an ascending bacterial infection of the bladder. It occurs more commonly in women and risk factors include pregnancy and urinary tract obstruction. Patients typically present with flank pain, costovertebral angle tenderness, fever, and other features of cystitis (e.g., dysuria, frequency). Urinalysis shows pyuria and bacteriuria. Urine cultures should be taken in all patients before initiating treatment to identify the pathogen and possible antibiotic resistance. Early empiric antibiotic treatment is essential to avoid renal complications and urosepsis. Definitive treatment depends on the drug sensitivities of the causative pathogen and the patient's clinical profile (e.g., possible comorbidities).

See also “Urinary tract infections.”

• Usually caused by an ascending bacterial infection of the bladder (cystitis)
• Less commonly due to hematogenous spread of infection to the kidney (e.g., infectious endocarditis)
• Pathogens
  • Gram-negative bacteria
    • Escherichia coli (∼ 75–90% of cases; leading cause of pyelonephritis)
    • Pseudomonas aeruginosa
    • Klebsiella pneumoniae
    • Proteus mirabilis
  • Gram-positive bacteria
    • Enterococcus faecalis
    • Staphylococcus aureus
    • Staphylococcus saprophyticus [2]
  • Candida infection (especially in immunocompromised patients) is possible
• Risk factors for pyelonephritis
  • Most common in women because they have shorter urethras
  • Pregnancy
  • Urinary tract obstruction (potentially leading to pyonephrosis)
    • Foreign bodies (e.g., indwelling urinary catheters or other urologic instrumentation)
    • Anatomical abnormalities (e.g., benign prostatic hyperplasia, vesicoureteral reflux, nephrolithiasis, ureteral strictures)
  • Cystitis
  • Recent administration of antibiotics (possible antibiotic resistance)
  • Immunosuppression; (e.g., HIV, diabetes mellitus)
  • Renal transplant [3][4]

The terminology used for classifying pyelonephritis is somewhat controversial and serves primarily to estimate the risk of atypical or antibiotic-resistant pathogens.

• Uncomplicated pyelonephritis: pyelonephritis in an immunocompetent, nonpregnant female with normal genitourinary anatomy and renal function [5][6][7][8]
• Complicated pyelonephritis: pyelonephritis associated with any of the following risk factors for complications: [6][8]
  • Failure of outpatient therapy
  • Sepsis
  • Male sex
  • Age > 60 years
  • Urinary tract abnormalities (e.g., obstruction, indwelling catheter)
  • History of surgery to the urinary tract or kidneys
  • Hospital-acquired infection
  • Renal impairment
  • History of nephrolithiasis
  • Immunosuppression and/or severe comorbidities (e.g., diabetes mellitus, chronic corticosteroid use)
  • Pregnancy

• Fever, chills
• Flank pain
• Costovertebral angle tenderness: pain upon percussion of the flank (usually unilateral, may be bilateral)
• Dysuria as well as other symptoms of cystitis (e.g., frequency, urgency)
• Weakness, nausea, vomiting (diarrhea may also be present)
• Possible abdominal or pelvic pain

Suspect pyelonephritis in any patient presenting with fevers, chills, and flank pain, irrespective of lower urinary tract symptoms.

Pyelonephritis symptoms may overlap with those of other life-threatening causes of flank pain (see “Differential diagnosis of pyelonephritis”).

Approach

• Pyelonephritis is a clinical diagnosis that is supported by positive urine culture.
• Routine diagnostic workup should include blood cultures (2 sets), urinalysis with microscopy, and urine culture with susceptibilities.
• Check CBC, BMP for signs of sepsis and organ dysfunction.
• Consider imaging in patients with suspected complicated pyelonephritis or treatment failure.

Laboratory tests

• Urinalysis [6]
  • Nonspecific findings of UTI
    • Pyuria (positive esterase on dipstick test)
    • Leukocyturia (WBCs > 5/hpf)
    • Bacteriuria
    • Positive nitrites on dipstick test indicate bacteria that convert nitrates to nitrites. [9]
    • Hematuria (including microhematuria)
  • Other findings
    • WBC casts; : rare finding, but considered to be a strong indicator for pyelonephritis [6][10]
    • Urine pH of ≥ 7.5–8.0: associated with urease-producing organisms [1][11][12]
    • Epithelial cells > 5/hpf: suggests contamination.
    • Gram stain: direct visualization of bacteria (seldom performed)
• Urine culture with susceptibilities
  • Perform in all patients with suspected pyelonephritis to determine the pathogen and any associated drug resistance.
  • ≥ 10⁵ colony-forming units/mL suggests bacterial infection (See “Urine culture” for more details.) [13][14]
• Blood cultures (2 sets): should be performed in all patients with suspected complicated pyelonephritis
• Urine pregnancy test in women of childbearing age
• Additional blood tests
  • CBC: leukocytosis
  • Inflammatory markers: ↑ CRP, ESR
  • BMP: may be normal or show elevated BUN and creatinine

Collect urine and blood cultures before administering empiric antibiotic therapy.

Imaging [15]

Indications

• Imaging is not routinely indicated in patients with suspected acute uncomplicated pyelonephritis.
• Imaging serves to identify obstruction, abscess, or emphysematous pyelonephritis.
• Consider in the following situations: [1]
  • Complicated pyelonephritis
  • Sepsis or septic shock
  • Known or suspected nephrolithiasis [16]
  • New decline in eGFR to < 40
  • Recurrent pyelonephritis [5]
  • No response to therapy within 2 days

CT is the imaging study of choice for assessing patients with suspected complicated pyelonephritis and ruling out differential diagnoses.

In the emergency department, renal POCUS may be helpful for quickly identifying hydronephrosis, but it does not preclude the need for CT in patients who require imaging. [17]

CT abdomen and pelvis with and without IV contrast [18]

Modality of choice in nonpregnant patients who need imaging

• CT findings in pyelonephritis
  • Renal parenchyma may appear normal (early) or edematous (hypodense areas)
  • Infected parenchyma may be visible as; wedge-shaped areas of streaky contrast enhancement (striated nephrogram). [18]
• CT findings in urinary tract obstruction
  • Hydroureter, hydronephrosis
  • Nephrolithiasis, urolithiasis (well-defined hyperintensities)
• Other findings that may be present
  • Congenital abnormalities of the renal tract
  • Abscess: intra-or extraparenchymal hypodense areas with peripheral contrast enhancement
  • Emphysematous pyelonephritis: presence of gas within the renal parenchyma, collecting system or perinephric space [19]
  • Hemorrhage in the parenchyma (hyperdense areas)

Ultrasound of the kidneys and bladder [18]

• Indications: patients with contraindications to CT scan (e.g., allergy to contrast)
• Findings supportive of pyelonephritis
  • Renal enlargement
  • Loss of corticomedullary differentiation
  • Edema (hypoechoic regions)
  • Hemorrhage (hyperechoic regions) in the parenchyma
  • Abscess: thick-walled hypoechoic region
• Findings supportive of urinary tract obstruction
  • Hydroureter, hydronephrosis
  • Thickened bladder wall
  • High bladder residual volume
  • Prostate enlargement
• Disadvantages: low sensitivity compared to CT, particularly in early acute infections [18]

MRI abdomen and pelvis

• Indications
  • Patients with contraindications to CT
  • Pregnancy [18]
• Findings: similar to CT scan (See “CT abdomen and pelvis with and without IV contrast.”) [18]

Additional imaging modalities

The following are rarely used, as CT, MRI, and ultrasound are more widely available.

• Intravenous pyelogram (IVP)
  • Indications: suspected obstruction or congenital abnormality [20]
  • Characteristic findings [18]
    • Enlarged kidney
    • Striated nephrogram
    • Delayed nephrogram and delayed calyceal opacification time [21]
    • Dilation or effacement of the collecting duct
• DMSA scan [18]
  • Indications: children with suspected pyelonephritis [22]
  • Characteristic findings: Acute pyelonephritis is visible as focal or global areas of decreased uptake.
• Additional imaging to consider
  • Voiding cystourethrogram: used to diagnose vesicoureteral reflux [23]
  • Urodynamic testing: to exclude neurogenic bladder or subvesical obstruction

• Acute pyelonephritis
  • Most commonly affects the cortex (spares glomeruli and vessels)
  • Purulent inflammation of the interstitium with destruction of the parenchyma, the renal tubules, and, in some cases, the renal pelvis
  • Histology
    • Neutrophilic infiltration of the renal tubules and the interstitium
    • Sparing of the glomeruli and intrarenal vessels
• Chronic pyelonephritis
  • Chronic inflammatory changes with rough, asymmetric scarring and fibrosis of the corticomedullary junction
  • Blunted calyces from recurrent urinary reflux
  • Histology: eosinophilic casts in the tubules that resemble thyroid tissue with coloid (thyroidization of the kidney)
  • Xanthogranulomatous pyelonephritis
    • A rare form of chronic pyelonephritis characterized by chronic destructive granuloma formation
    • Associated with Proteus mirabilis and Escherichia coli infections
    • Large, irregular, yellow-orange masses on gross examination of the kidney (may be mistaken for a true renal neoplasm)
    • Histology: granulomatous tissue with lipid-laden foamy macrophages and multinucleated giant cells

See also “Differential diagnoses of acute abdomen” and “Differential diagnoses of acute back pain.”

• Other kidney and urinary tract disorders
  • Lower UTIs
  • Renal colic
  • Renal vein thrombosis
  • Renal infarct
• Other intraabdominal, retroperitoneal, and pelvic disorders
  • Psoas abscess
  • Splenic infarct or abscess
  • Retroperitoneal hematoma or infection
  • Acute cholecystitis
  • Appendicitis
  • Diverticulitis
  • Pelvic inflammatory disease
  • Endometriosis
• Disorders outside the abdomen, pelvis, and retroperitoneum
  • Musculoskeletal disorders (e.g., spinal, paraspinal)
  • Pleural empyema
  • Pulmonary infarct
  • Shingles

The differential diagnoses listed here are not exhaustive.

Antibiotic therapy, source control, and supportive care are the mainstays of treatment of pyelonephritis. The choice of empiric antibiotic regimen should be guided by the risk of infection with resistant organisms (i.e., complicated vs. uncomplicated pyelonephritis) and antibiotics should be tailored as soon as culture results become available. Consider specialist consultation in cases of complicated pyelonephritis, especially if urinary tract obstruction is suspected.

Uncomplicated pyelonephritis [5][7][24]

• Empiric antibiotic therapy for uncomplicated pyelonephritis [24]
  • Most patients can be treated with an oral fluoroquinolone (e.g., ciprofloxacin; , levofloxacin ) for 5–7 days [1][24][25]
  • Alternatives
    • Trimethoprim/sulfamethoxazole , for 10–14 days (only recommended if susceptibility is known) [1]
    • Amoxicillin/clavulanate for 10–14 days [24]
    • Cefpodoxime for 10–14 days [24]
  • Consider a single dose of a broad-spectrum parenteral antibiotic prior to the administration of oral antibiotics, especially when the local rates of drug-resistant E. coli are unknown or known to be > 10%. [1][24]
    • Ceftriaxone
    • OR gentamicin [24][25]
• Supportive care
  • Encourage the patient to drink adequate amounts of fluids.
  • Consider an IV fluid bolus in patients with dehydration. [1]
  • Analgesia for pain (see “Pain management”) [1]
  • Antiemetics in patients with nausea and vomiting (e.g., ondansetron ) [1]
• Additional considerations
  • Outpatient treatment is generally appropriate.
  • If there is no response within 48 hours of starting empiric antibiotic therapy:
    • Consider imaging to evaluate for urinary tract obstruction or formation of renal abscess (see “Diagnostics”).
    • Check urine culture results and adjust treatment accordingly. [1]
  • Repeat urine culture (i.e., “test for cure”) is not routinely indicated. [5]

A single dose of a broad-spectrum parenteral antibiotic prior to the administration of oral antibiotics is recommended when local rates of E. coli resistance are > 10% (or unknown) or if trimethoprim/sulfamethoxazole is used empirically.

Complicated pyelonephritis [5][7][24]

Patients with complicated acute pyelonephritis should be admitted to the hospital and started on parenteral empiric antibiotic therapy as soon as possible. [1]

• The choice of empiric antibiotic therapy should be decided based on:
  • Clinical severity (i.e., presence of sepsis)
  • The presence of risk factors for infection with multidrug-resistant bacteria [1]
    • Age ≥ 65 years
    • Recent stay in hospital or long-term care facility
    • Recent antibiotic use
    • Indwelling urinary tract devices
    • Known abnormalities of the urological tract or urinary tract obstruction
    • Previous resistant infection
    • Recent travel to an area with high antibiotic resistance (e.g., Asia, Mexico)

Fluoroquinolone monotherapy should be avoided in severely ill patients with complicated pyelonephritis due to the high prevalence of fluoroquinolone-resistant pathogens!

• Supportive care
  • Analgesics as needed (see “Pain management”)
  • Antiemetics as needed
• Additional considerations
  • Aggressive IV resuscitation for patients with sepsis (see “IV fluid therapy”)
  • Source control: Consider imaging to identify urinary obstruction (see “Diagnostics” above).
  • Specialist consultations
    • Urology consultation if renal abscess or obstruction is present/suspected
    • Nephrology consultation in patients with AKI, electrolyte derangements, need for hemodialysis
    • Critical care consultation if septic shock is present
• Management of complications
  • Abscess
    • Abscess < 3 cm and no signs of sepsis: no drainage necessary
    • Abscess ≥ 3 cm and/or signs of sepsis present: percutaneous drainage of abscess
  • Life-threatening urosepsis: urology/surgery consultation for possible nephrectomy [27][28]
  • Shock: aggressive fluid resuscitation, vasopressors (see “Shock”)
  • Urinary tract obstruction: emergent urology and IR consultation for ureteral stenting or percutaneous nephrostomy
• Subsequent management
  • Duration of antibiotic therapy: 10–14 days [24]
  • Antibiotic therapy should be adjusted once blood and urine culture sensitivity reports are available.
  • Consider repeat urine culture in pregnant women and those with recurrent pyelonephritis 2–4 days after completion of the antibiotic course. [5][29]
  • Identify and treat the underlying cause.

Patients with concurrent urinary tract obstruction are at very high risk of clinical deterioration and require immediate intervention to remove the obstruction.

Admission criteria [1]

Consider inpatient management if any of the following are present:

• Complicated pyelonephritis
• Potential difficulties in following outpatient care and follow-up instructions
• No suitable oral antibiotic
• Ongoing hypovolemia
• Persistent nausea and vomiting

Uncomplicated pyelonephritis [5][7][24][25]

• Check urinalysis and order urine culture with susceptibilities (ideally before administering antibiotics).
• Consider a single initial dose of broad-spectrum empiric IV antibiotics.
• Start empiric oral antibiotic therapy.
• Encourage oral hydration.
• Consider inpatient admission if there is concern for a complicated course.
• Follow up on urine culture results and narrow antibiotic regimen accordingly.

Complicated pyelonephritis [5][7][24]

• Obtain blood cultures (2 sets) and urine culture with susceptibilities (ideally before administering antibiotics).
• Start parenteral empiric antibiotic therapy for complicated pyelonephritis.
• Establish source control: Check imaging to evaluate for an abscess and/or obstruction.
• Identify and treat sepsis.
• IV fluid therapy
• Identify and treat any urinary tract obstruction.
• Treat the underlying cause.
• Follow up on urine culture results and narrow antibiotic regimen accordingly.
• Inpatient admission

• Urosepsis, septic shock
• Perinephric abscess; , renal abscess
• Renal papillary necrosis
• Emphysematous pyelonephritis [18]
  • Rare form of pyelonephritis characterized by gas formation within and around the kidney
  • Most common in patients with poorly controlled diabetes or immunodeficiency
  • Typically caused by E. coli or K. pneumoniae
  • Treatment includes IV antibiotics, percutaneous drainage, and, in some cases, nephrectomy.
• Recurrent bacterial pyelonephritis
  • If recurrence is caused by the same organism despite adequate treatment, then prolong the course of antibiotics for 6 weeks.
  • If a new pathogen is identified, change antibiotics accordingly and treat for 2 weeks.
• Atrophic kidneys
• End-stage renal disease (ESRD): if both kidneys are affected, the patient has a single kidney, or the other kidney has been damaged by a different pathology

Rule out urosepsis in elderly patients with altered mental status!

We list the most important complications. The selection is not exhaustive.

Pyelonephritis in pregnancy [1][24]

• Epidemiology
  • The risk of pyelonephritis is increased during pregnancy.
  • As many as one-third of pregnant women with asymptomatic bacteriuria will progress to develop pyelonephritis (if left untreated).
  • One of the most common complications of pregnancy, with potentially severe consequences for both mother and fetus [1]
• Diagnosis: See “Diagnostics” above; use ultrasound or MRI for imaging. [30]
• Treatment [1][24]
  • Hospitalization is recommended; definitive indications for hospitalization are: [31]
    • Signs of sepsis
    • Dehydration (e.g., due to vomiting)
    • Contractions
  • A third- or fourth-generation cephalosporin for 7–10 days, such as:
    • Cefotaxime
    • Ceftazidime
    • Cefepime
  • In severe pyelonephritis (immunocompromised patients or poor urine output), consider one of the following for 10–14 days:
    • Piperacillin/tazobactam
    • Meropenem
    • Ticarcillin
  • Parenteral broad-spectrum antibiotics are recommended at least until the patient is afebrile, after which transition to oral antibiotics (e.g., penicillins, cephalosporins) is possible. [31]
  • See “Antibiotics during pregnancy” for additional drugs and dosages.
• Secondary prevention: Monthly urine culture or prophylactic nitrofurantoin until 4–6 weeks postpartum is recommended, as the recurrence rate of pyelonephritis in pregnancy is 25%. [32]

All asymptomatic cases of bacteriuria during pregnancy must be treated to prevent the development of pyelonephritis.

Avoid fluoroquinolones, trimethoprim/sulfamethoxazole, and aminoglycosides in pregnant women!

Acute pyelonephritis in children

See "Urinary tract infection in children and adolescents."

• Description: a consequence of recurrent or persistent acute pyelonephritis
• Predisposing factors
  • Vesicoureteric reflux
  • Urinary tract obstruction (e.g., nephrolithiasis, neurogenic bladder)
• Clinical features
  • Nonspecific (mild fever, anorexia, malaise)
  • Abdominal or flank pain
• Diagnostics
  • Urinalysis: pyuria, proteinuria, WBC casts
  • Imaging (ultrasound, intravenous urogram): corticomedullary scarring (mainly upper pole), blunt/clubbed renal calyces
  • Biopsy: thyroidization of the kidney (see ''Pathology'')
• Treatment
  • Treat the underlying cause.
  • Antibiotics