• Uncomplicated: Can be treated as an outpatient with oral (PO) antibiotics.
• Complicated: Inpatient treatment with intravenous (IV) antibiotics is required. Hospitalization is indicated for persistent vomiting, progression of uncomplicated UTI, suspected sepsis, immunosuppression, or urinary tract obstruction. This is a potentially life-threatening infection that can lead to renal parenchymal damage. Timely diagnosis and management can significantly impact patient outcomes.

Pyelonephritis is common in the U.S. with overall rates of 15 to 17 cases/10,000 women and 3 to 4 cases/10,000 men. Pyelonephritis accounts for 9.1% to 31% of severe sepsis cases annually, depending on geographic area. Average annual mortality is 16.1%, ranging from 5% for patients <25 yr to 43% for ages >64 yr.

Women are 5 times more likely to be hospitalized than men until the age of 65 yr. In men beyond the age of 65 yr, the difference in prevalence narrows. Risk factors associated with pyelonephritis in healthy women are sexual intercourse (≥3 times wk over the previous 30 days), a new sex partner in the past year, use of spermicide, UTI during the past 12 mo, mother with a history of UTI, diabetes mellitus, and urinary incontinence. Urinary tract obstruction is the most important risk factor for a complicated UTI.

Trimodal distribution described in female patients:

• Girls, ages 0 to 4 yr
• Women, ages 15 to 35 yr, especially if sexually active
• Gradual increase in frequency after age 50 yr, with peak incidence at 80 yr

Bimodal distribution in male patients:

• Boys, ages 0 to 4 yr
• Gradual increase in prevalence after age 35 yr, with peak incidence at 85 yr

Congenital urologic structural disorders associated with vesicoureteral reflux predispose individuals to infections at an early age (<5 yr) and produce renal scarring in most male and some female patients. Pyelonephritis may produce an Ask-Upmark kidney (segmental renal hypoplasia) that is found more often in young female patients with severe hypertension.

Obtained from and conducted on a clean-catch voided or catheterized specimen, if unable to void or cooperate. Dipstick and microscopic examination must be performed on a fresh specimen for preservation of formed elements (e.g., cells, casts, and microorganisms). Most cases demonstrate pyuria and positive leukocyte esterase in association with a positive blood reaction and microhematuria. Leukocyte casts are generally of kidney origin but may be absent.

Historically, clean, midstream cultures are obtained from all patients suspected of having acute pyelonephritis to guide antibiotic therapy. However, a clean-catch specimen may not be necessary. Recent evidence demonstrates no significant difference in the number of contaminated or unreliable culture results when urine is collected with or without preparatory cleansing. Obtain a catheterized urine sample if the patient is unable to void, uncooperative, or has an altered mental status. There is no difference in colony counts or organisms between catheterized and midstream voiding samples.

More than 95% of acute pyelonephritis cases exhibit >10⁵ colony forming units of a single bacterium per milliliter of urine. However, it is important to obtain an accurate history regarding the timing of culture acquisition and prior antibiotic administration. A negative culture with classic clinical and radiologic findings does not rule out acute pyelonephritis, as shown by a prospective study, in which only 23.5% of 196 patients with clinical and radiologic evidence of acute pyelonephritis had demonstrated positive urine cultures. A urine Gram stain may aid in the choice of empiric antimicrobial therapy pending urine culture. If gram-positive cocci are seen, consider Enterococcus species or S. saprophyticus as causative.

Posttreatment urinalysis and culture are unnecessary if symptomatic improvement occurs, but these studies should be obtained when symptomatic improvement does not occur after 2 or 3 days of antibiotic treatment, or if symptoms recur within 2 wk of treatment. Urinary tract imaging is recommended in such cases.

Cultures are obtained from hospitalized patients but may not be routinely required in uncomplicated cases. Approximately 15% to 30% of patients with acute pyelonephritis are bacteremic. Older adults and individuals with complicated acute pyelonephritis are more likely to develop bacteremia and sepsis.

Urine cultures yield a causative organism in nearly all cases of acute pyelonephritis. Therefore, a positive blood culture may be diagnostically redundant. However, in unclear cases, or when an alternative diagnosis to acute pyelonephritis is considered, blood cultures should be obtained.

The primary imaging modalities used in patients with pyelonephritis are computed tomography (CT), MRI, and ultrasound. Most uncomplicated cases of acute pyelonephritis do not require imaging studies unless symptoms do not improve, recurrence occurs, or if the patient has prolonged fever (>72 h) or persistent bacteremia. Abdominal radiographs (i.e., kidney, ureter, and bladder x-ray [KUB]) are of limited utility in acute pyelonephritis, unless staghorn calculi are present. Retrograde or antegrade pyelography may be helpful in severe obstruction that is not evident after noninvasive evaluations. Voiding cystourethrography demonstrates vesicoureteral reflux and generally is conducted routinely only in children.

Recommendations for radiologic tests:

• Healthy patients with uncomplicated pyelonephritis typically do not require radiologic evaluation when therapeutic responses occur within 72 h of antibiotic therapy.
• If no response to therapy occurs within 72 h, abdominal CT is the study of choice.
• Patients with diabetes and immunocompromised patients should undergo precontrast and postcontrast abdominal and pelvic CT scans (Fig. 1) within 24 h of diagnosis when response to therapy is not prompt.
• Ultrasound (Fig. 2) is reserved for patients in whom exposure to contrast or radiation is considered hazardous. There is a high false-negative rate for renal abscess with ultrasound. In a prospective study of acute pyelonephritis that included 213 patients who had a CT/nuclear magnetic resonance (NMR) study done, 50 patients (23.5%) had a renal abscess, yet only 2 were detected by ultrasound.
• All other adults with complicated cases (i.e., history of stones or other urologic conditions, prior urologic surgery, repeated episodes of pyelonephritis) should be evaluated early by CT.
• Helical CT detects calculi with high sensitivity.
• Urologic imaging studies should be conducted in all young men and boys.

Although the risk of contrast-induced nephropathy has declined substantially, exert caution during contrast administration in patients with chronic kidney disease or for those taking metformin. When evaluating kidney function, diagnostic decision-making must include estimated glomerular filtration rate trends, not serum creatinine levels, especially in older adults with reduced muscle mass. Patients with acute pyelonephritis and acutely elevated baseline serum creatinine concentrations may warrant CT imaging to rule out obstruction. If the risk of radiocontrast media administration outweighs its benefits, consider MRI or retrograde or antegrade pyelography.

The purpose of imaging is to identify underlying structural abnormalities such as occult obstruction from a stone or abscess and serious complications such as emphysematous pyelonephritis (EPN). In a prospective study of 213 patients with acute pyelonephritis, there were no differences in frequency of fever, leukocytosis, C-reactive protein, pyuria, urine cultures, and duration of symptoms before hospitalization for positive or negative CT. Accordingly, systematic CT or MRI is not required to exclude an anatomic abnormality. Such abnormalities cannot be predicted based on clinical, biochemical, or culture parameters.

EPN is a necrotizing infection that produces intraparenchymal kidney gas visualized by renal imaging. This disorder is associated with high mortality. Risk factors include diabetes mellitus and/or urinary tract obstruction. Gas-forming bacteria, most commonly E. coli, produce gas typically restricted within the Gerota fascia. Studies suggest an overall EPN mortality rate of 19%, reporting significant treatment success rates with percutaneous drainage and antibiotics (66%) and with nephrectomy (90%). EPN must be differentiated from a renal abscess, which can also be associated with a gas collection. With drainage and antibiotic treatment, a renal abscess has a favorable prognosis.

Close outpatient follow-up is possible for patients with minimal GI symptoms and the ability to maintain fluid intake and oral medications. Prompt antibiotic therapy prevents progression of infection and must be initiated following acquisition of appropriate cultures. Begin empiric therapy based on risk of adverse effects, local community bacterial profiles, and resistance rates. Antibiotics are revised after urine culture results are available.

The concept of requiring long-term treatment for acute pyelonephritis has been questioned. Women with acute pyelonephritis were randomized to PO treatment with ciprofloxacin 500 mg bid for 7 days or 14 days, and 27% of these patients experienced bacteremia from E. coli. No differences in the cure rates were found (87% and 96%, respectively).

Outpatient regimens:

• Fluoroquinolones are preferred in communities where the local prevalence of resistant E. coli is ≤10%.
• Ciprofloxacin 500 mg PO bid or a single, 1000-mg/day PO dose in the extended-release form for 7 days.
• Levofloxacin 750 mg/day PO for 5 to 7 days.
• The initial dose may be administered intravenously (ciprofloxacin 400 mg or levofloxacin 500 mg).
• When a fluoroquinolone is contraindicated, alternative treatment with trimethoprim-sulfamethoxazole (TMP-SMX) 160/800 mg PO bid for 10 to 14 days may be administered if the pathogen is susceptible.

Because of the high prevalence of resistance to PO beta-lactam antibiotics and TMP-SMX, these agents usually are reserved for cases in which susceptibility results are known. Additional factors (e.g., allergy history, potential drug-drug interactions, drug availability) may require empiric treatment with these agents before susceptibility testing results are known. In this circumstance, a long-acting, broad-spectrum parenteral drug (e.g., ceftriaxone 1 g or gentamicin 5 mg/kg) may be administered as a one-time dose or longer, until sensitivities of the organism are known. If the local prevalence of fluoroquinolone resistance to E. coli exceeds 10%, an initial IV dose of ceftriaxone or gentamicin is recommended, followed by an oral fluoroquinolone regimen.

Significant clinical improvement during appropriate empiric antibiotic therapy should occur within 48 to 72 h. If improvement does not occur, a complication of acute pyelonephritis or an alternative diagnosis such as an abscess, EPN, or an obstructing calculus should be considered. Any unexpected change in the clinical picture warrants immediate investigation with a CT scan.

Hospitalization is indicated for the following reasons:

• Toxic patients
• Complicated infections
• Diabetes or otherwise immunosuppressed
• Suspected bacteremia

Inpatient care includes supportive care, monitoring of culture results, adjustment of antibiotic regimen, and IV volume repletion as required. IV antibiotics are continued until defervescence occurs and clinical improvement occurs. Next, there is conversion to a PO antibiotic regimen for a total duration of 10 to 14 days.

• IV antibiotic options for more toxic patients pending cultures include IV ceftriaxone (once daily), IV ciprofloxacin (400 mg bid), IV levofloxacin (500 mg/day), piperacillin/tazobactam (3.375 g IV qid), or carbapenems such as meropenem (500 mg IV tid).
• Ceftazidime 1 to 2 g IV tid, piperacillin/tazobactam, or carbapenems are optimal choices for Pseudomonas because of increasing ciprofloxacin resistance.
• Aminoglycosides are potentially nephrotoxic. These agents should be used only if no better alternative exists.
• Vancomycin 1 g IV bid, linezolid 600 mg IV or PO bid, or daptomycin 4 to 6 mg/kg/day IV for gram-positive cocci (e.g., enterococci, staphylococci).
• Ampicillin 1 to 2 g IV every 4 to 6 h for ampicillin-sensitive enterococci with aminoglycoside for synergy. Urinary obstruction is promptly drained by nephrostomy tube. Surgical drainage of abscess formation(s).
• Pregnant women with acute pyelonephritis are hospitalized and treated initially with a second- or third-generation cephalosporin.

Cortical abscesses historically required surgical drainage; however, using current antibiotics is commonly sufficient for cure.

• Semisynthetic penicillin, cephalosporin, fluoroquinolone, or vancomycin with guidance from culture and sensitivity results.
  1. Parenteral therapy for 10 to 14 days followed by PO therapy for 2 to 4 wk.
  2. Fever should resolve in 5 to 6 days and pain within 24 h.
  3. If no clinical response occurs within 48 h, percutaneous (preferred) or open drainage should be considered. More extreme measures are occasionally required, including enucleation or nephrectomy.

• Parenteral therapy for at least 48 h is generally successful.
• May require incision and drainage and possibly, nephrectomy.
• If defervescence occurs, IV antibiotic treatment may be switched to complete a 2-wk course of PO antibiotic therapy.

• Serious complication with mortality in the 25% to 50% range.
• Lesions require early recognition, surgical drainage, and parenteral antibiotics (not adequate alone) to reduce mortality.
• Initial antibiotic therapy may include piperacillin-tazobactam, cefepime, or meropenem.
• Empiric therapy in the setting of S. aureus bacteremia includes nafcillin, oxacillin, cefazolin, or vancomycin (when methicillin-resistant Staphylococcus aureus is suspected).
• Tuberculosis and fungi are rare reported causes.
• deterioration despite aggressive therapy.

Chronic pyelonephritis may lead to formation of struvite stones (magnesium ammonium phosphate stones). Formation requires infection with a urease-producing organism such as Proteus or Klebsiella. Symptoms directly attributable to struvite stones are uncommon. Typically, patients will present with symptoms of a UTI, mild flank pain, or hematuria. The stone may grow rapidly over a period of weeks to months if treatment is inadequate. Medical treatment for struvite stones is often ineffective and only indicated when surgery is not an option. The most common surgical intervention is percutaneous nephrolithotomy. Open surgery, once the gold standard, is now rarely used.

Surgical intervention is generally recommended in patients with newly discovered stones or in patients with a solitary kidney or two equally functioning kidneys. Nephrectomy is a reasonable option in patients with a nonfunctional kidney, particularly when chronic infection is present.

• Admission for parenteral antibiotics:
  1. Initial therapy should cover E. coli, Enterobacter, Proteus, and Klebsiella species, pending culture results.
  2. For more serious infections, Pseudomonas and Enterococcus should also be covered.
  3. Empiric therapy agent options include the following:
     1. Aminoglycosides
     2. Cefotaxime
     3. Ceftriaxone
     4. Ceftazidime
     5. Cefepime
     6. Piperacillin-tazobactam
     7. Imipenem-cilastatin
     8. Meropenem
     9. Ciprofloxacin
  4. Continue parenteral therapy until fever and clinical symptoms improve.

Xanthogranulomatous pyelonephritis (XGP) is a rare variant of chronic pyelonephritis with destruction of renal parenchyma.

• Generally unilateral
• Affects women more than men from newborn to advanced age
• Usually in individuals with obstructing stones
• Presents with flank or abdominal pain, lower urinary tract symptoms, fever, palpable mass, gross hematuria, or weight loss
• Urine cultures commonly demonstrate E. coli or Proteus mirabilis
• CT is the diagnostic modality of choice and provides staging information
• Can be confused with malignancy
• Treatment is surgical nephrectomy

Chronic nephrolithiasis, especially in high-risk populations such as patients with diabetes or immunosuppressed patients, can predispose individuals and promote complicated infections leading to XGP and ENP. These are very rare disorders that are difficult to diagnose, and an unrecognized renal tumor can be hidden behind a suspected diagnosis of XGP and ENP.