What is the treatment for Pyelonephritis?

Treatment of Pyelonephritis

For uncomplicated pyelonephritis in outpatients, prescribe oral fluoroquinolones as first-line therapy—specifically ciprofloxacin 500-750 mg twice daily for 7 days or levofloxacin 750 mg once daily for 5 days—but only if local fluoroquinolone resistance rates are below 10%. 1, 2

Initial Assessment and Culture Requirements

• Always obtain urine culture and susceptibility testing before starting antibiotics to guide subsequent therapy adjustments. 1, 2
• Blood cultures should be reserved for patients with uncertain diagnosis, immunocompromised status, or suspected hematogenous infection. 3
• The combination of leukocyte esterase and nitrite tests has 75-84% sensitivity and 82-98% specificity for urinary tract infection. 3

Outpatient Treatment Algorithm

First-Line Therapy (Local Fluoroquinolone Resistance <10%)

• Ciprofloxacin 500 mg twice daily for 7 days (or 750 mg twice daily for severe cases). 1, 2, 4
• Levofloxacin 750 mg once daily for 5 days as an alternative fluoroquinolone option. 1, 2

When Fluoroquinolone Resistance Exceeds 10%

• Give one initial IV dose of a long-acting parenteral antibiotic (such as ceftriaxone 1g) followed by oral fluoroquinolone therapy while awaiting culture results. 1, 5, 6
• This approach bridges the gap until susceptibility data confirms appropriate oral therapy. 6

Alternative Oral Therapy (Only if Susceptibility Confirmed)

• Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 14 days is appropriate only when the uropathogen is proven susceptible. 7, 1, 2
• High resistance rates make TMP-SMX inappropriate for empiric therapy without culture confirmation. 7, 5

Oral β-Lactams (Less Preferred)

• Oral β-lactams are less effective than fluoroquinolones and require 10-14 days of treatment. 1, 2
• If an oral β-lactam must be used, always give an initial IV dose of ceftriaxone 1g first. 1
• Never use oral β-lactams as monotherapy without the initial parenteral dose—this is a common cause of treatment failure. 1, 2

Inpatient Treatment Indications

Hospitalize patients with: 7, 3, 6

• Complicated infections or sepsis
• Persistent vomiting preventing oral intake
• Failed outpatient treatment
• Extremes of age
• Immunocompromised status
• Suspected multidrug-resistant organisms

Inpatient IV Antibiotic Options

• Fluoroquinolones (ciprofloxacin 400 mg IV every 8-12 hours or levofloxacin 750 mg IV daily). 1, 4
• Extended-spectrum cephalosporins (ceftriaxone or cefepime). 1, 2
• Aminoglycosides with or without ampicillin (use cautiously in elderly or those with renal impairment). 1, 3
• Carbapenems for suspected extended-spectrum beta-lactamase-producing organisms. 1, 6
• Switch to oral therapy once the patient can tolerate oral intake and shows clinical improvement. 1

Special Populations Requiring Extra Vigilance

Patients with Diabetes or Chronic Kidney Disease

• Higher risk for complications including renal abscesses and emphysematous pyelonephritis. 1, 2
• Up to 50% may not present with typical flank tenderness, making diagnosis more challenging. 1
• Start with IV therapy and obtain imaging (CT scan) if no improvement occurs. 1

Pregnant Patients

• Must be admitted for initial parenteral therapy due to significantly elevated risk of severe complications. 6
• Avoid fluoroquinolones; use cephalosporins or aminoglycosides instead. 6

Other High-Risk Groups

• Anatomic urinary tract abnormalities, vesicoureteral reflux, renal obstruction, nosocomial infection, transplant recipients, and immunosuppressed patients all require more aggressive initial management. 1, 2

Duration of Therapy

• Fluoroquinolones: 5-7 days (levofloxacin 750 mg for 5 days, ciprofloxacin for 7 days). 7, 1, 2
• Trimethoprim-sulfamethoxazole: 14 days when susceptibility is confirmed. 7, 1, 2
• β-lactams: 10-14 days due to inferior efficacy. 1, 2

Monitoring and Follow-Up

• Most patients should improve within 48-72 hours of appropriate antibiotic therapy. 6
• If no improvement occurs, obtain imaging (preferably CT scan) to evaluate for complications such as abscess, obstruction, or stone disease. 1, 2, 6
• Repeat urine culture 1-2 weeks after completing antibiotics to confirm eradication. 3

Critical Pitfalls to Avoid

• Never use nitrofurantoin or oral fosfomycin for pyelonephritis—insufficient data supports their efficacy for upper urinary tract infections. 1
• Do not use oral β-lactams without an initial parenteral dose—this leads to treatment failure. 1, 2
• Avoid empiric TMP-SMX or oral β-lactams due to high resistance rates unless susceptibility is proven. 7, 5, 6
• Do not delay imaging in non-responders—complications like abscess or obstruction require urgent intervention. 1, 2
• Consider local resistance patterns when selecting empiric therapy—fluoroquinolone resistance exceeding 10% mandates alternative approaches. 1, 2, 6