What is the recommended treatment for pyelonephritis?

Treatment of Pyelonephritis

For uncomplicated pyelonephritis, the recommended first-line treatment is fluoroquinolones (such as levofloxacin 750 mg daily for 5-7 days) or trimethoprim-sulfamethoxazole (160/800 mg twice daily for 7-14 days) when local resistance is <20%, with an initial dose of a long-acting parenteral antibiotic like ceftriaxone recommended in areas with high resistance rates. 1

Initial Assessment and Diagnosis

• Obtain urinalysis and urine culture before starting antibiotics
• Culture confirmation is essential for tailoring therapy based on bacterial sensitivities
• Blood cultures are not needed for uncomplicated cases but should be considered for:
  • Patients with uncertain diagnosis
  • Immunocompromised patients
  • Suspected hematogenous infections

Treatment Algorithm

Outpatient Management (Uncomplicated Pyelonephritis)

1. First-line oral options (for patients who can tolerate oral therapy):

   • Fluoroquinolones: Levofloxacin 750 mg once daily for 5-7 days 1, 2
   • Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 7-14 days (if local resistance <20%) 1

2. When local resistance to chosen oral antibiotic likely exceeds 10%:

   • Administer one dose of a long-acting parenteral antibiotic (e.g., ceftriaxone) while awaiting susceptibility results 3, 4
   • Recent evidence shows long-acting IV antibiotics in the ED significantly decrease rates of initial inactive therapy 4

3. Alternative oral options:

   • Cephalexin 500 mg four times daily for 5-7 days
   • Amoxicillin-clavulanate (based on susceptibility testing) 1

Inpatient Management (Complicated Pyelonephritis)

Indications for hospitalization:

• Complicated infections
• Sepsis
• Persistent vomiting
• Failed outpatient treatment
• Extremes of age
• Pregnancy (high risk for complications)

Intravenous treatment options:

1. First-line IV options:

   • Fluoroquinolones (e.g., levofloxacin) 1, 5
   • Third-generation cephalosporins (e.g., ceftriaxone) 1, 6
   • ZERBAXA (ceftolozane-tazobactam) 1.5 g IV every 8 hours for 7 days 7

2. For suspected extended-spectrum beta-lactamase (ESBL) producing organisms:

   • Carbapenems
   • ZERBAXA (ceftolozane-tazobactam) 7, 3

Dosage Adjustments for Renal Impairment

Levofloxacin Dosing Based on Creatinine Clearance 1:

• CrCl ≥50 mL/min: 750 mg once daily
• CrCl 26-49 mL/min: 750 mg once daily
• CrCl 10-25 mL/min: 250 mg once daily

ZERBAXA (Ceftolozane-Tazobactam) Dosing Based on CrCl 7:

• CrCl >50 mL/min: 1.5 g every 8 hours
• CrCl 30-50 mL/min: 750 mg every 8 hours
• CrCl 15-29 mL/min: 375 mg every 8 hours
• ESRD on hemodialysis: Loading dose of 750 mg, then 150 mg every 8 hours

Duration of Therapy

• Standard duration: 7-14 days 1, 5
• Shorter courses (5-7 days) may be sufficient for uncomplicated cases with fluoroquinolones 1, 3
• Longer courses (10-14 days) for complicated cases 1

Follow-up

• Monitor for symptom resolution within 48-72 hours 1
• If no improvement after 48-72 hours:
  • Repeat urine culture
  • Consider imaging studies
  • Consider alternative diagnoses
  • Evaluate for urinary tract obstruction (may require urgent decompression)
• Repeat urine culture 1-2 weeks after completion of antibiotic therapy 5

Special Considerations

• Pregnancy: Admit for initial parenteral therapy due to high risk of complications 3
• Elderly patients: Consider renal function when selecting antibiotics 1
• Diabetic patients: Higher risk for complications; require careful follow-up 1
• CKD patients: Higher risk for antibiotic resistance; adjust doses based on renal function 1

Common Pitfalls to Avoid

1. Not obtaining urine culture before starting antibiotics

   • Always collect specimens before initiating treatment

2. Using fluoroquinolones as empiric therapy in areas with high resistance

   • Consider local resistance patterns; add a dose of parenteral antibiotic when resistance exceeds 10%

3. Inadequate treatment duration

   • Too short: risk of treatment failure
   • Too long: unnecessary exposure to antibiotics, increased resistance risk

4. Not adjusting therapy based on culture results

   • Always review and adjust treatment once susceptibility results are available

5. Missing concurrent urinary tract obstruction

   • Consider imaging in patients who don't respond to appropriate therapy