What is the recommended treatment for pyelonephritis?

Treatment of Pyelonephritis

The recommended first-line treatment for pyelonephritis is a 5-7 day course of fluoroquinolones, such as ciprofloxacin 500mg twice daily or levofloxacin 750mg once daily, with clinical cure rates exceeding 93%. 1

Initial Assessment and Diagnosis

• Obtain urine culture before starting antibiotics to guide treatment
• Select empiric therapy based on local resistance patterns
• Clinical features typically include fever, flank pain, and positive urinalysis
• Blood cultures should be reserved for immunocompromised patients or those with suspected hematogenous infections 2

Antibiotic Selection Algorithm

First-line options:

• Fluoroquinolones (when local resistance <10%):
  • Ciprofloxacin 500mg twice daily for 5-7 days
  • Levofloxacin 750mg once daily for 5-7 days 1, 3

Alternative options:

• Trimethoprim-sulfamethoxazole for 14 days (only after culture confirms susceptibility)
• β-lactams (cephalosporins) for 10-14 days
• Cefpodoxime for 10-14 days 1

Special Populations

Pregnant patients:

• Require admission for initial parenteral therapy
• Fluoroquinolones contraindicated due to teratogenic effects 1

Patients with complicated UTI factors:

• Structural abnormalities or immunocompromised state
• Require longer treatment courses (10-14 days) 1

Patients with chronic kidney disease:

• Closer monitoring due to increased risk of recurrence
• No dose adjustment needed for CrCl ≥50 mL/min
• Dose adjustments necessary for impaired renal function 1

Inpatient vs. Outpatient Management

Indications for hospitalization:

• Complicated infections
• Sepsis
• Persistent vomiting
• Failed outpatient treatment
• Extremes of age 2

Inpatient treatment options:

• IV fluoroquinolone
• Aminoglycoside with or without ampicillin
• Third-generation cephalosporin 2, 4

Monitoring and Follow-up

• Clinical improvement expected within 48-72 hours of starting treatment
• If no improvement, reassess diagnosis, consider imaging, and adjust antibiotic choice
• Follow-up urine culture may be considered in patients with recurrent UTIs
• Monitor with CBC and CMP at the end of therapy 1

Emerging Resistance Considerations

• Fluoroquinolone resistance rates are increasing (approximately 10% in community settings and 18% in hospital settings as of 2012) 5
• E. coli resistance to third-generation cephalosporins rose from 1% in 2005 to 10% in 2012 5
• Avoid using fluoroquinolones in patients treated with quinolones in preceding months or recently hospitalized patients 5

Common Pitfalls to Avoid

• Using trimethoprim-sulfamethoxazole empirically without culture results due to high resistance rates
• Prescribing fluoroquinolones when local resistance rates exceed 10%
• Failing to adjust therapy based on culture results
• Not considering anatomical abnormalities in patients who fail to respond to appropriate therapy
• Using broader-spectrum antibiotics than necessary, which contributes to resistance development 1, 5

The 2025 Urinary Tract Infection Treatment Guidelines strongly support the efficacy of shorter treatment courses with fluoroquinolones, with multiple randomized controlled trials demonstrating that 5-7 days of therapy is noninferior to longer courses 1. This is further supported by a 2012 randomized controlled trial showing that 7 days of ciprofloxacin was as effective as 14 days for treating acute pyelonephritis in women 3.