Treatment of Pyelonephritis
For outpatient treatment of acute pyelonephritis, oral ciprofloxacin 500 mg twice daily for 7 days is the first-line therapy when local fluoroquinolone resistance is below 10%, with levofloxacin 750 mg once daily for 5 days as an equally effective alternative. 1, 2
Initial Assessment
- Always obtain urine culture and susceptibility testing before initiating antibiotics to guide definitive therapy and adjust treatment based on culture results. 1, 2
- Tailor initial empirical therapy based on local resistance patterns, particularly fluoroquinolone resistance rates in your community. 1, 2
Outpatient Treatment Algorithm
When Fluoroquinolone Resistance is <10%:
First-line options:
- Ciprofloxacin 500 mg orally twice daily for 7 days (with or without an initial 400 mg IV dose). 1, 2
- Levofloxacin 750 mg orally once daily for 5 days as an equally effective alternative. 1, 2, 3
- Ciprofloxacin 1000 mg extended-release orally once daily for 7 days is also appropriate. 1, 2
The 7-day ciprofloxacin regimen is supported by high-quality evidence showing 97% short-term clinical cure rates and 93% long-term efficacy, with no difference compared to 14-day treatment. 4
When Fluoroquinolone Resistance is >10%:
- Administer an initial one-time IV dose of ceftriaxone 1 g OR a consolidated 24-hour dose of an aminoglycoside (e.g., gentamicin 5-7 mg/kg), followed by oral fluoroquinolone therapy. 1, 2
Alternative Therapy (when fluoroquinolones cannot be used):
- Trimethoprim-sulfamethoxazole 160/800 mg (double-strength tablet) twice daily for 14 days ONLY if the uropathogen is known to be susceptible. 1, 2
- If using TMP-SMX empirically when susceptibility is unknown, give an initial IV dose of ceftriaxone 1 g or aminoglycoside first. 1
Inpatient Treatment
Indications for hospitalization include: complicated infections, sepsis, persistent vomiting, failed outpatient treatment, or extremes of age. 5
IV antibiotic options:
- Fluoroquinolone (ciprofloxacin or levofloxacin) 2, 5
- Aminoglycoside with or without ampicillin 2, 5
- Extended-spectrum cephalosporin (e.g., ceftriaxone) 2, 5
- Extended-spectrum penicillin with or without aminoglycoside 2, 5
- Carbapenem 2
Choice should be based on local resistance patterns and adjusted according to culture results. 2
Treatment Duration by Antibiotic Class
- Fluoroquinolones: 5-7 days depending on the specific agent (levofloxacin 5 days, ciprofloxacin 7 days). 1, 2, 4
- Trimethoprim-sulfamethoxazole: 14 days (traditional recommendation). 1, 2
- β-lactams: 10-14 days (longer duration required due to inferior efficacy). 2
Evidence Considerations
The superiority of fluoroquinolones is well-established, with ciprofloxacin demonstrating significantly higher microbiological cure rates (99% vs 89%) and clinical cure rates (96% vs 83%) compared to trimethoprim-sulfamethoxazole. 1, 6 The 5-day levofloxacin 750 mg regimen was proven non-inferior to 10-day ciprofloxacin in a large randomized trial of 1109 patients. 3
Common Pitfalls to Avoid
- Never start antibiotics without obtaining urine cultures first - this is the most critical error that limits your ability to adjust therapy. 2
- Do not use fluoroquinolones empirically in areas with >10% resistance without adding an initial parenteral dose - this significantly reduces treatment failure. 2, 6
- Avoid oral β-lactams as monotherapy without an initial parenteral dose - they have inferior efficacy compared to fluoroquinolones. 1, 2, 6
- Do not use amoxicillin or ampicillin empirically - resistance rates are extremely high worldwide. 1
- Never fail to adjust therapy based on culture results - even if the patient is improving clinically. 2
- Avoid inadequate treatment duration with β-lactam agents - they require 10-14 days, not the shorter courses used for fluoroquinolones. 2