Pyelonephritis Antibiotic of Choice
For an otherwise healthy adult with acute uncomplicated pyelonephritis, oral ciprofloxacin 500 mg twice daily for 7 days is the first-line antibiotic when local fluoroquinolone resistance is below 10%. 1, 2
Primary Treatment Algorithm
First-Line: Oral Fluoroquinolones (when local resistance <10%)
Ciprofloxacin 500 mg orally twice daily for 7 days is the preferred regimen, achieving 96-97% clinical cure and 99% microbiological cure rates. 1, 2
Levofloxacin 750 mg orally once daily for 5 days is an equally effective once-daily alternative. 1, 2
Ciprofloxacin extended-release 1000 mg once daily for 7 days is another acceptable option. 1, 2
Modified Approach When Fluoroquinolone Resistance ≥10%
Give a single dose of ceftriaxone 1 g IV/IM first, then continue oral ciprofloxacin 500 mg twice daily for 5-7 days. 1, 2
Alternatively, administer gentamicin 5-7 mg/kg IV/IM once before starting the oral fluoroquinolone course. 1, 2
Second-Line: Trimethoprim-Sulfamethoxazole
TMP-SMX 160/800 mg (double-strength) twice daily for 14 days may be used only when the uropathogen is proven susceptible on culture. 1, 2
TMP-SMX achieves only 83% clinical cure and 89% microbiological cure—markedly inferior to fluoroquinolones' 96%/99% rates. 1
The 14-day duration is twice as long as fluoroquinolone therapy. 1, 2
If TMP-SMX must be started empirically, give ceftriaxone 1 g IV/IM first. 1, 2
Third-Line: Oral β-Lactams (Least Effective)
Oral β-lactams achieve only 58-60% clinical cure rates compared to 77-96% with fluoroquinolones and should be avoided when possible. 1
If an oral β-lactam must be used, an initial dose of ceftriaxone 1 g IV/IM is mandatory, followed by: 1, 2
- Amoxicillin-clavulanate 500/125 mg twice daily for 10-14 days, or
- Cefpodoxime 200 mg twice daily for 10-14 days, or
- Ceftibuten 400 mg once daily for 10 days
Treatment duration must be 10-14 days with β-lactams (longer than fluoroquinolones). 1, 2
Essential Management Principles
Always obtain urine culture and susceptibility testing before initiating antibiotics to guide definitive therapy. 1, 2
Adjust antimicrobial therapy promptly based on culture results. 1, 2
Approximately 95% of patients should become afebrile within 48 hours of appropriate therapy, and nearly 100% within 72 hours. 1
If the patient remains febrile at 72 hours, obtain CT imaging to evaluate for complications such as abscess or obstruction. 1
Critical Pitfalls to Avoid
Do not use fluoroquinolones empirically in regions with >10% resistance without first giving an IV ceftriaxone or aminoglycoside dose—this leads to treatment failure. 1, 2
Do not employ oral β-lactams as monotherapy without a preceding parenteral dose—their 58-60% cure rate is unacceptably low. 1, 2
Do not start TMP-SMX empirically without culture confirmation or without an initial parenteral dose—resistance rates often exceed 10%. 1, 2
Do not treat β-lactam regimens for fewer than 10 days—shorter courses increase recurrence risk. 1, 2
Do not use nitrofurantoin or oral fosfomycin for pyelonephritis—efficacy data are insufficient. 1