What is the first‑line empiric antibiotic regimen, including drug, dose, route, and duration, for an adult with uncomplicated community‑acquired acute pyelonephritis who has no drug allergies, normal renal function, is not pregnant, and has not been recently hospitalized?

First-Line Empiric Antibiotic Regimen for Uncomplicated Community-Acquired Acute Pyelonephritis

Oral ciprofloxacin 500 mg twice daily for 7 days is the first-line empiric regimen for uncomplicated acute pyelonephritis in adults when local fluoroquinolone resistance is below 10%. 1, 2

Primary Oral Regimen (Outpatient Management)

When local fluoroquinolone resistance is <10%:

• Ciprofloxacin 500 mg orally twice daily for 7 days is the preferred first-line option, achieving 96% clinical cure and 99% microbiological eradication rates. 1, 2

• Alternative once-daily regimens include:

  • Levofloxacin 750 mg orally once daily for 5 days 1, 2
  • Ciprofloxacin extended-release 1000 mg orally once daily for 7 days 1

When local fluoroquinolone resistance is ≥10%:

• Administer one initial dose of ceftriaxone 1 g IV or IM, then continue oral ciprofloxacin 500 mg twice daily for 7 days (or levofloxacin 750 mg daily for 5 days). 1, 2

• Alternatively, give a single consolidated aminoglycoside dose (gentamicin 5–7 mg/kg IV/IM once) before starting the oral fluoroquinolone course. 1

Second-Line Oral Option

• Trimethoprim-sulfamethoxazole (TMP-SMX) 160/800 mg (double-strength) orally 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%). 1

• If TMP-SMX must be started empirically before culture results, give an initial dose of ceftriaxone 1 g IV/IM first. 1

Third-Line Oral β-Lactam Options (Require Initial Parenteral Dose)

• Oral β-lactams alone achieve only 58–60% clinical cure rates versus 77–96% for fluoroquinolones and should never be used as monotherapy. 1, 2

• If an oral β-lactam must be used, always give ceftriaxone 1 g IV/IM first, then continue with one of the following for 10–14 days:

  • Amoxicillin-clavulanate 500/125 mg twice daily 1
  • Cefpodoxime 200 mg twice daily 1
  • Cefdinir for 10–14 days 1

Essential Management Principles

• Obtain urine culture and susceptibility testing before initiating antibiotics to allow subsequent therapy adjustment. 1, 2

• Adjust antimicrobial therapy based on culture results once available. 1, 2

• Approximately 95% of patients with uncomplicated pyelonephritis become afebrile within 48 hours of appropriate therapy, and nearly 100% within 72 hours. 2

Treatment Duration Summary

• Fluoroquinolones: 5–7 days 1, 2
• TMP-SMX: 14 days 1, 2
• Oral or IV β-lactams: 10–14 days 1, 2

Critical Pitfalls to Avoid

• Do not use fluoroquinolones empirically in regions with >10% resistance without first giving an initial parenteral dose (ceftriaxone or aminoglycoside). 1, 2

• Do not employ oral β-lactams as monotherapy without a preceding parenteral dose, as this leads to failure rates of 40–42%. 1, 2

• Do not start TMP-SMX empirically without culture confirmation when regional resistance is high or without an initial parenteral dose. 1

• Do not treat β-lactam regimens for less than 10 days, which increases recurrence risk. 1

• Do not omit urine cultures before initiating antibiotics; failing to adjust therapy based on culture results is a common error. 1, 2

• Do not use nitrofurantoin or oral fosfomycin for pyelonephritis, as efficacy data are insufficient for upper urinary tract infections. 2