What is the first-line treatment for an otherwise healthy adult patient with pyelonephritis?

First-Line Treatment for Pyelonephritis in Otherwise Healthy Adults

For outpatient treatment of acute uncomplicated pyelonephritis, oral fluoroquinolones are the first-line therapy when local fluoroquinolone resistance rates are ≤10%, specifically ciprofloxacin 500 mg twice daily for 7 days or levofloxacin 750 mg once daily for 5 days. 1

Treatment Algorithm Based on Local Resistance Patterns

When Fluoroquinolone Resistance ≤10%

• Preferred oral regimens for outpatient management:

  • Ciprofloxacin 500 mg twice daily for 7 days 1
  • Ciprofloxacin 1000 mg extended-release once daily for 7 days 1
  • Levofloxacin 750 mg once daily for 5 days 1, 2

• An initial one-time IV dose (ciprofloxacin 400 mg, ceftriaxone 1 g, or consolidated 24-hour aminoglycoside dose) may be added at clinician discretion but is not mandatory 1

When Fluoroquinolone Resistance >10%

If local resistance exceeds 10%, you must give an initial IV dose of a long-acting parenteral antimicrobial before starting oral fluoroquinolone therapy: 1

• Ceftriaxone 1 g IV once, OR
• Consolidated 24-hour aminoglycoside dose IV once
• Then proceed with oral fluoroquinolone regimen as above

Alternative Regimens (When Fluoroquinolones Cannot Be Used)

Trimethoprim-Sulfamethoxazole

• Only use if the pathogen is known to be susceptible 1
• Dose: 160/800 mg (one double-strength tablet) twice daily for 14 days 1
• If susceptibility unknown, give initial IV ceftriaxone 1 g or aminoglycoside before starting therapy 1
• Important caveat: Contemporary E. coli resistance rates limit utility as first-line empiric treatment 1

Beta-Lactam Agents

• Beta-lactams are less effective than fluoroquinolones or TMP-SMX for pyelonephritis 1
• If used, always give initial IV ceftriaxone 1 g or aminoglycoside dose 1
• Duration: 10-14 days 1
• Should be reserved for situations where other agents cannot be used 1

Inpatient Treatment (For Severe Illness or Complications)

Hospitalized patients require initial IV therapy with one of the following: 1

• IV fluoroquinolone (ciprofloxacin or levofloxacin)
• Aminoglycoside with or without ampicillin
• Extended-spectrum cephalosporin (e.g., ceftriaxone) with or without aminoglycoside
• Extended-spectrum penicillin with or without aminoglycoside
• Carbapenem

The choice should be based on local resistance data, and therapy should be tailored once susceptibility results are available 1

Essential Management Steps

Always Obtain Cultures

Urine culture and susceptibility testing must be performed in all patients with suspected pyelonephritis before initiating therapy 1. This allows tailoring of empiric therapy based on the infecting uropathogen 1.

Key Resistance Considerations

• E. coli causes 75-95% of uncomplicated pyelonephritis cases 1
• Local antimicrobial susceptibility patterns of E. coli should guide empiric selection 1
• Resistance rates vary considerably by geographic region 1
• High resistance rates have been documented for TMP-SMX (55%), ciprofloxacin (48%), and ceftriaxone (34%) in some regions 3

Common Pitfalls to Avoid

• Do not use amoxicillin or ampicillin empirically due to very high worldwide resistance rates and poor efficacy 1
• Do not use oral beta-lactams as first-line therapy without an initial parenteral dose, as they have inferior efficacy compared to fluoroquinolones 1
• Do not use TMP-SMX empirically without knowing susceptibility or without giving an initial parenteral dose, given contemporary resistance patterns 1
• Do not use fluoroquinolones empirically if local resistance exceeds 10% without an initial parenteral dose 1

Duration of Therapy Summary

• Fluoroquinolones: 5-7 days depending on agent 1, 2
• TMP-SMX: 14 days 1
• Beta-lactams: 10-14 days 1