What are the recommended antibiotics for treating pyelonephritis in adults?

Antibiotic Treatment for Pyelonephritis in Adults

For outpatient uncomplicated pyelonephritis, oral fluoroquinolones are first-line therapy: ciprofloxacin 500 mg twice daily for 7 days or levofloxacin 750 mg once daily for 5 days, but only when local fluoroquinolone resistance is below 10%. 1

Initial Assessment

• Always obtain urine culture and susceptibility testing before initiating antibiotics to allow therapy adjustment based on pathogen susceptibility 1
• Assess local fluoroquinolone resistance patterns—this determines whether empirical fluoroquinolone therapy is appropriate 1
• Determine if the patient requires hospitalization based on severity of illness, sepsis, persistent vomiting, extremes of age, or complicated infection 1

Outpatient Treatment Algorithm

When Local Fluoroquinolone Resistance is <10%

First-line options:

• Ciprofloxacin 500-750 mg orally twice daily for 7 days (with or without an initial 400 mg IV dose) 1, 2, 3
• Levofloxacin 750 mg orally once daily for 5 days 1, 2, 3
• Ciprofloxacin extended-release 1000 mg orally once daily for 7 days 1

These fluoroquinolone regimens achieve approximately 96% symptom resolution 2, 4

When Local Fluoroquinolone Resistance is ≥10%

Administer an initial IV dose of a long-acting parenteral antimicrobial before starting oral fluoroquinolone therapy: 1, 2

• Ceftriaxone 1 g IV once, then oral fluoroquinolone 1, 2
• OR consolidated 24-hour dose of aminoglycoside (gentamicin 5 mg/kg or amikacin 15 mg/kg), then oral fluoroquinolone 1

Alternative Oral Agents (Less Preferred)

• Trimethoprim-sulfamethoxazole 160/800 mg (one double-strength tablet) twice daily for 14 days—only use if the pathogen is known to be susceptible 1, 2

  • If susceptibility is unknown, give initial IV ceftriaxone 1 g or aminoglycoside before starting trimethoprim-sulfamethoxazole 1

• Oral β-lactam agents (cefpodoxime 200 mg twice daily for 10 days or ceftibuten 400 mg once daily for 10 days) are significantly less effective than fluoroquinolones 1, 2

  • If used, always give initial IV ceftriaxone 1 g or aminoglycoside 1
  • Require 10-14 days of therapy 1

Inpatient Treatment Algorithm

Hospitalized patients require initial IV antimicrobial therapy, with choice based on local resistance patterns: 1

First-line IV Options:

• Ciprofloxacin 400 mg IV twice daily 1, 2
• Levofloxacin 750 mg IV once daily 1, 2, 3
• Ceftriaxone 1-2 g IV once daily (lower dose studied but higher dose recommended) 1, 2
• Cefotaxime 2 g IV three times daily (not studied as monotherapy but recommended) 1
• Cefepime 1-2 g IV twice daily (lower dose studied but higher dose recommended) 1, 5
• Gentamicin 5 mg/kg IV once daily (with or without ampicillin; not studied as monotherapy) 1, 2
• Amikacin 15 mg/kg IV once daily 1, 2
• Piperacillin/tazobactam 2.5-4.5 g IV three times daily 1, 2

Reserve for Multidrug-Resistant Organisms Only:

Do not use carbapenems or novel broad-spectrum agents empirically—reserve them only for patients with early culture results showing multidrug-resistant organisms: 1, 2

• Imipenem/cilastatin 0.5 g IV three times daily 1
• Meropenem 1 g IV three times daily 1
• Ceftolozane/tazobactam 1.5 g IV three times daily 1
• Ceftazidime/avibactam 2.5 g IV three times daily 1

Special Clinical Scenarios

Pyelonephritis with Frank Hematuria

• Frank hematuria indicates a complicated infection requiring urgent upper urinary tract imaging (ultrasound or CT) to rule out obstruction, abscess, or stones 2, 6
• Manage as inpatient with IV antibiotics following the hospitalized patient algorithm above 2, 6
• If obstruction is present, urgent decompression of the collecting system must be performed alongside antimicrobial therapy 2, 6

Treatment Failure

• If no improvement after 72 hours, obtain additional imaging and modify therapy based on culture results 2
• Consider resistant organisms, underlying anatomic/functional abnormalities, or immunosuppression 7, 8
• Repeat blood and urine cultures 7

Duration of Therapy

• Fluoroquinolones: 5-7 days 1, 2, 3
• Trimethoprim-sulfamethoxazole: 14 days 1, 2
• Oral β-lactams: 10-14 days 1
• IV therapy: 7-10 days for most complicated infections 1

Critical Pitfalls to Avoid

• Never use oral β-lactams as first-line therapy—they are significantly less effective than fluoroquinolones 1, 2
• Do not use trimethoprim-sulfamethoxazole empirically without an initial parenteral dose unless susceptibility is confirmed 1, 2
• Avoid nitrofurantoin, oral fosfomycin, and pivmecillinam for pyelonephritis—insufficient efficacy data 1
• Do not use carbapenems empirically—reserve them for documented multidrug-resistant organisms to preserve their efficacy 1, 2
• Do not overlook the need for imaging in patients with hematuria, persistent symptoms, or suspected complications 2, 6
• Recent observational data show only 40.4% of ED patients with pyelonephritis receive empirical IV antibiotics, contributing to inactive therapy—administering long-acting IV antibiotics empirically reduces this risk 9

Follow-up

• Repeat urine culture 1-2 weeks after completion of antibiotic therapy 7
• Tailor ongoing therapy based on culture and susceptibility results as soon as available 1, 2