What are the recommended medications for treating pyelonephritis?

Recommended Medications for Pyelonephritis

For uncomplicated pyelonephritis, fluoroquinolones (ciprofloxacin or levofloxacin) are first-line oral therapy when local resistance is below 10%, while cephalosporins serve as alternatives or initial parenteral therapy when resistance exceeds this threshold. 1

Outpatient Oral Therapy

First-Line Options (when fluoroquinolone resistance <10%)

• Ciprofloxacin 500-750 mg twice daily for 7 days is the primary recommendation for outpatient treatment 1
• Levofloxacin 750 mg once daily for 5 days offers a convenient once-daily alternative with shorter duration 1, 2
• Ciprofloxacin extended-release 1000 mg once daily for 7 days is another once-daily option 1

When Fluoroquinolone Resistance Exceeds 10%

• Administer one initial IV dose of ceftriaxone 1-2 g or a consolidated 24-hour aminoglycoside dose, then transition to oral fluoroquinolone 1, 3
• This "loading dose" strategy bridges the gap while awaiting culture results in high-resistance areas 1

Alternative Oral Agents

• Trimethoprim-sulfamethoxazole 160/800 mg (double-strength) twice daily for 14 days is appropriate only if the pathogen is known to be susceptible 1

  • If used empirically without susceptibility data, give an initial IV dose of ceftriaxone 1 g or aminoglycoside first 1
  • Requires longer duration (14 days vs 5-7 days for fluoroquinolones) 1, 3

• Oral cephalosporins (cefpodoxime 200 mg twice daily for 10 days or ceftibuten 400 mg once daily for 10 days) are less effective than fluoroquinolones 1

  • Should be reserved for when fluoroquinolones cannot be used 1
  • Require 10-14 day treatment duration 1, 3
  • An initial IV dose of ceftriaxone or aminoglycoside is recommended if using oral β-lactams 1, 3

Inpatient Parenteral Therapy

Initial IV Regimens for Hospitalized Patients

Fluoroquinolones:

• Ciprofloxacin 400 mg IV twice daily 1
• Levofloxacin 750 mg IV once daily 1, 2

Cephalosporins:

• Ceftriaxone 1-2 g IV once daily (higher dose recommended) 1
• Cefotaxime 2 g IV three times daily 1
• Cefepime 1-2 g IV twice daily (higher dose recommended) 1

Extended-Spectrum Penicillins:

• Piperacillin-tazobactam 2.5-4.5 g IV three times daily 1

Aminoglycosides:

• Gentamicin 5 mg/kg IV once daily 1, 3
• Amikacin 15 mg/kg IV once daily 1
• Note: Not studied as monotherapy; typically combined with ampicillin 1

Reserve Agents for Multidrug-Resistant Organisms

Only use when early culture results indicate multidrug-resistant pathogens: 1

• 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
• Cefiderocol 2 g IV three times daily 1
• Meropenem-vaborbactam 2 g IV three times daily 1
• Plazomicin 15 mg/kg IV once daily 1

Treatment Duration

• Fluoroquinolones: 5-7 days depending on specific agent (levofloxacin 750 mg for 5 days, ciprofloxacin for 7 days) 1, 3
• Trimethoprim-sulfamethoxazole: 14 days 1, 3
• β-lactams: 10-14 days 1, 3

Critical Management Principles

Always Obtain Cultures First

• Urine culture with antimicrobial susceptibility testing is mandatory before initiating therapy in all pyelonephritis cases 1, 3
• Adjust empiric therapy based on culture results and local resistance patterns 1, 3

Local Resistance Patterns Drive Empiric Choice

• The 10% fluoroquinolone resistance threshold is the critical decision point for empiric therapy selection 1
• Base antibiotic selection on your institution's antibiogram, not national averages 1, 3

Avoid These Common Pitfalls

Do not use these agents for pyelonephritis: 1

• Nitrofurantoin (insufficient efficacy data for upper tract infections) 1
• Oral fosfomycin (insufficient efficacy data) 1
• Pivmecillinam (insufficient efficacy data) 1
• Amoxicillin or ampicillin alone (very high resistance rates) 1

Do not:

• Use fluoroquinolones empirically in areas with >10% resistance without an initial parenteral dose 1, 3
• Use oral β-lactams as monotherapy without an initial parenteral dose 1, 3
• Use carbapenems or novel broad-spectrum agents empirically—reserve for documented multidrug-resistant organisms 1
• Fail to adjust therapy once susceptibility results are available 3

Special Considerations

• Pregnant patients: Use ultrasound or MRI for imaging (avoid radiation), and these patients warrant hospitalization with initial parenteral therapy due to elevated complication risk 1, 4
• Elderly patients: Monitor closely for adverse effects, particularly with aminoglycosides and fluoroquinolones 3
• Suspected obstruction: Obtain imaging immediately and pursue urgent urological decompression 1, 4

When to Reassess

• If no clinical improvement within 48-72 hours, obtain imaging (contrast-enhanced CT) and repeat cultures while considering alternative diagnoses 1, 4
• Immediate imaging is warranted if clinical deterioration occurs 1