What is the recommended treatment for pyelonephritis?

Treatment of Pyelonephritis

For uncomplicated pyelonephritis in outpatients, oral ciprofloxacin 500 mg twice daily for 7 days or levofloxacin 750 mg once daily for 5 days is the first-line treatment when local fluoroquinolone resistance is below 10%. 1

Initial Diagnostic Steps

Before starting any antibiotic therapy, you must obtain:

• Urine culture with antimicrobial susceptibility testing in all patients 1, 2
• Urinalysis to confirm the diagnosis (leukocyte esterase and nitrite testing has 75-84% sensitivity) 3

Blood cultures are unnecessary in uncomplicated cases and should be reserved for immunocompromised patients, uncertain diagnoses, or suspected hematogenous infections 3, 2.

Outpatient Treatment Algorithm

When Fluoroquinolone Resistance is <10%:

First-line options:

• Ciprofloxacin 500 mg PO twice daily for 7 days 1
• Ciprofloxacin 1000 mg extended-release PO once daily for 7 days 1
• Levofloxacin 750 mg PO once daily for 5 days 1, 4

When Fluoroquinolone Resistance is ≥10%:

You must give one dose of a long-acting parenteral antibiotic first, then start oral therapy: 1, 2

• Ceftriaxone 1g IV once, followed by oral fluoroquinolone 1
• OR aminoglycoside (gentamicin 5-7 mg/kg) IV once, followed by oral fluoroquinolone 1

Alternative Oral Therapy (if pathogen is known to be susceptible):

• Trimethoprim-sulfamethoxazole 160/800 mg (double-strength) PO twice daily for 14 days 1

Critical pitfall: Oral β-lactams should not be used as monotherapy without an initial parenteral dose due to inferior efficacy 1. TMP-SMX and β-lactams have high resistance rates and should only be used when susceptibility is confirmed 5, 3.

Inpatient Treatment

Hospitalization is indicated for:

• Severe illness or sepsis 1, 2
• Inability to tolerate oral medications 3
• Failed outpatient treatment 3
• Pregnancy 2
• Suspected complications (obstruction, abscess) 2

Inpatient IV Antibiotic Options:

Choose based on local resistance patterns and adjust per culture results 1:

• Fluoroquinolone (levofloxacin 750 mg IV daily) 1
• Extended-spectrum cephalosporin (ceftriaxone 1-2g IV daily) 1, 6
• Aminoglycoside (gentamicin 5-7 mg/kg IV once daily) with or without ampicillin 1
• Extended-spectrum penicillin with or without aminoglycoside 1
• Carbapenem (for suspected extended-spectrum beta-lactamase producers or multidrug-resistant organisms) 1, 2

Treatment Duration by Antibiotic Class

• Fluoroquinolones: 5-7 days 1
• Trimethoprim-sulfamethoxazole: 14 days 1
• β-lactams: 10-14 days 1

Adjusting Therapy

Switch from IV to oral therapy when:

• Clinical improvement occurs (typically within 48-72 hours) 2
• Patient can tolerate oral medications 3
• Culture results confirm susceptibility to oral agent 1

Always adjust empiric therapy based on culture and susceptibility results 1, 2.

Special Populations

Elderly patients: Monitor closely for adverse effects, particularly nephrotoxicity with aminoglycosides and neuropsychiatric effects with fluoroquinolones 1, 6.

Pregnant patients: Require hospital admission and initial parenteral therapy due to significantly elevated risk of severe complications 2.

When Treatment Fails

If no improvement within 48-72 hours 2:

• Obtain repeat urine and blood cultures 3
• Perform imaging (contrast-enhanced CT) to evaluate for complications (abscess, obstruction) 5, 2
• Consider resistant organisms or anatomic abnormalities 3
• If obstruction is present, urgent urologic decompression is required 2

Key Resistance Patterns

E. coli (the causative organism in 75-95% of cases) shows increasing resistance 1, 7:

• Fluoroquinolone resistance: 10-18% in community settings, higher in hospitals 6
• Third-generation cephalosporin resistance: rising rapidly (10% in some areas) 6
• TMP-SMX resistance: approximately 55% 7

This is why obtaining cultures before starting antibiotics and adjusting therapy based on susceptibility results is non-negotiable 1, 2.

Common Pitfalls to Avoid

• Never start antibiotics without obtaining urine culture first 1
• Never use fluoroquinolones empirically in areas with >10% resistance without adding an initial parenteral dose 1
• Never use oral β-lactams or TMP-SMX empirically without confirmed susceptibility 1, 5
• Never use inadequate treatment duration, especially with β-lactams (must complete 10-14 days) 1
• Never fail to adjust therapy once culture results are available 1