Which antibiotics and treatment duration are recommended for an adult with acute uncomplicated pyelonephritis, including first‑line oral agents and alternatives for contraindications or severe cases?

Antibiotic Treatment for Acute Uncomplicated Pyelonephritis in Adults

Oral ciprofloxacin 500 mg twice daily for 7 days is the first-line treatment for acute uncomplicated pyelonephritis in adults when local fluoroquinolone resistance is below 10%. 1, 2, 3

First-Line Oral Therapy (Outpatient Management)

Fluoroquinolones are the preferred agents due to superior efficacy, achieving 96-97% clinical cure rates and 99% microbiological cure rates compared to all other oral options. 1, 2

When Fluoroquinolone Resistance is <10%:

• Ciprofloxacin 500 mg orally twice daily for 7 days 1, 2, 3
• Levofloxacin 750 mg orally once daily for 5 days (alternative once-daily option) 1, 2, 3
• Ciprofloxacin extended-release 1000 mg orally once daily for 7 days 1, 2

When Fluoroquinolone Resistance is ≥10%:

• Give ceftriaxone 1 g IV/IM as a single initial dose, then start oral fluoroquinolone for 5-7 days 1, 2, 3
• Alternatively, give a consolidated 24-hour aminoglycoside dose (gentamicin 5-7 mg/kg once) before starting oral fluoroquinolone 1, 2

Second-Line Oral Therapy

Trimethoprim-sulfamethoxazole (TMP-SMX) 160/800 mg (double-strength) orally twice daily for 14 days should only be used when the uropathogen is proven susceptible on culture. 1, 2, 3

• TMP-SMX has inferior efficacy: 83% clinical cure and 89% microbiological cure versus 96% and 99% for fluoroquinolones 2
• If TMP-SMX must be started empirically, give ceftriaxone 1 g IV/IM first 2, 3
• Requires 14 days of treatment (twice as long as fluoroquinolones) 1, 2, 3
• High resistance rates (>10% in many regions) make empiric use problematic 1, 4

Third-Line Oral Therapy (When Fluoroquinolones and TMP-SMX Cannot Be Used)

Oral β-lactams are markedly inferior with clinical cure rates of only 58-60% compared to 77-96% for fluoroquinolones. 2, 3

If oral β-lactams must be used:

• Always give ceftriaxone 1 g IV/IM as initial dose 1, 2, 3
• Then amoxicillin-clavulanate 500/125 mg orally twice daily for 10-14 days 2, 3
• Or cefpodoxime 200 mg orally twice daily for 10-14 days 3
• Or ceftibuten 400 mg orally once daily for 10 days 3

Inpatient IV Therapy (For Severe Cases or Inability to Tolerate Oral)

Indications for hospitalization: 2, 3

• Sepsis or hemodynamic instability
• Persistent vomiting preventing oral intake
• Immunosuppression or diabetes mellitus
• Suspected complicated infection (obstruction, abscess)
• Pregnancy
• Failed outpatient therapy

IV antibiotic options (choose based on local resistance patterns): 1, 2, 3

• Ciprofloxacin 400 mg IV twice daily 3
• Levofloxacin 750 mg IV once daily 3
• Ceftriaxone 1-2 g IV once daily 3, 5
• Cefepime 1-2 g IV twice daily 2, 3
• Piperacillin-tazobactam 2.5-4.5 g IV three times daily 3
• Gentamicin 5 mg/kg IV once daily (with or without ampicillin) 1, 2, 3
• Carbapenems (meropenem 1 g IV three times daily) for suspected multidrug-resistant organisms 2, 3

Total IV treatment duration: 10-14 days for β-lactams; switch to oral therapy once patient can tolerate and is clinically improving. 2, 3

Essential Management Principles

• Always obtain urine culture and susceptibility testing before starting antibiotics 1, 2, 3
• Adjust therapy based on culture results once available 1, 2, 3
• 95% of patients should be afebrile within 48 hours; nearly 100% within 72 hours 2, 3
• If no improvement by 48-72 hours, obtain CT imaging to evaluate for complications (abscess, obstruction, emphysematous pyelonephritis) 2, 3

Treatment Duration Summary

• Fluoroquinolones: 5-7 days 1, 2, 3
• TMP-SMX: 14 days 1, 2, 3
• β-lactams: 10-14 days 1, 2, 3

Critical Pitfalls to Avoid

• Never use fluoroquinolones empirically in areas with >10% resistance without an initial parenteral dose 1, 2, 3
• Never use oral β-lactams as monotherapy without an initial IV ceftriaxone or aminoglycoside dose 1, 2, 3
• Never use TMP-SMX empirically without culture confirmation or without an initial parenteral dose 2, 3
• Never use nitrofurantoin or oral fosfomycin for pyelonephritis (insufficient efficacy data) 3
• Never treat β-lactam regimens for less than 10 days (increases recurrence risk) 1, 2, 3
• Never fail to obtain urine cultures before starting antibiotics 1, 2, 3
• Never fail to adjust therapy based on culture results 1, 2, 3

Special Populations

Elderly patients: Monitor closely for adverse effects, particularly with aminoglycosides and fluoroquinolones; adjust doses for renal impairment. 2, 3

Patients with diabetes or chronic kidney disease: Higher risk for complications including renal abscess and emphysematous pyelonephritis; consider hospitalization for IV therapy. 2, 3

Pregnant patients: Require hospitalization; avoid fluoroquinolones and TMP-SMX; use ceftriaxone or other β-lactams. 3