What are the recommended oral and intravenous antibiotic options for an adult with acute uncomplicated community‑acquired pyelonephritis, assuming fluoroquinolone resistance is less than 10% and there are no contraindications?

Antibiotic Treatment for Acute Uncomplicated Community-Acquired Pyelonephritis

For adults with acute uncomplicated pyelonephritis in settings where fluoroquinolone resistance is less than 10%, oral ciprofloxacin 500 mg twice daily for 7 days or levofloxacin 750 mg once daily for 5 days should be the first-line treatment. 1

Outpatient Oral Antibiotic Regimens

First-Line: Fluoroquinolones (When Resistance <10%)

Fluoroquinolones are the superior choice, achieving 96-97% clinical cure rates and 99% microbiological cure rates, markedly outperforming all other oral agents. 1

Recommended regimens:

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

Second-Line: Trimethoprim-Sulfamethoxazole (Culture-Directed Only)

TMP-SMX should only be used when the uropathogen is proven susceptible on culture, as it achieves only 83% clinical cure and 89% microbiological cure—significantly inferior to fluoroquinolones. 1

• Dose: 160/800 mg (double-strength) orally twice daily for 14 days 1
• Note the treatment duration is twice as long as fluoroquinolone therapy 1
• High regional resistance rates (>10%) preclude empiric use 1

Third-Line: Oral β-Lactams (Avoid as Monotherapy)

Oral β-lactams are markedly inferior, with clinical cure rates of only 58-60% compared to 77-96% for fluoroquinolones. 1

If an oral β-lactam must be used, you must give an initial IV dose of ceftriaxone 1 g first, then continue with: 1

• Amoxicillin-clavulanate 500/125 mg twice daily for 10-14 days, or 1
• Cefpodoxime 200 mg twice daily for 10-14 days, or 1
• Ceftibuten 400 mg once daily for 10 days 1

Never use oral β-lactams as monotherapy without the initial parenteral dose—this is a common pitfall that leads to treatment failure. 1

Inpatient Intravenous Antibiotic Options

Indications for Hospitalization and IV Therapy

Admit patients with: 1

• Immunocompromised status (transplant recipients, HIV/AIDS, chronic corticosteroids)
• Complicated pyelonephritis (obstruction, calculi, anatomic abnormalities)
• Diabetes mellitus (50% lack typical flank tenderness; higher risk of abscess)
• Nosocomial infection or suspected multidrug-resistant pathogens
• Sepsis, persistent vomiting, or inability to tolerate oral medications

IV Antibiotic Regimens

Choose based on local resistance patterns: 1

First-line options:

• Ciprofloxacin 400 mg IV twice daily 1
• Levofloxacin 750 mg IV once daily 1
• Ceftriaxone 1-2 g IV once daily 1
• Cefepime 1-2 g IV twice daily 1
• Piperacillin-tazobactam 2.5-4.5 g IV three times daily 1

Aminoglycoside option (not as monotherapy):

• Gentamicin 5 mg/kg IV once daily (often combined with ampicillin) 1

For suspected multidrug-resistant organisms:

• Meropenem 1 g IV three times daily 1
• Ceftolozane-tazobactam, ceftazidime-avibactam, or other newer agents 1

Total IV treatment duration is 10-14 days for β-lactam-based regimens; switch to oral therapy once the patient is afebrile for 24-48 hours and can tolerate oral intake. 1

Essential Management Principles

Pre-Treatment Requirements

Always obtain urine culture and susceptibility testing before initiating antibiotics, and adjust therapy promptly based on culture results. 1 This is non-negotiable for appropriate antimicrobial stewardship.

Expected Clinical Response

Approximately 95% of patients with uncomplicated pyelonephritis become afebrile within 48 hours of appropriate therapy; nearly 100% are afebrile by 72 hours. 1

If fever persists beyond 72 hours despite appropriate antibiotics, obtain contrast-enhanced CT imaging immediately to assess for abscess, obstruction, or emphysematous pyelonephritis. 1 Do not delay imaging in non-responders.

Treatment Duration Summary

• Fluoroquinolones: 5-7 days 1
• TMP-SMX: 14 days 1
• Oral or IV β-lactams: 10-14 days 1

Critical Pitfalls to Avoid

Do not use fluoroquinolones empirically in regions with >10% resistance without an initial parenteral dose of ceftriaxone 1 g IV/IM or a consolidated 24-hour aminoglycoside dose (gentamicin 5-7 mg/kg). 1 This modified approach maintains fluoroquinolone efficacy in higher-resistance settings.

Do not employ oral β-lactams as monotherapy without a preceding IV ceftriaxone or aminoglycoside dose—cure rates drop to 58-60%. 1

Do not start TMP-SMX empirically without culture confirmation of susceptibility. 1 The 83% cure rate and high resistance prevalence make empiric use unacceptable.

Do not treat β-lactam regimens for fewer than 10 days, as this increases recurrence risk. 1

Do not assume diabetic patients will present with flank tenderness—about 50% have atypical presentations. 1 Maintain high clinical suspicion in this population.

Do not omit urine cultures before antibiotic initiation, and do not fail to modify therapy based on culture results. 1 This is the cornerstone of appropriate antimicrobial use and resistance prevention.