What are the recommended oral antibiotics for treating pyelonephritis?

Oral Antibiotics for Pyelonephritis

For outpatient treatment of acute uncomplicated pyelonephritis, use oral levofloxacin 750mg once daily for 5-7 days as first-line therapy if local fluoroquinolone resistance is <10%, or give a single dose of ceftriaxone 1g IV/IM followed by oral trimethoprim-sulfamethoxazole 160/800mg twice daily for 14 days if fluoroquinolone resistance exceeds 10%. 1

First-Line Oral Regimens

Fluoroquinolone Options (When Local Resistance <10%)

• Levofloxacin 750mg orally once daily for 5-7 days is the preferred fluoroquinolone regimen, offering superior outcomes compared to lower doses and once-daily convenience that improves adherence 1, 2
• Ciprofloxacin 500mg orally twice daily for 7 days is an alternative fluoroquinolone option 1, 3, 4
• Critical caveat: Always check your local antibiogram before prescribing fluoroquinolones—if resistance exceeds 10% in your area, choose an alternative regimen 1

Beta-Lactam-Based Regimen (When Fluoroquinolone Resistance >10%)

• Give ceftriaxone 1g IV or IM as a single dose, then transition to oral trimethoprim-sulfamethoxazole 160/800mg twice daily for 14 days (only if susceptible on culture) 1, 5
• This strategy is specifically recommended when fluoroquinolone resistance exceeds 10% in your practice area 1

Duration of Therapy by Antibiotic Class

• Fluoroquinolones (levofloxacin, ciprofloxacin): 5-7 days 1, 5
• Trimethoprim-sulfamethoxazole: 14 days 1, 3
• Beta-lactam antibiotics: 10-14 days 1, 3

Essential Pre-Treatment Actions

• Always obtain urine culture and susceptibility testing before starting empirical therapy and adjust treatment based on results 1, 3
• Check your local antibiogram to determine if fluoroquinolone resistance exceeds 10% in your practice area 1
• Obtain imaging (ultrasound) if you suspect obstruction, stones, or anatomic abnormalities—especially important with unusual pathogens or lack of clinical improvement 1, 5

Common Pitfalls to Avoid

• Never use oral cephalosporins (like cefdinir) as monotherapy for pyelonephritis—they lack sufficient evidence and have inferior outcomes 1
• Do not use amoxicillin or ampicillin for empirical treatment due to high resistance rates 3
• Do not assume all fluoroquinolones are equivalent—levofloxacin 750mg has better outcomes than lower doses or other fluoroquinolones like norfloxacin 1
• Beta-lactam antibiotics are less effective than fluoroquinolones for pyelonephritis and should be used with caution 3

When to Consider Inpatient Treatment

• Complicated infections (urinary tract abnormalities, recent instrumentation, indwelling catheters) 1
• Sepsis or signs of urosepsis 5
• Persistent vomiting preventing oral intake 6
• Failed outpatient treatment or lack of improvement after 72 hours 5
• Extremes of age or immunocompromised status 1, 6

Follow-Up and Treatment Failure

• Transition to oral therapy after clinical improvement, based on susceptibility results 5
• Repeat urine culture 1-2 weeks after completion of antibiotic therapy 6
• If no improvement after 72 hours, obtain additional imaging (contrast-enhanced CT scan) and consider alternative diagnoses or complications 5
• If urinary tract obstruction is present, urgent decompression should be performed alongside antimicrobial therapy 1, 5