What antibiotics are used to treat pyelonephritis?

Antibiotics for Pyelonephritis

For pyelonephritis, the first-line empiric therapy should be an IV third-generation cephalosporin (e.g., ceftriaxone 1-2g daily) before culture results, which has superior clinical and microbiological cure rates compared to fluoroquinolones. 1

First-Line Empiric Treatment Options

Inpatient Treatment

• Ceftriaxone: 1-2g IV once daily (higher dose recommended) 1
• Cefepime: 1-2g IV twice daily 1
• Piperacillin/tazobactam: 2.5-4.5g IV three times daily 1
• Ciprofloxacin: 400mg IV twice daily (consider local resistance patterns) 1
• Levofloxacin: 750mg IV once daily 1

Outpatient Treatment

• Fluoroquinolones:
  • Ciprofloxacin 500mg PO twice daily for 7 days 2, 3
  • Levofloxacin 750mg PO once daily for 5 days 4
• TMP-SMX: 14-day course when susceptibility is known 2
• Oral cephalosporins: Consider when fluoroquinolone resistance is high 5

Treatment Duration

• Fluoroquinolones:
  • 5-7 days for levofloxacin 750mg daily 1, 4
  • 7 days for ciprofloxacin (shown to be as effective as 14 days) 3
• TMP-SMX: 14 days when susceptibility is confirmed 2
• Total treatment duration: 10-14 days generally recommended 1

Evidence-Based Considerations

Recent evidence shows that shorter courses of antibiotics can be effective for pyelonephritis:

• A randomized controlled trial demonstrated that 7-day ciprofloxacin treatment was non-inferior to 14 days, with clinical cure rates of 97% vs 96% 3
• Three recent RCTs showed that a 5-day course of fluoroquinolones was noninferior to a 10-day course, with clinical cure rates above 93% 2
• The FDA label for levofloxacin supports a 5-day treatment regimen for acute pyelonephritis 4

Antibiotic Selection Based on Resistance Patterns

• Local E. coli resistance patterns should guide empiric therapy selection 1
• Fluoroquinolones should not be used empirically if local resistance rates exceed 10% 6
• TMP-SMX should not be used alone as empirical therapy without culture and susceptibility testing 2
• When fluoroquinolone resistance is high, consider starting with a third-generation cephalosporin 1, 7

Special Populations

Pregnant Women

• Avoid fluoroquinolones and aminoglycosides during pregnancy 1
• First-line options: Ceftriaxone or extended-spectrum cephalosporins 1
• Require inpatient management, especially with fever, severe flank pain, nausea/vomiting, signs of sepsis 1

Elderly Patients

• May present with atypical symptoms 1
• Up to 30% may have complicated infections requiring additional interventions 1
• Use caution with fluoroquinolones due to increased risk of tendon disorders 8

Immunocompromised Patients

• Consider broader initial coverage with combination therapy 1
• Tailor therapy based on culture results 1

Follow-up and Monitoring

• Evaluate clinical response within 48-72 hours of starting treatment 1
• Obtain follow-up urine culture 1-2 weeks after completing therapy 1
• For pregnant patients, monthly urine cultures should be obtained until delivery 1

Common Pitfalls to Avoid

1. Inadequate initial empiric coverage: Ensure coverage against the most common pathogens (E. coli accounts for >75% of cases) 2
2. Failure to adjust therapy based on culture results: Always tailor treatment once susceptibility results are available 1
3. Overlooking anatomical abnormalities: Consider imaging in cases of recurrent infections or treatment failure 1
4. Using broad-spectrum antibiotics unnecessarily: Reserve broader coverage for severe cases to prevent resistance development 7
5. Inadequate treatment duration: While shorter courses are becoming more accepted, ensure adequate duration based on clinical response 1

Recent evidence suggests oral cephalosporins may be as effective as first-line agents for outpatient treatment of pyelonephritis, with no significant difference in UTI recurrence rates (16% vs 17%) 5, providing an alternative when fluoroquinolone resistance is high.