What is the first-line treatment for pylonephritis?

First-Line Treatment for Pyelonephritis

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

Outpatient Treatment Algorithm

Primary Options for Uncomplicated Cases

• Fluoroquinolones remain the gold standard for outpatient management, with ciprofloxacin 500-750 mg twice daily for 7 days or levofloxacin 750 mg once daily for 5 days being the most effective options 1
• These agents achieve superior clinical cure rates (approximately 96% symptom resolution within 5-7 days) compared to other oral antibiotics 2

Critical Resistance Considerations

• If local fluoroquinolone resistance exceeds 10%, you must give an initial IV dose of a long-acting parenteral antimicrobial (such as ceftriaxone 1g) before starting oral therapy 1
• Always obtain urine culture and susceptibility testing before initiating antibiotics to guide subsequent therapy adjustments 3, 1
• Local resistance patterns should dictate your empiric therapy selection—this is not optional 3, 1

Alternative Oral Agents (When Fluoroquinolones Cannot Be Used)

• Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 14 days is appropriate ONLY if the uropathogen is known to be susceptible 1
• Oral β-lactams (including cefdinir) are significantly less effective than fluoroquinolones and require 10-14 days of treatment 1
• If you must use an oral β-lactam, an initial IV dose of ceftriaxone 1g is strongly recommended to improve outcomes 1

Inpatient Treatment Algorithm

Indications for Hospitalization

• Complicated infections, sepsis, persistent vomiting, failed outpatient treatment, extremes of age, or inability to tolerate oral medications 3, 1
• Patients with diabetes, chronic kidney disease, immunosuppression, or anatomic urinary tract abnormalities 1

Empiric IV Antibiotic Options

• Fluoroquinolones: Ciprofloxacin 400 mg IV twice daily or levofloxacin 750 mg IV once daily 3
• Extended-spectrum cephalosporins: Ceftriaxone 1-2 g IV once daily, cefotaxime 2 g IV three times daily, or cefepime 1-2 g IV twice daily 3
• Aminoglycosides: Gentamicin 5 mg/kg IV once daily or amikacin 15 mg/kg IV once daily (typically combined with other antibiotics, not as monotherapy) 3

Transition to Oral Therapy

• Switch to oral antibiotics when the patient shows clinical improvement (typically within 48-72 hours) 3
• Base oral therapy on culture results: ciprofloxacin 500-750 mg twice daily, levofloxacin 750 mg once daily, or trimethoprim-sulfamethoxazole 160/800 mg twice daily 3

Treatment Duration

• Fluoroquinolones: 5-7 days total 3
• Trimethoprim-sulfamethoxazole: 14 days 3
• β-lactam antibiotics: 10-14 days 3

Special Populations and Complicated Cases

Pyelonephritis with Frank Hematuria

• Frank hematuria indicates a complicated infection requiring urgent upper urinary tract imaging (ultrasound or CT) to rule out obstruction, abscess, or stone disease 4
• Start with IV therapy using the same agents as above, but expect longer treatment duration and more aggressive management 4

Patients with Renal Impairment

• Dose adjustments are required for moderate renal impairment (reduce standard dose by approximately 30-50%) 1
• Use aminoglycosides with extreme caution in elderly patients with impaired renal function due to nephrotoxicity risk 1
• Monitor renal function during treatment as both infection and antibiotics may affect kidney function 1

Multidrug-Resistant Organisms

• Reserve carbapenems and novel broad-spectrum antimicrobials for patients with confirmed multidrug-resistant organisms 3
• Consider piperacillin/tazobactam 2.5-4.5 g IV three times daily for broader coverage when needed 4

Critical Pitfalls to Avoid

• Never use oral β-lactams as monotherapy without an initial parenteral dose—this leads to treatment failure due to inferior efficacy 1
• Do not use nitrofurantoin or oral fosfomycin for pyelonephritis—insufficient data regarding efficacy 1
• Failing to obtain cultures before initiating antibiotics complicates management if the patient doesn't respond to empiric therapy 3
• Delayed recognition of urinary tract obstruction or abscess can lead to treatment failure and sepsis—obtain imaging if the patient remains febrile after 72 hours or shows clinical deterioration 3
• Aminoglycosides should never be used as monotherapy due to nephrotoxicity risk, especially in elderly patients 1

Monitoring and Follow-Up

• If the patient fails to improve within 48-72 hours, obtain imaging (preferably CT scan) and repeat blood and urine cultures 3, 1
• Urine culture should be repeated 1-2 weeks after completion of antibiotic therapy 5
• Treatment failure may indicate resistant organisms, underlying anatomic/functional abnormalities, or immunosuppressed states requiring alternative antibiotics or surgical intervention 5