Treatment of Unilateral Pyelonephritis (Kidney Infection)
For an otherwise healthy adult with uncomplicated pyelonephritis on one side, start with oral fluoroquinolones—either ciprofloxacin 500-750 mg twice daily for 7 days or levofloxacin 750 mg once daily for 5 days—provided your local fluoroquinolone resistance rate is below 10%. 1, 2
Outpatient Oral Treatment Algorithm
First-Line Options (if local fluoroquinolone resistance <10%)
These fluoroquinolones achieve clinical cure rates of 77-96%, significantly outperforming other oral options. 2
If Fluoroquinolone Resistance ≥10%
Give one initial IV dose of ceftriaxone 1-2 g, then follow with oral fluoroquinolone for the remaining 5-7 days. 1, 2 This approach bridges the gap when resistance patterns make empiric oral therapy alone risky.
Alternative Oral Agents (Second-Line)
- Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 14 days—but ONLY if culture confirms susceptibility 1, 2
- Oral cephalosporins (cefpodoxime 200 mg twice daily for 10 days or ceftibuten 400 mg daily for 10 days) 1
Critical caveat: Oral β-lactams have substantially lower cure rates (58-60%) compared to fluoroquinolones. 2 If you must use them, give an initial IV dose of ceftriaxone 1 g first. 1, 2
What NOT to Use for Pyelonephritis
Avoid these agents entirely for kidney infections:
These lack sufficient efficacy data for upper urinary tract infections and should be reserved for simple bladder infections only. 1
When to Hospitalize and Use IV Therapy
Admit patients and start IV antibiotics if they have: 2, 3
- Sepsis or hemodynamic instability
- Persistent vomiting (cannot tolerate oral medications)
- Immunosuppression or diabetes
- Pregnancy
- Failed outpatient treatment
- Suspected urinary obstruction
- Chronic kidney disease
IV Antibiotic Options for Hospitalized Patients
- 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
- Gentamicin 5 mg/kg IV once daily (with or without ampicillin) 1
- Piperacillin-tazobactam 2.5-4.5 g IV three times daily 1
Reserve carbapenems and novel agents (ceftolozane-tazobactam, ceftazidime-avibactam) for culture-proven multidrug-resistant organisms. 1
Essential Management Steps
Before Starting Antibiotics
Always obtain urine culture and susceptibility testing before initiating therapy. 1, 2 This is non-negotiable—you need to know what you're treating and adjust therapy based on results.
Expected Clinical Response
Approximately 95% of patients become afebrile within 48 hours of appropriate antibiotic therapy, and nearly 100% within 72 hours. 2, 3 If your patient isn't improving by 48-72 hours, obtain CT imaging to evaluate for complications like abscess, obstruction, or emphysematous pyelonephritis. 2, 3
Transition to Oral Therapy
Once the patient can tolerate oral intake and shows clinical improvement, switch from IV to oral antibiotics based on culture results to complete the full treatment course. 2
Common Pitfalls to Avoid
Don't use oral β-lactams as monotherapy without an initial parenteral dose—this leads to treatment failure due to their inferior efficacy. 2 The cure rate difference is clinically significant (58-60% vs 77-96% with fluoroquinolones). 2
Don't ignore local resistance patterns—if your community has high fluoroquinolone resistance and you use it empirically without the initial IV ceftriaxone dose, you risk treatment failure and contribute to further resistance. 1, 2
Don't assume typical presentation in all patients—up to 50% of diabetic patients may not have flank tenderness, making diagnosis more challenging. 2 Maintain high clinical suspicion even with atypical presentations.
Don't delay imaging in non-responders—failure to improve within 48-72 hours mandates CT imaging to rule out complications that may require surgical intervention. 2, 3