What is the recommended treatment for pyelonephritis (kidney infection)?

Treatment for Pyelonephritis

Immediate Action: Obtain Urine Culture Before Starting Antibiotics

Always obtain urine culture and susceptibility testing before initiating empirical therapy in all patients with suspected pyelonephritis 1, 2. This is mandatory to guide definitive therapy and adjust treatment if the patient fails to respond 2, 3.

Outpatient Treatment Algorithm

Step 1: Assess Local Fluoroquinolone Resistance

If local fluoroquinolone resistance is ≤10%:

• Oral ciprofloxacin 500 mg twice daily for 7 days is the first-line treatment 1, 2, 4. This regimen achieves 97% clinical cure rates and is superior to other oral options 4.
• Alternative once-daily options include ciprofloxacin 1000 mg extended-release for 7 days or levofloxacin 750 mg for 5 days 1, 2, 5.
• An optional initial single IV dose of ciprofloxacin 400 mg can be given before starting oral therapy 1.

If local fluoroquinolone resistance is >10%:

• Give an initial one-time IV dose of ceftriaxone 1g or a consolidated 24-hour dose of an aminoglycoside (gentamicin 5-7 mg/kg), then start oral fluoroquinolone therapy 1, 2, 3. This approach compensates for higher resistance rates while maintaining outpatient treatment feasibility.
• The parenteral agent can be administered intramuscularly if IV access is unavailable 1.

Step 2: Alternative Oral Regimens When Susceptibility is Known

• Trimethoprim-sulfamethoxazole 160/800 mg (double-strength) twice daily for 14 days is appropriate only if the uropathogen is documented as susceptible 1, 2. This agent has high resistance rates (up to 55% for E. coli) and should never be used empirically 6, 7.
• If TMP-SMX is used empirically (not recommended), give an initial IV dose of ceftriaxone 1g or aminoglycoside first 1.

Avoid These Common Pitfalls in Outpatient Treatment:

• Do not use oral β-lactams as monotherapy without an initial parenteral dose 2, 3. They have inferior efficacy compared to fluoroquinolones 1.
• Do not use fluoroquinolones empirically in areas with >10% resistance without adding an initial parenteral agent 2, 3, 8.
• Do not use amoxicillin or ampicillin empirically due to very high resistance rates worldwide 1.

Inpatient Treatment Algorithm

Indications for Hospitalization:

• Complicated infections, sepsis, persistent vomiting, failed outpatient treatment, or extremes of age 9.
• Suspected multidrug-resistant organisms or immunocompromised state 2, 3.

First-Line IV Antibiotic Options (Choose Based on Local Resistance):

If fluoroquinolone resistance ≤10%:

• Ciprofloxacin 400 mg IV twice daily 3
• Levofloxacin 750 mg IV once daily 3, 5

If fluoroquinolone resistance >10% or unknown:

• Ceftriaxone 1-2g IV once daily (use 2g dose for hospitalized patients) 2, 3
• Cefepime 1-2g IV twice daily 3
• Gentamicin 5 mg/kg IV once daily (must be combined with ampicillin when used empirically) 2, 3

Reserve carbapenems exclusively for culture-proven multidrug-resistant organisms:

• Imipenem/cilastatin 0.5g IV three times daily 3
• Meropenem 1g IV three times daily 3

Transition to Oral Therapy:

• Switch to oral antibiotics once the patient is clinically improving, afebrile for 24-48 hours, and able to tolerate oral intake 9.
• Tailor oral therapy based on culture results and susceptibility testing 2, 3.

Treatment Duration by Antibiotic Class

• Fluoroquinolones: 5-7 days 1, 2, 3, 4. Seven days of ciprofloxacin is as effective as 14 days with fewer adverse effects 4.
• Trimethoprim-sulfamethoxazole: 14 days 1, 2, 3.
• β-lactams (cephalosporins): 10-14 days 2, 3, 9. The longer duration compensates for their inferior efficacy 1.

Special Populations

Elderly Patients:

• Monitor closely for adverse effects, particularly aminoglycosides (nephrotoxicity, ototoxicity) and fluoroquinolones (CNS effects, tendinopathy) 2, 3.
• Adjust aminoglycoside dosing based on renal function 3.

Pediatric Patients:

• Ciprofloxacin is FDA-approved for complicated UTI and pyelonephritis in children ≥1 year old, but is not first-choice due to increased joint-related adverse events 10.
• Levofloxacin is approved for plague and anthrax in children ≥6 months but not specifically for pyelonephritis 5.

Follow-Up and Treatment Failure

• Repeat urine culture 1-2 weeks after completion of antibiotic therapy 9.
• If no clinical improvement within 48-72 hours, repeat blood and urine cultures, consider imaging (contrast-enhanced CT), and adjust antibiotics based on susceptibility results 9, 8.
• Treatment failure may indicate resistant organisms, anatomic abnormalities, or immunosuppression 9.

Key Causative Organisms and Resistance Patterns

• Escherichia coli causes 75-95% of pyelonephritis cases 2, 9, 8.
• Other pathogens include Klebsiella pneumoniae and Proteus mirabilis 2, 9.
• Resistance rates are rising rapidly: E. coli resistance to ciprofloxacin ranges from 10-48%, and to ceftriaxone from 10-34% 6, 7. This underscores the critical importance of obtaining cultures and adjusting therapy based on susceptibility results.