Treatment of Pyelonephritis
Initial Diagnostic Approach
Always obtain urine culture and susceptibility testing before initiating antibiotics in all patients with suspected pyelonephritis 1, 2. This is critical for guiding definitive therapy and should never be skipped, even when starting empiric treatment 2.
Outpatient Treatment (Uncomplicated Cases)
First-Line Therapy: Fluoroquinolones (if local resistance <10%)
Oral ciprofloxacin 500 mg twice daily for 7 days is the preferred first-line treatment for outpatient pyelonephritis when fluoroquinolone resistance in your community is below 10% 1, 2.
Alternative once-daily fluoroquinolone regimens include:
- Levofloxacin 750 mg orally once daily for 5 days 1, 2, 3
- Ciprofloxacin 1000 mg extended-release once daily for 7 days 1, 2
The FDA label confirms levofloxacin 750 mg for 5 days demonstrated equivalent efficacy to ciprofloxacin 500 mg twice daily for 10 days in clinical trials for acute pyelonephritis 3.
Modified Approach: When Fluoroquinolone Resistance Exceeds 10%
If local fluoroquinolone resistance exceeds 10%, administer a single intravenous dose of ceftriaxone 1g or a consolidated 24-hour dose of an aminoglycoside (e.g., gentamicin 5-7 mg/kg) before starting oral fluoroquinolone therapy 1, 2. This initial parenteral dose improves outcomes when resistance rates are elevated 2.
Alternative Oral Therapy: Trimethoprim-Sulfamethoxazole
Trimethoprim-sulfamethoxazole 160/800 mg (double-strength) twice daily for 14 days is appropriate only if the uropathogen is known to be susceptible 1, 2. If using TMP-SMX empirically when susceptibility is unknown, give an initial IV dose of ceftriaxone 1g or aminoglycoside first 1.
Note the longer duration required: 14 days for TMP-SMX versus 5-7 days for fluoroquinolones 2.
Oral β-Lactams: Use With Caution
Oral β-lactams are less effective than fluoroquinolones and should not be used as monotherapy without an initial parenteral dose 2. If used, treat for 10-14 days 2.
Inpatient Treatment (Complicated Cases or Severe Illness)
Indications for Hospitalization
Admit patients with:
- Sepsis or hemodynamic instability 4
- Persistent vomiting preventing oral intake 4
- Failed outpatient treatment 4
- Complicated infections (obstruction, abscess, immunocompromised) 2, 5
- Extremes of age 4
Intravenous Antibiotic Regimens
Initial IV therapy options include 2:
- Fluoroquinolone (levofloxacin 750 mg IV daily or ciprofloxacin 400 mg IV every 12 hours)
- Aminoglycoside with or without ampicillin (gentamicin 5-7 mg/kg once daily) 2
- Extended-spectrum cephalosporin (ceftriaxone 1g IV daily)
- Carbapenem (for resistant organisms or severe sepsis)
A 2021 study found ceftriaxone demonstrated superior microbiological eradication compared to levofloxacin (68.7% vs 21.4%, p=0.00028), though clinical cure rates were similar 6. This reflects increasing fluoroquinolone resistance, with 48% of E. coli and 100% of K. pneumoniae isolates showing ciprofloxacin resistance in that study 6.
Choose your initial regimen based on local antibiogram data and adjust according to culture results 2.
Treatment Duration
- Fluoroquinolones: 5-7 days (levofloxacin 750 mg for 5 days; ciprofloxacin for 7 days) 1, 2
- Trimethoprim-sulfamethoxazole: 14 days 1, 2
- β-Lactams: 10-14 days 2
Microbiology
E. coli causes 75-95% of pyelonephritis cases, with occasional Proteus mirabilis and Klebsiella pneumoniae 2, 4, 7.
Critical Pitfalls to Avoid
- Never skip urine cultures before starting antibiotics 2
- Do not use fluoroquinolones empirically in areas with >10% resistance without adding an initial parenteral dose 2
- Do not use oral β-lactams or TMP-SMX as monotherapy without initial parenteral therapy when resistance patterns are unknown 2
- Always adjust therapy based on culture results 2
- Avoid inadequate treatment duration, especially with β-lactams (minimum 10-14 days) 2
- Do not ignore local resistance patterns when selecting empiric therapy 2
Follow-Up
Repeat urine culture 1-2 weeks after completing antibiotic therapy to confirm eradication 4. If the patient fails to respond, obtain repeat blood and urine cultures and consider imaging (contrast-enhanced CT) to evaluate for complications such as abscess or obstruction 4, 7.