What is the recommended treatment for pyelonephritis?

Treatment for Pyelonephritis

For outpatient management of acute uncomplicated pyelonephritis, oral fluoroquinolones—specifically ciprofloxacin 500 mg twice daily for 7 days or levofloxacin 750 mg once daily for 5 days—are the first-line treatments when local fluoroquinolone resistance is below 10%. 1, 2

Initial Diagnostic Steps

• Obtain urine culture and susceptibility testing before initiating antibiotics in all patients with suspected pyelonephritis to guide definitive therapy and adjust empirical treatment based on results 1, 2
• Assess for flank pain, fever, chills, nausea, vomiting, and costovertebral angle tenderness as these are the hallmark clinical features 3, 4
• Perform urinalysis to evaluate for white blood cells, red blood cells, and nitrite 3

Outpatient Treatment Algorithm

When Local Fluoroquinolone Resistance is <10%:

• Ciprofloxacin 500 mg orally twice daily for 7 days 1, 2
• Levofloxacin 750 mg orally once daily for 5 days 1, 2, 5
• Ciprofloxacin 1000 mg extended-release orally once daily for 7 days is an alternative 1, 2

When Local Fluoroquinolone Resistance is ≥10%:

• Administer one initial intravenous dose of ceftriaxone 1 g OR a consolidated 24-hour dose of an aminoglycoside (e.g., gentamicin 5-7 mg/kg) before starting oral fluoroquinolone therapy 1, 2
• Follow with the same oral fluoroquinolone regimens listed above 1, 2

Alternative Oral Agents (When Susceptibility is Known):

• Trimethoprim-sulfamethoxazole 160/800 mg (double-strength) orally twice daily for 14 days if the uropathogen is confirmed susceptible 1, 2
• If using trimethoprim-sulfamethoxazole empirically when susceptibility is unknown, give an initial intravenous dose of ceftriaxone 1 g or aminoglycoside 1

Oral β-Lactam Agents (Less Preferred):

• Oral β-lactams are less effective than fluoroquinolones and should only be used with an initial intravenous dose of ceftriaxone 1 g or aminoglycoside 1, 2
• Duration should be 10-14 days if β-lactams are used 1

Inpatient Treatment for Severe or Complicated Cases

Indications for Hospitalization:

• Severe illness, sepsis, persistent vomiting, failed outpatient treatment, extremes of age, or suspected complications 6, 7
• Pregnancy (pregnant patients are at significantly elevated risk and should always be admitted) 7

Initial Intravenous Regimens:

• Fluoroquinolone (levofloxacin 750 mg IV once daily or ciprofloxacin 400 mg IV every 12 hours) 1, 2
• Aminoglycoside (gentamicin 5-7 mg/kg IV once daily) with or without ampicillin 1, 2
• Extended-spectrum cephalosporin (ceftriaxone 1-2 g IV once daily) or extended-spectrum penicillin, with or without aminoglycoside 1, 2
• Carbapenem (reserved for multidrug-resistant organisms or extended-spectrum beta-lactamase producers) 3, 7

Transitioning to Oral Therapy:

• Switch to oral antibiotics once the patient is clinically improving, afebrile for 24-48 hours, and able to tolerate oral intake 7
• Tailor oral therapy based on culture and susceptibility results 1, 2

Treatment Duration

• Fluoroquinolones: 5-7 days depending on the specific agent (levofloxacin 750 mg for 5 days, ciprofloxacin for 7 days) 1, 2
• Trimethoprim-sulfamethoxazole: 14 days 1, 2
• β-Lactam agents: 10-14 days 1, 2

Common Pitfalls to Avoid

• Failing to obtain urine cultures before initiating antibiotics prevents appropriate tailoring of therapy 2
• Not considering local resistance patterns when selecting empiric therapy can lead to treatment failure 2, 7
• Using fluoroquinolones empirically in areas with >10% resistance without adding an initial parenteral dose increases risk of inadequate coverage 1, 2
• Using oral β-lactams as monotherapy without an initial parenteral dose is associated with inferior outcomes 1, 2
• Not adjusting therapy based on culture results may perpetuate inappropriate antibiotic use 2
• Inadequate treatment duration, especially with β-lactam agents can lead to relapse 2

Follow-Up and Treatment Failure

• Most patients should respond within 48-72 hours of appropriate antibiotic therapy 7
• Repeat urine culture 1-2 weeks after completion of antibiotic therapy 6
• If no improvement occurs within 48-72 hours, obtain repeat blood and urine cultures and consider imaging (contrast-enhanced CT) to evaluate for complications such as abscess, obstruction, or resistant organisms 4, 7
• Treatment failure may indicate resistant organisms, underlying anatomic/functional abnormalities, immunosuppression, or need for surgical intervention 6, 7

Special Considerations

• The most common causative organism is Escherichia coli (75-95%), followed by other Enterobacteriaceae such as Proteus mirabilis and Klebsiella pneumoniae 1, 2
• In elderly patients, monitor closely for adverse effects, particularly with aminoglycosides (nephrotoxicity, ototoxicity) and fluoroquinolones (tendon disorders, neuropsychiatric effects, cardiac effects) 2, 8
• Fluoroquinolones should be used with caution during breastfeeding but are acceptable when benefits outweigh risks 3