What is the treatment for pyelonephritis?

Treatment of 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 is below 10%. 1, 2

Initial Assessment and Risk Stratification

Before initiating treatment, obtain urine culture with antimicrobial susceptibility testing in all patients to guide subsequent therapy adjustments. 1, 2 Blood cultures are only necessary for patients with uncertain diagnosis, immunocompromised status, or suspected hematogenous infection. 3

Determine if the infection is uncomplicated or complicated:

• Uncomplicated pyelonephritis occurs in non-pregnant, immunocompetent women without structural/functional urinary tract abnormalities 1
• Complicated pyelonephritis involves males, pregnancy, diabetes, immunosuppression, obstruction, foreign bodies, recent instrumentation, or multidrug-resistant organisms 1, 4

Outpatient Treatment Algorithm (Uncomplicated Cases)

First-line oral therapy options when fluoroquinolone resistance <10%:

• Ciprofloxacin 500-750 mg twice daily for 7 days 1, 2
• Levofloxacin 750 mg once daily for 5 days 1, 2, 5

When fluoroquinolone resistance exceeds 10% locally:

• Administer one initial dose of a long-acting parenteral antibiotic (ceftriaxone 1 g IV/IM or gentamicin 5-7 mg/kg once) before starting oral fluoroquinolone therapy 1, 4, 2
• This approach bridges therapy while awaiting susceptibility results 1

Alternative oral regimens (only if pathogen is known to be susceptible):

• Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 14 days - requires longer duration and should only be used with documented susceptibility 1, 2
• Oral cephalosporins (cefpodoxime 200 mg twice daily or ceftibuten 400 mg once daily for 10 days) - less effective than fluoroquinolones and require an initial IV dose of ceftriaxone 1 g 1, 2

Inpatient Treatment Algorithm (Hospitalized Patients)

Indications for hospitalization include: sepsis, persistent vomiting, failed outpatient treatment, complicated infection, extremes of age, inability to tolerate oral medications, or pregnancy. 3, 6

Initial empiric IV therapy options:

• Ciprofloxacin 400 mg IV twice daily 1, 4
• Levofloxacin 750 mg IV once daily 1, 4
• Ceftriaxone 1-2 g IV once daily 1, 4
• Cefotaxime 2 g IV three times daily 1, 4
• Cefepime 1-2 g IV twice daily 1, 4
• Piperacillin/tazobactam 2.5-4.5 g IV three times daily 1, 4
• Gentamicin 5 mg/kg IV once daily (with or without ampicillin) 1, 4
• Amikacin 15 mg/kg IV once daily 1, 4

Reserve carbapenems and novel broad-spectrum agents (imipenem, meropenem, ceftolozane/tazobactam, ceftazidime/avibactam) exclusively for patients with early culture results indicating multidrug-resistant organisms. 1, 4

Special Populations and Complicated Cases

Patients with diabetes or chronic kidney disease:

• Higher risk for complications including renal abscesses and emphysematous pyelonephritis 2
• Up to 50% may not present with typical flank tenderness 2
• Start with IV therapy and obtain imaging (CT scan preferred) if no improvement within 48-72 hours 2, 6
• Adjust antibiotic doses for renal impairment; reduce standard doses by 30-50% for moderate impairment 2

Patients with frank hematuria:

• Indicates complicated infection requiring urgent upper urinary tract imaging (ultrasound or CT) to rule out obstruction, abscess, or stones 4
• Initiate IV therapy as for hospitalized patients 4
• May require longer treatment duration and more aggressive management 4

Pregnant patients:

• Significantly elevated risk of severe complications 6
• Require hospital admission and initial parenteral therapy 6
• Antibiotic selection must consider pregnancy safety profile 7

Duration and Transition to Oral Therapy

Total treatment duration:

• Fluoroquinolones: 5-7 days (shorter courses are equivalent to longer therapy for clinical success but may have higher recurrence rates at 4-6 weeks) 1
• Trimethoprim-sulfamethoxazole: 14 days 1
• Oral cephalosporins: 10 days 1
• Beta-lactams (when used): 10-14 days 2

Transition from IV to oral therapy can occur once the patient is clinically improving, afebrile for 24-48 hours, and able to tolerate oral intake. 2 Switch to an appropriate oral agent based on culture and susceptibility results. 1, 2

Monitoring and Follow-Up

Expected response timeline:

• Most patients respond within 48-72 hours of appropriate therapy 6
• Repeat urine culture 1-2 weeks after completion of antibiotics 3

If no improvement within 48-72 hours:

• Obtain imaging (CT scan preferred) to evaluate for complications (abscess, obstruction, stones) 4, 2, 6
• Repeat blood and urine cultures 3
• Consider alternative diagnoses 6
• Evaluate for resistant organisms or underlying anatomic/functional abnormalities 3

If concurrent urinary tract obstruction is identified, pursue urgent urologic referral for decompression (percutaneous nephrostomy or definitive surgery). 8, 6

Critical Pitfalls to Avoid

• Never use oral beta-lactams as monotherapy without an initial parenteral dose - they have inferior efficacy compared to fluoroquinolones 2
• Do not use nitrofurantoin or oral fosfomycin for pyelonephritis - insufficient data regarding efficacy 2
• Avoid empiric use of fluoroquinolones or trimethoprim-sulfamethoxazole when local resistance exceeds 10% without initial parenteral broad-spectrum coverage 1, 6
• Do not use aminoglycosides as monotherapy due to nephrotoxicity risk, especially in elderly patients with renal impairment 2
• Do not delay appropriate antibiotic therapy - can lead to renal scarring, hypertension, and end-stage renal disease 2
• Do not rely solely on typical symptoms in diabetic patients - presentation may be atypical 2