What is the recommended treatment for inpatient management of pyelonephritis?

Inpatient Management of Pyelonephritis

For hospitalized patients with pyelonephritis, initiate intravenous therapy with a fluoroquinolone (ciprofloxacin 400 mg IV every 12 hours or levofloxacin 750 mg IV daily), an extended-spectrum cephalosporin (ceftriaxone 1-2 g IV daily or cefepime 1-2 g IV every 8-12 hours), an aminoglycoside with or without ampicillin, or a carbapenem, with selection based on local resistance patterns and severity of illness. 1, 2

Initial Assessment and Diagnostic Workup

Before initiating antibiotics, obtain:

• Urine culture and antimicrobial susceptibility testing to guide targeted therapy 1, 3
• Blood cultures for patients with uncertain diagnosis, immunocompromised status, or suspected hematogenous infection 4
• Urinary tract imaging (ultrasound or CT scan) to rule out obstruction, abscess, or structural abnormalities, particularly in complicated infections or when frank hematuria is present 2, 5

Empiric Antibiotic Selection Algorithm

First-Line Intravenous Options:

Fluoroquinolones (if local resistance <10%):

• Ciprofloxacin 400 mg IV every 12 hours 2
• Levofloxacin 750 mg IV once daily 2, 6

Extended-Spectrum Cephalosporins:

• Ceftriaxone 1-2 g IV once daily 2, 7
• Cefepime 1-2 g IV every 8-12 hours for severe infections 8

Aminoglycosides (with or without ampicillin):

• Gentamicin 5 mg/kg IV once daily 2
• Amikacin 15 mg/kg IV once daily 2

Carbapenems:

• Reserved for multidrug-resistant organisms or patients with risk factors for extended-spectrum beta-lactamase (ESBL) producers 2, 6

Selection Strategy:

Choose fluoroquinolones when:

• Local fluoroquinolone resistance is <10% 1, 9
• Patient has no recent fluoroquinolone exposure 9
• No recent hospitalization 9

Choose cephalosporins when:

• Fluoroquinolone resistance exceeds 10% locally 1, 6
• Patient has recent fluoroquinolone use 9
• Severe infection requiring broader coverage 8

Choose aminoglycosides when:

• High local resistance to fluoroquinolones and cephalosporins 1
• Used in combination with ampicillin for broader coverage 1, 2

Transition to Oral Therapy

Once clinical improvement occurs (typically 24-48 hours of afebrile status):

• Ciprofloxacin 500-750 mg orally twice daily to complete 7 days total 1, 6
• Levofloxacin 750 mg orally once daily to complete 5-7 days total 1, 6
• Trimethoprim-sulfamethoxazole 160/800 mg twice daily if susceptible, to complete 14 days total 1, 6

Duration of Therapy

• Fluoroquinolones: 5-7 days total (IV + oral) 1, 6
• Cephalosporins: 10-14 days total (IV + oral) 1, 6
• Trimethoprim-sulfamethoxazole: 14 days total 1, 6

Antimicrobial Resistance Considerations

Critical resistance patterns to consider:

• E. coli fluoroquinolone resistance ranges from 10-48% depending on region and patient population 7, 9
• Ceftriaxone resistance in E. coli has risen to 10-34% in some areas 7, 9
• Always tailor therapy based on culture and susceptibility results as soon as available 1, 2

Special Clinical Scenarios

Complicated Pyelonephritis:

• Requires longer duration of therapy (14 days minimum) 5
• Consider broader-spectrum coverage with piperacillin/tazobactam 2.5-4.5 g IV every 8 hours or carbapenems 2, 6
• If urinary obstruction is present, urgent decompression (percutaneous nephrostomy or surgical intervention) is mandatory alongside antibiotics 6, 5

Severe Infections or Sepsis:

• Use cefepime 2 g IV every 8 hours for Pseudomonas coverage 8
• Consider combination therapy with aminoglycoside 1, 2

Renal Impairment:

• Adjust cefepime dosing: for CrCl 30-60 mL/min, give 1-2 g IV every 24 hours; for CrCl 11-29 mL/min, give 0.5-1 g IV every 24 hours 8
• Fluoroquinolone doses generally do not require adjustment for mild-moderate renal impairment 1

Common Pitfalls and Caveats

Avoid these errors:

• Do not use oral beta-lactams (cefdinir, cephalexin) as monotherapy for pyelonephritis—they are inferior to fluoroquinolones 1, 6
• Do not use amoxicillin or ampicillin empirically due to high resistance rates (>30%) 3
• Do not assume all fluoroquinolones are equivalent—levofloxacin 750 mg has superior outcomes to lower doses 6
• Do not continue empiric therapy beyond 48-72 hours without reassessing based on culture results 1, 4

Monitoring and Follow-Up

• If no clinical improvement after 72 hours, obtain repeat imaging (contrast-enhanced CT) and repeat cultures 6, 4
• Repeat urine culture 1-2 weeks after completion of therapy to document eradication 4
• Treatment failure may indicate resistant organisms, anatomic abnormalities, or immunosuppression requiring further investigation 4, 5