What is the recommended management of acute pyelonephritis in adults, including criteria for outpatient oral therapy versus inpatient intravenous treatment?

Management of Acute Pyelonephritis in Adults

For uncomplicated acute pyelonephritis in hemodynamically stable adults without comorbidities, outpatient oral ciprofloxacin 500 mg twice daily for 7 days is the first-line treatment when local fluoroquinolone resistance is <10%. 1

Outpatient vs. Inpatient Decision Algorithm

Outpatient Management Criteria

Manage as outpatient if ALL of the following are met:

• Hemodynamically stable with ability to tolerate oral medications 1
• No persistent vomiting 1
• Non-pregnant, pre-menopausal adult 1
• No immunocompromised state (no organ transplant, HIV/AIDS, chronic corticosteroids) 1
• No diabetes mellitus 1
• No anatomic urinary tract abnormalities, vesicoureteral reflux, or urinary obstruction 1
• No suspected multidrug-resistant organisms or nosocomial infection 1
• Reliable follow-up available within 48-72 hours 1

Inpatient Management Criteria

Hospitalize if ANY of the following are present:

• Sepsis or hemodynamic instability 1
• Persistent vomiting preventing oral intake 1
• Immunocompromised status (transplant recipients, HIV/AIDS, chronic corticosteroids) 1
• Diabetes mellitus (50% lack typical flank tenderness; higher risk of abscess/emphysematous pyelonephritis) 1
• Complicated infection (obstruction, stones, anatomic abnormalities, vesicoureteral reflux) 1
• Pregnancy 1
• Failed outpatient treatment 1
• Suspected multidrug-resistant organisms 1

Outpatient Oral Antibiotic Regimens

First-Line: Fluoroquinolones (when local resistance <10%)

• Ciprofloxacin 500 mg PO twice daily for 7 days (96% clinical cure, 99% microbiological cure) 1, 2
• Levofloxacin 750 mg PO once daily for 5 days (comparable efficacy to ciprofloxacin) 1, 2

Modified Approach When Fluoroquinolone Resistance ≥10%

• Give ceftriaxone 1 g IV/IM as single dose, then start oral fluoroquinolone for 5-7 days 1, 2
• Alternative: gentamicin 5-7 mg/kg IV/IM once, then oral fluoroquinolone for 5-7 days 1

Second-Line: Trimethoprim-Sulfamethoxazole

• TMP-SMX 160/800 mg PO twice daily for 14 days 1, 2
• Use ONLY if pathogen proven susceptible on culture (83% clinical cure vs. 96% with fluoroquinolones) 1
• Requires initial ceftriaxone 1 g IV/IM dose if used empirically 1

Third-Line: Oral β-Lactams (Significantly Inferior)

Oral β-lactams achieve only 58-60% clinical cure vs. 77-96% with fluoroquinolones 1, 2

If oral β-lactam must be used:

• Mandatory initial ceftriaxone 1 g IV/IM, then: 1, 2
  • Amoxicillin-clavulanate 500/125 mg PO twice daily for 10-14 days, OR 1
  • Cefpodoxime 200 mg PO twice daily for 10-14 days, OR 1, 2
  • Ceftibuten 400 mg PO once daily for 10 days 1

Indications for oral β-lactams:

• Fluoroquinolone allergy or contraindication 2
• Known fluoroquinolone-resistant pathogen 2
• TMP-SMX resistance or allergy 2

Inpatient Intravenous Antibiotic Regimens

First-Line IV Options (choose based on local resistance patterns):

• Ciprofloxacin 400 mg IV twice daily 1, 2
• Levofloxacin 750 mg IV once daily 1, 2
• Ceftriaxone 1-2 g IV once daily 1, 2
• Cefepime 1-2 g IV twice daily 1, 2
• Piperacillin-tazobactam 2.5-4.5 g IV three times daily 1, 2
• Gentamicin 5 mg/kg IV once daily (with or without ampicillin; not as monotherapy due to nephrotoxicity risk) 1, 2

For Suspected Multidrug-Resistant Organisms:

• Meropenem 1 g IV three times daily 1, 2
• Reserve ceftolozane-tazobactam, ceftazidime-avibactam, cefiderocol, or meropenem-vaborbactam for culture-confirmed MDR organisms 1

Transition to Oral Therapy:

Switch to oral antibiotics once patient is afebrile for 24-48 hours and can tolerate oral intake 1

Treatment Duration Summary

Antibiotic Class	Duration
Fluoroquinolones (ciprofloxacin)	7 days [1,2]
Fluoroquinolones (levofloxacin)	5 days [1,2]
Trimethoprim-sulfamethoxazole	14 days [1,2]
Oral or IV β-lactams	10-14 days [1,2]

Essential Management Principles

Diagnostic Workup:

• Obtain urine culture and susceptibility testing BEFORE initiating antibiotics 1, 2
• Adjust therapy based on culture results within 48-72 hours 1, 2
• Blood cultures reserved for uncertain diagnosis, immunocompromised patients, or suspected hematogenous infection 3

Expected Clinical Response:

• 95% of uncomplicated cases become afebrile within 48 hours 1
• Nearly 100% afebrile by 72 hours 1

Imaging Indications:

• NOT required for uncomplicated cases responding within 48-72 hours 1
• Obtain contrast-enhanced CT if fever persists beyond 72 hours to evaluate for abscess, obstruction, or emphysematous pyelonephritis 1, 4
• Urgent imaging required for frank hematuria (suggests obstruction, stones, or structural abnormalities) 4

Critical Pitfalls to Avoid

• Never use oral β-lactams as monotherapy without initial IV ceftriaxone 1 g dose (cure rates only 58-60% vs. 96% with fluoroquinolones) 1, 2
• Never use fluoroquinolones empirically when local resistance >10% without initial parenteral broad-spectrum dose 1, 2
• Never use TMP-SMX empirically without culture confirmation or initial parenteral dose 1
• Never treat β-lactam regimens for <10 days (increases recurrence risk) 1
• Never assume diabetic patients will have flank tenderness (50% have atypical presentations) 1
• Never use nitrofurantoin or oral fosfomycin for pyelonephritis (insufficient efficacy data) 1
• Never use aminoglycosides as monotherapy (nephrotoxicity and ototoxicity risk) 1

Renal Impairment Dosing

For patients with creatinine clearance 30-50 mL/min: ciprofloxacin 250-500 mg PO every 12 hours 5

For creatinine clearance 5-29 mL/min: ciprofloxacin 250-500 mg PO every 18 hours 5

For hemodialysis patients: ciprofloxacin 250-500 mg PO every 24 hours (after dialysis) 5