What are the recommended IV antibiotics for pyelonephritis?

IV Antibiotics for Pyelonephritis

For hospitalized patients with pyelonephritis requiring IV therapy, fluoroquinolones (ciprofloxacin 400mg IV twice daily or levofloxacin 750mg IV once daily), extended-spectrum cephalosporins (ceftriaxone 1-2g IV daily or cefepime 1-2g IV twice daily), or aminoglycosides (gentamicin 5mg/kg IV once daily) are the recommended first-line options, with selection based on local resistance patterns and patient-specific factors. 1

First-Line IV Antibiotic Options

The 2024 European Association of Urology guidelines provide clear recommendations for empirical parenteral therapy:

Fluoroquinolones

• Ciprofloxacin 400mg IV twice daily 1
• Levofloxacin 750mg IV once daily (offers convenient once-daily dosing) 1, 2
• These should only be used empirically if local fluoroquinolone resistance is ≤10% 3, 4

Extended-Spectrum Cephalosporins

• Ceftriaxone 1-2g IV once daily (higher 2g dose recommended despite lower doses being studied) 1
• Cefotaxime 2g IV three times daily (not studied as monotherapy but recommended) 1
• Cefepime 1-2g IV twice daily (higher dose recommended; FDA-approved for severe pyelonephritis at 2g IV every 12 hours) 1, 5

Aminoglycosides

• Gentamicin 5mg/kg IV once daily (consolidated 24-hour dosing; not studied as monotherapy but effective) 1, 3
• Amikacin 15mg/kg IV once daily 1
• Should be combined with ampicillin when used empirically 1

Extended-Spectrum Penicillins

• Piperacillin/tazobactam 2.5-4.5g IV three times daily 1

When to Use Carbapenems and Broad-Spectrum Agents

Reserve carbapenems and novel broad-spectrum agents exclusively for patients with early culture results indicating multidrug-resistant organisms. 1 These include:

• Imipenem/cilastatin 0.5g IV three times daily 1
• Meropenem 1g IV three times daily 1
• Ceftolozane/tazobactam 1.5g IV three times daily 1
• Ceftazidime/avibactam 2.5g IV three times daily 1
• Cefiderocol 2g IV three times daily 1
• Meropenem-vaborbactam 2g IV three times daily 1
• Plazomicin 15mg/kg IV once daily 1

Using these agents empirically violates antimicrobial stewardship principles and should be avoided unless there is documented resistance 2, 3.

Treatment Algorithm

Step 1: Obtain Cultures Before Initiating Therapy

• Urine culture with antimicrobial susceptibility testing is mandatory in all pyelonephritis cases 1, 3, 4
• Blood cultures are generally unnecessary unless the patient is immunocompromised, has uncertain diagnosis, or suspected hematogenous infection 6

Step 2: Assess Local Resistance Patterns

• If local fluoroquinolone resistance >10%, avoid empiric fluoroquinolone monotherapy 3, 4
• In high-resistance areas, use an extended-spectrum cephalosporin or aminoglycoside instead 1, 3

Step 3: Select Initial IV Antibiotic Based on Clinical Scenario

For uncomplicated pyelonephritis in areas with low fluoroquinolone resistance (<10%):

• Ciprofloxacin 400mg IV twice daily OR levofloxacin 750mg IV once daily 1, 2

For uncomplicated pyelonephritis in areas with high fluoroquinolone resistance (>10%):

• Ceftriaxone 2g IV once daily OR cefepime 2g IV twice daily 1, 5
• Alternative: Gentamicin 5mg/kg IV once daily (with ampicillin) 1, 3

For patients with penicillin and sulfa allergies:

• IV fluoroquinolone (ciprofloxacin or levofloxacin) is preferred 2
• Alternative: Aminoglycoside monotherapy (though not extensively studied) 2

Step 4: Adjust Based on Culture Results

• Modify therapy once susceptibility results are available 3, 4
• De-escalate from broad-spectrum agents when possible 3

Step 5: Transition to Oral Therapy

• Switch to oral antibiotics when the patient is clinically improving, afebrile for 24-48 hours, and able to tolerate oral intake 3, 4
• Oral options include fluoroquinolones (if susceptible), trimethoprim-sulfamethoxazole (if susceptible), or oral β-lactams (though less effective) 3

Treatment Duration

• Fluoroquinolones: 5-7 days total 3
• Trimethoprim-sulfamethoxazole: 14 days total 3
• β-lactams: 10-14 days total 3, 5
• For febrile neutropenic patients: 7 days or until resolution of neutropenia 1, 5

Special Considerations for Elderly Patients

Monitor elderly patients closely for adverse effects, particularly:

• Aminoglycosides: nephrotoxicity and ototoxicity 2
• Fluoroquinolones: CNS effects (confusion, delirium) and tendinopathy 2
• Dose adjustments are required for renal impairment (see below) 5

Renal Dose Adjustments

For patients with creatinine clearance ≤60 mL/min, dose adjustments are necessary. Using cefepime as an example 5:

• CrCl 30-60 mL/min: Reduce frequency to every 24 hours (for most indications) 5
• CrCl 11-29 mL/min: Further dose reduction required 5
• CrCl <11 mL/min or hemodialysis: Significant dose reduction; administer after dialysis 5

Similar adjustments apply to other renally cleared antibiotics including fluoroquinolones and aminoglycosides 5.

Common Pitfalls to Avoid

• Failing to obtain urine cultures before starting antibiotics (prevents targeted therapy adjustment) 3, 4
• Using fluoroquinolones empirically in areas with >10% resistance without adding an initial parenteral agent 3, 4
• Using oral β-lactams as monotherapy without an initial parenteral dose (associated with treatment failure) 3
• Not considering local resistance patterns when selecting empiric therapy 1, 3
• Inadequate treatment duration, especially with β-lactam agents (requires 10-14 days) 3
• Using carbapenems empirically without documented resistance (violates stewardship principles) 2, 3

When to Obtain Imaging

Imaging is not necessary for uncomplicated pyelonephritis that responds to therapy. 1, 4 However, obtain contrast-enhanced CT or ultrasound if:

• Patient remains febrile after 72 hours of appropriate therapy 1
• Clinical deterioration occurs at any time 1
• History of urolithiasis, renal dysfunction, or high urine pH 1
• Suspected obstruction or complication 1, 4

Prompt imaging is crucial to differentiate uncomplicated from obstructive pyelonephritis, as the latter can rapidly progress to urosepsis. 1