What are the empiric antibiotics for acute pyelonephritis (infection of the kidney) in adults?

From the Guidelines

Empiric antibiotics for pyelonephritis in adults should include fluoroquinolones, such as ciprofloxacin or levofloxacin, or a third-generation cephalosporin like ceftriaxone, with the specific choice guided by local resistance patterns and patient risk factors for resistant organisms 1. The choice of empiric antibiotics for pyelonephritis in adults is crucial for effective treatment and prevention of complications.

• Fluoroquinolones, such as ciprofloxacin (500mg orally twice daily for 7 days) or levofloxacin (750mg orally once daily for 5-7 days), are commonly recommended due to their high urinary concentrations and coverage of the most common causative organism, Escherichia coli 1.
• Third-generation cephalosporins, like ceftriaxone (1-2g IV daily), are also effective and can be used as an alternative or in combination with other antibiotics 1.
• Local resistance patterns should guide therapy, particularly for fluoroquinolones where resistance rates exceed 10% in many regions 1.
• Patients with risk factors for resistant organisms, such as recent hospitalization, healthcare exposure, or recent antibiotic use, may require broader coverage with piperacillin-tazobactam or a carbapenem 1.
• Treatment should be adjusted based on urine culture results, which should be obtained before starting antibiotics whenever possible 1. The most recent and highest quality study, published in 2024, provides guidance on the appropriate duration of treatment for acute pyelonephritis, recommending 5-7 days of fluoroquinolone therapy or 7 days of dose-optimized β-lactam therapy 1. Overall, the choice of empiric antibiotics for pyelonephritis in adults should be guided by local resistance patterns, patient risk factors, and the most recent clinical guidelines, with the goal of achieving optimal treatment outcomes and minimizing the risk of complications and antibiotic resistance 1.

From the FDA Drug Label

1. 11 Acute Pyelonephritis: 5 or 10 Day Treatment Regimen Levofloxacin tablets are indicated for the treatment of acute pyelonephritis caused by Escherichia coli, including cases with concurrent bacteremia [see Clinical Studies (14.7,14.8)].
2. 7 Complicated Urinary Tract Infections and Acute Pyelonephritis: 5 Day Treatment Regimen To evaluate the safety and efficacy of the higher dose and shorter course of levofloxacin, 1109 patients with cUTI and AP were enrolled in a randomized, double-blind, multicenter clinical trial conducted in the U.S. from November 2004 to April 2006 comparing levofloxacin 750 mg I. V. or orally once daily for 5 days (546 patients) with ciprofloxacin 400 mg I. V. or 500 mg orally twice daily for 10 days (563 patients).
3. 8 Complicated Urinary Tract Infections and Acute Pyelonephritis: 10 Day Treatment Regimen To evaluate the safety and efficacy of the 250 mg dose, 10 day regimen of levofloxacin, 567 patients with uncomplicated UTI, mild-to-moderate cUTI, and mild-to-moderate AP were enrolled in a randomized, double-blind, multicenter clinical trial conducted in the U. S. from June 1993 to January 1995 comparing levofloxacin 250 mg orally once daily for 10 days (285 patients) with ciprofloxacin 500 mg orally twice daily for 10 days (282 patients).

The empiric antibiotics for pyelonephritis in adults are levofloxacin and ciprofloxacin.

• Levofloxacin is indicated for the treatment of acute pyelonephritis caused by Escherichia coli, including cases with concurrent bacteremia.
• The recommended treatment regimens are 5 days or 10 days of levofloxacin or ciprofloxacin therapy. These antibiotics are chosen because they have been shown to be effective in clinical trials, with bacteriologic cure rates and clinical success rates comparable to those of other antibiotics 2, 2.

From the Research

Empiric Antibiotics for Pyelonephritis in Adults

The choice of empiric antibiotics for pyelonephritis in adults depends on various factors, including the severity of the infection, the presence of underlying medical conditions, and the local resistance patterns of uropathogens.

• According to 3, practice guidelines recommend oral fluoroquinolones as initial outpatient therapy if the rate of fluoroquinolone resistance in the community is 10 percent or less.
• If the resistance rate exceeds 10 percent, an initial intravenous dose of ceftriaxone or gentamicin should be given, followed by an oral fluoroquinolone regimen 3.
• A study comparing levofloxacin and ceftriaxone for the treatment of acute pyelonephritis found that ceftriaxone was more effective than levofloxacin in terms of microbiological response 4.
• Another study suggested that fluoroquinolones, trimethoprim/sulfamethoxazole, and aminoglycosides are preferred over beta-lactams as first-choice agents for the therapy of gram-negative pyelonephritis due to their ability to penetrate the infected renal parenchyma 5.
• A rapid evidence review recommended that fluoroquinolones and trimethoprim/sulfamethoxazole are effective oral antibiotics in most cases, but increasing resistance makes empiric use problematic 6.
• When local resistance to a chosen oral antibiotic likely exceeds 10%, one dose of a long-acting broad-spectrum parenteral antibiotic should also be given while awaiting susceptibility data 6.

Duration of Antibiotic Therapy

The optimal duration of antibiotic therapy for pyelonephritis is also an important consideration.

• A systematic review and meta-analysis found that short-course antibiotic treatment is at least as effective as longer courses for both microbiological and clinical success in the treatment of acute uncomplicated pyelonephritis 7.
• The review suggested that current evidence is sufficient to consider short-course treatment at least as effective as long-course treatment 7.
• Selected guidelines recommend considering shorter courses, but do not cite most of the published randomized controlled trials 7.

Key Points to Consider

• The choice of empiric antibiotics should be guided by local resistance patterns and the severity of the infection.
• Fluoroquinolones, trimethoprim/sulfamethoxazole, and aminoglycosides are preferred over beta-lactams for the therapy of gram-negative pyelonephritis.
• Short-course antibiotic treatment may be as effective as longer courses for acute uncomplicated pyelonephritis.
• Urine culture with antimicrobial susceptibility testing should be performed in all patients to direct therapy 3, 6.