Is cefepime (a fourth-generation cephalosporin) an effective treatment option for a patient with a complicated urinary tract infection (UTI)?

Cefepime for Complicated Urinary Tract Infections

Cefepime is an effective and FDA-approved treatment option for complicated urinary tract infections (UTIs), including pyelonephritis, with recommended dosing of 0.5-2 g IV every 12 hours for 7-10 days depending on severity. 1

FDA-Approved Indications and Dosing

Cefepime is specifically FDA-approved for both uncomplicated and complicated UTIs, including pyelonephritis, caused by E. coli, K. pneumoniae, and P. mirabilis. 1 The FDA label provides clear dosing guidance:

• Mild to moderate UTI: 0.5-1 g IV every 12 hours for 7-10 days 1
• Severe UTI (including pyelonephritis caused by E. coli or K. pneumoniae): 2 g IV every 12 hours for 10 days 1
• For Pseudomonas aeruginosa, use 2 g IV every 8 hours 1

Guideline Support and Clinical Context

The European Association of Urology 2024 guidelines explicitly list cefepime (1-2 g twice daily) as a recommended parenteral option for uncomplicated pyelonephritis requiring hospitalization, though they note the lower dose was studied while the higher dose is recommended. 2 This aligns with the FDA dosing for severe infections. 1

For complicated UTIs specifically, cefepime is positioned as a first-line parenteral option alongside other extended-spectrum cephalosporins and carbapenems. 2, 3 The European guidelines recommend cefepime particularly when fluoroquinolone resistance exceeds 10% or in patients requiring initial parenteral therapy. 2

Clinical Efficacy Evidence

Multiple studies demonstrate cefepime's effectiveness in UTI treatment:

• A 1993 study of 204 hospitalized patients showed a 94% clinical cure rate with cefepime 1 g twice daily for UTIs, including a 97% cure rate in patients with concurrent bacteremia. 4
• A 1996 randomized trial comparing cefepime to ceftazidime (500 mg every 12 hours) demonstrated 89% clinical response in complicated UTI and 92% in uncomplicated UTI, with 85% pathogen eradication rates. 5
• Recent 2022 data on cefepime/enmetazobactam showed superiority over piperacillin/tazobactam for complicated UTI and pyelonephritis (79.1% vs 58.9% treatment success), though this combination is investigational. 6

Positioning in Treatment Algorithm

Start with cefepime 2 g IV every 12 hours for empiric treatment of complicated UTI or pyelonephritis when:

• The patient requires hospitalization or parenteral therapy 2, 3
• Local fluoroquinolone resistance exceeds 10% 2, 3
• The patient has recent fluoroquinolone exposure 3
• Multidrug-resistant organisms are not suspected (reserve newer agents for confirmed resistance) 2, 3

Adjust to cefepime 2 g IV every 8 hours if Pseudomonas aeruginosa is suspected or confirmed. 1

When to Choose Alternative Agents

Cefepime should NOT be first-line when:

• Carbapenem-resistant Enterobacterales (CRE) is suspected or confirmed—use ceftazidime/avibactam, meropenem/vaborbactam, or imipenem/cilastatin/relebactam instead 2
• ESBL-producing organisms are documented—carbapenems are preferred over cefepime 3
• Multidrug-resistant Pseudomonas is confirmed—consider ceftolozane/tazobactam or ceftazidime/avibactam 2, 3

Treatment Duration and Monitoring

• Standard duration: 7-10 days for complicated UTI 1
• Extended duration: 14 days for males when prostatitis cannot be excluded 3
• Transition to oral therapy: Consider step-down to fluoroquinolones (if susceptible) or oral cephalosporins once clinically stable for 24-48 hours 3, 7

Safety Profile

Cefepime demonstrates excellent tolerability comparable to other cephalosporins. 5 In clinical trials, treatment discontinuation due to adverse events occurred in only 2-3% of patients, with headache, diarrhea, and vomiting being the most common side effects. 4, 5 Local tolerance at infusion sites is similar to ceftazidime. 5

Critical Pitfalls to Avoid

• Do not use cefepime monotherapy for suspected CRE infections—this requires newer beta-lactam/beta-lactamase inhibitor combinations or carbapenems 2
• Do not underdose—use 2 g every 12 hours for severe infections, not the lower 0.5-1 g dose 1
• Always obtain urine culture before initiating therapy to guide targeted treatment 2, 3
• Replace indwelling catheters that have been in place ≥2 weeks at treatment initiation to improve outcomes 3