Is cefepime (antibiotic) a good option for treating complicated urinary tract infections (UTIs)?

Is Cefepime a Good Antibiotic for Complicated UTI?

Yes, cefepime is FDA-approved and effective for complicated UTIs, but it is not a preferred first-line agent according to current guidelines—carbapenems, newer β-lactam/β-lactamase inhibitor combinations, and aminoglycosides are recommended as first-line empiric therapy for complicated UTIs. 1, 2

FDA-Approved Indication and Dosing

Cefepime is specifically FDA-approved for both uncomplicated and complicated urinary tract infections (including pyelonephritis) caused by E. coli, K. pneumoniae, and Proteus mirabilis 2. The approved dosing regimens are:

• Mild to moderate complicated UTI: 0.5-1 g IV every 12 hours for 7-10 days 2
• Severe complicated UTI: 2 g IV every 12 hours for 10 days 2

Why Cefepime Is Not First-Line

Despite FDA approval, current European Urology guidelines (2025) do not list cefepime among the recommended first-line empiric options for complicated UTIs 1. The preferred empiric regimens are:

• Carbapenems: Imipenem/cilastatin 0.5 g three times daily, meropenem 1 g three times daily, or meropenem-vaborbactam 2 g three times daily 1
• Newer β-lactam/β-lactamase inhibitors: Ceftolozane/tazobactam 1.5 g three times daily, ceftazidime/avibactam 2.5 g three times daily, or cefiderocol 2 g three times daily 1
• Aminoglycosides: Gentamicin 5 mg/kg once daily, amikacin 15 mg/kg once daily, or plazomicin 15 mg/kg once daily 1

Evidence Concerns with Cefepime

The ESCMID guidelines (2022) raise significant safety concerns about cefepime for treating infections caused by ESBL-producing organisms and AmpC producers 3. Key findings include:

• In a Taiwanese study of 178 patients with ESBL-producing Enterobacterales bloodstream infections, cefepime treatment (only 17 patients) was associated with higher mortality in both multivariate and propensity-score matched analyses 3
• In patients with cephalosporin-resistant Enterobacter species and higher cefepime MICs (even within the susceptible dose-dependent category), mortality was significantly higher with cefepime (5 of 7 vs 2 of 11, p=0.045) 3
• The evidence quality was very low due to serious inconsistency and high risk of bias 3

When Cefepime May Be Appropriate

Cefepime can be considered in specific clinical scenarios:

1. Culture-directed therapy: When susceptibility testing confirms the pathogen is susceptible to cefepime with low MIC values, and the patient is clinically stable 2, 4

2. Non-ESBL, non-AmpC producers: Historical data shows cefepime achieved 89% clinical response and 85% bacterial eradication in complicated UTIs caused by susceptible organisms 4

3. Concurrent bacteremia: In older studies, cefepime successfully eradicated E. coli and P. mirabilis in 5 of 6 patients with UTI and concurrent bacteremia 4

Clinical Performance Data

Research evidence demonstrates:

• Cefepime 1 g twice daily achieved 94% clinical cure rate (191/204 patients) for various bacterial infections including UTIs, with 93% pathogen eradication 5
• Cefepime 500 mg every 12 hours produced 89% satisfactory clinical response and 85% bacterial eradication in complicated UTIs 4
• Treatment was well-tolerated with only 2-3% discontinuation rates due to adverse events 4, 5

Important Caveats

Do not use cefepime as empiric therapy for complicated UTIs in the following situations:

• Suspected or confirmed ESBL-producing organisms 3
• Suspected or confirmed AmpC-producing organisms (especially Enterobacter species) 3
• Multidrug-resistant organisms 1
• Patients with prior fluoroquinolone resistance or recent antibiotic exposure 1
• Healthcare-associated infections where resistance is more likely 1

Recommended Approach

For empiric therapy of complicated UTI, start with a carbapenem, newer β-lactam/β-lactamase inhibitor combination, or aminoglycoside 1. Once culture and susceptibility results are available, de-escalate to cefepime only if the organism is confirmed susceptible with favorable MIC values and the patient is clinically improving 2. Treatment duration should be 7-14 days depending on clinical response, with 14 days recommended for men when prostatitis cannot be excluded 1.