Treatment of Citrobacter freundii UTI
For uncomplicated Citrobacter freundii UTI, use nitrofurantoin 100 mg PO every 6 hours for 5-7 days or fosfomycin 3 g PO single dose as first-line therapy, while for complicated UTI or severe infection, carbapenems (meropenem or imipenem) remain the most reliable empiric choice pending susceptibility results. 1, 2
Severity-Based Treatment Algorithm
Uncomplicated Lower UTI (Simple Cystitis)
- Nitrofurantoin 100 mg PO every 6 hours for 5-7 days is the preferred first-line agent 2, 3
- Fosfomycin 3 g PO single dose is an excellent alternative with high urinary concentrations 2, 3
- Single-dose aminoglycoside can be considered if the organism is susceptible 4
Complicated UTI or Pyelonephritis
- Carbapenems (imipenem or meropenem) are the most active agents against C. freundii and should be used for empiric therapy in severe infections 1
- Cefepime is an alternative fourth-generation cephalosporin with good activity 1, 2
- Piperacillin-tazobactam can be used for moderate infections when susceptibility is confirmed 2, 3
Critical Resistance Considerations
C. freundii possesses inducible AmpC β-lactamase, making it inherently resistant to most first-, second-, and third-generation cephalosporins, as well as anti-pseudomonal penicillins 1. This is a common pitfall—avoid using ceftriaxone, cefotaxime, ceftazidime, or ampicillin-sulbactam as they will likely fail.
Agents to AVOID:
- First-, second-, and third-generation cephalosporins (high resistance rates) 1
- Trimethoprim-sulfamethoxazole (increasing resistance) 2
- Fluoroquinolones for empiric therapy (markedly decreased susceptibility over time, reserve for directed therapy only) 1, 2
- Aztreonam (high resistance) 1
If Multidrug Resistance is Suspected
For complicated UTI with concern for carbapenem resistance or ESBL production:
- Ceftazidime-avibactam 2.5 g IV q8h is recommended for carbapenem-resistant Enterobacterales 4
- Meropenem-vaborbactam 4 g IV q8h or imipenem-cilastatin-relebactam 1.25 g IV q6h are newer β-lactam/β-lactamase inhibitor combinations 4
- Plazomicin 15 mg/kg IV q12h (aminoglycoside) for complicated UTI due to resistant organisms 4
Duration of Therapy
- Uncomplicated cystitis: 5-7 days (or single dose for fosfomycin) 2, 3
- Complicated UTI/pyelonephritis: 7-14 days depending on clinical response 3, 5
- Severe infections with bacteremia: 14-21 days 5
Key Clinical Pearls
Always obtain urine culture and susceptibility testing before initiating therapy for complicated UTI, as resistance patterns are unpredictable 3, 5. De-escalate therapy once susceptibilities return to preserve carbapenem activity.
Consider prolonged infusion of β-lactams (administered over 3-4 hours) when treating organisms with elevated MICs to optimize pharmacodynamic targets 4.
Infectious disease consultation is strongly recommended for management of multidrug-resistant C. freundii infections 4.