What is the appropriate treatment for a patient with a urine culture positive for Citrobacter freundii?

Treatment of Urinary Tract Infection Caused by Citrobacter freundii

For patients with a urine culture positive for Citrobacter freundii, targeted antimicrobial therapy should be based on susceptibility testing, with carbapenems, cefepime, or ciprofloxacin (if susceptible) being the most effective options.

Understanding Citrobacter freundii Infections

• Citrobacter freundii is an opportunistic Gram-negative bacterium that can cause various infections, including urinary tract infections (UTIs), particularly in patients with underlying conditions 1, 2
• C. freundii has shown increasing resistance to many antimicrobial agents over time, making treatment challenging 3
• UTIs are the most common clinical syndrome associated with Citrobacter species, accounting for approximately 52.6% of Citrobacter infections 2

Antimicrobial Susceptibility Considerations

• C. freundii has demonstrated high resistance to:

  • Anti-pseudomonal penicillins
  • First, second, and third-generation cephalosporins
  • Some aminoglycosides (gentamicin, tobramycin)
  • Aztreonam 3

• Most effective agents against C. freundii based on susceptibility studies include:

  • Carbapenems (imipenem, meropenem) - 97.4% susceptibility
  • Cefepime - 73.7% susceptibility
  • Ciprofloxacin - 80.6% susceptibility (if local resistance patterns permit)
  • Gentamicin - 89.5% susceptibility
  • Colistin and fosfomycin - 100% susceptibility in some studies 2

Treatment Algorithm

Step 1: Obtain Appropriate Cultures and Susceptibility Testing

• Always obtain urine culture and susceptibility testing before initiating therapy 4
• Base final treatment on culture results and susceptibility patterns 4

Step 2: Initial Empiric Therapy (while awaiting culture results)

• For complicated UTI with systemic symptoms:

  • Consider a combination therapy with amoxicillin plus an aminoglycoside OR
  • A second-generation cephalosporin plus an aminoglycoside OR
  • An intravenous third-generation cephalosporin 4

• For uncomplicated UTI without systemic symptoms:

  • Consider ciprofloxacin if local resistance is <10% 4
  • Avoid ciprofloxacin if the patient has used fluoroquinolones in the past 6 months 4

Step 3: Targeted Therapy (after susceptibility results)

• Adjust therapy based on susceptibility results 4
• Preferred options (in order of preference):
  1. Carbapenems (imipenem or meropenem) - highest efficacy against C. freundii 3, 2
  2. Cefepime - good activity against C. freundii even with increasing resistance patterns 3
  3. Ciprofloxacin - if susceptible and no contraindications 5, 2
  4. Aminoglycosides (gentamicin or amikacin) - good option if susceptible 2

Step 4: Treatment Duration

• For uncomplicated UTI: 7 days of therapy 4
• For complicated UTI: 7-14 days of therapy 4
• For males where prostatitis cannot be excluded: 14 days 4

Special Considerations

Complicated UTI Factors

• Consider the following factors that may complicate treatment:
  • Urinary tract obstruction
  • Foreign body presence
  • Incomplete voiding
  • Immunosuppression
  • Diabetes mellitus
  • Healthcare-associated infections
  • Extended-spectrum β-lactamase (ESBL) production 4

Pediatric Considerations

• C. freundii UTIs in children are more common in those with underlying urinary tract/renal anomalies or neurologic impairment 6
• For pediatric patients, treat positive bacterial pathogens in urine with targeted antimicrobial therapy for a duration consistent with the nature of the disease, responsible organism, and response to treatment 4
• Ciprofloxacin is not a drug of first choice in the pediatric population due to increased adverse events 5

Monitoring and Follow-up

• If symptoms persist despite appropriate antimicrobial therapy, repeat urine culture to assess for ongoing bacteriuria 4
• For patients with recurrent UTIs, consider underlying anatomical or functional abnormalities 4

Antimicrobial Stewardship Considerations

• Use targeted therapy based on susceptibility to reduce the development of drug resistance 5
• Avoid broad-spectrum antibiotics when narrower-spectrum agents are effective 5
• Consider local resistance patterns when selecting empiric therapy 4