Is Citrobacter freundii susceptible to cefdinir (Cefdinir)?

Citrobacter freundii is NOT Susceptible to Cefdinir

Citrobacter freundii should NOT be treated with cefdinir as it demonstrates inherent resistance to this antibiotic, making it an ineffective treatment choice that could lead to treatment failure and increased morbidity and mortality. 1

Mechanism of Resistance

Citrobacter freundii possesses natural resistance to many cephalosporins, including cefdinir, through several mechanisms:

• Production of chromosomal AmpC β-lactamases
• Ability to develop resistance during therapy (inducible resistance)
• Decreased permeability of the outer membrane
• Alteration of penicillin-binding proteins (PBPs)

According to the FDA drug label for cefdinir, it specifically states that "Cefdinir is inactive against most strains of Enterobacter spp." 1 Citrobacter freundii belongs to the Enterobacteriaceae family and shares similar resistance mechanisms with Enterobacter species.

Evidence of Resistance

The FDA drug label for cefdinir clearly indicates which organisms cefdinir is active against, and Citrobacter freundii is notably absent from the list of susceptible gram-negative bacteria. While the label mentions that cefdinir exhibits in vitro activity against Citrobacter koseri, it does not include Citrobacter freundii, highlighting the distinction between these two Citrobacter species 1.

This distinction is further supported by historical research showing that 79% of Citrobacter freundii strains were resistant to early cephalosporins, while 96% of Citrobacter koseri strains were sensitive 2.

Increasing Resistance Patterns

Clinical studies have documented increasing resistance of Citrobacter freundii to cephalosporins:

• A retrospective study found increasing resistance to most third-generation cephalosporins in both nosocomial and community-acquired C. freundii bacteremia 3
• Another study comparing antimicrobial susceptibility in two different time periods found that most C. freundii isolates were resistant to first, second, and third-generation cephalosporins 4
• A more recent study found C. freundii strains co-producing multiple carbapenemases, further complicating treatment options 5

Appropriate Antibiotic Choices for C. freundii

For infections caused by Citrobacter freundii, more appropriate antibiotic choices include:

1. First-line options:

   • Carbapenems (imipenem/cilastatin, meropenem)
   • Fluoroquinolones (levofloxacin)
   • Fourth-generation cephalosporins (cefepime, cefpirome)

2. Alternative options:

   • Piperacillin/tazobactam (with increasing resistance noted)
   • Aztreonam/avibactam for multi-resistant strains

Clinical Implications

Using cefdinir to treat Citrobacter freundii infections would likely result in:

• Treatment failure
• Prolonged infection
• Potential for development of additional resistance
• Increased risk of mortality (documented at 22% for C. freundii bacteremia) 3

Pitfalls to Avoid

1. Do not confuse Citrobacter species: Citrobacter koseri may be susceptible to cefdinir while C. freundii typically is not 1, 2

2. Do not rely on older susceptibility data: Resistance patterns have increased over time 3, 4

3. Avoid empiric cephalosporin monotherapy: For suspected C. freundii infections, especially in healthcare settings or in patients with recent antibiotic exposure 6

4. Consider combination therapy: Studies have shown that combination antimicrobial therapy may be more effective for C. freundii infections 3

In conclusion, cefdinir should not be used for the treatment of Citrobacter freundii infections due to inherent resistance patterns and the availability of more effective alternative antibiotics.