Is Citrobacter susceptible to Cephalexin (a first-generation cephalosporin antibiotic)?

Citrobacter is Not Susceptible to Cephalexin

Citrobacter species are generally not susceptible to cephalexin (a first-generation cephalosporin) and this antibiotic should not be used for Citrobacter infections. 1, 2

Citrobacter Resistance Mechanisms

Citrobacter species possess an inducible AmpC β-lactamase that renders them naturally resistant to first-generation cephalosporins like cephalexin:

• Citrobacter has a chromosomal AmpC β-lactamase that is inducible and can be easily expressed at high levels 1
• This enzyme confers resistance to first-generation cephalosporins, including cephalexin
• The resistance mechanism is similar to that seen in Enterobacter and Serratia species 1

Antibiotic Susceptibility Profile

Citrobacter species typically show the following susceptibility pattern:

• Resistant to:

  • First-generation cephalosporins (cephalexin)
  • Many second-generation cephalosporins
  • Aminopenicillins

• Variable susceptibility to:

  • Third-generation cephalosporins (resistance can develop during therapy)
  • Fluoroquinolones
  • Aminoglycosides

• Usually susceptible to:

  • Carbapenems (imipenem, meropenem)
  • Fourth-generation cephalosporins (cefepime)
  • Some third-generation cephalosporins (initial susceptibility, but resistance can develop) 3, 4

Clinical Evidence

Case reports and studies support Citrobacter's resistance to cephalexin:

• A case report documented Citrobacter diversus developing resistance to cephalothin (another first-generation cephalosporin similar to cephalexin) during treatment of endocarditis 5
• Comparative studies have shown that first-generation cephalosporins have poor activity against Citrobacter species compared to newer antibiotics 6
• For serious Citrobacter infections, third-generation cephalosporins (like cefotaxime) or fluoroquinolones are often needed, but resistance can still develop 7

Treatment Recommendations

For Citrobacter infections, preferred antibiotics include:

1. Carbapenems (imipenem, meropenem)
2. Fluoroquinolones (ciprofloxacin)
3. Fourth-generation cephalosporins (cefepime)

Important Clinical Caveat

Citrobacter can develop resistance to third-generation cephalosporins during therapy due to selection of mutants that hyperproduce AmpC β-lactamase 1, 3. This phenomenon, known as "inducible resistance," makes treatment of serious Citrobacter infections challenging and requires careful antibiotic selection.

For serious Citrobacter infections, combination therapy or use of carbapenems may be necessary to prevent the emergence of resistance during treatment.