Citrobacter freundii isolates have demonstrated resistance to traditional agents of antimicrobial chemotherapy. These include ampicillin, carbenicillin, and cephalothin. They also exhibit resistance to agents like third-generation cephalosporins and monobactams  .
A 2019 in-vitro, multi-center study out of China by Zhou et al. found that among 20 Citrobacter strains isolated from animals, resistance was mostly to ampicillin, tetracycline, streptomycin, florfenicol, chloramphenicol, and aztreonam, while all the strains found in environmental samples were resistant to few antibiotics .
In 2018, Yang et al. isolated a highly multi-drug resistant, carbapenemase-producing Citrobacter freundii strain (CWH001) resistant to all tested antimicrobials except tetracycline .
This situation is disturbing because carbapenem is a class of antibiotics used to treat severe infections. Carbapenem-resistant Enterobacteriaceae become resistant to almost all available antibiotics. These bacteria produce carbapenemases, enzymes that can render most antibiotics ineffective. There are three classes of enzymes that drive carbapenem resistance. They are:
- class A carbapenemases,
- class B metallo-β-lactamases (MBL), and
- class D β-lactamases (OXA).
A carbapenemase enzyme called OXA-48 (class D) is being produced by a growing number of carbapenem-resistant bacteria and rapidly spreading in the Mediterranean region and the Middle East. Recently, even European countries like the Netherlands, Belgium, Italy, the United Kingdom, and Switzerland have found the presence of OXA-48. More drug-resistant OXA enzymes are being discovered, including OXA-181 and OXA-163.
These OXA enzymes can evade common diagnostic tests, which is problematic. More research is required to help improve the accuracy and effectiveness of diagnostic tests and therapies for carbapenemase-producing Enterobacteriaceae .