Can Enterobacter cloacae be treated with Ceftriaxone (a third-generation cephalosporin antibiotic)?

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Last updated: June 18, 2025View editorial policy

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From the Guidelines

Ceftriaxone is not recommended as a first-line treatment for Enterobacter cloacae infections due to the risk of inducible resistance and treatment failure. According to the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines 1, third-generation cephalosporin-resistant Enterobacterales, such as Enterobacter cloacae, are best treated with carbapenems (e.g., imipenem or meropenem) as targeted therapy, especially in patients with bloodstream infections and severe infections.

Some key points to consider when treating Enterobacter cloacae infections include:

  • The use of carbapenems, such as imipenem or meropenem, is recommended for severe infections due to their reliability against Enterobacter cloacae 1.
  • For patients with non-severe infections, options like piperacillin-tazobactam, amoxicillin/clavulanic acid, or quinolones may be considered, taking into account antibiotic stewardship principles 1.
  • The ESCMID guidelines also suggest that cephamycins (e.g., cefoxitin, cefmetazole, flomoxef) and cefepime should not be used for treating third-generation cephalosporin-resistant Enterobacterales infections, including those caused by Enterobacter cloacae, due to the risk of resistance 1.

In contrast to the British Thoracic Society guideline for bronchiectasis in adults 1, which suggests ceftriaxone as an option for treating coliforms, including Enterobacter species, the more recent and specific guidelines for multidrug-resistant Gram-negative bacilli from ESCMID 1 provide a clearer recommendation against the use of ceftriaxone for Enterobacter cloacae due to resistance concerns.

Therefore, when considering treatment for Enterobacter cloacae infections, carbapenems should be prioritized over ceftriaxone to minimize the risk of treatment failure and promote better patient outcomes in terms of morbidity, mortality, and quality of life.

From the FDA Drug Label

Ceftriaxone for Injection is indicated for the treatment of the following infections when caused by susceptible organisms: SKIN AND SKIN STRUCTURE INFECTIONS Caused by ... Enterobacter cloacae, ...

Yes, Enterobacter cloacae can be treated with Ceftriaxone, as it is listed as one of the susceptible organisms for skin and skin structure infections, as well as bone and joint infections (under Enterobacter species) 2.

From the Research

Treatment of Enterobacter cloacae with Ceftriaxone

  • Ceftriaxone is a third-generation cephalosporin antibiotic that has been used to treat various infections, including those caused by Enterobacter cloacae 3.
  • However, studies have shown that the use of ceftriaxone can lead to the development of resistance in E. cloacae, with a correlation between ceftriaxone use and increased resistance to third-generation cephalosporins 4.
  • Another study found that ceftriaxone selected resistance in E. cloacae at a faster rate than some other beta-lactam antibiotics, such as cefoperazone and meropenem 5.
  • In contrast, a case report described the successful treatment of a KPC-2 Enterobacter cloacae empyema with cefepime and levofloxacin, but not with ceftriaxone 6.
  • A recent study also reported emerging resistance to ceftriaxone treatment in Enterobacter roggenkampii due to different ampD mutations, highlighting the importance of careful antibiotic selection and combination therapy 7.

Resistance Mechanisms

  • The development of resistance to ceftriaxone in E. cloacae is often associated with the expression of AmpC β-lactamase and mutations in the ampD gene 7.
  • The high biliary elimination of ceftriaxone may also contribute to the selection of resistant strains in the digestive flora 4.
  • The use of ceftriaxone as monotherapy may not be effective in treating E. cloacae infections, especially in cases where resistance is suspected or confirmed 7.

Alternative Treatment Options

  • Cefepime and carbapenems may be preferred over ceftriaxone for the treatment of E. cloacae infections, especially in cases where source control is difficult 7.
  • Combination therapy with multiple antibiotics, such as cefepime and levofloxacin, may also be effective in treating E. cloacae infections 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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