From the Guidelines
Yes, Ceftriaxone is associated with Clostridioides difficile (C. diff) infection.
Risk Factors for C. diff Infection
- Advanced age
- Duration of hospitalization
- Exposure to antibiotic agents, particularly third-/fourth-generation cephalosporins such as Ceftriaxone 1
- Certain classes of antibiotics, including fluoroquinolones, carbapenems, and clindamycin 1
Mechanism of C. diff Infection
The disruption of the intestinal microbiota by antibiotics, including Ceftriaxone, provides a "niche" for C. difficile to flourish 1
Key Points
- The relative risk of therapy with a given antibiotic agent and its association with CDI depends on the local prevalence of strains that are highly resistant to that particular antibiotic agent 1
- The highest risk of CDI appears to be during and in the first month after antibiotic exposure 1
- Even very limited exposure, such as single-dose surgical antibiotic prophylaxis, increases a patient’s risk of C. difficile colonization and symptomatic disease 1
- Ceftriaxone, as a third-generation cephalosporin, has been implicated in the development of CDI, with an odds ratio of 3.2 for third-generation cephalosporins 1
From the FDA Drug Label
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including ceftriaxone, and may range in severity from mild diarrhea to fatal colitis CDAD must be considered in all patients who present with diarrhea following antibiotic use.
Ceftriaxone is associated with Clostridioides difficile (C. diff) infection, as it can alter the normal flora of the colon leading to overgrowth of C. difficile. Key points to consider:
- CDAD can occur with ceftriaxone use
- Severity can range from mild diarrhea to fatal colitis
- Diagnosis should be considered in patients with diarrhea following antibiotic use 2
From the Research
Association between Ceftriaxone and Clostridioides difficile (C. diff) Infection
- Ceftriaxone, a third-generation cephalosporin, has been associated with an increased risk of Clostridioides difficile infection (CDI) in several studies 3, 4, 5, 6.
- A study published in 2021 found that ceftriaxone induced CDI in an in vitro human gut model, whereas first-generation cephalosporins, such as cefalexin and cefradine, did not 3.
- Another study from 2013 found that both ceftaroline and ceftriaxone induced C. difficile spore germination, proliferation, and toxin production in an in vitro human gut model 4.
- A retrospective study published in 2023 found that ceftriaxone was one of the antibiotics associated with CDI, although the most common antibiotics associated with CDI were piperacillin/tazobactam, meropenem, and vancomycin 5.
- However, a study from 2012 found that doxycycline, when given in combination with ceftriaxone, was associated with a lower risk of CDI 7.
- A systematic review and meta-analysis published in 2021 found that third- and fourth-generation cephalosporin antibiotics, including ceftriaxone, were strongly associated with HCFA-CDI 6.
Key Findings
- Ceftriaxone is associated with an increased risk of CDI 3, 4, 5, 6.
- The use of ceftriaxone can induce CDI in in vitro human gut models 3, 4.
- Doxycycline may reduce the risk of CDI when given in combination with ceftriaxone 7.
- Third- and fourth-generation cephalosporin antibiotics, including ceftriaxone, are strongly associated with HCFA-CDI 6.