Risk of C. difficile Infection with Ceftriaxone Followed by Amoxicillin-Clavulanate
Yes, this antibiotic regimen places the patient at increased risk for C. difficile infection, with the risk elevated up to sixfold during therapy and for one month afterward. 1
Understanding the Specific Risk Profile
Both antibiotics in this sequential regimen are independently associated with CDI risk:
Ceftriaxone (third-generation cephalosporin) has traditionally been considered to pose significant CDI risk, with cephalosporins showing a weighted pooled resistance rate of 47% and an odds ratio of 4.47 for community-associated CDI 2, 3
Amoxicillin-clavulanate (penicillin combination) is among the antibiotics traditionally associated with increased CDI risk, with penicillins showing an odds ratio of 3.25 for community-associated CDI 1, 3
The 10-day duration of the Augmentin course further amplifies risk, as longer antibiotic duration is directly associated with increased CDI incidence—a 10-day course incurs 12% more risk compared to a 7-day course 4
Key Risk Factors to Assess
The patient's individual risk factors substantially modify CDI likelihood 1:
- Age >65 years 1
- Recent hospitalization or healthcare facility exposure 1
- Proton pump inhibitor (PPI) use, which increases CDI risk (OR 1.26-1.39) and should be avoided if possible during and after this antibiotic course 1, 5
- Previous CDI episode, which dramatically increases recurrence risk 1
- Immunocompromised status or immunosuppressive therapy 1
- Severe underlying disease or advanced comorbidities 1
Clinical Management Recommendations
Discontinue the inciting antibiotic as soon as clinically appropriate to reduce recurrence risk 6
Avoid unnecessary PPI use during and after this antibiotic course, as PPIs independently increase CDI risk 1
There is insufficient evidence to recommend prophylactic anti-C. difficile agents (like vancomycin) for patients receiving this regimen unless they have multiple prior CDI episodes 1, 5
Important Caveats
A single dose of ceftriaxone carries substantially less risk than prolonged courses, so the initial Rocephin administration contributes less to overall risk than the subsequent 10-day Augmentin course 1
The cumulative antibiotic exposure (sequential use of two different agents) compounds the risk beyond what either agent would pose individually 1
Even limited antibiotic exposure increases patients' risk for both C. difficile colonization and infection 1
The risk remains elevated for one month after completing antibiotics, so vigilance for CDI symptoms should extend beyond the treatment period 1