Antibiotic Exposure after Clostridium difficile infection (CDI) diagnosis in Pediatric Oncology Patients.

Background:  Antibiotic exposure is a known risk factor for CDI.   While stopping antibiotics after CDI may improve gut microbial recovery, it may be impractical in highly immunosuppressed patients at risk for severe infections.

Methods:  This was a single-center study of all laboratory-identified CDI cases in pediatric oncology patients from Jan 1 to Dec 31, 2015 based on a validated stool PCR assay of diarrheal stools.  All CDI samples were characterized by multilocus sequence typing (MLST) as part of infection control protocol.  Patients were categorized as 1) isolated infection 2) relapsed (recovery of same MLST from subsequent stool sample) 3) re-infected (different MLST) or 4) both relapsed and re-infected (recovery of both recurrent and novel MLSTs  from PCR positive stools) during the study period. Antibiotic utilization (excluding prophylaxis and CDI therapy) was measured as days of therapy (DOT) per drug in the 30 days prior and 8 weeks subsequent to CDI. Statistical analysis was conducted in SAS v 9.4.

Results: Of the 96 patients with CDI, 80 were inpatients within 8 weeks of testing positive, and the mean DOT was 13.3 (range 0-164).  Fourteen were classified as reinfected, 12 as relapsed and 5 had both relapse and reinfection.  Mean antibiotic DOT in the 30 days prior to initial CDI diagnosis was not significantly different among the 4 groups (p=0.71) (Figure 1).  The mean DOT in the 8 weeks following CDI diagnosis for each CDI category was also not significant (p=0.62), although the standard deviations among the groups were wide.  Although there was no significant difference in DOT before or after CDI diagnosis, there was a trend towards difference in patients who developed both relapse and reinfection, compared to those who developed either in isolation (Figure 2).

Conclusion: There was no significant difference in antibiotic exposure and subsequent CDI, owing perhaps to small sample size, inability to assess symptomatic CDI, drug class specific effects and non-standard retesting interval. However, there may be a correlation between DOT and relapse vs reinfection.    Further study of the relationship of antibiotic exposure and ongoing CDI is needed with particular attention to the need for post-diagnosis antibiotics in highly vulnerable populations. 

Figure 1.

Figure 2.