C-D-I wonder what’s new with our old friend

Reviewed by Sara Karaba, MD, PhD, MHS, Johns Hopkins University and Jen Cihlar, DO, Vanderbilt University Medical Center

Antibiotics and proton pump inhibitors (PPI) are both well-known individual risk factors for difficile infection (CDI), and Moreels et al sought to investigate the combined risk of initial and recurrent CDI between these two medication classes using a large nationwide population-based health registry out of Sweden with matched controls over between 2006-2019. They found that when used in combination, there was a higher risk of initial CDI in both recent (within 30 days) and preceding (within 31-180 days) use compared to either antibiotic or PPI use alone (ORcombo recent 17.51; ORcombo preceding =  9.13 vs ORabx recent= 15.37 ; ORabx preceding = 5.42 vs ORPPI recent= 2.65; ORPPI preceding = 2.08).  Authors hypothesized that the larger difference in impact of recent versus preceding antibiotic use when compared to that of PPI use could be linked to chronicity of PPI use on continued gut dysbiosis compared to the dramatic effect an acute disruption an antibiotic would have. While there was a slightly higher odds of CDI recurrence with recent antibiotic use compared to preceding antibiotic use (OR 1.3 vs 1.23), the risk of recurrence barely changed if combined with PPIs.  These trends were found throughout almost all antibiotic subclasses.

One of the most impactful interventions to be made is not only to reduce antibiotic use, but also consider a more conservative approach to PPI use commonly contributing polypharmacy.  As noted in this study an important risk factor for recurrence was prior history of CDI (OR = 1.84). 

Rao and colleagues led an open-label randomized trial examining the efficacy of fidaxomicin vs oral vancomycin among patients with C. difficile infection (CDI) who also require concomitant antibiotics (CA). In prior trials there were conservative definitions of CA (for example, excluded from trial if expected would require 7 or more days of CA). In this study, Rao et al enrolled patients with CDI and receiving one or more high- or medium-risk antibiotic for treatment of infection with anticipated duration of at least 5 days. The authors enrolled 144 patients (shy of the target enrollment of 200, and thus possibly under-powered), and while patients who received fidaxomicin had a numerically higher clinical cure at end of therapy, this difference was not statistically different (73.0% vs 62.9%, P=0.195). Recurrent CDI was low in both arms (3.3 and 4% in fidaxomicin and vancomycin arms, respectively), potentially reflecting extension of either agent to overlap with CA courses. This study does not suggest superiority of one agent over the other for the treatment of CDI while on CA, though given the trend of higher clinical cure with fidaxomicin, examining this question in a larger study is warranted.


Moreels N, Boven A, Gressani O, et al.. The combined effect of systemic antibiotics and proton pump inhibitors on Clostridioides difficile infection and recurrence. Journal of Antimicrobial Chemotherapy. 2024;79(3):608-616. doi:10.1093/jac/dkae012

Rao K, Zhao Q, Bell J, et al. An Open-Label, Randomized Trial Comparing Fidaxomicin With Oral Vancomycin for the Treatment of Clostridioides difficile Infection in Hospitalized Patients Receiving Concomitant Antibiotics for Concurrent Infections. Clin Infect Dis 2024; 78:277–282. doi: 10.1093/cid/ciad606

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