Should We Reconsider Eliminating Metronidazole as Therapy for Clostridium difficileColitis?

Abstract

Introduction: The new guidelines published in Clinical Infectious Disease in 4/18 recommend vancomycin or fidaxomicin for initial treatment of even mild Clostridium difficile infection (CDI) rather than metronidazole due to higher cure rates. However along with cost concerns, treatment failures need be considered. Our recent research analyzed the risk factors responsible for fulminant CDI requiring fecal microbiota transplant (FMT). The results of our study regarding metronidazole prompted us to think more about these new guidelines and raised the question of if we should reconsider eliminating metronidazole as initial therapy for CDI. Methods: A retrospective chart review was conducted to collect data on patients with CDI responding to antibiotic therapy alone (Group A) vs patients with fulminant recurrent CDI requiring FMT (Group B). The data was analyzed using a logistic regression model to associate the two groups with multiple variables including age, sex, comorbidities, antibiotic use as therapy for CDI, number of recurrences, inpatient status at time of initial infection, and PPI use. Odds ratios corresponding to each covariate were reported with a 95% confidence interval and significance level of 0.05. Results: 152 total subjects were reviewed with 87 in Group A and 66 in Group B. Significant differences found between the two groups included history of ASHD, type of antibiotic used, inpatient status at the time of initial infection, and number of recurrences (the latter having no estimated odds ratio due to sparse information). No significant differences were found between the two groups regarding age, sex, diabetes, hypertension, CVA, chronic kidney disease, appendectomy status, and PPI use. Conclusion: Our results indicated history of ASHD and inpatient status at the time of initial infection were significantly associated with lower risks (0.08OR and 0.43OR, respectively) of fulminant CDI requiring FMT. Additionally, metronidazole treatment of CDI was also associated with a significantly lower (0.3OR) risk of developing fulminant CDI. In contrast, the use of vancomycin and fidaxomicin were both associated with a higher risk (16.29OR and 6.71OR, respectively) of developing fulminant CDI. Thus, it is important to consider treatment failure when recommending vancomycin or fidaxomicin over metronidazole as initial therapy; while these therapies may be associated with a higher cure rate, it may be at the expense of more fulminant infections requiring FMT.2740 Figure 1. Odds Ratios for fulminant CDI requiring FMT according to choice of antibiotic therapy