The 2021 Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) focused update guidelines on the management of Clostridioides difficile infection (CDI) in adults provides recommendations regarding the use of fidaxomicin and vancomycin for the treatment of CDI Prophylaxis for CDI is not addressed within the guidelines. [1]
The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) 2021 update on the treatment guidance for CDI identified the most important risk factors for severe CDI as age over 65 years old and the presence of multiple comorbidities. For recurrent CDI, most important risk factors included age over 65 and prior CDI episodes. Routine administration of anti-CDI antibiotics when on systemic antibiotic treatment is not recommended, based on expert opinion (i.e., Good Practice Statement). In very selected patients with a history of multiple recurrent CDI precipitated by systemic antibiotic use, prophylaxis with microbiota-sparing anti-CDI antibiotics may be warranted with careful consideration of risk versus benefits and suggested expert consultation/decision by case. (Good Practice Statement). The guidelines acknowledge recent retrospective observational studies reporting reductions of 5 to 30% in CDI occurrence with oral vancomycin prophylaxis (OVP), however these studies primarily included patients at high risk for CDI (e.g., hematological patients, patients with prior CDI episodes, or transplant patients). The panel considered the findings of other vancomycin studies and the fidaxomicin study by Mullane et al (Table 1) to conclude there is potential benefit of prophylaxis in selected patients but cautioned widespread application due to potential side-effects, microbiome distortion, and potential for antimicrobial resistance and associated risk for recurrent CDI. Studies assessing vancomycin-resistant Enterococci (VRE) are limited by short follow-ups, unclear methods, or focus on VRE infections rather than colorizations, thus leaving ongoing concerns. [2]
A 2021 review article describes CDI prophylactic treatment strategies and their implementation in clinical practice. Overall, it is suggested that antibiotic prophylaxis may be considered in very specific cases, such as elderly patients with a history of recurrent CDI or immunosuppressed patients undergoing treatments that previously led to CDI. Both fidaxomicin and vancomycin have been shown to be effective in reducing CDI in high-risk patients. While there is more existing literature on prophylaxis with vancomycin, it is suggested that fidaxomicin may be a more suitable prophylactic option for preserving the intestinal microbiota; however, its high cost may limit feasibility. Regimens utilized in available data are fidaxomicin 200 mg once daily and vancomycin 125 mg once daily administered for the duration of the treatment/procedure that poses the risk for CDI. However, the strength of evidence supporting this prophylactic strategy is limited. Given the scarcity of data, the authors note that there are currently no proven effective, evidence-based prophylaxis options for primary CDI. [3]
A 2022 meta-analysis and trial sequential analysis of 11 studies evaluated the efficacy and safety of OVP in both primary and secondary prevention of CDI in patients undergoing systemic antibiotic therapy. Data compiled from 1 randomized controlled trial (RTC) and 10 retrospective observational studies included 929 patients who received OVP compared to 2,011 patients in the comparator group with no active prophylaxis. The dose of oral vancomycin varied, but in most instances was 125 mg once or twice daily. The overall incidence of CDI was 11.2% in the OVP group compared to 14.9% in the comparator group (odds ratio [OR] 0.13, 95% confidence interval [CI] 0.04 to 0.38, I2 54%). Four studies (3 retrospective cohorts and 1 open label RCT) evaluated OVP in the primary prevention subgroup (OR 0.03, 95% CI 0.0 to 0.18, I2 0%) while the remaining 7 studies evaluated OVP for the recurrent CDI subgroup (OR 0.31, 95% CI 0.13 to 0.71, I2 71%). Results of the subgroup analysis suggested a significant subgroup effect (p= 0.02). The overall number needed to treat (NNT) in patients undergoing systemic antibiotic therapy was 6. The overall incidence of vancomycin-resistant Enterococci (VRE) infections was 2.4% in the OVP group compared to 0.9% in the comparator group, suggesting OVP was not associated with higher risk of VRE infection complication (risk difference [RD] equal to zero, 95% CI -0.02 to 0.01). The authors concluded the use of OVP appears efficacious for both primary and secondary prevention of CDI in high-risk subjects, although the optimal dose and duration are not yet defined. [4]
Another meta-analysis published in 2021 evaluated the use of OVP in the prevention of CDI with systemic antimicrobial therapy in hospitalized adults. Fourteen studies were included: 13 retrospective observational studies and 1 open-label prospective trial. The dose of OVP varied, with duration ranging from 7-29 days and follow-up for CDI recurrence ranging from 30 days to 1 year. Five studies (4 retrospective cohorts and 1 open label RCT), including 402 OVP patients compared to 950 without OVP, evaluated the use of OVP in patients with no prior CDI episode and on systemic antibiotics (primary prevention). The pooled data revealed a non-significant trend towards a decrease in risk of primary CDI with OVP (OR 0.18, 95% CI 0.03 to 1.09, p= 0.06). The remaining 10 studies evaluated efficacy in secondary prevention which found a statistically significant reduction in rates of future CDI with OVP. Overall, 3 studies assessed the risk of VRE infections after OVP with no significant difference found when compared to no OVP. Authors note the observational data from low-quality studies demonstrated a decreased risk of future CDI (secondary prevention) in patients requiring systemic antimicrobial therapy, suggesting a reasonable use for patients with a history of multiple CDI episodes. Further data is needed to guide other use scenarios such as primary prevention, as well as determining the optimal dosing and potential risks such as resistance. [5]