Fidaxomicin, Oral Metronidazole Demonstrate Similar Clinical Efficacy Among Patients With C Diff

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A retrospective study of patients with Clostridioides difficile infection (CDI) treated with fidaxomicin or oral metronidazole found no significant differences in global or clinical cure rate, but highlighted increased first line drug changes among patients treated with metronidazole.

“Unfortunately, real-world comparative studies assessing the clinical efficacy of [metronidazole] and [fidaxomicin], along with their associated recurrence rates, remain limited,” wrote investigators.¹ “This study aimed to comprehensively evaluate the clinical efficacy of [fidaxomicin] and oral [metronidazole] in the treatment of CDI and the associated recurrence rates. By directly comparing these two treatment modalities, we aimed to elucidate the potential advantages and disadvantages of each regimen, which might aid clinicians in making informed decisions regarding CDI management.”

Natural gut immunity may resolve CDI without additional treatment. However, antibiotics including fidaxomicin, metronidazole, and vancomycin are commonly prescribed to treat more severe cases of CDI.²

To assess the efficacy and recurrence rates associated with fidaxomicin and oral metronidazole, a team of investigators led by Hiroshige Mikamo, MD, professor in the department of Clinical Infectious Diseases at Aichi Medical University in Nagakute, Japan, retrospectively evaluated data from patients diagnosed with CDI between January 2015 and March 2023. Investigators assessed 264 patients diagnosed with CDI for eligibility and selected 105 to participate in the study based on treatment with fidaxomicin or oral metronidazole and symptom improvement within 10 days of treatment.¹

The primary outcome of interest was global cure rate. Secondary outcomes included factors contributing to the CDI global cure rate, the rate of medication change due to initial treatment failure, and incidence rates of clinical cure, recurrence, and all-cause mortality within 30 days.¹

Of the 105 patients included, 75 were treated withoral metronidazole and 30 were treated with fidaxomicin. Among all participants, the median age was 76 years (interquartile range 68–83) and most patients were male (n = 56) . Investigators noted the 2 groups were well matched in terms of baseline characteristics such as age, sex, and comorbidities. However, investigators pointed out 36.7% of patients in the fidaxomicin group were using potassium-competitive acid blockers compared to 8.0% of patients in the metronidazole group (P < .01). Additionally, more patients in the metronidazole group (18.7%) were using probiotics than the fidaxomicin group (3.3%) prior to CDI diagnosis (P = .04).¹

Upon analysis, there was no difference in the global cure rate between the metronidazole and fidaxomicin groups (53.3% vs 70.0%; P = .12). Investigators also highlighted no significant difference was observed between oral metronidazole and fidaxomicin groups, respectively, for the following outcomes:

• Clinical cure (78.7% vs 86.7%; P = .35)
• Recurrence rate (25.3% vs 16.7%; P = .34)
• Cause of death within 30 days (1.4% vs 3.4%; P = .50)

Of note, there were significantly more first-line drug changes during CDI treatment in the metronidazole group than in the fidaxomicin group (18.7% vs. 0.0%; P = 0.01). In the metronidazole group, 12 patients were switched to vancomycin or fidaxomicin after failure of initial treatment, and 2 were switched to intravenous metronidazole instead of oral metronidazole. Investigators also noted there were no adverse events observed in the fidaxomicin group, while 2 patients in the metronidazole group switched treatment due to nausea and a decrease in blood count.¹

“Our findings suggest the need for caution in the therapeutic management of CDI by using oral [metronidazole]. Although there was no significant difference in the global cure rate between the oral [metronidazole] and [fidaxomicin] groups in this study, it should be considered that the initial treatment failed in approximately 18% of the patients in the [metronidazole] group, resulting in a change in the treatment drug,” concluded investigators.¹

References:

1. Mori N, Hirai J, Ohashi W, et al. Clinical Efficacy of Fidaxomicin and Oral Metronidazole for Treating Clostridioides difficile Infection and the Associated Recurrence Rate: A Retrospective Cohort Study. Antibiotics. 2023; 12(8):1323. https://doi.org/10.3390/antibiotics12081323
2. Cleveland Clinic. C. diff (Clostridioides difficile) Infection. Diseases & Conditions. Accessed September 7, 2023. https://my.clevelandclinic.org/health/diseases/15548-c-diff-infection