Oral fidaxomicin versus vancomycin for the treatment of Clostridioides difficile infection: A systematic review and meta-analysis of randomized controlled trials

Sho Tashiro; Takayuki Mihara; Moe Sasaki; Chiaki Shimamura; Rina Shimamura; Shiho Suzuki; Maiko Yoshikawa; Tatsuki Hasegawa; Yuki Enoki; Kazuaki Taguchi; Kazuaki Matsumoto; Hiroki Ohge; Hiromichi Suzuki; Atsushi Nakamura; Nobuaki Mori; Yoshitomo Morinaga; Yuka Yamagishi; Sadako Yoshizawa; Katsunori Yanagihara; Hiroshige Mikamo; Hiroyuki Kunishima

doi:10.1016/j.jiac.2022.08.008

Oral fidaxomicin versus vancomycin for the treatment of Clostridioides difficile infection: A systematic review and meta-analysis of randomized controlled trials

J Infect Chemother. 2022 Nov;28(11):1536-1545. doi: 10.1016/j.jiac.2022.08.008. Epub 2022 Aug 11.

Authors

Sho Tashiro¹, Takayuki Mihara¹, Moe Sasaki¹, Chiaki Shimamura¹, Rina Shimamura¹, Shiho Suzuki¹, Maiko Yoshikawa¹, Tatsuki Hasegawa¹, Yuki Enoki², Kazuaki Taguchi¹, Kazuaki Matsumoto¹, Hiroki Ohge³, Hiromichi Suzuki⁴, Atsushi Nakamura⁵, Nobuaki Mori⁶, Yoshitomo Morinaga⁷, Yuka Yamagishi⁸, Sadako Yoshizawa⁹, Katsunori Yanagihara¹⁰, Hiroshige Mikamo¹¹, Hiroyuki Kunishima¹²

Affiliations

¹ Division of Pharmacodynamics, Keio University Faculty of Pharmacy, Tokyo, Japan.
² Division of Pharmacodynamics, Keio University Faculty of Pharmacy, Tokyo, Japan. Electronic address: enoki-yk@pha.keio.ac.jp.
³ Department of Infectious Diseases, Hiroshima University Hospital, Hiroshima, Japan.
⁴ Department of Infectious Diseases, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
⁵ Department of Infection Prevention and Control, Graduate School of Medical Sciences, Nagoya City University, Aichi, Japan.
⁶ Department of General Internal Medicine and Infectious Diseases, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
⁷ Department of Microbiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
⁸ Department of Clinical Infectious Diseases, Kochi Medical School, Kochi, Japan.
⁹ Department of Clinical Laboratory / Department of Microbiology and Infectious Diseases, Toho University Faculty of Medicine, Tokyo, Japan.
¹⁰ Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
¹¹ Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Aichi, Japan.
¹² Department of Infectious Diseases, St. Marianna University School of Medicine, Kanagawa, Japan.

PMID: 35964806
DOI: 10.1016/j.jiac.2022.08.008

Abstract

Background: Fidaxomicin (FDX) has received considerable attention as a novel therapeutic alternative agent to vancomycin (VCM) for Clostridioides difficile infection (CDI). However, the superiority and efficacy profile of FDX are not sufficiently determined by high-quality evidence. This study aimed to clarify the superiority of FDX for CDI treatment through a systematic review and meta-analysis.

Methods: We conducted a meta-analysis of randomized controlled trials (RCTs) which evaluated the efficacy and safety of FDX and VCM in patients with CDI. Electronic databases (PubMed, Cochrane Library, Web of Science, and Clinicaltrials.gov) were searched for studies published until October 15, 2021. The primary endpoint was global cure. The secondary endpoints were clinical cure, recurrence, and adverse event. Risk ratios (RRs), risk differences (RDs), and 95% confidence intervals were calculated using Mantel-Haenszel random-effects model. The risk of bias was assessed using Cochrane Handbook for Systematic Reviews of Interventions and Assessment Criteria.

Results: Six RCTs were included in this meta-analysis. Compared to VCM, FDX was associated with significantly higher global cure rates (RR = 1.18, P < 0.00001; RD = 0.11, 95% CI = 0.07-0.16). In addition, clinical cure rates were comparable between FDX and VCM (P = 0.31). FDX was associated with significantly lower recurrence rates compared to VCM (RR = 0.59, P < 0.0001). In addition, adverse event rates were not significantly different between the drugs (P = 0.41).

Conclusion: FDX achieves significantly higher global cure rates and lower recurrence rates and is comparable to VCM in clinical cure rates and adverse event rates in patients with CDI. Collectively, FDX is superior to VCM as a therapeutic agent for CDI.

Keywords: Clostridioides difficile infection; Fidaxomicin; Global cure; Meta-analysis; Recurrence; Vancomycin.

Publication types

Meta-Analysis
Systematic Review

MeSH terms

Anti-Bacterial Agents / adverse effects
Clostridioides difficile*
Clostridium Infections* / drug therapy
Fidaxomicin / therapeutic use
Humans
Randomized Controlled Trials as Topic
Vancomycin / adverse effects

Substances

Anti-Bacterial Agents
Vancomycin
Fidaxomicin