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Optimal therapeutic recommendation for Clostridioides difficile infection in pediatric and adolescent populations: a systematic review and meta-analysis

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Abstract

We conducted a systematic review and meta-analysis to examine the efficacy profiles of metronidazole (MNZ) and vancomycin (VCM) in pediatric and adolescent patients with Clostridioides difficile infection (CDI). A systematic review and meta-analysis was conducted using four electronic databases (PubMed, Cochrane Library, Web of Science, and Clinicaltrials.gov) through July 6, 2022. We analyzed the clinical cure and recurrence rates to determine the efficacy of MNZ and VCM. The clinical cure rates in all included studies were not significantly different between MNZ and VCM (OR = 0.63; 95% CI = 0.36–1.10; I2 = 0%; P = 0.10). Subgroup analyses were performed separately for each region to account for regional differences in the CDI. MNZ treatment achieved significantly lower clinical cure rates than did VCM in the United States of America (USA) and Europe (OR = 0.42, 95% CI = 0.19–0.93, I2 = 0%, P = 0.03). Recurrence rates were not significantly different between MNZ and VCM (OR = 1.48, 95% CI = 0.62–3.53, I2 = 28%, P = 0.38).

   Conclusion: MNZ exhibited significantly lower clinical cure rates than did VCM in the US and Europe; therefore, it is not recommended for the management of CDI in pediatric and adolescent populations.

What is Known:

• The unavailability of robust data on recommendations of therapeutic agents for the management of Clostridioides difficile infections in children precludes effective antibiotic choice.

What is New:

• Metronidazole exhibited significantly lower clinical cure rates than did vancomycin in the United States of America and Europe and recurrence rate was not significantly different between metronidazole and vancomycin; therefore, it is not recommended for the management of Clostridioides difficile infection in children.

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Data availability

The datasets generated or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

CDI:

Clostridioides difficile Infection

CIs:

Confidence intervals

FDX:

Fidaxomicin

MNZ:

Metronidazole

ORs:

Odd ratios

RCTs:

Randomized controlled trials

VCM:

Vancomycin

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Acknowledgements

Sho Tashiro wishes to thank the Nagai Memorial Research Scholarship of the Pharmaceutical Society of Japan and JST SPRING (Grant Number JPMJSP2123). The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Division of Pharmacodynamics, Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo, 105-8512, Japan

    Sho Tashiro, Takayuki Mihara, Rikiya Okawa, Yoko Tanaka, Masaru Samura, Yuki Enoki, Kazuaki Taguchi & Kazuaki Matsumoto

  2. Department of Clinical Infectious Diseases, Kochi Medical School, Kochi, Japan

    Yuka Yamagishi

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  1. Sho Tashiro
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  2. Takayuki Mihara
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Contributions

All authors contributed to the conception and design of this study. Material preparation, data collection, and analyses were performed by Sho Tashiro, Takayuki Mihara, Rikiya Okawa, Yoko Tanaka, and Yuki Enoki. The first draft of the manuscript was written by Sho Tashiro and Yuki Enoki, and all authors commented on previous versions of the manuscript. All the authors have read and approved the final version of the manuscript.

Corresponding author

Correspondence to Yuki Enoki.

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Competing interests

Kazuaki Matsumoto received grant support funding from Meiji Seika Pharma Co., Ltd., Sumitomo Pharma Co., Ltd., and Shionogi & Co., Ltd., and speaker honoraria from Meiji Seika Pharma Co., Ltd. Yuka Yamagishi received speaker honoraria from MSD K.K. The authors declare no conflicts of interest.

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Tashiro, S., Mihara, T., Okawa, R. et al. Optimal therapeutic recommendation for Clostridioides difficile infection in pediatric and adolescent populations: a systematic review and meta-analysis. Eur J Pediatr 182, 2673–2681 (2023). https://doi.org/10.1007/s00431-023-04944-y

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