Advances in the treatment of Clostridium difficile infection in children

GAN Yu; WU Zhi-Hong; LI Qian-Long; LU Zhao-Xia; CHEN Lin-Lin

doi:10.7499/j.issn.1008-8830.2405055

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Chinese Journal of Contemporary Pediatrics ›› 2024, Vol. 26 ›› Issue (9) : 995-1001. DOI: 10.7499/j.issn.1008-8830.2405055

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Advances in the treatment of Clostridium difficile infection in children

GAN Yu¹, WU Zhi-Hong¹, LI Qian-Long², LU Zhao-Xia³, CHEN Lin-Lin^1,2

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Abstract

Clostridium difficile infection (CDI) is a major cause of hospital-acquired gastrointestinal infections in children. Current treatment for pediatric CDI primarily involves antibiotics; however, some children experience recurrence after antibiotic treatment, and those with initial recurrence remain at risk for further recurrences following subsequent antibiotic therapy. In such cases, careful consideration of treatment options is necessary. Fecal microbiota transplantation has been shown to be effective for recurrent CDI and has a high safety profile. This article reviews the latest research on the pathogenesis, risk factors, diagnosis, and treatment of pediatric CDI domestically and internationally, with a particular focus on fecal microbiota transplantation therapy.

Key words

Clostridium difficile infection / Treatment / Fecal microbiota transplantation / Child

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GAN Yu, WU Zhi-Hong, LI Qian-Long, LU Zhao-Xia, CHEN Lin-Lin. Advances in the treatment of Clostridium difficile infection in children[J]. Chinese Journal of Contemporary Pediatrics. 2024, 26(9): 995-1001 https://doi.org/10.7499/j.issn.1008-8830.2405055

References

1 Kociolek LK, Crews JD, Schwenk HT. Recent advances in Clostridioides difficile infection epidemiology, diagnosis and treatment in children[J]. Curr Opin Infect Dis, 2021, 34(5): 527-532. PMID: 34232137. DOI: 10.1097/QCO.0000000000000753.
2 Oliva-Hemker M, Kahn SA, Steinbach WJ, et al. Fecal microbiota transplantation: information for the pediatrician[J]. Pediatrics, 2023, 152(6): e2023062922. PMID: 37981872. DOI: 10.1542/peds.2023-062922.
3 Joachim A, Schwerd T, H?lz H, et al. Fecal microbiota transfer (FMT) in children and adolescents: review and statement by the GPGE microbiome working group[J]. Z Gastroenterol, 2022, 60(6): 963-969. PMID: 35533688. DOI: 10.1055/a-1801-0284.
4 Sattler MM, Crews JD. Challenges in the diagnosis and management of recurrent and severe Clostridioides difficile infection in children[J]. J Pediatric Infect Dis Soc, 2021, 10(Supplement_3): S27-S33. PMID: 34791399. DOI: 10.1093/jpids/piab079.
5 Parnell JM, Nicholson MR, Kellermayer R, et al. Pediatric fecal microbiota transplantation in recurrent Clostridioides difficile[J]. Pediatr Ann, 2021, 50(12): e515-e521. PMID: 34889135. DOI: 10.3928/19382359-20211111-01.
6 Ruan W, Kellermayer R. Alternative diagnoses in pediatric fecal microbiota transplant referral patients[J]. J Pediatr Gastroenterol Nutr, 2021, 72(5): 693-696. PMID: 33534360. DOI: 10.1097/MPG.0000000000003060.
7 Nicholson MR, Mitchell PD, Alexander E, et al. Efficacy of fecal microbiota transplantation for Clostridium difficile infection in children[J]. Clin Gastroenterol Hepatol, 2020, 18(3): 612-619.e1. PMID: 31009795. PMCID: PMC7549313. DOI: 10.1016/j.cgh.2019.04.037.
8 Hourigan SK, Nicholson MR, Kahn SA, et al. Updates and challenges in fecal microbiota transplantation for Clostridioides difficile infection in children[J]. J Pediatr Gastroenterol Nutr, 2021, 73(4): 430-432. PMID: 34238831. PMCID: PMC8455422. DOI: 10.1097/MPG.0000000000003229.
9 Nicholson MR, Alexander E, Ballal S, et al. Efficacy and outcomes of faecal microbiota transplantation for recurrent Clostridioides difficile infection in children with inflammatory bowel disease[J]. J Crohns Colitis, 2022, 16(5): 768-777. PMID: 34788420. PMCID: PMC9228903. DOI: 10.1093/ecco-jcc/jjab202.
10 Gu X, Chen ZH, Zhang SC. Fecal microbiota transplantation in childhood: past, present, and future[J]. World J Pediatr, 2023, 19(9): 813-822. PMID: 36484871. PMCID: PMC9734408. DOI: 10.1007/s12519-022-00655-w.
11 Bishop EJ, Tiruvoipati R. Management of Clostridioides difficile infection in adults and challenges in clinical practice: review and comparison of current IDSA/SHEA, ESCMID and ASID guidelines[J]. J Antimicrob Chemother, 2022, 78(1): 21-30. PMID: 36441203. PMCID: PMC9780550. DOI: 10.1093/jac/dkac404.
12 Johnson S, Lavergne V, Skinner AM, et al. Clinical practice guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 focused update guidelines on management of Clostridioides difficile infection in adults[J]. Clin Infect Dis, 2021, 73(5): 755-757. PMID: 34492699. DOI: 10.1093/cid/ciab718.
13 Cheng YW, Fischer M. Clinical management of severe, fulminant, and refractory Clostridioides difficile infection[J]. Expert Rev Anti Infect Ther, 2020, 18(4): 323-333. PMID: 32057278. DOI: 10.1080/14787210.2020.1730814.
14 Kelly CR, Fischer M, Allegretti JR, et al. ACG clinical guidelines: prevention, diagnosis, and treatment of Clostridioides difficile infections[J]. Am J Gastroenterol, 2021, 116(6): 1124-1147. PMID: 34003176. DOI: 10.14309/ajg.0000000000001278.
15 Minkoff NZ, Aslam S, Medina M, et al. Fecal microbiota transplantation for the treatment of recurrent Clostridioides difficile (Clostridium difficile)[J]. Cochrane Database Syst Rev, 2023, 4(4): CD013871. PMID: 37096495. PMCID: PMC10125800. DOI: 10.1002/14651858.CD013871.pub2.
16 Wu Q, Boonma P, Badu S, et al. Donor-recipient specificity and age-dependency in fecal microbiota therapy and probiotic resolution of gastrointestinal symptoms[J]. NPJ Biofilms Microbiomes, 2023, 9(1): 54. PMID: 37537181. PMCID: PMC10400536. DOI: 10.1038/s41522-023-00421-4.
17 Kelly CP, Poxton IR, Shen J, et al. Effect of endogenous Clostridioides difficile toxin antibodies on recurrence of C. difficile infection[J]. Clin Infect Dis, 2020, 71(1): 81-86. PMID: 31628838. DOI: 10.1093/cid/ciz809.
18 王晓亚, 安彦波, 戴敏高, 等. 艰难梭菌感染与肠道微生态的研究进展[J]. 中国人兽共患病学报, 2021, 37(9): 833-838. DOI: 10.3969/j.issn.1002-2694.2021.00.107.
19 Rousseau C, Levenez F, Fouqueray C, et al. Clostridium difficile colonization in early infancy is accompanied by changes in intestinal microbiota composition[J]. J Clin Microbiol, 2011, 49(3): 858-865. PMID: 21177896. PMCID: PMC3067754. DOI: 10.1128/JCM.01507-10.
20 Bernard R, Hourigan SK, Nicholson MR. Fecal microbiota transplantation and microbial therapeutics for the treatment of Clostridioides difficile infection in pediatric patients[J]. J Pediatric Infect Dis Soc, 2021, 10(Supplement_3): S58-S63. PMID: 34791396. PMCID: PMC8600035. DOI: 10.1093/jpids/piab056.
21 Tariq R, Syed T, Yadav D, et al. Outcomes of fecal microbiota transplantation for C. difficile infection in inflammatory bowel disease: a systematic review and meta-analysis[J]. J Clin Gastroenterol, 2023, 57(3): 285-293. PMID: 34864789. DOI: 10.1097/MCG.0000000000001633.
22 Chandrakumar A, Zohni H, El-Matary W. Clostridioides difficile infection in children with inflammatory bowel disease[J]. Inflamm Bowel Dis, 2020, 26(11): 1700-1706. PMID: 31765471. DOI: 10.1093/ibd/izz285.
23 张文婷, 赵红梅, 罗艳红, 等. 儿童炎症性肠病艰难梭菌感染及其易感因素分析[J]. 中国当代儿科杂志, 2021, 23(7): 718-723. PMID: 34266530. PMCID: PMC8292652. DOI: 10.7499/j.issn.1008-8830.2103129.
24 Reasoner SA, Fazili IF, Bernard R, et al. Prevalence, risk factors, and sequelae of asymptomatic Clostridioides difficile colonization in children with cystic fibrosis[J]. J Cyst Fibros, 2023, 22(5): 884-887. PMID: 36585317. PMCID: PMC10300225. DOI: 10.1016/j.jcf.2022.12.014.
25 Yang E, Sajhwani D, Fassnacht R, et al. High rates of acquisition of toxigenic Clostridioides difficile colonization without subsequent infection during acute lymphoblastic leukemia treatment in children[J]. Clin Infect Dis, 2024, 78(4): 1076-1078. PMID: 37818855. PMCID: PMC11006112. DOI: 10.1093/cid/ciad628.
26 Fang SB, Song YQ, Zhang CY, et al. Risk factors for Clostridioides difficile infection in children and adolescents with inflammatory bowel disease: a systematic review and meta-analysis[J]. World J Pediatr, 2022, 18(1): 27-36. PMID: 34800281. DOI: 10.1007/s12519-021-00486-1.
27 Reasoner SA, Nicholson MR. Clostridioides difficile infection in pediatric inflammatory bowel disease[J]. Curr Gastroenterol Rep, 2023, 25(11): 316-322. PMID: 37646895. PMCID: PMC10843265. DOI: 10.1007/s11894-023-00890-9.
28 Mani J, Levy S, Angelova A, et al. Epidemiological and microbiome associations of Clostridioides difficile carriage in infancy and early childhood[J]. Gut Microbes, 2023, 15(1): 2203969. PMID: 37096914. PMCID: PMC10132246. DOI: 10.1080/19490976.2023.2203969.
29 McDonald LC, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)[J]. Clin Infect Dis, 2018, 66(7): e1-e48. PMID: 29462280. PMCID: PMC6018983. DOI: 10.1093/cid/cix1085.
30 Parnell JM, Fazili I, Bloch SC, et al. Two-step testing for Clostridioides difficile is inadequate in differentiating infection from colonization in children[J]. J Pediatr Gastroenterol Nutr, 2021, 72(3): 378-383. PMID: 32925555. PMCID: PMC7870537. DOI: 10.1097/MPG.0000000000002944.
31 Krutova M, de Meij TGJ, Fitzpatrick F, et al. How to: Clostridioides difficile infection in children[J]. Clin Microbiol Infect, 2022, 28(8): 1085-1090. PMID: 35283312. DOI: 10.1016/j.cmi.2022.03.001.
32 Hurst JH, Heston SM, Kelly MS. Host microbiome-pathogen interactions in pediatric infections[J]. Curr Opin Infect Dis, 2023, 36(5): 399-404. PMID: 37462955. PMCID: PMC10529085. DOI: 10.1097/QCO.0000000000000949.
33 Yin J, Kociolek LK, Same RG, et al. Oral vancomycin may be associated with earlier symptom resolution than metronidazole for hospitalized children with nonsevere Clostridiodes difficile infections[J]. Open Forum Infect Dis, 2019, 6(12): ofz492. PMID: 31950069. PMCID: PMC6954469. DOI: 10.1093/ofid/ofz492.
34 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[J]. Eur J Pediatr, 2023, 182(6): 2673-2681. PMID: 37000258. DOI: 10.1007/s00431-023-04944-y.
35 Bao H, Lighter J, Dubrovskaya Y, et al. Oral vancomycin as secondary prophylaxis for Clostridioides difficile infection[J]. Pediatrics, 2021, 148(2): e2020031807. PMID: 34330867. DOI: 10.1542/peds.2020-031807.
36 Wolf J, Kalocsai K, Fortuny C, et al. Safety and efficacy of fidaxomicin and vancomycin in children and adolescents with Clostridioides (Clostridium) difficile infection: a phase 3, multicenter, randomized, single-blind clinical trial (SUNSHINE)[J]. Clin Infect Dis, 2020, 71(10): 2581-2588. PMID: 31773143. PMCID: PMC7744996. DOI: 10.1093/cid/ciz1149.
37 van Prehn J, Reigadas E, Vogelzang EH, et al. European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults[J]. Clin Microbiol Infect, 2021, 27 Suppl 2: S1-S21. PMID: 34678515. DOI: 10.1016/j.cmi.2021.09.038.
38 Rotondo-Trivette S, Wang B, Gayer C, et al. Decreased secondary faecal bile acids in children with ulcerative colitis and Clostridioides difficile infection[J]. Aliment Pharmacol Ther, 2021, 54(6): 792-804. PMID: 34218431. PMCID: PMC8384671. DOI: 10.1111/apt.16496.
39 Chen LA, Oliva-Hemker M, Radin A, et al. Longitudinal bile acid composition changes following faecal microbiota transplantation for Clostridioides difficile infection in children with and without underlying inflammatory bowel disease[J]. J Crohns Colitis, 2023, 17(8): 1364-1368. PMID: 36988432. PMCID: PMC10441560. DOI: 10.1093/ecco-jcc/jjad057.
40 Silva YP, Bernardi A, Frozza RL. The role of short-chain fatty acids from gut microbiota in gut-brain communication[J]. Front Endocrinol (Lausanne), 2020, 11: 25. PMID: 32082260. PMCID: PMC7005631. DOI: 10.3389/fendo.2020.00025.
41 Spinner JA, Bocchini CE, Luna RA, et al. Fecal microbiota transplantation in a toddler after heart transplant was a safe and effective treatment for recurrent Clostridiodes difficile infection: a case report[J]. Pediatr Transplant, 2020, 24(1): e13598. PMID: 31617299. PMCID: PMC6982574. DOI: 10.1111/petr.13598.
42 Rodig NM, Weatherly M, Kaplan AL, et al. Fecal microbiota transplant in pediatric solid organ transplant recipients[J]. Transplantation, 2023, 107(9): 2073-2077. PMID: 37211643. DOI: 10.1097/TP.0000000000004656.
43 Conover KR, Absah I, Ballal S, et al. Fecal microbiota transplantation for Clostridioides difficile infection in immunocompromised pediatric patients[J]. J Pediatr Gastroenterol Nutr, 2023, 76(4): 440-446. PMID: 36720105. PMCID: PMC10627107. DOI: 10.1097/MPG.0000000000003714.
44 Nicholson MR, Hourigan SK, Conrad M, et al. Current challenges in fecal microbiota transplantation for Clostridioides difficile infection in children[J]. Am J Gastroenterol, 2021, 116(9): 1954-1956. PMID: 34140459. PMCID: PMC8410642. DOI: 10.14309/ajg.0000000000001350.
45 Lee CH, Steiner T, Petrof EO, et al. Frozen vs fresh fecal microbiota transplantation and clinical resolution of diarrhea in patients with recurrent Clostridium difficile infection: a randomized clinical trial[J]. JAMA, 2016, 315(2): 142-149. PMID: 26757463. DOI: 10.1001/jama.2015.18098.
46 Baunwall SMD, Lee MM, Eriksen MK, et al. Faecal microbiota transplantation for recurrent Clostridioides difficile infection: an updated systematic review and meta-analysis[J]. EClinicalMedicine, 2020, 29-30: 100642. PMID: 33437951. PMCID: PMC7788438. DOI: 10.1016/j.eclinm.2020.100642.
47 Youngster I, Mahabamunuge J, Systrom HK, et al. Oral, frozen fecal microbiota transplant (FMT) capsules for recurrent Clostridium difficile infection[J]. BMC Med, 2016, 14(1): 134. PMID: 27609178. PMCID: PMC5016994. DOI: 10.1186/s12916-016-0680-9.
48 Marcella C, Cui B, Kelly CR, et al. Systematic review: the global incidence of faecal microbiota transplantation-related adverse events from 2000 to 2020[J]. Aliment Pharmacol Ther, 2021, 53(1): 33-42. PMID: 33159374. DOI: 10.1111/apt.16148.
49 van Lier YF, Davids M, Haverkate NJE, et al. Donor fecal microbiota transplantation ameliorates intestinal graft-versus-host disease in allogeneic hematopoietic cell transplant recipients[J]. Sci Transl Med, 2020, 12(556): eaaz8926. PMID: 32801142. DOI: 10.1126/scitranslmed.aaz8926.
50 Goldenberg JZ, Yap C, Lytvyn L, et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children[J]. Cochrane Database Syst Rev, 2017, 12(12): CD006095. PMID: 29257353. PMCID: PMC6486212. DOI: 10.1002/14651858.CD006095.pub4.
51 Su GL, Ko CW, Bercik P, et al. Aga clinical practice guidelines on the role of probiotics in the management of gastrointestinal disorders[J]. Gastroenterology, 2020, 159(2): 697-705. PMID: 32531291. DOI: 10.1053/j.gastro.2020.05.059.
52 Blair HA. SER-109 (VOWSTTM): a review in the prevention of recurrent Clostridioides difficile infection[J]. Drugs, 2024, 84(3): 329-336. PMID: 38441806. DOI: 10.1007/s40265-024-02006-7.