Elsevier

Journal of Pediatric Health Care

Volume 36, Issue 2, March–April 2022, Pages 181-192
Journal of Pediatric Health Care

Continuing Education
Pharmacological Management of Pediatric Clostridioides difficile Infection: Clarifying the Controversies

https://doi.org/10.1016/j.pedhc.2021.06.005Get rights and content

Clostridioides difficile infection (CDI) is a major public health concern for pediatric and adult patients. The management of pediatric CDI poses a challenge to healthcare providers due to lack of strong randomized controlled trials to guide pharmacological management. Additionally, recent updates to CDI guidelines recommend oral vancomycin over metronidazole for the management of CDI in adults, leaving questions regarding how to best manage pediatric patients. This continuing education pharmacotherapy review describes available evidence for the safety and efficacy of medications used in the treatment and management of pediatric CDI and aims to clarify discrepancies between pediatric and adult recommendations.

Section snippets

INTRODUCTION

Clostridioides difficile (C. difficile), formerly Clostridium difficile, is a gram-positive, spore-forming organism normally colonized in the gut microbiota (Shim, 2014; Tamma & Sandora, 2012). Over the last two decades, CDI has become a major public health concern for both adult and pediatric patients (Gupta & Khanna, 2014). There has also been a notable rise in pediatric CDI hospitalizations, with an estimated increased incidence from 3,565 patients in 1997 to 7,779 patients in 2006 (p <.001)

WHAT RISK FACTORS HAVE BEEN IDENTIFIED FOR PEDIATRIC PATIENTS?

Risk factors for CDI are well-defined in the adult population, including a variety of pharmacological, host-specific, and clinical intervention-related factors (Eze, Balsells, Kyaw, & Nair, 2017). Few studies have evaluated risk factors in pediatric patients (Kim et al., 2012; Samady, Pong, & Fisher, 2014). In general, risk factors can be separated into two major categories: modifiable and nonmodifiable (McDonald et al., 2018).

The most prominent modifiable risk factor defined in the pediatric

Which Agent Should Be First-Line: Metronidazole or Oral Vancomycin?

The IDSA CDI guidelines published in 2018 drastically changed pharmacological management in adult patients with the recommendation of oral vancomycin over metronidazole (McDonald et al., 2018). The role of vancomycin in the management of pediatric patients with CDI remains unclear as either metronidazole or oral vancomycin are recommended for pediatric patients with an initial episode or first recurrence (Table 2).

Metronidazole forms a toxic metabolite that is thought to disrupt the

What Is the Preferred Dosing Regimen of Oral Vancomycin?

Various dosing regimens for oral vancomycin have been recommended in the pediatric population. Current guideline dosing recommendations depend on the severity of the disease (McDonald et al., 2018). In patients with an initial episode or first recurrence of nonsevere disease, a dosage of 10 mg/kg/dose four times daily with a maximum of 125 mg per dose is recommended. In patients with an initial severe episode or second/subsequent recurrence, a dosage of 10 mg/kg/dose four times daily with a

What Is the Role Of Fidaxomicin in Pediatric Patients?

Clinical trials have recently been published describing the safety and efficacy of fidaxomicin in pediatric patients, which was previously only recommended in adults. An open-label pharmacokinetic study was completed in pediatric patients to measure the safety and efficacy of fidaxomicin (O'Gorman et al., 2018). Patients with C. difficile associated diarrhea were given oral fidaxomicin 16 mg/kg/day divided twice daily with a maximum dosage of 200 mg for 10 days (O'Gorman et al., 2018). A total

When Should FMT Be Considered in Pediatric Patients?

FMT was first used in the fourth century by Chinese doctors who administered stool to patients with severe diarrhea or food poisoning with reported excellent outcomes (Zhang, Luo, Shi, Fan, & Ji, 2012). FMT is used when a patient is assumed to have an altered microbiome resulting in disease caused by CDI (Vindigni & Surawicz, 2017). The primary goal is to restore the normal microbiome and replace the pathogenic flora (Gupta & Khanna, 2014). Potential routes of administration include

Bezlotoxumab

Bezlotoxumab is a monoclonal antibody that binds to and neutralizes C. difficile toxin B to prevent toxic effects (Bezlotoxumab, 2016). This agent was approved in October of 2016 as adjunctive therapy to reduce the recurrence of CDI in adult patients receiving antibacterial medication treatment of CDI and who are at high risk for recurrence. It is not indicated for the treatment of CDI. Although pediatric-specific data regarding the newer toxin-binding agents are not yet available, adult data

Mackenzie N. DeVine, Pediatric Clinical Pharmacist, Department of Pharmacy, Children's Hospital Colorado, Aurora, CO.

CE QUESTIONS

  • 1.

    Which of the following is a modifiable risk factor in pediatric patients?

    • a.

      Age

    • b.

      Immunosuppression

    • c.

      Antibiotic exposure

    • d.

      HIV

  • 2.

    Proton pump inhibitors are thought to increase the risk of Clostridioides difficile infection (CDI) through which mechanism?

    • a.

      Alterations in gastric pH, which deem therapy options like metronidazole ineffective

    • b.

      Alterations in gastric acid production, leading to increased toxin production

    • c.

      Alterations in gastric pH, allowing for bacterial survival

    • d.

      Alterations in gastric acid production,

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    • Cited by (0)

    Mackenzie N. DeVine, Pediatric Clinical Pharmacist, Department of Pharmacy, Children's Hospital Colorado, Aurora, CO.

    Christine E. MacBrayne, Antimicrobial Stewardship and Infectious Diseases Clinical Pharmacist Specialist, Department of Pharmacy, Children's Hospital Colorado, Aurora, CO.

    Jason Child, HIV/Infectious Diseases and Antimicrobial Stewardship Clinical Specialist, Children's Hospital Colorado, Aurora, CO.

    Allison B. Blackmer, Director, Clinical Practice, Quality and Advocacy; American Society for Parenteral and Enteral Nutrition and Adjunct Associate Professor of Pharmacy; University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO.

    Conflicts of interest: None to report.

    Jason Child and Allison B. Blackmer performed consultative services for Wolters Kluwer, Pediatric and Neonatal Lexi-Drugs in 2020. In addition, Allison B. Blackmer serves as a member of the Drug Utilization Review Board for Colorado Department of Health Care Policy and Financing.

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