Evidence is not substantial for the treatment of Clostridioides difficile infection (CDI), but authors of a review of available evidence provide recommendations for resources and testing.
Clostridioides difficile infection (CDI) is a major public health problem in adults and increasingly in children; however, less clinical evidence is available to guide treatment decisions in pediatric care. Authors of a review paper looked at available treatment options and made recommendations based on existing data.
CDI produces toxins that bind to cell receptors and cause apoptosis or cell death, resulting in inflammation that causes diarrhea and colitis. “The management of pediatric CDI presents a challenge for healthcare providers due to the lack of strong randomized controlled trials to guide pharmacological management,” the authors wrote.
They cited a worrying increase in the incidence of pediatric CDI hospitalizations from 3,565 patients in 1997 to 7,779 patients in 2006 (P < 0.001), although the incidence is lower in the pediatric population (24.2 per 100,000) than for all age groups. (147.2). per 100,000), according to a 2015 study.
They attributed this increase to the increased use of antibiotics, especially cephalosporins and fluoroquinolones. Antibiotics alter the microbiota in the gastrointestinal tract, allowing overgrowth of C. difficile and the development of CDI.
But despite this higher incidence in the pediatric population, there is no commensurate increase in case severity, they wrote. “Significant efforts have been made by the Centers for Disease Control and Prevention to reduce the incidence of CDI and prevent the development of antibiotic resistance.”
The authors describe robust evidence available for treatment options in CDI in adults, but said the reverse is the case for pediatric infections. That raises questions about whether treatments approved for adults are appropriate for use in children, such as the front-line oral vancomycin versus metronidazole for treating CDI.
In adults, oral vancomycin is recommended in this setting, but both agents are recommended for pediatric patients with a first episode or first relapse of CDI. However, failure rates of metronidazole of 11% and 18% were observed in 2 studies of pediatric patients with CDI, and in the second of the studies, no failure was observed in patients receiving oral vancomycin.
“These data suggest that metronidazole should not be used as the first line for a first episode of severe CDI in pediatric patients,” the authors wrote. “Additional well-designed studies are needed to confirm this finding.”
The recommended dose for vancomycin in pediatric patients is 10 mg/kg 4 times daily with a maximum of 125 mg per dose, the authors wrote. That dosage is for patients with a first episode or first recurrence of non-serious disease. “Based on clinical data,” the individual dosage may be increased to 500 mg in severe cases of CDI, they wrote.
Their assessment included other agents. Fidaxomicin was previously only recommended for adults, but a pediatric study found that 92% of patients had an early clinical response and 66% had a sustained response after 30 days. “Fidaxomicin was well tolerated in pediatric patients and the pharmacokinetic profile was very similar to that seen in adults with a high clinical response,” they wrote.
Fecal microbiota transplantation (FMT) has been very successful in restoring normal microbiota in patients with CDI. However, the authors cautioned that special care is needed when applying FMT to pediatric treatment. “There is less evidence for use, more concern about side effects and fear of long-term outcomes when the microbiota is manipulated,” they wrote.
In addition, the FDA has warned against the development of multidrug-resistant organisms after FMT transplantation. However, the authors recommended considering FMT in pediatric CDI that has relapsed or develops after therapeutic failure after at least 1 course of vancomycin.
Other CDI Issues in Pediatrics
There is no standard in pediatric management of knowing when to test for CDI during a series of diarrhea episodes. The Infectious Diseases Society of America recommends considering testing “in people with unexplained and newly formed unformed stools at a frequency of at least 3 in a 24-hour period, although this is based on low-quality evidence.”
Another major concern is that the rate of asymptomatic colonization of CDI (development of infection) is higher in children (2%-50%) than in adults (3%-20%). In infants under 1 month of age, colonization rates are as high as 37%; however, in neonates and infants, clinical CDI is rare because at that age they do not have the cell receptors that facilitate the development of CDI, so the authors did not recommend testing for CDI in patients 2 years of age and younger.
Few studies have elucidated the risk factors for CDI in pediatrics, they wrote. But it is possible to split the categories into ‘adjustable risk factors’ and ‘non-adjustable risk factors’. In the first group is exposure to antibiotics.
“A recent study of pediatric patients in the inpatient and outpatient settings identified cephalosporins and clindamycin as the most common antibiotics received within 30 days of CDI diagnosis,” the review authors wrote. Infections are more common in those who have received more than 1 class of antibiotics.
“Proton pump inhibitors and other gastric acid suppressants have been documented to increase the risk of CDI,” they wrote.
Non modifiable risk factors include co-morbidities, such as transplants, pancreatitis, inflammatory bowel disease, and HIV. “Hospitalization has also been reported as a major risk factor for CDI in children in several studies, with nearly 50% of patients in some studies having a history of hospitalization within the past month,” the authors wrote.
DeVine MN, MacBrayne CE, Child J, Blackmer AB. Pharmacological treatment of pediatric Clostridioides difficile infection: clarifying the controversies. J Child health care. Published online August 17, 2021. doi:10.1016/j.pedhc.2021.06.005.