CF Children With Higher BMI at Risk for Asymptomatic C. difficile

Colonization risk also from recent exposure to certain antibiotics

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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A higher body mass index (BMI) and recent exposure to certain antibiotics are risk factors for asymptomatic intestinal colonization with Clostridioides difficile in children with cystic fibrosis (CF), a new study suggests.

The study, “Prevalence, Risk Factors, and Sequelae of Asymptomatic Clostridioides difficile Colonization in Children with Cystic Fibrosis,” was published in the Journal of Cystic Fibrosis.

People with CF often need antibiotics to treat lung infections. But high antibiotic use, together with an altered gut microbiome — the friendly microbes living in the digestive tract — constitute risk factors for Clostridioides difficile (C. difficile) infections.

C. difficile colonization, defined as the presence of the bacteria in the intestines without clinical symptoms, occurs in 22–50% of adults with CF compared to 5–10% in the general population. Infections caused by these bacteria are uncommon, however.

Asymptomatic colonization by C. difficile is a diagnostic challenge in patients with symptoms of infection. Also, C. difficile colonization is a known risk factor for progressing to C. difficile infections and has been associated with chronic inflammatory intestinal conditions prevalent in CF patients.

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To establish the rates, risk factors, and effects of C. difficile colonization in children with CF, researchers analyzed fecal samples of 108 children with CF without acute gastrointestinal symptoms who were recruited between 2017 and 2019 at the Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville. The group’s mean age was 9.2, 50.9% were males, and 43.2% had a F508del mutation in both CFTR gene copies.

The bacteria were present in 35 patients (32.4%), similar to what’s been reported in adults with CF. No participants developed an infection caused by the bacteria during the 90-day follow-up study.

A higher BMI, a measure of body fat, and recent exposure to the antibiotic classes cephalosporin, fluoroquinolone, or vancomycin, were significantly associated with C. difficile colonization when analyzing each variant separately.

The only risk factor that remained statistically significant was higher BMI in a subsequent multivariate analysis, which evaluates multiple variables together.

The mean BMI for CF children positive for C. difficile colonization was 19.9 kg per square meters (kg/m2) compared to 18.1 kg/m2 in those without these bacteria, indicating a better nutritional status may be related to gut colonization by C. difficile.

Exposure to cephalosporins, fluroquinolones and vancomycin was significantly correlated with hospitalization, which may explain why antibiotic treatment was no longer a significant risk factor in the multivariable analysis, the team suggested.

More than 40% of CF patients positive for C. difficile were hospitalized in the preceding 90 days versus 26% negative for the bacteria.

“As C. difficile remains a frequent [hospital-acquired] infection, additional environmental surveillance is warranted to identify potential areas of contamination and spread,” the researchers wrote.

It’s been hypothesized that the absence of symptoms of C. difficile infection might be associated with the lack of CFTR function that’s a hallmark of CF. As such, treatment with CFTR modulators might predispose patients to symptomatic C. difficile infections, the scientists noted. Their study found no difference in the rates of C. difficile colonization among a minority of participants (20.4%) taking CFTR modulators, however.

“This small sample size may not have adequately assessed the role of CFTR modulators, but our studies will continue to assess … whether restoration of CFTR function predisposes to symptomatic C. difficile,” the researchers wrote. “In sum, using a large cohort of [children with CF], we established a rate of asymptomatic C. difficile colonization, the lack of symptomatic [infections] during the study follow-up, and identified higher BMI and exposure to specific antibiotic classes (cephalosporins, fluoroquinolones, and vancomycin) as risk factors for colonization.”

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