Prophylactic vancomycin during active CDI treatment cuts risk of recurrence in kids

In children with a history of Clostridioides difficile infection (CDI), secondary prophylaxis with oral vancomycin (OVP) while receiving systemic antibiotics to treat the initial episode appears to protect against the risk of recurrence, as shown in a study.

“Findings from this retrospective observational study suggest that OVP is effective in preventing CDI recurrence in paediatric patients, and ∼5 patients would need secondary OVP to prevent [a single] recurrence,” according to a team of US-based investigators.

For the analysis, the investigators screened a total of 148 patients aged ≤18 years with any history of clinical CDI and who were subsequently treated with systemic antibiotics. Of these, 30 patients (median age 9.6 years, 73 percent male) received OVP while 44 (median age 6.1 years, 50 percent male) did not. A significant proportion of patients in both groups received high-risk antibiotics, with the most common being third- and fourth-generation cephalosporins.

OVP duration lasted a median of 12 days, administered a median of 1 day after starting antibiotics. Most of the patients received the secondary prophylactic treatment in the inpatient setting (93 percent), whereas completion occurred more often in the outpatient setting (60 percent).

Significantly fewer patients who received OVP another bout of CDI within 8 weeks of antibiotic exposure (3 percent vs 25 percent; p=0.02). Furthermore, none of the patients in either treatment arm developed vancomycin-resistant enterococci infections. [Pediatrics 2021;148:e2020031807]

Multivariable logistic regression showed that secondary OVP lowered the likelihood of recurrence by as much as 90 percent (odds ratio, 0.10, 95 percent confidence interval, 0.01–0.86; p=0.04).

“Notably, patients who received OVP were at much higher risk for recurrence, as compared with those who did not, for several reasons,” the investigators noted.

Specifically, the OVP group received more classes of antibiotics (median, 2 vs 1.5; p=0.004) and longer duration of high-risk antibiotics (median, 11.5 vs 5.5 days; p=0.003) compared with the non-OVP group. The former also had longer hospital stays, representing a more ill population with an increased risk of nosocomial acquisition of C. difficile at baseline. Lastly, the majority of patients in the overall cohort had comorbid conditions, particularly malignancy. 

“Despite the presence of these risk factors, the potentially beneficial effect of OVP in preventing CDI recurrence was still able to be revealed,” the team said. “To our knowledge, this is the first analysis of CDI prophylactic strategies in the paediatric population.”

The potential benefit of secondary OVP in reducing the risk of CDI recurrence has been reported in several retrospective studies in adult patients. [Am J Gastroenterol 2016;111:1834-1840; Infect Control Hosp Epidemiol 2019;40:662-667; Clin Infect Dis 2016;63:651-653; J Pharm Pract 2012;33:633-639]

However, unlike in previous studies, the investigators pointed out that they did not restrict the inclusion criteria to a specific time frame with regard to initial CDI occurrence and subsequent antibiotic exposure. “This reflects current practice at our institution because providers may still consider OVP in paediatric patients with remote CDI episodes, if other risk factors for CDI recurrence are present. Regardless, most patients in our study had their latest CDI episodes within 6 months before the study encounter, indicating recent rather than remote CDI.”

Meanwhile, the follow-up period was limited to 8 weeks after systemic antibiotic exposure to account for the period of greatest risk for CDI recurrence, as previously described in both adults and children, the team said.  [Hosp Pediatr 2016;6:339-344; Pediatr Infect Dis J 2019;38:32-36; J Antimicrob Chemother 2012;67:742-748]

“Although our guidelines recommend a short extension of OVP for an additional 5 days after antibiotic cessation, only 10 patients received an extended regimen, and none experienced recurrence. The ability to assess for recurrence on the basis of cessation of OVP on the last day of systemic antibiotics compared with 5 days afterward was limited by the presence of only one recurrence in recipients of OVP,” they acknowledged.

A such, the investigators called for randomized controlled trials to validate the findings from the present study.