Oral Vancomycin May Resolve C Diff Symptoms Faster Than Metronidazole in Children

In February, 2019, a review of existing studies supported the Infectious Diseases Society of America’s updated guidelines for management of Clostridiodies difficile (C diff) in adults. These guidelines recommended the use of vancomycin over metronidazole for an initial episode of C diff. However, there is a scarcity of data concerning the issue in children, and national guidelines continue to recommend metronidazole for children with non-severe C diff.

A new study in Open Forum Infectious Diseases suggests that oral vancomycin may be associated with earlier symptom resolution than metronidazole for children hospitalized with non-severe C diff infections. Study authors expressed that, to their knowledge, this was the first comparative effectiveness study of metronidazole and vancomycin for children with non-severe C diff infection.

Investigators from Johns Hopkins University and the Ann & Robert H. Lurie Children’s Hospital of Chicago conducted an observational study of children hospitalized with non-severe C diff treated with vancomycin versus metronidazole using an inverse probability of treatment weighted propensity score analysis. Patients were hospitalized at the Johns Hopkins Hospital, Bayview Medical Center, or Howard County General Hospital.

In addition to positive C diff testing, study eligibility required >3 new-onset unformed stools within a 24-hour period, age between 2 to 17 years, hospitalization for >48 hours for C diff, no laxative use for <48 hours, no previous C diff episode <3 months, no alternate etiology for diarrhea, no concurrent non-C diff targeted antibiotic therapy, and no severe or fulminant C diff infection.

The primary outcome was resolution or improvement of diarrhea documented by the treating clinician within 5 days of initiating antibiotic treatment.

From January 2012 to December 2018 there were 273 children hospitalized with a positive C diff identification. A total of 192 patients met eligibility criteria, with 141 receiving oral metronidazole and 51 receiving oral vancomycin. In the metronidazole group, 101 of 141 patients saw clinical improvement within 5 days, whereas 44 of 51 cases resolved with vancomycin. This indicated 71.6% and 86.3% case resolution, respectively. Odds of recurrence within 12 weeks were comparable between the groups.

Study authors wrote that there are “several possible explanations for the apparent improved effectiveness of vancomycin compared with metronidazole for the treatment of C diff. Some studies have suggested that metronidazole minimum inhibitory concentration against C diff are rising, while vancomycin resistance remains rare.”

Additionally, they note that the reduced effectiveness of metronidazole could relate to the differential absorption and fecal concentrations of the 2 agents. Vancomycin is poorly absorbed, which results in high fecal concentrations after oral administration. On the other hand, metronidazole is very well absorbed and only 6-15% is excreted in stool.

Despite their results, investigators cautioned that individual clinicians would still have to weigh several factors in deciding which of the studied medications to administer. Study authors pointed to the cost of vancomycin capsules. They expressed hope that with the publication of recent guidelines, “both the cost and barriers associated the inconsistent coverage of oral vancomycin by insurance coverage will be reduced.” They also recommended future, larger interventional studies to evaluate the reproducibility of their findings.