Antimicrobial stewardship to reduce multidrug resistance and opportunistic Clostridioides difficile infection (CDI) could also guide shorter treatment.
A shortened duration of vancomycin or fidaxomicin for Clostridioides difficile infection (CDI) was comparably effective to the standard 10 days of treatment and was associated with less recurrent infection, in a preliminary, observational study1.
MUDr Marek Ďuríček Department of Infectious Diseases, 3rd Faculty of Medicine, Charles University and University Hospital Bulovka, Prague, Czech Republic, and colleagues point out that stewardship programs encouraging appropriate antimicrobial selection and application have been an impetus for studying shorter treatment regimens for a range of infections, including pharyngitis, pneumonia and urinary tract.
They posited that treatment of CDI with vancomycin or fidaxomicin could also be shortened from the standard 10 days, given that their concentrations in the stool reaches hundreds- to thousands-fold the minimum inhibitory concentrations (MIC) within 2 to 3 days, and that has coincided with clinical resolution of diarrhea for some patients.
"The general idea was to eradicate viable bacterial cells capable of toxin production and spare the rest of the microbiome so it can recover more quickly and can provide colonization resistance," Ďuríček told Contagion.
The investigators conducted the observational study with 47 adult patients hospitalized with CDI from January 2022 to May 2023, and treated with either vancomycin 125mg every 6 hours or 200mg of fidaxomicin every 12 hours. Twenty-two participants (median age 74.5 years) in the control group received the standard 10-day treatment, and 25 (median age76 years) received 5 or 7 days of vancomycin (n=21) or 5 days of fidaxomicin (n=4).
The acuity at admission and history of prior CDI were similar in both groups, with 5 patients in each group presenting with CDI characterized as severe from a leukocyte count >15.0x109/L. Three participants in each group had history of recurrent CDI.The admissions were the first episode of CDI for 17 of the standard treatment participants and 22 of those receiving shorter regimens.
"We are currently in the process of preparing a double-blinded, randomized placebo-controlled trial (RCT) with a larger cohort of patients," Ďuríček commented. "The equality of severe CDI cases at admission will be one of the conditions in the randomization process."
Shortened durations of vancomycin or fidaxomicin treatment, when compared to the standard 10-day regimen, showed comparable effectiveness in treating CDI.
The study was motivated by stewardship programs that promote appropriate antibiotic use.
The study's authors are preparing for a double-blinded, randomized placebo-controlled trial (RCT) with a larger cohort of patients to further investigate the effectiveness of shorter treatment regimens.
Examinations were performed daily throughout the hospitalization, with response to treatment evaluated by clinical measures such as resolution of diarrhea and abdominal pain; and laboratory markers of WBC count and serum C-reactive protein (CRP) level at the beginning and end of the antibiotic course. Causative C difficile strains were characterized by ribotyping and toxin gene detection when available. Follow-up was conducted by outpatient visit or telephone 60 days after the illness, or at time of a recurrence.
Two patients in the study group died from cormorbid conditions unrelated to CDI. All other participants achieved CDI resolution by clinical and laboratory indications at completion of treatment. A sustained cure through follow-up was achieved in all participants with severe CDI in both groups.
The investigators reported that the recurrence rate in the study group during follow-up was 8.0% (2 of 25) patients, compared to numerically higher 22% (5 of 22) in the control group.
Although the lower recurrence rate with shortened therapy was not statistically significantly different than in those receiving the standard 10 days of treatment, Ďuríček is hopeful that the apparent advantage will be affirmed in the planned RCT. He also hopes to ascertain any interaction of illness severity to response to the shortened treatment.
"We realize that there was just a small number of severe CDI cases in both groups and hopefully the larger RCT will answer the question on effectiveness differences between the patients with severe vs milder symptoms," Ďuríček said.
Reference
1.Duricek M, Halmova K, Krutova M, et al. Is shorter also better in the treatment of Clostridioides difficle infection? J Antimicrob Chemother2024; Aprl 25:dkae119. doi: 10.1093/jac/dkae119. Online ahead of print. Acessed May 9, 2024.
