Study dives into the complexities of using Oral Vancomycin Prophylaxis to combat Clostridioides difficile in hematopoietic stem cell transplantation recipients with insights from researcher Alexander Vartanov, MD.
Clostridioides difficile infection (CDI) presents a risk of up to 9 times higher for patients undergoing hematopoietic stem cell transplantation (HSCT) compared to the general population. This is attributed to factors including prolonged neutropenia, extensive exposure to antimicrobials, and chemotherapy-induced damage to the mucosal barrier. While the use of Oral Vancomycin Prophylaxis (OVP) has been effective in reducing the incidence of C difficile infection, it has been concurrently linked to a rise in the rate of gram-negative bacteremia among HSCT recipients, escalating from 13% to 21.8%. Although the outcomes related to Graft-versus-Host Disease (GVHD) were broadly similar across the board, the onset of these outcomes occurred earlier in the OVP group.
Out of 441 patients, 181 were administered prophylactic vancomycin. In the control group, 34 patients developed CDI, compared to 13 in group B (13 vs 7%; p=0.048). The rate of positive blood cultures was comparable between the groups: 27% vs 33%. Nonetheless, the occurrence of gram-negative bacteremia was higher, with 34 cases in group A and 41 in group B (13 vs 21.8%; p=0.008), which also included further data on engraftment and GVHD.
“The dual outcomes here is really what we explored in our study we sequentially gave patients all vancomycin prophylaxis, so that consisted of 125 milligram doses twice per day,” explains Alexander Vartanov, MD. “Then after that, we administered oral vancomycin to all our patients. We compare the outcomes our primary outcome measure was we reduced the incidence of C Diff infection that outcome and there was a reduction in the rates of C Diff infection, both 14 Compared to 7% in the patients who received the prophylaxis.”
This observation raises the possibility that OVP may induce alterations in the gut microbiome, especially in individuals who are already susceptible to bacterial translocation and at an elevated risk for GVHD. Further investigation is necessary to identify the HSCT recipients who would most benefit from C difficile prophylaxis. Considering the heightened occurrence of gram-negative infections noted in our retrospective study, the implementation of this prophylactic approach should be carefully weighed.
“We were delighted to see that this intervention did succeed in reducing the rate of infections, which somewhat mirrors the limited data that's out there,” said Alexander Vartanov, MD. “The surprising piece is one of the key secondary outcomes that we had an increased rate of gram-negative bacteremia. It is an important safety signal because gram-negative bacteremia is a spectrum of infection. With a gram-negative organism, many of those can live in our bodies. They are particularly for patients who are undergoing chemotherapy infections can range from a minor infection that just requires attention and treatment to a potentially life-threatening infection that can lead to septic shock or death.”
A review of medical records was conducted for consecutive patients who underwent HSCT in the program from March 2021 to May 2023. The 441 patients were divided into 2 groups, Group A, serving as the control group, and Group B, consisting of patients who received OVP during their inpatient stay for HSCT. The prophylactic regimen entailed the administration of 125mg of vancomycin twice daily from the day of hospital admission until the day of discharge.
“People who have C diff infections are at higher risk for various complications, morbidity, and mortality are increased in those patients,” Alexander Vartanov, MD explains. “We always must have a higher suspicion for anything that can go wrong, not just gram-negative bacteremia. What we'd like to do as we go forward and collect more data over the coming years is ask and answer the questions, is there a change in this outcome with our new strategy of being more selective and who we use OVP for? Do we still observe a similar result? Do those patients still have a higher incidence of gram-negative bacteremia? Or have we mitigated the risk by selecting patients with more clear risk factors for developing the C Diff infection? That's where we'd like to go in a future direction from the infectious perspective.”
All in all, Alexander Vartanov, MD offered great insights on how OVP presents a promising strategy to reduce C difficile, and its association with an increased risk of gram-negative bacteremia highlights the complexity of microbial dynamics within the human body. This study underscores the importance of medical interventions, advocating for a strategic, evidence-based application of prophylactic measures. The findings emphasize the necessity for ongoing research, careful patient selection, and a holistic view of prophylaxis outcomes to truly safeguard the health of HSCT recipients.
Reference
Vartanov A, Shestovska, Hamby M, Styler, M, et, al. Using Oral Vancomycin As Prophylaxis Against Clostridioides Difficile Infection in Stem Cell Transplant Recipients Is Associated with Increased Gram Negative Bacteremia. Published February 2024. Accessed February 26, 2024. DOI: https://doi.org/10.1016/j.jtct.2023.12.633
