The following is a summary of “Analysis of Antibiotic Exposure and Development of Acute Graft-vs-Host Disease Following Allogeneic Hematopoietic Cell Transplantation,” published in the June 2023 issue of Hematology by Rashidi et al.
The impact of antibiotic exposures on acute graft-vs-host disease (aGVHD) rates following allogeneic hematopoietic cell transplantation (allo-HCT) is complex due to the interplay between antibiotics, infections, and various confounding factors. This analysis requires a substantial sample size and innovative approaches to account for time-dependent exposure and prior antibiotic use.
For a study, researchers objective was to identify the specific antibiotics and corresponding antibiotic exposure timeframes linked to subsequent aGVHD. This study evaluated the outcomes of allo-HCT at a single center from 2010 to 2021. The participants were individuals aged 18 years or older who had received their initial T-cell-replete allo-HCT and had been followed up for a minimum of six months.
Data analysis for this study was conducted between August 1 and December 15, 2022. The exposure of interest in this study was using antibiotics between 7 days before and 30 days after the transplant. The analysis resulted in the primary outcome of grades II to IV of aGVHD. They also examined the occurrence of grade III to IV aGVHD as a secondary outcome. To analyze the data, investigators employed 3 different methods: conventional cox proportional hazard regression, marginal structural models, and machine learning.
They included a total of 2,023 patients (median [range] age, 55 [18-78] years; 1,153 [57%] male) who were eligible. Analysis revealed that the highest-risk periods for developing aGVHD occurred during the 1st and 2nd weeks after hematopoietic HCT. Multiple instances of antibiotic exposure during these critical time intervals were associated with increased rates of subsequent aGVHD. Carbapenem exposure during the first and second weeks following allo-HCT consistently demonstrated an increased risk of aGVHD (minimum hazard ratio [HR] among models, 2.75; 95% CI, 1.77-4.28), use of penicillins combined with a β-lactamase inhibitor during the first week after allo-HCT was consistently associated with a higher risk of aGVHD (minimum HR among models, 6.55; 95% CI, 2.35-18.20).
They concluded rates of aGVHD in allo-HCT recipients were found to be influenced by the selection and timing of antibiotics during the early stages of transplantation. These findings emphasize the importance of considering these factors in antibiotic stewardship programs.