Several antibiotics were found to associate with increased rates of acute graft-vs-host disease (aGVHD) in patients who have recently undergone allogeneic hematopoietic cell transplantation (allo-HCT). These study findings were published in JAMA Network Open.
A team of researchers embarked upon a cohort study to identify antibiotics that could be problematic for patients undergoing allo-HCT, as well as identify exposure timeframes associated with subsequent aGVHD.
Data from patients who underwent their first transplant from 2010 to 2021 at a single comprehensive cancer center with at least 6 months of follow-up were analyzed. The study included 2023 patients, median age 55 years.
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The primary endpoint was grade 2-4 aGVHD, and the secondary endpoint was grade 3-4 aGVHD. Fluoroquinolones, third-generation or newer cephalosporins, intravenous vancomycin, trimethroprim-sulfamethoxazole, and carbapenems were the most frequently used antibiotics.
By day 180 posttransplant, 1461 patients (72%) developed grade 2-4 aGVHD, with a median time to onset of 29 days. Grade 3-4 occurred in 295 patients (15%).
There were 206 deaths (14%) among those with grade 2-4 aGVHD and 102 deaths (35%) among those with grade 3-4 aGVHD by 180 days posttransplant. Additionally, 98% (1990 patients) engrafted neutrophils at a median 17 days (range, 14 to 20) posttransplant.
The researchers found aGVHD associated with carbapenems in weeks 1 and 2 posttransplant. Combinations of pencillins with a β-lactamase inhibitor had a significant association with aGVHD in week 1 posttransplant.
However, an association between an increased risk of aGVHD and exposure to any of the 9 most commonly used antibiotics was found in at least 1 of the 5 intervals. This suggested that general patterns of microbiota injury could be important.
“The most consistent finding in this study and prior reports, and with recent mechanistic support from murine studies, is a detrimental association of aGVHD with carbapenem exposure in weeks 1 and 2 after HCT,” the researchers wrote. “Avoiding this class of antibiotics early after transplant seems prudent.”
Various protective treatments targeting the microbiota are under investigation with the hope of serving as effective treatment or prophylaxis but sparing the microbiota. Prebiotics and fecal microbiota transplantation are potentially restorative treatments.
“If our results are replicated in independent cohorts, antibiotic-associated risk of aGVHD could become a consideration in antibiotic stewardship programs,” the researchers concluded.
Disclosures: One study author declared affiliation with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Rashidi A, Gao F, Fredricks DN, et al. Analysis of antibiotic exposure and development of acute graft-vs-host disease following allogeneic hematopoietic cell transplantation. JAMA Netw Open. Published online June 7, 2023. doi:10.1001/jamanetworkopen.2023.17188
