The association between the incidence of intestinal graft‐vs‐host disease and antibiotic use after allogeneic hematopoietic stem cell transplantation

Abstract

Intestinal microbiota plays an important role in the regulation of allogeneic immune reaction after allogeneic hematopoietic stem cell transplantation (allo-SCT). Intestinal graft-vs-host disease (GVHD) is one of the major causes of mortality after allo-SCT and often complicated with intestinal dysbiosis. Recent studies suggest that antibiotic-induced dysbiosis is a risk factor for intestinal GVHD. We retrospectively evaluated the impacts of antibiotic use on the incidence of intestinal GVHD occurring before day 100 after allo-SCT. Among 213 patients who underwent allo-SCT, 200 patients achieving engraftment were analyzed. Antibiotics were classified into carbapenem, quinolone, penicillin, cephem, and glycopeptide. Among 128 patients who developed acute GVHD, intestinal GVHD developed in 36 patients. Patients with intestinal GVHD received significantly longer administration of carbapenem and glycopeptide compared to those without it in periengraftment period. In multivariate analysis, use of carbapenem for greater than 7 days was associated with an increased risk of intestinal GVHD. However, use of antibiotics for greater than 7 days was not associated with poor overall survival and high nonrelapse mortality. Long use of carbapenem in periengraftment period may be a risk for intestinal GVHD. Prospective studies are required to validate our findings.

Roles of the intestinal microbiota and microbial metabolites in acute GVHD

“…Exposure to piperacillin-tazobactam increased the incidence of grade II-IV GVHD and GI GVHD, and increased GVHD-related mortality [47,[119][120][121] Carbapenems Carbapenems were associated with the increased risk of grade II-IV aGVHD and intestinal GVHD. Early and longer use of carbapenem especially increased aGVHD risk [119][120][121][122][123] Fourth-generation cephalosporins The cumulative incidence of GI aGVHD was significantly higher in patients who received fourth-generation cephalosporins than in those who did not [124] Cephalosporins There was no association between cephalosporins treatment and aGVHD incidence [119] Glycopeptide Patients with GI GVHD received significantly longer administration of glycopeptide compared to those without GI GVHD [122] Aminoglycosides There was no association between aminoglycosides treatment and aGVHD incidence [124] Quinolones There was no association between quinolones treatment and aGVHD incidence [122,124] Aztreonam Treatment with aztreonam was associated with a decreased GVHD-related mortality by univariate analyses [47] Cefepime Antibiotic exposure to cefepime was significantly correlated with reduced GVHD-related mortality by univariate analyses [47] Rifaximin Patients received rifaximin showed lower transplant-related mortality and higher overall survival [56,125] Page 13 of 19 CD2 lozenges prevented oral mucositis in HSCT patients undergoing high-dose chemotherapy [137]. Supplementation with Lactobacillus rhamnosus GG has been demonstrated to improve survival and reduce aGVHD severity in a mouse model [138].…”

Antimicrobial Prophylaxis and Modifications of the Gut Microbiota in Children with Cancer

“…After HCT, a shift towards Enterococcus domination was observed, which was particularly evident in patients under antibiotic treatment who developed gut GvHD. This was one of the first studies to provide evidence that alteration of the microbiota by HCT-related procedures (such as antibiotic exposure) is directly linked to GvHD, as confirmed in more recent analyses [87][88][89][90]. Italian researchers have been particularly active in defining how microbiota dysbiosis impacts pediatric patients undergoing HCT.…”

Mucosal microbiotas and their role in stem cell transplantation

“…Eventually, controlled clinical studies were not able to document any benefit of ‘gut decontamination’ [ 19 ]. While prophylactic antibiotic regimens are still a standard of care for HSCT patients today, recent research indicates that the gain of preventing infections by antimicrobial prophylaxis might be compromised by adverse clinical outcomes such as GvHD and treatment‐related mortality that accompany the loss of specific commensal taxa [ 20 , 21 , 22 , 23 , 24 ].…”