Impact of choice, timing, sequence and combination of broad-spectrum antibiotics on the outcome of allogeneic haematopoietic stem cell transplantation

Abstract

Recent data link the incidence of intestinal GvHD (iGvHD) after allogeneic haematopoietic stem cell transplantation (aSCT) to exposure with piperacillin-tazobactam or imipenem-cilastatin. To assess relevance of timing, duration, sequence and combination of antibiotic treatment in this setting, we applied a time-dependent model to our aSCT cohort. Patients from the prospective Cologne Cohort of Neutropenic Patients (CoCoNut) undergoing aSCT from January 2007 to April 2013 were included into a time-dependent multivariate Cox proportional hazards regression model with backward-stepwise selection. In 399 eligible patients, cumulative antibiotic exposure (hazard ratio (HR) 2.46; 95% confidence interval (95% CI) 1.59-3.81; P<0.001) and exposure to sequential treatment with penicillin derivatives and carbapenems (HR 6.22, 95% CI 1.27-30.31), but not to the individual classes, were associated with iGvHD at day 100. Glycopeptides were assessed as a risk factor (HR 3.73, 95% CI 1.51-9.19), but not considered independent, since their use was dependent on previous exposure to penicillin derivatives and carbapenems. Patients with iGvHD presented with increased non-relapse mortality at day 365 (HR 3.51; 95% CI 2.10-5.89; P<0.001). We identified sequential exposure to penicillin derivatives and carbapenems as well as overall exposure to antibiotics as independent risk factors for iGVHD. Confirmation of these findings in larger, prospective cohorts is necessary.

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

“…On the other hand, use of carbapenem for greater than 7 days was not associated with poor OS and high NRM. Farowski et al reported that cumulative antibiotic exposure was related to the incidence of acute GVHD. Long‐term administration of carbapenem may cause loss of beneficial anaerobic bacteria for regulating alloreactive response, such as Clostridia and Blautia .…”

Assessment of urinary 3-indoxyl sulfate as a marker for gut microbiota diversity and abundance of Clostridiales

“…In line with these findings, we recently confirmed exposure to these antibiotic classes as an independent risk factor for intestinal GvHD in allo-HCT patients. 18 Concordantly, other studies have demonstrated these antibiotics as risk factors of CDI. 15,19 Yet other studies have confirmed a link between development of CDI and intestinal GvHD.…”

Clinical and pharmacoeconomic evaluation of antifungal prophylaxis with continuous micafungin in patients undergoing allogeneic stem cell transplantation: A six‐year cohort analysis

“…In comparison with all above‐mentioned RCTs, it must be noted that our study results are based on real‐life observational patient data outside the highly controlled environment of a clinical trial. To the authors’ knowledge, our data were extracted from one of the world’s largest single‐centre cohorts of haematological patients who are at high risk developing healthcare‐associated infections 22–24 …”