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Effects of Pre-transplantation Antibiotic Use on Clinical Outcomes in HSCT Patients

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This project would not have been possible without the support and guidance of my supervisor, Emma Elizabeth Ilett. Emma helped me establish the specific research question and structure of the study. She also assisted with statistical analysis, provided helpful advice during each step of the project, and taught me so much about clinical study logistics and the background for the current study. I would also like to thank the staff at PERSIMUNE who were very welcoming, friendly, and helpful with any questions I had.

Hematopoietic stem cell transplantation (HSCT) recipients receive pre-transplantation treatment regimens varying in conditioning intensity and antibiotic administration. Broad-spectrum, antianaerobic antibiotics have the potential to disrupt the normal gut microbiome balance and reduce immune function. We aimed to retrospectively examine the impact of pre-transplantation conditioning and antibiotics on rates of mortality, Clostridium difficile infection (CDI), and graft versus host disease (GvHD) in 59 adults receiving HSCT at Copenhagen University Hospital, Rigshospitalet, between June 18th 2015 and March 9th 2017. Patients had received either nonmyeloablative (mini) or myeloablative (MAC) conditioning prior to HSCT. To assess antibiotic use, patients were classified into two groups: those who received high risk antibiotics within 6 months prior to transplantation and those who did not. At transplantation, MAC HSCT patients had a younger median age of 50 compared to a median age of 63 in mini HSCT patients (pvalue=0.001). MAC HSCT patients more often received pre-transplantation radiation (pvalue<0.0001) and high risk antibiotics (p-value=0.0073) compared to mini HSCT patients. A total of 6 mini HSCT patients (21%) died compared to 2 MAC HSCT patients (7%). However, differences in mortality were not statistically significant (IRR 0.24, p-value=0.097, 95% CI 0.04-1.3). A total of 7 patients (18%) that received high risk antibiotics died compared to 1 patient (5%) in the control group but these differences also were not statistically significant (IRR 4.67, p-value=0.167, 95% CI 0.52-41.8). CDI and GvHD rates did not differ significantly between groups. Overall, there was no evidence that pre-transplantation conditioning and antibiotics could predict clinical outcomes. Treatment with high risk antibiotics may be a risk factor for adverse clinical outcomes, but a larger sample size is necessary to determine whether this trend is significant.

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  • 02/12/2018
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