Secular Trends of Blood Stream Infections in the 72 Hours Prior to Death in Allogeneic Hematopoietic Cell Transplant Recipients

Blood stream infections (BSI) are a common cause of morbidity and mortality in hematopoietic cell transplant (HCT) recipients especially in the first year post transplant. With emergence of multi- drug resistant (MDR) organisms, especially enterobacteriaceae and enterococci, early treatment with targeted antibiotics remains challenging. Despite antimicrobial prophylaxis and initiation of empiric broad spectrum antimicrobials early in the course of treatment, BSI is an independent predictor of mortality after HCT, with mortality rates after BSI as high as 27% in the first 30 days following HCT. The characteristics of specific organisms identified shortly before death have not been well described. This information may guide empiric antimicrobial treatment and eventually primary prevention of these infections. We conducted a retrospective single center study of 529 patients who received an allogeneic HCT and died between 2000- 2013. Among these patients, 216 had a clinical indication for a blood culture within 72 hours prior to death and we investigated secular trends in BSI (microbiological spectrum and antimicrobial susceptibility pattern) for all pathogens in this population. Overall, 104 BSI were identified from 91 patients. Blood stream infection and criteria for drug resistance in different organisms were defined according to the CDC and National Healthcare Safety Network surveillance definitions. Bacterial infections were the most common comprising of 87% of 104 BSI. Gram positive bacteria accounted for 50% and gram negative bacteria for 37% of infections. Amongst these, enterococcus (30%), staphylococcus (16%), pseudomonas (16%), klebsiella (5%) and E. coli (4%) were the most commonly identified organisms. Most of the enterococci were vancomycin resistant (VRE 87%), all staphylococci—both coagulase negative and S. aureus—were methicillin resistant, 64% of pseudomonas were multidrug resistant and all Klebsiella and E. Coli isolates were either extended spectrum Beta lactamase producers or carbapenem resistant. Over time there was a significant increase in VRE (7.7/100 deaths in 2000 to 12.5/100 deaths in 2013, p=0.017) and gram negative bacterial infections (7.7 in 2000 to 12.5 in 2013, p=0.011), particularly Klebsiella, E. coli and Stenotrophomonas infections. Interestingly there was a decrease in staphylococcal (15.4 in 2000 to 0 in 2013, p=0.041) and streptococcal (p=0.06) infections. Fungal infections comprised of 12% of all BSI, with Candida being the most common organism identified (50%), but there was no significant change in trend over time. Blood stream infection was either the primary or secondary cause of death in 53% of patients who had a positive culture. In conclusion, Vancomycin resistant enterococcal infections are the most common BSI identified 72 hours prior to death in allogeneic transplant recipients; prompting us to consider appropriate antibiotic coverage even empirically in critically ill HSCT recipients. With the increase in MDR pseudomonas and resistant E. coli and Klebsiella, we might need to consider appropriate empiric gram negative coverage, and escalating antibiotics earlier if there is no response clinically. With the proper central/peripheral intravenous catheter care, we have seen a decrease in staphylococcal BSI over time, reinforcing primary prevention of BSI.