A Multicenter Study of Bacterial Blood Stream Infections in Pediatric Allogeneic Hematopoietic Cell Transplantation Recipients: The Role of Acute Gastrointestinal Graft-versus-Host Disease

Abstract

Blood stream infections (BSI) caused by enteric organisms are associated with a particularly high mortality rate in allogeneic hematopoietic cell transplantation (alloHCT) recipients. We conducted a retrospective multicenter study aiming to analyze the risk factors associated with antibiotic resistance and impact of BSI on transplantation-related mortality (TRM) in children after alloHCT. During the study period from 2004 to 2014, 395 children (mean age, 9.4 years) with at least 1 BSI were included. The incidences of resistant gram-negative rods were 20.7% to piperacillin-tazobactam, 10.9% to cefepime, 21% to ceftazidime, 11.4% to levofloxacin, and 8.16% to meropenem. Thirty-eight percent of Enterococcus spp. isolates were resistant to vancomycin. More than 1 episode of BSI was associated with significant increase in the risk of resistance to piperacillin-tazobactam, cefepime, and vancomycin. On multivariate analysis of risk factors for TRM, achievement of neutrophil engraftment by day 30 was associated with lower TRM (P = .002). However, infection with an antibiotic-resistant organism was not associated with TRM. Development of enteric bacterial BSI after the onset of acute gastrointestinal graft-versus-host disease (GVHD) was the strongest predictor of TRM (hazard ratio, 4.786; 95% confidence interval, 2.833 to 8.087; P < .001). In patients with acute gastrointestinal GVHD who subsequently developed enteric bacterial BSI, the incidence of 1-year TRM was 33.4% (SE = 7%), compared with 15.3% (SE = 2%) for those without acute gastrointestinal GVHD (P = .004). Primary prevention of a first episode of BSI is arguably the most important intervention to decrease antibiotic resistance. It is also imperative that we develop strategies to maintain gastrointestinal health, especially in patients with gastrointestinal GVHD, in an effort to prevent subsequent enteric bacterial BSI and improve survival.

Antimicrobial Resistance in Gram-Negative Rods Causing Bacteremia in Hematopoietic Stem Cell Transplant Recipients: Intercontinental Prospective Study of the Infectious Diseases Working Party of the European Bone Marrow Transplantation Group

“…Data on resistance rates in post-HSCT children are scarce [12,16,29]. Surpr resistance rates were mostly similar in children and in adults in our study.…”

“…Several studies reported risk factors for cephalosporin-resistant, ESBL-pro or MDR bacteria in cancer and HSCT patients [10,12,13,16,22,29,32]. Onl handful describe risk factors for carbapenem-resistant infections in popula involving but not limited to transplant patients, mainly for K. pneumoniae.…”

“…The risk of infection is influenced by local factors, amo prevalence of resistance, prophylactic practices, empiric treatment, and antimicrobial stewardship. Only a handful of studies focus on children and autologous HSCT (auto-HSCT) patients [12,15,16]. This study aimed to des resistance rates and risk factors in GNR bacteremia in HSCT patients, based intercontinental data.…”

Multiple bloodstream infections in pediatric stem cell transplant recipients: A case series

“…Recurrent BSIs in patients undergoing SCT are associated with increased mortality . To our knowledge, this is the first case series describing patients with three or more BSIs after SCT.…”

“…The majority of BSI occurs during the preengraftment period and is associated with prolonged hospitalization, intensive care unit admission, and protracted antibiotic exposure, leading to increased morbidity and mortality . In particular, it has recently been shown that patients who have more than one BSI within the first year following SCT have a higher rate of nonrelapsed mortality (NRM) than patients experiencing a single BSI …”