Prevalence of Resistant Gram-Negative Bacilli in Bloodstream Infection in Febrile Neutropenia Patients Undergoing Hematopoietic Stem Cell Transplantation: A Single Center Retrospective Cohort Study

Abstract

Bloodstream infection (BSI) is an important cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). To evaluate the causative bacteria and identify risk factors for BSI associated mortality in febrile neutropenia patients undergoing HSCT, we collected the clinical and microbiological data from patients underwent HSCT between 2008 and 2014 and performed a retrospective analysis. Throughout the study period, among 348 episodes of neutropenic fever in patients underwent HSCT, 89 episodes in 85 patients had microbiological defined BSI with a total of 108 isolates. Gram-negative bacteria (GNB) were the most common isolates (76, 70.3%) followed by gram-positive bacteria (GPB, 29, 26.9%) and fungus (3, 2.8%). As to the drug resistance, 26 multiple drug resistance (MDR) isolates were identified. Resistant isolates (n = 23) were more common documented in GNB, mostly Escherichia coli (9/36, 25%) and Klebsiella pneumonia (6/24, 25%). A total of 12 isolated were resistant to carbapenem including 4 K pneumoniae (4/24, 16.7%), 3 Stenotrophomonas maltophilia, and 1 Pseudomonas aeruginosa and other 4 GNB isolates (Citrobacter freumdii, Pseudomonas stutzeri, Acinetobacter baumanii, and Chryseobacterium indologenes). As to the GPB, only 3 resistant isolates were documented including 2 methicillin-resistant isolates (Staphylococcus hominis and Arcanobacterium hemolysis) and 1 vancomycin-resistant Enterococcus faecium. Among these 85 patients with documented BSI, 11 patients died of BSI as primary or associated cause with a BSI-related mortality of 13.1 ± 3.7% and 90-day overall survival after transplantation at 80.0 ± 4.3%. Patients with high-risk disease undergoing allo-HSCT, prolonged neutropenia (≥15 days) and infection with carbapenem-resistant GNB were associated with BSI associated mortality in univariate and multivariate analyses. Our report revealed a prevalence of GNB in BSI of neutropenic patients undergoing HSCT. Patients with high-risk diseases with prolonged neutropenia and carbapenem-resistant GNB were independent risk factors for BSI-related mortality.

FIGURE 1

(A) The BSI-related mortality after documentation of BSI. (B) The 90-d overall survival of 85 patients who had BSI during the neutropenia. BSI = bloodstream infection.

FIGURE 2

(A) Comparison of BSI-related mortality in patients receiving autologous HSCT (0) and allogeneic HSCT (17.8 ± 4.9%, P = 0.04). (B) Comparison of BSI-related mortality in patients undergoing HSCT with standard-risk (22.6 ± 6.6%) and high-risk disease (4.5 ± 3.1%, P = 0.014). (C) Comparison of BSI-related mortality in patients with carbapenem-resistant gram-negative bacteria infection (70.0 ± 14.5%) and non-CRE infection (5.4 ± 2.6%, P < 0.001). (D) Comparison of BSI-related mortality in patients with neutropenia <15 d CRE (1.7 ± 1.7%) and prolonged neutropenia (≥15 d, 38.5 ± 9.5%, P < 0.001). BSI = bloodstream infection; CRE = carbapenem-resistant enterobacteriaceae; HSCT = hematopoietic stem cell transplant.

FIGURE 3

Comparison of patients with 0 to 1, 2, and 3 risk factors for BSI-related mortality: BSI-related mortality rate were 4.5 ± 1.5%, 41.7 ± 14.2%, and 83.3 ± 15.2%, respectively. BSI = bloodstream infection.