Gram-Negative Bacteremia in Children with Hematological Malignancies and Following Hematopoietic Stem Cell Transplantation (Hsct): Epidemiology, Risk Factors for Resistance and Mortality

Michal Vinker-Shuster 1 Polina Stepensky 2 Mira Harit 2 Yair Peled 2 Michael Weintraub 2 Reem Masarwa 3 Shoshana Revel-Vilk 2 Dan Engelhard 1 Dina Averbuch 1
1Pediatric Infectious Diseases, Pediatric Division, Hadassah Medical Center
2Pediatric Hematology Oncology and HSCT, Pediatric Division, Hadassah Medical Center
3Clinical Pharmacy, Pediatric Division, Hadassah Medical Center

Background: Gram-negative bacteremia (GNB) is a major cause for morbidity and mortality in immunocompromised patients, especially in the era of rising antibiotic resistance. Data on GNB epidemiology and resistance pattern in children is scarce.

Methods: We retrospectively analyzed episodes of GNB in children with hematological malignancy and/or following HSCT in our pediatric hemato-oncology department, during the years 2010-2014. In each episode we described: background information, pathogen and its susceptibility patterns, clinical, laboratory, antibiotic treatment and outcome data. We compared these parameters in episodes caused by carbapenem-resistant vs. sensitive bacteria; and by multi-drug-resistant (MDR) vs. non-MDR bacteria. MDR was defined as resistance to three or more antibiotic classes. Complicated clinical course was defined as presence of at least one of: shock, chills, local infection or hospitalization in pediatric intensive care unit during the course of bacteremia.

Results: 65/270 (24%) children developed 85 GNB episodes; 61(63%) Enterobacteriaceae, 28 (29%) non-fermentatives and 8(8%) others. The highest rate of bacteremia was observed in allogeneic HSCT patients (32.3%). Resistance rates were: to ceftazidime-28.6%, piperacillin-tazobactam-17.4%, aminoglycosides-19.3%, quinolones-27.2%, carbapenems-10%, MDR-13.4%. In the multivariate analysis, prolonged neutropenia (>7 days, p=0.01) and longer duration of hospitalization in the 3 months before bacteremia (p=0.049) were risk factors for bacteremia due to carbapenem-resistant bacteria; breakthrough bacteremia was a risk factor for MDR bacteremia, p=0.007). 30-days mortality was 8.2%. In the multivariate analysis, significant risk factors for mortality were complicated clinical course (p=0.043) and bacteremia caused by carbapenem-resistant GNB (p=0.015).

Conclusion: Resistance to carbapenems negatively affects patients’ outcome. Empirical antibiotic therapy should be adjusted to the local resistance pattern.









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