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Early versus late onset bloodstream infection during neutropenia after high-dose chemotherapy for hematologic malignancy

  • Andreas F. WidmerEmail author
  • Winfried V. Kern
  • Jan A. Roth
  • Markus Dettenkofer
  • Tim Goetting
  • Hartmut Bertz
  • Christian Theilacker
  • the Hospital Infection Surveillance System for Patients with Hematologic/Oncologic Malignancies Study Group (ONKO-KISS)
Original Paper



The length of neutropenia has a significant impact on the incidence of bloodstream infection (BSI) in cancer patients, but limited information is available about the pathogen distribution in late BSI.


Between 2002 and 2014, BSI episodes in patients with neutropenia receiving chemotherapy for hematologic malignancies were prospectively identified by multicenter, active surveillance in Germany, Switzerland and Austria. The incidence of first BSI episodes, their microbiology and time to BSI onset during the first episode of neutropenia of 15,988 patients are described.


The incidence rate of BSI episodes was 14.7, 8.7, and 4.7 per 1000 patient-days in the first, second, and third week of neutropenia, respectively. BSI developed after a median of 5 days of neutropenia (interquartile range [IQR] 3–10 days). The medium duration of neutropenia to BSI onset was 4 days in Escherichia coli (IQR 3–7 days), Klebsiella spp. (2–8 days), and Staphylococcus aureus (3–6 days). In contrast, BSI due to Enterococcus faecium occurred after a median of 9 days (IQR 6–14 days; p < 0.001 vs. other BSI). Late onset of BSI (occurring after the first week of neutropenia) was also observed for Stenotrophomonas maltophilia (12 days, IQR 7–17 days; p < 0.001), and non-albicans Candida spp. (13 days, IQR 8–19 days; p < 0.001).


Over the course of neutropenia, the proportion of difficult to treat pathogens such as E. faecium, S. maltophilia, and Candida spp. increased. Among other factors, prior duration of neutropenia may help to guide empiric antimicrobial treatment in febrile neutropenia.


Bacteremia Bloodstream infection Hematologic malignancy Neutropenia 



We would like to thank Dr. Maja Weisser and Dr. Nina Khanna for their help in infection documentation and data analysis. We also would like to thank Regina Babikir, Winfried Ebner for their support in managing the study and data collection. In addition, we would like to thank the medical staff and study nurses at all the participating centers for the invaluable support they provided to the studies over the years. This study has been presented in part at the 26th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) in Amsterdam, the Netherlands.The study was supported in part with funds from the German Federal Ministry of Health.

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Supplementary material

15010_2019_1327_MOESM1_ESM.docx (55 kb)
Supplementary material 1 (DOCX 54 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Andreas F. Widmer
    • 1
    Email author
  • Winfried V. Kern
    • 2
  • Jan A. Roth
    • 1
  • Markus Dettenkofer
    • 3
  • Tim Goetting
    • 3
  • Hartmut Bertz
    • 4
  • Christian Theilacker
    • 1
    • 2
  • the Hospital Infection Surveillance System for Patients with Hematologic/Oncologic Malignancies Study Group (ONKO-KISS)
  1. 1.Division of Infectious Diseases and Hospital Epidemiology, University Hospital BaselUniversity of BaselBaselSwitzerland
  2. 2.Division of Infectious Diseases, Department of Medicine II, University Hospital and Medical Center, Faculty of MedicineAlbert-Ludwigs-UniversityFreiburgGermany
  3. 3.Department of Environmental Health Sciences and Hospital Infection Control, University Hospital and Medical Center, Faculty of MedicineAlbert-Ludwigs-UniversityFreiburgGermany
  4. 4.Division of Hematology, Oncology, and Stem Cell Transplantation, Department of Medicine I, University Hospital and Medical Center, Faculty of MedicineAlbert-Ludwigs-UniversityFreiburgGermany

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