Annals of Hematology

, Volume 98, Issue 5, pp 1209–1216 | Cite as

Doripenem versus meropenem as first-line empiric therapy of febrile neutropenia in patients with acute leukemia: a prospective, randomized study

  • Tatsuo OyakeEmail author
  • Yuka Takemasa-Fujisawa
  • Norifumi Sugawara
  • Takahiro Mine
  • Yasuhiko Tsukushi
  • Ichiro Hanamura
  • Yukiteru Fujishima
  • Yusei Aoki
  • Shugo Kowata
  • Shigeki Ito
  • Yoji Ishida
Original Article


Febrile neutropenia is often observed in patients with hematologic malignancies, especially in those with acute leukemia. Meropenem has potent and broad antibacterial activity against gram-positive and gram-negative bacteria, and is recommended as first-line empiric therapy for febrile neutropenia. In contrast, the safety and efficacy of doripenem in patients with febrile neutropenia and hematologic malignancies is limited. In this randomized, prospective, cooperative, open-label trial, we compared doripenem (1.0 g every 8 h) to meropenem (1.0 g every 8 h) as first-line empiric antibacterial treatment of febrile neutropenia. To evaluate efficacy and safety, 133 hospitalized patients with acute leukemia or high-risk myelodysplastic syndrome, who developed febrile neutropenia during or after chemotherapy, were randomized to each drug. Resolution of fever within 3 to 5 days without treatment modification (i.e., the primary endpoint) did not significantly differ between the doripenem and meropenem groups (60.0% vs. 45.6%, respectively; P = 0.136). However, resolution of fever within 7 days of treatment was significantly higher in the doripenem group than in the meropenem group (78.4% vs. 60.2%, respectively; P = 0.037). Similar rates of adverse events (grades 1–2) were observed in both groups. Thus, we conclude that both drugs are safe and well-tolerated for the treatment of febrile neutropenia in patients with acute leukemia or high-risk myelodysplastic syndrome, and that the clinical efficacy of doripenem is noninferior to that of meropenem. UMIN Clinical Trial Registry number: 000006124


Doripenem Meropenem Febrile neutropenia Acute leukemia High-risk myelodysplastic syndrome 



The authors would like to thank all institutions and staff members that contributed to this study.

Author contributions

YI was the principal investigator and takes primary responsibility for the paper. TO and YI designed the study. YF, NS, TM, YT, IH, and YA recruited the patients. TO, YTF, and SK reviewed and analyzed the data collected from each institute. YA and SI participated in statistical analysis. TO and YI wrote the paper.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all participants included in the study.


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Copyright information

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

Authors and Affiliations

  • Tatsuo Oyake
    • 1
    Email author
  • Yuka Takemasa-Fujisawa
    • 1
  • Norifumi Sugawara
    • 2
  • Takahiro Mine
    • 3
  • Yasuhiko Tsukushi
    • 4
  • Ichiro Hanamura
    • 5
  • Yukiteru Fujishima
    • 1
  • Yusei Aoki
    • 1
  • Shugo Kowata
    • 1
  • Shigeki Ito
    • 6
  • Yoji Ishida
    • 1
  1. 1.Division of Hematology and Oncology, Department of Internal MedicineIwate Medical University School of MedicineMorioka CityJapan
  2. 2.Division of Hematology, Department of Internal MedicineIwate Prefectural Chubu HospitalKitakamiJapan
  3. 3.Division of Hematology, Department of Internal MedicineMorioka Red Cross HospitalMoriokaJapan
  4. 4.Division of Hematology, Department of Internal MedicineHachinohe Red Cross HospitalHachinoheJapan
  5. 5.Division of Hematology, Department of Internal MedicineAichi Medical University School of MedicineNagoyaJapan
  6. 6.Department of Clinical OncologyIwate Medical University School of MedicineMoriokaJapan

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