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Characteristics of gram-negative bacteremia during febrile neutropenia among allogeneic hematopoietic stem cell transplant recipients on levofloxacin prophylaxis

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Abstract

The aim of this study is to clarify the characteristics of gram-negative bacteremia (GNB), including extended-spectrum β-lactamase (ESBL)-producing pathogens, among allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients on levofloxacin (LVFX) prophylaxis. A retrospective analysis on GNB at the first episode of febrile neutropenia (FN) was conducted among allo-HSCT recipients (age ≥ 20 years) on 500 mg/day of oral LVFX prophylaxis. Epidemiological and microbiological features of GNB were investigated and compared between the inappropriate and appropriate empiric therapy groups. In total, FN occurred in 414 allo-HSCT cases, and bacteremia at the first episode of FN occurred in 169 cases. Overall, 29 GNB cases were documented, and the causative organisms identified were Escherichia coli in 21 cases (including 10 ESBLs), Klebsiella pneumoniae in 2, Pseudomonas aeruginosa in 2, and other in 4. The crude 30-day mortality rate was not significantly different among cases of GNB (6.9%), gram-positive bacteremia (GPB) (7.1%), or non-bacteremia (5.4%; P = 0.78). Cefepime (CFPM) was administered in all cases in the inappropriate empiric therapy group, and all causative organisms were ESBL-producing E. coli (ESBL-EC). All patients in the inappropriate empiric therapy group had a low Pitt bacteremia score (≤ 2). Thirty-day mortality did not differ significantly between the inappropriate and appropriate empiric therapy groups (1/10 vs. 1/15, P = 0.61). In conclusion, GNB was not a significant cause of death. In LVFX breakthrough ESBL-EC bacteremia among allo-HSCT recipients, the administration of CFPM as empiric therapy did not lead to significantly poor prognosis. Empiric CFPM administration might be an acceptable strategy.

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Data availability

The dataset generated during and/or analyzed during the current study is available from the corresponding author on reasonable request.

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Acknowledgments

We thank the staff of the microbiology laboratory of Toranomon Hospital (Ms Chikako Okada, Ms. Reiko Yabusaki, Ms. Mayumi Yamanaka, Ms. Hiromi Baba, Ms. Noriko Watahiki, Mr. Masaru Baba, Ms. Emiko Miyajima, Ms. Chiemi Yoshino, Ms. Ayumi Takamura, and Mr. Yusuke Endo) for performing tests for identification and antimicrobial susceptibility of ESBL-EC. This research is supported by the Okinaka Memorial Institute for Medical Research, Tokyo, Japan. 

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Authors and Affiliations

  1. Department of Infectious Diseases, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan

    Sho Ogura, Muneyoshi Kimura & Hideki Araoka

  2. Department of Hematology, Toranomon Hospital, Tokyo, Japan

    Shinsuke Takagi, Takashi Mitsuki, Mitsuhiro Yuasa, Kosei Kageyama, Daisuke Kaji, Aya Nishida, Yuki Taya, Kazuya Ishiwata, Hisashi Yamamoto, Yuki Asano-Mori, Go Yamamoto, Naoyuki Uchida, Atsushi Wake & Shuichi Taniguchi

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  1. Sho Ogura
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Contributions

SO and MK designed the study and collected data. SO, MK, and HA analyzed the clinical data. SO and MK wrote the manuscript. SO, MK, ST, TM, MY, KK, DK, AN, YT, KI, HY, YA-M, GY, NU, AW, SU-T, and HA interpreted the results and reviewed the final draft of the manuscript. All authors read and revised the final manuscript before submission.

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Correspondence to Muneyoshi Kimura.

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The authors declare that they have no conflict of interest.

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The protocol of this retrospective study was evaluated by the Human Ethics Review Committee of Toranomon Hospital and waived from the requirement of patient informed consent.

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All the authors reviewed this study and agreed to publish this manuscript.

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This study was approved by the Human Ethics Review Committee of Toranomon Hospital.

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Ogura, S., Kimura, M., Takagi, S. et al. Characteristics of gram-negative bacteremia during febrile neutropenia among allogeneic hematopoietic stem cell transplant recipients on levofloxacin prophylaxis. Eur J Clin Microbiol Infect Dis 40, 941–948 (2021). https://doi.org/10.1007/s10096-020-04096-z

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