Severe drug eruption after antibiotic administration in patients receiving immune checkpoint inhibitors: A monocentric case series

Author:

Nishizawa Aya12ORCID,Takeda Koichi3,Urasaki Tetsuya4,Ono Makiko4,Mochizuki Toshiaki5,Shiga Taro6,Fujiwara Motohiro7,Yuasa Takeshi7,Murakami Atsushi8,Koike Ryo8,Yunokawa Mayu8,Kanao Hiroyuki8,Shimozaki Keitaro9,Takahari Daisuke9,Kogawa Takahiro10,Takahashi Shunji4,Kitano Shigehisa1011

Affiliation:

1. Department of Dermatology, Advanced Medical Development Center The Cancer Institute Hospital of the Japanese Foundation for Cancer Research Tokyo Japan

2. Department of Dermatology, Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital Tokyo Japan

3. Department of Onco‐rheumatology, Advanced Medical Development Center The Cancer Institute Hospital of the Japanese Foundation for Cancer Research Tokyo Japan

4. Department of Medical Oncology, Advanced Medical Development Center The Cancer Institute Hospital of the Japanese Foundation for Cancer Research Tokyo Japan

5. Department of Emergency Medicine, Advanced Medical Development Center The Cancer Institute Hospital of the Japanese Foundation for Cancer Research Tokyo Japan

6. Department of Onco‐Cardiology/Cardiovascular Medicine, Advanced Medical Development Center The Cancer Institute Hospital of the Japanese Foundation for Cancer Research Tokyo Japan

7. Department of Urology, Advanced Medical Development Center The Cancer Institute Hospital of the Japanese Foundation for Cancer Research Tokyo Japan

8. Department of Gynecologic Oncology, Advanced Medical Development Center The Cancer Institute Hospital of the Japanese Foundation for Cancer Research Tokyo Japan

9. Department of Gastroenterological Chemotherapy, Advanced Medical Development Center The Cancer Institute Hospital of the Japanese Foundation for Cancer Research Tokyo Japan

10. Division of Early Clinical Development, Advanced Medical Development Center The Cancer Institute Hospital of the Japanese Foundation for Cancer Research Tokyo Japan

11. Cancer Immunotherapy Development, Advanced Medical Development Center The Cancer Institute Hospital of the Japanese Foundation for Cancer Research Tokyo Japan

Abstract

AbstractImmune checkpoint inhibitor (ICI) therapy is often associated with cutaneous immune‐related adverse events (irAEs). Drug eruptions stemming from concomitantly or consecutively administered medications are also frequent and tend to be severe. We herein present three cases of severe drug eruption in patients receiving antibiotics during ICI therapy in which hypotensive shock occurring during antibiotic administration was followed by generalized erythema and prolonged organ damage. Three patients received tazobactam/piperacillin (TAZ/PIPC) for an infection during ICI treatment. A high fever developed in all the patients after a switch was made to other antibiotics (Figures 2–4). Since no skin rash was observed at fever onset, a flare‐up of the infection was suspected, and TAZ/PIPC administration was resumed. Thereafter, the patients suddenly experienced hypotensive shock and respiratory failure requiring ICU management for generalized erythema and organ damage. Since anaphylaxis caused by TAZ/PIPC is rare, the patients’ clinical findings might be a manifestation of synergistic, complementary, immunomodulatory effects of ICI. In patients receiving ICI therapy, a fever occurring during antibiotic administration may indicate the onset of an immune hypersensitivity reaction to the drug. Resumption of antibiotic administration, especially TAZ/PIPC, during such a period may trigger an excessive inflammatory response, leading to an anaphylaxis‐like reaction and organ damage.

Publisher

Wiley

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