Risk factors of breakthrough aspergillosis in lung transplant recipients receiving itraconazole prophylaxis

Yoshiki Katada, Shunsaku Nakagawa, Miki Nagao, Yuko Yoshida, Yuya Matsuda, Yuki Yamamoto, Kotaro Itohara, Satoshi Imai, Atsushi Yonezawa, Takayuki Nakagawa, Kazuo Matsubara, Satona Tanaka, Daisuke Nakajima, Hiroshi Date, Tomohiro Terada

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


Introduction: Invasive Aspergillus infection (IA) in lung transplantation can result in poor outcomes. Itraconazole has been shown to be effective for fungal prophylaxis in lung transplant recipients. However, IA remains a major cause of death after lung transplantation. Therefore, we aimed to clarify the risk factors for IA on itraconazole prophylaxis. Methods: We examined 120 recipients to uncover their IA epidemiology, clinical characteristics, and outcomes. In addition, a case-control study was performed to identify risk factors of IA. Results: Of the 120 patients, 12 developed IA under itraconazole prophylaxis. The patient demographics and clinical characteristics were compared among the following two groups: IA group, 12 patients, and control group, 108 patients. Significant differences were observed in age (p = 0.004), history of interstitial pneumonia (p = 0.032), and CMV infection (p < 0.001) between the groups. Before the onset of IA, 92% (11/12) of the patients received itraconazole with trough concentrations above the therapeutic range. IA developed at 272.9 ± 114.1 days after lung transplantation. Of the 12 patients who developed IA, 66.7% (8/12) had early cessation of cytomegalovirus (CMV) prophylaxis due to toxicity of valganciclovir, as follows: leukocytopenia in 4 patients, and renal dysfunction in 4 patients. Of the 8 patients who stopped valganciclovir, 75% (6/8) developed CMV infection subsequently. Conclusion: This study suggests that older age, history of interstitial pneumonia, and CMV infection may be important risk factors for IA on itraconazole prophylaxis. These results may help clinicians optimize prophylactic strategies for IA.

Original languageEnglish
Pages (from-to)54-60
Number of pages7
JournalJournal of Infection and Chemotherapy
Issue number1
Publication statusPublished - 2022 Jan
Externally publishedYes


  • 6): invasive Aspergillus infection
  • Breakthrough aspergillosis
  • Itraconazole
  • Lung transplantation
  • Prophylaxis
  • Risk factor

ASJC Scopus subject areas

  • Microbiology (medical)
  • Pharmacology (medical)
  • Infectious Diseases


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