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

  • Yoshiki Katada
    Affiliations
    Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, 54 Shogoin- Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Department of Infection Control and Prevention, Kyoto University Hospital, 54 Shogoin- Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
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  • Shunsaku Nakagawa
    Affiliations
    Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, 54 Shogoin- Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
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  • Miki Nagao
    Affiliations
    Department of Infection Control and Prevention, Kyoto University Hospital, 54 Shogoin- Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Department of Clinical Laboratory Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin- Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
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  • Yuko Yoshida
    Affiliations
    Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, 54 Shogoin- Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Department of Infection Control and Prevention, Kyoto University Hospital, 54 Shogoin- Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
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  • Yuya Matsuda
    Affiliations
    Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, 54 Shogoin- Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
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  • Yuki Yamamoto
    Affiliations
    Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, 54 Shogoin- Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
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  • Kotaro Itohara
    Affiliations
    Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, 54 Shogoin- Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
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  • Satoshi Imai
    Affiliations
    Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, 54 Shogoin- Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
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  • Atsushi Yonezawa
    Affiliations
    Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, 54 Shogoin- Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
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  • Takayuki Nakagawa
    Affiliations
    Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, 54 Shogoin- Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
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  • Kazuo Matsubara
    Affiliations
    Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, 54 Shogoin- Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Department of Pharmacy, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8509, Japan
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  • Satona Tanaka
    Affiliations
    Department of Thoracic Surgery, Kyoto University Graduate School of Medicine, 54 Shogoin- Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
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  • Daisuke Nakajima
    Affiliations
    Department of Thoracic Surgery, Kyoto University Graduate School of Medicine, 54 Shogoin- Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
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  • Hiroshi Date
    Affiliations
    Department of Thoracic Surgery, Kyoto University Graduate School of Medicine, 54 Shogoin- Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
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  • Tomohiro Terada
    Correspondence
    Corresponding author. Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
    Affiliations
    Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, 54 Shogoin- Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
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Published:October 11, 2021DOI:https://doi.org/10.1016/j.jiac.2021.09.020

      Abstract

      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.

      Keywords

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