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Scientific article
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Frequency and causes of antifungal treatment changes in allogeneic haematopoïetic cell transplant recipients with invasive mould infections

Published inMycoses, vol. 65, no. 2, p. 199-210
Publication date2022-02
First online date2021-12-29
Abstract

Antifungal treatment duration and changes for invasive mould infections (IMI) have been poorly described.

We performed a 10-year cohort study of adult (≥18-year-old) allogeneic haematopoietic cell transplant recipients with proven/probable IMI to describe the duration and changes of antifungal treatment. All-cause-12-week mortality was described.

Sixty-one patients with 66 IMI were identified. Overall treatment duration was 157 days (IQR: 14-675) and 213 (IQR: 90-675) days for patients still alive by Day 84 post-IMI diagnosis. There was at least one treatment change in 57/66 (86.4%) cases: median 2, (IQR: 0-6, range:0-8). There were 179 antifungal treatment changes due to 193 reasons: clinical efficacy (104/193, 53.9%), toxicity (55/193, 28.5%), toxicity or drug interactions resolution (15/193, 7.8%) and logistical reasons (11/193, 5.7%) and 15/193 (7.8%) changes due to unknown reasons. Clinical efficacy reasons included lack of improvement (34/104, 32.7%), targeted treatment (30/104, 28.8%), subtherapeutic drug levels (14/104, 13.5%) and other (26/104, 25%). Toxicity reasons included hepatotoxicity, nephrotoxicity, drug interactions, neurotoxicity and other in 24 (43.6%), 12 (21.8%), 12 (21.8%), 4 (7.4%) and 3 (5.5%) cases respectively. All-cause 12-week mortality was 31% (19/61), higher in patients whose antifungal treatment (logrank 0.04) or appropriate antifungal treatment (logrank 0.01) was started >7 days post-IMI diagnosis. All-cause 1-year mortality was higher in patients with ≥2 changes of treatment during the first 6 weeks post-IMI diagnosis (logrank 0.008) with an OR: 4.00 (p = .04).

Patients with IMI require long treatment courses with multiple changes for variable reasons and potential effects on clinical outcomes, demonstrating the need more effective and safer treatment options. Early initiation of appropriate antifungal treatment is associated with improved outcomes.

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Keywords
  • Allogeneic haematopoietic cell transplant recipients
  • Antifungal treatment changes
  • Invasive aspergillosis
  • Invasive mould infections
  • Mortality
  • Surgical treatment
  • Adult
  • Antifungal Agents / classification
  • Antifungal Agents / therapeutic use
  • Cohort Studies
  • Drug Substitution
  • Fungi
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Humans
  • Invasive Fungal Infections / drug therapy
  • Transplant Recipients
Funding
  • Pfizer - [59276319-WP2485056]
Citation (ISO format)
ROTH, Romain et al. Frequency and causes of antifungal treatment changes in allogeneic haematopoïetic cell transplant recipients with invasive mould infections. In: Mycoses, 2022, vol. 65, n° 2, p. 199–210. doi: 10.1111/myc.13416
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Article (Published version)
Secondary files (1)
Identifiers
ISSN of the journal0933-7407
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Creation03/01/2022 1:17:00 PM
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