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Clinical effectiveness of itraconazole as antifungal prophylaxis in AML patients undergoing intensive chemotherapy in the modern era

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European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

Antifungal prophylaxis regimens vary between centres, informed by local epidemiology and antifungal stewardship practices. The advantages of itraconazole over posaconazole prophylaxis include maintaining the utility of azole therapy for suspected breakthrough invasive fungal infection (bIFI). We examined the effectiveness and tolerability of itraconazole as prophylaxis in acute myeloid leukaemia (AML) patients. We sought to determine the rate of probable and proven bIFI in the context of itraconazole prophylaxis in a real-life setting. Eighty-four patients corresponded to 175 episodes of primary antifungal prophylaxis with itraconazole solution (200 mg twice daily) as prophylaxis supported by a dedicated clinical pharmacist during induction, re-induction and consolidation chemotherapy for AML between January 2010 and January 2014. Assessment of clinical course included blinded review of all radiology scans. Episodes of bIFI were categorised according to consensus criteria. A low rate of bIFI (6/175, 3.4 %) occurred with the use of itraconazole. Tolerance was excellent with adverse events consisting predominantly of deranged liver function tests reported in 7/175 (4 %). Therapeutic drug monitoring performed at clinicians’ discretion demonstrated appropriate levels in 12/14 (86 %). Persisting fever and suspicion of invasive fungal infection (IFI) led to empiric antifungal therapy with voriconazole or caspofungin in 33/175 episodes (19 %), ceased after a median of 5 days following investigation in 16/175 (9 %). In this setting, itraconazole is effective and well-tolerated as prophylaxis. An additional benefit was seen in empiric therapy of suspected bIFI with amphotericin formulations kept in reserve. Local epidemiology is vital in guiding prophylaxis strategy.

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Abbreviations

alloHCT:

Allogeneic haematopoietic stem cell transplant

AML:

Acute myeloid leukaemia

BAL:

Broncho-alveolar lavage

bIFI:

Breakthrough invasive fungal infection

G-CSF:

Granulocyte colony stimulating factor

HRCT:

High-resolution computed tomography

IFI:

Invasive fungal infection

L-AMB:

Liposomal amphotericin B

NNT:

Number needed to treat

TDM:

Therapeutic drug monitoring

TPN:

Total parenteral nutrition

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Acknowledgments

The authors would like to thank Dr Kirby Wong and Dr Kim Lam for their intellectual input into radiology assessment.

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Authors and Affiliations

  1. Department of Microbiology and Infectious Diseases, Royal Prince Alfred Hospital, Camperdown, Sydney, Australia

    C. L. Keighley & S. van Hal

  2. Department of Medicine, University of Sydney, Camperdown, Sydney, Australia

    C. L. Keighley

  3. Department of Pharmacy, Royal Prince Alfred Hospital, Missenden Road, Camperdown, Sydney, Australia

    C. L. Keighley & P. Manii

  4. Department of Haematology, Royal Prince Alfred Hospital, Missenden Road, Camperdown, Sydney, Australia

    S. R. Larsen

Authors
  1. C. L. Keighley
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  2. P. Manii
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  3. S. R. Larsen
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  4. S. van Hal
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Corresponding author

Correspondence to C. L. Keighley.

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We received no funding, fellowships or grants for this work.

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There are no conflicting interests to declare.

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This study was approved by the Sydney South West Area Health Service (SSWAHS) ethics committee.

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Keighley, C.L., Manii, P., Larsen, S.R. et al. Clinical effectiveness of itraconazole as antifungal prophylaxis in AML patients undergoing intensive chemotherapy in the modern era. Eur J Clin Microbiol Infect Dis 36, 213–217 (2017). https://doi.org/10.1007/s10096-016-2780-z

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  • DOI: https://doi.org/10.1007/s10096-016-2780-z

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