Voriconazole plus terbinafine combination antifungal therapy for invasive Lomentospora prolificans infections: analysis of 41 patients from the FungiScope® registry 2008-2019

J D Jenks; D Seidel; O A Cornely; S Chen; S van Hal; C Kauffman; M H Miceli; M Heinemann; M Christner; A Jover Sáenz; A Burchardt; B Kemmerling; R Herbrecht; J Steinmann; S Shoham; S Gräber; L Pagano; D Deeren; S Aslam; R Taplitz; S G Revankar; J Baddley; S R Mehta; S Reed; M A Slavin; M Hoenigl

doi:10.1016/j.cmi.2020.01.012

Voriconazole plus terbinafine combination antifungal therapy for invasive Lomentospora prolificans infections: analysis of 41 patients from the FungiScope® registry 2008-2019

Clin Microbiol Infect. 2020 Jun;26(6):784.e1-784.e5. doi: 10.1016/j.cmi.2020.01.012. Epub 2020 Jan 20.

Authors

J D Jenks¹, D Seidel², O A Cornely², S Chen³, S van Hal⁴, C Kauffman⁵, M H Miceli⁵, M Heinemann⁶, M Christner⁷, A Jover Sáenz⁸, A Burchardt⁹, B Kemmerling⁹, R Herbrecht¹⁰, J Steinmann¹¹, S Shoham¹², S Gräber¹³, L Pagano¹⁴, D Deeren¹⁵, S Aslam¹⁶, R Taplitz¹⁶, S G Revankar¹⁷, J Baddley¹⁸, S R Mehta¹⁶, S Reed¹⁹, M A Slavin²⁰, M Hoenigl²¹

Affiliations

¹ Department of Medicine, University of California San Diego, San Diego, CA, USA; Clinical and Translational Fungal Research Group, University of California San Diego, San Diego, CA, USA. Electronic address: jjenks@ucsd.edu.
² Department I of Internal Medicine, ECMM Excellence Centre of Medical Mycology, CECAD-Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University Hospital Cologne, Cologne, Germany.
³ Centre for Infectious Diseases and Microbiology, Westmead Hospital, and Sydney Medical School, The University of Sydney, Camperdown, NSW, Australia.
⁴ Department of Microbiology and Infectious Diseases, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
⁵ Department of Medicine, University of Michigan, Ann Arbor, MI, USA.
⁶ Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
⁷ Department of Medical Microbiology, Virology and Hygiene, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
⁸ Territorial Unit of Nosocomial Infection and Antibiotic Policy (TUNI), University Hospital Arnau de Vilanova, Lleida, Spain.
⁹ Department of Haematology, Hospital of Justus Liebig University Giessen, Germany.
¹⁰ Department of Oncology and Haematology, Strasbourg University Hospital, Strasbourg, France.
¹¹ Institute of Clinical Hygiene, Medical Microbiology and Infectiology, Klinikum Nürnberg, Paracelsus Medical University, Nuremberg, Germany; Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
¹² Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹³ Institute of Medical Microbiology and Epidemiology of Infectious Diseases, University Hospital Leipzig, Leipzig, Germany.
¹⁴ Department of Haematology, Fondazione Policlinico A. Gemelli - IRCCS, Rome, Italy; Department of Haematology, Università Cattolica del Sacro Cuore, Rome, Italy.
¹⁵ Department of Haematology, AZ Delta, Roeselare, Belgium.
¹⁶ Department of Medicine, University of California San Diego, San Diego, CA, USA; Clinical and Translational Fungal Research Group, University of California San Diego, San Diego, CA, USA.
¹⁷ Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
¹⁸ Department of Medicine, Wayne State University, Detroit, MI, USA.
¹⁹ Department of Medicine, University of California San Diego, San Diego, CA, USA; Clinical and Translational Fungal Research Group, University of California San Diego, San Diego, CA, USA; Department of Pathology, University of California San Diego, San Diego, CA, USA.
²⁰ Department of Infectious Diseases, and National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
²¹ Department of Medicine, University of California San Diego, San Diego, CA, USA; Clinical and Translational Fungal Research Group, University of California San Diego, San Diego, CA, USA; Department of Medicine, ECMM Excellence Centre of Medical Mycology, Medical University of Graz, Graz, Austria. Electronic address: hoeniglmartin@gmail.com.

PMID: 31972317
DOI: 10.1016/j.cmi.2020.01.012

Abstract

Objectives: Lomentospora prolificans is an emerging cause of serious invasive fungal infections. Optimal treatment of these infections is unknown, although voriconazole-containing treatment regimens are considered the treatment of choice. The objective of this study was to evaluate the role of combination antifungal therapy for L. prolificans infections.

Methods: We performed a retrospective review of medical records of patients with invasive L. prolificans infection diagnosed between 1 January 2008 and 9 September 2019 that were documented in the FungiScope® registry of rare invasive fungal infections. We compared clinical outcomes between antifungal treatment strategies.

Results: Over the study period, 41 individuals with invasive L. prolificans infection from eight different countries were documented in the FungiScope® registry. Overall, 17/40 (43%) had treatment response/stable disease and 21/40 (53%) had a fatal outcome attributed to invasive fungal infection. Combination antifungal therapy was associated with increased 28-day survival (15/24 survived versus 4/16 receiving monotherapy; p 0.027) and the combination voriconazole plus terbinafine trended to be associated with higher rates of treatment success (10/16, 63%, 95% CI 35%-85%) compared with other antifungal treatment regimens (7/24, 29%, 95% CI 13%-51%, p 0.053). In Kaplan-Meier survival analysis there was a higher survival probability in individuals receiving the voriconazole/terbinafine combination compared with other antifungal regimens (median survival 150 days versus 17 days).

Conclusions: While overall mortality was high, combination antifungal treatment, and in particular combination therapy with voriconazole plus terbinafine may be associated with improved treatment outcomes compared with other antifungal regimens for the treatment of invasive L. prolificans infections.

Keywords: Fungal infections; Lomentospora prolificans; Olorofim; Outcomes; Scedosporium; Terbinafine; Treatment; Voriconazole.

MeSH terms

Adult
Aged
Antifungal Agents / therapeutic use*
Drug Therapy, Combination
Female
Humans
Invasive Fungal Infections / blood
Invasive Fungal Infections / drug therapy*
Male
Microbial Sensitivity Tests
Middle Aged
Registries
Retrospective Studies
Scedosporium / drug effects
Terbinafine / therapeutic use*
Treatment Outcome
Voriconazole / therapeutic use*

Substances

Antifungal Agents
Terbinafine
Voriconazole

Supplementary concepts

scedosporiosis