Skip to main content

Advertisement

SpringerLink
Log in

First Case of Rhinocerebral Mucormycosis Caused by Lichtheimia ornata, with a Review of Lichtheimia Infections

  • Review
  • Published:
Mycopathologia Aims and scope Submit manuscript

Abstract

Background

Lichtheimia species are emerging opportunistic fungal pathogens in the Mucorales, causing serious skin and respiratory infections in immunocompromised patients. Established agents are Lichtheimia corymbifera and L. ramosa, while L. ornata is a novel agent. Available data on a species-specific analysis of Lichtheimia infections are limited.

Methods

The first case of a fatal rhino-orbital-cerebral infection in a hematopoietic stem cell transplantation recipient caused by L. ornata is reported; the agent was identified by sequencing the ITS ribosomal region. We reviewed the literature on mucormycosis due to Lichtheimia species between 2009 and 2018, with an analysis of risk factors and epidemiological and clinical data.

Results

In addition to our Lichtheimia ornata case, 44 cases of human Lichtheimia were analyzed. Lichtheimia predominated in Europe (68.2%), followed by Asia (16%), and Africa (9%). The most common underlying condition was hematological malignancy (36.3%), followed by trauma/major surgery (27.3%), while diabetes mellitus was rare (11.4%). Site of infection was mostly skin and soft tissues (45.5%) and lung (25%), while relatively few cases were disseminated (13.6%) or rhinocerebral (11.4%). Mortality (36.4%) was mainly due to disseminated and rhinocerebral infections.

Conclusion

In contrast to Rhizopus, the most common agent of mucormycosis recorded in patients with diabetes mellitus, Lichtheimia infections were primarily associated with hematological malignancies and major skin barrier damage. Given the fact that classical rhinocerebral mucormycosis remains difficult to treat, independent of causative species, timely application of amphotericin B accessory to debridement may be required for patient survival.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Schwartze VU, Jacobsen ID. Mucormycoses caused by Lichtheimia species. Mycoses. 2014;57:73–8.

    Article  Google Scholar 

  2. Lanternier F, Dannaoui E, Morizot G, Elie C, Garcia-Hermoso D, Huerre M, et al. A global analysis of mucormycosis in France: the RetroZygo Study (2005–2007). Clin Infect Dis. 2012;54(Suppl 1):S35–43.

    Article  CAS  Google Scholar 

  3. Guinea J, Escribano P, Vena A, Muñoz P, Martínez-Jiménez MDC, Padilla B, et al. Increasing incidence of mucormycosis in a large Spanish hospital from 2007 to 2015: epidemiology and microbiological characterization of the isolates. PLoS ONE. 2017;12(6):e0179136.

    Article  Google Scholar 

  4. Pana ZD, Seidel D, Skiada A, Groll AH, Petrikkos G, Cornely OA, et al. Invasive mucormycosis in children: an epidemiologic study in European and non-European countries based on two registries. BMC Infect Dis. 2016;16:667.

    Article  Google Scholar 

  5. De Hoog GS, Guarro J, Gené J, Figueras MJ. Atlas of Clinical Fungi. E-version 4.1.4. Utrecht/Reus 2016: Westerdijk Fungal Biodiversity Institute/Universitat Rovira i Virgili.

  6. Schwartze VU, Hoffmann K, Nyilasi I, Vágvölgyi C, de Hoog S, Voigt K, et al. Lichtheimia species exhibit differences in virulence potential. PLoS ONE. 2012;7:e40908.

    Article  CAS  Google Scholar 

  7. Alastruey-Izquierdo A, Hoffmann K, de Hoog GS, Rodriguez-Tudela JL, Voigt K, Bibashi E, et al. Species recognition and clinical relevance of the zygomycetous genus Lichtheimia (syn. Absidia pro parte, Mycocladus). J Clin Microbiol. 2010;48:2154–70.

    Article  CAS  Google Scholar 

  8. Ronquist F, Huelsenbeck JP. MrBayes 3: Bayesian phylogenetic inference under mixed models. Bioinformatics. 2003;19:1572–4.

    Article  CAS  Google Scholar 

  9. CLSI. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi. CLSI standard M38. 3rd ed. Wayne, PA: Clinical and Laboratory Standards Institute; 2017.

    Google Scholar 

  10. Borras R, Rosello P, Chilet M, Bravo D, de Lomas JG, Navarro D. Positive result of the Aspergillus galactomannan antigen assay using bronchoalveolar lavage fluid from a patient with an invasive infection due to Lichtheimia ramosa. J Clin Microbiol. 2010;48:3035–6.

    Article  Google Scholar 

  11. Blazquez D, Ruiz-Contreras J, Fernández-Cooke E, González-Granado I, Delgado MD, Menendez MT, et al. Lichtheimia corymbifera subcutaneous infection successfully treated with amphotericin B. J Pediatric Surg. 2010;45:E13–E1515.

    Article  Google Scholar 

  12. Woo PC, Lau SK, Ngan AH, Tung ET, Leung SY, To KK, et al. Lichtheimia hongkongensis sp. nov., a novel Lichtheimia sp. associated with rhinocerebral, gastrointestinal, and cutaneous mucormycosis. Diagn Microbiol Infect Dis. 2010;66:274–84.

    Article  CAS  Google Scholar 

  13. Bibashi E, de Hoog GS, Pavlidis TE, Symeonidis N, Sakantamis A, Walther G. Wound infection caused by Lichtheimia ramosa due to a car accident. Med Mycol. 2012;2:7–10.

    Google Scholar 

  14. Nikitina YA, Klimko NN, Kolbin AS, Boychenko GE, Garbuzova AI, Golubeva V. Successful treatment of pulmonary mucormycosis in a child with aplastic anemia. Oncohematol 2013;8:52–8.

    Google Scholar 

  15. Kleinotiene G, Posiunas G, Raistenskis J, Zurauskas E, Stankeviciene S, Daugelaviciene V, et al. Liposomal amphotericin B and surgery as successful therapy for pulmonary Lichtheimia corymbifera zygomycosis in a pediatric patient with acute promyelocytic leukemia on antifungal prophylaxis with posaconazole. Med Oncol. 2013;30:433.

    Article  Google Scholar 

  16. Guymer C, Khurana S, Suppiah R, Hennessey I, Cooper C. Successful treatment of disseminated mucormycosis in a neutropenic patient with T-cell acute lymphoblastic leukaemia. BMJ Case Rep. 2013;10:1–5.

    Google Scholar 

  17. Eickhardt S, Braendstra P, Clasen-Linde E, Jensen KE, Alhede M, Bjarnsholt T, et al. A non-fatal case of invasive zygomycete (Lichtheimia corymbifera) infection in an allogeneic haematopoietic cell transplant recipient. APMIS 2013;121:456–9.

    Article  Google Scholar 

  18. Irtan S, Lamerain M, Lesage F, Verkarre V, Bougnoux ME, Lanternier F, et al. Mucormycosis as a rare cause of severe gastrointestinal bleeding after multivisceral transplantation. Transpl Infect Dis. 2013;15:E235–E238238.

    Article  CAS  Google Scholar 

  19. Cateau E, Randriamalala E, Elsendoorn A, Giot JP, du Sorbier CM, Rodier MH. Fatal-mixed cutaneous zygomycosis–aspergillosis: a case report. Mycopathologia. 2013;176:423–7.

    Article  Google Scholar 

  20. Poirier P, Nourrisson C, Gibold L, Chalus E, Guelon D, Descamp S, et al. Three cases of cutaneous mucormycosis with Lichtheimia spp (ex Absidia/ Mycocladus) in ICU. Possible cross-transmission in an intensive care unit between 2 cases. J Mycol Méd. 2013;23:265–9.

    Article  CAS  Google Scholar 

  21. Millon L, Larosa F, Lepiller Q, Legrand F, Rocchi S, Daguindau E, et al. Quantitative polymerase chain reaction detection of circulating DNA in serum for early diagnosis of mucormycosis in immunocompromised patients. Clin Infect Dis. 2013;56:e95–e101.

    Article  CAS  Google Scholar 

  22. Klimko NN, Khostelidi SN, Volkova AG, Popova MO, Bogomolova TS, Zuborovskaya LS, et al. Mucormycosis in haematological patients: case report and results of prospective study in Saint Petersburg, Russia. Mycoses. 2014;57:91–6.

    Article  Google Scholar 

  23. Shigemura T, Nakazawa Y, Matsuda K, Motobayashi M, Saito S, Koike K. Evaluation of Mucorales DNA load in cerebrospinal fluid in a patient with possible cerebral mucormycosis treated with intravenous liposomal amphotericin B. Int J Infect Dis. 2014;29:200–2.

    Article  Google Scholar 

  24. Kutlu M, Ergin C. Pulmonary mucormycosis due to Lichtheimia ramosa in a patient with HIV infection. Mycopathologia. 2014;178:111–5.

    Article  Google Scholar 

  25. De Chaumont A, Pierret C, Janvier F, Goudard Y, De Kerangal X, Chapuis O. Mucormycosis: a rare complication of an amputation. Ann Vasc Surg. 2014;28:1035.e15–e19.

    Article  Google Scholar 

  26. Sherif MZ, Iman ME, Nadia AE, Abdel-Ghany K. Mucormycosis in Cairo, Egypt: review of 10 reported cases. Med Mycol. 2014;52:73–80.

    Google Scholar 

  27. Lambert D, Nerot C, Huguenin A, Diallo S, Mzabi A, OhI X, et al. Post-traumatic mucormycosis due to Lichtheimia corymbifera: three case reports. J Mycol Méd. 2014;2:345–50.

    Article  Google Scholar 

  28. Stefan Z, Ralf B. Lichtheimia infection in a lymphoma patient: case report and a brief review of the available diagnostic tools. Mycopathologia. 2016;181:561–6.

    Article  Google Scholar 

  29. Mouronte-Roibás C, Leiro-Fernández V, Botana-Rial M, Ramos-Hernández C, Lago-Preciado G, Fiaño-Valverde C, et al. Lichtheimia ramosa: a fatal case of mucormycosis. Can Respir J. 2016;2016:2178218. https://doi.org/10.1155/2016/2178218.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Tyll T, Lyskova P, Hubka V, Muller M, Zelenka L, Curdova M, et al. Early diagnosis of cutaneous mucormycosis due to Lichtheimia corymbifera after a traffic accident. Mycopathologia. 2016;181:119–24.

    Article  Google Scholar 

  31. Suzuki D, Kobayashi R, Hori D, Kishimoto K, Sano H, Yasuda K, et al. Stem cell transplantation for acute myeloid leukemia with pulmonary and cerebral mucormycosis. Pediatr Int. 2016;58:569–72.

    Article  Google Scholar 

  32. Gupta N, Singh G, Aggarwal K, Thakar A, Xess I. Invasive mucormycosis in a case of aluminium phosphide poisoning. J Clin Diagn Res. 2017;11:001–2.

    Article  CAS  Google Scholar 

  33. Geng C, Lv X, Li J, Jiang Q, Yang R, Zhan P. Chronic subcutaneous infection due to Lichtheimia ramosa. J Eur Acad Dermatol Venereol. 2019;33(1):e26–e2929. https://doi.org/10.1111/jdv.15137.

    Article  CAS  PubMed  Google Scholar 

  34. Thielen BK, Barnes AMT, Sabin AP, Huebner B, Nelson S, Wesenberg E, et al. Widespread Lichtheimia infection in a patient with extensive burns: opportunities for novel antifungal agents. Mycopathologia. 2019;184(1):121–8. https://doi.org/10.1007/s11046-018-0281-6.

    Article  CAS  PubMed  Google Scholar 

  35. Garcia-Hermoso D, Hoinard D, Gantier JC, Grenouillet F, Dromer F, Dannaoui E. Molecular and phenotypic evaluation of Lichtheimia corymbifera (formerly Absidia corymbifera) complex isolates associated with human mucormycosis: rehabilitation of L. ramosa. J Clin Microbiol. 2009;47:3862–70.

    Article  CAS  Google Scholar 

  36. Schulze B, Rambach G, Schwartze VU, Voigt K, Schubert K, Speth C, et al. Ketoacidosis alone does not predispose to mucormycosis by Lichtheimia in a murine pulmonary infection model. Virulence. 2017;8:1657–67.

    Article  CAS  Google Scholar 

  37. Chakrabarti A, Singh R. Mucormycosis in India: unique features. Mycoses. 2014;57(Suppl 3):85–90.

    Article  Google Scholar 

  38. Yang LW, Ho HM, Chien CY. Notes on zygomycetes of Taiwan (X): the genus Lichtheimia in Taiwan. Fung Sci. 2012;27:109–20.

    Google Scholar 

  39. Alastruey-Izquierdo A, Cuesta I, Walther G, Cuenca-Estrella M, Rodriguez-Tudela JL. Antifungal susceptibility profile of human-pathogenic species of Lichtheimia. Antimicrob Agents Chemother. 2010;54(7):3058–60.

    Article  CAS  Google Scholar 

  40. Bouchara JP, Chaturvedi V. The curious case of “case report” of infections caused by human and animal fungal pathogens: an educational tool, an online archive, or a format in need of retooling. Mycopathologia. 2018;183(6):879–91.

    Article  Google Scholar 

Download references

Acknowledgments

The authors thank Xinlei Fan from Beijing Forestry University and Bingbing Zhang from School of Public Health, Guizhou Medical University, for their important contributions to the methodology.

Funding

This work was supported by the District Science Foundation Program (NSFC No. 81960368) from National Natural Science Foundation of China.

Author information

Authors and Affiliations

  1. Department of Dermatology, The Affiliated Hospital, Guizhou Medical University, Beijing Road 4, Yunyan District, Guiyang, China

    Junling Pan, Yu Cao, Hongguang Lu & Yanping Jiang

  2. Department of Pathology, Sidra Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar

    Clement Tsui

  3. Department of Pathology and Laboratory Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar

    Clement Tsui

  4. Division of Infectious Diseases, Faculty of Medicine, University of British Columbia, Vancouver, Canada

    Clement Tsui

  5. Department of Hematology, The Affiliated Hospital, Guizhou Medical University, Guiyang, China

    Mengxing Li

  6. Department of Radiology, Guiyang Third People’s Hospital, Guiyang, China

    Kun Xiao

  7. Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, Netherlands

    G. Sybren de Hoog, Paul E. Verweij & Yanping Jiang

  8. Center of Expertise in Mycology of Radboud University Medical Center, Canisius Wilhelmina Hospital, Nijmegen, Netherlands

    G. Sybren de Hoog, Paul E. Verweij & Yanping Jiang

Authors
  1. Junling Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Clement Tsui
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mengxing Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kun Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. Sybren de Hoog
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Paul E. Verweij
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yu Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hongguang Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yanping Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

YJ formulated the hypothesis, carried out strains collection, DNA extraction and sequencing, phylogenetic tree construction, and physiology tests, and participated in the data analysis and manuscript revision; JP drafted the manuscript, carried out the literature search, and performed the systematic analysis and data extraction. CT performed the phylogenetic tree construction and wrote parts of the manuscript. ML and KX had access to the data and participated in preparation of the manuscript. YC participated in the data interpretation and analysis. PEV supervised the statistical analyses and reviewed the manuscript. HL and SdH participated in the design of the study, statistical analysis, and manuscript revision and review. All authors read and approved the manuscript.

Corresponding author

Correspondence to Yanping Jiang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Statement

The authors confirm that this material is original and has not been published in whole or in part elsewhere; that the manuscript is not currently being considered for publication in another journal; and that all authors have been personally and actively involved in substantive work leading to the manuscript and will hold themselves jointly and individually responsible for its content. In addition, the authors confirm that they have completed the checklist for submission of a case report to Mycopathologia published by Bouchara et al. [40].

Additional information

Handling Editor: José Francisco Cano Lira.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pan, J., Tsui, C., Li, M. et al. First Case of Rhinocerebral Mucormycosis Caused by Lichtheimia ornata, with a Review of Lichtheimia Infections. Mycopathologia 185, 555–567 (2020). https://doi.org/10.1007/s11046-020-00451-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11046-020-00451-y

Keywords

Search

Navigation