Molecular identification of Fusarium species complex isolated from clinical samples and its antifungal susceptibility patterns

Document Type : Original Articles


1 Department of Microbiology, Government Medical College Hospital, Chandigarh, India

2 Department of Ophthalmology, Government Medical College Hospital, Chandigarh, India


Background and Purpose: More than 300 Fusarium species are grouped into approximately 23 species complexes out of which around 70 are involved in human infections. The nomenclature of these species has undergone considerable changes in recent years. These species cause localized infections in individuals while inducing systemic infections mainly in immunocompromised patients. The present study was conducted to identify Fusarium species in clinical isolates by molecular methods and determine their in vitro minimum inhibitory concentration (MIC) patterns to address the lack of data in this domain in Northern India.
Materials and Methods: For the purpose of the study, Fusarium isolates obtained from various clinical samples were sent to the Westerdijk Fungal Biodiversity Institute, Utrecht, the Netherlands, for molecular identification. The MIC testing was performed using the microbroth dilution method as per the Clinical and Laboratory Standards Institute reference method (M38-A2).
Results: Fusarium was isolated from 33 patients (i.e., 1, 1, 2, 14, and 15 cases with endophthalmitis, sinusitis, pulmonary involvement, onychomycosis, and keratitis, respectively). These 33 isolates belonged to three species complexes, namely F. solani species complex (FSSC; n=13), F. fujikuroi species complex (FFSC; n=13), and F. incarnatum equiseti species complex (FIESC; n=7). The species identified within FSSC, FFSC, and FIESC included F. keratoplasticum (n=6)/F. falciforme (n=6)/F. solani (n=1), F. proliferatum (n=7)/F. sacchari (n=5)/F. anthophilum (n=1), and F. incarnatum SC species (n=6)/F. equiseti SC species (n=1), respectively. The MIC results showed that all isolates had a lower MIC against amphotericin B than against the other antifungal agents.
Conclusion: Timely diagnosis and appropriate treatment will facilitate the improvement of patient outcomes.


1. Costa-Orlandi CB, Sardi JCO, Pitangui NS, de Oliveira HC, Scorzoni L, Galeane MC, et al. Fungal biofilms and polymicrobial diseases. J Fungi (Basel). 2017; 3(2):22.
2. Nucci M, Anaissie EJ. Fusarium infections in immune-compromised patients. Clin Micro Rev. 2007; 20(4):695-704.
3. Tupaki-Sreepurna A, Kindo AJ. Fusarium: the versatile pathogen. Indian J Med Microbiol. 2018; 36(1):8-17.
4. Moretti ML, Busso-Lopes AF, Tararam CA, Moraes R, Muraosa Y, Mikami Y, et al. Airborne transmission of invasive fusariosis in patients with hematologic malignancies. PloS One. 2018; 13(4):e0196426.
5. Chilaka CA, De Boevre M, Atanda OO, De Saeger S. The status of Fusarium mycotoxins in Sub-Saharan Africa: a review of emerging trends and post-harvest mitigation strategies towards food control. Toxins (Basel). 2017; 9(1):E19.
6. Jacobs-Venter A, Laraba I, Geiser DM, Busman M, Vaughan MM, Proctor RH, et al. Molecular systematics of two sister clades, the Fusarium concolor and F. babinda species complexes and the discovery of a novel microcycle macroconidium-producing species from South Africa. Mycologia. 2018; 110(6):1189-204.
7. Guarro J. Fusariosis, a complex infection caused by a high diversity of fungal species refractory to treatment. Eur J Clin Microbiol Infect Dis. 2013; 32(12):1491-500.
8. Douglas AP, Chen SC, Slavin MA. Emerging infections caused by non-Aspergillus filamentous fungi. Clin Microbiol Infect. 2016; 22(8):670-80.
9. Harpaz R, Dahl RM, Dooling KL. Prevalence of immunosuppression among US adults, 2013. JAMA. 2016; 316(23):2547-8.
10. Nucci M, Varon AG, Garnica M, Akiti T, Barreiros G, Trope BM, et al. Increased incidence of invasive fusariosis with cutaneous portal of entry, Brazil. Emerg Infect Dis. 2013; 19(10):1567-72.
11. Schroers HJ, Gräfenhan T, Nirenberg HI, Seifert KA. A revision of Cyanonectria and Geejayessia gen. nov., and related species with Fusarium-like anamorphs. Stud Mycol. 2011; 68:115-38.
12. Gräfenhan T, Schroers HJ, Nirenberg HI, Seifert KA. An overview of the taxonomy, phylogeny, and typification of nectriaceous fungi in Cosmospora, Acremonium, Fusarium, Stilbella and Volutella. Stud Mycol. 2011; 68:79-113.
13. Hawksworth D. A new dawn for the naming of fungi: impacts of decisions made in Melbourne in July 2011 on the future publication and regulation of fungal names. IMA Fungus. 2011; 2(2):155-62.
14. Hawksworth DL, May TW, Redhead SA. Fungal nomenclature evolving: changes adopted by the 19(th) International Botanical Congress in Shenzhen 2017, and procedures for the Fungal Nomenclature Session at the 11(th) International Mycological Congress in Puerto Rico 2018. IMA Fungus. 2017; 8(2):211-8.
15. Abastabar M, Al-Hatmi AMS, Vafaei Moghaddam M, de Hoog GS, Haghani I, Aghili SR, et al. Potent activities of luliconazole, lanoconazole, and eight comparators against molecularly characterized fusarium species. Antimicrob Agents Chemother. 2018; 62(5):e00009-18.
16. van Diepeningen AD, Brankovics B, Iltes J, van der Lee TA, Waalwijk C. Diagnosis of Fusarium infections: approaches to identification by the clinical mycology laboratory. Curr Fungal Infect Rep. 2015; 9(3):135-43.
17. Al-Hatmi AMS, Curfs-Breuker I, de Hoog GS, Meis JF, Verweij PE. Antifungal susceptibility testing of fusarium: a practical approach. J Fungi (Basel). 2017; 3(2):E19.
18. Al-Hatmi AM, Hagen F, Menken SB, Meis JF, de Hoog GS. Global molecular epidemiology and genetic diversity of Fusarium, a significant emerging group of human opportunists from 1958 to 2015. Emerg Microbes Infect. 2016; 5(12):e124.
19. Taj-Aldeen SJ. Reduced multidrug susceptibility profile is a common feature of opportunistic fusarium species: fusarium multi-drug resistant pattern. J Fungi (Basel). 2017; 3(2):E18.
20. de Hoog GS, Guarro J, Gené J, Figueras MJ. Atlas of clinical fungi. 2nd ed. Spain: Centraalbureau voor Schimmelcultures (CBS); 2000.
21. van Diepeningen AD, Feng P, Ahmed S, Sudhadham M, Bunyaratavej S, de Hoog GS. Spectrum of Fusarium infections in tropical dermatology evidenced by multilocus sequencing typing diagnostics. Mycoses. 2015; 58(1):48-57.
22. Davari M, Wei SH, Babay-Ahari A, Arzanlou M, Waalwijk C, van der Lee TAJ, et al. Geographic differences in trichothecene chemotypes of Fusarium graminearum in the Northwest and North of Iran. World Mycotoxin J. 2013; 6(2):137-50.
23. Clinical and Laboratory Standards Institute. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; approved standard. 2nd ed. CLSI document M38-A2. Wayne, PA: CLSI; 2008.
24. Indian Council of Medical Research (ICMR). Ethical guidelines for biomedical research on human subjects. New Delhi: Indian Council of Medical Research; 2006.
25. World Medical Association Declaration of Helsinki. Ethical principles for medical research involving human subjects. 59th WMA General Assembly, Seoul; 2008.
26. Herkert PF, Al-Hatmi AMS, de Oliveira Salvador GL, Muro MD, Pinheiro RL, Nucci M, et al. Molecular characterization and antifungal susceptibility of clinical Fusarium species from Brazil. Front Microbiol. 2019; 10:737.
27. Tortorano AM, Prigitano A, Esposto MC, Arsic Arsenijevic V, Kolarovic J, Ivanovic D, et al. European Confederation of Medical Mycology (ECMM) epidemiological survey on invasive infections due to Fusarium species in Europe. Eur J Clin Microbiol Infect Dis. 2014; 33(9):1623-30.
28. Bansal Y, Chander J, Kaistha N, Singla N, Sood S, van Diepeningen AD. Fusarium sacchari, a cause of mycotic keratitis among sugarcane farmers - a series of four cases from North India. Mycoses. 2016; 59(11):705-9.
29. Tosti A, Elewski BE. Onychomycosis: practical approaches to minimize relapse and recurrence. Skin Appendage Disord. 2016; 2(1-2):83-7.
30. Diongue K, Ndiaye M, Seck MC, Diallo MA, Badiane AS, Ndiaye D. Onychomycosis caused by Fusarium spp. in Dakar, Senegal: epidemiological, clinical, and mycological study. Dermatol Res Pract. 2017; 2017:1268130.
31. Ranawaka RR, Nagahawatte A, Gunasekara TA. Fusarium onychomycosis: prevalence, clinical presentations, response to itraconazole and terbinafine pulse therapy, and 1-year follow-up in nine cases. Int J Dermatol. 2015; 54(11):1275-82.
32. Esnakula AK, Summers I, Naab TJ. Fatal disseminated fusarium infection in a human immunodeficiency virus positive patient. Case Rep Infect Dis. 2013; 2013:379320.
33. Marom EM, Holmes AM, Bruzzi JF, Truong MT, O'Sullivan PJ, Kontoyiannis DP. Imaging of pulmonary fusariosis in patients with hematologic malignancies. AJR Am J Roentgenol. 2008; 190(6):1605-9.
34. Tortorano AM, Richardson M, Roilides E, van Diepeningen A, Caira M, Munoz P, et al. ESCMID and ECMM joint guidelines on diagnosis and management of hyalohyphomycosis: Fusarium spp., Scedosporium spp. and others. Clin Microbiol Infect. 2014; 20(Suppl 3):27-46.
35. Nucci M, Marr KA, Vehreschild MJ, de Souza CA, Velasco E, Cappellano P, et al. Improvement in the outcome of invasive fusariosis in the last decade. Clin Microbiol Infect. 2014; 20(6):580-5.
36. Al-Hatmi AMS, Bonifaz A, Ranque S, de Hoog GS, Verweij PE, Meis JF. Current antifungal treatment of fusariosis. Int J Antimicrob Agents. 2018; 51(3):326-32.