Advertisement

Mycopathologia

, Volume 175, Issue 1–2, pp 107–114 | Cite as

Disseminated Amphotericin-Resistant Fusariosis in Acute Leukemia Patients: Report of Two Cases

  • Graziella Hanna PereiraEmail author
  • Derlene Attili de Angelis
  • Roosecelis Araujo Brasil
  • Marilena dos Anjos Martins
  • Dulcilena de Matos Castro e Silva
  • Maria Walderez Szeszs
  • Marcia de Souza Carvalho Melhem
Article

Abstract

Disseminated fusariosis has emerged as a significant, usually fatal infection in immunocompromised hosts despite antifungal treatment. We describe here two patients with acute leukemia who developed disseminated amphotericin-resistant fusariosis, and review of six studies of cases series in the literature. Two Fusarium solani strains were isolated from blood and skin cultures of one patient, and one strain from the blood culture of the second patient. Both patients died despite antifungal treatment. Strains were identified by sequencing of ITS1 and ITS4 regions. Random amplified polymorphic DNA analysis of the three F. solani isolates showed a low degree of similarity. Screening for Fusarium spp. contaminants within our facility was negative. Using the CLSI M-38-A2 broth dilution method and E tests®, we found that the MICs were low for voriconazole (0.12 and 0.5 mg/L, respectively), unexpectedly high for amphotericin B (≥8 and ≥32 μg/mL, respectively) and itraconazole (≥16 mg/ml). Patients with leukemia or persistent neutropenia should be assessed for disseminated fungal infections, including biopsy and skin cultures. Antifungal susceptibility tests are important due to the possibility of the strains being amphotericin resistant. Treatments must be aggressive, with high doses of antifungals or combined therapy.

Keywords

Fusariosis Fusarium solani Amphotericin resistant Leukemia Antifungal 

References

  1. 1.
    Tezcan G, Ozhak-Baysan B, Alastruey-Izquierdo A, Ogunc D, Ongut G, Yıldıran ST, Hazar V, Cuenca-Estrella M, Rodriguez-Tudela JL. Disseminated fusariosis caused by Fusarium verticillioides in an acute lymphoblastic leukemia patient after allogeneic hematopoietic stem cell transplantation. J Clin Microbiol. 2009;47:278–81.PubMedCrossRefGoogle Scholar
  2. 2.
    Jossi M, Ambrosioni J, Macedo-Vinas M, Garbino J. Invasive fusariosis with prolonged fungemia in a patient with acute lymphoblastic leukemia: case report and review of the literature. Int J Infect Dis. 2010;14:e354–6.PubMedCrossRefGoogle Scholar
  3. 3.
    Selleslag D. A case of fusariosis in an immunocompromised patient successfully treated with liposomal amphotericin B. Acta Biomed. 2006;77:32–5.PubMedGoogle Scholar
  4. 4.
    Kontoyiannis DP, Bodey GP, Hanna H, Hachem R, Boktour M, Girgaway E, et al. Outcome determinants of fusariosis in a tertiary care cancer center: the impact of neutrophil recovery. Leuk Lymphoma. 2004;45:139–41.PubMedCrossRefGoogle Scholar
  5. 5.
    Farina C, Vailati F, Manisco A, Goglio A. Fungaemia survey: a 10-year experience in Bergamo, Italy. Mycoses. 1999;42:543–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Nucci M, Anaissie E. Fusarium infections in immunocompromised patients. Clin Microbiol Rev. 2007;20:695–704.PubMedCrossRefGoogle Scholar
  7. 7.
    Tortorano AM, Prigitano A, Dho G, Esposto MC, Gianni C, Grancini A, Ossi C, Viviani MA. Species distribution and in vitro antifungal susceptibility patterns of 75 clinical isolates of Fusarium spp. from Northern Italy. Antimicrob Agents Chemother. 2008;52:2683–5.PubMedCrossRefGoogle Scholar
  8. 8.
    Girmenia C, Pagano L, Corvatta L, Mele L, del Favero A, Martino P. The epidemiology of fusariosis in patients with haematological diseases. Gimema Infection Programme. Br J Haematol. 2000;111:272–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Martino P, Gastaldi R, Raccah R, Girmenia C. Clinical patterns of Fusarium infections in immunocompromised patients. J Infect. 1994;28:7–15.PubMedCrossRefGoogle Scholar
  10. 10.
    White TJ, Bruns T, Lee S, Taylor JW. Amplification and direct sequencing of fungal ribosomal RNA genes for phylogenetics. In: Innis MA, Gelfand DH, Sninsky JJ, White TJ, editors. PCR protocols: a guide to methods and applications. New York: Academic Press Inc.; 1990. p. 315–22.Google Scholar
  11. 11.
    Hall TA. BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucl Acids Symp Ser UK. 1999;41:95–8.Google Scholar
  12. 12.
    Soll DR. The ins and outs of DNA fingerprinting the infectious fungi. Clin Microbiol Rev. 2000;13:332–70.PubMedCrossRefGoogle Scholar
  13. 13.
    Kovacicova G, Spanik S, Kunova A, et al. Prospective study of fungaemia in a single cancer institution over a 10-y period: aetiology, risk factors, consumption of antifungals and outcome in 140 patients. Scand J Infect Dis. 2001;33:367–74.PubMedCrossRefGoogle Scholar
  14. 14.
    Boutati EI, Anaissie EJ. Fusarium, a significant emerging pathogen in patients with hematologic malignancy: ten years’ experience at a cancer center and implications for management. Blood. 1997;90:999–1008.PubMedGoogle Scholar
  15. 15.
    Guzman-Cottrill JA, Zheng X, Chadwick EG. Fusarium solani endocarditis successfully treated with liposomal amphotericin B and voriconazole. Pediatr Infect Dis J. 2004;23(11):1059–61.PubMedCrossRefGoogle Scholar
  16. 16.
    Nelson PE, Dignani MC, Anaissie EJ. Taxonomy, biology, and clinical aspects of Fusarium species. Clin Microbiol Rev. 1994;7(4):479–504.PubMedGoogle Scholar
  17. 17.
    Gupta AK, Baran R, Summerbell RC. Fusarium infections of the skin. Curr Opin Infect Dis. 2000;13:121–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Azor M, Gene J, Cano J, Manikandan P, Venkatapathy N, Guarro JV. Less-frequent Fusarium species of clinical interest: correlation between morphological and molecular identification and antifungal susceptibility. J Clin Microbiol. 2009;47:1463–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Paphitou NI, Ostrosky-Zeichner L, Paetznick VL, Rodriguez JR, Chen E, Rex JH. In vitro activities of investigational triazoles against Fusarium species: effects of inoculum size and incubation time on broth microdilution susceptibility test results. Antimicrob Agents Chemother. 2002;46:3298–300.PubMedCrossRefGoogle Scholar
  20. 20.
    Arikan S, Lozano-Chiu M, Paetznick V, Nangia S, Rex JH. Microdilution susceptibility testing of amphotericin B, itraconazole, and voriconazole against clinical isolates of Aspergillus and Fusarium species. J Clin Microbiol. 1999;37:3946–51.PubMedGoogle Scholar
  21. 21.
    Alastruey-Izquierdo A, Cuenca-Estrella M, Monzón A, Mellado E, Rodrıguez-Tudela JL. Antifungal susceptibility profile of clinical Fusarium spp. isolates identified by molecular methods. Antimicrob Chemother. 2008;61:805–9.CrossRefGoogle Scholar
  22. 22.
    Radford SA, Johnson EM, Warnock DW. In vitro studies of activity of voriconazole (UK-109,496), a new triazole antifungal agent, against emerging and less-common mold pathogens. Antimicrob Agents Chemother. 1997;41:841–3.PubMedGoogle Scholar
  23. 23.
    Nalim FA, Samuels GJ, Wijesundera RL, Geiser DM. New species from the Fusarium solani species complex derived from perithecia and soil in the old World tropics. Mycologia. 2011;103:1302–30.PubMedCrossRefGoogle Scholar
  24. 24.
    Espinel-Ingroff A. In vitro activity of the new triazole voriconazole (UK-109,496) against opportunistic filamentous and dimorphic fungi and common and emerging yeast pathogens. J Clin Microbiol. 1998;36:198–202.PubMedGoogle Scholar
  25. 25.
    Teixeira AB, Moretti ML, Trabasso P, von Nowakonski A, Aoki FH, Vigorito AC, Miyaji M, Nishimura K, Taguchi H, Schreiber AZ. Evaluation of Fusarium solani hyphae and conidia susceptibility to amphotericin B and itraconazole: study of a clinical case. Mycopathologia. 2005;160:291–6.PubMedCrossRefGoogle Scholar
  26. 26.
    Pujol I, Guarro J, Gené J, Sala J. In vitro antifungal susceptibility of clinical and environmental Fusarium spp. strains. J Antimicrob Chemother. 1997;39:163–7.PubMedCrossRefGoogle Scholar
  27. 27.
    Taylan Sekeroglu H, Erdem E, Yagmur M, Gumral R, Ersoz R, Ilkit M, Harbiyeli II. Successful medical management of recalcitrant Fusarium solani Keratitis: molecular identification and susceptibility patterns. Mycopathologia. 2012;174:233–727.PubMedCrossRefGoogle Scholar
  28. 28.
    Denning DW, Venkateswarlu K, Oakley KL, Anderson MJ, Manning NJ, Stevens DA, Warnock DW, Kelly SL. Itraconazole resistance in Aspergillus fumigatus. Antimicrob Agents Chemother. 1997;41:1364–8.PubMedGoogle Scholar
  29. 29.
    Nucci M, Marr KA, Queiroz-Telles F, Martins CA, Trabasso P, Costa S, Voltarelli JC, Colombo AL, Imhof A, Pasquini R, Maiolino A, Souza CA, Anaissie E. Fusarium infection in hematopoietic stem cell transplant recipients. Clin Infect Dis. 2004;38:1237–42.PubMedCrossRefGoogle Scholar
  30. 30.
    Pagano L, Caira M, Candoni A, Offidani M, Fianchi L, Martino B, Pastore D, Picardi M, Bonini A, Chierichini A, Fanci R, Caramatti C, Invernizzi R, Mattei D, Mitra ME, Melillo L, Aversa F, Van Lint MT, Falcucci P, Valentini CG, Girmenia C. Nosari AThe epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study. Haematologica. 2006;91:1068–75.PubMedGoogle Scholar
  31. 31.
    Campo M, Lewis RE, Kontoyiannis DP. Invasive fusariosis in patients with hematologic malignancies at a cancer center: 1998–2009. J Infect. 2010;60:331–7.PubMedCrossRefGoogle Scholar
  32. 32.
    Lortholary O, Obenga G, Biswas P, Caillot D, Chachaty E, Bienvenu AL, Cornet M, Greene J, Herbrecht R, Lacroix C, Grenouillet F, Raad I, Sitbon K. French Mycoses Study Group. International retrospective analysis of 73 cases of invasive fusariosis treated with voriconazole. Antimicrob Agents Chemother. 2010;54:4446–50.PubMedCrossRefGoogle Scholar
  33. 33.
    Carneiro HA, Coleman JJ, Restrepo A, Mylonakis E. Fusarium infection in lung transplant patients: report of 6 cases and review of the literature. Medicine. 2011;90:69–80.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Graziella Hanna Pereira
    • 1
    Email author
  • Derlene Attili de Angelis
    • 2
  • Roosecelis Araujo Brasil
    • 3
  • Marilena dos Anjos Martins
    • 4
  • Dulcilena de Matos Castro e Silva
    • 4
  • Maria Walderez Szeszs
    • 4
  • Marcia de Souza Carvalho Melhem
    • 4
  1. 1.Department of Infection DiseasesBrigadeiro HospitalSão PauloBrazil
  2. 2.Department of Biochemistry and MicrobiologyUNESP-São Paulo State UniversitySão PauloBrazil
  3. 3.Department of PathologyAdolfo Lutz InstituteSão PauloBrazil
  4. 4.Department of MycologyAdolfo Lutz InstituteSão PauloBrazil

Personalised recommendations