Infect Chemother.  2015 Mar;47(1):49-54. 10.3947/ic.2015.47.1.49.

Fatal Breakthrough Mucormycosis in an Acute Myelogenous Leukemia Patient while on Posaconazole Prophylaxis

Affiliations
  • 1Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea. symonlee@catholic.ac.kr
  • 2Catholic Blood and Marrow Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Abstract

Posaconazole is a new oral triazole with broad-spectrum antifungal activity. Posaconazole has also shown a significant advantage of preventing invasive fungal infection compared to fluconazole or itraconazole in patients with prolonged neutropenia. Indeed, posaconazole has been commonly used for antifungal prophylaxis in patients undergoing remission induction chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome. We experienced a case of fatal mucormycosis despite posaconazole prophylaxis. To our knowledge, this is the first reported case of fatal breakthrough mucormycosis in a patient receiving posaconazole prophylaxis during remission induction chemotherapy in Korea. This case demonstrated that breakthrough fungal infection can occurs in patients receiving posaconazole prophylaxis because of its limited activity against some mucorales.

Keyword

Posaconazole; Mucormycosis; Prophylaxis; Leukemia, Myeloid, Acute

MeSH Terms

Drug Therapy
Fluconazole
Humans
Itraconazole
Korea
Leukemia, Myeloid, Acute*
Mucorales
Mucormycosis*
Myelodysplastic Syndromes
Neutropenia
Remission Induction
Fluconazole
Itraconazole

Figure

  • Figure 1 Chest X-ray (A) and CT scan of the chest (B) showed lobar pneumonia in the upper lobe and the superior segment of the right lower lobe on day 12 after chemotherapy. Follow-up chest X-ray (C) and CT scan of the chest (D) showed aggravation of pneumonia with pulmonary arterial invasion (red arrow) on day 26.

  • Figure 2 Microscopic analysis of the biopsy specimen showed broad width, non-septate, non-parallel sided, non-dichotomous branching and ribbon like hyphae consistent with mucormycosis (A: hematoxylin & eosin stain, ×400, B: periodic acid Schiff stain, ×400, C: Gomori methenamine silver stain, ×400).

  • Figure 3 Schematic presentation of the patient's clinical course. TEC, teicoplanin; TZP, piperacillin/tazobactam; MEM, meropenem; PSC, posaconazole; AMB, amphotericin B deoxycholate; LAB, liposomal amphotericin B; IVIG, intravenous immunoglobulin; G-CSF, granulocyte-colony stimulating factor; ANC, absolute neutrophil count.


Cited by  3 articles

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Hyeon Jeong Suh, Inho Kim, Joo-Youn Cho, Sang-In Park, Seo Hyun Yoon, Jeong-Ok Lee, Youngil Koh, Kyoung-Ho Song, Pyoeng Gyun Choe, Kyung-Sang Yu, Eu Suk Kim, Hong Bin Kim, Soo-Mee Bang, Nam Joong Kim, Sang Hoon Song, Wan Beom Park, Myoung-don Oh
Infect Chemother. 2017;49(2):135-139.    doi: 10.3947/ic.2017.49.2.135.

Catheter-Related Trichosporon asahii Bloodstream Infection in a Neutropenic Patient with Myelodysplastic Syndrome
Se-Eun Go, Kyung-Jin Lee, Yaeni Kim, Jae-Ki Choi, Yoo-Jin Kim, Dong-Gun Lee
Infect Chemother. 2018;50(2):138-143.    doi: 10.3947/ic.2018.50.2.138.

Advances in prophylaxis and treatment of invasive fungal infections: perspectives on hematologic diseases
Hyojin Ahn, Raeseok Lee, Sung-Yeon Cho, Dong-Gun Lee
Blood Res. 2022;57(S1):101-111.    doi: 10.5045/br.2022.2022036.


Reference

1. Bow EJ, Laverdiere M, Lussier N, Rotstein C, Cheang MS, Ioannou S. Antifungal prophylaxis for severely neutropenic chemotherapy recipients: a meta analysis of randomized-controlled clinical trials. Cancer. 2002; 94:3230–3246.
Article
2. Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard JR, Infectious Diseases. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011; 52:e56–e93.
Article
3. Lee DG, Kim SH, Kim SY, Kim CJ, Min CK, Park WB, Park YJ, Song YG, Jang JS, Jang JH, Jin JY, Choi JH. Evidence-based guidelines for empirical therapy of neutropenic fever in Korea. Infect Chemother. 2011; 43:285–321.
Article
4. Cornely OA, Maertens J, Winston DJ, Perfect J, Ullmann AJ, Walsh TJ, Helfgott D, Holowiecki J, Stockelberg D, Goh YT, Petrini M, Hardalo C, Suresh R, Angulo-Gonzalez D. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med. 2007; 356:348–359.
Article
5. Rachwalski EJ, Wieczorkiewicz JT, Scheetz MH. Posaconazole: an oral triazole with an extended spectrum of activity. Ann Pharmacother. 2008; 42:1429–1438.
Article
6. Frampton JE, Scott LJ. Posaconazole: a review of its use in the prophylaxis of invasive fungal infections. Drugs. 2008; 68:993–1016.
7. Mousset S, Bug G, Heinz WJ, Tintelnot K, Rickerts V. Breakthrough zygomycosis on posaconazole prophylaxis after allogeneic stem cell transplantation. Transpl Infect Dis. 2010; 12:261–264.
Article
8. Schlemmer F, Lagrange-Xélot M, Lacroix C, de La Tour R, Socié G, Molina JM. Breakthrough Rhizopus infection on posaconazole prophylaxis following allogeneic stem cell transplantation. Bone Marrow Transplant. 2008; 42:551–552.
Article
9. Lekakis LJ, Lawson A, Prante J, Ribes J, Davis GJ, Monohan G, Baraboutis IG, Skoutelis AT, Howard DS. Fatal rhizopus pneumonia in allogeneic stem cell transplant patients despite posaconazole prophylaxis: two cases and review of the literature. Biol Blood Marrow Transplant. 2009; 15:991–995.
Article
10. Almyroudis NG, Sutton DA, Fothergill AW, Rinaldi MG, Kusne S. In vitro susceptibilities of 217 clinical isolates of zygomycetes to conventional and new antifungal agents. Antimicrob Agents Chemother. 2007; 51:2587–2590.
Article
11. Skiada A, Lanternier F, Groll AH, Pagano L, Zimmerli S, Herbrecht R, Lortholary O, Petrikkos GL. European Conference on Infections in Leukemia. Diagnosis and treatment of mucormycosis in patients with hematological malignancies: guidelines from the 3rd European Conference on Infections in Leukemia (ECIL 3). Haematologica. 2013; 98:492–504.
Article
12. Walsh TJ, Raad I, Patterson TF, Chandrasekar P, Donowitz GR, Graybill R, Greene RE, Hachem R, Hadley S, Herbrecht R, Langston A, Louie A, Ribaud P, Segal BH, Stevens DA, van Burik JA, White CS, Corcoran G, Gogate J, Krishna G, Pedicone L, Hardalo C, Perfect JR. Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: an externally controlled trial. Clin Infect Dis. 2007; 44:2–12.
Article
13. Krishna G, Martinho M, Chandrasekar P, Ullmann AJ, Patino H. Pharmacokinetics of oral posaconazole in allogeneic hematopoietic stem cell transplant recipients with graft-versus-host disease. Pharmacotherapy. 2007; 27:1627–1636.
Article
14. Lebeaux D, Lanternier F, Elie C, Suarez F, Buzyn A, Viard JP, Bougnoux ME, Lecuit M, Jullien V, Lortholary O. Therapeutic drug monitoring of posaconazole: a monocentric study with 54 adults. Antimicrob Agents Chemother. 2009; 53:5224–5229.
Article
15. Dannaoui E. Molecular tools for identification of Zygomycetes and the diagnosis of zygomycosis. Clin Microbiol Infect. 2009; 15:Suppl 5. 66–70.
Article
16. Dannaoui E, Schwarz P, Slany M, Loeffler J, Jorde AT, Cuenca-Estrella M, Hauser PM, Shrief R, Huerre M, Freiberger T, Gaustad P, Rodriguez-Tudela JL, Bille J, Denning DW, Bretagne S, Lortholary O. Molecular detection and identification of zygomycetes species from paraffin-embedded tissues in a murine model of disseminated zygomycosis: a collaborative European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Fungal Infection Study Group (EFISG) evaluation. J Clin Microbiol. 2010; 48:2043–2046.
Article
17. Marr KA, Laverdiere M, Gugel A, Leisenring W. Antifungal therapy decreases sensitivity of the Aspergillus galactomannan enzyme immunoassay. Clin Infect Dis. 2005; 40:1762–1769.
Article
18. Hong HL, Lee YM, Kim T, Lee JY, Chung YS, Kim MN, Kim SH, Choi SH, Kim YS, Woo JH, Lee SO. Risk factors for mortality in patients with invasive mucormycosis. Infect Chemother. 2013; 45:292–298.
Article
19. Chamilos G, Lewis RE, Kontoyiannis DP. Delaying amphotericin B-based frontline therapy significantly increases mortality among patients with hematologic malignancy who have zygomycosis. Clin Infect Dis. 2008; 47:503–509.
Article
20. Tedder M, Spratt JA, Anstadt MP, Hegde SS, Tedder SD, Lowe JE. Pulmonary mucormycosis: results of medical and surgical therapy. Ann Thorac Surg. 1994; 57:1044–1050.
Article
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