This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sammassimo, S.
Right arrow Articles by Lauria, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sammassimo, S.
Right arrow Articles by Lauria, F.

 Previous Article  |  Next Article 

Journal of Clinical Microbiology, January 2004, p. 487-489, Vol. 42, No. 1
0095-1137/04/$08.00+0     DOI: 10.1128/JCM.42.1.487-489.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Disseminated Mucormycosis in a Patient with Acute Myeloblastic Leukemia Misdiagnosed as Infection by Enterococcus faecium

S. Sammassimo,1* S. Mazzotta,1 M. Tozzi,1 S. Gentili,1 M. Lenoci,1 R. Santopietro,2 A. Bucalossi,1 M. Bocchia,1 and F. Lauria1

Department of Hematology and Hematopoietic Stem Cell Transplantation,1 Pathology Division, Policlinico Le Scotte, University of Siena, Siena, Italy2

Received 16 June 2003/ Returned for modification 11 August 2003/ Accepted 11 October 2003


arrow
ABSTRACT
 
Mucormycosis is a rare complication in cancer patients. This report presents the case of a acute myeloblastic leukemia patient who developed an ascending paralysis due to disseminated mucormycosis. The presentation was unusual because the early symptoms were fever and pain, and the disease was misdiagnosed because of a concomitant infection by Enterococcus faecium.


arrow
CASE REPORT
 
A 70-year-old female was admitted to our hospital for acute myeloblastic leukemia (French-American-British type M1). On day 4 after induction chemotherapy, during the treatment-related aplasia, the patient became febrile, and Staphylococcus epidermidis and Staphylococcus mitis were detected in blood cultures. She was given antibiotics (ceftazidime and amikacin), and the fever rapidly resolved. On day 11, the patient presented a right flank pain that, in the following days, spread into the lumbar region bilaterally, with a band irradiation in the upper abdomen. At this time there was no evidence, either clinically or in the chest X ray or in the echo tomography of the kidney and liver, of any localized infection. On day 16, the patient presented again high fever and abruptly developed an acute paraplegia, which rapidly became an ascending paralysis. The lumbar pain was still present, and it extended to each thigh's anterior surface, with hyperesthesia and numbness in the legs. Nuclear magnetic resonance imaging of the spinal marrow showed altered T1-T2 signal intensity between D12 and L1, suggestive of an edematous ischemic lesion. Blood and spinal fluid cultures at that time were positive for Enterococcus faecium, and a specific antibiotic therapy was started (meropenem). However, the patient rapidly developed a comatose status and died on day 18. The postmortem examination showed mucormycosis invasion of blood vessels associated with tissue necrosis in the central nervous system, liver, lung, and heart (Fig. 1). The morphological pattern (large ribbon-like nonseptate hyphae with irregular diameters and branches arising from almost all main hyphal trunks) was so typical for mucormycosis that a postmortem fungal culture was felt not to be needed for diagnosis.



View larger version (155K):
[in this window]
[in a new window]
  		FIG. 1. Photomicrograph of liver (a; hematoxylin and eosin), heart (b; hematoxylin and eosin), lung (c; Grocott), and brain (d; hematoxylin and eosin), demonstrating the broad, irregularly shaped hyphae with right-angle branching typical of Mucorales. The arrows indicate the most evident fungal hyphae.

The Mucoraceae are ubiquitous fungi and are common inhabitants of decomposing plant and animal matter. There are 14 families in this order, 4 of which have been associated with human diseases. Large numbers of small sporangiospores are released into the air, and therefore inhalation of conidia must be a daily experience (14). However the potential virulence in the human host is very low, as witnessed by the low incidence of such infection in the general population; infection is mainly observed in patients with severe immunodeficiency, diabetes mellitus, or trauma (14). In addition invasive fungal infections, including mucormycosis, are common complications in cancer patients (6, 8), particularly in those with hematological malignancies (1, 4, 5), as a consequence of myeloablative chemotherapies and compromised immune system. The infection rate is strongly correlated with the type of cytotoxic regimens administered and with the duration of bone marrow aplasia (2). In recent years, pulmonary mucormycosis has been reported in patients with leukemia and lymphoma as well as in bone marrow transplant recipients, with an extremely poor prognosis in all of them (3, 10, 12).

The most common symptom of mucormycosis infection is fever, occurring in 51% of patients (12). Moreover, on the basis of clinical presentation, this infectious disease can be arbitrarily divided into separate entities: rhinocerebral, pulmonary, cutaneous, gastrointestinal, central nervous system related, and miscellaneous, in addition to a disseminated disease resulting from progression of localized infection. Confirmation of the clinically suspected diagnosis of systemic mycosis and exact identification of the fungal pathogen are often difficult. The hallmarks of disease caused by the Mucorales are vascular invasion and tissue necrosis, due to their special affinity for blood vessels. Diagnosis depends on demonstrating the organism in the tissue of a biopsy specimen. Typically, the fungi appear as broad (10 to 20 µm in diameter), nonseptate hyphae with ramifications. At the present, serodiagnosis of mucormycosis remains investigational and cannot yet be recommended for routine clinical use (7, 9, 16).

Establishing the diagnosis is the central issue in the management of mucormycosis. Nevertheless antemortem diagnosis is uncommon because blood cultures are invariably negative; in addition, pulmonary disease sputum cultures are seldom helpful and bronchial washings have yielded hyphal forms only on rare occasions. Thus a correct diagnosis in vivo is reached only by invasive methods (biopsy) (11).

In oncohematological patients the most important favorable prognostic factor is the outcome of the underlying disease (12). Timing of neutrophil recovery is particularly important because neutrophils play an important role in the host defense against Mucorales (13).

In our patient, clinical signs and symptoms caused by the fungal infection developed during severe neutropenia (neutrophil count < 0.5 x 109/liter). The initial physical findings were fever and pain, which were suggestive of a pulmonary infection with pleural involvement as well as of a subfrenic abscess despite a normal chest X ray and kidney and liver echo tomography. It is clear, now, that the pain was a consequence of spinal localization of the infective disease with metameric distribution (T10-S2). Additional factors which contributed to the misdiagnosis were the documentation in the blood and spinal fluid of E. faecium sepsis and the clinical evolution as ascending paralysis, previously described in only one case of disseminated mucormycosis (15). According to our interpretation, the presence of E. faecium in the spinal fluid could be attributed to abnormal vascular permeability due to the fungal invasion of blood vessels.

In conclusion, a suspicious infection and careful clinical and radiological examinations are the keys for the early identification of infected patients. In the most severely ill neutropenic patients, only aggressive antifungal therapy together with immune reconstitution appears to improve the prognosis. The outcome remains critical because, in these patients, mucormycosis is frequently characterized by disseminated disease leading to a rapid and fatal outcome.


arrow
FOOTNOTES
 
* Corresponding author. Mailing address: Department of Hematology and Hematopoietic Stem Cell Transplantation, University of Siena, Policlinico Le Scotte, Viale Bracci 53100, Siena, Italy. Phone: 39-0577-586798. Fax: 39-0577-586185. E-mail: sammassimo{at}unisi.it. Back


arrow
REFERENCES
 
    1
  1. Bohme, A., M. Karthaus, and D. Hoelzer. 1999. Antifungal prophylaxis in neutropenic patients with hematologic malignancies: is there a real benefit? Chemotherapy 45:224-232.[CrossRef][Medline]
    2. 2
  2. Bow, E. J., R. Loewen, M. S. Cheang, and B. Schacter. 1995. Invasive fungal disease in adults undergoing remission-induction therapy for acute myeloid leukemia: the pathogenic role of the antileukemic regimen. Clin. Infect. Dis. 21:361-369.[Medline]
    3. 3
  3. Burch, P. A., J. E. Karp, W. G. Merz, J. E. Kulhman, and E. K. Fishman. 1987. Favorable outcome of invasive aspergillosis in patients with acute leukemia J. Clin. Oncol. 5:1985-1993.[Abstract/Free Full Text]
    4. 4
  4. De Paw, B. E., and F. Meunier. 1999. The challenge of invasive fungal infection. Chemotherapy 45(Suppl. 1):1-14.
    5. 5
  5. Gozdasoglu, S., M. Ertem, Z. Buyukkececi, S. Yavuzdemir, S. Bengisun, H. Ozenci, N. Tacyildiz, E. Unal, G. Yavuz, G. Deda, and D. Aysev. 1999. Fungal colonization and infection in children with acute leukemia and lymphoma during induction therapy. Med. Pediatr. Oncol. 32:344-348.[CrossRef][Medline]
    6. 6
  6. Guoit, H. F. L., W. E. Fibbe, and J. W. van't Wout. 1994. Risk factors for fungal infection in patients with malignant hematologic disorders: implications for empirical therapy and prophylaxis. Clin. Infect. Dis. 18:525-532.[Medline]
    7. 7
  7. Hessian, P. A., and J. M. B. Smith. 1982. Antigenic characterization of some potentially pathogenic mucoraceous fungi. Sabouraudia 20:209-216.[Medline]
    8. 8
  8. Krcmery, V., Jr., E. Kunova, Z. Jesenska, J. Trupl, S. Spanik, J. Mardiak, M. Studena, and E. Kukuckova. 1996. Invasive mold infections in cancer patients: 5 years' experience with Aspergillus, Mucor, Fusarium, and Acremonium infections. Support Care Cancer 41:39-45.
    9. 9
  9. Levy, S. A., K. W. Schmitt, and L. Kaufman. 1986. Systemic zygomycosis diagnosed by fine needle aspiration and confirmed with enzyme immunoassay. Chest 89:146-148.[Abstract/Free Full Text]
    10. 10
  10. Morrison, V. A., and P. B. McGlave. 1993. Mucormycosis in the BMT population. Bone Marrow Transplant. 11:383-388.[Medline]
    11. 11
  11. Nosari, A., P. Oreste, M. Montillo, G. Carrafiello, M. Draisci, G. Muti, A. Molteni, and E. Morra. 2000. Mucormicosis in hematologic malignancies: an emerging fungal infection. Haematologica 85:1068-1071.[Abstract/Free Full Text]
    12. 12
  12. Pagano, L., P. Ricci, A. Tonso, A. Nosari, L. Cudillo, M. Montillo, A. Cenacchi, L. Pacilli, F. Fabbiano, and A. Del Favero. 1997. Mucormycosis in patients with hematological malignancies: a retrospective clinical study of 37 cases Br. J. Haematol. 99:331-336.
    13. 13
  13. Pizzo, P. A. 1993. Management of fever in patients with cancer and treatment-induced neutropenia N. Engl. J. Med. 328:1323-1332.[Free Full Text]
    14. 14
  14. Sugar A. M. 1995. Agents of mucormycosis and related species, p. 2311-2317. In G. L. Mandell, J. E. Bennet, and R. Dolin (ed.), Mandell, Douglas and Bennett's principles and practice of infectious disease, 4th ed. Churchill Livingston, New York, N.Y.
    15. 15
  15. Von Pohle, W. R. 1996. Disseminated mucormycosis presenting with lower extremity weakness. Eur. Respir. J. 9:1751-1753.[Abstract]
    16. 16
  16. Wysong, D. R., and A. R. Waldorf. 1987. Electrophoretic and immunoblot analyses of Rhizopus arrhizus antigens. J. Clin. Microbiol. 25:358-363.[Abstract/Free Full Text]

Journal of Clinical Microbiology, January 2004, p. 487-489, Vol. 42, No. 1
0095-1137/04/$08.00+0     DOI: 10.1128/JCM.42.1.487-489.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sammassimo, S.
Right arrow Articles by Lauria, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sammassimo, S.
Right arrow Articles by Lauria, F.

Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»