A Case of Disseminated Infection with Skin Manifestation due to Non-neoformans and Non-gattii
Cryptococcus in a Patient with Refractory Acute Myeloid Leukemia

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Abstract

Cryptococcus spp. other than Cryptococcus neoformans or Cryptococcus gattii were previously considered saprophytes and thought to be non-pathogenic to humans. However, opportunistic infections associated with non- neoformans and non- gattii species, such as Cryptococcus laurentii and Cryptococcus albidus, have increased over the past four decades. We experienced a case of cryptococcosis caused by non- neoformans and non- gattii spp. in a 47-year-old female with refractory acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation. The patient underwent salvage chemotherapy with fluconazole prophylaxis and subsequently developed neutropenic fever with multiple erythematous umbilicated papules. A skin biopsy revealed fungal hyphae and repetitive blood cultures showed yeast microorganisms that were identified later as C. laurentii by Vitek-II ^®. Skin lesions and fever began to improve with conventional amphotericin B therapy. The treatment regimen was continued for 21 days until the disseminated cryptococcosis was completely controlled.

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Most cited references 11

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Practice guidelines for the management of cryptococcal disease. Infectious Diseases Society of America.

M S Saag, R J Graybill, R A Larsen … (2000)

An 8-person subcommittee of the National Institute of Allergy and Infectious Diseases (NIAID) Mycoses Study Group evaluated available data on the treatment of cryptococcal disease. Opinion regarding optimal treatment was based on personal experience and information in the literature. The relative strength of each recommendation was graded according to the type and degree of evidence available to support the recommendation, in keeping with previously published guidelines by the Infectious Diseases Society of America (IDSA). The panel conferred in person (on 2 occasions), by conference call, and through written reviews of each draft of the manuscript. The choice of treatment for disease caused by Cryptococcus neoformans depends on both the anatomic sites of involvement and the host's immune status. For immunocompetent hosts with isolated pulmonary disease, careful observation may be warranted; in the case of symptomatic infection, indicated treatment is fluconazole, 200-400 mg/day for 36 months. For those individuals with non-CNS-isolated cryptococcemia, a positive serum cryptococcal antigen titer >1:8, or urinary tract or cutaneous disease, recommended treatment is oral azole therapy (fluconazole) for 36 months. In each case, careful assessment of the CNS is required to rule out occult meningitis. For those individuals who are unable to tolerate fluconazole, itraconazole (200-400 mg/day for 6-12 months) is an acceptable alternative. For patients with more severe disease, treatment with amphotericin B (0.5-1 mg/kg/d) may be necessary for 6-10 weeks. For otherwise healthy hosts with CNS disease, standard therapy consists of amphotericin B, 0.7-1 mg/kg/d, plus flucytosine, 100 mg/kg/d, for 6-10 weeks. An alternative to this regimen is amphotericin B (0.7-1 mg/kg/d) plus 5-flucytosine (100 mg/kg/d) for 2 weeks, followed by fluconazole (400 mg/day) for a minimum of 10 weeks. Fluconazole "consolidation" therapy may be continued for as along as 6-12 months, depending on the clinical status of the patient. HIV-negative, immunocompromised hosts should be treated in the same fashion as those with CNS disease, regardless of the site of involvement. Cryptococcal disease that develops in patients with HIV infection always warrants therapy. For those patients with HIV who present with isolated pulmonary or urinary tract disease, fluconazole at 200-400 mg/d is indicated. Although the ultimate impact from highly active antiretroviral therapy (HAART) is currently unclear, it is recommended that all HIV-infected individuals continue maintenance therapy for life. Among those individuals who are unable to tolerate fluconazole, itraconazole (200-400 mg/d) is an acceptable alternative. For patients with more severe disease, a combination of fluconazole (400 mg/d) plus flucytosine (100-150 mg/d) may be used for 10 weeks, followed by fluconazole maintenance therapy. Among patients with HIV infection and cryptococcal meningitis, induction therapy with amphotericin B (0.7-1 mg/kg/d) plus flucytosine (100 mg/kg/d for 2 weeks) followed by fluconazole (400 mg/d) for a minimum of 10 weeks is the treatment of choice. After 10 weeks of therapy, the fluconazole dosage may be reduced to 200 mg/d, depending on the patient's clinical status. Fluconazole should be continued for life. An alternative regimen for AIDS-associated cryptococcal meningitis is amphotericin B (0.7-1 mg/kg/d) plus 5-flucytosine (100 mg/kg/d) for 6-10 weeks, followed by fluconazole maintenance therapy. Induction therapy beginning with an azole alone is generally discouraged. Lipid formulations of amphotericin B can be substituted for amphotericin B for patients whose renal function is impaired. Fluconazole (400-800 mg/d) plus flucytosine (100-150 mg/kg/d) for 6 weeks is an alternative to the use of amphotericin B, although toxicity with this regimen is high. In all cases of cryptococcal meningitis, careful attention to the management of intracranial pressure is imperative to assure optimal c

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Cryptococcus neoformans infection in organ transplant recipients: variables influencing clinical characteristics and outcome.

Tupur S Husain, M. M. Wagener, N. Singh (2001)

Unique clinical characteristics and other variables influencing the outcome of Cryptococcus neoformans infection in organ transplant recipients have not been well defined. From a review of published reports, we found that C. neoformans infection was documented in 2.8% of organ transplant recipients (overall death rate 42%). The type of primary immunosuppressive agent used in transplantation influenced the predominant clinical manifestation of cryptococcosis. Patients receiving tacrolimus were significantly less likely to have central nervous system involvement (78% versus 11%, p =0.001) and more likely to have skin, soft-tissue, and osteoarticular involvement (66% versus 21%, p = 0.006) than patients receiving nontacrolimus- based immunosuppression. Renal failure at admission was the only independently significant predictor of death in these patients (odds ratio 16.4, 95% CI 1.9-143, p = 0.004). Hypotheses based on these data may elucidate the pathogenesis and may ultimately guide the management of C. neoformans infection in organ transplant recipients.

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Non- neoformans Cryptococcal Infections: a Systematic Review

T Khawcharoenporn, A Apisarnthanarak, L M Mundy (2007)

Non-neoformans cryptococci have been generally regarded as saprophytes and rarely reported as human pathogens. However, the incidence of infection due to these organisms has increased over the past 40 years, with Cryptococcus laurentii and Cryptococcus albidus, together, responsible for 80% of reported cases. Conditions associated with impaired cell-mediated immunity are important risks for non-neoformans cryptococcal infections and prior azole prophylaxis has been associated with antifungal resistance. The presence of invasive devices was a significant risk factor for Cryptococcus laurentii infection (adjusted OR = 8.7; 95% CI = 1.48–82.9; p = 0.003), while predictors for mortality included age ≥45 years (aOR = 8.4; 95% CI = 1.18–78.82; p = 0.004) and meningeal presentation (aOR = 7.0; 95% CI = 1.85–60.5; p= 0.04). Because clinical manifestations of non-neoformans cryptococcal infections are most often indistinguishable from Cryptococcus neoformans, a high index of suspicion remains important to facilitate early diagnosis and prompt treatment for such infections.

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Author and article information

Journal

Journal ID (nlm-ta): Infect Chemother

Journal ID (iso-abbrev): Infect Chemother

Journal ID (publisher-id): IC

Title: Infection & Chemotherapy

Publisher: The Korean Society of Infectious Diseases and Korean Society for Chemotherapy

ISSN (Print): 2093-2340

ISSN (Electronic): 2092-6448

Publication date (Print): June 2017

Publication date (Electronic): 16 January 2017

Volume: 49

Issue: 2

Pages: 142-145

Affiliations

[1 ]Department of Internal Medicine, National Cancer Center, Goyang, Korea.

[2 ]Hematologic Oncology Clinic, National Cancer Center, Goyang, Korea.

[3 ]Department of Pathology, National Cancer Center, Goyang, Korea.

[4 ]Department of Laboratory Medicine, National Cancer Center, Goyang, Korea.

[5 ]Infectious Disease Clinic, National Cancer Center, Goyang, Korea.

Author notes

Corresponding author: Hyeon-Seok Eom, MD, PhD. Department of Internal Medicine, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, Korea. Tel: +82-31-920-2402, Fax: +82-31-920-1163, hseom@ 123456ncc.re.kr

Author information

Sun Seob Park https://orcid.org/0000-0001-6091-4873

Hyeon-Seok Eom https://orcid.org/0000-0002-0484-2067

Article

DOI: 10.3947/ic.2017.49.2.142

PMC ID: 5500271

PubMed ID: 28271644

SO-VID: 5e95c41e-424f-4b65-a93c-1c4eba6b67df

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 16 March 2015

Date accepted : 13 July 2015

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A Case of Disseminated Infection with Skin Manifestation due to Non- neoformans and Non- gattii Cryptococcus in a Patient with Refractory Acute Myeloid Leukemia

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Decoding Infection and Transmission

Most cited references 11

Practice guidelines for the management of cryptococcal disease. Infectious Diseases Society of America.

Cryptococcus neoformans infection in organ transplant recipients: variables influencing clinical characteristics and outcome.

Non- neoformans Cryptococcal Infections: a Systematic Review

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