Fusarium

Background

Fusarium infections are rare but devastating infections caused by this common fungus. It is more commonly known as a fungus that destroys crops. However, immunocompromised patients are increasingly at risk for contracting an infection.

OUTLINE

Epidemiology

Disease Associations

Laboratory/Radiologic/Other Diagnostic Testing

Gross Appearance and Clinical Variants

Prognosis and Treatment

Commonly Used Terms

Internet Links

EPIDEMIOLOGY CHARACTERIZATION

GEOGRAPHY

Epidemiology, molecular mycology, and environmental sources of Fusarium infection in patients with cancer.

Raad I, Tarrand J, Hanna H, Albitar M, Janssen E, Boktour M, Bodey G, Mardani M, Hachem R, Kontoyiannis D, Whimbey E, Rolston K.

Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.

Infect Control Hosp Epidemiol 2002 Sep;23(9):532-7 Abstract quote
OBJECTIVE: To investigate the epidemiology and environmental sources of Fusarium infections in patients with cancer.

DESIGN: Retrospective case-control study conducted following surveillance environmental cultures and DNA analysis of isolated organisms.

SETTING: A tertiary-care, university cancer center.

METHODS: In 1996 and 1997, environmental cultures were performed on air samples and water systems. A retrospective chart review was performed for 70 patients with cancer identified with fusariosis between 1987 and 1997. Patients with fusariosis were compared with 49 uninfected control patients who occupied hospital rooms with positive environmental cultures for Fusarium. With the use of random amplification of polymorphic DNA, organisms isolated from infected patients were compared with environmental organisms.

RESULTS: Most of the patients with Fusarium (40, 57%) were infected on or within 3 days of admission, indicating community rather than nosocomial acquisition. Patients were comparable in terms of underlying immunocompromised status to 49 uninfected control patients. However, the duration from admission to infection in the patients with fusariosis tended to be shorter than the duration from admission to discharge in the exposed control patients (P = .06). Water cultured from the hospital tanks and from sinks and water fountains was negative for Fusarium. With the use of polymerase chain reaction, environmental isolates did not match clinical ones. Quantitative air sampling showed that the quantitative outdoor Fusarium levels were eightfold higher than the indoor levels. During the rainy summer season, outdoor air concentrations of Fusarium were at their highest, coinciding with the peak incidence of fusariosis at our center.

CONCLUSION: The most likely source of fusariosis was the external environment rather than nosocomial sources, such as water.

DISEASE ASSOCIATIONS CHARACTERIZATION

CANCER

Epidemiology, molecular mycology, and environmental sources of Fusarium infection in patients with cancer.

Raad I, Tarrand J, Hanna H, Albitar M, Janssen E, Boktour M, Bodey G, Mardani M, Hachem R, Kontoyiannis D, Whimbey E, Rolston K.

Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.

Infect Control Hosp Epidemiol 2002 Sep;23(9):532-7 Abstract quote
OBJECTIVE: To investigate the epidemiology and environmental sources of Fusarium infections in patients with cancer.

DESIGN: Retrospective case-control study conducted following surveillance environmental cultures and DNA analysis of isolated organisms.

SETTING: A tertiary-care, university cancer center.

METHODS: In 1996 and 1997, environmental cultures were performed on air samples and water systems. A retrospective chart review was performed for 70 patients with cancer identified with fusariosis between 1987 and 1997. Patients with fusariosis were compared with 49 uninfected control patients who occupied hospital rooms with positive environmental cultures for Fusarium. With the use of random amplification of polymorphic DNA, organisms isolated from infected patients were compared with environmental organisms.

RESULTS: Most of the patients with Fusarium (40, 57%) were infected on or within 3 days of admission, indicating community rather than nosocomial acquisition. Patients were comparable in terms of underlying immunocompromised status to 49 uninfected control patients. However, the duration from admission to infection in the patients with fusariosis tended to be shorter than the duration from admission to discharge in the exposed control patients (P = .06). Water cultured from the hospital tanks and from sinks and water fountains was negative for Fusarium. With the use of polymerase chain reaction, environmental isolates did not match clinical ones. Quantitative air sampling showed that the quantitative outdoor Fusarium levels were eightfold higher than the indoor levels. During the rainy summer season, outdoor air concentrations of Fusarium were at their highest, coinciding with the peak incidence of fusariosis at our center.

CONCLUSION: The most likely source of fusariosis was the external environment rather than nosocomial sources, such as water.

TRANSPLANTATION

Disseminated Fusarium infections in patients following bone marrow transplantation.

Minor RL Jr, Pfaller MA, Gingrich RD, Burns LJ.

Department of Medicine, University of Iowa College of Medicine, Iowa City 52247.
Bone Marrow Transplant 1989 Nov;4(6):653-8 Abstract quote
Intensive immunosuppressive therapy and broad spectrum antibiotics predispose cancer patients to opportunistic fungal infections. Fusarium has rarely been reported as a pathogen in immunocompromised patients, but is almost uniformly fatal.

Only six cases of disseminated Fusarium infection have been described in patients following bone marrow transplantation (BMT). We report here two additional cases. Fusarium infection initially presented with pyomyositis in one patient and with embolic skin lesions in another following T cell-depleted BMT. Both patients died with active Fusarium infection despite an extensive course of amphotericin B, rifampicin and granulocyte transfusions.

From this experience and from a review of the literature, Fusarium infections appear to be increasing in prevalence as significant pathogens in immunocompromised hosts and are resistant to many conventional forms of therapy.

LABORATORY/RADIOLOGIC/
OTHER TESTS
CHARACTERIZATION

RADIOLOGIC

LABORATORY MARKERS

BLOOD CULTURES

Effect of fluconazole prophylaxis on fungal blood cultures: an autopsy-based study involving 720 patients with haematological malignancy.

Kami M, Machida U, Okuzumi K, Matsumura T, Mori Si S, Hori A, Kashima T, Kanda Y, Takaue Y, Sakamaki H, Hirai H, Yoneyama A, Mutou Y.

Department of Hematology, Toranomon Hospital, Tokyo, Japan.
Br J Haematol 2002 Apr;117(1):40-6 Abstract quote
To investigate the utility of blood culture of invasive fungal infections in patients with haematological malignancies, an autopsy survey was conducted in 720 patients who were treated between 1980 and 1999.

We identified 252 patients with invasive mycosis. These included Candida (n = 94), Aspergillus (n = 91), Zygomycetes (n = 34), Cryptococcus (n = 7), Trichosporon (n = 11), Fusarium (n = 1), and unknown fungi (n = 20). Of the 94 patients with invasive candidiasis, 20 had positive blood cultures. Of the 11 patients with invasive trichosporonosis, seven had positive blood cultures. The sensitivities of blood cultures were 1.1%, 0% and 14% for detecting invasive aspergillosis, zygomycosis and cryptococcosis respectively.

Multiple regression analysis showed a significant correlation between results of Candida blood cultures and some variables, including prophylactic use of absorbable antifungals (P = 0.0181) and infection by Candida albicans (P = 0.0086).

The sensitivity of blood cultures decreased when patients received antifungal chemoprophylaxis. Unless these agents are inactivated in culture bottles, conventional blood cultures might produce false-negative results.

POLYMERASE CHAIN REACTION

Specific detection of fusarium species in blood and tissues by a PCR technique.
Hue FX, Huerre M, Rouffault MA, de Bievre C.

Laboratoire de Mycologie Medicale, Institut Pasteur, 75724 Paris cedex 15, France.

J Clin Microbiol 1999 Aug;37(8):2434-8 Abstract quote
Fusarium species are opportunistic nosocomial pathogens that often cause fatal invasive mycoses. We designed a primer pair that amplifies by PCR a fragment of a gene coding for the rRNA of Fusarium species.

The DNAs of the main Fusarium species and Neocosmospora vasinfecta but not the DNAs from 11 medically important fungi were amplified by these primers. The lower limit of detection of the PCR system was 10 fg of Fusarium solani DNA by ethidium bromide staining. To test the ability of this PCR system to detect Fusarium DNA in tissues, we developed a mouse model of disseminated fusariosis. Using the PCR, we detected Fusarium DNA in mouse tissues and in spiked human blood. Furthermore, F. solani, Fusarium moniliforme, and Fusarium oxysporum were testing by random amplified polymorphic DNA (RAPD) analysis. The bands produced by RAPD analysis were purified, cloned, and sequenced.

The information was used to design primer pairs that selectively amplified one or several Fusarium species. The method developed may be useful for the rapid detection and identification of Fusarium species both from culture and from clinical samples.

GROSS APPEARANCE/
CLINICAL VARIANTS CHARACTERIZATION

GENERAL

Cutaneous infection by Fusarium species in healthy and immunocompromised hosts: implications for diagnosis and management.

Nucci M, Anaissie E.

University Hospital, Universidade Federal do Rio de Janeiro, Brazil.

Clin Infect Dis 2002 Oct 15;35(8):909-20 Abstract quote
Infections by Fusarium species frequently involve the skin, either as the primary or the metastatic site. To better understand the pathophysiology of these infections, 43 new patients with fusariosis were evaluated, and the literature was reviewed.

A total of 259 patients (232 immunocompromised and 27 immunocompetent) were identified. Skin involvement was present in 70% of patients, particularly in immunocompromised patients (72% vs. 52%; P=.03). In immunocompetent patients, cutaneous infections were characterized by preceding skin breakdown, localized involvement, slow pace of progression, and good response to therapy. In contrast, skin involvement in immunocompromised patients was only occasionally preceded by skin breakdown and typically was presented as rapidly progressive disseminated lesions at various stages of evolution.

Metastatic skin lesions were associated with fungemia, neutropenia, and death. Skin was the single source of diagnosis for the majority of immunocompromised and immunocompetent patients. Recommendations for the prevention of fatal fusariosis originating from skin are presented.

VARIANTS

EYE

The epidemiological features and laboratory results of fungal keratitis: a 10-year review at a referral eye care center in South India.

Gopinathan U, Garg P, Fernandes M, Sharma S, Athmanathan S, Rao GN.

Jhaveri Microbiology Center, L.V. Prasad Eye Institute, L.V. Prasad Marg, Banjara Hills, Hyderabad 500 034, India.
Cornea 2002 Aug;21(6):555-9 Abstract quote
PURPOSE: To report the epidemiological features and laboratory results of 1,352 cases of fungal keratitis diagnosed at the L.V. Prasad Eye Institute (LVPEI) in south India.

METHODS: The medical and microbiology records of 1,352 culture proven cases (1,354 eyes) of fungal keratitis diagnosed at the LVPEI between January 1991 to December 2000 was retrospectively reviewed for demographic features, risk factors, seasonal variation, and laboratory findings.

RESULTS: Males (962) were affected significantly more (p< 0.0001) than females (390). Of 1,352 patients, 853 (64.4%) were in the younger age group (16-49 years). Ocular trauma predisposed to infection in 736 (54.4%) of 1,354 eyes. There was a higher incidence of fungal keratitis during the monsoon and winter than summer. A fungal cause was established by smears of corneal scrapings in 1,277 (95.4%) eyes. The potassium hydroxide preparation (KOH), Calcofluor white (CFW), Gram-, and Giemsa-stained smears revealed fungus in 1,219 (91.0%), 1,224 (91.4%), 1,181 (88.2%), and 1,139 (85.1%) eyes, respectively. Fusarium(506, 37.2%) and Aspergillus species (417, 30.7%) predominated the hyaline fungal spectrum (1,133) and Curvularia species (39, 2.8%) were the highest among the dematiaceous isolates (218).

CONCLUSIONS: To the best of our knowledge, this review presents the epidemiological features and laboratory results of the largest series of fungal keratitis ever reported in the literature. Keratomycosis is predominant in young adults with trauma as the major predisposing factor. With fungal keratitis being a major ophthalmologic problem in the tropical regions of the world, data available on the epidemiological features of a large series would greatly help medical practitioners at primary and secondary health care centers in the management of the disease. A simple KOH preparation of corneal scraping alone is highly beneficial in confirming the diagnosis.

ORBITAL

Necrotizing periorbital Fusarium infection--an emerging pathogen in immunocompetent individuals.

Pushker N, Chra M, Bajaj MS, Ghose S, Naik N, Kashyap S, Satpathy G.

Oculoplastic and Paediatric Ophthalmology Services, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi 110 029, India.
J Infect 2002 May;44(4):236-9 Abstract quote
Fungal infections of the skin and deeper tissues of the periorbital region are quite rare.

We report a case of a localized, deep periorbital necrotizing Fusarium infection in an otherwise healthy, elderly lady. Since the clinical features and histopathological findings of Fusarium infection are by no means characteristic, the definitive diagnosis was achieved with the help of microbiological examination of cultured organisms. A combined medical and surgical therapy led to adequate control of infection. To conclude, localized, deep periorbital necrotizing soft tissue infection by Fusarium in an immunocompetent lady is not reported in literature.

One should have a high index of suspicion for emerging fungal pathogens in the differential diagnosis of necrotizing orbital or adnexal conditions, even in an immunocompetent patient. The histologic findings of septate, branching hyphae and vascular invasion cannot distinguish Fusarium species from various other moulds such as Aspergillus species; microbiologic studies are essential for confirming the diagnosis.

SKIN

Chronic infection due to Fusarium oxysporum mimicking lupus vulgaris: case report and review of cutaneous involvement in fusariosis.

Pereiro M Jr, Abalde MT, Zulaica A, Caeiro JL, Florez A, Peteiro C, Toribio J.

Department of Dermatology, Complejo Hospitalario Universitario, Santiago de Compostela, Spain
Acta Derm Venereol 2001 Jan-Feb;81(1):51-3 Abstract quote
A 67-year-old female presented with a 20-year-old lesion involving the right ear and preauricular area mimicking tuberculous lupus. Fusarium oxysporum infection was confirmed by biopsy studies and cultures. The biopsy specimen showed an unusually extensive dermal invasion with fungal hyphae. This is an uncommon clinical presentation for Fusarium infection in a healthy patient.

When referred to us, the patient had received antifungal therapy with itraconazole without any benefit. Improvement was obtained with fluconazole therapy.

The spectrum of cutaneous involvement related to Fusarium spp. includes toxic reactions, colonization, superficial indolent infection, deep cutaneous or subcutaneous infections and disseminated infection.

Fusarium infections of the skin.

Gupta AK, Baran R, Summerbell RC.

Division of Dermatology, Department of Medicine, Sunnybrook and Women's College Health Sciences Center (Sunnybrook site), and the University of Toronto, Toronto, Canada, bThe Nail Center, Cannes, France, and cOntario Ministry of Health Mycology Laboratory and the Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
Curr Opin Infect Dis 2000 Apr;13(2):121-128 Abstract quote
Fusarium species are ubiquitous and may be found in the soil, air and on plants. Fusarium species can cause mycotoxicosis in humans following ingestion of food that has been colonized by the fungal organism. In humans, Fusarium species can also cause disease that is localized, focally invasive or disseminated. The pathogen generally affects immunocompromised individuals with infection of immunocompetent persons being rarely reported. Localized infection includes septic arthritis, endophthalmitis, osteomyelitis, cystitis and brain abscess. In these situations relatively good response may be expected following appropriate surgery and oral antifungal therapy. Disseminated infection occurs when two or more noncontiguous sites are involved. Over eighty cases have been reported, many of which had a hematologic malignancy including neutropenia. The species most commonly involved include Fusarium solani, Fusarium oxysporum, and Fusarium moniliforme (also termed F. verticillioides). The diagnosis of Fusarium infection may be made on histopathology, gram stain, mycology, blood culture, or serology. Portals of entry of disseminated infection include the respiratory tract, the gastrointestinal tract, and cutaneous sites.The skin can be an important and an early clue to diagnosis since cutaneous lesions may be observed at an early stage of the disease and in about seventy-five cases of disseminated Fusarium infection. Typical skin lesions may be painful red or violaceous nodules, the center of which often becomes ulcerated and covered by a black eschar. The multiple necrotizing lesions are often observed on the trunk and the extremities. Onychomycosis most commonly due to F. oxysporum or F. solani has been reported. The onychomycosis may be of several types: distal and lateral subungual (DLSO), white superficial (WSO), and proximal subungual (PSO). In proximal subungual onychomycosis there may be associated leukonychia and/or periungual inflammation. Patients with Fusarium onychomycosis have been cured following therapy with itraconazole, terbinafine, ciclopirox olamine lacquer, or topical antifungal agent. In other instances nail avulsion plus antifungal therapy has been successful. In patients with hematologic malignancy or bone marrow transplant, who may experience prolonged or severe neutropenia during the course of therapy, the skin and nails should be carefully examined and consideration given to treating potential infection sites that may serve as portals for systemic dissemination.

When disseminated Fusarium infection is present therapy with antifungal agents has generally been disappointing with the chances of a successful resolution being enhanced if the neutropenia can be corrected in a timely manner.

Skin lesions associated with Fusarium infection.

Bodey GP, Boktour M, Mays S, Duvic M, Kontoyiannis D, Hachem R, Raad I.

University of Texas M. D. Anderson Cancer Center.
J Am Acad Dermatol 2002 Nov;47(5):659-66 Abstract quote
Infections caused by Fusarium species are increasing in frequency among immunocompromised hosts.

We identified 35 patients with cancer who had Fusarium skin lesions. Twenty patients had disseminated infection, 6 had primary localized skin infections, 4 had skin lesions associated with sinus infections, and 5 had onychomycosis.

All patients (except 3 with onychomycosis) had hematologic malignancies and neutropenia. Skin lesions associated with disseminated infection included red or gray macules, papules (some with central necrosis or eschar), pustules, and subcutaneous nodules. Most patients had a variety of lesions simultaneously. Multiple red or gray macules with central ulceration or black eschar are characteristic of Fusarium infection.

Disseminated infection may originate from skin lesions or onychomycosis. Most infections fail to respond to antifungal therapy unless there is resolution of the patient's neutropenia.

PROGNOSIS AND TREATMENT CHARACTERIZATION

PROGNOSTIC FACTORS

TREATMENT

GENERAL

Fusarium, a significant emerging pathogen in patients with hematologic malignancy: ten years' experience at a cancer center and implications for management.

Boutati EI, Anaissie EJ.

The University of Texas M.D. Anderson Cancer Center, Houston, USA.
Blood 1997 Aug 1;90(3):999-1008 Abstract quote
Despite increasing reports of life-threatening Fusarium infections, little is known about its pathogenesis and management.

To evaluate the epidemiology, clinicopathologic features, and outcome of invasive fusariosis in patients with hematologic cancer, we conducted a retrospective study of invasive fusarial infections in patients with hematologic malignancy treated at a referral cancer center over a 10-year period (1986 to 1995), as well as a literature review. Forty patients with disseminated and three patients with invasive lung infection were included in the analysis. All patients were immunocompromised.

The infection occurred in three patients postengraftment following bone marrow transplantation. All patients were diagnosed antemortem.

AMPHOTERICIN B

Efficacy of liposomal amphotericin B in treatment of systemic murine fusariosis.

Ortoneda M, Capilla J, Pastor FJ, Pujol I, Guarro J.

Unitat de Microbiologia, Facultat de Medicina i Ciencies de la Salut and Institut d'Estudis Avancats. Laboratori de Microbiologia, Hospital Universitari de Sant Joan de Reus, Universitat Rovira i Virgili, 43201 Reus, Spain.
Antimicrob Agents Chemother 2002 Jul;46(7):2273-5 Abstract quote
We have compared the activities of liposomal amphotericin B (LAMB) at 3, 5, 10, and 20 mg/kg/day and amphotericin B deoxycholate (AMB) at 1.5 and 2.5 mg/kg/day in a murine systemic infection by Fusarium verticillioides. Survival was improved by all treatments except AMB at 1.5 mg/kg/day.

The tissue burden in liver was reduced by LAMB at all dosages and by AMB at 2.5 mg/kg/day. The two highest dosages of LAMB showed significant reductions in the spleen.

Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Eight Edition. Mosby 1996.
Sternberg S. Diagnostic Surgical Pathology. Third Edition. Lipincott Williams and Wilkins 1999.
Weedon D. Weedon's Skin Pathology. Second Edition. Churchill Livingstone. 2002.
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Robbins Pathologic Basis of Disease. Sixth Edition. WB Saunders 1999.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.

Commonly Used Terms

Fungus

Internet Links

Microscopic Photo

Last Updated 11/15/2002

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
GENERAL
Cutaneous infection by Fusarium species in healthy and immunocompromised hosts: implications for diagnosis and management. Nucci M, Anaissie E. University Hospital, Universidade Federal do Rio de Janeiro, Brazil.	Clin Infect Dis 2002 Oct 15;35(8):909-20 Abstract quote Infections by Fusarium species frequently involve the skin, either as the primary or the metastatic site. To better understand the pathophysiology of these infections, 43 new patients with fusariosis were evaluated, and the literature was reviewed. A total of 259 patients (232 immunocompromised and 27 immunocompetent) were identified. Skin involvement was present in 70% of patients, particularly in immunocompromised patients (72% vs. 52%; P=.03). In immunocompetent patients, cutaneous infections were characterized by preceding skin breakdown, localized involvement, slow pace of progression, and good response to therapy. In contrast, skin involvement in immunocompromised patients was only occasionally preceded by skin breakdown and typically was presented as rapidly progressive disseminated lesions at various stages of evolution. Metastatic skin lesions were associated with fungemia, neutropenia, and death. Skin was the single source of diagnosis for the majority of immunocompromised and immunocompetent patients. Recommendations for the prevention of fatal fusariosis originating from skin are presented.
VARIANTS
EYE
The epidemiological features and laboratory results of fungal keratitis: a 10-year review at a referral eye care center in South India. Gopinathan U, Garg P, Fernandes M, Sharma S, Athmanathan S, Rao GN. Jhaveri Microbiology Center, L.V. Prasad Eye Institute, L.V. Prasad Marg, Banjara Hills, Hyderabad 500 034, India.	Cornea 2002 Aug;21(6):555-9 Abstract quote PURPOSE: To report the epidemiological features and laboratory results of 1,352 cases of fungal keratitis diagnosed at the L.V. Prasad Eye Institute (LVPEI) in south India. METHODS: The medical and microbiology records of 1,352 culture proven cases (1,354 eyes) of fungal keratitis diagnosed at the LVPEI between January 1991 to December 2000 was retrospectively reviewed for demographic features, risk factors, seasonal variation, and laboratory findings. RESULTS: Males (962) were affected significantly more (p< 0.0001) than females (390). Of 1,352 patients, 853 (64.4%) were in the younger age group (16-49 years). Ocular trauma predisposed to infection in 736 (54.4%) of 1,354 eyes. There was a higher incidence of fungal keratitis during the monsoon and winter than summer. A fungal cause was established by smears of corneal scrapings in 1,277 (95.4%) eyes. The potassium hydroxide preparation (KOH), Calcofluor white (CFW), Gram-, and Giemsa-stained smears revealed fungus in 1,219 (91.0%), 1,224 (91.4%), 1,181 (88.2%), and 1,139 (85.1%) eyes, respectively. Fusarium(506, 37.2%) and Aspergillus species (417, 30.7%) predominated the hyaline fungal spectrum (1,133) and Curvularia species (39, 2.8%) were the highest among the dematiaceous isolates (218). CONCLUSIONS: To the best of our knowledge, this review presents the epidemiological features and laboratory results of the largest series of fungal keratitis ever reported in the literature. Keratomycosis is predominant in young adults with trauma as the major predisposing factor. With fungal keratitis being a major ophthalmologic problem in the tropical regions of the world, data available on the epidemiological features of a large series would greatly help medical practitioners at primary and secondary health care centers in the management of the disease. A simple KOH preparation of corneal scraping alone is highly beneficial in confirming the diagnosis.
ORBITAL
Necrotizing periorbital Fusarium infection--an emerging pathogen in immunocompetent individuals. Pushker N, Chra M, Bajaj MS, Ghose S, Naik N, Kashyap S, Satpathy G. Oculoplastic and Paediatric Ophthalmology Services, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi 110 029, India.	J Infect 2002 May;44(4):236-9 Abstract quote Fungal infections of the skin and deeper tissues of the periorbital region are quite rare. We report a case of a localized, deep periorbital necrotizing Fusarium infection in an otherwise healthy, elderly lady. Since the clinical features and histopathological findings of Fusarium infection are by no means characteristic, the definitive diagnosis was achieved with the help of microbiological examination of cultured organisms. A combined medical and surgical therapy led to adequate control of infection. To conclude, localized, deep periorbital necrotizing soft tissue infection by Fusarium in an immunocompetent lady is not reported in literature. One should have a high index of suspicion for emerging fungal pathogens in the differential diagnosis of necrotizing orbital or adnexal conditions, even in an immunocompetent patient. The histologic findings of septate, branching hyphae and vascular invasion cannot distinguish Fusarium species from various other moulds such as Aspergillus species; microbiologic studies are essential for confirming the diagnosis.
SKIN
Chronic infection due to Fusarium oxysporum mimicking lupus vulgaris: case report and review of cutaneous involvement in fusariosis. Pereiro M Jr, Abalde MT, Zulaica A, Caeiro JL, Florez A, Peteiro C, Toribio J. Department of Dermatology, Complejo Hospitalario Universitario, Santiago de Compostela, Spain	Acta Derm Venereol 2001 Jan-Feb;81(1):51-3 Abstract quote A 67-year-old female presented with a 20-year-old lesion involving the right ear and preauricular area mimicking tuberculous lupus. Fusarium oxysporum infection was confirmed by biopsy studies and cultures. The biopsy specimen showed an unusually extensive dermal invasion with fungal hyphae. This is an uncommon clinical presentation for Fusarium infection in a healthy patient. When referred to us, the patient had received antifungal therapy with itraconazole without any benefit. Improvement was obtained with fluconazole therapy. The spectrum of cutaneous involvement related to Fusarium spp. includes toxic reactions, colonization, superficial indolent infection, deep cutaneous or subcutaneous infections and disseminated infection.
Fusarium infections of the skin. Gupta AK, Baran R, Summerbell RC. Division of Dermatology, Department of Medicine, Sunnybrook and Women's College Health Sciences Center (Sunnybrook site), and the University of Toronto, Toronto, Canada, bThe Nail Center, Cannes, France, and cOntario Ministry of Health Mycology Laboratory and the Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.	Curr Opin Infect Dis 2000 Apr;13(2):121-128 Abstract quote Fusarium species are ubiquitous and may be found in the soil, air and on plants. Fusarium species can cause mycotoxicosis in humans following ingestion of food that has been colonized by the fungal organism. In humans, Fusarium species can also cause disease that is localized, focally invasive or disseminated. The pathogen generally affects immunocompromised individuals with infection of immunocompetent persons being rarely reported. Localized infection includes septic arthritis, endophthalmitis, osteomyelitis, cystitis and brain abscess. In these situations relatively good response may be expected following appropriate surgery and oral antifungal therapy. Disseminated infection occurs when two or more noncontiguous sites are involved. Over eighty cases have been reported, many of which had a hematologic malignancy including neutropenia. The species most commonly involved include Fusarium solani, Fusarium oxysporum, and Fusarium moniliforme (also termed F. verticillioides). The diagnosis of Fusarium infection may be made on histopathology, gram stain, mycology, blood culture, or serology. Portals of entry of disseminated infection include the respiratory tract, the gastrointestinal tract, and cutaneous sites.The skin can be an important and an early clue to diagnosis since cutaneous lesions may be observed at an early stage of the disease and in about seventy-five cases of disseminated Fusarium infection. Typical skin lesions may be painful red or violaceous nodules, the center of which often becomes ulcerated and covered by a black eschar. The multiple necrotizing lesions are often observed on the trunk and the extremities. Onychomycosis most commonly due to F. oxysporum or F. solani has been reported. The onychomycosis may be of several types: distal and lateral subungual (DLSO), white superficial (WSO), and proximal subungual (PSO). In proximal subungual onychomycosis there may be associated leukonychia and/or periungual inflammation. Patients with Fusarium onychomycosis have been cured following therapy with itraconazole, terbinafine, ciclopirox olamine lacquer, or topical antifungal agent. In other instances nail avulsion plus antifungal therapy has been successful. In patients with hematologic malignancy or bone marrow transplant, who may experience prolonged or severe neutropenia during the course of therapy, the skin and nails should be carefully examined and consideration given to treating potential infection sites that may serve as portals for systemic dissemination. When disseminated Fusarium infection is present therapy with antifungal agents has generally been disappointing with the chances of a successful resolution being enhanced if the neutropenia can be corrected in a timely manner.
Skin lesions associated with Fusarium infection. Bodey GP, Boktour M, Mays S, Duvic M, Kontoyiannis D, Hachem R, Raad I. University of Texas M. D. Anderson Cancer Center.	J Am Acad Dermatol 2002 Nov;47(5):659-66 Abstract quote Infections caused by Fusarium species are increasing in frequency among immunocompromised hosts. We identified 35 patients with cancer who had Fusarium skin lesions. Twenty patients had disseminated infection, 6 had primary localized skin infections, 4 had skin lesions associated with sinus infections, and 5 had onychomycosis. All patients (except 3 with onychomycosis) had hematologic malignancies and neutropenia. Skin lesions associated with disseminated infection included red or gray macules, papules (some with central necrosis or eschar), pustules, and subcutaneous nodules. Most patients had a variety of lesions simultaneously. Multiple red or gray macules with central ulceration or black eschar are characteristic of Fusarium infection. Disseminated infection may originate from skin lesions or onychomycosis. Most infections fail to respond to antifungal therapy unless there is resolution of the patient's neutropenia.

Epidemiology
Disease Associations
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Prognosis and Treatment
Commonly Used Terms
Internet Links

DISEASE ASSOCIATIONS	CHARACTERIZATION
CANCER
Epidemiology, molecular mycology, and environmental sources of Fusarium infection in patients with cancer. Raad I, Tarrand J, Hanna H, Albitar M, Janssen E, Boktour M, Bodey G, Mardani M, Hachem R, Kontoyiannis D, Whimbey E, Rolston K. Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.	Infect Control Hosp Epidemiol 2002 Sep;23(9):532-7 Abstract quote OBJECTIVE: To investigate the epidemiology and environmental sources of Fusarium infections in patients with cancer. DESIGN: Retrospective case-control study conducted following surveillance environmental cultures and DNA analysis of isolated organisms. SETTING: A tertiary-care, university cancer center. METHODS: In 1996 and 1997, environmental cultures were performed on air samples and water systems. A retrospective chart review was performed for 70 patients with cancer identified with fusariosis between 1987 and 1997. Patients with fusariosis were compared with 49 uninfected control patients who occupied hospital rooms with positive environmental cultures for Fusarium. With the use of random amplification of polymorphic DNA, organisms isolated from infected patients were compared with environmental organisms. RESULTS: Most of the patients with Fusarium (40, 57%) were infected on or within 3 days of admission, indicating community rather than nosocomial acquisition. Patients were comparable in terms of underlying immunocompromised status to 49 uninfected control patients. However, the duration from admission to infection in the patients with fusariosis tended to be shorter than the duration from admission to discharge in the exposed control patients (P = .06). Water cultured from the hospital tanks and from sinks and water fountains was negative for Fusarium. With the use of polymerase chain reaction, environmental isolates did not match clinical ones. Quantitative air sampling showed that the quantitative outdoor Fusarium levels were eightfold higher than the indoor levels. During the rainy summer season, outdoor air concentrations of Fusarium were at their highest, coinciding with the peak incidence of fusariosis at our center. CONCLUSION: The most likely source of fusariosis was the external environment rather than nosocomial sources, such as water.
TRANSPLANTATION
Disseminated Fusarium infections in patients following bone marrow transplantation. Minor RL Jr, Pfaller MA, Gingrich RD, Burns LJ. Department of Medicine, University of Iowa College of Medicine, Iowa City 52247.	Bone Marrow Transplant 1989 Nov;4(6):653-8 Abstract quote Intensive immunosuppressive therapy and broad spectrum antibiotics predispose cancer patients to opportunistic fungal infections. Fusarium has rarely been reported as a pathogen in immunocompromised patients, but is almost uniformly fatal. Only six cases of disseminated Fusarium infection have been described in patients following bone marrow transplantation (BMT). We report here two additional cases. Fusarium infection initially presented with pyomyositis in one patient and with embolic skin lesions in another following T cell-depleted BMT. Both patients died with active Fusarium infection despite an extensive course of amphotericin B, rifampicin and granulocyte transfusions. From this experience and from a review of the literature, Fusarium infections appear to be increasing in prevalence as significant pathogens in immunocompromised hosts and are resistant to many conventional forms of therapy.

LABORATORY/RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
RADIOLOGIC
LABORATORY MARKERS
BLOOD CULTURES
Effect of fluconazole prophylaxis on fungal blood cultures: an autopsy-based study involving 720 patients with haematological malignancy. Kami M, Machida U, Okuzumi K, Matsumura T, Mori Si S, Hori A, Kashima T, Kanda Y, Takaue Y, Sakamaki H, Hirai H, Yoneyama A, Mutou Y. Department of Hematology, Toranomon Hospital, Tokyo, Japan.	Br J Haematol 2002 Apr;117(1):40-6 Abstract quote To investigate the utility of blood culture of invasive fungal infections in patients with haematological malignancies, an autopsy survey was conducted in 720 patients who were treated between 1980 and 1999. We identified 252 patients with invasive mycosis. These included Candida (n = 94), Aspergillus (n = 91), Zygomycetes (n = 34), Cryptococcus (n = 7), Trichosporon (n = 11), Fusarium (n = 1), and unknown fungi (n = 20). Of the 94 patients with invasive candidiasis, 20 had positive blood cultures. Of the 11 patients with invasive trichosporonosis, seven had positive blood cultures. The sensitivities of blood cultures were 1.1%, 0% and 14% for detecting invasive aspergillosis, zygomycosis and cryptococcosis respectively. Multiple regression analysis showed a significant correlation between results of Candida blood cultures and some variables, including prophylactic use of absorbable antifungals (P = 0.0181) and infection by Candida albicans (P = 0.0086). The sensitivity of blood cultures decreased when patients received antifungal chemoprophylaxis. Unless these agents are inactivated in culture bottles, conventional blood cultures might produce false-negative results.
POLYMERASE CHAIN REACTION
Specific detection of fusarium species in blood and tissues by a PCR technique. Hue FX, Huerre M, Rouffault MA, de Bievre C. Laboratoire de Mycologie Medicale, Institut Pasteur, 75724 Paris cedex 15, France.	J Clin Microbiol 1999 Aug;37(8):2434-8 Abstract quote Fusarium species are opportunistic nosocomial pathogens that often cause fatal invasive mycoses. We designed a primer pair that amplifies by PCR a fragment of a gene coding for the rRNA of Fusarium species. The DNAs of the main Fusarium species and Neocosmospora vasinfecta but not the DNAs from 11 medically important fungi were amplified by these primers. The lower limit of detection of the PCR system was 10 fg of Fusarium solani DNA by ethidium bromide staining. To test the ability of this PCR system to detect Fusarium DNA in tissues, we developed a mouse model of disseminated fusariosis. Using the PCR, we detected Fusarium DNA in mouse tissues and in spiked human blood. Furthermore, F. solani, Fusarium moniliforme, and Fusarium oxysporum were testing by random amplified polymorphic DNA (RAPD) analysis. The bands produced by RAPD analysis were purified, cloned, and sequenced. The information was used to design primer pairs that selectively amplified one or several Fusarium species. The method developed may be useful for the rapid detection and identification of Fusarium species both from culture and from clinical samples.

PROGNOSIS AND TREATMENT	CHARACTERIZATION
PROGNOSTIC FACTORS
TREATMENT
GENERAL
Fusarium, a significant emerging pathogen in patients with hematologic malignancy: ten years' experience at a cancer center and implications for management. Boutati EI, Anaissie EJ. The University of Texas M.D. Anderson Cancer Center, Houston, USA.	Blood 1997 Aug 1;90(3):999-1008 Abstract quote Despite increasing reports of life-threatening Fusarium infections, little is known about its pathogenesis and management. To evaluate the epidemiology, clinicopathologic features, and outcome of invasive fusariosis in patients with hematologic cancer, we conducted a retrospective study of invasive fusarial infections in patients with hematologic malignancy treated at a referral cancer center over a 10-year period (1986 to 1995), as well as a literature review. Forty patients with disseminated and three patients with invasive lung infection were included in the analysis. All patients were immunocompromised. The infection occurred in three patients postengraftment following bone marrow transplantation. All patients were diagnosed antemortem.
AMPHOTERICIN B
Efficacy of liposomal amphotericin B in treatment of systemic murine fusariosis. Ortoneda M, Capilla J, Pastor FJ, Pujol I, Guarro J. Unitat de Microbiologia, Facultat de Medicina i Ciencies de la Salut and Institut d'Estudis Avancats. Laboratori de Microbiologia, Hospital Universitari de Sant Joan de Reus, Universitat Rovira i Virgili, 43201 Reus, Spain.	Antimicrob Agents Chemother 2002 Jul;46(7):2273-5 Abstract quote We have compared the activities of liposomal amphotericin B (LAMB) at 3, 5, 10, and 20 mg/kg/day and amphotericin B deoxycholate (AMB) at 1.5 and 2.5 mg/kg/day in a murine systemic infection by Fusarium verticillioides. Survival was improved by all treatments except AMB at 1.5 mg/kg/day. The tissue burden in liver was reduced by LAMB at all dosages and by AMB at 2.5 mg/kg/day. The two highest dosages of LAMB showed significant reductions in the spleen.