Localized oral Fusarium infection in an AIDS patient with malignant lymphoma

We report here a case of localized oral Fusarium infection in an AIDS patient who developed an ulceration in the soft palate. Fusarium solani was identified by histopathology and culture. We believe this to be the second reported case of oral Fusarium infection in a patient with haematological malignancy and the first reported association of oral Fusarium infection with AIDS.     

Successful treatment of disseminated Fusarium infection in an infant with leukemia

Disseminated Fusarium infection in an immunocompromised host is intractable and results in high mortality. We provide the first full case report on successful treatment of a disseminated Fusarium infection in an infant. The 6-month-old infant, whose family raised livestock, had infantile leukemia. During the neutropenic period after intensive chemotherapy, vomiting, diarrhea, fever, subcutaneous nodes, and coughing appeared. Pneumonia was diagnosed, and Fusarium moniliforme was isolated from blood culture. A central venous catheter was removed. Granulocyte colony-stimulating factor (G-CSF) and amphotericin B (AMPH-B) (total dose, 65 mg/kg) were administered continuously for 8 weeks. The infection was resolved according to improvement of clinical and laboratory findings, and intensive chemotherapy was restarted for the leukemia. Cord blood stem cell transplantation from an unrelated donor was performed. The Fusarium infection did not recur, but after transplantation, leukemia relapsed. Treatment of neutrophils using G-CSF, AMPH-B, and local treatment induced resolution of the disseminated Fusarium infection in this immunocompromised host with malignancy. We suggest caution for patients living in an environment conducive to the development of Fusarium infection because of the particular risk of infection.     

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

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.     

Fusarium osteomyelitis: case report and review of the literature

We present a case of Fusarium osteomyelitis attributed to innocuous trauma in a patient with significant peripheral vascular disease and diabetes mellitus type 2. Fusarium species have been reported to cause an increasing number of infections, particularly in severely immunocompromized patients. Colonization of normal skin has also been reported. To the best of the author's knowledge, there are 5 cases of Fusarium osteomyelitis described in English-language literature. There is also a report with little detail of Fusarium infection involving bone in 3 patients with hematologic malignancy. We tabulated the pertinent facts of the 5 detailed cases and compared them to ours. Early diagnosis requires some suspicion of invasive fungal infection. Tissue culture and pathologic examination are necessary for definitive diagnosis and to distinguish infection from colonization. Therapy includes antifungal drugs and aggressive surgical debridement, and even when these modalities are readily implemented the outcome may not be optimal because of the angioinvasive character of the organism.     

Recurrence ofFusarium solani abscess formation in an otherwise healthy patient

Summary Fusarium spp. are usually considered opportunistic fungi in humans. A case ofFusarium solani abscess formation of the foot in an immunocompetent patient in whom recurrence occurred even after intravenous amphotericin B treatment is presented here.

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Rezidivierende, abszedierendeFusarium solani -Infektion bei einer sonst gesunden Patientin

Zusammenfassung Fusarium wird im allgemeinen als opportunistischer Pilz beim Menschen angesehen. Im Fuß einer Patientin ohne Abwehrschwäche trat eine abszedierende Infektion durchFusarium solani auf, die sogar nach intravenöser Amphotericin B-Therapie rezidivierte.

     

Fusarium osteomyelitis of the foot in a patient with diabetes mellitus

Diabetic foot osteomyelitis is among the most common and serious complications in patients with diabetes mellitus. It is often a polymicrobial infection. We report the first case of foot osteomyelitis in a diabetic patient caused by Fusarium solani.     

Invasive fusariosis with prolonged fungemia in a patient with acute lymphoblastic leukemia: case report and review of the literature

Fusariumspp are rare but important opportunistic pathogens in immunocompromised patients. Disseminated fusarial infections occur mostly in patients with hematologic malignancies with myelosuppressive chemotherapy or in patients with severe immunodeficiency. Although more frequent than Aspergillus fungemia, Fusarium fungemia remains a rare event. We describe the case of a female patient with febrile neutropenia and persistent fungemia due to Fusarium solani, treated with posaconazole and liposomal amphotericin B. A review of the literature for Fusariumspp fungemia was carried out.     

Fusarium infections in patients with severe aplastic anemia: review and implications for management

BACKGROUND AND OBJECTIVE: The prognosis of severe fungal infections, such as fusarium infections, in patients with aplastic anemia is directly related to the recovery of bone marrow functions. In this study, in vitro anti-Fusarium activity of granulocytes was investigated, the case of disseminated infection in a child with very severe aplastic anemia is reported, and implications for management of such infective complications are discussed. DESIGN AND METHODS: The in vitro efficiency of PMNL from three untreated, normal blood donors and from two G-CSF-treated WBC donors in contrasting the growth of the Fusarium sp strain isolated from the patient we present was measured by a 3H-glucose uptake inhibition assay and confirmed by microscopic examination. RESULTS: Basic growth inhibitory activity of unstimulated PMNL on Fusarium cells was significantly enhanced in the presence of GM-CSF in all three blood donors tested. In one of the two G-CSF-treated donors, in vitro efficiency of PMNL in contrasting the growth of the fungus increased notably after G-CSF treatment. We report the case of a 3-year-old girl with very severe aplastic anemia unresponsive to conventional immunosuppressant therapy who developed a disseminated fusarium infection. The child initially responded to liposomal amphotericin B and granulocyte transfusions from G-CSF stimulated donors. Subsequently she was given a cord blood stem cell transplantation but died of disseminated infection. INTERPRETATION AND CONCLUSIONS: Including the present case, there are only ten reports of invasive infections caused by the genus Fusarium in aplastic anemia patients and only two of the patients survived. In vitro data seem to suggest that in vivo treatment with rh-G-CSF could have a stimulatory effect on the anti-Fusarium activity of neutrophils. Despite the efficacy of granulocyte transfusions by G-CSF-stimulated donors in the temporary control of fusarium infection, treatment of the underlying hematologic disease is required to cure the infection in patients with severe aplastic anemia. Granulocyte transfusions by G-CSF-stimulated donors while awaiting bone marrow recovery following the blood stem cell transplant should be considered.     

Successful treatment of Fusarium keratitis with cornea transplantation and topical and systemic voriconazole

A case of invasive Fusarium keratitis in a previously healthy male patient was treated successfully with cornea transplantation and systemic and topical voriconazole after treatment failure with topical amphotericin B and systemic itraconazole. Topical voriconazole was well tolerated, and, in conjunction with the oral administration, it resulted in a high level of the drug in the anterior chamber of the eye (which was 160% of the plasma drug level).     

Skin lesion in a patient after hematopoietic stem cell transplant

We present a case of a 61‐year‐old Caucasian woman who was hospitalized with fever on day 176 after a matched unrelated stem cell transplant for acute myelogenous leukemia. She developed hemorrhagic bullae on the skin of her right thigh, and both blood cultures and skin biopsy confirmed Fusarium proliferatum. Despite antifungal therapy, her condition worsened and she died while on comfort‐only measures.     

Disseminated Fusarium infections in patients following bone marrow transplantation

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.     

Fusarium infection after solid-organ transplantation.

We describe a case of soft tissue infection caused by Fusarium species in a heart-liver transplant recipient, and review the cases of fusarial infection reported among solid-organ transplant (SOT) recipients. Unlike fusarial infection in patients with hematologic malignancies or bone marrow transplants, fusarial infection in SOT recipients tends to be localized, occurs later in the posttransplantation period, and has a better outcome. Surgical resection, when possible, and prolonged treatment with amphotericin provide the most effective form of therapy.     

The emerging role of Fusarium infections in patients with cancer

Infection due to Fusarium species is an increasing cause of serious potentially fatal disease in patients with cancer. We described 9 patients with infection caused by Fusarium species during a 4-year period at the M. D. Anderson Hospital. The spectrum of infections included disseminated disease in 4 patients, skin or soft-tissue infections in 3, pneumonia in 1, and fungemia in 1. All 4 patients with disseminated infection had culture- and biopsy-proven skin lesions caused by Fusarium species and the blood cultures yielded the organism in 3 of these 4 patients. Maxillary sinusitis was the presenting manifestation of Fusarium infection in 2 of these 4 patients, suggesting that paranasal sinuses are potential portals of entry for the infection. Eight patients had a hematological malignancy and 7 were neutropenic at the onset of their infection. Patients with deep-seated infections remained neutropenic and died from infection despite treatment with amphotericin B. All 5 isolates tested in vitro showed resistance to ketoconazole and miconazole, whereas 3 were susceptible to amphotericin B. Fusarium species could play a role in producing myelosuppression and fungal cultures are required to differentiate it from the more commonly encountered Aspergillus species. Fusarium species are emerging as a serious, potentially fatal, pathogen in patients with cancer.     

Invasive Fusarium infections in bone marrow transplant recipients

From November 1982 to September 1983, three cases of invasive infection due to Fusarium species were documented in bone marrow transplant recipients. Fusarium was cultured from discrete skin nodules (one patient), maxillary sinus (one patient), or from the blood and surgically excised nasal septum (one patient). All three isolates were resistant to 5-fluorocytosine, whereas only one isolate was resistant to amphotericin B. Although all three patients died, two of the patients had clearing of their Fusarium infection. From this experience and from a review of the literature, it is concluded that despite the dismal prognosis for immunocompromised patients with Fusarium, beneficial therapies would include systemic amphotericin B, local surgical resection, and possibly leukocyte transfusions.     

The spectrum of Fusarium infection in immunocompromised patients with haematological malignancies and in non-immunocompromised patients: a single institution experience over 10 years

Fusarium is a newly emerging fungal pathogen associated with significant morbidity and mortality in the immunocompromised host. We have reviewed our hospital's experience with Fusarium between 1985 and 1995. Fusarium species were isolated from 22 specimens, representing 11 patients. Cases were not clustered by time period. The median age of the patients was 36.5 years (range 17-69 years). The sources of the organism were 12 skin lesions from eight patients, seven blood cultures from two patients and one specimen each from a Hickman catheter tip, nail clippings and a bronchoalveolar lavage. Seven of the patients had chemotherapy-induced neutropenia when the Fusarium was isolated. Five of them developed invasive fusarosis during acute leukaemia induction treatment. They remained neutropenic, and none survived. The other two patients recovered from neutropenia and were treated successfully for this infection. The remaining four patients were not neutropenic or immunocompromised. Three grew Fusarium from skin or nail clippings and one from bronchial alveolar lavage (BAL). There was no evidence of invasive disease in any of the four. None of them received antifungal therapy, and they were all alive at last follow-up. We conclude that Fusarium is a newly emerging infection in neutropenic patients. A high index of suspicion, especially for skin lesions, will help in early diagnosis before systemic and visceral dissemination. Excision of the initial focus of infection and antifungal therapy, aided by speedy neutrophil recovery, are likely to protect patients threatened with these fatal infections. Fusarium isolated from non-neutropenic, non-immunosuppressed patients is not significant and does not merit systemic antifungal treatment.     

Fusarium infections of the skin

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.     

Fusarium dimerum infection in a stem cell transplant recipient treated successfully with voriconazole

We report the first case, to our knowledge, of a proven Fusarium dimerum soft-tissue infection in a stem cell transplant recipient treated successfully with voriconazole. There is a well-documented increase in the incidence, diversity and antifungal resistance of invasive mould infections in the immunocompromised patient population. The management of these infections is changing as new, more efficacious and less toxic antifungal agents become available. We present the case of a 19-year-old female diagnosed with a proven F. dimerum soft-tissue infection of the foot and possible pulmonary infection with the same organism 10 days following a sibling allogeneic stem cell transplant for severe aplastic anaemia. The infection developed despite treatment with 3 mg/kg AmBisome for a concurrent chest infection. She was treated successfully with voriconazole.     

Successful treatment of disseminated Fusarium infection after autologous bone marrow transplantation for acute myeloid leukemia

Disseminated Fusarium is a rare but life-threatening infection of severely immunocompromised patients. A fatal outcome has been described in all reported cases of Fusarium infection occurring after bone marrow transplantation. We describe a patient who developed disseminated Fusarium infection with a secondary fungal endophthalmitis after an autologous bone marrow transplant for acute myeloid leukemia. This infection was successfully eradicated after neutrophil recovery by prolonged systemic administration of amphotericin B as well as aggressive local therapy including enucleation of the affected eye. The patient remains free of both leukemia and fungal disease more than 4 years after transplant.     

Disseminated infection with Fusarium in recipients of bone marrow transplants.

Clinical data from 10 episodes of disseminated infection with Fusarium among eight recipients of bone marrow transplants and from 31 cases reported previously in the literature were analyzed in an effort to characterize the natural history of this rare infection and its response to therapy. The characteristic signs of fusarial infection--disseminated skin nodules, fungemia, and multiple-organ involvement--are results of its propensity for early spread. From a review of the literature and our own experience, it appears that recovery of phagocytic mechanisms (the primary immunologic defenses against Fusarium) in the form of rising neutrophil counts is mandatory for clinical resolution. Even after a graft begins to function adequately, Fusarium may not be completely eradicated, as evidenced by the high incidence of recurrence among patients with subsequent neutropenic episodes. Fusarium is highly resistant to conventional antifungal drugs in vitro, but its progression may be slowed by intensive antifungal therapy until the recovery of adequate neutrophil levels.     

Successful salvage treatment of disseminated cutaneous fusariosis with liposomal amphotericin B and terbinafine after allogeneic stem cell transplantation

Abstract: Fusarium infections are associated with high mortality after allogeneic stem cell transplantation. We report on successful treatment of a disseminated cutaneous Fusarium proliferatum infection using liposomal amphotericin B and terbinafine. In vitro susceptibility tests of antifungal drugs suggest that terbinafine is a potent additional antifungal drug for disseminated cutaneous fusariosis.