Invasive fusariosis masquerading as extramedullary disease in rapidly progressive acute lymphoblastic leukemia.

Invasive fusariosis (IF) most commonly occurs in patients with hematologic malignancies and severe neutropenia, particularly during concomitant corticosteroid use. Breakthrough infections can occur in high-risk patients despite Aspergillus-active antifungal prophylaxis. We describe a patient with rapid acute lymphoblastic leukemia (ALL) progression who presented with multifocal skin nodules thought to be choloromatous disease. These lesions were ultimately diagnosed as IF and the patient had two simultaneously active disease processes. This case highlights the importance of pathologic diagnosis of new skin lesions in ALL patients, even during leukemia progression, and demonstrates that IF can occur despite normal neutrophil counts and Aspergillus-active prophylaxis.

[Successful treatment of pre-engraftment disseminated fusariosis with high-dose liposomal amphotericin B in a cord blood transplant recipient].

A 47-year-old man with acute myeloid leukemia and myelodysplastic-related changes relapsed after an allogenic bone marrow transplant and received a cord blood transplant as salvage therapy. The patient developed febrile neutropenia that was resistant to broad-spectrum antibiotics and multiple, painful, nodular skin lesions on his trunk and extremities before engraftment. A skin biopsy and blood culture found mold, and the subsequent microscopic examination, mass spectrometry, and DNA sequencing of the fungal colonies identified Fusarium solani. The patient's fever and skin lesions began to improve with the administration of liposomal amphotericin B at 5 mg/kg/day. Neutrophilic engraftment occurred on day 19. Stage 3 acute skin graft-versus-host disease was cured by the application of topical steroid. Unexpectedly, a change from liposomal amphotericin B to voriconazole on day 38 exacerbated the Fusarium infection. The Fusarium infection was finally cured by the administration of liposomal amphotericin B for a total of 19 weeks. Neutrophilic engraftment, an immediate definitive diagnosis, the sufficient and long-term administration of appropriate antifungal medication, and avoidance of the systemic administration of steroids might have contributed to the successful outcome of this patient.

Case Report: Corneal Coinfection with Fungus and Amoeba: Report of Two Patients and Literature Review.

We report two cases of corneal coinfection with Acanthamoeba and Fusarium sp. along with the review of published literature. A 35-year-old woman and 65-year-old man presented to the institute with corneal ulcer refractory for treatment with topical antibiotics. Microbiological examination revealed the presence of Acanthamoeba cysts along with septate, hyaline fungal filaments. After emergency therapeutic penetrating keratoplasty (TPK) in both, the corneal tissue was sent for histopathologic examination, which confirmed the presence of Acanthamoeba and fungal coinfection. One patient had a recurrence of fungal infection after TPK. In subjects with a rapid progression of mycotic ulcer, coinfection with other microorganisms including Acanthamoeba should be suspected. The two cases presented here emphasize the importance of microbiology in making prompt diagnosis and appropriate management of these cases at an early stage.

Endogenous Fusarium Endophthalmitis During Treatment for Acute Myeloid Leukemia, Successfully Treated with 25-Gauge Vitrectomy and Antifungal Medications.

Endogenous fungal endophthalmitis (EFE) caused by disseminated fusariosis is a rare condition that generally has a poor outcome, even with intensive therapy. Here, we describe a case in which this type of EFE was diagnosed with vitreous sampling and was successfully treated with 25-gauge vitrectomy and antifungals, including liposomal amphotericin B and voriconazole. A 16-year-old male patient undergoing treatment for acute myeloid leukemia complained of eye pain and blurred vision in his right eye. Treatment was initiated for a vitreous opacity, possibly associated with herpetic retinitis, but the patient worsened and he was referred to us. Right-eye visual acuity was limited to light perception. We suspected endogenous endophthalmitis and performed 25-gauge vitrectomy with antibiotic perfusion of ceftazidime, vancomycin, and voriconazole. Vitreous culturing revealed the presence of Fusarium solani species complex, and enhanced computed tomography revealed disseminated fusariosis lesions in the lung, spleen, and the soft tissue of the left upper arm. The patient received antifungal treatment with liposomal amphotericin B and voriconazole, and these conditions were eliminated. Visual acuity recovered to 20/400 after additional vitrectomy for tractional retinal detachment and was maintained at this level during the 6-month follow-up period. The success of our treatment allowed the capture of optical coherence tomography images of the retina during fusarium-associated endogenous endophthalmitis and the follow-up period. Furthermore, this case showed that immediate vitrectomy for suspected EFE and intensive treatment can lead to a good clinical outcome.

Trasplante de médula ósea alogénico en un paciente con fusariosis diseminada y leucemia mieloide aguda / Allogeneic hematopoietic cell transplantation in a patient with disseminated fusariosis and acute myeloid leukemia

La infección diseminada por Fusarium se ha convertido en un problema creciente en las personas con neoplasias hematológicas malignas, principalmente en pacientes con leucemias agudas; se describen cada vez más casos en aquellos sometidos a un trasplante de médula ósea. No existe un tratamiento óptimo establecido para la fusariosis diseminada. La mortalidad global comunicada de esta infección oscila entre el 50 y el 80%. Se presenta a continuación el caso de un paciente de sexo masculino de 29 años, con diagnóstico de leucemia mieloide aguda, que presenta como complicación una fusariosis diseminada, y logra sobrellevar un trasplante alogénico de médula ósea en el Hospital Italiano de San Justo (Argentina) de forma exitosa. (AU)

Disseminated fusariosis has become an increasing problem in people with hematopoietic neoplasms, mainly in patients affected by acute leukemias, and even more in those who undergo hematopoietic cell transplantation. There is not an optimal treatment for disseminated fusariosis. The global mortality described in the literature is between 50% and 80%. We introduce a case of a 29 year old patient with diagnosis of acute myeloid leukemia complicated with disseminated fusariosis, who copes with an allogeneic hematopoietic cell transplantation with a successful outcome in the "Hospital Italiano de San Justo" (Argentina). (AU)

Eosinophil fungal rhinosinusitis caused by Fusarium infection secondary to odontogenic maxillary sinus disease: when collaboration between otolaryngologist and allergologist leads to the correct diagnosis and therapy.

SUMMARY: Rhinitis and sinusitis usually coexist and are concurrent in most individuals; thus, the correct terminology is now "rhinosinusitis". On the basis of numerous causative factors, often co-existing in the same patient, the diagnosis of rhinosinusitis is also made by a wide variety of practitioners (allergologists, otolaryngologists, pulmonologists, primary care physicians, paediatricians, and many others). Approximately 5-15% of the population suffers from chronic rhinosinusitis, and in 10-12% of them, it is of dental origin. The treatment of odontogenic maxillary sinus disease is directed to the management of the rhinosinusitis and of the odontogenic source. The widespread use of dental implants and reconstructive procedures for dental implant placement has led to new types of complication, as in this case report, due to chronic eosinophilic rhinosinusitis secondary to Fusarium infection in the maxillary sinus. The patient was initially evaluated by the allergologist, and subsequently successfully treated by the otolaryngologist with Functional Endoscopic Sinus Surgery. The advantages of endoscopic sinus surgery include more accurate visualization, no external incision, reduced soft tissue dissection, and reduced hospital stay. Chronic maxillary sinusitis of dental origin is a common disease that requires treatment of the sinusitis as well as of the odontogenic source.

[Fusarium keratitis with dramatic outcome]. / Fusarienkeratitis mit dramatischem Ausgang.

BACKGROUND: Fungal keratitis is much less common in Europe than in Asia. Antifungal therapy can be applied topically as well as systemically and in advanced situations surgical intervention can become necessary. CASE REPORT: We present the case of a 60-year-old woman who suffered from Fusarium keratitis that showed progression to endophthalmitis following contact lens wearing. Due to numerous resistances against antimycotic drugs the eye had to be enucleated to prevent the pathogens from spreading. Histologically, major inflammatory activity could be detected but no causative organism could be found. The failure to detect a pathogen was in clear contrast to the clinical findings and was interpreted as being an overreaction of the immune response even after the Fusarium had been destroyed. CONCLUSION: If a fungal infection of the cornea is suspected, antimycotic therapy should be initiated as early as possible. In cases involving highly resistant pathogens the eye cannot always be saved.

Invasive fungal sinusitis in the pediatric population: Systematic review with quantitative synthesis of the literature.

BACKGROUND: Invasive fungal sinusitis (IFS) represents an often fatal condition within the pediatric population. In an effort to characterize demographics, treatment modalities, and prognostic factors, we performed a systematic review. METHODS: We systematically reviewed EMBASE, Medline, TRIPdatabase, SCOPUS and the Cochrane database for invasive fungal nasal and sinus infections limited to individuals <18 years of age. Case series including 3 or more patients were included. Demographics, treatment and outcomes were analyzed using R Gui statistical software. RESULTS: Twelve studies met inclusion criteria (103 patients). There was male preponderance of 48.5% with median age of 11 years old. Majority of patients had underlying leukemia (44.6%). Aspergillus was the predominant organism (47%). Isolated nasal findings occurred in 14% of patients and nasal findings occurred in 49% overall. Absolute neutrophil count (ANC) of immunocompromised patients was below 600 in most patients (99%). Average and median length of neutropenia was 2 weeks. All patients were prescribed amphoterocin with 50% as single medicinal therapy. Surgery occurred in 82.8% of cases. The mortality rate was 46%. Univariate analysis identified presenting with facial pain as a negative predictor of overall mortality (OR 0.296, 95% CI: 0.104-0.843, p < 0.05). CONCLUSION: Mortality remains high in pediatric patients with IFS. An ANC of <600 occurred in the majority of immunocompromised patients at a duration of 2 weeks. Presenting with facial pain was a negative predictor of mortality. Many studies label this condition as invasive fungal sinusitis; however, approximately one seventh presented with only nasal findings and half overall had nasal involvement.

Anterior Segment Optical Coherence Tomography of Patients With Late-Onset Tunnel Fungal Infections With Endophthalmitis After Cataract Surgery.

PURPOSE: To report the use of anterior segment optical coherence tomography for characterization of late-onset tunnel fungal infections with endophthalmitis after cataract surgery. METHODS: Case reports. RESULTS: A 77-year-old female (case 1) and a 76-year-old male (case 2) who received cataract surgery 15 and 1 year before their initial visits, respectively, were treated with topical steroids based on a diagnosis of uveitis, because they showed growing white lesions on the upper iris and beneath the cataract scleral wound. Irrigation of the anterior chambers and removal of the white lesions were performed in each case, and microbiological tests were positive for fungi (case 1, a positive culture of Fusarium sp.; case 2, a filamentous fungus present in a direct smear) in the white lesions. Both cases were diagnosed as late-onset fungal endophthalmitis after cataract surgery and were treated with topical and systemic antifungal agents. However, the white lesions reappeared, and the inflammation in the anterior chambers worsened. Anterior segment optical coherence tomography showed the spread of the white lesions into the scleral incisions from cataract surgery. Deroofing of the tunnel and sclerocorneal patch grafts were performed in both cases to treat the fungal tunnel infections. After these treatments, inflammation of both corneas and anterior chambers subsided. CONCLUSIONS: Anterior segment optical coherence tomography can be used to identify late-onset fungal tunnel infections with endophthalmitis after cataract surgery.

Risk factors and impact of non-Aspergillus mold infections following allogeneic HCT: a CIBMTR infection and immune reconstitution analysis.

Risk factors for non-Aspergillus mold infection (NAMI) and the impact on transplant outcome are poorly assessed in the current era of antifungal agents. Outcomes of 124 patients receiving allogeneic hematopoietic cell transplantation (HCT) diagnosed with either mucormycosis (n=72) or fusariosis (n=52) between days 0 and 365 after HCT are described and compared with a control cohort (n=11 856). Patients with NAMI had more advanced disease (mucormycois: 25%, fusariosis: 23% and controls: 18%; P=0.004) and were more likely to have a Karnofsky performance status (KPS) <90% at HCT (mucormycosis: 42%, fusariosis: 38% and controls: 28%; P=0.048). The 1-year survival after HCT was 22% (15-29%) for cases and was significantly inferior compared with controls (65% (64-65%); P<0.001). Survival from infection was similarly dismal regardless of mucormycosis: 15% (8-25%) and fusariosis: 21% (11-33%). In multivariable analysis, NAMI was associated with a sixfold higher risk of death (P<0.0001) regardless of the site or timing of infection. Risk factors for mucormycosis include preceding acute GvHD, prior Aspergillus infection and older age. For fusariosis, increased risks including receipt of cord blood, prior CMV infection and transplant before May 2002. In conclusion, NAMI occurs infrequently, is associated with high mortality and appears with similar frequency in the current antifungal era.

Bone and joint infections by Mucorales, Scedosporium, Fusarium and even rarer fungi.

Mucorales, Scedosporium and Fusarium species are rarely considered as cause for bone and joint infections. However, these moulds are emerging as important fungal pathogens in immunocompromised and immunocompetent patients. Typical pre-disposing host conditions are immunosuppression and diabetes. Most common causative pathogens are Mucorales followed by Scedosporium and Fusarium. Acremonium and Phialemonium species are rare but some case reports exist. MRI is the gold standard imaging technique. Tissue specimens obtained as aspirates, imaging guided biopsy or open surgery need mycological and histopathological work-up for genus and species identification. Multimodal treatment strategies combine surgical debridement, drainage of joints or abscesses, removal of infected prosthetic joints and systemic antifungals. The treatment of mucormycosis is polyene based and may be combined with either posaconazole or - in rare cases - caspofungin. As Scedosporium species are intrinsically resistant to polyenes and azoles show absence of in vitro activity, voriconazole plus synergistic treatment regimens become the therapeutic standard. In fusariosis, fungal susceptibility is virtually impossible to predict, so that combination treatment of voriconazole and lipid-based amphotericin B should be the first-line strategy while susceptibility results are pending. In the absence of randomized controlled trials, infections due to the above moulds should be registered, e.g. in the registries of the European Confederation of Medical Mycology (ECMM).

Antifungal wound penetration of amphotericin and voriconazole in combat-related injuries: case report.

BACKGROUND: Survivors of combat trauma can have long and challenging recoveries, which may be complicated by infection. Invasive fungal infections are a rare but serious complication with limited treatment options. Currently, aggressive surgical debridement is the standard of care, with antifungal agents used adjunctively with uncertain efficacy. Anecdotal evidence suggests that antifungal agents may be ineffective in the absence of surgical debridement, and studies have yet to correlate antifungal concentrations in plasma and wounds. CASE PRESENTATION: Here we report the systemic pharmacokinetics and wound effluent antifungal concentrations of five wounds from two male patients, aged 28 and 30 years old who sustained combat-related blast injuries in southern Afghanistan, with proven or possible invasive fungal infection. Our data demonstrate that while voriconazole sufficiently penetrated the wound resulting in detectable effluent levels, free amphotericin B (unbound to plasma) was not present in wound effluent despite sufficient concentrations in circulating plasma. In addition, considerable between-patient and within-patient variability was observed in antifungal pharmacokinetic parameters. CONCLUSION: These data highlight the need for further studies evaluating wound penetration of commonly used antifungals and the role for therapeutic drug monitoring in providing optimal care for critically ill and injured war fighters.

Role of granulocyte transfusions in invasive fusariosis: systematic review and single-center experience.

BACKGROUND: Invasive Fusarium infection is relatively refractory to available antifungal agents. Invasive fusariosis (IF) occurs almost exclusively in the setting of profound neutropenia and/or systemic corticosteroid use. Treatment guidelines for IF are not well established, including the role of granulocyte transfusions (GTs) to counter neutropenia. STUDY DESIGN AND METHODS: We conducted a systematic review, identifying IF cases where GTs were used as adjunctive therapy to antifungal agents and also report a single-center case series detailing our experience (1996-2012) of all IF cases treated with antifungal agents and GTs. In the systematic review cases, GTs were predominantly collected from nonstimulated donors whereas, in the case series, they were universally derived from dexamethasone- and granulocyte-colony-stimulating factor-stimulated donors. RESULTS: Twenty-three patients met inclusion criteria for the systematic review and 11 for the case series. Response rates after GTs were 30 and 91% in the review and case series, respectively. Survival to hospital discharge remained low at 30 and 45%, respectively. Ten patients in the systematic review and three in the case series failed to achieve hematopoietic recovery and none of these survived. In the case series, donor-stimulated GTs generated mean "same-day" neutrophil increments of 3.35 × 10(9) ± 1.24 × 10(9) /L and mean overall posttransfusion neutrophil increments of 2.46 × 10(9) ± 0.85 × 10(9) /L. Progressive decrements in neutrophil response to GTs in two cases were attributed to GT-related HLA alloimmunization. CONCLUSION: In patients with IF, donor-stimulated GTs may contribute to high response rates by effectively bridging periods of neutropenia or marrow suppression. However, their utility in the absence of neutrophil recovery remains questionable.

[Invasive fungal disease due to Scedosporium, Fusarium and mucorales]. / Enfermedad fúngica invasora por Scedosporium, Fusarium y Mucor.

The number of emerging organisms causing invasive fungal infections has increased in the last decades. These etiological agents include Scedosporium, Fusarium and mucorales. All of them can cause disseminated, virulent, and difficult-to treat infections in immunosuppressed patients, the most affected, due to their resistance to most available antifungal agents. Current trends in transplantation including the use of new immunosuppressive treatments, the common prescription of antifungal agents for prophylaxis, and new ecological niches could explain the emergence of these fungal pathogens. These pathogens can also affect immunocompetent individuals, especially after natural disasters (earthquakes, floods, tsunamis), combat wounds or near drowning. All the invasive infections caused by Scedosporium, Fusarium, and mucorales are potentially lethal and a favourable outcome is associated with rapid diagnosis by direct microscopic examination of the involved tissue, wide debridement of infected material, early use of antifungal agents including combination therapy, and an improvement in host defenses, especially neutropenia.

An unusual cause of an ankle mass.

We report the case of a patient who presented with a 7-year history of a mass over the medial aspect of his right ankle, which had been gradually increasing in size. He had given up his occupation as a bus driver due to decreased movement of his ankle. An initial diagnosis of endemic syphilis was made after treponemal antibody and treponema pallidum particle agglutination tests were positive. However, following surgical debulking, cultures grew Fusarium solani and the diagnosis was changed to eumycetoma. He received prolonged treatment with antifungal agents and at 18 months follow-up remains well.