Intravenous Amphotericin Research Articles

Oropharyngeal histoplasmosis: a report of 10 cases.

A wide differential diagnosis must be entertained in patients with unusual oral and pharyngeal ulcerations. A mucosal biopsy is essential. We retrospectively reviewed 10 cases from the Infectious Diseases Division at Mayo Clinic Rochester (MN, USA), in which the diagnosis proved to be Histoplasma capsulatum infection. Between 1995 and 2016, 10 patients were diagnosed with oropharyngeal histoplasmosis. Common presenting symptoms included weight loss, weakness and oropharyngeal pain with ulcerations. Despite specialty evaluation at other facilities, diagnostic delay occurred in six patients due to lack of biopsy or fungal staining. Yeast forms consistent with H.capsulatum were identified in the biopsy specimens of all our patients. Treatment included intravenous amphotericin B and prolonged courses of azoles. Oral histoplasmosis occurred in both immunocompetent and immunosuppressed patients, and was a manifestation of disseminated infection. Severe pain involving all areas of the mouth was typical. Diagnostic delay may be avoided by early biopsy using fungal stains.

Single-Dose Amphotericin B for HIV Patients with Cryptococcal Meningitis?

Cryptococcal meningitis (CM) accounts for 20% of deaths due to HIV-1 infection in resource-limited settings. Although intravenous amphotericin B

Contemporary management and clinical outcomes of mucormycosis: A systematic review and meta-analysis of case reports

With the advent of newer antifungals, optimum treatment of mucormycosis remains to be fully elucidated. This study systematically evaluated the contemporary management and outcomes of mucormycosis. Mucormycosis cases in patients aged ≥18 years published between January 2000 and January 2017 were identified through Ovid MEDLINE and Embase. Of the 3619 articles identified, 600 (851 individual patient cases) were included in the review. Of the 851 patient cases, antifungal treatment details were available for 785. Intravenous (i.v.) amphotericin B formulations remained the most commonly prescribed first-line antifungals (760/785; 96.8%): 88.2% (670/760) were initiated as monotherapy and 11.8% (90/760) as combination antifungal therapy. Posaconazole oral suspension monotherapy was prescribed as an initial antifungal in 11 cases. It was also administered as maintenance or salvage therapy in 39 and 25 cases, respectively. Itraconazole capsule monotherapy (n = 10) was prescribed primarily for cutaneous disease in patients not receiving any immunosuppressive therapy. All-cause 90-day mortality was 41.0% (349/851). Initial treatment with combination antifungals did not reduce 90-day mortality compared with i.v. conventional amphotericin B or i.v. liposomal amphotericin B monotherapy [35/90 (38.9%) vs. 146/369 (39.6%) vs. 91/258 (35.3%), respectively; P = 0.541]. Concomitant surgical and antifungal therapy was associated with significantly lower 90-day mortality compared with treatment with antifungals alone (OR = 0.23, 95% CI 0.13-0.41; P < 0.001). The findings suggest that first-line antifungals with good efficacy remain an urgent unmet need. Whilst surgery is fundamental to improving survival, the clinical utility of combination antifungal therapy or posaconazole monotherapy requires further investigation.

Rhinocerebral mucormycosis: A prospective analysis of an effective treatment protocol

Objective:The objective of this study was to prospectively analyze the effectiveness of a treatment protocol in patients diagnosed with rhinocerebral mucormycosis.Materials and Methods:This series included ten patients who reported with suspicious clinical signs of mucormycosis. The diagnosis was established by histopathology, and computed tomography imaging was used to assess the extent of spread. All patients were treated with immediate radical surgical debridement and antifungal chemotherapy with amphotericin B. Simultaneous correction of the underlying immunosuppressive condition was carried out. The primary outcome assessed was disease-free survival, and the patients were followed up for up to 6 months after discharge.Results:In this series, the cause of immunosuppression was uncontrolled diabetes mellitus in all patients. All the patients responded to the treatment protocol and were free of the disease up to 6 months of follow-up.Conclusion:Mucormycosis is an invasive and potentially fatal disease. Prognosis can be improved by early recognition and prompt treatment with aggressive resection, intravenous amphotericin B, and control of the patient's underlying systemic condition.

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332. Phaeohyphomycosis Due to Scopulariopsis brumptii in a Hematopoietic Stem Cell Transplant (HSCT) Recipient

BackgroundWe present a rare case of Scopulariopsis brumptii endophthalmitis and discuss therapeutic strategies including systemic and intraocular anti-fungal therapy, and surgical intervention. The combination of highly resistant pathogen, unique sanctuary site, and vulnerable host makes this a challenging case.MethodsWe reviewed medical records of a patient who received HSCT for acute myelogenous leukemia and presented with acute right-sided eye pain and photophobia seven months posttransplant while on posaconazole prophylaxis.ResultsOphthalmological examination showed pan-uveitis and vitritis. Skin examination was normal. Labs revealed leukopenia of 0.5 × 109/mL and (1,3)-β-d-glucan of >500 pg/mL. CT of chest and sinuses was unremarkable. Patient received intravitreal amphotericin B followed by voriconazole thrice weekly and oral posaconazole. Vitreous aspirate was negative for bacterial, mycobacterial, and fungal cultures and broad-range PCR. Subsequently patient developed new pre-retinal lesions and posaconazole was switched to intravenous liposomal amphotericin B. Intravitreal amphotericin B deoxycholate was continued. Vitrectomy was performed with cultures yielding S. brumptii. Susceptibility data demonstrated high minimal inhibitory concentrations (MICs) for posaconazole and voriconazole and low MICs for isavuconazole, amphotericin, and echinocandins. He was treated with 2 weeks of local and systemic amphotericin B therapy before developing acute kidney injury. He was then transitioned to isavuconazole. Intraocular injections were discontinued after 6 weeks when (1,3)-β-d-glucan was 46 pg/mL and resolution of retinal lesions. Patient was kept on isavuconazole chronic suppression.Conclusion S. brumptii is known for resistance to many antifungal agents. Our case highlights the importance of vitrectomy and intraocular drug injection due to poor penetration from systemic therapy. With aggressive local and systemic therapy and surgery, our patient had good outcome. Figure 1. Funduscopic examination revealing retinal lesions. Figure 2. Scopulariopsis brumptii microscopic appearance.Disclosures All authors: No reported disclosures.

High Mortality in HIV-Associated Cryptococcal Meningitis Patients Treated With Amphotericin B-Based Therapy Under Routine Care Conditions in Africa.

BackgroundCryptococcal meningitis (CM) causes 10%–20% of HIV-related deaths in Africa. Due to limited access to liposomal amphotericin and flucytosine, most African treatment guidelines recommend amphotericin B deoxycholate (AmB-d) plus high-dose fluconazole; outcomes with this treatment regimen in routine care settings have not been well described.MethodsElectronic national death registry data and computerized medical records were used to retrospectively collect demographic, laboratory, and 1-year outcome data from all patients with CM between 2012 and 2014 at Botswana’s main referral hospital, when recommended treatment for CM was AmB-d 1 mg/kg/d plus fluconazole 800 mg/d for 14 days. Cumulative survival was estimated at 2 weeks, 10 weeks, and 1 year.ResultsThere were 283 episodes of CM among 236 individuals; 69% (163/236) were male, and the median age was 36 years. All patients were HIV-infected, with a median CD4 count of 39 cells/mm3. Two hundred fifteen person-years of follow-up data were captured for the 236 CM patients. Complete outcome data were available for 233 patients (99%) at 2 weeks, 224 patients (95%) at 10 weeks, and 219 patients (93%) at 1 year. Cumulative mortality was 26% (95% confidence interval [CI], 20%–32%) at 2 weeks, 50% (95% CI, 43%–57%) at 10 weeks, and 65% (95% CI, 58%–71%) at 1 year.ConclusionsMortality rates following HIV-associated CM treated with AmB-d and fluconazole in a routine health care setting in Botswana were very high. The findings highlight the inadequacies of current antifungal treatments for HIV-associated CM and underscore the difficulties of administering and monitoring intravenous amphotericin B deoxycholate therapy in resource-poor settings.

Transfer Factor Revisited: Treatment of Chronic Mucocutaneous Candidiasis in a Child with Autoimmune Polyendocrinopathy Syndrome Type-1

A 5-year-old boy was diagnosed as having chronic mucocutaneous candidiasis at the age of three months. He showed no improvement despite treatment with two courses of intravenous amphotericin B, 2½ years of oral 5-fluorocytosine, and daily treatment with topical Mycostatin. An immune assessment revealed that he was anergic and had low levels of circulating FCγR+ monocytes. Buccal smears revealed numerous candida and no inflammatory response. On treatment with transfer factor his FCγR+ monocyte count increased from 10 to 429 cells/cumm.

Local Skin Inflammation in Cutaneous Leishmaniasis as a Source of Variable Pharmacokinetics and Therapeutic Efficacy of Liposomal Amphotericin B.

Disfiguring skin lesions caused by several species of the Leishmania parasite characterize cutaneous leishmaniasis (CL). Successful treatment of CL with intravenous (i.v.) liposomal amphotericin B (LAmB) relies on the presence of adequate antibiotic concentrations at the dermal site of infection within the inflamed skin. Here, we have investigated the impact of the local skin inflammation on the pharmacokinetics (PK) and efficacy of LAmB in two murine models of localized CL (Leishmania major and Leishmania mexicana) at three different stages of disease (papule, initial nodule, and established nodule). Twenty-four hours after the administration of one 25 mg/kg of body weight LAmB (i.v.) dose to infected BALB/c mice (n = 5), drug accumulation in the skin was found to be dependent on the causative parasite species (L. major > L. mexicana) and the disease stage (papule > initial nodule > established nodule > healthy skin). Elevated tissue drug levels were associated with increased vascular permeability (Evans blue assay) and macrophage infiltration (histomorphometry) in the infected skin, two pathophysiological parameters linked to tissue inflammation. After identical treatment of CL in the two models with 5 × 25 mg/kg LAmB (i.v.), intralesional drug concentrations and reductions in lesion size and parasite load (quantitative PCR [qPCR]) were all ≥2-fold higher for L. major than for L. mexicana In conclusion, drug penetration of LAmB into CL skin lesions could depend on the disease stage and the causative Leishmania species due to the influence of local tissue inflammation.

Retrobulbar optic neuropathy associated with sphenoid sinus mucormycosis.

Because fungi usually spread from the paranasal sinuses to the orbital apex in invasive fungal sinusitis (IFS), IFS often presents as an orbital apex syndrome (OAS) characterized by dysfunction of cranial nerves II, III, IV, V1, and VI. We report a case of sphenoid sinus mucormycosis that presented as isolated retrobulbar optic neuropathy. A 94‐year‐old woman presented with acute blindness in the right eye. Examination revealed the absence of light perception and pupillary reflex in the right eye. Head MRI showed a mass in the right sphenoid sinus, which was contiguous with the right optic nerve. She underwent endoscopic surgery, and a histopathological diagnosis of mucormycosis was established. Treatment with intravenous liposomal amphotericin B reduced the size of the mass. She has survived for more than 1 year without recurrence. Clinicians should consider that IFS can present as isolated retrobulbar optic neuropathy.

Cutaneous Manifestations of Disseminated Histoplasmosis in a Patient with AIDS

Introduction: Disseminated histoplasmosis is often seen in immunocompromised individuals, such those with acquired immunodeficiency syndrome (AIDS). The initial infection mainly involves the lungs but it may develop into a disseminated form especially in immunocompromised patients. Since it can be a systemic disease with cutaneous manifestations, dermatologists must be able to recognize its clinical presentation to ensure prompt management.Case: We present a man in his 50s with past medical history of AIDS who developed disseminated histoplasmosis with skin and gastrointestinal involvement over a one-month period of time. Despite receiving induction therapy with intravenous amphotericin B followed by oral itraconazole, the patient expired. His death was attributed to his persistently low CD4 T-cell count and secondary bacteremia.Discussion: This condition should be recognized early and treated aggressively. However, patients with multiple comorbidities are at increased risk of mortality even despite adequate treatment. This case highlights the significant mortality risk of disseminated histoplasmosis in patients with AIDS.

Systemic Antifungal Prophylaxis in Patients Hospitalized in Hematology Units in France: The AFHEM Cross-Sectional Observational Study.

IntroductionThe frequency of invasive fungal diseases (IFDs) has increased in recent years. Within a context where both treatments and guidelines are fast evolving, we aim to shed new light on IFD management in hematologic departments in France.MethodsA multicenter cross-sectional observational study was prospectively conducted in 24 French centers in September and October 2013.ResultsFour hundred ninety-four hospitalized children and adult patients suffering from hematologic malignancy were enrolled: 147 (30%) were allogeneic hematopoietic stem cell transplant (HSCT) recipients, 131 (27%) were patients with acute myeloblastic leukemia or myelodysplastic syndrome (MDS), 71 (14%) were patients with acute lymphoblastic leukemia who did not undergo allogeneic HSCT, and the 145 (29%) remaining patients did not belong to the three above groups. Two hundred forty-six patients (50%) received antifungal treatment, which was prophylactic in 187 (76%) treated patients. These rates were similar across all groups (63–80%). Patients received prophylaxis with an azole (79%), intravenous amphotericin B formulation (10%), echinocandin (9%), or two combination drugs (2%).ConclusionResults indicate that prophylaxis is the leading antifungal strategy in French hematology units, regardless of the disease condition, representing 76% of prescriptions for antifungal therapy.FundingAstellas Pharma France.

Sinonasal Mucormycosis: A to Z.

Mucormycosis caused by one of the members of Mucoraceae family, is one of the most rapidly spreading and fatal fungal infection occurring mostly in Diabetic or Immunocompromised patients especially in developing countries. 26 patients suffering from sinonasal mucormycosis admitted in SGRRIM&HS, Dehradun from January 2013 to January 2017 are discussed. Diagnosis of mucormycosis was established on strong clinical suspicion with presence of grayish black crusting on nasal endoscopy which is confirmed by histopathology examination. Immediate correction ofunderlying immunocompromised status with debridement with intravenous liposomal amphotericin B was done in all the 26 cases out of which 10 patients were cured. Early detection and aggressive multidisciplinary management is must for the successful treatment of mucormycosis.

Intracranial Cryptococcoma—Clinicopathologic Correlation and Surgical Outcome: A Single-Institution Experience

To describe clinical characteristics of patients with intracranial cryptococcoma, clinicopathologic findings, and outcomes after surgery. Clinical data were collected from hospital case records, and pathologic confirmation was done by a neuropathologist. Clinical details, imaging features, and treatment modalities were evaluated and correlated with outcomes based on regular follow-up. This case series included 5 cases of histology- and culture-proven intracranial cryptococcoma. Three patients (60%) were aged between the 3rd and 5th decades. Three cases were supratentorial in location, and 2 were in the posterior fossa. One patient presented with seizures. Three patients (60%) presented with fever. Three patients (60%) had papilledema, and 4 (80%) had signs of meningeal irritation. Four patients (80%) were immunocompetent. Only 1 patient was immunocompromised. All lesions were peripherally enhancing on computed tomography. Four of 5 patients underwent surgical decompression without any residue. Only 1 patient underwent stereotactic biopsy. All patients received antifungal therapy. One patient who was immunocompromised developed multiorgan failure and died after 2 months after surgery (20%). Of 5 cases, 4 (80%) had a good outcome with a mean follow-up of 5 years. Cryptococcus gattii is a rarer species implicated in intracranial cryptococcoma that is seen along with the more common Cryptococcus neoformans. Early diagnosis and surgical decompression followed by intravenous amphotericin B therapy for at least 6 weeks and concomitant therapy with fluconazole for prolonged periods may reduce morbidity and mortality.

Fungaemia caused by obstructive renal candida bezoars leads to bilateral chorioretinitis: a case report

BackgroundRenal fungal bezoars are remarkably rare and mostly occur in immunodeficient patients. Only a small number of cases with immunocompetent patients have been published so far. The published treatment approaches comprised systemic antimycotic therapy and surgical or minimal invasive removal of the fungal balls. In some cases irrigation of the renal duct system with amphotericin B was performed.By obstruction of the urinary tract bezoars can lead to infected hydronephrosis and severe urosepsis with high lethality. Fungaemia can cause fungal colonization in different distant organs. Fulminant chorioretinitis and irreversible visual impairment can be the consequence of ocular fundus colonization. The following report highlights that a co-operation between urologists and ophthalmologists is absolutely indispensible in case of fungaemia.Case presentationHereinafter we describe a case of an immunocompetent 56 years old woman, presenting with flank pain and shivering. The diagnosis turned out to be difficult due to initially negative urine culture. The fungaemia caused by obstructive nephropathy led to bilateral candida chorioretinitis. The patient was treated with intravenous amphotericin b and the bezoar was removed by percutaneous “nephrolitholapaxy”.After two months, a follow up revealed the patient felt well, chorioretinal lesions regressed and urine culture did not show any fungal growth.ConclusionTo the best of our knowledge, this is the first case reporting on obstructive renal bezoars, which lead to haematogenous fungus spread and bilateral chorioretinitis.It points out that extensive ophthalmologic examination should be performed in case of fungaemia even if the patient is not suffering from any visual impairment.

Mucopolysaccharidosis type VI, 9 sibling pairs and 1 set of three siblings: single center experience from Turkey

Invasive Trichosporon infections are rarely seen opportunistic fungal infections in children and mainly affect immunocompromised patients. This multicenter retrospective study has rewieved the characteristics, risk factors, treatment modalities and outcomes of bloodstream infections caused by Trichosporon species in children diagnosed over the past ten years in Turkey.The study was performed with the participation of 12 of 55 hospitals invited from Turkey. In each center, the patients with bloodstream infections caused by Trichosporon spp. between January 2010 and December 2020 were retrospectively ascertained and the results were reported to the study coordinator by means of a simple case report. Data were collected on patient demographics, underlying condition(s), treatment of.infections caused by Trichosporon spp, and 7 and 30- day mortality rates.A total of 28 cases with fungemia caused by Trichosporon spp. were included in the study. The most common underlying disease was paediatric cancers (39.3%). T. asahii infections were detected in 78.5 % (n=22) of patients. A various spectrum of antifungal treatment regimens were used including intravenous amphotericin B monotherapy in 35.7%, intravenous amphotericin B and voriconazole combination in 32.1% and intravenous voriconazole monotherapy in 28.6% of the patients. The overall mortality rate was 28.5 %. The mortality rates were 12.5% in the voricanozole, 30% in the amphotericin B and 33.3% in combined voriconazole -amphotericin B armsInvasive Trichosporon infections with an important impact of patients quality of life are almost related to underlying diseases with an overall mortality rate of 28.5%. Voriconazole was found to be associated with lower mortality rates when compared with other treatment regimens.

Cryptococcal Meningitis in Patient with Chronic Myeloid Leukemia

Objective: This study aimed to report the case of a female patient with chronic myeloid leukemia affected by cryptococcal meningitis. Case report: ML, white, 48 years old, female sex, previously diagnosed with chronic myeloid leukemia that has been refractive to the use of imatinib and who has recently begun using nilotinib, was admitted complaining of sudden and disabling migraine in the last 1 month associated with asthenia, adinamia, anorexia, disinterest for daily activities, dizziness, nausea, and vomiting. She evolved with ataxia, and started to stroll with help and showed decrease of muscular strength in her upper limbs. She also presented episodes of decrease of consciousness, with look fixation, no respond to sound stimulation, and short-term hearing loss. The cerebrospinal fluid showed presence of Cryptococcus sp. and, therefore, we began treatment with intravenous liposomal amphotericin B in the dose of 3 mg/kg/day, for 6 weeks. A new cerebrospinal fluid analysis, at the end of treatment, also showed rare structures that are compatible with Cryptococcus sp. As sequelae, she continued with hearing loss in her right ear and enhancement in her right auditory canal, seen in the magnetic resonance imaging. After stabilization and clinical improvement, she was discharged. After 3 weeks, she was hospitalized again with degeneration of the condition, and died due to intracranial hypertension secondary to cryptococcal infection. Final Considerations: This report reinforces the need of reflecting on fungi pathologies, especially in immunosuppressant patients, as well as the importance of early diagnosing and making a fast intervention, with the aims of providing quality of life and comfort to the patient and of minimizing neurological sequelae to the patient.

Periocular Cutaneous Mucormycosis Caused by Saksenaea erythrospora

Abstract Saksenaea erythrospora is a rare pathogen in humans. Ten adult cases have been previously reported, eight manifested with cutaneous infection, and two presented with invasive rhinosinusitis infection. The authors present a 16-month-old boy with progressive painful mass at the right medial canthus and upper cheek that was unresponsive to broad-spectrum antibiotics. He underwent an anterior orbitotomy and biopsy. Histopathology revealed broad nonseptate sterile hyphae and grew S. erythrospora, which was confirmed by molecular techniques. The patient was treated with intravenous liposomal amphotericin B and oral itraconazole combined with aggressive surgical debridement. The patient made a complete recovery without long-term complications at 4 months of follow-up. Primary cutaneous mucormycosis caused by S. erythrospora may rarely involve the periocular region and mimic chronic dacryocystitis. We report the first case of pediatric periocular cutaneous mucormycosis caused by S. erythrospora.

Aspergillus tamarii keratitis in a contact lens wearer

Keratitis produced by Aspergillus tamarii has been previously described associated to an ocular injury. We report a case in a contact lens wearer with a history of previous bilateral myopic LASIK ablation, bilateral intracorneal rings and vitrectomy and scleral buckling in his left eye. The fungus could be quickly identified combining phenotype, microscopy and mass spectrometry. Treatment with intravenous amphotericin, oral voriconazole, and topical amphotericin and natamycin and voriconazole was needed for corneal preservation.

Non-Exenteration Management of Sino-Orbital Fungal Disease.

To describe the non-exenteration management of sino-orbital fungal infection, a life-threatening condition for which orbital exenteration is generally considered a first-line treatment. A retrospective case series is presented of 7 orbits in 6 consecutive patients admitted and treated at 2 major metropolitan tertiary teaching hospitals in Sydney, New South Wales, Australia. Seven orbits in 6 consecutive patients with sino-orbital fungal infection were treated conservatively with surgical debridement and intravenous antifungal agents. Four patients were immunosuppressed and the other 2 patients were otherwise healthy. All presented with pain, proptosis, or loss of vision. Causative organisms found were Mucormycoses, Aspergillus, and Scedosporium prolificans. Exenteration was avoided in all patients as part of their planned management and 5 patients, including 1 with bilateral disease, survived their disease without exenteration. Medical treatment included intravenous liposomal amphotericin B or voriconazole. A single immunosuppressed patient deteriorated and as a last resort, exenteration was performed, but this made no difference to his clinical course and in retrospect could have been avoided as he died of multiple cerebral metastases diagnosed shortly after his deterioration. The authors recommend that patients with sino-orbital fungal disease preferably be treated conservatively, without orbital exenteration.