RESUMEN

Cladosporium cladosporioides are the pigmented soil fungi containing melanin. The aim of this work was to determine the influence of amphotericin B on free radicals in the natural melanin isolated from pigmented fungi Cladosporium cladosporioides and to compare it with the effect in synthetic DOPA-melanin. Electron paramagnetic resonance (EPR) spectra were measured at X-band (9.3 GHz) with microwave power in the range of 2.2-70 mW. Amplitudes, integral intensities, linewidths of the EPR spectra, and g factors, were analyzed. The concentrations of free radicals in the tested melanin samples were determined. Microwave saturation of EPR lines indicates the presence of pheomelanin in addition to eumelanin in Cladosporium cladosporioides. o-Semiquinone free radicals in concentrations ~1020 [spin/g] exist in the tested melanin samples and in their complexes with amphotericin B. Changes in concentrations of free radicals in the examined synthetic and natural melanin point out their participation in the formation of amphotericin B binding to melanin. A different influence of amphotericin B on free radical concentration in Cladosporium cladosporioides melanin and in DOPA-melanin may be caused by the occurrence of pheomelanin in addition to eumelanin in Cladosporium cladosporioides. The advanced spectral analysis in the wide range of microwave powers made it possible to compare changes in the free radical systems of different melanin polymers. This study is important for knowledge about the role of free radicals in the interactions of melanin with drugs.

Asunto(s)

Anfotericina B , Cladosporium , Melaninas , Melaninas/metabolismo , Cladosporium/efectos de los fármacos , Espectroscopía de Resonancia por Spin del Electrón/métodos , Anfotericina B/farmacología , Radicales Libres/metabolismo , Dihidroxifenilalanina/química , Dihidroxifenilalanina/metabolismo , Dihidroxifenilalanina/análogos & derivados

RESUMEN

The global rate of Amphotericin B (AmB) resistance in Candida auris has surpassed 12%. However, there is limited data on available clinical treatments and microevolutionary analyses concerning reduced AmB sensitivity. In this study, we collected 18 C. auris isolates from five patients between 2019 and 2022. We employed clinical data mining, genomic, and transcriptomic analyses to identify genetic evolutionary features linked to reduced AmB sensitivity in these isolates during clinical treatment. We identified six isolates with a minimum inhibitory concentration (MIC) of AmB below 0.5 µg/mL (AmB0.5) and 12 isolates with an AmB-MIC of 1 µg/mL (AmB1) or ≥ 2 µg/mL (AmB2). All five patients received 24-hour AmB (5 mg/L) bladder irrigation treatment. Evolutionary analyses revealed an ERG3 (c923t) mutation in AmB1 C. auris. Additionally, AmB2 C. auris was found to contain a t2831c mutation in the RAD2 gene. In the AmB1 group, membrane lipid-related gene expression (ERG1, ERG2, ERG13, and ERG24) was upregulated, while in the AmB2 group, expression of DNA-related genes (e.g. DNA2 and PRI1) was up-regulated. In a series of C.auris strains with reduced susceptibility to AmB, five key genes were identified: two upregulated (IFF9 and PGA6) and three downregulated (HGT7, HGT13,and PRI32). In this study, we demonstrate the microevolution of reduced AmB sensitivity in vivo and further elucidate the relationship between reduced AmB sensitivity and low-concentration AmB bladder irrigation. These findings offer new insights into potential antifungal drug targets and clinical markers for the "super fungus", C. auris.

Asunto(s)

Anfotericina B , Antifúngicos , Candida auris , Candidiasis , Farmacorresistencia Fúngica , Pruebas de Sensibilidad Microbiana , Humanos , Anfotericina B/farmacología , Antifúngicos/farmacología , China/epidemiología , Farmacorresistencia Fúngica/genética , Candidiasis/microbiología , Candidiasis/tratamiento farmacológico , Candida auris/genética , Candida auris/efectos de los fármacos , Evolución Molecular , Masculino , Mutación , Femenino , Persona de Mediana Edad , Proteínas Fúngicas/genética

RESUMEN

INTRODUCTION: Hemophagocytic lymphohistiocytosis characterized by hemophagocytosis leading to uncontrolled inflammation; the most common etiology in secondary cases of hemophagocytic lymphohistiocytosis is viral infections, especially Epstein-Barr virus. Visceral leishmaniasis is a vectorborne protozoal disease caused by Leishmania donovani complex. It is common in tropical and subtropical regions, with 50,000-90,000 new cases annually. CASE PRESENTATION: A 15-month-old Arab female was admitted to our hospital with 15 days of fever and decreased weight. On clinical examination, she had a markedly enlarged liver and spleen that were palpable 4 cm and 6 cm below the costal margin, respectively. The peripheral blood smear showed hypochromic microcytic anemia, poikilocytosis, reactive lymphocytosis, and mild thrombocytopenia. Bone marrow aspiration did not show malignancy or any other pathological findings. The patient was put on antibiotic therapy without improvement. Repeated bone marrow aspiration showed erythrophagocytosis; intracellular small round organisms looked like the amastigote form of Leishmania (Donovan bodies) with no evidence of malignancies. Her lab values showed ferritin greater than 500 ug/L, pancytopenia, and hypertriglyceridemia. The patient was diagnosed with hemophagocytic lymphohistiocytosis secondary to visceral leishmaniasis. CONCLUSION: Hemophagocytic lymphohistiocytosis secondary to visceral leishmaniasis is an extensively rare phenomenon in the medical literature that causes challenges in diagnosis and management. Steroids should be used wisely to not cover the symptoms of infections or malignancy, and amphotericin B resistance should be kept in mind in unresponsive Leishmania cases.

Asunto(s)

Anfotericina B , Antiprotozoarios , Leishmaniasis Visceral , Linfohistiocitosis Hemofagocítica , Leishmaniasis Visceral/tratamiento farmacológico , Leishmaniasis Visceral/complicaciones , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Linfohistiocitosis Hemofagocítica/complicaciones , Humanos , Femenino , Anfotericina B/uso terapéutico , Antiprotozoarios/uso terapéutico , Lactante , Resistencia a Medicamentos

RESUMEN

Objective: To investigate the efficacy and safety of liposomal amphotericin B (L-AmB) for the salvage treatment of invasive fungal disease (IFD) in patients with hematological diseases. Methods: Data were retrospectively collected from 80 patients with hematological issues treated with L-AmB between June 2023 and December 2023 after failure of previous antifungal therapy. Baseline patient information, clinical efficacy, and factors affecting the efficacy of L-AmB were analyzed by logistic regression. Moreover, adverse effects associated with L-AmB were evaluated. Results: Among the 80 patients, 9 (11.2%) had proven IFD, 43 (53.8%) had probable IFD, and 28 (35.0%) had possible IFD. The efficacy rate of L-AmB salvage therapy for IFD was 77.5%, with a median daily dose of 3 (range: 1-5) mg·kg(-1)·d(-1) and a median dosing course of 14 (range: 8-25) days. Multivariate logistic regression analysis showed that the disease remission status (OR=4.337, 95% CI 1.167-16.122, P=0.029) and duration of medication (OR=1.127, 95% CI 1.029-1.234, P=0.010) were independent factors affecting the efficacy of L-AmB. The incidence of infusion reactions associated with L-AmB, including fever and chills, was 5.0%. The incidence of hypokalemia was 28.8% (predominantly grades 1-2), and the incidence of nephrotoxicity was 11.3% (predominantly grades 1-2) . Conclusion: L-AmB is safe and effective in the treatment of patients with IFD who are intolerant to or who have experienced no effect of previous antifungal therapy, with a low rate of adverse reactions.

Asunto(s)

Anfotericina B , Antifúngicos , Enfermedades Hematológicas , Infecciones Fúngicas Invasoras , Terapia Recuperativa , Humanos , Anfotericina B/administración & dosificación , Anfotericina B/efectos adversos , Anfotericina B/uso terapéutico , Estudios Retrospectivos , Antifúngicos/administración & dosificación , Antifúngicos/efectos adversos , Antifúngicos/uso terapéutico , Terapia Recuperativa/métodos , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Enfermedades Hematológicas/complicaciones , Resultado del Tratamiento , Masculino , Femenino , Persona de Mediana Edad

RESUMEN

BACKGROUND: Reports of pulmonary aspergillosis and mucormycosis co-infections are rare; thus, limited guidance is available on early diagnosis and treatment. We present a case of mixed pulmonary Aspergillus and Mucor infection and review the literature regarding this co-infection. The diagnosis and treatment methods are summarized to improve clinicians' understanding of the disease and to facilitate early diagnosis and treatment. CASE PRESENTATION: A 60-year-old male farmer with poorly controlled diabetes mellitus was admitted to hospital with a fever of unknown origin that had been present for 15 days and pulmonary aspergillosis complicated by Mucor spp. INFECTION: Because multiple lobes were involved, the infection worsened despite surgical resection and antifungal therapy. Finally, we treated this patient with a bronchoscopic infusion of amphotericin B. After four courses of bronchoscopic amphotericin B infusion, we observed rapid clinical improvement and subsequent resolution of pulmonary infiltrates. CONCLUSION: Our case highlights the use of bronchoscopy in the successful clinical treatment of invasive fungal diseases of the lung.

Asunto(s)

Anfotericina B , Antifúngicos , Broncoscopía , Mucormicosis , Aspergilosis Pulmonar , Humanos , Masculino , Anfotericina B/administración & dosificación , Anfotericina B/uso terapéutico , Persona de Mediana Edad , Mucormicosis/tratamiento farmacológico , Mucormicosis/diagnóstico , Antifúngicos/administración & dosificación , Antifúngicos/uso terapéutico , Aspergilosis Pulmonar/tratamiento farmacológico , Aspergilosis Pulmonar/diagnóstico , Coinfección/tratamiento farmacológico , Mucor/aislamiento & purificación , Tomografía Computarizada por Rayos X

RESUMEN

Amphotericin B has long been crucial for treating many serious infectious diseases, such as invasive fungal infections and visceral leishmaniasis, particularly for patients who are immunocompromised, including those with advanced HIV infection. The conventional amphotericin B deoxycholate formulation has largely been replaced in high-income countries with liposomal amphotericin B (LAmB), which has many advantages, including lower rates of adverse events, such as nephrotoxicity and anaemia. Despite an evident need for LAmB in low-income and middle-income countries, where mortality from invasive fungal infections is still substantial, many low-income and middle-income countries still often use the amphotericin B deoxycholate formulation because of a small number of generic formulations and the high price of the originator LAmB. The pricing of LAmB is also highly variable between countries. Overcoming supply barriers through the availability of additional quality-assured, generic formulations of LAmB at accessible prices would substantially facilitate equitable access and have a substantial effect on mortality attributable to deadly fungal infections.

Asunto(s)

Anfotericina B , Antifúngicos , Humanos , Anfotericina B/economía , Antifúngicos/economía , Antifúngicos/provisión & distribución , Antifúngicos/uso terapéutico , Accesibilidad a los Servicios de Salud , Salud Global , Países en Desarrollo , Medicamentos Genéricos/economía , Medicamentos Genéricos/provisión & distribución

RESUMEN

Histoplasmosis capsulatum is a dimorphic fungus, recognised for its endemic presence in multiple global regions. It may cause severe opportunistic disseminated infection in immunocompromised individuals. This is a case report of a 33-year-old man from Thailand who was admitted at a Danish hospital with fever, weight loss, cough, nosebleeds, and newly diagnosed HIV. The clinical condition rapidly deteriorated with lung and kidney failure. The patient was diagnosed with H. capsulatum fungaemia first detected on blood smear. He was treated with intravenous amphotericin B followed by oral itraconazole as well as antiretroviral therapy.

Asunto(s)

Infecciones Oportunistas Relacionadas con el SIDA , Antifúngicos , Histoplasma , Histoplasmosis , Humanos , Masculino , Adulto , Histoplasmosis/tratamiento farmacológico , Histoplasmosis/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Histoplasma/aislamiento & purificación , Antifúngicos/uso terapéutico , Antifúngicos/administración & dosificación , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Anfotericina B/uso terapéutico , Anfotericina B/administración & dosificación , Itraconazol/uso terapéutico , Itraconazol/administración & dosificación , Huésped Inmunocomprometido

RESUMEN

Mucormycosis is an invasive fungal infection that can result in severe lung infections, with pulmonary mucormycosis (PM) being one of the most prevalent manifestations. Prompt diagnosis is crucial for patient survival, as PM often exhibits rapid clinical progression and carries a high fatality rate. Broncho-alveolar lavage fluid or endobronchial biopsy (EBB) has been commonly employed for diagnosing PM, although there is limited mention of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the literature. In this report, we present a case of PM in a patient with diabetes. While EBB did not yield evidence of Rhizopus infection, a definitive diagnosis was obtained through EBUS-TBNA. The patient underwent combination therapy, including oral medication, nebulization, and EBUS-guided intrafocal amphotericin B injection, which resulted in significant improvement following the failure of initial therapy with amphotericin B injection cholesterol sulfate complex. Our case highlights the potential of EBUS-TBNA not only for mediastinal lymphadenopathy but also for obtaining extraluminal lesion specimens. Furthermore, for patients with an inadequate response to mono-therapy and no access to surgical therapy, the addition of EBUS-guided intralesional amphotericin B injection to systemic intravenous therapy may yield unexpected effects.

Asunto(s)

Anfotericina B , Antifúngicos , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Enfermedades Pulmonares Fúngicas , Mucormicosis , Humanos , Anfotericina B/administración & dosificación , Mucormicosis/diagnóstico , Mucormicosis/tratamiento farmacológico , Antifúngicos/administración & dosificación , Enfermedades Pulmonares Fúngicas/tratamiento farmacológico , Enfermedades Pulmonares Fúngicas/diagnóstico , Enfermedades Pulmonares Fúngicas/microbiología , Masculino , Resultado del Tratamiento , Inyecciones Intralesiones , Persona de Mediana Edad , Broncoscopía

RESUMEN

INTRODUCTION: The present study investigated the impact of immune recovery and the duration of antifungal adherence in the consolidation phase of disseminated histoplasmosis (DH) in acquired immune deficiency syndrome (AIDS) patients living in a hyperendemic area in northeastern Brazil. MATERIAL AND METHODS: Sixty-nine patients with DH/AIDS, admitted to the São José Hospital between 2010 and 2015, who continued histoplasmosis consolidation therapy at the outpatient clinic were studied. The follow-up duration was at least 24 months. RESULTS: Sixty-eight patients used itraconazole 200-400 mg/day or amphotericin B deoxycholate weekly during the consolidation phase, and six patients relapsed during follow-up. The overall median duration of consolidation antifungal use was 250 days [IQR 101 - 372]. Antifungal withdrawal by medical decision occurred in 41 patients (70.7 %) after a median of 293 days [IQR 128 - 372] of use; 16 patients discontinued by their own decision, with a median of 106 days [IQR 37 - 244] of therapy; three patients had no information available, and nine continued on AF therapy. The median CD4+ T-cell count in the group without relapse was 248 cells/µL [IQR 115-355] within 6 months after admission; conversely, in the relapse group, the median cell count remained below 100 cells/µL. Irregular adherence to highly active antiretroviral therapy (HAART) was the leading risk factor associated with relapse and death (p< 0.01). DISCUSSION: The regular use of HAART, combined with immune recovery, proved to be highly effective in preventing relapses in DH/AIDS patients, suggesting that long-term antifungal therapy may not be necessary.

Asunto(s)

Infecciones Oportunistas Relacionadas con el SIDA , Síndrome de Inmunodeficiencia Adquirida , Anfotericina B , Antifúngicos , Ácido Desoxicólico , Histoplasmosis , Humanos , Histoplasmosis/tratamiento farmacológico , Histoplasmosis/inmunología , Masculino , Femenino , Antifúngicos/uso terapéutico , Antifúngicos/administración & dosificación , Adulto , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/inmunología , Persona de Mediana Edad , Ácido Desoxicólico/uso terapéutico , Ácido Desoxicólico/administración & dosificación , Anfotericina B/uso terapéutico , Anfotericina B/administración & dosificación , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/inmunología , Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Recuento de Linfocito CD4 , Brasil/epidemiología , Itraconazol/uso terapéutico , Itraconazol/administración & dosificación , Reconstitución Inmune , Combinación de Medicamentos , Quimioterapia de Consolidación , Estudios Retrospectivos , Cumplimiento de la Medicación/estadística & datos numéricos , Recurrencia , Duración de la Terapia , Resultado del Tratamiento , Estudios de Seguimiento , Terapia Antirretroviral Altamente Activa

RESUMEN

PURPOSE: Visceral leishmaniasis (VL) is caused by an intracellular parasite that is transmitted to humans by sandfly bites. It is prevalent throughout Asia, Africa, the Americas, and the Mediterranean area, where 147 million people are at risk of contracting the illness. The manifestation of heterotrophic illness relies on both Leishmania implicated and the host's immunological response, ranging from asymptomatic to severe leishmaniasis with potentially lethal effects. METHOD: We reviewed the literature (published till 31st December 2023) on the worldwide situation of leishmaniasis, standard and novel detection techniques, and traditional and modern treatment strategies and endeavors to eliminate VL. Moreover, epidemiological data was collected from the World Health Organization's publicly available databases. GraphPad Prism Version 8 was used to analyze and produce figures based on the epidemiological data. RESULTS: Diagnosis of parasites in tissues or serology is commonly employed. Diagnosis by identifying parasite DNA using molecular techniques is becoming more popular. Despite recent findings of L. donovani resistance to pentavalent antimoniate medications, it continues to be the cornerstone in the medical management of VL. Amphotericin B and its lipid formulations, injectable paromomycin, and oral miltefosine are among the new therapy options being researched. The number of reported VL cases has reduced remarkably over the last decade due to human interventions made to eliminate VL. Particularly countries from the South East Asian region have experienced momentous progress in reducing VL cases and eliminating this disease from this region. Owing to the robust elimination programs, countries such as Bangladesh has eliminated VL as a public health concern. India and Nepal are on the verge of its elimination. CONCLUSION: Rapid diagnosis, effective and inexpensive treatment, simple access to newly discovered medications, appropriate vector control, and a well-designed vaccine are all required for the elimination of this disease burden in impoverished areas of the globe.

Asunto(s)

Leishmaniasis Visceral , Leishmaniasis Visceral/epidemiología , Leishmaniasis Visceral/tratamiento farmacológico , Leishmaniasis Visceral/diagnóstico , Leishmaniasis Visceral/prevención & control , Humanos , Asia Sudoriental/epidemiología , Antiprotozoarios/uso terapéutico , Erradicación de la Enfermedad , Leishmania donovani/inmunología , Leishmania donovani/efectos de los fármacos , Animales , Anfotericina B/uso terapéutico

RESUMEN

Introduction. Sporotrichosis is a subcutaneous infection caused by dimorphic Sporothrix species embedded in the clinical clade. Fungi have virulence factors, such as biofilm and melanin production, which contribute to their survival and are related to the increase in the number of cases of therapeutic failure, making it necessary to search for new options.Gap statement. Proton pump inhibitors (PPIs) have already been shown to inhibit the growth and melanogenesis of other fungi.Aim. Therefore, this study aimed to evaluate the effect of the PPIs omeprazole (OMP), rabeprazole (RBP), esomeprazole, pantoprazole and lansoprazole on the susceptibility and melanogenesis of Sporothrix species, and their interactions with itraconazole, terbinafine and amphotericin B.Methodology. The antifungal activity of PPIs was evaluated using the microdilution method, and the combination of PPIs with itraconazole, terbinafine and amphotericin B was assessed using the checkerboard method. The assessment of melanogenesis inhibition was assessed using grey scale.Results. The OMP and RBP showed significant MIC results ranging from 32 to 256 µg ml-1 and 32 to 128 µg ml-1, respectively. Biofilms were sensitive, with a significant reduction (P<0.05) in metabolic activity of 52% for OMP and 50% for RBP at a concentration of 512 µg ml-1 and of biomass by 53% for OMP and 51% for RBP at concentrations of 512 µg ml-1. As for the inhibition of melanogenesis, only OMP showed inhibition, with a 54% reduction.Conclusion. It concludes that the PPIs OMP and RBP have antifungal activity in vitro against planktonic cells and biofilms of Sporothrix species and that, in addition, OMP can inhibit the melanization process in Sporothrix species.

Asunto(s)

Anfotericina B , Antifúngicos , Melanogénesis , Inhibidores de la Bomba de Protones , Sporothrix , Esporotricosis , Humanos , Anfotericina B/farmacología , Anfotericina B/uso terapéutico , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Itraconazol/farmacología , Melaninas/biosíntesis , Melaninas/metabolismo , Melanogénesis/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Inhibidores de la Bomba de Protones/farmacología , Inhibidores de la Bomba de Protones/uso terapéutico , Sporothrix/efectos de los fármacos , Sporothrix/metabolismo , Esporotricosis/tratamiento farmacológico , Esporotricosis/microbiología , Terbinafina/farmacología

RESUMEN

INTRODUCTION: New diagnostic methods and antifungal strategies may improve prognosis of mucormycosis. We describe the diagnostic value of metagenomic next⁃generation sequencing (mNGS) and identify the prognostic factors of mucormycosis. METHODS: We conducted a retrospective study of hematologic patients suffered from mucormycosis and treated with monotherapy [amphotericin B (AmB) or posaconazole] or combination therapy (AmB and posaconazole). The primary outcome was 84-day all-cause mortality after diagnosis. RESULTS: Ninety-five patients were included, with "proven" (n = 27), "probable" (n = 16) mucormycosis confirmed by traditional diagnostic methods, and "possible" (n = 52) mucormycosis with positive mNGS results. The mortality rate at 84 days was 44.2%. Possible + mNGS patients and probable patients had similar diagnosis processes, overall survival rates (44.2% vs 50.0%, p = 0.685) and overall response rates to effective drugs (44.0% vs 37.5%, p = 0.647). Furthermore, the median diagnostic time was shorter in possible + mNGS patients than proven and probable patients (14 vs 26 days, p < 0.001). Combination therapy was associated with better survival compared to monotherapy at six weeks after treatment (78.8% vs 53.1%, p = 0.0075). Multivariate analysis showed that combination therapy was the protective factor (HR = 0.338, 95% CI: 0.162-0.703, p = 0.004), though diabetes (HR = 3.864, 95% CI: 1.897-7.874, p < 0.001) and hypoxemia (HR = 3.536, 95% CI: 1.874-6.673, p < 0.001) were risk factors for mortality. CONCLUSIONS: Mucormycosis is a life-threatening infection. Early management of diabetes and hypoxemia may improve the prognosis. Exploring effective diagnostic and treatment methods is important, and combination antifungal therapy seems to hold potential benefits.

Asunto(s)

Anfotericina B , Antifúngicos , Enfermedades Hematológicas , Secuenciación de Nucleótidos de Alto Rendimiento , Mucormicosis , Humanos , Mucormicosis/diagnóstico , Mucormicosis/tratamiento farmacológico , Mucormicosis/mortalidad , Mucormicosis/microbiología , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Pronóstico , Antifúngicos/uso terapéutico , Adulto , Anciano , Enfermedades Hematológicas/complicaciones , Anfotericina B/uso terapéutico , Metagenómica/métodos , Triazoles/uso terapéutico , Adulto Joven , Quimioterapia Combinada , Análisis de Supervivencia , Resultado del Tratamiento

RESUMEN

Mucormycosis is a rare fungal infection caused by fungi of the Mucorales order that occurs in immunocompromised individuals or with loss of skin or mucosa barrier integrity. This report presents four cases of rhinocerebral mucormycosis attended at a third-level hospital in Cali (Colombia) during a period of three years. All patients had different case histories and times of evolution. All four had a previous or de novo diagnosis of type 2 diabetes mellitus, with glycated hemoglobin higher than 10% on admission. We ruled out other possible pathologies that could explain their immunocompromised condition. Mucormycosis diagnosis was made with direct visualization of hyaline coenocytic hyphae on biopsies. The basis of treatment was liposomal amphotericin B and surgical debridement. Two patients presented bacterial coinfection. One asked for voluntary discharge without having completed the treatment, and another one died. The remaining two have attended controls and had an adequate evolution.

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La mucormicosis es una infección fúngica poco frecuente causada por hongos del orden Mucorales, la cual se presenta en individuos inmunocomprometidos o con pérdida de la integridad de la barrera de piel o mucosas. Se reportan cuatro casos de mucormicosis rinocerebral atendidos en un hospital de tercer nivel de Cali (Colombia) durante un periodo de tres años. Los cuatro pacientes presentaron diferentes cuadros clínicos y tiempos de evolución. Todos tenían diagnóstico de diabetes mellitus de tipo 2, de novo o previo, con una hemoglobina glucosilada de ingreso mayor del 10 % y en todos se descartaron otras enfermedades que explicaran su compromiso inmunitario. La mucormicosis se diagnosticó por la visualización directa de hifas hialinas sincitiales (coenocytic) en las biopsias tomadas. El pilar del tratamiento fue la anfotericina B liposómica junto con el desbridamiento quirúrgico. Dos pacientes presentaron coinfección bacteriana. De los cuatro, uno firmó su egreso voluntario sin completar el tratamiento y otro falleció. Los dos pacientes restantes han asistido a los controles y han mostrado una adecuada evolución.

Asunto(s)

Anfotericina B , Mucormicosis , Humanos , Mucormicosis/diagnóstico , Masculino , Persona de Mediana Edad , Anfotericina B/uso terapéutico , Femenino , Antifúngicos/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Anciano , Desbridamiento , Huésped Inmunocomprometido

RESUMEN

Leishmaniasis, attributed to the protozoan parasite Leishmania, manifests in diverse clinical forms, including cutaneous, mucocutaneous, and visceral leishmaniasis; VL constitutes a significant global health menace. Prevalent in tropical and subtropical regions, this affliction disproportionately impacts individuals below the poverty threshold, transmitted through the bite of female sandflies. Existing treatments, such as pentavalent antimony, miltefosine, and Amphotericin B, exhibit limitations. Despite the emergence of liposomal Amphotericin B (AmBisome) as a promising antileishmanial agent, its utility is impeded by adverse effects, elevated production expenses, and cytotoxicity. To address these challenges, our investigation introduces a potential remedy─a citrate-coated gold Amphotericin B nanoparticle formulation. Characterized using dynamic light scattering and transmission electron microscopy, this pioneering formulation exhibited efficacy against L. donovani Ag83 promastigotes as demonstrated by MTT cell viability testing. Evaluating internal reactive oxygen species (ROS) levels and dual staining with acridine orange and ethidium bromide unveiled its consequential impact on cell death. Significantly, our study discloses this novel nanoformulation's unprecedented inhibition of the trypanothione reductase enzyme. The findings posit the citrate-coated gold Amphotericin B nanoformulation as a promising and targeted antileishmanial agent, representing potential advancements in leishmaniasis therapeutics.

Asunto(s)

Anfotericina B , Antiprotozoarios , Oro , Nanopartículas del Metal , Oro/química , Oro/farmacología , Anfotericina B/farmacología , Anfotericina B/química , Antiprotozoarios/farmacología , Antiprotozoarios/química , Antiprotozoarios/síntesis química , Nanopartículas del Metal/química , Tamaño de la Partícula , Nanoconjugados/química , Ensayo de Materiales , Leishmania donovani/efectos de los fármacos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/síntesis química , Supervivencia Celular/efectos de los fármacos , Pruebas de Sensibilidad Parasitaria , Especies Reactivas de Oxígeno/metabolismo , Humanos

Asunto(s)

Anfotericina B , Antifúngicos , Candida , Farmacorresistencia Fúngica Múltiple , Sinergismo Farmacológico , Lansoprazol , Anfotericina B/farmacología , Antifúngicos/farmacología , Lansoprazol/farmacología , Humanos , Candida/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Candidiasis/microbiología , Candidiasis/tratamiento farmacológico

RESUMEN

The scintillating association between Leishmania and HIV has contributed exceptionally towards expansion of Visceral Leishmaniasis (VL) with Acquired Immunodeficiency Syndrome (AIDS). The co-infection poses a grievous threat to elimination of VL and containment of Human Immunodeficiency Virus (HIV). When coinfected, Leishmania and HIV complement each other's proliferation and survival by inducing immunesenescence, T cell fatigue and exhaustion. Antigen presentation is lost, co-stimulatory molecules are diminished whereas co-inhibitory molecules such as CTLA-4, TIGIT, LAG-3 etc. are upregulated to ensure a Th2-baised immune environment. As a consequence, Leishmania-HIV coinfection causes poor outcomes, inflates the spread of Leishmania parasites, enhances the severity of side-effects to drugs, as well as escalate the probability of treatment failure and mortality. What makes control extremely strenuous is that there are frequent episodes of VL relapse with no prognostic markers, no standard immunophenotype(s) and appearance of atypical clinical symptoms. Thus, a standard therapeutic regimen has been difficult to develop and treatment is majorly dependent upon a combination of liposomal Amphotericin B and Miltefosine, a therapy that is expensive and capable of causing drastic side-effects in recipients. As World Health Organization is committed to eliminate both VL and HIV in due course of future, the existing therapeutic interventions require advancements to grapple and overcome this hazardous co-infection. In this context, an overview of HIV-VL co-infection, immunopathology of HIV and Leishmania co-inhabitance, available therapeutic options and their limitations in the treatment of co-infection are discussed in-depth.

Asunto(s)

Coinfección , Infecciones por VIH , Leishmaniasis Visceral , Humanos , Coinfección/parasitología , Infecciones por VIH/complicaciones , Infecciones por VIH/inmunología , Infecciones por VIH/tratamiento farmacológico , Leishmaniasis Visceral/inmunología , Leishmaniasis Visceral/tratamiento farmacológico , Leishmaniasis Visceral/complicaciones , Leishmaniasis Visceral/epidemiología , Anfotericina B/uso terapéutico , Comorbilidad , Antiprotozoarios/uso terapéutico , Fosforilcolina/uso terapéutico , Fosforilcolina/análogos & derivados , Fosforilcolina/farmacología , Leishmania/inmunología

RESUMEN

Cryptococcosis is a fungal infection that is becoming increasingly prevalent worldwide, particularly among individuals with compromised immune systems, such as HIV patients. Amphotericin B (AmB) is the first-line treatment mainly combined with flucytosine. The scarcity and the prohibitive cost of this regimen urge the use of fluconazole as an alternative, leading to increased rates of treatment failure and relapses. Therefore, there is a critical need for efficient and cost-effective therapy to enhance the efficacy of AmB. In this study, we evaluated the efficacy of the HIV protease inhibitors (PIs) to synergize the activity of AmB in the treatment of cryptococcosis. Five PIs (ritonavir, atazanavir, saquinavir, lopinavir, and nelfinavir) were found to synergistically potentiate the killing activity of AmB against Cryptococcus strains with Æ©FICI ranging between 0.09 and 0.5 against 20 clinical isolates. This synergistic activity was further confirmed in a time-kill assay, where different AmB/PIs combinations exhibited fungicidal activity within 24 hrs. Additionally, PIs in combination with AmB exhibited an extended post-antifungal effect on treated cryptococcal cells for approximately 10 hrs compared to 4 hours with AmB alone. This promising activity against cryptococcal cells did not exhibit increased cytotoxicity towards treated kidney cells, ruling out the risk of drug combination-induced nephrotoxicity. Finally, we evaluated the efficacy of AmB/PIs combinations in the Caenorhabditis elegans model of cryptococcosis, where these combinations significantly reduced the fungal burden of the treated nematodes by approximately 2.44 Log10 CFU (92.4%) compared to the untreated worms and 1.40 Log10 ((39.4%) compared to AmB alone. The cost-effectiveness and accessibility of PIs in resource-limited geographical areas compared to other antifungal agents, such as flucytosine, make them an appealing choice for combination therapy.

Asunto(s)

Anfotericina B , Antifúngicos , Criptococosis , Sinergismo Farmacológico , Inhibidores de la Proteasa del VIH , Anfotericina B/farmacología , Anfotericina B/uso terapéutico , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Inhibidores de la Proteasa del VIH/uso terapéutico , Inhibidores de la Proteasa del VIH/farmacología , Animales , Criptococosis/tratamiento farmacológico , Humanos , Caenorhabditis elegans/microbiología , Caenorhabditis elegans/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Cryptococcus neoformans/efectos de los fármacos , Quimioterapia Combinada , Ritonavir/uso terapéutico , Ritonavir/farmacología , Cryptococcus/efectos de los fármacos

RESUMEN

Mucormycosis is a rare opportunistic infection caused by Mucorales fungi. Cutaneous mucormycosis typically present as chronic indolent infection, whereas rhino-orbital mucormycosis is rapidly progressive disease often invade the adjacent cerebral tissue associated with high mortality. This case represents the atypical clinical history of rhino-orbital-cutaneous mucormycosis. The patient was presented with a right orbital cellulitis associated with an extensive multiple suppurative deep cutaneous infection and worsening headache. The skin lesion was initiated from a localized abscess at the right periorbital area nine months before admission. Suspicion of fungal infection was raised after weeks of non-responsive antibiotics treatment. Aggressive treatment with exoneration of the right eye and surgical debridement was undertaken. Periodic acid Schiff staining from healthy periorbital tissue revealed ribbon-like hyphae with pauciseptate and 90° branching identified as Mucoraceaefamily. The resolution was seen after four weeks of antifungal treatment with Amphotericin B.

Asunto(s)

Anfotericina B , Antifúngicos , Desbridamiento , Mucormicosis , Humanos , Mucormicosis/diagnóstico , Antifúngicos/administración & dosificación , Anfotericina B/administración & dosificación , Anfotericina B/uso terapéutico , Masculino , Desbridamiento/métodos , Dermatomicosis/diagnóstico , Dermatomicosis/microbiología , Dermatomicosis/tratamiento farmacológico , Inmunocompetencia , Celulitis Orbitaria/diagnóstico , Celulitis Orbitaria/microbiología , Enfermedades Orbitales/diagnóstico , Enfermedades Orbitales/microbiología , Enfermedades Orbitales/terapia , Mucorales/aislamiento & purificación , Persona de Mediana Edad , Cefalea/etiología

RESUMEN

We present a case of a 56-year-old female with rheumatoid arthritis (RA) who has been on methotrexate for 9 years and has been complaining of high-grade fever for the past 1 month with no localizing signs and symptoms. She was thoroughly evaluated before being labeled as pyrexia of unknown origin. Histoplasmosis was suspected after bone marrow aspiration smear examination. The presence of histoplasma antigen in the urine confirmed our diagnosis. Fever responded after 2 weeks of liposomal amphotericin B and patient discharged in stable condition on tablet itraconazole.

Asunto(s)

Anfotericina B , Artritis Reumatoide , Fiebre de Origen Desconocido , Histoplasmosis , Humanos , Histoplasmosis/diagnóstico , Histoplasmosis/complicaciones , Histoplasmosis/tratamiento farmacológico , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/diagnóstico , Femenino , Persona de Mediana Edad , Fiebre de Origen Desconocido/etiología , Fiebre de Origen Desconocido/diagnóstico , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Histoplasma/aislamiento & purificación , Itraconazol/uso terapéutico

RESUMEN

This study aimed to estimate the cost-effectiveness of four therapeutic approaches available for mucosal leishmaniasis in Brazil: miltefosine, meglumine antimoniate, combined with and without pentoxifylline, and liposomal amphotericin B. The perspective adopted was that of the Brazilian Unified National Health System (SUS). The outcome of interest was "cured patient", which was analyzed using a decision tree model. Estimates of direct costs and effectiveness were obtained from the scientific literature. Meglumine antimoniate alone was the base comparator strategy; liposomal amphotericin B showed an incremental cost-effectiveness ratio (ICER) of USD 7,409.13 per cured patient, and the combination of meglumine antimoniate with pentoxifylline presented an ICER of USD 85.13. Miltefosine was absolutely dominated, with higher cost and similar effectiveness when compared to meglumine antimoniate. Sensitivity analyses, varying the cost by ±25%, did not change the results. However, when the cost of miltefosine was estimated at less than USD 171.23, this strategy was dominant over meglumine antimoniate alone. The results confirm that treatment with liposomal amphotericin B remains the option with the highest ICER among the approaches analyzed. Miltefosine may be cost-effective based on the variation in the acquisition price, which deserves attention because it is the only available oral option. The non-accounting of other aspects prevent the use of these results immediately to support decision-making, but they point out the need to negotiate the prices of drugs available for mucosal leishmaniasis and indicates the need of encouraging technology transfer or other actions aimed at expanding the performance of the Brazilian national industrial complex.

Asunto(s)

Anfotericina B , Antiprotozoarios , Análisis Costo-Beneficio , Leishmaniasis Mucocutánea , Antimoniato de Meglumina , Meglumina , Compuestos Organometálicos , Pentoxifilina , Fosforilcolina , Humanos , Fosforilcolina/análogos & derivados , Fosforilcolina/economía , Fosforilcolina/uso terapéutico , Leishmaniasis Mucocutánea/tratamiento farmacológico , Leishmaniasis Mucocutánea/economía , Antiprotozoarios/economía , Antiprotozoarios/uso terapéutico , Anfotericina B/economía , Anfotericina B/uso terapéutico , Brasil , Meglumina/economía , Meglumina/uso terapéutico , Antimoniato de Meglumina/uso terapéutico , Antimoniato de Meglumina/economía , Compuestos Organometálicos/uso terapéutico , Compuestos Organometálicos/economía , Pentoxifilina/economía , Pentoxifilina/uso terapéutico , Quimioterapia Combinada/economía , Programas Nacionales de Salud/economía