Could the Lung Be a Gateway for Amphotericin B to Attack the Army of Fungi?

Fungal diseases are a significant cause of morbidity and mortality worldwide, primarily affecting immunocompromised patients. Aspergillus, Pneumocystis, and Cryptococcus are opportunistic fungi and may cause severe lung disease. They can develop mechanisms to evade the host immune system and colonize or cause lung disease. Current fungal infection treatments constitute a few classes of antifungal drugs with significant fungi resistance development. Amphotericin B (AmB) has a broad-spectrum antifungal effect with a low incidence of resistance. However, AmB is a highly lipophilic antifungal with low solubility and permeability and is unstable in light, heat, and oxygen. Due to the difficulty of achieving adequate concentrations of AmB in the lung by intravenous administration and seeking to minimize adverse effects, nebulized AmB has been used. The pulmonary pathway has advantages such as its rapid onset of action, low metabolic activity at the site of action, ability to avoid first-pass hepatic metabolism, lower risk of adverse effects, and thin thickness of the alveolar epithelium. This paper presented different strategies for pulmonary AmB delivery, detailing the potential of nanoformulation and hoping to foster research in the field. Our finds indicate that despite an optimistic scenario for the pulmonary formulation of AmB based on the encouraging results discussed here, there is still no product registration on the FDA nor any clinical trial undergoing ClinicalTrial.gov.

Esporotricose pulmonar em paciente imunocompetente: relato de caso / Pulmonary sporotrichosis in immunocompetent patient: case report

A forma extracutânea pulmonar da esporotricose, uma infecção causada por espécies geneticamente distintas de um fungo dimórfico do gênero Sporothrix, é rara, com poucos casos relatados na literatura. Trata-se de um caso de uma mulher de 55 anos, residente da região do Barreiro de Belo Horizonte/Minas Gerais, que buscou o serviço de infectologia de um hospital público de Belo Horizonte com história de emagrecimento, dispneia aos pequenos esforços, tosse crônica e calafrios vespertinos de três anos de evolução. Foi tratada para pneumonia bacteriana, em cinco ocasiões, sem melhora clínica. Apresentou tomografia computadorizada de tórax com cavitação residual e lesões escavadas pulmonares. A paciente foi internada com quadro de dispneia aos pequenos esforços, tosse e expectoração purulenta, sendo sua cultura de escarro positiva para Sporothrix spp. Foi instituído o tratamento padrão ouro para esporotricose pulmonar, inicialmente, com itraconazol, 200 mg, duas vezes ao dia, entretanto, após 10 meses, a melhora clínica e radiológica não foi satisfatória e optou-se pela internação a administração de anfotericina B complexo lipídico endovenosa 4 mg/kg/dia. Em menos de 1 mês a paciente apresentou piora do quadro e evoluiu a óbito, apesar de ter recebido 2g de dose acumulada de anfotericina

The pulmonary extracutaneous form of sporotrichosis, an infection caused by genetically distinct species of a dimorphic fungus of the genus Sporothrix, is rare, with few cases reported in the literature. This is a case of a 55-year-old woman, resident of the Barreiro region in Belo Horizonte/ Minas Gerais, who sought the infectious disease service of a public hospital in Belo Horizonte with a history of weight loss, dyspnea at small efforts, chronic cough and three-year-old vespertinus chills. She was treated for bacterial pneumonia on five occasions without clinical improvement. He presented computed tomography of the chest with residual cavitation and excavated pulmonary lesions. The patient was hospitalized with dyspnea on small efforts, cough and purulent sputum, and her sputum culture was positive for Sporothrix spp. The gold standard treatment for pulmonary sporotrichosis was instituted, initially with itraconazole, 200 mg twice a day, however, after 10 months, the clinical and radiological improvement was not satisfactory and the administration of intravenous amphotericin B lipid complex 4 mg/kg/day was chosen. In less than 1 month the patient presented worsening of the condition and died, despite receiving 2g of accumulated dose of amphotericin B lipid complex.

Regulatory T cells in paracoccidioidomycosis.

This review addresses the role of regulatory T cells (Tregs), which are essential for maintaining peripheral tolerance and controlling pathogen immunity, in the host response against Paracoccidioides brasiliensis, a primary fungal pathogen. A brief introduction on the general features of Treg cells summarizes their main functions, subpopulations, mechanisms of suppression and plasticity. The main aspects of immunity in the diverse forms of the P. brasiliensis infection are presented, as are the few extant studies on the relevance of Treg cells in the control of severity of the human disease. Finally, the influence of Toll-like receptors, Dectin-1, NOD-like receptor P3 (NLRP3), Myeloid differentiation factor-88 (MyD88), as well as the enzyme indoleamine 2,3 dioxygenase (IDO) on the expansion and function of Treg cells in a murine model of pulmonary paracoccidioidomycosis (PCM) is also discussed. It is demonstrated that some of these components are involved in the negative control of Treg cell expansion, whereas others positively trigger the proliferation and activity of these cells. Finally, the studies here summarized highlight the dual role of Treg cells in PCM, which can be protective by controlling excessive immunity and tissue pathology but also deleterious by inhibiting the anti-fungal immunity necessary to control fungal growth and dissemination.

Cavitary Pulmonary Sporotrichosis: Case Report and Literature Review.

A case of cavitary pulmonary sporotrichosis without mucocutaneous involvement caused by Sporothrix schenckii is reported in a sexagenarian woman with a long smoking history. The patient was hospitalized for septic shock with multiorgan failure from a respiratory focus. The diagnosis was delayed due to the fungal etiological agent was not initially considered in the differential diagnosis. A good clinical and radiological evolution was obtained with the antifungal therapy. Occasional cases of primary pulmonary sporotrichosis have been reported in the literature. Due to its low incidence, this is a less-known and underestimated clinical form. Both clinical suspicion and microbiological studies are needed to reach pulmonary sporotrichosis diagnosis.

Tuberculosis and pulmonary candidiasis co-infection present in a previously healthy patient.

BACKGROUND: The coexistance among fungal pathogens and tuberculosis pulmonary is a clinical condition that generally occurs in immunosuppressive patients, however, immunocompetent patients may have this condition less frequently. OBJECTIVE: We report the case of an immunocompetent patient diagnosed with coinfection Mycobacterium tuberculosis and Candida albicans. CASE DESCRIPTION: A female patient, who is a 22-years old, with fever and a new onset of hemoptysis. CLINICAL FINDINGS AND DIAGNOSIS: Diminished vesicular breath sounds in the apical region and basal crackling rales in the left lung base were found in the physical examination. Microbiological tests include: chest radiography and CAT scan pictograms in high resolution, Ziehl-Neelsen stain, growth medium for fungus and mycobacteria through Sabouraudís agar method with D-glucose. Medical examinations showed Candida albicans fungus and Mycobacterium tuberculosis present in the patient. TREATMENT AND OUTCOME: Patient was treated with anti-tuberculosis and anti-fungal medications, which produced good responses. CLINICAL RELEVANCE: Pulmonary tuberculosis and fungal co-infection are not common in immunocompetent patients. However, we can suspect that there is a presence of these diseases by detecting new onset of hemoptysis in patients.

ANTECEDENTES: La coexistencia entre los hongos patógenos y la tuberculosis pulmonar es una condición clínica que se produce generalmente en pacientes inmunosuprimidos, sin embargo, los pacientes inmunocompetentes puede tener esta condición con menor frecuencia. OBJETIVO: Presentamos el caso de un paciente inmunocompetente con diagnóstico de una coinfección de tuberculosis Mycobacterium tuberculosis y Candida albicans. CASO CLÍNICO: Paciente femenina de 22 años con cuadro abrupto de tos, fiebre y hemoptisis sin antecedentes de enfermedad. HALLAZGOS CLÍNICOS Y MÉTODOS DIAGNÓSTICOS: Al examen respiratorio se halló disminución del murmullo vesicular en la región apical y estertores crepitantes basales en el pulmón izquierdo. Se realizó estudios microbiológicos de muestras tomadas por expectoración y por fibrobroncoscopia en el que se incluyó la tinción de Ziehl-Neelsen, cultivo para micobacteria y hongos en medio Agar Dextrosa Sabouraud y filamentización en suero obteniéndose positividad para Mycobacterium tuberculosis y Candida albicans. TRATAMIENTO Y RESULTADO: Se le realizó manejo con antifímicos de primera categoría y antimicóticos con buena respuesta clínica. RELEVANCIA CLÍNICA: La coinfección fúngica y tuberculosis pulmonar no es frecuente en pacientes inmunocompetentes, debe sospecharse en episodios abruptos de hemoptisis.

Tuberculosis and fungal co-infection present in a previously healthy patient / Coinfección de tuberculosis y candidiasis pulmonar en paciente previamente sana

Background: The coexistance among fungal pathogens and tuberculosis pulmonary is a clinical condition that generally occurs in immunosuppressive patients, however, immunocompetent patients may have this condition less frequently. Objective: We report the case of an immunocompetent patient diagnosed with coinfection Mycobacterium tuberculosis and Candida albicans. Case Description: A female patient, who is a 22-years old, with fever and a new onset of hemoptysis. Clinical findings and diagnosis: PDiminished vesicular breath sounds in the apical region and basal crackling rales in the left lung base were found in the physical examination. Microbiological tests include: chest radiography and CAT scan pictograms in high resolution, Ziehl-Neelsen stain, growth medium for fungus and mycobacteria through Sabouraudís agar method with D-glucose. Medical examinations showed Candida albicans fungus and Mycobacterium tuberculosis present in the patient. Treatment and Outcome: Patient was treated with anti-tuberculosis and anti-fungal medications, which produced good responses. Clinical relevance: Pulmonary tuberculosis and fungal co-infection are not common in immunocompetent patients. However, we can suspect that there is a presence of these diseases by detecting new onset of hemoptysis in patients.

Antecedentes: La coexistencia entre los hongos patógenos y la tuberculosis pulmonar es una condición clínica que se produce generalmente en pacientes inmunosuprimidos, sin embargo, los pacientes inmunocompetentes puede tener esta condición con menor frecuencia. Objetivo: Presentamos el caso de un paciente inmunocompetente con diagnóstico de una coinfección de tuberculosis Mycobacterium tuberculosis y Candida albicans. Caso clínico: Paciente femenina de 22 años con cuadro abrupto de tos, fiebre y hemoptisis sin antecedentes de enfermedad. Hallazgos clínicos y métodos diagnósticos: Al examen respiratorio se halló disminución del murmullo vesicular en la región apical y estertores crepitantes basales en el pulmón izquierdo. Se realizó estudios microbiológicos de muestras tomadas por expectoración y por fibrobroncoscopia en el que se incluyó la tinción de Ziehl-Neelsen, cultivo para micobacteria y hongos en medio Agar Dextrosa Sabouraud y filamentización en suero obteniéndose positividad para Mycobacterium tuberculosis y Candida albicans. Tratamiento y resultado: Se le realizó manejo con antifímicos de primera categoría y antimicóticos con buena respuesta clínica. Relevancia clínica: La coinfección fúngica y tuberculosis pulmonar no es frecuente en pacientes inmunocompetentes, debe sospecharse en episodios abruptos de hemoptisis.

Invasive pulmonary fungal infections in patients with connective tissue disease: a retrospective study from northern China

Invasive pulmonary fungal infection (IPFI) is a potentially fatal complication in patients with connective tissue disease (CTD). The current study aimed to uncover the clinical characteristics and risk factors of patients with IPFI-CTD. The files of 2186 CTD patients admitted to a single center in northern China between January 2011 and December 2013 were retrospectively reviewed. A total of 47 CTD patients with IPFI were enrolled into this study and assigned to the CTD-IPFI group, while 47 uninfected CTD patients were assigned to the control group. Clinical manifestations were recorded, and risk factors of IPFI were calculated by stepwise logistical regression analysis. Forty-seven (2.15%) CTD patients developed IPFI. Systemic lupus erythematosus patients were responsible for the highest proportion (36.17%) of cases with IPFI. Candida albicans (72.3%) accounted for the most common fungal species. CTD-IPFI patients had significantly elevated white blood cell count, erythrocyte sedimentation rate, C-reactive protein and fasting glucose values compared to controls (P<0.05). Cough, sputum and blood in phlegm were the most common symptoms. Risk factors of IPFI in CTD included maximum prednisone dose ≥30 mg/day within 3 months prior to infection, anti-microbial drug therapy, and interstitial pneumonia. CTD patients who have underlying interstitial pneumonia, prior prednisone or multiple antibiotics, were more likely to develop IPFI.