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Aspergilose invasiva por Aspergillus fumigatus refractária à terapêutica : breakthrough infection vs resistência aos anti-micóticos
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doente hemato-oncológico reveste-se de grande complexidade, que se apresenta em crescendo ao longo dos anos com o advento de novas terapêuticas-alvo para as neoplasias hematopoiéticas, mas também na profilaxia da infecção como grande complicação no decorrer do tratamento e da doença. A abordagem quer-se cada vez mais personalizada, princípio da prática clínica que também rege a profilaxia das infecções destes doentes profundamente imunodeprimidos. A utilização de anti-fúngicos e as suas novas formulações, em esquema de profilaxia, torna-se um desafio, na medida em que há que conseguir uma harmonia entre os anti-neoplásicos e os mesmos, para mitigar toxicidades, sem que haja detrimento da cobertura dos agentes causadores. Por vezes, mesmo sob profilaxia, surgem Breaktrough Invasive Mold infections (bIMIs). A propósito de um caso clínico de uma doente de 61 anos, com uma LMA secundária à terapêutica, complicada por uma aspergilose pulmonar invasiva, e sob profilaxia com anfotericina B Lipossómica, propõe-se discutir a gestão desta infecção como paradigma das bIMIs. Simultaneamente, e partindo das especificidades deste caso, pretende-se expor a problemática das breakthrough infections em doentes sob profilaxia, a optimização da abordagem, do diagnóstico, qual a pertinência do fungigrama e os obstáculos à sua aplicação, as variáveis condicionantes da escolha do anti-fúngico adequado, quer para profilaxia, quer para tratamento, e o impacto da actuação clínica em termos de pressão selectiva farmacológica quanto à emergência de estirpes resistentes.
The haemato-oncological patient is highly complex, and this complexity has grown over the years with the advent of new target therapies for haematopoietic malignancies, but also in the prophylaxis of infection as a major complication during treatment and illness. The approach is becoming increasingly personalised, a principle of clinical practice that also governs the prophylaxis of infections in these profoundly immunosuppressed patients. The use of anti-fungals and their new formulations in prophylaxis schemes is becoming a challenge, as harmony must be achieved between anti-neoplastics and anti-fungals in order to mitigate toxicities without jeopardising coverage of the causative agents. Sometimes, even under prophylaxis, breakthrough invasive mould infections (bIMIs) occur. Based on a clinical case of a 61-year-old patient with AML secondary to therapy, complicated by invasive pulmonary aspergillosis and under prophylaxis with liposomal amphotericin B, we propose to discuss the management of this infection as a paradigm for bIMIs. At the same time, and based on the specifics of this case, the aim is to explain the problem of breakthrough infections in patients under prophylaxis, the optimisation of the approach, the diagnosis, the relevance of the fungigram and the obstacles to its application, the variables implicated in the choice of the appropriate anti-fungal, both for prophylaxis and treatment, and the clinical impact of the selective pharmacological pressure on the emergence of resistant strains.
The haemato-oncological patient is highly complex, and this complexity has grown over the years with the advent of new target therapies for haematopoietic malignancies, but also in the prophylaxis of infection as a major complication during treatment and illness. The approach is becoming increasingly personalised, a principle of clinical practice that also governs the prophylaxis of infections in these profoundly immunosuppressed patients. The use of anti-fungals and their new formulations in prophylaxis schemes is becoming a challenge, as harmony must be achieved between anti-neoplastics and anti-fungals in order to mitigate toxicities without jeopardising coverage of the causative agents. Sometimes, even under prophylaxis, breakthrough invasive mould infections (bIMIs) occur. Based on a clinical case of a 61-year-old patient with AML secondary to therapy, complicated by invasive pulmonary aspergillosis and under prophylaxis with liposomal amphotericin B, we propose to discuss the management of this infection as a paradigm for bIMIs. At the same time, and based on the specifics of this case, the aim is to explain the problem of breakthrough infections in patients under prophylaxis, the optimisation of the approach, the diagnosis, the relevance of the fungigram and the obstacles to its application, the variables implicated in the choice of the appropriate anti-fungal, both for prophylaxis and treatment, and the clinical impact of the selective pharmacological pressure on the emergence of resistant strains.
Descrição
Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2024
Palavras-chave
Leucemia mielóide aguda (LMA) Venetoclax Anfotericina B lipossómica Breakthrough invasive mould infection (bIMI) Aspergillus fumigatus Doenças transmissíveis