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Mycobacterium tuberculosis e resistência a fármacos
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Resumo(s)
A acumulação de resistências do Mycobacterium tuberculosis aos antibióticos deu origem a estirpes multirresistentes, causando Tuberculose Multirresistente (MDR-TB) e Tuberculose Extensivamente Resistente (XDR-TB), o que constitui um grave problema de saúde pública tanto em países desenvolvidos como subdesenvolvidos.
Objetivos: caraterização da epidemiologia da tuberculose resistente a fármacos (DR-TB) e seu tratamento, mecanismos de resistência aos fármacos de primeira linha e aos mais utilizados de segunda linha, testes de suscetibilidade, coinfecção com o HIV/SIDA, caso particular da resistência associada à etnia e cenário português.
Conclusões: A OMS estima que cerca de 3,7% dos novos casos e 20% dos casos previamente tratados possuem MDR-TB, com a XDR-TB a representar cerca de 9% dos casos de MDR-TB a nível mundial. O tratamento da MDR-TB dura 20 meses e é feito com 4 fármacos de segunda linha e pirazinamida; a XDR-TB segue a mesma linha, mas podem ter de ser adicionados fármacos de terceira linha. As mutações que conferem resistência aos principais fármacos estão maioritariamente descritas, permitindo o desenvolvimento de novos fármacos e testes de suscetibilidade. Os Testes de Suscetibilidade a Fármacos (DST) mais rápidos não estão acessíveis a todos os países devido aos elevados custos, colocando em risco o tratamento adequado do doente. A coinfecção com o HIV/SIDA pode acelerar a propagação e alcance da DR-TB. As etnias hispânica e asiática são as mais associadas à DR-TB. Portugal apresenta taxas de DR-TB preocupantes, especialmente em Lisboa, com relatos de 52,3% de XDR-TB entre os casos de MDR-TB. Tal pode dever-se à pobre contenção das estirpes da Família Lisboa e à prescrição frequente de fluoroquinolonas.
The accumulation of antibiotic resistance by Mycobacterium tuberculosis has resulted in multiresistant strains, leading to Multidrug-resistant tuberculosis (MDR-TB) and Extensively drug-resistant tuberculosis (XDR-TB), being a major public health problem in both developed and underdeveloped countries. Objectives: characterization of drug-resistant tuberculosis (DR-TB) epidemiology and treatment, resistance mechanisms to first line and main second line antibiotics, drug susceptibility testing, HIV/AIDS co-infection, ethnic associated resistance and the Portuguese case scenario. Conclusions: The WHO estimates that 3.7% of new cases and 20% of retreatment cases possess MDR-TB, with XDR-TB representing about 9% of MDR-TB cases worldwide. MDR-TB treatment lasts for 20 months and is consists of 4 second-line drugs in addition to pyrazinamide; XDR-TB treatment follows the same lines, although third-line drugs may have to be added. Most resistance conferring mutations for the mainly used drugs are already described, allowing the development of new drugs and drug susceptibility tests (DST). The fastest DST is not accessible to every country due to their high price, risking patient adequate treatment. HIV/AIDS co-infection can accelerate propagation and reach of DR-TB. Asian and Hispanic ethnicities are the most associated with DR-TB. Portugal presents worrisome DR-TB rates, especially in Lisbon, where reports claim 52.3% of XDR-TB among MDR-TB cases. Poor containment of the Lisboa Family strains and high fluoroquinolone prescription are plausible explanations for that fact.
The accumulation of antibiotic resistance by Mycobacterium tuberculosis has resulted in multiresistant strains, leading to Multidrug-resistant tuberculosis (MDR-TB) and Extensively drug-resistant tuberculosis (XDR-TB), being a major public health problem in both developed and underdeveloped countries. Objectives: characterization of drug-resistant tuberculosis (DR-TB) epidemiology and treatment, resistance mechanisms to first line and main second line antibiotics, drug susceptibility testing, HIV/AIDS co-infection, ethnic associated resistance and the Portuguese case scenario. Conclusions: The WHO estimates that 3.7% of new cases and 20% of retreatment cases possess MDR-TB, with XDR-TB representing about 9% of MDR-TB cases worldwide. MDR-TB treatment lasts for 20 months and is consists of 4 second-line drugs in addition to pyrazinamide; XDR-TB treatment follows the same lines, although third-line drugs may have to be added. Most resistance conferring mutations for the mainly used drugs are already described, allowing the development of new drugs and drug susceptibility tests (DST). The fastest DST is not accessible to every country due to their high price, risking patient adequate treatment. HIV/AIDS co-infection can accelerate propagation and reach of DR-TB. Asian and Hispanic ethnicities are the most associated with DR-TB. Portugal presents worrisome DR-TB rates, especially in Lisbon, where reports claim 52.3% of XDR-TB among MDR-TB cases. Poor containment of the Lisboa Family strains and high fluoroquinolone prescription are plausible explanations for that fact.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2013
Palavras-chave
DST MDR-TB Mutações XDR-TB Mestrado Integrado - 2013