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Trimethoprim-sulfamethoxazole resistance in Staphylococcus Aureus in Africa: distribution of resistance genes and evaluation of the success of major MRSA clones

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Resumo:Staphylococcus aureus is a major pathogen worldwide due to its remarkable ability to develop resistance to antibiotics coupled with the emergence of highly virulent strains. Trimethoprim-sulfamethoxazole (SXT) is a fixed-dose combination of the antifolate compounds trimethoprim and sulfamethoxazole, which act synergistically by inhibiting distinct steps in the synthesis of bacterial folic acid. SXT is recommended as a first-line treatment of uncomplicated urinary tract infections and skin and soft tissue infections. It is also prescribed for respiratory infections and is widely used in resource-constrained areas as a prophylaxy among HIV-infected or HIV-exposed children. Very high SXT resistance rates have been reported among S. aureus isolates from the African continent, namely among major methicillin-resistant S. aureus (MRSA) clonal types circulating in Portuguese-speaking African countries, such as Angola, São Tomé and Príncipe and Cape Verde. The aim of the present study was to provide new insights on the high rates of SXT-resistant S. aureus isolates in the African continent. Furthermore, we also evaluated the success of three major MRSA clones in Portuguese-speaking African countries by comparing with the Brazilian MRSA-ST239-III (or variant ST241-III), also resistant to SXT, which is widely spread all over the word but not detected so far in Portuguese-speaking African countries. Our results demonstrated for the first time an SXT-hetero-resistance phenotype, highly frequent in S. aureus isolates from Africa. We also evidenced a wide prevalence of dfrG gene in Portuguese-speaking African countries, reinforcing its potential origin in the African continent. Since these countries present important demographic and economic exchanges with Portugal, future spread of dfrG within MRSA in populations where antifolate resistance is currently considered to be low should be monitored. Moreover, we showed that the epidemiological success of the major MRSA clones in Portuguese-speaking African countries may be due to their capacity to survive under different stress situations including a better adaptation to alkaline conditions, and to their potential to outgrow other epidemic SXT-resistant MRSA lineages such as the Brazilian clone.
Autores principais:Coelho, Céline Catherine Bottineau
Assunto:Staphylococcus aureus MRSA Resistência aos antibióticos Sulfametoxazol Trimetoprim Timetoprim-sulfametoxazol África Teses de mestrado - 2016
Ano:2016
País:Portugal
Tipo de documento:dissertação de mestrado
Tipo de acesso:acesso aberto
Instituição associada:Universidade de Lisboa
Idioma:inglês
Origem:Repositório da Universidade de Lisboa
Descrição
Resumo:Staphylococcus aureus is a major pathogen worldwide due to its remarkable ability to develop resistance to antibiotics coupled with the emergence of highly virulent strains. Trimethoprim-sulfamethoxazole (SXT) is a fixed-dose combination of the antifolate compounds trimethoprim and sulfamethoxazole, which act synergistically by inhibiting distinct steps in the synthesis of bacterial folic acid. SXT is recommended as a first-line treatment of uncomplicated urinary tract infections and skin and soft tissue infections. It is also prescribed for respiratory infections and is widely used in resource-constrained areas as a prophylaxy among HIV-infected or HIV-exposed children. Very high SXT resistance rates have been reported among S. aureus isolates from the African continent, namely among major methicillin-resistant S. aureus (MRSA) clonal types circulating in Portuguese-speaking African countries, such as Angola, São Tomé and Príncipe and Cape Verde. The aim of the present study was to provide new insights on the high rates of SXT-resistant S. aureus isolates in the African continent. Furthermore, we also evaluated the success of three major MRSA clones in Portuguese-speaking African countries by comparing with the Brazilian MRSA-ST239-III (or variant ST241-III), also resistant to SXT, which is widely spread all over the word but not detected so far in Portuguese-speaking African countries. Our results demonstrated for the first time an SXT-hetero-resistance phenotype, highly frequent in S. aureus isolates from Africa. We also evidenced a wide prevalence of dfrG gene in Portuguese-speaking African countries, reinforcing its potential origin in the African continent. Since these countries present important demographic and economic exchanges with Portugal, future spread of dfrG within MRSA in populations where antifolate resistance is currently considered to be low should be monitored. Moreover, we showed that the epidemiological success of the major MRSA clones in Portuguese-speaking African countries may be due to their capacity to survive under different stress situations including a better adaptation to alkaline conditions, and to their potential to outgrow other epidemic SXT-resistant MRSA lineages such as the Brazilian clone.