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Antibiotic combination therapy vs monotherapy for Pseudomonas aeruginosa infections : a systematic review
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Contextualização: Pseudomonas aeruginosa é um agente oportunista prevalente tanto em infeções nosocomiais como adquiridas na comunidade. Constitui uma ameaça à saúde pública, dado associar-se a infeções difíceis de tratar com elevadas taxas de morbilidade e mortalidade. A capacidade deste microrganismo de desenvolver resistência a múltiplos antibióticos torna a abordagem destas infeções um verdadeiro desafio. Esta revisão sistemática pretende comparar a eficácia da terapia antibiótica combinada versus monoterapia no tratamento de infeções por P. aeruginosa. Ao avaliar vários outcomes clínicos, esta revisão tem como objetivo fornecer informações para otimizar a estratégias de tratamento para este microrganismo multirresistente. Métodos: Foi realizada uma pesquisa através das bases de dados PubMed, Scopus e Cochrane. Foram incluídos 25 estudos observacionais prospetivos e retrospetivos, com um total de 5767 participantes e 5824 episódios de infeções a P. aeruginosa. A validade interna dos estudos foi avaliada através da escala de Newcastle-Ottawa. Resultados: A evidência sugere que não há diferenças significativas entre terapêutica combinada e monoterapia em termos de mortalidade, cura clínica, cura microbiológica, duração da hospitalização, emergência de resistência, recorrência da infeção e efeitos adversos para tratamento empírico e dirigido. A terapia inapropriada está associada a uma maior taxa de mortalidade do que terapia apropriada, o que se mostrou importante na abordagem antibiótica inicial. A terapêutica combinada está associada a uma maior probabilidade de atingir uma estratégia empírica inicial apropriada. Para além disso, a antibioterapia combinada mostrou melhores resultados em doentes neutropénicos, com mais comorbilidades e em doentes com infeções graves, com sépsis ou choque. Conclusão: Por aumentar a probabilidade de uma estratégia antibiótica inicial apropriada, a terapêutica combinada deve ser utilizada no tratamento empírico. Após conhecimento do resultado dos testes de susceptibilidade aos antibióticos, a monoterapia é considerada uma opção segura na maioria das situações clínicas.
Background: Pseudomonas aeruginosa, an opportunistic pathogen prevalent in both environmental and hospital settings, poses a substantial threat to public health by causing infections that are notoriously difficult to treat, frequently leading to severe morbidity and mortality. Its ability to develop resistance to multiple antibiotics further complicates treatment strategies, making effective management a clinical challenge. This systematic review aims to analyse the comparative effectiveness of antibiotic combination therapy versus monotherapy in managing P. aeruginosa infections. By evaluating a broad spectrum of clinical outcomes, this review aims to provide valuable insights into optimizing treatment protocols for this resilient pathogen. Methods: A systematic search was performed using PubMed, Scopus and Cochrane databases. 25 observational prospective and retrospective studies were included, with a total of 5767 participants and 5824 evaluable episodes of P. aeruginosa infections. The internal validity was assessed using the Newcastle-Ottawa scale for cohort studies. Results: The findings suggest that there were no significant differences between combination therapy and monotherapy regarding mortality, clinical cure, microbiological cure, length of hospital stay, emergence of resistance, recurrence of infection, and adverse events for both empirical and definitive treatment. Inappropriate therapy was associated with higher mortality rates than appropriate therapy, which is particularly important during initial treatment. Combination therapy demonstrated an increased likelihood of providing an appropriate initial empirical therapy. Additionally, combination therapy showed better outcomes for neutropenic patients, those with multiple comorbidities, and severely ill patients with conditions such as sepsis or shock. Conclusion: Combination therapy should be employed in empirical treatment as it enhances the likelihood of reaching appropriate therapy. Therefore, the recommended approach for these infections is to initiate combination therapy until the results of antibiotic susceptibility tests are obtained, after what monotherapy is considered safe for most indications.
Background: Pseudomonas aeruginosa, an opportunistic pathogen prevalent in both environmental and hospital settings, poses a substantial threat to public health by causing infections that are notoriously difficult to treat, frequently leading to severe morbidity and mortality. Its ability to develop resistance to multiple antibiotics further complicates treatment strategies, making effective management a clinical challenge. This systematic review aims to analyse the comparative effectiveness of antibiotic combination therapy versus monotherapy in managing P. aeruginosa infections. By evaluating a broad spectrum of clinical outcomes, this review aims to provide valuable insights into optimizing treatment protocols for this resilient pathogen. Methods: A systematic search was performed using PubMed, Scopus and Cochrane databases. 25 observational prospective and retrospective studies were included, with a total of 5767 participants and 5824 evaluable episodes of P. aeruginosa infections. The internal validity was assessed using the Newcastle-Ottawa scale for cohort studies. Results: The findings suggest that there were no significant differences between combination therapy and monotherapy regarding mortality, clinical cure, microbiological cure, length of hospital stay, emergence of resistance, recurrence of infection, and adverse events for both empirical and definitive treatment. Inappropriate therapy was associated with higher mortality rates than appropriate therapy, which is particularly important during initial treatment. Combination therapy demonstrated an increased likelihood of providing an appropriate initial empirical therapy. Additionally, combination therapy showed better outcomes for neutropenic patients, those with multiple comorbidities, and severely ill patients with conditions such as sepsis or shock. Conclusion: Combination therapy should be employed in empirical treatment as it enhances the likelihood of reaching appropriate therapy. Therefore, the recommended approach for these infections is to initiate combination therapy until the results of antibiotic susceptibility tests are obtained, after what monotherapy is considered safe for most indications.
Descrição
Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2024
Palavras-chave
Pseudomonas aeruginosa Terapia combinada Monoterapia Mortalidade Cura clínica Emergência de resistência Doenças transmissíveis