Inhaled amikacin for pneumonia treatment and dissemination prevention

Pseudomonas aerugino sa pneumonia is commonly treated with systemic antibiotics to ensure adequate treatment of multidrug resistant (MDR) bacteria. However, intravenous (IV) antibiotics often achieve suboptimal pulmonary concentrations. We therefore aimed to evaluate the effect of inhaled amikacin (...

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Detalles Bibliográficos
Autores: Motos, Ana|||0000-0002-3757-1232, Yang, Hua, Li Bassi, Gianluigi, Yang, Minlan, Meli, Andrea, Battaglini, Denise, Cabrera, Roberto, Bobi, Joaquim|||0000-0002-9026-5226, Pagliara, Francesco, Frigola, Gerard|||0000-0001-6794-6456, Camprubí-Rimblas, Marta|||0000-0002-4085-5324, Fernández Barat, Laia|||0000-0001-7528-9636, Rigol, Montserrat, Ferrer-Segarra, Antoni, Kiarostami, Kasra, Martínez Hernández, Daniel|||0000-0001-7492-5311, Nicolau, David P., Artigas Raventós, Antoni|||0000-0002-8029-1017, Pelosi, Paolo|||0000-0001-5055-3023, Vila Estapé, Jordi|||0000-0002-8025-3926, Torres, Antoni|||0000-0002-8643-2167
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:273245
Acceso en línea:https://ddd.uab.cat/record/273245
https://dx.doi.org/urn:doi:10.1186/s13054-023-04331-x
Access Level:acceso abierto
Palabra clave:Inhaled amikacin
Severe pneumonia
Pseudomonas aeruginosa
Animal model
Multidrug resistance
Monolateral pneumonia
Descripción
Sumario:Pseudomonas aerugino sa pneumonia is commonly treated with systemic antibiotics to ensure adequate treatment of multidrug resistant (MDR) bacteria. However, intravenous (IV) antibiotics often achieve suboptimal pulmonary concentrations. We therefore aimed to evaluate the effect of inhaled amikacin (AMK) plus IV meropenem (MEM) on bactericidal efficacy in a swine model of monolateral MDR P. aeruginosa pneumonia. We ventilated 18 pigs with monolateral MDR P. aeruginosa pneumonia for up to 102 h. At 24 h after the bacterial challenge, the animals were randomized to receive 72 h of treatment with either inhaled saline (control), IV MEM only, or IV-MEM plus inhaled AMK (MEM + AMK). We dosed IV MEM at 25 mg/kg every 8 h and inhaled AMK at 400 mg every 12 h. The primary outcomes were the P. aeruginosa burden and histopathological injury in lung tissue. Secondary outcomes included the P. aeruginosa burden in tracheal secretions and bronchoalveolar lavage fluid, the development of antibiotic resistance, the antibiotic distribution, and the levels of inflammatory markers. The median (25-75th percentile) P. aeruginosa lung burden for animals in the control, MEM only, and MEM + AMK groups was 2.91 (1.75-5.69), 0.72 (0.12-3.35), and 0.90 (0-4.55) log CFU/g (p = 0.009). Inhaled therapy had no effect on preventing dissemination compared to systemic monotherapy, but it did have significantly higher bactericidal efficacy in tracheal secretions only. Remarkably, the minimum inhibitory concentration of MEM increased to.

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