Inhaled amikacin for pneumonia treatment and dissemination prevention : an experimental model of severe monolateral Pseudomonas aeruginosa pneumonia
Motos, Ana (Centro de Investigación Biomédica en Red de Enfermedades Respiratorias)
Yang, Hua (Universitat de Barcelona)
Li Bassi, Gianluigi (Critical Care Research Group, The Prince Charles Hospital, University of Queensland, Queensland University of Technology, UnitingCare Hospitals, Wesley Medical Research, Brisbane, Australia)
Yang, Minlan (Universitat de Barcelona)
Meli, Andrea (Università degli Studi di Milano)
Battaglini, Denise (San Martino Policlinico Hospital)
Cabrera, Roberto (Centro de Investigación Biomédica en Red de Enfermedades Respiratorias)
Bobi, Joaquim (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Pagliara, Francesco (IRCCS for Oncology and Neurosciences. Anesthesia and Critical Care, San Martino Policlinico Hospital)
Frigola, Gerard (Hospital Clínic i Provincial de Barcelona)
Camprubí-Rimblas, Marta (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Fernández-Barat, Laia (Centro de Investigación Biomédica en Red de Enfermedades Respiratorias)
Rigol, Montserrat (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Ferrer-Segarra, Antoni (Parc de Salut MAR de Barcelona)
Kiarostami, Kasra (Universitat de Barcelona)
Martinez, Daniel (Hospital Clínic i Provincial de Barcelona)
Nicolau, David P. (Hartford Hospital)
Artigas Raventós, Antoni (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Pelosi, Paolo (Università degli Studi di Genova)
Vila, Jordi (Centro de Investigación Biomédica en Red de Enfermedades Infecciosas)
Torres, Antoni (Centro de Investigación Biomédica en Red de Enfermedades Respiratorias)
Universitat Autònoma de Barcelona

Fecha:	2023
Resumen:	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 > 32 mg/L after 72-h exposure to monotherapy in 83% of animals, while the addition of AMK prevented this increase (p = 0. 037). Adjunctive therapy also slightly affected interleukin-1β downregulation. Despite finding high AMK concentrations in pulmonary samples, we found no paired differences in the epithelial lining fluid concentration between infected and non-infected lungs. Finally, a non-significant trend was observed for higher amikacin penetration in low-affected lung areas. In a swine model of monolateral MDR P. aeruginosa pneumonia, resistant to the inhaled AMK and susceptible to the IV antibiotic, the use of AMK as an adjuvant treatment offered no benefits for either the colonization of pulmonary tissue or the prevention of pathogen dissemination. However, inhaled AMK improved bacterial eradication in the proximal airways and hindered antibiotic resistance. The online version contains supplementary material available at 10. 1186/s13054-023-04331-x.
Ayudas:	Ministerio de Sanidad y Consumo CB06/06/0028 Fundació la Marató de TV3 201831-10 Agència de Gestió d'Ajuts Universitaris i de Recerca SGR/944
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Inhaled amikacin ; Severe pneumonia ; Pseudomonas aeruginosa ; Animal model ; Multidrug resistance ; Monolateral pneumonia
Publicado en:	Critical Care, Vol. 27 (february 2023) , ISSN 1466-609X

DOI: 10.1186/s13054-023-04331-x
PMID: 36788582

11 p, 3.7 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Instituto de Investigación e Innovación Parc Taulí (I3PT)
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