Artículo
Carbapenem Combinations for Infections Caused by Carbapenemase-Producing Pseudomonas aeruginosa: Experimental In Vitro and In Vivo Analysis
Autor/es | Herrera Espejo, Soraya
Del Barrio-Tofiño, Ester Cebrero Cangueiro, Tania López Causapé, Carla Álvarez Marín, Rocío Cisneros, José Miguel ![]() ![]() ![]() ![]() ![]() ![]() ![]() Pachón Díaz, Jerónimo ![]() ![]() ![]() ![]() ![]() ![]() ![]() Oliver, Antonio Pachón Ibáñez, María Eugenia |
Departamento | Universidad de Sevilla. Departamento de Medicina |
Fecha de publicación | 2022-09-07 |
Fecha de depósito | 2023-04-28 |
Publicado en |
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Resumen | In the context of difficult-to-treat carbapenem-resistant Pseudomonas aeruginosa infections, we evaluated imipenem, meropenem, and doripenem combinations against eleven carbapenemase-producing P. aeruginosa isolates. ... In the context of difficult-to-treat carbapenem-resistant Pseudomonas aeruginosa infections, we evaluated imipenem, meropenem, and doripenem combinations against eleven carbapenemase-producing P. aeruginosa isolates. According to the widespread global distribution of high-risk clones and carbapenemases, four representative isolates were selected: ST175 (OXA-2/VIM-20), ST175 (VIM-2), ST235 (GES-5), and ST111 (IMP-33), for efficacy studies using a sepsis murine model. Minimum inhibitory concentration (mg/L) ranges were 64–256 for imipenem and 16–128 for meropenem and doripenem. In vitro, imipenem plus meropenem was synergistic against 72% of isolates and doripenem plus meropenem or imipenem against 55% and 45%, respectively. All combinations were synergistic against the ST175, ST235, and ST155 clones. In vivo, meropenem diminished the spleen and blood bacterial concentrations of four and three isolates, respectively, with better efficacy than imipenem or doripenem. The combinations did not show efficacy compared with the more active monotherapies, except for imipenem plus meropenem, which reduced the ST235 bacterial spleen concentration. Mortality decreased with imipenem plus meropenem or doripenem for the ST175 isolate. Results suggest that carbapenem combinations are not an alternative for severe infections by carbapenemase-producing P. aeruginosa. Meropenem monotherapy showed in vivo efficacy despite its high MIC, probably because its dosage allowed a sufficient antimicrobial exposure at the infection sites. |
Agencias financiadoras | CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III Fondo Europeo de Desarrollo Regional (FEDER) Instituto de Salud Carlos III, Proyectos de Investigacion en Salud Servicio Andaluz de Salud, Junta de Andalucia Red Española de Investigación en Enfermedades Infecciosas (REIPI) Ministerio de Economía, Industria y Competitividad |
Identificador del proyecto | CB21/13/00006
![]() CB21/13/00099 ![]() PI18-01842 ![]() C1-0038-2019 ![]() RD16/0016/0004 ![]() RD16/0016/0009 ![]() |
Cita | Herrera Espejo, S., Del Barrio-Tofiño, E., Cebrero Cangueiro, T., López Causapé, C., Álvarez Marín, R., Cisneros, J.M.,...,Pachón Ibáñez, M.E. (2022). Carbapenem Combinations for Infections Caused by Carbapenemase-Producing Pseudomonas aeruginosa: Experimental In Vitro and In Vivo Analysis. Antibiotics, 11 (9), 1212. https://doi.org/10.3390/antibiotics11091212. |
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