Carbapenem Combinations for Infections Caused by Carbapenemase-Producing <i>Pseudomonas aeruginosa</i>: Experimental In Vitro and In Vivo Analysis
In the context of difficult-to-treat carbapenem-resistant <i>Pseudomonas aeruginosa</i> infections, we evaluated imipenem, meropenem, and doripenem combinations against eleven carbapenemase-producing <i>P. aeruginosa</i> isolates. According to the widespread global distributi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-09-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/11/9/1212 |
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| author | Soraya Herrera-Espejo Ester Del Barrio-Tofiño Tania Cebrero-Cangueiro Carla López-Causapé Rocío Álvarez-Marín José Miguel Cisneros Jerónimo Pachón Antonio Oliver María Eugenia Pachón-Ibáñez |
| author_facet | Soraya Herrera-Espejo Ester Del Barrio-Tofiño Tania Cebrero-Cangueiro Carla López-Causapé Rocío Álvarez-Marín José Miguel Cisneros Jerónimo Pachón Antonio Oliver María Eugenia Pachón-Ibáñez |
| author_sort | Soraya Herrera-Espejo |
| collection | DOAJ |
| description | In the context of difficult-to-treat carbapenem-resistant <i>Pseudomonas aeruginosa</i> infections, we evaluated imipenem, meropenem, and doripenem combinations against eleven carbapenemase-producing <i>P. aeruginosa</i> 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 <i>P. aeruginosa</i>. Meropenem monotherapy showed in vivo efficacy despite its high MIC, probably because its dosage allowed a sufficient antimicrobial exposure at the infection sites. |
| first_indexed | 2024-03-10T00:54:31Z |
| format | Article |
| id | doaj.art-1c8e6b36b7f44bc9ab3a84a1b000384f |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-10T00:54:31Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-1c8e6b36b7f44bc9ab3a84a1b000384f2023-11-23T14:44:56ZengMDPI AGAntibiotics2079-63822022-09-01119121210.3390/antibiotics11091212Carbapenem Combinations for Infections Caused by Carbapenemase-Producing <i>Pseudomonas aeruginosa</i>: Experimental In Vitro and In Vivo AnalysisSoraya Herrera-Espejo0Ester Del Barrio-Tofiño1Tania Cebrero-Cangueiro2Carla López-Causapé3Rocío Álvarez-Marín4José Miguel Cisneros5Jerónimo Pachón6Antonio Oliver7María Eugenia Pachón-Ibáñez8Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Virgen del Rocío University Hospital, 41013 Seville, SpainMicrobiology Service, Son Espases University Hospital, Instituto de Investigación Sanitaria Illes Balears (IdISBa), 07010 Palma de Mallorca, SpainUnit of Infectious Diseases, Microbiology, and Preventive Medicine, Virgen del Rocío University Hospital, 41013 Seville, SpainMicrobiology Service, Son Espases University Hospital, Instituto de Investigación Sanitaria Illes Balears (IdISBa), 07010 Palma de Mallorca, SpainUnit of Infectious Diseases, Microbiology, and Preventive Medicine, Virgen del Rocío University Hospital, 41013 Seville, SpainUnit of Infectious Diseases, Microbiology, and Preventive Medicine, Virgen del Rocío University Hospital, 41013 Seville, SpainInstitute of Biomedicine of Seville (IbiS), Virgen del Rocío University Hospital/CSIC/University of Seville, 41013 Seville, SpainMicrobiology Service, Son Espases University Hospital, Instituto de Investigación Sanitaria Illes Balears (IdISBa), 07010 Palma de Mallorca, SpainUnit of Infectious Diseases, Microbiology, and Preventive Medicine, Virgen del Rocío University Hospital, 41013 Seville, SpainIn the context of difficult-to-treat carbapenem-resistant <i>Pseudomonas aeruginosa</i> infections, we evaluated imipenem, meropenem, and doripenem combinations against eleven carbapenemase-producing <i>P. aeruginosa</i> 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 <i>P. aeruginosa</i>. Meropenem monotherapy showed in vivo efficacy despite its high MIC, probably because its dosage allowed a sufficient antimicrobial exposure at the infection sites.https://www.mdpi.com/2079-6382/11/9/1212carbapenemase-producing <i>Pseudomonas aeruginosa</i>doripenemefficacy studiesimipenemmeropenemmurine sepsis model |
| spellingShingle | Soraya Herrera-Espejo Ester Del Barrio-Tofiño Tania Cebrero-Cangueiro Carla López-Causapé Rocío Álvarez-Marín José Miguel Cisneros Jerónimo Pachón Antonio Oliver María Eugenia Pachón-Ibáñez Carbapenem Combinations for Infections Caused by Carbapenemase-Producing <i>Pseudomonas aeruginosa</i>: Experimental In Vitro and In Vivo Analysis Antibiotics carbapenemase-producing <i>Pseudomonas aeruginosa</i> doripenem efficacy studies imipenem meropenem murine sepsis model |
| title | Carbapenem Combinations for Infections Caused by Carbapenemase-Producing <i>Pseudomonas aeruginosa</i>: Experimental In Vitro and In Vivo Analysis |
| title_full | Carbapenem Combinations for Infections Caused by Carbapenemase-Producing <i>Pseudomonas aeruginosa</i>: Experimental In Vitro and In Vivo Analysis |
| title_fullStr | Carbapenem Combinations for Infections Caused by Carbapenemase-Producing <i>Pseudomonas aeruginosa</i>: Experimental In Vitro and In Vivo Analysis |
| title_full_unstemmed | Carbapenem Combinations for Infections Caused by Carbapenemase-Producing <i>Pseudomonas aeruginosa</i>: Experimental In Vitro and In Vivo Analysis |
| title_short | Carbapenem Combinations for Infections Caused by Carbapenemase-Producing <i>Pseudomonas aeruginosa</i>: Experimental In Vitro and In Vivo Analysis |
| title_sort | carbapenem combinations for infections caused by carbapenemase producing i pseudomonas aeruginosa i experimental in vitro and in vivo analysis |
| topic | carbapenemase-producing <i>Pseudomonas aeruginosa</i> doripenem efficacy studies imipenem meropenem murine sepsis model |
| url | https://www.mdpi.com/2079-6382/11/9/1212 |
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