In vitro activity of cefiderocol against European Pseudomonas aeruginosa and Acinetobacter spp., including isolates resistant to meropenem and recent β-lactam/β-lactamase inhibitor combinations
Carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter spp. represent major threats and have few approved therapeutic options. Non-fermenting Gram-negative isolates were collected from hospitalized inpatients from 49 sites in 6 European countries between 01 January 2020 and 31 December 2020...
| Autores: | , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Conselleria de Salut i Consum del Govern de les Illes Balears |
| Repositorio: | Docusalut |
| Idioma: | inglés |
| OAI Identifier: | oai:docusalut.com:20.500.13003/20359 |
| Acceso en línea: | https://hdl.handle.net/20.500.13003/20359 |
| Access Level: | acceso abierto |
| Palabra clave: | Meropenem Anti-Bacterial Agents Microbial Sensitivity Tests Humans Lactams Acinetobacter Cephalosporins Gram-Negative Bacteria beta-Lactamases beta-Lactamase Inhibitors Pseudomonas aeruginosa Pseudomonas Infections Lactamas Pruebas de Sensibilidad Microbiana Humanos Cefalosporinas Bacterias Gramnegativas Inhibidores de beta-Lactamasas Infecciones por Pseudomonas Antibacterianos beta-Lactamasas |
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In vitro activity of cefiderocol against European Pseudomonas aeruginosa and Acinetobacter spp., including isolates resistant to meropenem and recent β-lactam/β-lactamase inhibitor combinations |
| title |
In vitro activity of cefiderocol against European Pseudomonas aeruginosa and Acinetobacter spp., including isolates resistant to meropenem and recent β-lactam/β-lactamase inhibitor combinations |
| spellingShingle |
In vitro activity of cefiderocol against European Pseudomonas aeruginosa and Acinetobacter spp., including isolates resistant to meropenem and recent β-lactam/β-lactamase inhibitor combinations Santerre Henriksen, Anne Meropenem Anti-Bacterial Agents Microbial Sensitivity Tests Humans Lactams Acinetobacter Cephalosporins Gram-Negative Bacteria beta-Lactamases beta-Lactamase Inhibitors Pseudomonas aeruginosa Pseudomonas Infections Meropenem Lactamas Pruebas de Sensibilidad Microbiana Humanos Cefalosporinas Bacterias Gramnegativas Inhibidores de beta-Lactamasas Infecciones por Pseudomonas Pseudomonas aeruginosa Antibacterianos beta-Lactamasas Acinetobacter |
| title_short |
In vitro activity of cefiderocol against European Pseudomonas aeruginosa and Acinetobacter spp., including isolates resistant to meropenem and recent β-lactam/β-lactamase inhibitor combinations |
| title_full |
In vitro activity of cefiderocol against European Pseudomonas aeruginosa and Acinetobacter spp., including isolates resistant to meropenem and recent β-lactam/β-lactamase inhibitor combinations |
| title_fullStr |
In vitro activity of cefiderocol against European Pseudomonas aeruginosa and Acinetobacter spp., including isolates resistant to meropenem and recent β-lactam/β-lactamase inhibitor combinations |
| title_full_unstemmed |
In vitro activity of cefiderocol against European Pseudomonas aeruginosa and Acinetobacter spp., including isolates resistant to meropenem and recent β-lactam/β-lactamase inhibitor combinations |
| title_sort |
In vitro activity of cefiderocol against European Pseudomonas aeruginosa and Acinetobacter spp., including isolates resistant to meropenem and recent β-lactam/β-lactamase inhibitor combinations |
| dc.creator.none.fl_str_mv |
Santerre Henriksen, Anne Jeannot, Katy Oliver, Antonio Perry, John D Pletz, Mathias W Stefani, Stefania Morrissey, Ian Longshaw, Christopher |
| author |
Santerre Henriksen, Anne |
| author_facet |
Santerre Henriksen, Anne Jeannot, Katy Oliver, Antonio Perry, John D Pletz, Mathias W Stefani, Stefania Morrissey, Ian Longshaw, Christopher |
| author_role |
author |
| author2 |
Jeannot, Katy Oliver, Antonio Perry, John D Pletz, Mathias W Stefani, Stefania Morrissey, Ian Longshaw, Christopher |
| author2_role |
author author author author author author author |
| dc.contributor.none.fl_str_mv |
|
| dc.subject.none.fl_str_mv |
Meropenem Anti-Bacterial Agents Microbial Sensitivity Tests Humans Lactams Acinetobacter Cephalosporins Gram-Negative Bacteria beta-Lactamases beta-Lactamase Inhibitors Pseudomonas aeruginosa Pseudomonas Infections Meropenem Lactamas Pruebas de Sensibilidad Microbiana Humanos Cefalosporinas Bacterias Gramnegativas Inhibidores de beta-Lactamasas Infecciones por Pseudomonas Pseudomonas aeruginosa Antibacterianos beta-Lactamasas Acinetobacter |
| topic |
Meropenem Anti-Bacterial Agents Microbial Sensitivity Tests Humans Lactams Acinetobacter Cephalosporins Gram-Negative Bacteria beta-Lactamases beta-Lactamase Inhibitors Pseudomonas aeruginosa Pseudomonas Infections Meropenem Lactamas Pruebas de Sensibilidad Microbiana Humanos Cefalosporinas Bacterias Gramnegativas Inhibidores de beta-Lactamasas Infecciones por Pseudomonas Pseudomonas aeruginosa Antibacterianos beta-Lactamasas Acinetobacter |
| description |
Carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter spp. represent major threats and have few approved therapeutic options. Non-fermenting Gram-negative isolates were collected from hospitalized inpatients from 49 sites in 6 European countries between 01 January 2020 and 31 December 2020 and underwent susceptibility testing against cefiderocol and β-lactam/β-lactamase inhibitor combinations. Meropenem-resistant (MIC >8 mg/L), cefiderocol-susceptible isolates were analyzed by PCR, and cefiderocol-resistant isolates were analyzed by whole-genome sequencing to identify resistance mechanisms. Overall, 1,451 (950 P. aeruginosa; 501 Acinetobacter spp.) isolates were collected, commonly from the respiratory tract (42.0% and 39.3%, respectively). Cefiderocol susceptibility was higher than β-lactam/β-lactamase inhibitor combinations against P. aeruginosa (98.9% vs 83.3%-91.4%), and P. aeruginosa resistant to meropenem (n = 139; 97.8% vs 12.2%-59.7%), β-lactam/β-lactamase inhibitor combinations (93.6%-98.1% vs 10.7%-71.8%), and both meropenem and ceftazidime-avibactam (96.7% vs 5.0%-45.0%) or ceftolozane-tazobactam (98.4% vs 8.1%-54.8%), respectively. Cefiderocol and sulbactam-durlobactam susceptibilities were high against Acinetobacter spp. (92.4% and 97.0%) and meropenem-resistant Acinetobacter spp. (n = 227; 85.0% and 93.8%) but lower against sulbactam-durlobactam- (n = 15; 13.3%) and cefiderocol- (n = 38; 65.8%) resistant isolates, respectively. Among meropenem-resistant P. aeruginosa and Acinetobacter spp., the most common β-lactamase genes were metallo-β-lactamases [30/139; blaVIM-2 (15/139)] and oxacillinases [215/227; blaOXA-23 (194/227)], respectively. Acquired β-lactamase genes were identified in 1/10 and 32/38 of cefiderocol-resistant P. aeruginosa and Acinetobacter spp., and pirA-like or piuA mutations in 10/10 and 37/38, respectively. Conclusion: cefiderocol susceptibility was high against P. aeruginosa and Acinetobacter spp., including meropenem-resistant isolates and those resistant to recent β-lactam/β-lactamase inhibitor combinations common in first-line treatment of European non-fermenters. This was the first study in which the in vitro activity of cefiderocol and non-licensed β-lactam/β-lactamase inhibitor combinations were directly compared against Pseudomonas aeruginosa and Acinetobacter spp., including meropenem- and β-lactam/β-lactamase inhibitor combination-resistant isolates. A notably large number of European isolates were collected. Meropenem resistance was defined according to the MIC breakpoint for high-dose meropenem, ensuring that data reflect antibiotic activity against isolates that would remain meropenem resistant in the clinic. Cefiderocol susceptibility was high against non-fermenters, and there was no apparent cross resistance between cefiderocol and β-lactam/β-lactamase inhibitor combinations, with the exception of sulbactam-durlobactam. These results provide insights into therapeutic options for infections due to resistant P. aeruginosa and Acinetobacter spp. and indicate how early susceptibility testing of cefiderocol in parallel with β-lactam/β-lactamase inhibitor combinations will allow clinicians to choose the effective treatment(s) from all available options. This is particularly important as current treatment options against non-fermenters are limited. |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024 2024-04-02 2024 2024-04-02 |
| dc.type.none.fl_str_mv |
research article http://purl.org/coar/resource_type/c_2df8fbb1 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/20.500.13003/20359 |
| url |
https://hdl.handle.net/20.500.13003/20359 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Atribución 4.0 Internacional http://creativecommons.org/licenses/by/4.0/ |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Atribución 4.0 Internacional http://creativecommons.org/licenses/by/4.0/ |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
ASM Journals |
| publisher.none.fl_str_mv |
ASM Journals |
| dc.source.none.fl_str_mv |
reponame:Docusalut instname:Conselleria de Salut i Consum del Govern de les Illes Balears |
| instname_str |
Conselleria de Salut i Consum del Govern de les Illes Balears |
| reponame_str |
Docusalut |
| collection |
Docusalut |
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|
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|
| _version_ |
1869421230630633472 |
| spelling |
In vitro activity of cefiderocol against European Pseudomonas aeruginosa and Acinetobacter spp., including isolates resistant to meropenem and recent β-lactam/β-lactamase inhibitor combinationsSanterre Henriksen, AnneJeannot, KatyOliver, AntonioPerry, John DPletz, Mathias WStefani, StefaniaMorrissey, IanLongshaw, ChristopherMeropenemAnti-Bacterial AgentsMicrobial Sensitivity TestsHumansLactamsAcinetobacterCephalosporinsGram-Negative Bacteriabeta-Lactamasesbeta-Lactamase InhibitorsPseudomonas aeruginosaPseudomonas InfectionsMeropenemLactamasPruebas de Sensibilidad MicrobianaHumanosCefalosporinasBacterias GramnegativasInhibidores de beta-LactamasasInfecciones por PseudomonasPseudomonas aeruginosaAntibacterianosbeta-LactamasasAcinetobacterCarbapenem-resistant Pseudomonas aeruginosa and Acinetobacter spp. represent major threats and have few approved therapeutic options. Non-fermenting Gram-negative isolates were collected from hospitalized inpatients from 49 sites in 6 European countries between 01 January 2020 and 31 December 2020 and underwent susceptibility testing against cefiderocol and β-lactam/β-lactamase inhibitor combinations. Meropenem-resistant (MIC >8 mg/L), cefiderocol-susceptible isolates were analyzed by PCR, and cefiderocol-resistant isolates were analyzed by whole-genome sequencing to identify resistance mechanisms. Overall, 1,451 (950 P. aeruginosa; 501 Acinetobacter spp.) isolates were collected, commonly from the respiratory tract (42.0% and 39.3%, respectively). Cefiderocol susceptibility was higher than β-lactam/β-lactamase inhibitor combinations against P. aeruginosa (98.9% vs 83.3%-91.4%), and P. aeruginosa resistant to meropenem (n = 139; 97.8% vs 12.2%-59.7%), β-lactam/β-lactamase inhibitor combinations (93.6%-98.1% vs 10.7%-71.8%), and both meropenem and ceftazidime-avibactam (96.7% vs 5.0%-45.0%) or ceftolozane-tazobactam (98.4% vs 8.1%-54.8%), respectively. Cefiderocol and sulbactam-durlobactam susceptibilities were high against Acinetobacter spp. (92.4% and 97.0%) and meropenem-resistant Acinetobacter spp. (n = 227; 85.0% and 93.8%) but lower against sulbactam-durlobactam- (n = 15; 13.3%) and cefiderocol- (n = 38; 65.8%) resistant isolates, respectively. Among meropenem-resistant P. aeruginosa and Acinetobacter spp., the most common β-lactamase genes were metallo-β-lactamases [30/139; blaVIM-2 (15/139)] and oxacillinases [215/227; blaOXA-23 (194/227)], respectively. Acquired β-lactamase genes were identified in 1/10 and 32/38 of cefiderocol-resistant P. aeruginosa and Acinetobacter spp., and pirA-like or piuA mutations in 10/10 and 37/38, respectively. Conclusion: cefiderocol susceptibility was high against P. aeruginosa and Acinetobacter spp., including meropenem-resistant isolates and those resistant to recent β-lactam/β-lactamase inhibitor combinations common in first-line treatment of European non-fermenters. This was the first study in which the in vitro activity of cefiderocol and non-licensed β-lactam/β-lactamase inhibitor combinations were directly compared against Pseudomonas aeruginosa and Acinetobacter spp., including meropenem- and β-lactam/β-lactamase inhibitor combination-resistant isolates. A notably large number of European isolates were collected. Meropenem resistance was defined according to the MIC breakpoint for high-dose meropenem, ensuring that data reflect antibiotic activity against isolates that would remain meropenem resistant in the clinic. Cefiderocol susceptibility was high against non-fermenters, and there was no apparent cross resistance between cefiderocol and β-lactam/β-lactamase inhibitor combinations, with the exception of sulbactam-durlobactam. These results provide insights into therapeutic options for infections due to resistant P. aeruginosa and Acinetobacter spp. and indicate how early susceptibility testing of cefiderocol in parallel with β-lactam/β-lactamase inhibitor combinations will allow clinicians to choose the effective treatment(s) from all available options. This is particularly important as current treatment options against non-fermenters are limited.ASM Journals20242024-04-0220242024-04-02research articlehttp://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.13003/20359reponame:Docusalutinstname:Conselleria de Salut i Consum del Govern de les Illes BalearsInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docusalut.com:20.500.13003/203592026-06-22T12:44:07Z |
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15,81155 |