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...
| Authors: | , , , , , , , , , |
|---|---|
| Format: | article |
| Status: | Published version |
| Publication Date: | 2024 |
| Country: | España |
| Institution: | Universidad de Sevilla (US) |
| Repository: | idUS. Depósito de Investigación de la Universidad de Sevilla |
| OAI Identifier: | oai:idus.us.es:11441/171365 |
| Online Access: | https://hdl.handle.net/11441/171365 https://doi.org/10.1128/spectrum.03836-23 |
| Access Level: | Open access |
| Keyword: | Cefiderocol Pseudomonas aeruginosa Acinetobacter spp. β-lactam/β-lactamase inhibitor combinations Meropenem Ceftazidime-avibactam Ceftolozane-tazobactam Meropenem-vaborbactam Imipenem-relebactam Aztreonam-avibactam Cefepime-taniborbactam Sulbactam-durlobactam Resistance Meropenem-resistant β-lactamases Europe In vitro |
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España |
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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 Cefiderocol Pseudomonas aeruginosa Acinetobacter spp. β-lactam/β-lactamase inhibitor combinations Meropenem Ceftazidime-avibactam Ceftolozane-tazobactam Meropenem-vaborbactam Imipenem-relebactam Aztreonam-avibactam Cefepime-taniborbactam Sulbactam-durlobactam Resistance Meropenem-resistant β-lactamases Europe In vitro |
| 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 ARTEMIS Study Investigators López Cerero, Lorena |
| 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 ARTEMIS Study Investigators López Cerero, Lorena |
| author_role |
author |
| author2 |
Jeannot, Katy Oliver, Antonio Perry, John D. Pletz, Mathias W. Stefani, Stefania Morrissey, Ian Longshaw, Christopher ARTEMIS Study Investigators López Cerero, Lorena |
| author2_role |
author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Microbiología CTS210: Resistencia a Antimicrobianos |
| dc.subject.none.fl_str_mv |
Cefiderocol Pseudomonas aeruginosa Acinetobacter spp. β-lactam/β-lactamase inhibitor combinations Meropenem Ceftazidime-avibactam Ceftolozane-tazobactam Meropenem-vaborbactam Imipenem-relebactam Aztreonam-avibactam Cefepime-taniborbactam Sulbactam-durlobactam Resistance Meropenem-resistant β-lactamases Europe In vitro |
| topic |
Cefiderocol Pseudomonas aeruginosa Acinetobacter spp. β-lactam/β-lactamase inhibitor combinations Meropenem Ceftazidime-avibactam Ceftolozane-tazobactam Meropenem-vaborbactam Imipenem-relebactam Aztreonam-avibactam Cefepime-taniborbactam Sulbactam-durlobactam Resistance Meropenem-resistant β-lactamases Europe In vitro |
| 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. IMPORTANCEThis 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 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/11441/171365 https://doi.org/10.1128/spectrum.03836-23 |
| url |
https://hdl.handle.net/11441/171365 https://doi.org/10.1128/spectrum.03836-23 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Microbiology Spectrum, 12 (4), e03836-23. https://journals.asm.org/doi/epub/10.1128/spectrum.03836-23 |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf application/pdf |
| dc.publisher.none.fl_str_mv |
American Society for Microbiology |
| publisher.none.fl_str_mv |
American Society for Microbiology |
| dc.source.none.fl_str_mv |
reponame:idUS. Depósito de Investigación de la Universidad de Sevilla instname:Universidad de Sevilla (US) |
| instname_str |
Universidad de Sevilla (US) |
| reponame_str |
idUS. Depósito de Investigación de la Universidad de Sevilla |
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idUS. Depósito de Investigación de la Universidad de Sevilla |
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|
| _version_ |
1869415051027283968 |
| 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 D.Pletz, Mathias W.Stefani, StefaniaMorrissey, IanLongshaw, ChristopherARTEMIS Study InvestigatorsLópez Cerero, LorenaCefiderocolPseudomonas aeruginosaAcinetobacter spp.β-lactam/β-lactamase inhibitor combinationsMeropenemCeftazidime-avibactamCeftolozane-tazobactamMeropenem-vaborbactamImipenem-relebactamAztreonam-avibactamCefepime-taniborbactamSulbactam-durlobactamResistanceMeropenem-resistantβ-lactamasesEuropeIn vitroCarbapenem-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. IMPORTANCEThis 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.American Society for MicrobiologyMicrobiologíaCTS210: Resistencia a Antimicrobianos2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/171365https://doi.org/10.1128/spectrum.03836-23reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésMicrobiology Spectrum, 12 (4), e03836-23.https://journals.asm.org/doi/epub/10.1128/spectrum.03836-23info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1713652026-06-17T12:51:07Z |
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