In vitro Activity of Cefiderocol and Comparators against Carbapenem-Resistant Gram-Negative Pathogens from France and Belgium
Infections with carbapenem-resistant (CR) Gram-negative (GN) pathogens have increased in many countries worldwide, leaving only few therapeutic options. Cefiderocol (CFDC) is approved in Europe for the treatment of aerobic GN infections in adults with limited treatment options. This study evaluated...
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MDPI AG
2022-10-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/11/10/1352 |
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| author | Saoussen Oueslati Pierre Bogaerts Laurent Dortet Sandrine Bernabeu Hend Ben Lakhal Christopher Longshaw Youri Glupczynski Thierry Naas |
| author_facet | Saoussen Oueslati Pierre Bogaerts Laurent Dortet Sandrine Bernabeu Hend Ben Lakhal Christopher Longshaw Youri Glupczynski Thierry Naas |
| author_sort | Saoussen Oueslati |
| collection | DOAJ |
| description | Infections with carbapenem-resistant (CR) Gram-negative (GN) pathogens have increased in many countries worldwide, leaving only few therapeutic options. Cefiderocol (CFDC) is approved in Europe for the treatment of aerobic GN infections in adults with limited treatment options. This study evaluated the in vitro activity of cefiderocol and comparators against multidrug-resistant (MDR) bacteria including meropenem-resistant (MR) or pandrug-resistant (PR) GN clinical isolates from France and Belgium. The minimum inhibitory concentrations (MICs) of CFDC were determined by broth microdilution, using iron-depleted cation-adjusted Mueller–Hinton broth, and were compared to those of 10 last-line antibiotics. The MICs were interpreted according to EUCAST and CLSI breakpoints, and in the absence of species-specific breakpoints, non-species-related pharmacokinetic/pharmacodynamic breakpoints were used. Among the 476 isolates tested, 322 were carbapenemase producers (CP), 58 non-CP-CRs, 52 intrinsically CR, 41 expanded-spectrum cephalosporin resistant and 5 were multi-susceptible. Susceptibility to CFDC was high using EUCAST breakpoints 81%, 99% and 84%, and was even higher using CLSI breakpoints to 93%, 100% and 88% for Enterobacterales, <i>Pseudomonas aeruginosa</i> and <i>Acinetobacter baumannii</i>, respectively. Susceptibility to cefiderocol using non-species-related breakpoints for <i>Stenotrophomonas maltophilia</i>, <i>Achromobacter xylosoxydans</i> and <i>Burkholderia cepacia</i>, was 100%, 100% and 92.3%, respectively. The susceptibility rates were lower with the NDM producers, with values of 48% and 30% using EUCAST breakpoints and 81% and 50% using CLSI breakpoints for Enterobacterales and <i>Acinetobacter</i> spp, respectively. CFDC demonstrated high in vitro susceptibility rates against a wide range of MDR GN pathogens, including MR and PR isolates. |
| first_indexed | 2024-03-09T20:50:53Z |
| format | Article |
| id | doaj.art-ae55c1bd69414362946aef757a888286 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-09T20:50:53Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
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| series | Antibiotics |
| spelling | doaj.art-ae55c1bd69414362946aef757a8882862023-11-23T22:35:02ZengMDPI AGAntibiotics2079-63822022-10-011110135210.3390/antibiotics11101352In vitro Activity of Cefiderocol and Comparators against Carbapenem-Resistant Gram-Negative Pathogens from France and BelgiumSaoussen Oueslati0Pierre Bogaerts1Laurent Dortet2Sandrine Bernabeu3Hend Ben Lakhal4Christopher Longshaw5Youri Glupczynski6Thierry Naas7Team ReSIST, LabEx LERMIT, INSERM U1184, School of Medicine, Université Paris-Saclay, 94270 Le Kremlin-Bicêtre, FranceLaboratory of Clinical Microbiology, National Reference Center for Monitoring Antimicrobial Resistance in Gram-Negative Bacteria, CHU UCL Namur, 5530 Yvoir, BelgiumTeam ReSIST, LabEx LERMIT, INSERM U1184, School of Medicine, Université Paris-Saclay, 94270 Le Kremlin-Bicêtre, FranceTeam ReSIST, LabEx LERMIT, INSERM U1184, School of Medicine, Université Paris-Saclay, 94270 Le Kremlin-Bicêtre, FranceCentre Hospitalier d’Orsay, Service de Réanimation, 91400 Orsay, FranceMedical Affairs Europe, Shionogi Europe, London WC2B 6UF, UKLaboratory of Clinical Microbiology, National Reference Center for Monitoring Antimicrobial Resistance in Gram-Negative Bacteria, CHU UCL Namur, 5530 Yvoir, BelgiumTeam ReSIST, LabEx LERMIT, INSERM U1184, School of Medicine, Université Paris-Saclay, 94270 Le Kremlin-Bicêtre, FranceInfections with carbapenem-resistant (CR) Gram-negative (GN) pathogens have increased in many countries worldwide, leaving only few therapeutic options. Cefiderocol (CFDC) is approved in Europe for the treatment of aerobic GN infections in adults with limited treatment options. This study evaluated the in vitro activity of cefiderocol and comparators against multidrug-resistant (MDR) bacteria including meropenem-resistant (MR) or pandrug-resistant (PR) GN clinical isolates from France and Belgium. The minimum inhibitory concentrations (MICs) of CFDC were determined by broth microdilution, using iron-depleted cation-adjusted Mueller–Hinton broth, and were compared to those of 10 last-line antibiotics. The MICs were interpreted according to EUCAST and CLSI breakpoints, and in the absence of species-specific breakpoints, non-species-related pharmacokinetic/pharmacodynamic breakpoints were used. Among the 476 isolates tested, 322 were carbapenemase producers (CP), 58 non-CP-CRs, 52 intrinsically CR, 41 expanded-spectrum cephalosporin resistant and 5 were multi-susceptible. Susceptibility to CFDC was high using EUCAST breakpoints 81%, 99% and 84%, and was even higher using CLSI breakpoints to 93%, 100% and 88% for Enterobacterales, <i>Pseudomonas aeruginosa</i> and <i>Acinetobacter baumannii</i>, respectively. Susceptibility to cefiderocol using non-species-related breakpoints for <i>Stenotrophomonas maltophilia</i>, <i>Achromobacter xylosoxydans</i> and <i>Burkholderia cepacia</i>, was 100%, 100% and 92.3%, respectively. The susceptibility rates were lower with the NDM producers, with values of 48% and 30% using EUCAST breakpoints and 81% and 50% using CLSI breakpoints for Enterobacterales and <i>Acinetobacter</i> spp, respectively. CFDC demonstrated high in vitro susceptibility rates against a wide range of MDR GN pathogens, including MR and PR isolates.https://www.mdpi.com/2079-6382/11/10/1352CFDCMICmultidrug-resistant bacteria |
| spellingShingle | Saoussen Oueslati Pierre Bogaerts Laurent Dortet Sandrine Bernabeu Hend Ben Lakhal Christopher Longshaw Youri Glupczynski Thierry Naas In vitro Activity of Cefiderocol and Comparators against Carbapenem-Resistant Gram-Negative Pathogens from France and Belgium Antibiotics CFDC MIC multidrug-resistant bacteria |
| title | In vitro Activity of Cefiderocol and Comparators against Carbapenem-Resistant Gram-Negative Pathogens from France and Belgium |
| title_full | In vitro Activity of Cefiderocol and Comparators against Carbapenem-Resistant Gram-Negative Pathogens from France and Belgium |
| title_fullStr | In vitro Activity of Cefiderocol and Comparators against Carbapenem-Resistant Gram-Negative Pathogens from France and Belgium |
| title_full_unstemmed | In vitro Activity of Cefiderocol and Comparators against Carbapenem-Resistant Gram-Negative Pathogens from France and Belgium |
| title_short | In vitro Activity of Cefiderocol and Comparators against Carbapenem-Resistant Gram-Negative Pathogens from France and Belgium |
| title_sort | in vitro activity of cefiderocol and comparators against carbapenem resistant gram negative pathogens from france and belgium |
| topic | CFDC MIC multidrug-resistant bacteria |
| url | https://www.mdpi.com/2079-6382/11/10/1352 |
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