Aztreonam Combinations with Avibactam, Relebactam, and Vaborbactam as Treatment for New Delhi Metallo-β-Lactamase-Producing Enterobacterales Infections—In Vitro Susceptibility Testing
Antimicrobial resistance is a major global health issue. Metallo-β-lactamases (MBL), in particular, are problematic because they can inactivate all classes of β-lactams except aztreonam. Unfortunately, the latter may be simultaneously inactivated by serine β-lactamases. The most dangerous known MBL...
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MDPI AG
2024-03-01
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| Online Access: | https://www.mdpi.com/1424-8247/17/3/383 |
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| author | Małgorzata Brauncajs Filip Bielec Marlena Malinowska Dorota Pastuszak-Lewandoska |
| author_facet | Małgorzata Brauncajs Filip Bielec Marlena Malinowska Dorota Pastuszak-Lewandoska |
| author_sort | Małgorzata Brauncajs |
| collection | DOAJ |
| description | Antimicrobial resistance is a major global health issue. Metallo-β-lactamases (MBL), in particular, are problematic because they can inactivate all classes of β-lactams except aztreonam. Unfortunately, the latter may be simultaneously inactivated by serine β-lactamases. The most dangerous known MBL is New Delhi Metallo-β-lactamase (NDM). This study aimed to test the in vitro susceptibility to aztreonam in combination with novel β-lactamase inhibitors (avibactam, relebactam, and vaborbactam) in clinical strains of Enterobacterales NDM which is resistant to aztreonam. We investigated 21 NDM isolates—including <i>Klebsiella pneumoniae</i>, <i>Escherichia coli</i>, and <i>Citrobacter freundii</i>—which are simultaneously resistant to aztreonam, ceftazidime/avibactam, imipenem/relebactam, and meropenem/vaborbactam. MICs for aztreonam combinations with novel inhibitors were determined using the gradient strip superposition method. The most effective combination was aztreonam/avibactam, active in 80.95% strains, while combinations with relebactam and vaborbactam were effective in 61.90% and 47.62%, respectively. In three studied strains, none of the studied inhibitors restored aztreonam susceptibility. Aztreonam/avibactam has the most significant antimicrobial potential for NDM isolates. However, combinations with other inhibitors should not be rejected in advance because we identified strain susceptible only to tested combinations with inhibitors other than avibactam. Standardization committees should, as soon as possible, develop official methodology for antimicrobial susceptibility testing for aztreonam with β-lactamase inhibitors. |
| first_indexed | 2024-04-24T17:55:02Z |
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| language | English |
| last_indexed | 2024-04-24T17:55:02Z |
| publishDate | 2024-03-01 |
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| series | Pharmaceuticals |
| spelling | doaj.art-5fc6696da9f9457ab17ba21498a882722024-03-27T13:59:27ZengMDPI AGPharmaceuticals1424-82472024-03-0117338310.3390/ph17030383Aztreonam Combinations with Avibactam, Relebactam, and Vaborbactam as Treatment for New Delhi Metallo-β-Lactamase-Producing Enterobacterales Infections—In Vitro Susceptibility TestingMałgorzata Brauncajs0Filip Bielec1Marlena Malinowska2Dorota Pastuszak-Lewandoska3Department of Microbiology and Laboratory Medical Immunology, Medical University of Lodz, ul. Pomorska 251/C5, 92-213 Lodz, PolandDepartment of Microbiology and Laboratory Medical Immunology, Medical University of Lodz, ul. Pomorska 251/C5, 92-213 Lodz, PolandDepartment of Microbiology and Laboratory Medical Immunology, Medical University of Lodz, ul. Pomorska 251/C5, 92-213 Lodz, PolandDepartment of Microbiology and Laboratory Medical Immunology, Medical University of Lodz, ul. Pomorska 251/C5, 92-213 Lodz, PolandAntimicrobial resistance is a major global health issue. Metallo-β-lactamases (MBL), in particular, are problematic because they can inactivate all classes of β-lactams except aztreonam. Unfortunately, the latter may be simultaneously inactivated by serine β-lactamases. The most dangerous known MBL is New Delhi Metallo-β-lactamase (NDM). This study aimed to test the in vitro susceptibility to aztreonam in combination with novel β-lactamase inhibitors (avibactam, relebactam, and vaborbactam) in clinical strains of Enterobacterales NDM which is resistant to aztreonam. We investigated 21 NDM isolates—including <i>Klebsiella pneumoniae</i>, <i>Escherichia coli</i>, and <i>Citrobacter freundii</i>—which are simultaneously resistant to aztreonam, ceftazidime/avibactam, imipenem/relebactam, and meropenem/vaborbactam. MICs for aztreonam combinations with novel inhibitors were determined using the gradient strip superposition method. The most effective combination was aztreonam/avibactam, active in 80.95% strains, while combinations with relebactam and vaborbactam were effective in 61.90% and 47.62%, respectively. In three studied strains, none of the studied inhibitors restored aztreonam susceptibility. Aztreonam/avibactam has the most significant antimicrobial potential for NDM isolates. However, combinations with other inhibitors should not be rejected in advance because we identified strain susceptible only to tested combinations with inhibitors other than avibactam. Standardization committees should, as soon as possible, develop official methodology for antimicrobial susceptibility testing for aztreonam with β-lactamase inhibitors.https://www.mdpi.com/1424-8247/17/3/383aztreonamavibactamvaborbactamrelebactamantimicrobialsβ-lactamase inhibitors |
| spellingShingle | Małgorzata Brauncajs Filip Bielec Marlena Malinowska Dorota Pastuszak-Lewandoska Aztreonam Combinations with Avibactam, Relebactam, and Vaborbactam as Treatment for New Delhi Metallo-β-Lactamase-Producing Enterobacterales Infections—In Vitro Susceptibility Testing Pharmaceuticals aztreonam avibactam vaborbactam relebactam antimicrobials β-lactamase inhibitors |
| title | Aztreonam Combinations with Avibactam, Relebactam, and Vaborbactam as Treatment for New Delhi Metallo-β-Lactamase-Producing Enterobacterales Infections—In Vitro Susceptibility Testing |
| title_full | Aztreonam Combinations with Avibactam, Relebactam, and Vaborbactam as Treatment for New Delhi Metallo-β-Lactamase-Producing Enterobacterales Infections—In Vitro Susceptibility Testing |
| title_fullStr | Aztreonam Combinations with Avibactam, Relebactam, and Vaborbactam as Treatment for New Delhi Metallo-β-Lactamase-Producing Enterobacterales Infections—In Vitro Susceptibility Testing |
| title_full_unstemmed | Aztreonam Combinations with Avibactam, Relebactam, and Vaborbactam as Treatment for New Delhi Metallo-β-Lactamase-Producing Enterobacterales Infections—In Vitro Susceptibility Testing |
| title_short | Aztreonam Combinations with Avibactam, Relebactam, and Vaborbactam as Treatment for New Delhi Metallo-β-Lactamase-Producing Enterobacterales Infections—In Vitro Susceptibility Testing |
| title_sort | aztreonam combinations with avibactam relebactam and vaborbactam as treatment for new delhi metallo β lactamase producing enterobacterales infections in vitro susceptibility testing |
| topic | aztreonam avibactam vaborbactam relebactam antimicrobials β-lactamase inhibitors |
| url | https://www.mdpi.com/1424-8247/17/3/383 |
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