In vitro activity of aztreonam in combination with relebactam against gram-negative pathogens producing various serine and metallo-β-lactamases
Objectives: Infections caused by carbapenemase-producing Gram-negative pathogens have become a significant global public health challenge due to limited treatment options. Pathogens producing metallo-β-lactamase are particularly problematic since they are not inhibited by conventional β-lactamase in...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-05-01
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| Series: | Journal of Global Antimicrobial Resistance |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213716525000396 |
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| author | Kengo Hayashi Masahiro Suzuki Yoshikazu Ishii Yasufumi Matsumura Kazuaki Matsumoto Sho Saito Yohei Doi |
| author_facet | Kengo Hayashi Masahiro Suzuki Yoshikazu Ishii Yasufumi Matsumura Kazuaki Matsumoto Sho Saito Yohei Doi |
| author_sort | Kengo Hayashi |
| collection | DOAJ |
| description | Objectives: Infections caused by carbapenemase-producing Gram-negative pathogens have become a significant global public health challenge due to limited treatment options. Pathogens producing metallo-β-lactamase are particularly problematic since they are not inhibited by conventional β-lactamase inhibitors. Herein, we assess the in vitro activity of aztreonam in combination with relebactam against a collection carbapenemase producing organisms, including strains producing both serine‑β-lactamase and IMP-type metallo-β-lactamase that are commonly encountered in Japan. Methods: A total of 119 carbapenemase-producing clinical isolates were used in this study. Minimum inhibitory concentrations (MICs) of aztreonam and imipenem alone and aztreonam/relebactam, aztreonam/avibactam and imipenem/relebactam combinations were determined by the broth microdilution method. Results: Aztreonam MICs were reduced in combination with relebactam for strains producing ESBL or AmpC in addition to IMP-type, NDM-type, GES-type or OXA-48 carbapenemases and for Stenotrophomonas spp. Additionally, aztreonam/relebactam combination MICs were significantly lower than MICs of aztreonam alone among IMP producers, NDM producers and Stenotrophomonas spp. Significant differences between aztreonam/relebactam and aztreonam MICs were also observed for strains of E. coli, K. pneumoniae and Enterobacter spp., many of which produced both metallo-β-lactamase and serine‑β-lactamase. The aztreonam/relebactam combination showed comparable to higher MICs compared with the aztreonam/avibactam combination. Conclusion: The addition of relebactam has a potential to restore the activity of aztreonam against strains that produce metallo-β-lactamase and serine‑β-lactamase. The combination may have a role in the treatment of infections due to these strains in countries without access to ceftazidime-avibactam. |
| format | Article |
| id | doaj-art-9ae0a68acbeb4de4b9b71e86d976fd14 |
| institution | Kabale University |
| issn | 2213-7165 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Global Antimicrobial Resistance |
| spelling | doaj-art-9ae0a68acbeb4de4b9b71e86d976fd142025-08-20T03:52:43ZengElsevierJournal of Global Antimicrobial Resistance2213-71652025-05-0142737910.1016/j.jgar.2025.02.008In vitro activity of aztreonam in combination with relebactam against gram-negative pathogens producing various serine and metallo-β-lactamasesKengo Hayashi0Masahiro Suzuki1Yoshikazu Ishii2Yasufumi Matsumura3Kazuaki Matsumoto4Sho Saito5Yohei Doi6Department of Microbiology, Fujita Health University School of Medicine, Aichi, JapanDepartment of Microbiology, Fujita Health University School of Medicine, Aichi, JapanCenter for the Planetary Health and Innovation Science, The IDEC Institute, Hiroshima University, Hiroshima, JapanClinical Laboratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, JapanDivision of Pharmacodynamics, Keio University Faculty of Pharmacy, Tokyo, JapanDisease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, JapanDepartment of Microbiology, Fujita Health University School of Medicine, Aichi, Japan; Department of Infectious Diseases, Fujita Health University School of Medicine, Aichi, Japan; Center for Innovative Antimicrobial Therapy, Division of Infectious Diseases, University of Pittsburgh School of Medicine, PA, USA; Center for Infectious Disease Research, Fujita Health University, Aichi, Japan; Corresponding author. Mailing address: Department of Microbiology, Fujita Health University School of Medicine, Aichi, Japan.Objectives: Infections caused by carbapenemase-producing Gram-negative pathogens have become a significant global public health challenge due to limited treatment options. Pathogens producing metallo-β-lactamase are particularly problematic since they are not inhibited by conventional β-lactamase inhibitors. Herein, we assess the in vitro activity of aztreonam in combination with relebactam against a collection carbapenemase producing organisms, including strains producing both serine‑β-lactamase and IMP-type metallo-β-lactamase that are commonly encountered in Japan. Methods: A total of 119 carbapenemase-producing clinical isolates were used in this study. Minimum inhibitory concentrations (MICs) of aztreonam and imipenem alone and aztreonam/relebactam, aztreonam/avibactam and imipenem/relebactam combinations were determined by the broth microdilution method. Results: Aztreonam MICs were reduced in combination with relebactam for strains producing ESBL or AmpC in addition to IMP-type, NDM-type, GES-type or OXA-48 carbapenemases and for Stenotrophomonas spp. Additionally, aztreonam/relebactam combination MICs were significantly lower than MICs of aztreonam alone among IMP producers, NDM producers and Stenotrophomonas spp. Significant differences between aztreonam/relebactam and aztreonam MICs were also observed for strains of E. coli, K. pneumoniae and Enterobacter spp., many of which produced both metallo-β-lactamase and serine‑β-lactamase. The aztreonam/relebactam combination showed comparable to higher MICs compared with the aztreonam/avibactam combination. Conclusion: The addition of relebactam has a potential to restore the activity of aztreonam against strains that produce metallo-β-lactamase and serine‑β-lactamase. The combination may have a role in the treatment of infections due to these strains in countries without access to ceftazidime-avibactam.http://www.sciencedirect.com/science/article/pii/S2213716525000396AztreonamRelebactamMetallo-β-lactamaseSerine‑β-lactamaseCarbapenemase-producing pathogensCo-producers |
| spellingShingle | Kengo Hayashi Masahiro Suzuki Yoshikazu Ishii Yasufumi Matsumura Kazuaki Matsumoto Sho Saito Yohei Doi In vitro activity of aztreonam in combination with relebactam against gram-negative pathogens producing various serine and metallo-β-lactamases Journal of Global Antimicrobial Resistance Aztreonam Relebactam Metallo-β-lactamase Serine‑β-lactamase Carbapenemase-producing pathogens Co-producers |
| title | In vitro activity of aztreonam in combination with relebactam against gram-negative pathogens producing various serine and metallo-β-lactamases |
| title_full | In vitro activity of aztreonam in combination with relebactam against gram-negative pathogens producing various serine and metallo-β-lactamases |
| title_fullStr | In vitro activity of aztreonam in combination with relebactam against gram-negative pathogens producing various serine and metallo-β-lactamases |
| title_full_unstemmed | In vitro activity of aztreonam in combination with relebactam against gram-negative pathogens producing various serine and metallo-β-lactamases |
| title_short | In vitro activity of aztreonam in combination with relebactam against gram-negative pathogens producing various serine and metallo-β-lactamases |
| title_sort | in vitro activity of aztreonam in combination with relebactam against gram negative pathogens producing various serine and metallo β lactamases |
| topic | Aztreonam Relebactam Metallo-β-lactamase Serine‑β-lactamase Carbapenemase-producing pathogens Co-producers |
| url | http://www.sciencedirect.com/science/article/pii/S2213716525000396 |
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