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Neutralizing Carbap...
Neutralizing Carbapenem Resistance by Co-Administering Meropenem with Novel β-Lactam-Metallo-β-Lactamase Inhibitors
- Article/chapterEnglish2023
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LIBRIS-ID:oai:prod.swepub.kib.ki.se:152766286
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http://kipublications.ki.se/Default.aspx?queryparsed=id:152766286URI
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https://doi.org/10.3390/antibiotics12040633DOI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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Virulent Enterobacterale strains expressing serine and metallo-β-lactamases (MBL) genes have emerged responsible for conferring resistance to hard-to-treat infectious diseases. One strategy that exists is to develop β-lactamase inhibitors to counter this resistance. Currently, serine β-lactamase inhibitors (SBLIs) are in therapeutic use. However, an urgent global need for clinical metallo-β-lactamase inhibitors (MBLIs) has become dire. To address this problem, this study evaluated BP2, a novel beta-lactam-derived β-lactamase inhibitor, co-administered with meropenem. According to the antimicrobial susceptibility results, BP2 potentiates the synergistic activity of meropenem to a minimum inhibitory concentration (MIC) of ≤1 mg/L. In addition, BP2 is bactericidal over 24 h and safe to administer at the selected concentrations. Enzyme inhibition kinetics showed that BP2 had an apparent inhibitory constant (Kiapp) of 35.3 µM and 30.9 µM against New Delhi Metallo-β-lactamase (NDM-1) and Verona Integron-encoded Metallo-β-lactamase (VIM-2), respectively. BP2 did not interact with glyoxylase II enzyme up to 500 µM, indicating specific (MBL) binding. In a murine infection model, BP2 co-administered with meropenem was efficacious, observed by the >3 log10 reduction in K. pneumoniae NDM cfu/thigh. Given the promising pre-clinical results, BP2 is a suitable candidate for further research and development as an (MBLI).
Added entries (persons, corporate bodies, meetings, titles ...)
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Girdhari, L
(author)
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Shungube, M
(author)
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Gouws, AC
(author)
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Peters, BK
(author)
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Rajbongshi, KK
(author)
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Baijnath, S
(author)
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Mdanda, S
(author)
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Ntombela, T
(author)
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Arumugam, T
(author)
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Bester, LA
(author)
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Singh, SD
(author)
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Chuturgoon, A
(author)
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Arvidsson, PIKarolinska Institutet
(author)
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Maguire, GEM
(author)
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Kruger, HG
(author)
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Govender, T
(author)
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Naicker, T
(author)
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Karolinska Institutet
(creator_code:org_t)
Related titles
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In:Antibiotics (Basel, Switzerland): MDPI AG12:42079-6382
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Reddy, N
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Girdhari, L
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Shungube, M
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Gouws, AC
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Peters, BK
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Rajbongshi, KK
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Baijnath, S
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Mdanda, S
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Ntombela, T
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Arumugam, T
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Bester, LA
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Singh, SD
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Chuturgoon, A
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Arvidsson, PI
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Maguire, GEM
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Kruger, HG
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Govender, T
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Naicker, T
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Antibiotics (Bas ...
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Karolinska Institutet