The Urgent Need for Developing Metallo-β-Lactamase Inhibitors

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Novel Antimicrobial Agents".

Deadline for manuscript submissions: closed (1 August 2022) | Viewed by 4197

Special Issue Editors


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Guest Editor
Department of Chemistry and Biochemistry, Miami University, Oxford, OH 45056, USA
Interests: antibiotic resistance; protein chemistry; evolution and function of β-lactamases; metallo-β-lactamase inhibitors

E-Mail Website
Guest Editor
Department of Chemistry and Biochemistry, Miami University, Oxford, OH 45056, USA
Interests: antibiotic resistance; native state mass spectrometry; mechanism of metallo- β-lactamase inhibitors; protein chemistry

Special Issue Information

Dear Colleagues,

The β-lactam class remains the largest class of antibiotics for treating bacterial infections. The widespread use of this class of antibiotics has led to the emergence of different resistance mechanisms, including (a) the production of altered penicillin-binding proteins (PBP) with lower binding affinities for most β-lactam antibiotics and (b) the production of β-lactamases, which is the most common resistance mechanism in Gram-negative bacteria. β-Lactamases can be categorized into serine-β-lactamases (SBLs) and metallo-β-lactamases (MBLs). Although SBLs have become more clinically prevalent over the past seventy years, there exist inhibitors, which can be given in combination with β-lactam containing antibiotics to treat bacteria that produce some of the SBLs. However, despite considerable efforts to develop such inhibitors, there are no clinically approved inhibitors available for MBLs, making infections from MBL-producing bacteria a severe challenge. In addition, the COVID-19 crisis further emphasizes the urgency to find MBL inhibitors because co-infections containing SBLs and MBLs have been reported in COVID-19 patients. This Special Issue focuses on characteristics of MBLs and ways to combat their action.

Dr. Zishuo Cheng
Dr. Caitlyn A. Thomas
Guest Editors

Manuscript Submission Information

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Keywords

  • antimicrobial resistance
  • β-Lactamases
  • metallo-β-lactamases
  • inhibition
  • mechanism

Published Papers (1 paper)

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Review

14 pages, 306 KiB  
Review
Treatment of Severe Infections Due to Metallo-Betalactamases Enterobacterales in Critically Ill Patients
by Jean-François Timsit, Paul-Henri Wicky and Etienne de Montmollin
Antibiotics 2022, 11(2), 144; https://doi.org/10.3390/antibiotics11020144 - 24 Jan 2022
Cited by 7 | Viewed by 3906
Abstract
Metallo-beta-lactamases-producing (MBL) Enterobacterales is a growing problem worldwide. The optimization of antibiotic therapy is challenging. The pivotal available therapeutic options are either the combination of ceftazidime/avibactam and aztreonam or cefiderocol. Colistin, fosfomycin, tetracyclines and aminoglycosides are also frequently effective in vitro, but are [...] Read more.
Metallo-beta-lactamases-producing (MBL) Enterobacterales is a growing problem worldwide. The optimization of antibiotic therapy is challenging. The pivotal available therapeutic options are either the combination of ceftazidime/avibactam and aztreonam or cefiderocol. Colistin, fosfomycin, tetracyclines and aminoglycosides are also frequently effective in vitro, but are associated with less bactericidal activity or more toxicity. Prior to the availability of antibiotic susceptibility testing, severe infections should be treated with a combination therapy. A careful optimization of the pharmacokinetic/pharmacodynamic properties of antimicrobials is instrumental in severe infections. The rules of antibiotic therapy are also reported and discussed. To conclude, treatment of severe MBL infections in critically ill patients is difficult. It should be individualized with a close collaboration of intensivists with microbiologists, pharmacists and infection control practitioners. Full article
(This article belongs to the Special Issue The Urgent Need for Developing Metallo-β-Lactamase Inhibitors)
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