The DOI matches its Crossref record; 462 of the 464 references it cites were found in a registry or an index.
Three Decades of β-Lactamase Inhibitors
Open accessAbstract
Since the introduction of penicillin, beta-lactam antibiotics have been the antimicrobial agents of choice. Unfortunately, the efficacy of these life-saving antibiotics is significantly threatened by bacterial beta-lactamases. beta-Lactamases are now responsible for resistance to penicillins, extended-spectrum cephalosporins, monobactams, and carbapenems. In order to overcome beta-lactamase-mediated resistance, beta-lactamase inhibitors (clavulanate, sulbactam, and tazobactam) were introduced into clinical practice. These inhibitors greatly enhance the efficacy of their partner beta-lactams (amoxicillin, ampicillin, piperacillin, and ticarcillin) in the treatment of serious Enterobacteriaceae and penicillin-resistant staphylococcal infections. However, selective pressure from excess antibiotic use accelerated the emergence of resistance to beta-lactam-beta-lactamase inhibitor combinations. Furthermore, the prevalence of clinically relevant beta-lactamases from other classes that are resistant to inhibition is rapidly increasing. There is an urgent need for effective inhibitors that can restore the activity of beta-lactams. Here, we review the catalytic mechanisms of each beta-lactamase class. We then discuss approaches for circumventing beta-lactamase-mediated resistance, including properties and characteristics of mechanism-based inactivators. We next highlight the mechanisms of action and salient clinical and microbiological features of beta-lactamase inhibitors. We also emphasize their therapeutic applications. We close by focusing on novel compounds and the chemical features of these agents that may contribute to a "second generation" of inhibitors. The goal for the next 3 decades will be to design inhibitors that will be effective for more than a single class of beta-lactamases.
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“Clavulanic acid, a potent β-lactamase inhibitor, was developed to overcome this limitation by binding irreversibly to the active site of β-lactamase enzymes, thereby protecting amoxicillin from enzymatic degradation and restoring its antimicrobial spectrum [3].”
From Clinical Outcomes and Real-World Effectiveness of Amoxicillin-Clavulanic Acid Across Indian Healthcare Settings: A Retrospective Multicenter Study (2026) · cites this paper as [3]
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Cites
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Metadata
- Authors
- Drawz, S. M., & Bonomo, R. A.
- Affiliations
- Departments of Pathology
- United States Department of Veterans Affairs (US)
- Corresponding author
- Bonomo, Robert A.
- ORCID
- Bonomo, Robert A.
- Venue
- Clinical Microbiology Reviews
- Publisher
- American Society for Microbiology
- Published
- 2010-01
- Volume
- 23
- Issue
- 1
- Pages
- 160-201
- ISSN
- 0893-8512 (ISSN-L)
- 1098-6618
- PMC
- PMC2806661
- OpenAlex
- W1895007034
- Cited by
- 1,709
- References
- 464
- Citations by year
- 2026: 83 · 2025: 100 · 2024: 87 · 2023: 86 · 2022: 106 · 2021: 126 · 2020: 151 · 2019: 130 · 2018: 131 · 2017: 119 · 2016: 120 · 2015: 108 · 2014: 93 · 2013: 88 · 2012: 81
- FWCI
- 4.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Microbiology Reviews (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (1R01A1063517-01)
- National Institute of General Medical Sciences (T32GM007250, T32GM07250)
- Topics
- Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
- Health Sciences › Medicine › Pharmacology (medical) › Antibiotics Pharmacokinetics and Efficacy
- Physical Sciences › Chemistry › Organic Chemistry › Synthesis of β-Lactam Compounds
- Keywords
- beta-lactamase inhibitors, beta-lactamase, beta-lactam resistance, clavulanic acid, sulbactam, tazobactam, mechanism-based inactivators, carbapenemase inhibitors, extended-spectrum cephalosporin resistance, Enterobacteriaceae, penicillin-resistant staphylococci
- MeSH terms
- Bacteria, Bacterial Infections, Bacterial Proteins, beta-Lactamases, Enzyme Inhibitors, Humans, beta-Lactam Resistance, beta-Lactamase Inhibitors
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