β-Lactam/β-Lactamase Inhibitor Combinations: From Then to Now
Abstract
Objective To review the available evidence regarding the utility of the currently available β-lactam/β-lactamase inhibitor combinations (BLICs) as well as the emerging body of data for the novel agents in the pipeline. Data sources A MEDLINE literature search (1960-August 2014) was performed using the search terms β-lactamase, β-lactamase inhibitor, clavulanate, sulbactam, tazobactam, avibactam, NXL104, MK-7655, and RPX7009. Current studies focusing on new agents were obtained from clinicaltrials.gov. Additional references were identified from a review of literature citations and meeting abstracts. Study selection and data extraction All English-language studies pertaining to BLICs were evaluated. Data synthesis Historical clinical and in vitro data focusing on the characteristics of the conventional BLICs are reviewed. Avibactam, relebactam (formerly MK-7655), and RPX7009 are new β-lactamase inhibitors that are being studied in combination with β-lactams. Clinical and in vitro data that provide support for their use for multidrug-resistant organisms are reviewed. β-Lactam antibiotics are a mainstay for the treatment of many infections. The addition of β-lactamase inhibitors enhances their activity against organisms that produce β-lactamases; however, organisms that produce extended-spectrum β-lactamases, AmpC β-lactamases, and carbapenemases are proliferating. The BLICs (amoxicillin/clavulanate, ticarcillin/clavulanate, ampicillin/sulbactam, and piperacillin/tazobactam) lack…
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Bacteria can resist β-lactam antibiotics by producing β-lactamase, which cleaves the β-lactam ring.
“One of the strategies deployed by this group of bacteria to survive against β-lactam antibiotics is by the production of a β-lactam-hydrolyzing enzyme – β-lactamase; which functions to neutralize these antibiotics by cleaving the β-lactam ring (Wilke et al., 2005; Toussaint and Gallagher, 2015).”
From Fermentation Conditions that Affect Clavulanic Acid Production in Streptomyces clavuligerus: A Systematic Review (2016) · cites this paper as Toussaint and Gallagher, 2015
Clavulanic acid is commercially used with amoxicillin (Augmentin) and is listed as an important antibacterial in the WHO list of essential medicines (2015).
“Clavulanic acid or clavulanate, is commercially used along with amoxicillin (Augmentin) and this combination has been listed as an important antibacterial agents in the WHO list of essential medicines (2015) (Toussaint and Gallagher, 2015).”
From Fermentation Conditions that Affect Clavulanic Acid Production in Streptomyces clavuligerus: A Systematic Review (2016) · cites this paper as Toussaint and Gallagher, 2015
Clavulanic acid is used in combination with β-lactam antibiotics to treat a wide spectrum of infectious diseases.
“The β-lactamase inhibitor, clavulanic acid is frequently used in combination with β-lactam antibiotics to treat a wide spectrum of infectious diseases.”
From Fermentation Conditions that Affect Clavulanic Acid Production in Streptomyces clavuligerus: A Systematic Review (2016) · cites this paper as Toussaint and Gallagher, 2015
Cites
Three Decades of β-Lactamase Inhibitors
Drawz, S. M., & Bonomo, R. A. (2010) · Clinical Microbiology Reviews · doi:10.1128/cmr.00037-09 · Cited by 1,709 · see citing works
Carbapenem-Resistant Enterobacteriaceae: Epidemiology and Prevention
Gupta, N., Limbago, B. M., Patel, J. B., & Kallen, A. J. (2011) · Clinical Infectious Diseases · doi:10.1093/cid/cir202 · Cited by 1,033 · see citing works
Naturally-occurring beta-lactamase inhibitors with antibacterial activity
BROWN, A. G., BUTTERWORTH, D., COLE, M., HANSCOMB, G., HOOD, J. D., READING, C., & ROLINSON, G. N. (1976) · The Journal of Antibiotics · doi:10.7164/antibiotics.29.668 · Cited by 399 · see citing works
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Ser, H.-L., Law, J. W.-F., Chaiyakunapruk, N., Jacob, S. A., Palanisamy, U. D., Chan, K.-G., Goh, B.-H., & Lee, L.-H. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.00522 · Cited by 90 · see citing works
- Authors
- Toussaint, K. A., & Gallagher, J. C.
- Affiliations
- Temple University (US)
- ORCID
- Gallagher, Jason C.
- Venue
- Annals of Pharmacotherapy
- Publisher
- SAGE Publications
- Published
- 2014-10-31
- Volume
- 49
- Issue
- 1
- Pages
- 86-98
- ISSN
- 0012-6578 (ISSN-L)
- 1060-0280
- 1542-6270
- OpenAlex
- W2129772896
- Cited by
- 136
- References
- 3
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 10 · 2023: 8 · 2022: 12 · 2021: 10 · 2020: 12 · 2019: 9 · 2018: 14 · 2017: 16 · 2016: 21 · 2015: 17 · 2013: 1
- FWCI
- 1.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Pharmacotherapy (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
- Health Sciences › Medicine › Pharmacology › Antibiotics Pharmacokinetics and Efficacy
- Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Antibiotic Use and Resistance
- Keywords
- beta-lactam/beta-lactamase inhibitor combinations, beta-lactamase inhibitors, avibactam, relebactam, clavulanic acid, sulbactam, tazobactam, amoxicillin-clavulanic acid, ticarcillin-clavulanic acid, ampicillin-sulbactam, piperacillin-tazobactam, multidrug-resistant organisms, extended-spectrum beta-lactamase, AmpC beta-lactamase, carbapenemase, antimicrobial resistance, novel antibiotics
- MeSH terms
- Anti-Bacterial Agents, Bacterial Proteins, beta-Lactamases, Drug Therapy, Combination, Humans, beta-Lactams, beta-Lactamase Inhibitors
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