Abstract
β-Lactam antibiotics are the most commonly prescribed antibiotics
worldwide; however, antimicrobial resistance (AMR)
is a global challenge. The β-lactam resistance in Gram-negative
bacteria is due to the production of β-lactamases, including
extended-spectrum β-lactamases, metallo-β-lactamases,
and carbapenem-hydrolyzing class D β-lactamases.
To restore the efficacy of BLAs, the most successful strategy
is to use them in combination with β-lactamase inhibitors
(BLI). Here we review the medically relevant β-lactamase
families and penicillins, diazabicyclooctanes, boronic acids,
and novel chemical scaffold-based BLIs, in particular approved
and under clinical development.
Citations
Citations to this article as recorded by

- Functional and structural analyses of IMP-27 metallo-β-lactamase: evolution of IMP-type enzymes to overcome Zn(II) deprivation
Yoshiki Kato, Toshio Yamaguchi, Haruka Nakagawa-Kamura, Yoshikazu Ishii, Akiko Shimizu-Ibuka, Pablo Power
Microbiology Spectrum.2024;[Epub] CrossRef - Current Strategy for Targeting Metallo-β-Lactamase with Metal-Ion-Binding Inhibitors
Jessica L. Ortega-Balleza, Lenci K. Vázquez-Jiménez, Eyra Ortiz-Pérez, Guadalupe Avalos-Navarro, Alma D. Paz-González, Edgar E. Lara-Ramírez, Gildardo Rivera
Molecules.2024; 29(16): 3944. CrossRef - Understanding the Functional Dynamics of the TokK Enzyme in Carbapenem Biosynthesis via MD Simulations and QM/MM Calculations
Shakir Ali Siddiqui, Kshatresh Dutta Dubey
Inorganic Chemistry.2024; 63(40): 18963. CrossRef - Recent advances in functionalized macrocyclic polyamines for medicine applications
Hao Chang, Renzhong Qiao, Chao Li
Chinese Chemical Letters.2024; : 110675. CrossRef - Exploring the dynamics of gut microbiota, antibiotic resistance, and chemotherapy impact in acute leukemia patients: A comprehensive metagenomic analysis
Ying Luo, Taha Majid Mahmood Sheikh, Xin Li, YuMeng Yuan, Fen Yao, Meimei Wang, Xiaoling Guo, Jilong Wu, Muhammad Shafiq, Qingdong Xie, Xiaoyang Jiao
Virulence.2024;[Epub] CrossRef - Decrypting biocontrol functions and application modes by genomes data of three Trichoderma Strains/Species
Shida Ji, Bin Liu, Jing Han, Ning Kong, Yongfeng Yang, Yucheng Wang, Zhihua Liu
Fungal Genetics and Biology.2024; 172: 103889. CrossRef - Revisiting the Checkerboard to Inform Development of β-Lactam/β-Lactamase Inhibitor Combinations
Darren J. Bentley
Antibiotics.2024; 13(4): 337. CrossRef - Role of β-Lactamase Inhibitors as Potentiators in Antimicrobial Chemotherapy Targeting Gram-Negative Bacteria
Song Zhang, Xinyu Liao, Tian Ding, Juhee Ahn
Antibiotics.2024; 13(3): 260. CrossRef - The C5α-Methyl-Substituted Carbapenem NA-1-157 Exhibits Potent Activity against Klebsiella spp. Isolates Producing OXA-48-Type Carbapenemases
Clyde A. Smith, Nichole K. Stewart, Marta Toth, Pojun Quan, John D. Buynak, Sergei B. Vakulenko
ACS Infectious Diseases.2023; 9(5): 1123. CrossRef - Phenotypes, genotypes and breakpoints: an assessment of β-lactam/β-lactamase inhibitor combinations against OXA-48
Tomefa E Asempa, Abigail K Kois, Christian M Gill, David P Nicolau
Journal of Antimicrobial Chemotherapy.2023; 78(3): 636. CrossRef - Characteristics of Extended-Spectrum β-Lactamase-Producing Escherichia coli Derived from Food and Humans in Northern Xinjiang, China
Yushuang Wu, Shudi Huang, Donglai Zhang, Hua Ji, Yongqing Ni, Xueling Zhang, Juan Dong, Baokun Li
Foodborne Pathogens and Disease.2023; 20(7): 270. CrossRef - Sequential C−H Methylation Catalyzed by the B12‐Dependent SAM Enzyme TokK: Comprehensive Theoretical Study of Selectivities
Wen‐Hao Deng, Rong‐Zhen Liao
Chemistry – A European Journal.2023;[Epub] CrossRef - CMOS Spectrophotometric Microsystem for Malaria Detection
Gabriel M. Ferreira, Vitória Baptista, Vítor Silva, Maria I. Veiga, Graça Minas, Susana O. Catarino
IEEE Transactions on Biomedical Engineering.2023; 70(8): 2318. CrossRef - Synthesis and β-Lactamase Inhibition Activity of Imidates of Diazabicyclooctane
Lijuan Zhai, Jian Sun, Jingwen Ji, Lili He, Yuanyu Gao, Jinbo Ji, Yuanbai Liu, Yangxiu Mu, Xueqin Ma, Dong Tang, Haikang Yang, Zafar Iqbal, Zhixiang Yang
Russian Journal of Bioorganic Chemistry.2022; 48(5): 1059. CrossRef - Recent Developments to Cope the Antibacterial Resistance via β-Lactamase Inhibition
Zafar Iqbal, Jian Sun, Haikang Yang, Jingwen Ji, Lili He, Lijuan Zhai, Jinbo Ji, Pengjuan Zhou, Dong Tang, Yangxiu Mu, Lin Wang, Zhixiang Yang
Molecules.2022; 27(12): 3832. CrossRef - Retracted and replaced: Phenotypes, genotypes and breakpoints: an assessment of β-lactam/ β-lactamase inhibitor combinations against OXA-48
Tomefa E Asempa, Abigail K Kois, Christian M Gill, David P Nicolau
Journal of Antimicrobial Chemotherapy.2022; 77(10): 2622. CrossRef - Carbapenemase producing Klebsiella pneumoniae: implication on future therapeutic strategies
Ilias Karaiskos, Irene Galani, Vassiliki Papoutsaki, Lamprini Galani, Helen Giamarellou
Expert Review of Anti-infective Therapy.2022; 20(1): 53. CrossRef - Antimicrobial Activity of Dihydroisocoumarin Isolated from Wadi Lajab Sediment-Derived Fungus Penicillium chrysogenum: In Vitro and In Silico Study
Raha Orfali, Shagufta Perveen, Mohamed Fahad AlAjmI, Safina Ghaffar, Md Tabish Rehman, Abdullah R. AlanzI, Saja Bane Gamea, Mona Essa Khwayri
Molecules.2022; 27(11): 3630. CrossRef - The Odd Couple(s): An Overview of Beta-Lactam Antibiotics Bearing More Than One Pharmacophoric Group
Margherita De Rosa, Anna Verdino, Annunziata Soriente, Anna Marabotti
International Journal of Molecular Sciences.2021; 22(2): 617. CrossRef - Drugs That Changed Society: History and Current Status of the Early Antibiotics: Salvarsan, Sulfonamides, and β-Lactams
Søren Brøgger Christensen
Molecules.2021; 26(19): 6057. CrossRef - In Crystallo Time-Resolved Interaction of the Clostridioides difficile CDD-1 enzyme with Avibactam Provides New Insights into the Catalytic Mechanism of Class D β-lactamases
Nichole K. Stewart, Marta Toth, Anastasiya Stasyuk, Sergei B. Vakulenko, Clyde A. Smith
ACS Infectious Diseases.2021; 7(6): 1765. CrossRef - Inhibition of the Clostridioides difficile Class D β-Lactamase CDD-1 by Avibactam
Nichole K. Stewart, Marta Toth, Anastasiya Stasyuk, Mijoon Lee, Clyde A. Smith, Sergei B. Vakulenko
ACS Infectious Diseases.2021; 7(5): 1164. CrossRef