The Chemical Relationship Among Beta-Lactam Antibiotics and Potential Impacts on Reactivity and Decomposition

Abstract

Beta-lactam antibiotics remain one of the most commonly prescribed drug classes, but they are limited by their propensity to cause hypersensitivity reactions (e.g., from allergy to anaphylaxis) as well as by the emergence of bacteria with a myriad of resistance mechanisms such as β-lactamases. While development efforts continue to focus on overcoming resistance, there are ongoing concerns regarding cross-contamination of β-lactams during manufacturing and compounding of these drugs. Additionally, there is a need to reduce levels of drugs such as β-lactam antibiotics in waste-water to mitigate the risk of environmental exposure. To help address future development of effective remediation chemistries and processes, it is desired to better understand the structural relationship among the most common β-lactams. This study includes the creation of a class-wide structural ordering of the entire β-lactam series, including both United States Food and Drug Association (US-FDA)-approved drugs and experimental therapies. The result is a structural relational map: the “Lactamome,” which positions each substance according to architecture and chemical end-group. We utilized a novel method to compare the structural relationships of β-lactam antibiotics among the radial cladogram and describe the positioning with respect to efficacy, resistance to hydrolysis, reported hypersensitivity, and Woodward height. The resulting classification scheme may help with the development of broad-spectrum treatments that reduce the risk of occupational exposure and negative environmental impacts, assist practitioners with avoiding adverse patient reactions, and help direct future drug research.

Chimeric Tobramycin-Based Adjuvant TOB-TOB-CIP Potentiates Fluoroquinolone and β-Lactam Antibiotics against Multidrug-Resistant Pseudomonas aeruginosa

“…aeruginosa are generally treated by aminoglycosides, polymyxins, β-lactam/β-lactamase inhibitor (BL/BLI) combinations, and fluoroquinolones (FQs). Among these antibiotics, β-lactams (BLs) and FQs have been widely prescribed to treat a broad range of Gram-positive and Gram-negative bacteria. − BLs covalently attach to penicillin-binding proteins (PBPs), thereby compromising the bacterial cell wall’s integrity and thus reducing the organism’s ability to proliferate . Resistance mechanisms toward BLs include modifications to PBPs’ active site, low outer membrane (OM) permeability, and the production of β-lactamases that hydrolyze the four-membered ring of BLs. , …”

“…20−23 BLs covalently attach to penicillinbinding proteins (PBPs), thereby compromising the bacterial cell wall's integrity and thus reducing the organism's ability to proliferate. 24 Resistance mechanisms toward BLs include modifications to PBPs' active site, low outer membrane (OM) permeability, and the production of β-lactamases that hydrolyze the four-membered ring of BLs. 25,26 On the other hand, FQs exert their antibacterial activity by inhibiting two bacterial enzymes, DNA gyrase and DNA topoisomerase IV.…”

Multi-drug resistant bacteria isolates from lymphatic filariasis patients in the Ahanta West District, Ghana

“…This trend is similar to reports of amoxicillin, flucloxacillin, tetracycline and ampicillin being the commonest pharmacy antibiotic medicines used in Ghana [ 43 ]. In a similar report, amoxicillin is one of the most prescribed antibiotics in the United States of America [ 44 ].…”

Mycobacterium abscessus: It’s Complex

“…Furthermore, T405 combined with probenecid exhibited bactericidal efficacy in the C3HeB/FeJ in vivo mouse model against the well-characterized ATCC29977 reference strain (Rimal B. et al, AAC, 2022, PMID:35638855). Beta-lactam antibiotics are known to interfere with bacterial cell wall peptidoglycan biosynthesis (for the mechanism of activity of b-lactams, see a recent review by Turner et al) [ 142 ].…”