The chemicals that might be candidates for decontamination of surfaces in facilities or for waste-water treatment should be effective against a broad range of drugs at levels that are already employed for disinfection and be readily biodegradable themselves.Īs such, it was desired to assess the structural relationships among β-lactams to understand if a subset of drugs can serve as a proxy for others during development and testing. Because of their perceived or actual potential to cause allergic responses in a substantial portion of the host population, governmental guidelines and regulations involve special precautions to reduce the risk of cross-contamination from β-lactams ( Food and Drug Administration, 2013). While many previous studies have investigated the intricacies of drug binding and the impacts on efficacy and resistance, the relationship of molecular structure on the ability of chemical compounds and processes to decontaminate β-lactam residues from manufacturing and compounding facilities as well as terrestrial and aquatic environments has received less attention. Those synthetic efforts have resulted in four major β-lactam classes: monobactam, penams, penems, and cephems ( Figure 1). Interest in β-lactam antibiotics spurred scientists to explore a breadth of structural derivatives and platforms well beyond the above-mentioned natural substances in efforts to expand the spectrum. The first cephem, cephalothin, became available for patients in the United States as a parenteral drug in 1964 ( Greenwood, 2008). Shortly after the introduction of the penam penicillin, the first chemical compounds of the cephem group were isolated from the fungus Cephalosporium acremonium by Giuseppe Brotzu in 1948, when crude filtrates of a culture were found to inhibit the growth of Staphylococcus aureus ( Singh and Arrieta, 1999 Foye et al., 2008). By 1944 penicillin was being manufactured at the rate of over a billion doses a year ( Aldridge et al., 1999). Since the first clinical uses of penicillin G in the 1930s and 1940s, β-lactam antimicrobials have enjoyed marked success in the treatment of bacterial infections. 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. 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 result is a structural relational map: the “Lactamome,” which positions each substance according to architecture and chemical end-group. 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. 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. 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. 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.
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