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Christine C. Sanders, W. Eugene Sanders, Emergence of Resistance During Therapy with the Newer β-Lactam Antibiotics: Role of Inducible β-Lactamases and Implications for the Future, Reviews of Infectious Diseases, Volume 5, Issue 4, July 1983, Pages 639–648, https://doi.org/10.1093/clinids/5.4.639
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Abstract
A number of β-lactam antibiotics that are relatively resistant to hydrolysis by β-lactamases have been developed. This characteristic has expanded the antibacterial spectrum of the drugs beyond that of their progenitors. However, it also appears responsible for several problems that have been observed with the new drugs, including the development of microbial cross-resistance to multiple β-lactam antibiotics and occasionally to the aminoglycosides. Strains most often involved are Enterobacter, Serratia, and Pseudomonas—genera that characteristically possess inducible β-lactamases. Derepression of these enzymes is one mechanism shown to be responsible for the development of resistance to multiple β-lactam antibiotics. Since in most instances the drugs are not susceptible to hydrolysis by these enzymes, resistance is produced by a nonhydrolytic barrier mechanism; i.e., the β-lactamases bind the drugs, thus preventing their access to target proteins. Alterations in permeability and in penicillin-binding proteins are other possible mechanisms by which resistance may develop; however, these have not been investigated extensively. In addition to the problem of emergence of resistance, potential problems include the impact of multiply β-lactam-resistant strains as nosocomial pathogens and antagonism between β-lactam antibiotics used in combination. Only through a careful assessment of the relative advantages and disadvantages of these new β-lactam antibiotics can their appropriate place in chemotherapy and chemoprophylaxis be identified.
