Enzyme inactivation is the main mode of resistance to:
Correct Answer: Aminoglycosides
Description: Resistance to aminoglycosides is acquired by one of the following mechanisms: (a) Acquisition of cell membrane bound inactivating enzymes which phosphorylate/ adenylate or acetylate the antibiotic. The conjugated aminoglycosides do not bind to the target ribosomes and are incapable of enhancing active transpo like the unaltered drug. These enzymes are acquired mainly by conjugation and transfer of plasmids. Nosocomial microbes have become rich in such plasmids, some of which encode for multidrug resistance. This is the most impoant mechanism of development of resistance to aminoglycosides. Susceptibility of different aminoglycosides to these enzymes differs. Thus, cross resistance among different members is paial or absent. (b) Mutation decreasing the affinity of ribosomal proteins that normally bind the aminoglycoside: this mechanism can confer high degree resistance, but operates to a limited extent, e.g. E. coli that develop streptomycin resistance by single step mutation do not bind the antibiotic on the polyribosome. Only a few other instances are known. This type of resistance is specific for a paicular amino glycoside. (c) Decreased efficiency of the aminoglycoside transpoing mechanism: either the pores in the outer coat become less permeable or the actiYe transpo is interfered. This again is not frequently encountered in the clinical setting. In some Pseudomonas which develop resistance, the antibiotic induced 2nd phase active transpo has been found to be deficient. ESSENTIALS OF MEDICAL PHARMACOLOGY Page no.744
Category:
Pharmacology
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