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Rifampin Bacteria rapidly become resistant to rifampin by developing mutations in the B subunit of RNA polymerase that render the enzyme unable to bind the antibiotic. The rapid selection of resistant mutants is the major limitation to the use of this antibiotic against otherwise-susceptible staphylococci and requires that the drug be used in combination with another antistaphylococcal agent. Linezolid Enterococci, streptococci, and staphylococci become resistant to linezolid in vitro by mutation of the 23S rRNA binding site. Clinical isolates of E. faecium and E. faecalis acquire resistance to linezolid readily by this mechanism, often during therapy, but linezolid-resistant staphylococcal and streptococcal. | Chapter 127. Treatment and Prophylaxis of Bacterial Infections Part 6 Rifampin Bacteria rapidly become resistant to rifampin by developing mutations in the B subunit of RNA polymerase that render the enzyme unable to bind the antibiotic. The rapid selection of resistant mutants is the major limitation to the use of this antibiotic against otherwise-susceptible staphylococci and requires that the drug be used in combination with another antistaphylococcal agent. Linezolid Enterococci streptococci and staphylococci become resistant to linezolid in vitro by mutation of the 23S rRNA binding site. Clinical isolates of E. faecium and E. faecalis acquire resistance to linezolid readily by this mechanism often during therapy but linezolid-resistant staphylococcal and streptococcal isolates are rare. Multiple Antibiotic Resistance The acquisition by one bacterium of resistance to multiple antibacterial agents is becoming increasingly common. The two major mechanisms are the acquisition of multiple unrelated resistance genes and the development of mutations in a single gene or gene complex that mediate resistance to a series of unrelated compounds. The construction of multiresistant strains by acquisition of multiple genes occurs by sequential steps of gene transfer and environmental selection in areas of high-level antimicrobial use. In contrast mutations in a single gene can conceivably be selected in a single step. Bacteria that are multiresistant by virtue of the acquisition of new genes include hospital-associated strains of gram-negative bacteria enterococci and staphylococci and community-acquired strains of salmonellae gonococci and pneumococci. Mutations that confer resistance to multiple unrelated antimicrobial agents occur in the genes encoding outer-membrane porins and efflux proteins of gram-negative bacteria. These mutations decrease bacterial intracellular and periplasmic accumulation of 0-lactams quinolones tetracyclines chloramphenicol and aminoglycosides. .
