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.