Drug tolerant: loss of affinity of the target biomolecule of the microorganism for a particular AMA. E.g., resistant Staph.aureus and E.coli developa RNA polymerase that does not bind rifampin.
Drug destroying: β - lactamase by Staphylococci, Haemophilus, Gonococci etc., which inactivate penicillin G. Chloramphenicol acetyl transferase is acquired by resistant E.coli, H.influenzae and S.typhi.
Aminoglycoside resistant coliforms – produce enzymes which adenulate/acetylate/phosphorylate specific aminoglycoside antibitotics.
c) Drug impermeable: Many hydrophilic antibiotics access though porins, or need specific transport mechanisms. Glycosides and tetracyclines in the resistant gram negative bacterial strains.