Structure-activity relationships in the beta-lactam family: an impossible dream

The difficulty of establishing structure-activity relationships in the beta-lactam family of antibiotics stems from the fact that: (1) The targets in various bacteria exhibit widely different sensitivities. (2) Some bacteria produce beta-lactamases, enzymes capable of destroying the antibiotics. The rates of the reactions with the beta-lactamases and the target enzymes are not necessarily related. (3) In Gram-negative bacteria, the diffusion rate through the outer membrane varies independently from the two other factors.