Inhibits the synthesis of a component of the mycobacterial cell wall.
Inhibits synthesis of mycolic acid, a major component of the mycobacterial cell wall.
the critical b-lactam ring, destroying the activity of the antibiotic. Just as there are many b-lactam drugs, there are various b-lactamases; these differ in the range of drugs they destroy. A b-lactamase that was originally detected in some strains of staphylococci only inactivates members of the penicillin family. To reflect this fact, it is often called a penicillinase. In contrast, some of the b-lactamases produced by Gram-negative organisms inactivate a wide variety of b-lactam drugs. The extended-spectrum b-lactamases inactivate both the penicillins and the cephalosporins. As a whole, Gram-negative bacteria can produce a much more extensive array of b-lactamases than can Gram-positive organisms.
The Penicillins Each member of the family of penicillins shares a common basic structure. Only the side chain has been modified in the laboratory to create penicillin derivatives, each with unique characteristics (figure 21.6). Currently the family of penicillins can be loosely grouped into several categories, each of which consists of several different drugs:
■ Natural penicillins. These are the original penicillins produced naturally by the mold Penicillium chrysogenum. Natural penicillins are narrow-spectrum antibiotics, effective against Gram-positive bacteria and some Gramnegative cocci. Strains of bacteria that produce penicillinase are resistant to the natural penicillins. Penicillin V is more stable in acid and, therefore, better absorbed than penicillin G when taken orally.
■ Penicillinase-resistant penicillins. These drugs were developed in the laboratory as a response to the problem of penicillinase-producing staphylococci. Their side chains prevent penicillinase from inactivating them. Unfortunately, some strains of penicillinase-producing Staphylococcus aureus have responded by synthesizing altered PBPs to which b-lactam drugs, including the penicillins, no longer bind. Penicillinase-resistant penicillins include methicillin and dicloxicillin.
■ Broad-spectrum penicillins. The modified side chains of these drugs give them a broad spectrum of activity. They retain their activity against penicillin-sensitive Gram-positive bacteria, yet they are also active against Gram-negative organisms. They can be inactivated, however, by many b-lactamases. Broad-spectrum penicillins include ampicillin and amoxicillin.
■ Extended-spectrum penicillins. These have greater activity against Pseudomonas species, Gram-negative bacteria that are unaffected by many conventional antimicrobial drugs. The extended-spectrum penicillins, however, have less activity against Gram-positive organisms. Like the other broad-spectrum penicillins, they are destroyed by many b-lactamase-producing organisms. Extended-spectrum penicillins include ticarcillin and piperacillin.
■ Penicillins + b-lactamase inhibitor. Rather than a new drug, this is a novel combination of therapeutic agents.
Nester-Anderson-Roberts: I III. Microorganisms and I 21. Antimicrobial I I © The McGraw-Hill
Microbiology, A Human Humans Medications Companies, 2003
Perspective, Fourth Edition
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