ß-lactams belong to a family of antibiotics which is characterized by a ß-lactam ring. Penicillins, cephalosporins, clavams (or oxapenams), cephamycins and carbapenems are members of this family. The integrity of the ß-lactam ring is necessary for the activity which results in the inactivation of a set of transpeptidases that catalyze the final cross-linking reactions of peptidoglycan synthesis.
In gram positive bacteria, especially staphylococcus aureus, resistance of penicillin G is mainly through the production of beta-lactamase enzymes that break the beta-lactam ring. S.aureus secretes beta-lactamse enzyme extracellularly as inducible exoenzymes that are plasmid-mediated. The inherent resistance to penicillin G of many gram negative bacteria result from low permeability of the gram negative cell wall, lack of PBP`s, and a wide variety of beta-lactamse enzymes. Most gram negative bacteria inherently express low levels of species-specific, chromosomally mediated beta-lactamase enzyme within the periplasmic space, which sometimes contribute to resistance. These enzymes hydrolyze susceptible cephalosphorins more rapidly than penicillin G, but they hydrolyze ampicillin, carbenicillin, and beta-lactamase-resistant penicillins poorly.
In gram positive bacteria, especially staphylococcus aureus, resistance of penicillin G is mainly through the production of beta-lactamase enzymes that break the beta-lactam ring. S.aureus secretes beta-lactamse enzyme extracellularly as inducible exoenzymes that are plasmid-mediated. The inherent resistance to penicillin G of many gram negative bacteria result from low permeability of the gram negative cell wall, lack of PBP`s, and a wide variety of beta-lactamse enzymes. Most gram negative bacteria inherently express low levels of species-specific, chromosomally mediated beta-lactamase enzyme within the periplasmic space, which sometimes contribute to resistance. These enzymes hydrolyze susceptible cephalosphorins more rapidly than penicillin G, but they hydrolyze ampicillin, carbenicillin, and beta-lactamase-resistant penicillins poorly.
Production of plasmid-mediated beta-lactamase is widespread among common gram negative primary and opportunist bacterial pathogens. The enzymes are constitutively expressed, present in the periplasmic space, and cause high-level resistamce. The majority are penicillinases rather than cephalosphorinases. The most widespread are those classified on the basis of their hydrolytic activity as TEM-type beta-lactamases, which readily hydrolyze penicillin G and ampicillin rather than methicillin, cloxacillin, or carbenicillin. The less widespread OXA-type beta-lactamases hydrolyze penicillinase-stable penicillins (oxacillin, cloxacillin, and related drugs). Beta-lactamases probably evolved from PBP`s as a protective mechanism for soil organisms exposed to beta-lactamase in nature, in which they are thought to be widespread through their production by molds. Because of transferable resistance, beta-lactamase production by pathogens is now widespread.
A major advance has been the discovery of broad-spectrum beta-lactamase-inhibitory drugs (e.g. clavulanic acid, sulbactam, tazobactam). These drugs have weak antibacterial activity but show extraordinary synergism when administered with penicillin G, ampicilin, or amoxicillin because of irreversible binding to the beta-lactamase enzymes of resistant bacteria. Other beta-;actamase inhibitors, such as cefotaxime and carbapenems, have potent antibacterial activity in their own right.
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