Beta Lactam Resistance

Beta Lactam Resistance

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.
Resistance to ß-lactams in clinical isolates is primarily due to the hydrolysis of the antibiotic by a ß-lactamase. Mutational events resulting in the modification of PBPs (penicillin binding proteins) or cellular permeability can also lead to ß-lactam resistance.
ß-lactamases constitute a heterogenous group of enzymes. Several classification schemes have been proposed according to their hydrolytic spectrum, susceptibility to inhibitors, genetic localisation (plasmidic or chromosomal), gene or amino-acid protein sequence. The functional classification scheme of ß-lactamases proposed by Bush, Jacoby and Medeiros (1995) defines four groups according to their substrate and inhibitor profiles. Group 1 are cephalosporinases that are not well inhibited by clavulanic acid; group 2 penicillinases, cephalosporinases, and broad-spectrum ß-lactamases that are generally inhibited by active site-directed ß-lactamase inhibitors; group 3 metallo-ß-lactamases that hydrolyze penicillins, cephalosporins, and carbapenems and that are poorly inhibited by almost all ß-lactam-containing molecules; group 4 penicillinases that are not well inhibited by clavulanic acid. Subgroups were also defined according to rates of hydrolysis of carbenicillin or cloxacillin (oxacillin) by group 2 penicillinases. The classification initially introduced by Ambler (1980) and based on the amino-acid sequence recognizes four molecular classes designated A to D. Classes A, C, and D gather evolutionarily distinct groups of serine enzymes, and class B the zinc-dependent ("EDTA-inhibited") enzymes.