Antibacterial agents

Antibacterial agents are categorized as narrow-, broad-, or extended-spectrum agents. Narrow-spectrum agents (e.g., penicillin G) affect primarily gram-positive bacteria. Broad-spectrum antibiotics, such as tetracyclines and chloramphenicol, affect both gram-positive and some gram-negative bacteria. An extended-spectrum antibiotic is one that, as a result of chemical modification, affects additional types of bacteria, usually gram-negative bacteria.

Whether an antimicrobial agent affects a microorganism depends on several factors. The drug must be delivered to a sensitive site in the cell, such as an enzyme that is involved in the synthesis of a cell wall or a protein or enzyme responsible for the synthesis of proteins, nucleic acids, or the cell membrane. Whether the antibiotic enters thecell depends on the ability of the drug to penetrate the outer membrane of the cell, or on the presence or absence of transport systems for the antimicrobial agent, or on the availability of channels in the cell surface. In some cases the microorganism prevents the entry of the antibiotic by producing an enzyme that destroys or modifies the antibiotic by transferring a chemical group. If the aintimicrobial agent does not penetrate the organism or is destroyed or modified, or if the organism does not contain a sensitive site, then the microorganism will not be affected; in such a case it is said to be resistant.

A major problem associated with the use of antibacterial drugs is that an organism that originally was sensitive to a given drug can become resistant. For example, bacteria undergo spontaneous mutations; and exposure of these bacteria to an antimicrobial can eradicate sensitive organisms, thereby selecting a population resistant to that drug and sometimes to related drugs. Bacteria sensitive to anitimicrobial agents can become resistant by acquiring from resistant organisms deoxyribonucleic acid (DNA) containing genes coding for resistance (resistance genes). Bacteria sensitive to an antimicrobial can mate (conjugation) with bacteria containing resistance genes, or they can acquire these resistance genes by transduction. In transduction, a bacterial virus (bacteriophage) incorporates resistance genes into its genome by infecting a resistant bacterium. When the bacterial virus infects another bacterium, the phage DNA (containing resistance genes) can be incorporated into that bacterium and center resistance. Some bacteria may acquire multiple resistance genes simultaneously and become resistant to several antibiotics. This is possible because circular pieces of DNA (plasmids) can, by recombination, acquire several genes, each of which codes for resistance to a different agent. Plasmids containing these multiple resistance genes can transfer to sensitive bacteria and thereby confer multiple resistance. Transfer of genes into the chromosome or into plasmids is facilitated in many cases because the genes are found on transposons, which are sequences of DNA that can excise themselves from plasmids and chromosomes and insert themselves into other plasmids and chromosomes. Bacteria resistant to as many as 10 different antimicrobial agents are known. One of the major problems associated with the transfer of resistance genes is that they can be transferred not only among similar but also to quite different bacteria.

Resistance to antimicrobial agents results from (1) decreased permeability of the organism to the drug; (2) deactivation or modification of the drug by an enzyme; (3) modification of the drug receptor or binding site; (4) increased synthesis of an essential metabolite whose production is blocked by the antimicrobial agent; or (5) production of an enzyme that is altered so that it is not inhibited or affected by the drug.