18.01.2 Introduction to Antibiotics

The term chemotherapy is used to describe the use of drugs to treat infections caused by invading cells and therefore cover the anti-infective drugs and anti-cancer drugs. However, many people think of chemotherapy only in the treatment of cancer. The term selective toxicity is mainly used to describe the anti-microbials. Selective toxicity relates to a drug having toxicity to the invading microbial without toxicity to the host (e.g. the human).

Selective toxicity relies on differences in bacterial (prokaryote cells) and human/mammalian cells (eukaryote cells). Selective toxicity can be achieved by drugs attacking processes or pathways which are present in the microbial cell, but not the mammalian cell. For example, both prokaryote and eukaryote cells have cell membranes, but only the prokaryote cells have cell walls. Bacterial cell walls are often made of peptidoglycan, and the bacterial cell wall is a site at which antibacterial agents can attack. Eukaryote cells have their genetic material contained within a nucleus, whereas prokaryote cells only have a single chromosome containing all their genetic material. Some of the structures and processed involved in bacterial DNA synthesis, RNA synthesis and protein synthesis are different from those in the mammalian cells and can be targets for antibacterial agents. For example, the ribosomes are the place where protein synthesis takes place, and there are structural differences between the ribosomes in eukaryote and prokaryote cells. Thus, the bacterial ribosomes are a site at which antibacterial agents can attack. This chapter considers antibiotics that attack at these different sites.

Antibiotics can be classed as bactericidal or bacteriostatic. Antibiotics that are bactericidal cause the death of the bacteria. To be bactericidal, antibiotics usually interfere with cell wall synthesis or disrupt the cell membrane. Antibiotics that are bacteriostatic prevent the growth or division of bacteria. Once the growth of the bacteria has been arrested, it is hoped that the body’s own immune system will takes care of the remaining bacteria by killing them. To be bacteriostatic, drugs usually interfere with protein or nucleic acid synthesis in the bacteria.

Antimicrobials can be narrow or broad spectrum. Narrow spectrum anti-microbials are only effective against a small number of microbials. Broad spectrum anti-microbials are anti-microbials that are effective against a wider range of microbial species.

One topic about antibiotics that is commonly in the news is the emergence of drug-resistant organisms, which is largely blamed on the overuse and misuse of antibiotics. There are two main types of resistance. The first is due to chromosomal mutations in the bacteria, so that they take on a form that is no longer susceptible to the antibiotics. The best know example of this is Methicillin-resistant Staphylococcus Aureus (MRSA), which is resistant to the drug methicillin, which is one of the penicillins. MRSA causes severe infections, and is a problem in many hospitals. The second type of resistance is due to the induction of enzymes or transporters/carriers in the microbe. For example, microbials that have been treated successfully with the β-lactam penicillins in the past, have now induced their levels of the enzyme β-lactamase. The induced β-lactamases increase the breakdown of the penicillins, making them less effective.