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Publication Date: November 2005
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Date Published: November 2005
Antibiotics are naturally occurring or synthetic substances that kill or interfere with the growth of specific bacteria. They are the most widely used drugs to treat or prevent infections. Infections that were fatal before antibiotics were discovered are now under almost complete control, if not for the development of resistant bacterial strains. This course is divided into five sections.
This course provides a medical background on antibiotic therapy. It is divided into the following sections:
The first section, HOW ANTIBIOTICS WORK, presents an overview of the types of antibiotic activity and the general mechanisms of action of antibiotics.
The second section, PHARMACOKINETICS OF ANTIBIOTICS, describes how antibiotics move through the body, the processes by which they are modified, and how these processes determine their efficacy and optimum dosage.
The third section, CLASSES OF ANTIBIOTICS, lists the general classes of antibiotics, their pharmacokinetic profiles, modes of action, antibacterial spectrum and side effects.
The fourth section, BACTERIAL RESISTANCE, describes the extent of bacterial resistance to antibiotics and conditions that favour the development of resistance.
The fifth section, ANTIBIOTIC SELECTION, presents criteria for the selection of antibiotics, tests for bacterial sensitivity, principles of combination therapy and antibiotic prophylaxis.
Antibiotics have either bactericidal or bacteriostatic activity, or both. This section describes a number of mechanisms underlying such activities.
These are the objectives for this section. You will be tested on these objectives in the final assessment.
After you finish this section, you should be able to:
Antibiotics are naturally occurring, synthetic, or semi-synthetic chemical substances that can kill microorganisms or inhibit their reproduction. This lesson presents an overview of the discovery of antibiotics, and the general features of these agents that are relevant to the treatment of infectious diseases.
An antibiotic is a substance produced by a microorganism, or partly or wholly by chemical synthesis, that has the ability to kill microorganisms or prevent their growth and reproduction.
Antibiotic agents were first discovered in the 1870s by the French chemist Louis Pasteur, who discovered that inoculating animals with common airborne bacteria at the same time that they were experimentally infected with pathogenic anthrax bacilli protected the animals from developing anthrax. Those common airborne bacteria that he added to the inoculum acted as the first known antibiotic agents.
The first antibiotic drug was discovered in 1928 in a now-famous accident. The Scottish biologist Alexander Fleming was about to throw away some bacteria culture dishes that had been contaminated with mold, when he noticed that the mold colony was surrounded by a clear area where the bacteria had stopped growing. After further studying the mold, Penicillium notatum, Fleming discovered that it secreted a substance that inhibited bacterial growth, which he named "penicillin."
By growing microorganisms in liquid and creating fermentation broths, scientists were able to extract and purify pharmacologic penicillins and many other antibiotic substances on a large scale. In addition, other agents with antibiotic activity have been synthesised chemically. Currently, both synthetic and microorganism-produced agents are called "antibiotics", or "antimicrobials".
An antibiotic’s usefulness in the clinic is a reflection of its therapeutic index, or the ratio between the highest tolerated dose and the lowest effective dose. Two properties that play important roles in determining these values are its antibacterial spectrum and selective toxicity. The antibacterial spectrum of an agent is the range of pathogens against which it is effective. Thus, a broad-spectrum antibiotic is effective against a wide range of microorganisms, while an antibiotic that has a narrow spectrum of activity is effective only against a narrow range of microorganisms.
Selective toxicity is an antibiotic’s property of being far more toxic to the invading microorganism than to the human host. Usually, an agent that inhibits a microbial function that is not found in eucaryotic animal cells has a higher therapeutic index because of its greater selective toxicity. These properties are affected by the drug’s structure, chemistry, pharmacology, and modes of action.
Antibiotics act against the diseases caused by bacteria in one of two ways. Bacteriostatic actions interfere with bacterial growth, while bactericidal actions kill bacteria directly. These actions are accomplished by different mechanisms, including disruption of the bacterial cell wall and plasma membrane, and interference with protein synthesis, nucleic acid synthesis, or other vital metabolic processes.
Antibiotics are either bactericidal or bacteriostatic. The first set of illustrations represents bacterial growth in the absence of any antibiotic.
The second set shows that bactericidal agents directly kill the bacterial cells, causing irreversible destruction of the bacterial population.
Bacteriostatic agents do not kill individual bacterial cells, but interfere with bacterial growth and reproduction by inhibiting essential metabolic processes such as the synthesis of proteins or nucleic acids. Thus, when existing bacteria die naturally after completing their life spans, there are no new bacteria to replace them. If administration of a bacteriostatic drug is stopped before the existing bacteria have died, the bacterial population often begins to grow again.
Some antibiotics can be both bactericidal and bacteriostatic, depending upon the concentration of drug that is present.
Antibiotics kill or prevent growth of bacteria by their effect on vital bacterial structures and processes. These include disruption of cell wall synthesis, interference with the plasma membrane, and inhibition of protein synthesis, nucleic acid synthesis, and other vital metabolic processes in the bacterial cell.
The essential component of bacterial cell walls are peptidoglycans, which are made primarily of sugars and proteins that form cross-linked chains. The resulting structure provides stability and protection for the bacterial cell. Peptidoglycan synthesis involves more than two dozen bacterial enzymes and takes place in three distinct stages.
The components of the bacterial cell wall must constantly be replaced as they wear out or undergo injury. Bacteria that are undergoing this process can be killed by an antibiotic that disrupts cell wall synthesis at any stage of the process. Drugs that act in this way are bactericidal because they weaken, lyse, and eventually kill the bacterial cell. Examples of these agents are the beta-lactam antibiotics, including the penicillins, carbapenems and cephalosporins.
The bacterial cell contents are enclosed by the plasma membrane. The membrane is referred to as semipermeable, or selectively permeable; it allows some molecules to flow into and out of the cell interior, but it acts as a barrier to others.
Some antibiotics, including the now rarely used polymyxins, disrupt the permeability of this vital cell component by binding to structures in the membrane. This binding alters the membrane chemistry and destroys its selective permeability. The vital cell contents leak out of the cell, and the bacterium is destroyed. Therefore, this action is bactericidal.
Ribosomes are the protein "factories" of the cells. Protein is vital for growth, so actively growing cells contain numerous ribosomes in their cytoplasm. A ribosome is made up of two subunits. Bacterial ribosomes consist of a small 30s subunit and a large 50s subunit. These subunits differ from those found in human cells.
Antibiotics exert both bacteriostatic and bactericidal actions by interfering with the functions of both the 30s and 50s ribosome subunits of bacterial cells. Examples of these are the tetracyclines, which inhibit protein synthesis by binding to the 30s subunit, and erythromycin, which acts in the same way on the 50s subunit.
Antibiotics such as the quinolones exert bactericidal actions by interfering with the normal synthesis of the nucleic acids DNA and RNA. These nucleic acids form the genetic material and serve as templates for protein synthesis. The rapid bactericidal action of the quinolones, such as nalidixic acid, results from direct interference with the enzymes of DNA replication. Failure of the DNA to replicate leads to failure of the bacterial cell to reproduce.
Antibiotics such as the sulphonamides exert bacteriostatic actions by blocking the synthesis of folic acid, a B vitamin that bacteria must produce in order to manufacture amino acids and DNA. Folic acid is produced from para-aminobenzoic acid (or PABA) through an enzyme-catalysed pathway. Sulfa drugs mimic the structure of PABA and compete for binding sites on the enzyme involved, interfering with its action and effectively blocking folic acid synthesis. Since folic acid is required for DNA synthesis, this leads to a block in DNA replication, inability of the bacterial cells to reproduce, and death of the bacterial population.
Roll your cursor on each mechanism to review its effect on bacterial structures and processes.
This "drag and drop" progress check will test your knowledge of the information presented in this section. Because your score will not be recorded, you may take the progress check as many times as you would like.
Please feel free to review the lessons as often as required to successfully complete the progress check.
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