Antibiotics

Overview

• If bacteria make it past our immune system and start reproducing inside our bodies, they cause disease.

• Certain bacteria produce chemicals that damage or disable parts of our bodies.

• Antibiotics work to kill bacteria.Antibiotics are specific to certain bacteria and disrupt their function.

What is an Antibiotic?• An antibiotic is a selective poison.

• It has been chosen so that it will kill the desired bacteria, but not the cells in your body. Each different type of antibiotic affects different bacteria in different ways.

• For example, an antibiotic might inhibit a bacteria's ability to turn glucose into energy, or the bacteria's ability to construct its cell wall. Therefore the bacteria dies instead of reproducing.

History• Although for centuries preparations derived

from living matter were applied to wounds to destroy infection, the fact that a microorganism is capable of destroying one of another species was not established until the latter half of the 19th cent. when Pasteur noted the antagonistic effect of other bacteria on the anthrax organism and pointed out that this action might be put to therapeutic use.

History• Meanwhile the German chemist Paul Ehrlich

developed the idea of selective toxicity: that certain chemicals that would be toxic to some organisms, e.g., infectious bacteria, could be killed but not other organisms, e.g., humans.

• In 1928, Sir Alexander Fleming, a Scottish biologist, observed that Penicillium notatum, a common mold, had destroyed staphylococcus bacteria in culture.

History• In 1939 the American microbiologist René Dubos

demonstrated that a soil bacterium was capable of decomposing the starchlike capsule of the pneumococcus bacterium, without which the pneumococcus is harmless and does not cause pneumonia. Dubos then found in the soil a microbe, Bacillus brevis, from which he obtained a product, tyrothricin, that was highly toxic to a wide range of bacteria. Tyrothricin, a mixture of the two peptides gramicidin and tyrocidine, was also found to be toxic to red blood and reproductive cells in humans but could be used to good effect when applied as an ointment on body surfaces.

History continued

• Dubos then found in the soil a microbe, Bacillus brevis, from which he obtained a product, tyrothricin, that was highly toxic to a wide range of bacteria. Tyrothricin, a mixture of the two peptides gramicidin and tyrocidine, was also found to be toxic to red blood and reproductive cells in humans but could be used to good effect when applied as an ointment on body surfaces.

History

• Penicillin was finally isolated in 1939, and in 1944 Selman Waksman and Albert Schatz, American microbiologists, isolated streptomycin and a number of other antibiotics from Streptomyces griseus.

Antibiotics today

The antibiotics we take today are still produded by bacteria

Many are now chemically synthesized

Classification

Antibiotics can be classified in several ways.

1.Spectrum

2.Bactericidal or bacteriostatic

3.Modes of action

4.Chemical structure

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SpectrumBroad

They target a number of bacteria or they are specific to one type

Used for diseases like meningitis

e.g. amoxicillin

Narrow

Target only a group of bacteria

Good for preventing antibiotic resistance

Eg. vancomycin

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Classification

1. Bactericidal or bacteriostatic

Bactericidal – kills bacteria

Bacteriostatic – stops bacterial growth

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Classification

Modes of action

• Some antibiotics attack the cell wall; some disrupt the cell membrane; and others inhibit the synthesis of nucleic acids and proteins.

Penicillin• All penicillin like antibiotics inhibit synthesis of

peptidoglycan, an essential part of the cell wall. They do not interfere with the synthesis of other intracellular components.

• The continuing buildup of materials inside the cell exerts ever greater pressure on the membrane, which is no longer properly supported by peptidoglycan.

• The membrane gives way, the cell contents leak out, and the bacterium dies. These antibiotics do not affect human cells because human cells do not have cell walls.

Mechanisms of Action

• Many antibiotics operate by inhibiting the synthesis of various intracellular bacterial molecules, including DNA, RNA, ribosomes, and proteins. The synthetic sulfonamides are among the antibiotics that indirectly interfere with nucleic acid synthesis. Some antibacterials affect the assembly of messenger RNA, thus causing its genetic message to be garbled. When these faulty messages are translated, the protein products are nonfunctional.

Classificationby chemical structure

• Beta-Lactams – Penicillins– Cephalosporins

• Macrolides

• Fluoroquinolones

• Tetracyclines

• Aminoglycosides

Administration and Side Effects

• Antibiotics are either injected, given orally, or applied to the skin in ointment form. Many, while potent anti-infective agents, also cause toxic side effects. Some, like penicillin, are highly allergenic and can cause skin rashes, shock, and other manifestations of allergic sensitivity. Others, such as the tetracyclines, cause major changes in the intestinal bacterial population and can result in superinfection by fungi and other microorganisms.

Production of Antibiotics

• The mass production of antibiotics began during World War II with streptomycin and penicillin. Now most antibiotics are produced by staged fermentations in which strains of microorganisms producing high yields are grown under optimum conditions in nutrient media in fermentation tanks holding several thousand gallons.

Production of Antibiotics• The mold is strained out of the fermentation broth, and

then the antibiotic is removed from the broth by filtration, precipitation, and other separation methods. In some cases new antibiotics are laboratory synthesized, while many antibiotics are produced by chemically modifying natural substances; many such derivatives are more effective than the natural substances against infecting organisms or are better absorbed by the body, e.g., some semisynthetic penicillins are effective against bacteria resistant to the parent substance.

Antimicrobial Resistance

• Relative or complete lack of effect of antimicrobial against a previously susceptible microbe

• Increase in MIC

• Enzymatic destruction of drug• Prevention of penetration of drug• Alteration of drug's target site• Rapid ejection of the drug

Mechanisms of Antibiotic Resistance

Antibiotic Selection for Resistant Bacteria

What Factors Promote Antimicrobial Resistance?

• Exposure to sub-optimal levels of antimicrobial

• Exposure to microbes carrying resistance genes

Inappropriate Antimicrobial Use

• Prescription not taken correctly• Antibiotics for viral infections• Antibiotics sold without medical

supervision• Spread of resistant microbes in

hospitals due to lack of hygiene

Inappropriate Antimicrobial Use

• Lack of quality control in manufacture or outdated antimicrobial

• Inadequate surveillance or defective susceptibility assays

• Poverty or war• Use of antibiotics in foods

Antibiotics in Foods

• Antibiotics are used in animal feeds and sprayed on plants to prevent infection and promote growth

• Multi drug-resistant Salmonella typhi has been found in 4 states in 18 people who ate beef fed antibiotics

Consequences of Antimicrobial Resistance

• Infections resistant to available antibiotics

• Increased cost of treatment

Multi-Drug Resistant TB

MRSA “mer-sah”

• Methicillin-Resistant Staphylococcus aureus

• Most frequent nosocomial (hospital-acquired) pathogen

• Usually resistant to several other antibiotics

Vancomycin Resistant Enterococci

Vancomycin Use USA

Proposals to Combat Antimicrobial Resistance

• Speed development of new antibiotics

• Track resistance data nationwide

• Restrict antimicrobial use

• Direct observed dosing (TB)

Proposals to Combat Antimicrobial Resistance

• Use more narrow spectrum antibiotics

• Use antimicrobial cocktails