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Dynamics of Antimicrobial Action (Introduction and Action rates of Antimicrobial chemicals)

Submitted to:
Dr. Sufia Islam

Submitted by:
Farzana Haque 2009-3-70-019

East West University Course name: Pharmaceutical Microbiology (305) Section: 2 Date: 8 December, 2010

Dynamics of Antimicrobial Action


Antimicrobial chemicals or agents
An anti-microbial is a substance that kills or inhibits the growth of microorganisms such as bacteria, fungi, or protozoans. Antimicrobial drugs either kill microbes (microbicidal) or prevent the growth of microbes (microbistatic). Disinfectants are antimicrobial substances used on non-living objects.

Classes of Antimicrobial agents


There are four main classes of antimicrobial agents. They are: I. Antibiotics II. Antivirals III. Antifungals IV. Antiphrastics

Antibiotics
Antibiotics are generally used to treat bacterial infections. The toxicity to humans and other animals from antibiotics is generally considered to be low. However, prolonged use of certain antibiotics can decrease the number of gut flora, which can have a negative impact on health. Some recommend that, during or after prolonged antibiotic use, one should consume probiotics and eat reasonably to replace destroyed gut flora..

3 Antibiotics are among the most commonly used drugs. For example, 30% or more hospitalized patients are treated with one or more courses of antibiotic therapy. Antibiotics are also among the drugs commonly misused by physicians, e.g. usage of antibiotic agents in viral respiratory tract infections.

Antivirals
Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics, specific antivirals are used for specific viruses. They are relatively harmless to the host, and therefore can be used to treat infections. They should be distinguished from viricides, which actively deactivate virus particles outside the body. Most of the antivirals now available are designed to help deal with

HIV; Herpes viruses, best known for causing cold sores and genital

herpes, The hepatitis B and C viruses, which can cause liver cancer, and

influenza A and B viruses. How it works

4 Antiviral drugs work by inhibiting the virus before it enters the cell, stopping it from reproducing, or, in some cases, preventing it from exiting the cell.

Antifungals
An antifungal drug is medication used to treat fungal infections such as Athlete's foot, Ringworm, Candidiasis (thrush), Serious systemic infections such as cryptococcal meningitis, and

others. How it works

Antifungals work by exploiting differences between

mammalian and fungal cells to kill off the fungal organism without dangerous effects on the host. Unlike bacteria, both fungi and humans are eukaryotes. Thus,

fungal and human cells are similar at the molecular level, making it more difficult to find a target for an antifungal drug to attack that does not also exist in the infected organism. Consequently, there are often side effects to some of these

drugs. Some of these side effects can be life-threatening if the drug is not used properly.

Antiparasitics
Antiparasitics are a class of medications which are indicated for the treatment of infection by parasites, such as Nematodes Cestodes Trematodes Infectious Protozoa and Amoebae. How it works Like antifungals, they must kill the infecting pest without

serious damage to the host.

Common antimicrobial agents and their uses

Use

Agents
Sulfonamides, isoniazid, p-aminosalicylic acid, penicillin, streptomycin, tetracyclines,

Antibacterials

chloramphenicol, erythromycin,

6 novobiocin, neomycin, bacitracin, polymyxin

Antipar asitics (humans) Emetine, quinine

Use
Antiparasitics (animal)

Agents
Hygromycin, phenothiazine, piperazine

Antifungals

Griseofulvin, nystatin Captan (N-trichlorothiotetrahydrophthalimide), maneb (manganese

Chemotherapeutics (plants)

ethylene bisdithiocarbamate), thiram (tetramethylthiuram disulfide) Alcohols, iodine, mercurials, silver compounds, quaternary ammonium

Skin disinfectants

compounds, neomycin

Water disinfectants

Chlorine, sodium hypochlorite

Air disinfectants

Propylene glycol, lactic acid, glycolic acid, levulinic acid

Gaseous disinfectants

Ethylene oxide, -propiolactone, formaldehyde

Clothing disinfectants

Neomycin

Use
Animal-growth stimulants

Agents
Penicillin, streptomycin, bacitracin, tetracyclines, hygromycin

Food preservatives

Sodium benzoate, tetracycline

Action Rates of Antimicrobial Chemicals


Mechanistic theories Quantitative expressions for rates of disinfection date from the beginning of the twentieth century. Rideal and Walker (1903) and Chick (1908) carried out many determinations on the effect of chemicals on bacteria. Watson (1908) derived mathematical expressions from Chicks data and showed that the reaction rate could be expressed in the same form as a first order chemical reaction , the

8 determinant being the number of cells in the culture. Interpretations of this kind that are based on theoratical mechanisms are called mechanistic theories. The resulting expression isK= log (a\a x )* t Where K is the rate constant, t is the time of contact before the sample is removed, a is the initial number of bacteria in the culture and

a-x is the number of organisms in the same volume after exposure for time t For mathematical convenience, this equation is usually written in its log form and graphs are drawn of log number of survivors against log time of exposure in minutes. When killing occurs at a first rate, the plot is a straight line : hence the term logarithmic order of death is often used to describe this type of death rate. (Fig :1)

Probit of percentage survivors

Logarithm of exposure time

9 Figure:(1) The logarithm order of bacterial death

Vitalistic theory Later workers, using lower concentrations of bactericides and therefore slower rates of kill, found that the plot was not straight but S-shaped (sigmoid) in (Fig:2.)

Fig:(2) A sigmoid time survivor curve Many suggestions were made and much experimental work was done in attempts to explain this type of curve. The same result is obtained in toxicity testing when the number of animals killed by doses of a drugs are being investigated.

10 It has been shown that this response is obtained because the sensitivities of the animals to tht toxic agent are not the same but follow a normal distribution. It therefore seemed possible that the resistant of a population of micro-organisms to a bactericide would also be distributed normally in relation to the log of the time of exposure since the latter is a form of dosage. This assumption led to a mathematical treatment that took into accout the variation in resistance in a population of organisms in a culture and produce a straight line graph. Because this interpretation allows for natural variation it is sometimes known as the vitalistic theory. Gaddums(1933) technique Gaddum (1933) used the following technique in biological assays that involved the death of proportion of groups of animals and he called the the numerical values derived from the normal distribution . normal equivalent deviates (NED) The 50 per cent value was designated zero and values to the left and right of this were given negative and positive values respectively.(Fig:3) represents a normal distribution curve.

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Figure (3) Properties of the Normal(Gaussian) distributoion curve The point 0 represents the mean resistance and -2 and +2 are spaced so that the distance of each from 0 along the log time axis represents two standard deviations. The part to the left of -2 represnts 2.5 per cent ; 0 represents 50 per cent and +2 represents 97.5 pr cent. This means that at the times corresponding to -2 , 0 and +2 , 2.5. 50 and 97.5 per cent respectively of the total population would be killed.

Per cent 2.5 50 97.5 Table:1

NED -2 0 +2

For the above example the following values would be allocated-

12 This interpretation produced a straight line with biological toxicity data, but in mathematical processing the negative sign was an encumbrance.

Bliss (1934). Working on population mortality statistics, suggested that it would be more convenient if 50 per cent were given the valu of 5 instead of zero and 5 was added to all of Gaddums NED values, ao that a negative value would be rare. The new units so obtained were named probability units, eventually shortened to probits. Since about 1947 , this system has been used in evaluating survivor data in studies of the action of bactericides. When probits are plotted against log of exposure a straight line generally results the (Fig :4)

Probit of percent mortality

Logarithm of time

Figure (4): Log time versus probit time mortality

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Although in pharmacy and microbiology Vitalistic theory has been widely applied to the destruction of bacteria by chemicals and by others lethal agents, it is not widely used outside these fields.

Bibliography

Charter.S.J; Tutorial Pharmacy; Dynamics of Antimicrobial Action; 6th edition; New Delhi;CBS Publishers & Distributors, 2000.

Antimicrobial agents; Retrieved: 2010; from: http://www.Answer.com.Antimicrobial agents.

Antimicrobial; Retrieved: 29 October 2010; from: Antimicrobial%20%20Wikipedia, %20the%20free%20encyclopedia.mht.