SIUST Antibiotics

8/14/2019 SIUST Antibiotics

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Louis Pasteur portrait in

his later years.

Photomicrograph of

Bacillus anthracis

(fuchsin-methylene blue

spore stain).

Image ofVibrio choleraeProf.SirAlexander Fleming

Antibiotics1The word antibiotic is derived from the term Antibiosis, which means against life. antibiotics

are chemical compounds produced by micro organisms (M.O) which, in low concentrations,

have the capacity to inhibit or kill, selectively, other micro organisms.

The selectivity or selective toxicity, means that the antibiotic compound inhibits or kills the

M.O without having a similar effect on the host organism (e.g. humans).

Essentially all definitions limit antibiotics to compounds that exert their action in low

concentrations.

This definition excludes compounds such as: ethanol that are active at higher concentrations.

The term antimicrobial agent is a general term which includes:

1-Natural, antibiotics from M.O

2-Synthetic, chemotherapeutic agents ,or synthetic not found in nature, obtained by chemical synthesis

3-Natural, obtained from non-microbial sources, from higher plants and animal...etc.

The first scientific recording of antibiotic activity was made by Louis Pasteurwho in 1877 reported that animals injected with an inoculation containing

Bacillusanthracis and certain other commonBacilli failed to develop anthrax2.

anthrax2. Ten years after Pasteur's discovery, another scientist called

Emmerich ( 1887 ) accidently discovered that a guinea-pig3

which had

previously been injected with Streptococcus erysipelatis failed to develop

Cholera4

when injected with virulent cultures ofVibriocholerae.

The recognition of the phenomenon of antibiosis had now been established but

in 1928, SirAlexander Flemingobserved the inhibition of bacteria by a colony

ofPenicilliumnotatum that had developed as a contaminant on a Petri dish. Hereported in 1929 the possible clinical use of the substance formed by the

penicillium culture. These findings stimulated large scale production and testing

of the substance which is now known as penicillin, and the search for other

antibiotics.

This led to the discovery ofStreptomycin, Chloramphenicol, and many other

antibiotics.

1Chemicalsubstancethatindilutesolutionscaninhibitthegrowthofmicroorganismsordestroythemwithlittleorno

harmto

the

infected

host.

2Fataldiseasecharacterizedbyinfectionsoftheskinlungsanddigestivesystemthatiscausedbythepoisonousbacteria

Bacillusanthracis(thisbacteriaisusedinbiologicalweapons).3Somebodyorsomethingusedasthesubjectofanexperiment,test,ortrial.

4Anacuteandoftenfatalintestinaldiseasethatproducesseveregastrointestinal symptomsandisusuallycausedbythe

bacteriumVibriocholera.


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Screening for Antibiotic:

In searching for new antibiotics, relatively simple and rapid methods have been developed for

screening M.O for antibiotic producing ability.

Soil samples are commonly employed in the screen programme because they are a rich source

of antibiotic-producing organisms. Most of these organisms are members of a group called

Actinomycetes1

(have morphologic characteristics between fungi and bacteria). In general the

screening method involves:

1- Treating the soil sample (or sample from another source) with chemicals that inhibit the

growth of interfering bacteria and fungi but do not affect Actinomycetes.

Cycloheximide is used as antifungal agent for this purpose, and a 1:140 dilution of

phenol is used as an antibacterial agent.

2- Various dilutions of the treated samples are streaked on agar2

plates containing medium

that support the growth ofActinomycetes .

3- After incubation3 for 3 to 7 days at 25 to 30 C, the plates are examined for

characteristic colonies ofActinomycetes. These colonies are then selectively transferredonto fresh medium.

4- Giant colonies of the selected organisms are grown, and plugs are cut from the colonies

that include the organism and the underlying agar.

5- The plugs are then placed on an agar plates that has been seeded with a test organism

that gives an indication of the potential usefulness of the antibiotic.

6- The test plates are incubated under conditions suitable for maximum growth of the test

M.O, and if after incubation there is a clear zone (zone of inhibition) around the plug of

Actinomycetes, it can be assumed that an antibiotic is produced byActinomycetes which

inhibited the growth of the test organism.

7- The next step in the screening procedure is to determine whether the chemical substance

(antibiotic) that produced the inhibition is a new antibiotic or a known compound.

This can be determined by chromatographic and spectroscopic methods, and the data

(result) obtained are compared to previously identified antibiotic from which the

produced compound cab be determined whether a new antibiotic or not.

1Rodshapedbacterium:arodshapedorfilamentousbacteriumbelongingtoalargegroupthatincludessomethatcause

diseasesandsomethatarethesourcesofantibiotics.2Aculturemediumbasedonaseaweedextract.Use:growingmicroorganismsinlaboratories.

3Themaintenanceofcellsormicroorganismsunderacontrolledtemperatureinoronamediumsothattheycan

multiply.


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Commercial Production Of AntibioticWhen a new antibiotic has been discovered by the usual screening method, the next important

step is investigation into the chemical, physical and biologic properties of the antibiotic before

the commercial production is decided (or started).The important requirements for production

of antibiotics are:

1- The organism must produce the antibiotic in submerged culture as opposed to surface

culture.

2- The organism must excrete the antibiotic into the culture medium .

These requirements are important considerations in production costs to determine whether the

antibiotic can compete with other antibiotics for a portion of the market.

Other important considerations are:

- Chemical stability.

- The minimum inhibitory concentration (MIC) against strains of pathogenic organism.

-

Toxic manifestations in mammals, and activity in VIVO.

The commercial production of antibiotics by fermentation almost always involves growth of

the producing organism in aerated tanks containing thousands of gallons of nutrient medium.

Spores or vegetative growth from a stock culture of the organism are used to start the

fermentation process.

It is important to maintain stock cultures (e.g. by lyophilization1

) for repeated fermentative

production. The several hundred gallons of vegetative growth that are necessary for

inoculating2 the large fermentation tanks are obtained by successively transferring the

organism to increasingly larger volumes of nutrient.

In the production of antibiotics by fermentation process, there are two distinct phases:

1- The growth phase of the organism, which also termed the Trophophase.

2- The antibiotic production phase, also termed theIdiophase.

The following diagram illustrates these phases during the production of a typical penicillin by

fermentation process carried out in a culture medium containing:

1- Glucose and lactose as the sources of carbon nutrition.

2-

Corn steep liquor for nitrogen sources.3- Phosphate buffer.

1Drybloodplasmaorotherbiologicalsubstancesbyfreezinginavacuum(alsolyophilisation).

2Tointroducemicroorganismsintoaculturemedium.


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Mycelium of

Streptomyces

During the growth phase, the culture becomes thick due to the formation of

aggregates of fungal growth (cells) calledMycelium1.

The growth is indicated in the diagram by the curve showing an increase in

mycelial nitrogen and last from the beginning of the culture period to about one

day ( 0 to 24 hours ).

During the growth phase, glucose rather than lactose is utilized by organism

because it can be used directly as a source of carbon. In the growth process,

ammonia is liberated by deamination of amino acids of the corn steep liquor. This

liberation raises the PH of the medium to 7, which is the optimum PH for penicillin stability,

and buffers in the medium maintain the PH close to neutrality.

Penicillin production increases rapidly between 24 to80 hours. At the start of the antibiotic

production phase, glucose has been used up, and the fungus (organism) then uses lactose for a

carbon source. Little additional growth occurs because the lactose cannot be utilized by the

organism until it is hydrolyzed to glucose and galactose. The decreased availability of a carbon

source is thought to stimulate (trigger) the mechanism for penicillin production.

Factors affecting commercial production:

Optimal conditions for antibiotic formation are quite different from those for maximum

vegetative growth.

Factors that are observed to have qualitative and quantitative importance for antibiotic

production including:

1- Sources of nutritional carbon and nitrogen.

2- Ratio of carbon/nitrogen nutrients.

3-

Mineral composition of medium.4- Incubation temperature.

5- Initial PH and control of PH during the fermentation period.

6- Rate and method of aeration.

7- Addition and timing of addition of special growth and antibiotic producing substances.

Selection of optimal fermentation conditions is usually based on empirical observations, but

careful attention to such as factors is critical. For example, some strains ofBacillussubtilis

produce optimal yields ofBacitracin2

when the C/N ratio is about 15, but at lower ratio the

yield is less, and when the ratio is reduced to about 6, related but commercially unwanted

antibiotic is produced.

The practical benefit of adding special chemicals to the fermentation cultures has some

beneficial effect on the antibiotic production. For example, the presence of phenylacetic acid

derivatives in the nutrient mixture favoured the formation ofPenicillinG.

The addition ofmercaptothiazole to the fermentation mixture (or culture ) of certain strains of

Streptomyces favours the production oftetracycline rather than chlortetracycline. Tetracycline

has greater therapeutic utility overchlortetracycline (hepatotoxic3).

1Mainpartoffungus:aloosenetworkofthedelicatefilamentshyphaethatformthebodyofafungus,consistingofthe

feedingandreproducinghyphae.2Antibioticforskininfections:anantibioticproducedbyastrainofbacterium.Use:topically,inthetreatmentofskin

infections.3Toxictoliver:describesaconditioninwhichtheliverisdamaged.


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Mercaptothiazole or any other compounds that inhibit the chlorination process favours the

production of tetracycline.

Some additives may increase antibiotic production through an enzyme induction effect.

For example, the additions ofMethionine1

to a Cephalosporin C2

fermentation during the

trophophase (growth phase) stimulates the production of the antibiotic.

It is assumed that methionine stimulates the production of the cephalosporin C through

biosynthetic enzymes.

Another important approach to increasing the yield of antibiotic is mutation and strain

selection. Mutation induced by exposing the parent strain to ultraviolet light, X-rays or various

mutagenic chemicals such as nitrogen mustards3

and analogs ofpurines andpyrimidines.

Mutation is the major approach for selecting improved strains, but a search of natural sources

for new wild-type or different species that produce the antibiotic in higher yield than the

original producing organism is also employed. For example, in the early natural selection it

was found that a strain ofPenicilium notatum produced Penicillin 4 mg/litter of culture

medium, and later on another strain ofPenicillium (Penicilliumchrysogenum ) was discovered

that yieldedPenicillin 40mg/liter, and by utilizing procedures of mutation and strain selection,

the yield has been increased to 21000mg/liter of culture medium.

Recovery and Isolation:

Most of the commercially important antibiotics are excreted

into the nutrient medium where they accumulate. Isolation of

antibiotic substances is basically recovery from the culture

broth4. Recovery and isolation of antibiotics from their culturemedium can be achieved by:

1- Selective precipitation.

2- Selective adsorption.

3- Selective extraction with an immiscible solvent.

The method used depends mainly on the chemical

characteristics of the various antibiotics and their

accompanying metabolites.

The isolation procedure should be efficient, selective, and economic to give the best yield and

to facilitate purification of the products.

Liquid-liquid extraction using some water-immiscible organic solvents is the suitable method

used for most antibiotics that have low polarity. Highly polar antibiotics, such as Neomycin5

andStreptomycin6are usually recovered from the culture broth by adsorption on some suitable

adsorbent. Many adsorbents remove antibiotics of this type from culture broths with varying

1Aminoacid:anessentialaminoacidthatcontainssulfur.

2Antibiotic:anantibioticbelongingtoagroupofsemisyntheticantibioticswithabroadrangeofeffectiveness.

3Nitrogencompoundusedintreatingcancer:acompoundsimilartomustardgasinwhichthesulfurisreplacedbyamino

nitrogen.

4Saucebase.

5Antibioticfortreatingbacterialinfections:anantibioticwithawiderangeofeffectiveness.Source:thebacterium

Streptomycesfradiae.Use:treatmentofskin,eye,andintestinalinfections.6Antibioticusedfortuberculosis: anantibioticproducedfromthesoilbacteriumStreptomycesgriseus.Use:treatmentof

bacterialinfectionssuchastuberculosis.

Penicillium chrysogenum


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degrees of selectivity, the major limitation to selecting adsorbents is the need to recover the

antibiotics by reversing the adsorption process without destruction of the antibiotic.

Use of charcoal of controlled activity grades and elution of the antibiotic with dilute acid is a

typical example of this isolation approach.

When the crude antibiotic has been recovered from the nutrient broth, it is subjected to

chromatography crystallization, or other standard techniques to achieve an appropriate degree

of purification. The purity of an appropriate degree of purification the purity of an antibiotic is

important to eliminate or reduce side effects, and once purification procedures were improved

and impurities were removed, the incidence of side effects or unwanted reactions will be

highly reduced.

Accepted standards of purity for antibiotics and antibiotic preparations are controlled by the

united states pharmacopoeia. Qualitative and quantitative evaluations of antibiotic preparations

according to established standards utilize both biological and chemical tests.

Classes Of Antibiotics:

-Lactam antibiotics:

The most important and widely employed -lactam antibiotics include: the Penicillins, and

cephalosporins.

They have in common the four-membered -lactam ring.

Penicillins have a 5-membered Thiazoidine ring attached to the -lactam ring.

Similarly, Cephalosporins have a 6-membered dihydrothiazine ring fused to the -lactam ring.

Penicillins:

Discovery in the late 1950's of a strain ofPenicilliumchrysogenum that accumulate high yields

of 6-aminopenicillanic acid (6-APA) provided an alternate approach to preparing unusual

penicillins, such as penicillin G and provided an opportunity for even greater modification in

the antibiotic molecules.

6-aminopenicillanic acid has no significant antibiotic activity, but it can be chemically

acylatedto give a wide range of biologically active penicillins.

The penicillins are the oldest of the clinical antibiotics and are still the most widely used.The first of the many penicillins to be employed was penicillin G (benzyl penicillins ),

obtained from the fungus culture Penicillium chrysogenum in the presence of phenyl acetic

acid.


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A wide-range of clinically useful Penicillins can be obtained from 6-APA by using suitable

side-chain precursors, as shown in the table, page 34. For example supplementation of the

culture medium with acids other thanphenylacetic acidwas used to produce otherpenicillins,

such as phenoxymethyl penicillin ( Penicillin V) is obtained by adding Phenoxy aceticacid to

the fermentation culture medium.

Biosynthesis of penicillin:

The amino acids, Cysteine and Valine are incorporated into the 6-APA nucleus of penicillins

and the acyl group of penicillin G is derived from phenylacetic acid. The biosynthetic pathway,

page 36 shows that the tripeptide -aminoadiphyl cysteiyl-valine ( ACV ) is synthesized from

-aminoadipicacid, cysteine and valine by an enzyme called ACVsynthetase.

The tripeptide is then cyclizedto form isopenicillin N.

The -aminoadipylside chain ofisopenicillin is cleaved at the amide bond and replaced with

phenylacetic acidto give penicillin G .

Properties of penicillins :

The chemical structure of the penicillin nucleus is unusual and is characterized by a4-membered-lactam ring fused to a thiazolidine ring. This ring system contains three

asymmetric (chiral) carbon atoms in a fixed spatial arrangement, and any destruction of this

arrangement by rupturing either the -lactam ring or the thiazolidine ring results in a complete

loss of antibacterial activity.

-Penicillin G is destroyed by gastric acid, and thus is not suitable fororaladministration, and

is best given by injection (I.M or I.V).

Decomposition under acidic conditions (low PH) or basic conditions (high PH) is shown on

page 35.

-Penicillin V has the advantage of begin acid stable, and thus it is suitable for oral

administration, and still has particular value for respiratory tract infections and tonsillitis1.

1Inflammationofthetonsilsofthemouth,causedeitherbybacteriaoravirus,whichmakesthethroatverysoreandcan

leadtofeverandearache.


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Penicillins with side-chain containing a basic amino group, Example, Ampicillin and

Amoxicillin are also acid stable. In addition, these agent were found to have a broader

spectrum of activity than penicillin G or penicillin V.

Penicillins are inactivated (hydrolysed) by penicilinase (-lactamase) enzyme produced by

resistant bacteria (pathogenic strains).

However, other penicillins such as Cloxacillin and Flucloxacillin are not hydrolysed by

bacterial-lactamase enzymes, i.e. can be used against penicillin resistance bacteria.

Another way of overcoming the penicillin-hydrolysing effect of-lactamase is to combine a

-lactamase-sensitive agent. Example amoxycilin with clavulanic acid1

which is specific

inhibitor of-lactamase (penicilinase).

Penicillin and other -lactam drugs exert their antibacterial effects (activity) by binding to

proteins (penicillin-binding proteins) that are involved in the biosynthesis of the bacterial cell

wall, i.e. penicillins inhibit the cell wall biosynthesis and kill or inhibit the growth of bacteria.

Bactericidal and bacteriostatic antibiotics:

Most of the cell wall synthesis inhibitors (irreversible inhibition of protein synthesis) are

bactericidal agent2. These agents kill rather than inhibit the growth of bacteria, because the

cells will lyse in the absence of an intact cell wall.

On the other hand, most protein synthesis inhibitors have a reversible action and will be

bacteriostatic3, i.e. inhibit the growth rather than kill the organism, because the cells will

continue to grow once the antibiotic is removed.

Cephalosporins and Cephamycins

The Cephalosporins4, such as Cephalosporin C are group of antibiotic having a

-lactam-dihydrothiazin ring system, and are produced by species of Cephalosporium.

They are biosynthetically related to the penicillin and resemble these antibiotics in many of

their biological and chemical properties.

The major difference is a 7-aminocephalosporanic acidnucleus (7-ACA) which has a fused

dihydrothiszine -lactam ring system rather than the fused thiazolidine -lactam system of

6-aminopenicillanic acidnucleus (6-APA) in penicillin.

1Adjuncttoantibiotictreatment:adrugthataugmentsantibiotics.Use:treatmentofantibioticresistantbacterial

infections.2Asubstanceoragentthatdestroysbacteria.

3Bacteriainhibitingsubstance:asubstancethatrestrictsthegrowthandactivityofbacteriawithoutkillingthem.

4Anantibioticbelongingtoagroupofsemisyntheticantibioticswithabroadrangeofeffectiveness.


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Cephalosporin C is produced commercially by fermentation using cultures of high-yielding

strains of Cephalosporium acremonium. Removal of the amide side-chain by hydrolysis of

Cephalosporin C gives 7-aminocephalosporanic acid (7-ACA), which is the key for the

chemical production of semi-synthetic Cephalosporin antibiotics, as shown in the tables, pages

37, 38, 39.

The Cephalosporin antibiotics are acid stable and penicillinase resistant, but they are

inactivated by another -lactamase enzyme called Cephlosporinase. Another group of

-lactam antibiotics termed Cephamycins are closely related chemically to the

Cephalosporins. They are characterized by having a 7-methoxycephalosporin nucleus.

Cephamycin C, which is produced by certain species ofStreptomyces acts as a starting material

for the chemical synthesis of Cefoxitin antibiotic. The cephamycins are resistant to

-lactamase hydrolysis.

The Cephalosporins may be classified into generations according to the antibacterial spectrum

(activity) of the drugs.

First generation Cephalosporins have:

1-

good activity against gram-postive bacteria,

2-but low activity against gram-negative bacteria.

- They have similar activity toAmpicillin, and effective againstpenicillinase enzyme,

- But they are inactivated by another-lactamase (cephalosporinase) enzyme.

Second generation Cephalosporins have:

1- A broader spectrum of activity against gram-negative bacteria

2- Better resistance to -lactamases that hydrolysis the first generation.

Third generation have extended gram-negative spectrum of activity, and more resistant to

the -lactamases.

The cephalosporins and related -lactam antibiotics inhibit cell wall formation.

Cephaosporins are especially useful for treating infections in patients who are allergic to

penicillins.

Hypersensitivity to cephalosporins is much less common, and only about 10% of penicillin

sensitive patients will also be allergic to cephalosporins.


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-Lactamase inhibitors:These are group of natural products containing the basic -lactam ring system.

Of special importance are:

1- Clavulanic acid: produced by cultures Streptomycesclavuligerus.

It is structurally related topenicillins. Clavulanic acid has weak antibacterial activatity, but it is

capable of irreversibly inactivating (hydrolyzing) bacterial -lactamases responsible for

antibiotic resistance.

Clavulanic acid acts synergistically with -lactamase sensitive penicillins and cephalosporins,

for example: the combination of amoxicillin and clavulanic acid (augmentin, or co-amoxyclav)

is a -lactam antibiotic with a -Lactamase inhibitor.

2- Olivanic acid: produced by cultures ofStreptomycesolivaceus.

The olivanic acid is a potent -lactamase inhibitor, especially towards the Cephalosporinases,

which are poorly inhibited by clavulanic acid.

3- Sulbactam: it is structurally related to penicillins, but prossesses only weak

antibacterial activity.

The combination of ampicillin and sulbactam inhibits irreversibly a variety of-lactamases

and restores ampicillin activity against -lactamases producing strains of bacteria.

4-

Tazobactum: it is also structurally related to the penicilins and used as a -lactamase

inhibitor.

In general, these -lactam inhibitors provide protection against -lactamases, thus extending

the effect of the antibiotic against a wider range of -lactamases producing organisms. This

means that organisms resistant to the action of-lactam antibiotics produce -lactamas which

hydrolyse the -lactam ring to form inactive product(see page 35).


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TetracyclinesThe Tetracycines are a group of broad-spectrum, orally active antibiotics produced by cultures

of Streptomyces species. Strain selection and control of chlorination and methylation have

proved useful in the fermentation production of various tetracycline compounds. The presence

ofaminopterine or other methylation inhibitors in the nutrient mixture favours the formation

6-demethyl tetracyclines.

Compounds such as Mercaptothiazole favours tetracycline production by inhibiting the

chlorination process. Structures of commercially available tetracyclines are shown on page 40.

Because of the sequence of phenol and carbonyl substituents in the structure of tetracyclines,

they acts as chelators1and complex with metal ions, especially calcium, aluminium , iron and

magnesium. Therefore they should not be administered with foods such as milk and dairy

products (which have a high calcium content), aluminium and magnesium based antacid2

preparations, etc, Otherwise unsatisfactory absorption will occur.

Chelation of tetracyclines with calcium also precludes their use in children developing theiradult teeth, and inpregnant women, because the tetracyclines become deposited in the growing

teeth and bone in the children (up to age 10) this would cause permanent staining of teeth with

the chelated yellow tetracycline.

Hypersensitivity to tetracyclines may occur, the most serious is photosensitivity.

The antimicrobial activity of tetracyclines arises by inhibition of protein synthesis.

Macrolide AntibioticsThe Macrolide3 antibiotics are characterized by a macrolactone ring that is glycosidicallylinked to one or more sugar units. These antibiotics have a narrow spectrum of antibacterial

activity, their antibacterial activity (spectrum) resembles, but is not identical to, that of the

penicillins.

-Erythromycin is the principal macrolide antibacterial currently used in medicine.

-TheErythromycins are macrolide antibiotics produced by cultures ofStreptomyceserythreus.

-It is used (prescribed) for patients allergic to penicillins, and also used against penicillin

resistant strains of bacteria.

-Erythromycin exerts its antibacterial action by inhibiting protein synthesis in sensitive

organisms. It binds reversibly to the bacterial ribosome, thus inhibiting RNA-dependent

protein synthesis.

-Erythromycin is unstable under acidic conditions. To reduce this acid instability,

semi-synthetic analogues of erythromycin, such as Clarithromycin and Azithromycin4

have

been developed, page 41.

In both analogues, the changes enhance activity compared with that oferythromycin.

1Compoundofmetalandnonmetal:achemicalcompoundinwhichmetallicandnonmetallic,usuallyorganic,atomsare

combined.

Thesecompounds

are

characterized

by

aring

structure

in

which

ametal

ion

is

attached

to

two

nonmetal

ions

bycovalentbonds.2Antaciddrug:adrugthatreducesorneutralizesstomachacid.

3Widespectrumantibiotic:anantibioticthathasawidespectrumofantibacterialactionandcanbeusedasan

alternativetopenicillin.Themacrolidegroupincludeserythromycin.4Anantibiotictakenincombinationwithotherdrugs.Use:treatmentoftoxoplasmosis,heartdisease,AIDS.


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Aminoglycoside1

AntibioticsThe Aminoglycosides form an important groups of antibiotic agents derived from carbohydrate

metabolism. They have two or three uncommon sugars attached through glycoside linkages to

an amino-substituted cyclohexanyl aglycone.

The aminoglycoside antibiotics include: Streptomycin2, Gentamycin3,Kanamycin4,Neomycin5,

Amikacin6

and Tobramycin, page 42, which are obtained by fermentation cultures of differentstrains of micro-organisms.

The chemical and biological properties of these antibiotics are similar. Common chemical

properties include water solubility, a strong basic character and stability.

These antibiotics are not absorbed from the GIT, and so they must be administered by injection

for the treatment of systemic infections. However, they can be administered orally to control

intestinal flora7.

The widespread use of aminoglycoside antibiotics is limited by theirNephrotoxicity8

which

results in impaired kidney function, and by theirOtotoxicity9

which is a serious side effect and

can lead to irreversible of loss hearing.

Therefore the aminoglycoside antibiotics are indicated only for the treatment of serious

infections when less toxic antibiotics are proved ineffective or contraindicated.

LincosamidesThis class of antibiotics include:Lincomycin (page 44) and Clindamycin

10.

Lincomycin is obtained from cultures of certain strains ofStreptomyces, whereas Clindamycin

is a semi-synthetic derivative obtained by chlorination of theLincomycin at carbon number 7.

i.e Clindamycin is 7-Chloro-7-deoxylincomycin.

Both antibiotics have some clinical uses, but their application is limited by their side effects

including diarrhea11

and overgrowth of resistant strains of organisms, which can cause

fatalities12

in elderly patients. These antibiotics are useful in the treatment of joint and bone

infections such as: Osteomyelitis13

.

Clindamycin phosphate is of value in the topical treatment of Acne14

vulgaris.

1Anantibioticbelongingtoagroupinwhichaminosugarsarelinkedasglycosides,e.g.streptomycin.Source:speciesof

StreptomycesorMicromonospora.Use:treatmentofaerobicbacterialinfections.2Antibioticusedfortuberculosis: anantibioticproducedfromthesoilbacteriumStreptomycesgriseus.Use:treatmentof

bacterialinfectionssuchastuberculosis.3Abroadspectrumantibiotic,usuallyadministeredbyinjection.

4Anantibioticobtainedfromasoilbacterium.Use:treatmentofinfectionsresistanttootherantibiotics.

5Antibioticfortreatingbacterialinfections:anantibioticwithawiderangeofeffectiveness.Source:thebacterium

Streptomycesfradiae.Use:treatmentofskin,eye,andintestinalinfections.6Asyntheticantibiotic.Use:treatmentofinfectionscausedbyaerobicbacteria.

7Bacteriainhealthyintestine:bacteriapresentinahealthyintestinethatcompletedigestion,synthesizevitaminK,and

createanacidenvironmentthatpreventsinfectionbyharmfulbacteria.8Beingpoisonoustokidneycells.

9Ototoxic:adverselyaffectinghearingandbalance:toxictotheearandhenceimpairinghearingorbalance.

10Antibioticdrug:apotentantibioticadministeredininjectionsorexternally.Use:severeinfections,acne,bacterial

vaginosis.

11Frequentandexcessivedischargingofthebowelsproducingthinwateryfeces,usuallyasasymptomofgastrointestinal

upsetorinfection.12

Unexpecteddeath.13

Inflammationofboneandbonemarrow,causedbyinfection.14

Skindisordercharacterizedbypimplesandotherpustulareruptionswhichgenerallyappearontheface.

SIUST Antibiotics

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