22

 
Antibiotics1
The 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 Pasteur
who in 1877 reported that animals injected with an inoculation containing
Bacillus anthracis and certain other common Bacilli 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 of Vibrio cholerae.
The recognition of the phenomenon of antibiosis had now been established but  
Louis Pasteur portrait in
in 1928, Sir Alexander Fleming observed the inhibition of bacteria by a colony his later years.
of Penicillium notatum that had developed as a contaminant on a Petri dish. He
reported 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 of Streptomycin, Chloramphenicol, and many other Photomicrograph of
antibiotics. Bacillus anthracis
(fuchsin-methylene blue
spore stain).

 
Image of Vibrio cholerae  
Prof.Sir Alexander Fleming

 
                                                             
1
Chemical substance that in dilute solutions can inhibit the growth of microorganisms or destroy them with little or no 
harm to the infected host. 
2
Fatal disease characterized by infections of the skin lungs and digestive system that is caused by the poisonous bacteria 
Bacillus anthracis (this bacteria is used in biological weapons). 
3
Somebody or something used as the subject of an experiment, test, or trial. 
4
An acute and often fatal intestinal disease that produces severe gastrointestinal symptoms and is usually caused by the 
bacterium Vibrio cholera. 
   23
 
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 of Actinomycetes .
3- After incubation3 for 3 to 7 days at 25 to 30 ˚C, the plates are examined for
characteristic colonies of Actinomycetes. These colonies are then selectively transferred
onto 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 by Actinomycetes 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.

                                                             
1
Rod‐shaped bacterium: a rod‐shaped or filamentous bacterium belonging to a large group that includes some that cause 
diseases and some that are the sources of antibiotics. 
2
A culture medium based on a seaweed extract. Use: growing microorganisms in laboratories. 
3
The maintenance of cells or microorganisms under a controlled temperature in or on a medium so that they can 
multiply. 
   24
 
Commercial Production Of Antibiotic
When 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 the Idiophase.
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.

                                                             
1
Dry blood plasma or other biological substances by freezing in a vacuum (also lyophilisation). 
2
To introduce microorganisms into a culture medium. 
   25
 
During the growth phase, the culture becomes thick due to the formation of
aggregates of fungal growth (cells) called Mycelium1.
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
Mycelium of
because it can be used directly as a source of carbon. In the growth process, Streptomyces

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 of Bacillus subtilis
produce optimal yields of Bacitracin2 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 of Penicillin G.
The addition of mercaptothiazole to the fermentation mixture (or culture ) of certain strains of
Streptomyces favours the production of tetracycline rather than chlortetracycline. Tetracycline
has greater therapeutic utility over chlortetracycline (hepatotoxic3).
                                                             
1
Main part of fungus: a loose network of the delicate filaments hyphae that form the body of a fungus, consisting of the 
feeding and reproducing hyphae. 
2
Antibiotic for skin infections: an antibiotic produced by a strain of bacterium. Use: topically, in the treatment of skin 
infections. 
3
Toxic to liver: describes a condition in which the liver is damaged. 
   26
 
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 of Methionine1 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 of purines and pyrimidines.

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 of Penicilium notatum produced Penicillin 4 mg/litter of culture
medium, and later on another strain of Penicillium (Penicillium chrysogenum ) was discovered
that yielded Penicillin 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 culture
medium 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 Penicillium chrysogenum
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
and Streptomycin6 are usually recovered from the culture broth by adsorption on some suitable
adsorbent. Many adsorbents remove antibiotics of this type from culture broths with varying

                                                             
1
Amino acid: an essential amino acid that contains sulfur. 
2
Antibiotic: an antibiotic belonging to a group of semisynthetic antibiotics with a broad range of effectiveness. 
3
Nitrogen compound used in treating cancer: a compound similar to mustard gas in which the sulfur is replaced by amino 
nitrogen. 
4
Sauce base. 
5
Antibiotic for treating bacterial infections: an antibiotic with a wide range of effectiveness. Source: the bacterium 
Streptomyces fradiae. Use: treatment of skin, eye, and intestinal infections. 
6
Antibiotic used for tuberculosis: an antibiotic produced from the soil bacterium Streptomyces griseus. Use: treatment of 
bacterial infections such as tuberculosis. 
   27
 
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:

β-Lactam antibiotics:
The most important and widely employed β-lactam antibiotics include: the Penicillins, and
cephalosporins.
They have in common the four-membered β-lactam ring.
Penicillins have a 5-membered Thiazoidine ring attached to the β-lactam ring.
Similarly, Cephalosporins have a 6-membered dihydrothiazine ring fused to the β-lactam ring.

Penicillins:
Discovery in the late 1950's of a strain of Penicillium chrysogenum 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
acylated to 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.
   28
 

 
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 than phenylacetic acid was used to produce other penicillins,
such as phenoxymethyl penicillin (Penicillin V) is obtained by adding Phenoxy acetic acid 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 α-aminoadiphyl cysteiyl-valine ( ACV ) is synthesized from
α-aminoadipic acid, cysteine and valine by an enzyme called ACV synthetase.
The tripeptide is then cyclized to form isopenicillin N.
The α-aminoadipyl side chain of isopenicillin is cleaved at the amide bond and replaced with
phenylacetic acid to give penicillin G .

Properties of penicillins :
The chemical structure of the penicillin nucleus is unusual and is characterized by a
4-membered β-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 β-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 for oral administration, 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.
                                                             
1
Inflammation of the tonsils of the mouth, caused either by bacteria or a virus, which makes the throat very sore and can 
lead to fever and earache. 
   29
 
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 (β-lactamase) enzyme produced by
resistant bacteria (pathogenic strains).
However, other penicillins such as Cloxacillin and Flucloxacillin are not hydrolysed by
bacterial β-lactamase enzymes, i.e. can be used against penicillin resistance bacteria.
Another way of overcoming the penicillin-hydrolysing effect of β-lactamase is to combine a
β-lactamase-sensitive agent. Example amoxycilin with clavulanic acid1 which is specific
inhibitor of β-lactamase (penicilinase).
Penicillin and other β-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

β-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 acid nucleus (7-ACA) which has a fused
dihydrothiszine β-lactam ring system rather than the fused thiazolidine β-lactam system of
6-aminopenicillanic acid nucleus (6-APA) in penicillin.

                                                             
1
Adjunct to antibiotic treatment: a drug that augments antibiotics. Use: treatment of antibiotic‐resistant bacterial 
infections. 
2
A substance or agent that destroys bacteria. 
3
Bacteria‐inhibiting substance: a substance that restricts the growth and activity of bacteria without killing them. 
4
An antibiotic belonging to a group of semisynthetic antibiotics with a broad range of effectiveness. 
   30
 
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 β-lactamase enzyme called Cephlosporinase. Another group of
β-lactam antibiotics termed Cephamycins are closely related chemically to the
Cephalosporins. They are characterized by having a 7α-methoxycephalosporin nucleus.
Cephamycin C, which is produced by certain species of Streptomyces acts as a starting material
for the chemical synthesis of Cefoxitin antibiotic. The cephamycins are resistant to
β-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 to Ampicillin, and effective against penicillinase enzyme,
- But they are inactivated by another β-lactamase (cephalosporinase) enzyme.

Second generation Cephalosporins have:

1- A broader spectrum of activity against gram-negative bacteria
2- Better resistance to β-lactamases that hydrolysis the first generation.

Third generation have extended gram-negative spectrum of activity, and more resistant to
the β-lactamases.
The cephalosporins and related β-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.
   31
 
β-Lactamase inhibitors:
These are group of natural products containing the basic β-lactam ring system.
Of special importance are:
1- Clavulanic acid: produced by cultures Streptomyces clavuligerus.
It is structurally related to penicillins. Clavulanic acid has weak antibacterial activatity, but it is
capable of irreversibly inactivating (hydrolyzing) bacterial β-lactamases responsible for
antibiotic resistance.
Clavulanic acid acts synergistically with β-lactamase sensitive penicillins and cephalosporins,
for example: the combination of amoxicillin and clavulanic acid (augmentin, or co-amoxyclav)
is a β-lactam antibiotic with a β-Lactamase inhibitor.

2- Olivanic acid: produced by cultures of Streptomyces olivaceus.

The olivanic acid is a potent β-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 β-lactamases
and restores ampicillin activity against β-lactamases – producing strains of bacteria.
4- Tazobactum: it is also structurally related to the penicilins and used as a β-lactamase
inhibitor.

In general, these β-lactam inhibitors provide protection against β-lactamases, thus extending
the effect of the antibiotic against a wider range of β-lactamases –producing organisms. This
means that organisms resistant to the action of β-lactam antibiotics produce β-lactamas which
hydrolyse the β-lactam ring to form inactive product(see page 35).
   32
 
Tetracyclines
The 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
of aminopterine 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 chelators 1and 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 their
adult teeth, and in pregnant 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 Antibiotics
The Macrolide3 antibiotics are characterized by a macrolactone ring that is glycosidically
linked 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.
-The Erythromycins are macrolide antibiotics produced by cultures of Streptomyces erythreus.
-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 of erythromycin.

                                                             
1
Compound of metal and nonmetal: a chemical compound in which metallic and nonmetallic, usually organic, atoms are 
combined .These compounds are characterized by a ring structure in which a metal ion is attached to two nonmetal ions 
by covalent bonds. 
2
Antacid drug: a drug that reduces or neutralizes stomach acid. 
3
Wide‐spectrum antibiotic: an antibiotic that has a wide spectrum of antibacterial action and can be used as an 
alternative to penicillin. The macrolide group includes erythromycin. 
4
An antibiotic taken in combination with other drugs. Use: treatment of toxoplasmosis, heart disease, AIDS. 
   33
 

Aminoglycoside1 Antibiotics
The 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 different
strains 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 their Nephrotoxicity8 which
results in impaired kidney function, and by their Ototoxicity9 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.

Lincosamides
This class of antibiotics include: Lincomycin (page 44) and Clindamycin10.
Lincomycin is obtained from cultures of certain strains of Streptomyces, whereas Clindamycin
is a semi-synthetic derivative obtained by chlorination of the Lincomycin 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.

                                                             
1
An antibiotic belonging to a group in which amino sugars are linked as glycosides, e.g. streptomycin. Source: species of 
Streptomyces or Micromonospora. Use: treatment of aerobic bacterial infections. 
2
Antibiotic used for tuberculosis: an antibiotic produced from the soil bacterium Streptomyces griseus. Use: treatment of 
bacterial infections such as tuberculosis. 
3
A broad‐spectrum antibiotic, usually administered by injection. 
4
An antibiotic obtained from a soil bacterium. Use: treatment of infections resistant to other antibiotics. 
5
Antibiotic for treating bacterial infections: an antibiotic with a wide range of effectiveness. Source: the bacterium 
Streptomyces fradiae. Use: treatment of skin, eye, and intestinal infections. 
6
A synthetic antibiotic. Use: treatment of infections caused by aerobic bacteria. 
7
Bacteria in healthy intestine: bacteria present in a healthy intestine that complete digestion, synthesize vitamin K, and 
create an acid environment that prevents infection by harmful bacteria. 
8
Being poisonous to kidney cells. 
9
Ototoxic: adversely affecting hearing and balance: toxic to the ear and hence impairing hearing or balance. 
10
Antibiotic drug: a potent antibiotic administered in injections or externally. Use: severe infections, acne, bacterial 
vaginosis. 
11
Frequent and excessive discharging of the bowels producing thin watery feces, usually as a symptom of gastrointestinal 
upset or infection. 
12
Unexpected death. 
13
Inflammation of bone and bone marrow, caused by infection. 
14
Skin disorder characterized by pimples and other pustular eruptions which generally appear on the face.