Macrolide Antibiotics

Dr Amged 1

Introduction

The term Macrolide was originally given to antibiotics produced by species of Strptomyces

In 1950 the first drug of this class was isolatedPicromycin

In 1952 Erythromycin and Carbomycin were introduced into clinic

Dr Amged 2

General Structure

They all contain three characteristics parts in the molecule

A highly substituted macrocyclic lactone aglycone part

A ketone group

An amino desoxysugar glycon and in some of the macrolides a

neutral desoxysugar which are glycosidically attached to the

aglycone ring

Dr Amged 3

The lactone ring usually has 12 14 or 16 atoms

Having a dimethyl amino group on the glycon part macrolideantibiotics are weak bases and different salts with pKa range of 60-90 can be formed on the amino group

Macrolides are water-insoluble molecules Salts prepared byglucoheptonic and lactobionic salts are water soluble whereasstearic acid and laurylsulfuric acid salts are water-insoluble

Macrolides are stable in aqueous solutions at or below roomtemperature They are unstable in acidic or basic conditions or athigh temperatures

Dr Amged 4

Mechanism of Antimicrobial Activity

Macrolides attach to the 50s portion of bacterial

ribosomes and inhibit the protein synthesis

They block the enzymes that catalyse the transfer of

the new amino acid residue to the peptide chain

that is prevent elongation in prokaryotic cells

Dr Amged 5

Mechanism of Microbial Resistance

Methylation of a guanine residue on ribosomal RNA

leads to lower affinity toward macrolides The

mutant rRNA has a lower ability for protein

synthesis too The macrolide producing

microorganism uses the same way to protect its

rRNAs against this antibiotic

Hypothesis Maybe the antibiotic producing

microorganisms are the source of R factors that

cause the microbial reistance

In some bacterial strains an active efflux system is

responsible for the resistance against macrolidesDr Amged 6

Mechanism of hellipcontinued

Some investigations suppose that macrolides attach

to the rRNA through an interaction with the

Adenine 2058 in the region V of it Mutation of this

nucleotide causes a 10000 fold decrease in the

attachment of the drug and a resistance in the

bacteria against macrolides

Lack of cell wall permeability to macrolides is the

reason why G(-) bacteria are resistant to

antibacterial effects of these agents

Dr Amged 7

Introduction

The term Macrolide was originally given to antibiotics produced by species of Strptomyces

In 1950 the first drug of this class was isolatedPicromycin

In 1952 Erythromycin and Carbomycin were introduced into clinic

Dr Amged 2

General Structure

They all contain three characteristics parts in the molecule

A highly substituted macrocyclic lactone aglycone part

A ketone group

An amino desoxysugar glycon and in some of the macrolides a

neutral desoxysugar which are glycosidically attached to the

aglycone ring

Dr Amged 3

The lactone ring usually has 12 14 or 16 atoms

Having a dimethyl amino group on the glycon part macrolideantibiotics are weak bases and different salts with pKa range of 60-90 can be formed on the amino group

Macrolides are water-insoluble molecules Salts prepared byglucoheptonic and lactobionic salts are water soluble whereasstearic acid and laurylsulfuric acid salts are water-insoluble

Macrolides are stable in aqueous solutions at or below roomtemperature They are unstable in acidic or basic conditions or athigh temperatures

Dr Amged 4

Mechanism of Antimicrobial Activity

Macrolides attach to the 50s portion of bacterial

ribosomes and inhibit the protein synthesis

They block the enzymes that catalyse the transfer of

the new amino acid residue to the peptide chain

that is prevent elongation in prokaryotic cells

Dr Amged 5

Mechanism of Microbial Resistance

Methylation of a guanine residue on ribosomal RNA

leads to lower affinity toward macrolides The

mutant rRNA has a lower ability for protein

synthesis too The macrolide producing

microorganism uses the same way to protect its

rRNAs against this antibiotic

Hypothesis Maybe the antibiotic producing

microorganisms are the source of R factors that

cause the microbial reistance

In some bacterial strains an active efflux system is

responsible for the resistance against macrolidesDr Amged 6

Mechanism of hellipcontinued

Some investigations suppose that macrolides attach

to the rRNA through an interaction with the

Adenine 2058 in the region V of it Mutation of this

nucleotide causes a 10000 fold decrease in the

attachment of the drug and a resistance in the

bacteria against macrolides

Lack of cell wall permeability to macrolides is the

reason why G(-) bacteria are resistant to

antibacterial effects of these agents

Dr Amged 7

General Structure

They all contain three characteristics parts in the molecule

A highly substituted macrocyclic lactone aglycone part

A ketone group

An amino desoxysugar glycon and in some of the macrolides a

neutral desoxysugar which are glycosidically attached to the

aglycone ring

Dr Amged 3

The lactone ring usually has 12 14 or 16 atoms

Having a dimethyl amino group on the glycon part macrolideantibiotics are weak bases and different salts with pKa range of 60-90 can be formed on the amino group

Macrolides are water-insoluble molecules Salts prepared byglucoheptonic and lactobionic salts are water soluble whereasstearic acid and laurylsulfuric acid salts are water-insoluble

Macrolides are stable in aqueous solutions at or below roomtemperature They are unstable in acidic or basic conditions or athigh temperatures

Dr Amged 4

Mechanism of Antimicrobial Activity

Macrolides attach to the 50s portion of bacterial

ribosomes and inhibit the protein synthesis

They block the enzymes that catalyse the transfer of

the new amino acid residue to the peptide chain

that is prevent elongation in prokaryotic cells

Dr Amged 5

Mechanism of Microbial Resistance

Methylation of a guanine residue on ribosomal RNA

leads to lower affinity toward macrolides The

mutant rRNA has a lower ability for protein

synthesis too The macrolide producing

microorganism uses the same way to protect its

rRNAs against this antibiotic

Hypothesis Maybe the antibiotic producing

microorganisms are the source of R factors that

cause the microbial reistance

In some bacterial strains an active efflux system is

responsible for the resistance against macrolidesDr Amged 6

Mechanism of hellipcontinued

Some investigations suppose that macrolides attach

to the rRNA through an interaction with the

Adenine 2058 in the region V of it Mutation of this

nucleotide causes a 10000 fold decrease in the

attachment of the drug and a resistance in the

bacteria against macrolides

Lack of cell wall permeability to macrolides is the

reason why G(-) bacteria are resistant to

antibacterial effects of these agents

Dr Amged 7

The lactone ring usually has 12 14 or 16 atoms

Having a dimethyl amino group on the glycon part macrolideantibiotics are weak bases and different salts with pKa range of 60-90 can be formed on the amino group

Macrolides are water-insoluble molecules Salts prepared byglucoheptonic and lactobionic salts are water soluble whereasstearic acid and laurylsulfuric acid salts are water-insoluble

Macrolides are stable in aqueous solutions at or below roomtemperature They are unstable in acidic or basic conditions or athigh temperatures

Dr Amged 4

Mechanism of Antimicrobial Activity

Macrolides attach to the 50s portion of bacterial

ribosomes and inhibit the protein synthesis

They block the enzymes that catalyse the transfer of

the new amino acid residue to the peptide chain

that is prevent elongation in prokaryotic cells

Dr Amged 5

Mechanism of Microbial Resistance

Methylation of a guanine residue on ribosomal RNA

leads to lower affinity toward macrolides The

mutant rRNA has a lower ability for protein

synthesis too The macrolide producing

microorganism uses the same way to protect its

rRNAs against this antibiotic

Hypothesis Maybe the antibiotic producing

microorganisms are the source of R factors that

cause the microbial reistance

In some bacterial strains an active efflux system is

responsible for the resistance against macrolidesDr Amged 6

Mechanism of hellipcontinued

Some investigations suppose that macrolides attach

to the rRNA through an interaction with the

Adenine 2058 in the region V of it Mutation of this

nucleotide causes a 10000 fold decrease in the

attachment of the drug and a resistance in the

bacteria against macrolides

Lack of cell wall permeability to macrolides is the

reason why G(-) bacteria are resistant to

antibacterial effects of these agents

Dr Amged 7

Mechanism of Antimicrobial Activity

Macrolides attach to the 50s portion of bacterial

ribosomes and inhibit the protein synthesis

They block the enzymes that catalyse the transfer of

the new amino acid residue to the peptide chain

that is prevent elongation in prokaryotic cells

Dr Amged 5

Mechanism of Microbial Resistance

Methylation of a guanine residue on ribosomal RNA

leads to lower affinity toward macrolides The

mutant rRNA has a lower ability for protein

synthesis too The macrolide producing

microorganism uses the same way to protect its

rRNAs against this antibiotic

Hypothesis Maybe the antibiotic producing

microorganisms are the source of R factors that

cause the microbial reistance

In some bacterial strains an active efflux system is

responsible for the resistance against macrolidesDr Amged 6

Mechanism of hellipcontinued

Some investigations suppose that macrolides attach

to the rRNA through an interaction with the

Adenine 2058 in the region V of it Mutation of this

nucleotide causes a 10000 fold decrease in the

attachment of the drug and a resistance in the

bacteria against macrolides

Lack of cell wall permeability to macrolides is the

reason why G(-) bacteria are resistant to

antibacterial effects of these agents

Dr Amged 7

Mechanism of Microbial Resistance

Methylation of a guanine residue on ribosomal RNA

leads to lower affinity toward macrolides The

mutant rRNA has a lower ability for protein

synthesis too The macrolide producing

microorganism uses the same way to protect its

rRNAs against this antibiotic

Hypothesis Maybe the antibiotic producing

microorganisms are the source of R factors that

cause the microbial reistance

In some bacterial strains an active efflux system is

responsible for the resistance against macrolidesDr Amged 6

Mechanism of hellipcontinued

Some investigations suppose that macrolides attach

to the rRNA through an interaction with the

Adenine 2058 in the region V of it Mutation of this

nucleotide causes a 10000 fold decrease in the

attachment of the drug and a resistance in the

bacteria against macrolides

Lack of cell wall permeability to macrolides is the

reason why G(-) bacteria are resistant to

antibacterial effects of these agents

Dr Amged 7

Mechanism of hellipcontinued

Some investigations suppose that macrolides attach

to the rRNA through an interaction with the

Adenine 2058 in the region V of it Mutation of this

nucleotide causes a 10000 fold decrease in the

attachment of the drug and a resistance in the

bacteria against macrolides

Lack of cell wall permeability to macrolides is the

reason why G(-) bacteria are resistant to

antibacterial effects of these agents

Dr Amged 7

Chemical Instability of Macrolide

Antibiotics

bull Macrolides are unstable under acidic conditions

and undergo an intramolecular reaction to form

an inactive cyclic ketal

Dr Amged 8

Intramolecular ketal formation in

erythromycin

Dr Amged 9

Chemical Instability

bull The cyclic ketal cause intestinal cramp which is reported after

the use of erythromycin

bull Water-insoluble salts and enteric coated dosage forms of

macrolides have less such a side effect

bull Water insoluble forms cannot take part in the reactions which

occur in aqueous solutions

bull Stearate salt is an example of insoluble salts of erytromycin

bull One way of preventing acid sensitivity is to protect the hydroxy

groups For example clarithromycin is a methoxy analogue of

erythromycin which is more stable to gastric juices and has

improved oral absorption

bull Another method of increasing acid stability is to increase the

size of the macrocycle to a 16-membered ring

Dr Amged 11

Therapeutic Agents

Erythromycin

It has been the subject of chemical

manipulations to

a) Increase the water solubility of the drug for

parenteral dosage forms

b) Increase the lipid solubility and hence chemical

stability of the drug against aqueous acidic

conditions as well as increase in oral absorption and

masking the bitter taste of the drug

Dr Amged 13

ErythromycinThe chemical manipulations are

1 Preparation of acidic salts such as glucoheptonate

lactobionate and stearate on the dimethyl amino group

2 Ester formation on the 2`-OH of the amino sugar

Ethylsuccinate and propionate are examples

Dr Amged 14

Erythromycin EstersErythromycin Ethyl Succinate

A mixed double ester prodrug of erythromycin

Better oral absorption

In oral suspensions for children without the bitter taste

Erythromycin PropionateA lipid-soluble ester of propionic acid

Better oral absorption

Dr Amged 15

Erythromycin SaltsErythromycin Stearate

A lipid-soluble salt of stearic acid

Better oral absorption

Acid-sensitive Enteric coated form is Acid-stable

In the small intestine base exchange occurs and free erythromycin

releases

Erythromycin Lactobionate

A water-soluble salt of lactobionic acid for parenteral dosage forms

Erythromycin Glucoheptonate

A water-soluble salt of glucoheptonic acid for parenteral dosage

forms

Dr Amged 16

Clinical Application of Erythromycin

It is used to treat

The upper part of the respiratory tract infections

Soft tissue G(+) infections

Mycoplasma pneumonia caused pneumonia

Campylobacter jejuni enteritis

Clamidia infections

Gonorrhoea

It is a good choice for penicillin-sensitive cases

Dr Amged 17

Clarithromycin

6-Methyl ether of erythromycin

Cannot undergo cyclic ketal formation so doesnrsquot cause

cramp in GI

Higher blood concentrations

More lipophilic

Lower doses with less intervals

Dr Amged 18

Azithromycin Azalide a semisynthetic macrolide with a15 membered

ring

Stable under acidic conditions because it doesnrsquot formcyclic ketal

In the treatment of urogenital infections caused by Ngonorrhoeae and Chlamidia trachomatis

Longer half-life

Dr Amged 19

Dr Amged 20

Dirithromycin

A more lipophyl prodrug with high oral absorption

Unstable 9N11O oxazine ring which easily hydrolysis to

erythromyclamine

Dirithromycin is protected against gastric acid with the enteric coated

form

Dr Amged 21

Ketolides Ketolides is a group of recently analogues of macrolides developed

to reduce side effects of macrolides and broaden their antimicrobial

spectra

The cladinose sugar in erythromycin has been replaced with a keto-

group

They are active against erythromycin resistant microorganisms

Dr Amged 22

Telithromycin

Telithromycin is orally effective in the treatment of community

acquired pneumonia acute bacterial exacerbations of chronic

bronchitis and acute sinusitis

Main structure modifications are

The cladinose sugar in erythromycin has been replaced with a keto-

group and a carbamate ring has been fused to the macrocyclic ring

The two hydroxyl groups that cause the intramolecular ketal formation in

erythromycin have been masked one as a methoxy group and the other

as part of the carbamate ring Dr Amged 23

Dr Amged 24

Miscellaneous

Fusidic Acid (Fucidin)

Fusidic acid is the only steroidal antibiotic and is isolated

from the fermentation broth of Fusidium coccineum

How does it work

It kills bacteria by interfering with the synthesis

of proteins inside the bacterial cells

Medicinal uses

Bacterial conjunctivitis and Bacterial infections

of the eye

Osteomyelitis (bone and joint infections)

Skin and soft tissue infections

Dr Amged 26

Clindamycin is the 7-chloro-7-deoxy

derivative of lincomycin with greater

antibacterial activity and better

pharmacokinetic properties

The Lincosamides

Sulphur-containing antibiotics ldquoLincomycin and

Clindamycinrdquo

Have similar antibacterial properties to the macrolides and

act in the same fashion

Dr Amged 27

Polypeptides

Polypeptidesbull These are among the most powerful bactericidal

antibiotics but unfortunately their clinical use is

limited due to undesirable side reactions

particularly renal toxicity

bull They are neutral acidic or basic in nature

bull Some of them are active against gram-positive

bacteria while others as polymyxins are active

against gram-negative

bull Colistin and bacitracin are also members of this

class

Dr Amged 29

Mechanism of action

These antibiotics act on the plasma membrane structure of bacterial cells allowing

uncontrolled movements of ions across the cell membrane

Dr Amged 30

Polymyxin B1

BacitracinDr Amged 31

Dr Amged 32

Intramolecular ketal formation in

erythromycin

Dr Amged 9

Chemical Instability

bull The cyclic ketal cause intestinal cramp which is reported after

the use of erythromycin

bull Water-insoluble salts and enteric coated dosage forms of

macrolides have less such a side effect

bull Water insoluble forms cannot take part in the reactions which

occur in aqueous solutions

bull Stearate salt is an example of insoluble salts of erytromycin

bull One way of preventing acid sensitivity is to protect the hydroxy

groups For example clarithromycin is a methoxy analogue of

erythromycin which is more stable to gastric juices and has

improved oral absorption

bull Another method of increasing acid stability is to increase the

size of the macrocycle to a 16-membered ring

Dr Amged 11

Therapeutic Agents

Erythromycin

It has been the subject of chemical

manipulations to

a) Increase the water solubility of the drug for

parenteral dosage forms

b) Increase the lipid solubility and hence chemical

stability of the drug against aqueous acidic

conditions as well as increase in oral absorption and

masking the bitter taste of the drug

Dr Amged 13

ErythromycinThe chemical manipulations are

1 Preparation of acidic salts such as glucoheptonate

lactobionate and stearate on the dimethyl amino group

2 Ester formation on the 2`-OH of the amino sugar

Ethylsuccinate and propionate are examples

Dr Amged 14

Erythromycin EstersErythromycin Ethyl Succinate

A mixed double ester prodrug of erythromycin

Better oral absorption

In oral suspensions for children without the bitter taste

Erythromycin PropionateA lipid-soluble ester of propionic acid

Better oral absorption

Dr Amged 15

Erythromycin SaltsErythromycin Stearate

A lipid-soluble salt of stearic acid

Better oral absorption

Acid-sensitive Enteric coated form is Acid-stable

In the small intestine base exchange occurs and free erythromycin

releases

Erythromycin Lactobionate

A water-soluble salt of lactobionic acid for parenteral dosage forms

Erythromycin Glucoheptonate

A water-soluble salt of glucoheptonic acid for parenteral dosage

forms

Dr Amged 16

Clinical Application of Erythromycin

It is used to treat

The upper part of the respiratory tract infections

Soft tissue G(+) infections

Mycoplasma pneumonia caused pneumonia

Campylobacter jejuni enteritis

Clamidia infections

Gonorrhoea

It is a good choice for penicillin-sensitive cases

Dr Amged 17

Clarithromycin

6-Methyl ether of erythromycin

Cannot undergo cyclic ketal formation so doesnrsquot cause

cramp in GI

Higher blood concentrations

More lipophilic

Lower doses with less intervals

Dr Amged 18

Azithromycin Azalide a semisynthetic macrolide with a15 membered

ring

Stable under acidic conditions because it doesnrsquot formcyclic ketal

In the treatment of urogenital infections caused by Ngonorrhoeae and Chlamidia trachomatis

Longer half-life

Dr Amged 19

Dr Amged 20

Dirithromycin

A more lipophyl prodrug with high oral absorption

Unstable 9N11O oxazine ring which easily hydrolysis to

erythromyclamine

Dirithromycin is protected against gastric acid with the enteric coated

form

Dr Amged 21

Ketolides Ketolides is a group of recently analogues of macrolides developed

to reduce side effects of macrolides and broaden their antimicrobial

spectra

The cladinose sugar in erythromycin has been replaced with a keto-

group

They are active against erythromycin resistant microorganisms

Dr Amged 22

Telithromycin

Telithromycin is orally effective in the treatment of community

acquired pneumonia acute bacterial exacerbations of chronic

bronchitis and acute sinusitis

Main structure modifications are

The cladinose sugar in erythromycin has been replaced with a keto-

group and a carbamate ring has been fused to the macrocyclic ring

The two hydroxyl groups that cause the intramolecular ketal formation in

erythromycin have been masked one as a methoxy group and the other

as part of the carbamate ring Dr Amged 23

Dr Amged 24

Miscellaneous

Fusidic Acid (Fucidin)

Fusidic acid is the only steroidal antibiotic and is isolated

from the fermentation broth of Fusidium coccineum

How does it work

It kills bacteria by interfering with the synthesis

of proteins inside the bacterial cells

Medicinal uses

Bacterial conjunctivitis and Bacterial infections

of the eye

Osteomyelitis (bone and joint infections)

Skin and soft tissue infections

Dr Amged 26

Clindamycin is the 7-chloro-7-deoxy

derivative of lincomycin with greater

antibacterial activity and better

pharmacokinetic properties

The Lincosamides

Sulphur-containing antibiotics ldquoLincomycin and

Clindamycinrdquo

Have similar antibacterial properties to the macrolides and

act in the same fashion

Dr Amged 27

Polypeptides

Polypeptidesbull These are among the most powerful bactericidal

antibiotics but unfortunately their clinical use is

limited due to undesirable side reactions

particularly renal toxicity

bull They are neutral acidic or basic in nature

bull Some of them are active against gram-positive

bacteria while others as polymyxins are active

against gram-negative

bull Colistin and bacitracin are also members of this

class

Dr Amged 29

Mechanism of action

These antibiotics act on the plasma membrane structure of bacterial cells allowing

uncontrolled movements of ions across the cell membrane

Dr Amged 30

Polymyxin B1

BacitracinDr Amged 31

Dr Amged 32

Chemical Instability

bull The cyclic ketal cause intestinal cramp which is reported after

the use of erythromycin

bull Water-insoluble salts and enteric coated dosage forms of

macrolides have less such a side effect

bull Water insoluble forms cannot take part in the reactions which

occur in aqueous solutions

bull Stearate salt is an example of insoluble salts of erytromycin

bull One way of preventing acid sensitivity is to protect the hydroxy

groups For example clarithromycin is a methoxy analogue of

erythromycin which is more stable to gastric juices and has

improved oral absorption

bull Another method of increasing acid stability is to increase the

size of the macrocycle to a 16-membered ring

Dr Amged 11

Therapeutic Agents

Erythromycin

It has been the subject of chemical

manipulations to

a) Increase the water solubility of the drug for

parenteral dosage forms

b) Increase the lipid solubility and hence chemical

stability of the drug against aqueous acidic

conditions as well as increase in oral absorption and

masking the bitter taste of the drug

Dr Amged 13

ErythromycinThe chemical manipulations are

1 Preparation of acidic salts such as glucoheptonate

lactobionate and stearate on the dimethyl amino group

2 Ester formation on the 2`-OH of the amino sugar

Ethylsuccinate and propionate are examples

Dr Amged 14

Erythromycin EstersErythromycin Ethyl Succinate

A mixed double ester prodrug of erythromycin

Better oral absorption

In oral suspensions for children without the bitter taste

Erythromycin PropionateA lipid-soluble ester of propionic acid

Better oral absorption

Dr Amged 15

Erythromycin SaltsErythromycin Stearate

A lipid-soluble salt of stearic acid

Better oral absorption

Acid-sensitive Enteric coated form is Acid-stable

In the small intestine base exchange occurs and free erythromycin

releases

Erythromycin Lactobionate

A water-soluble salt of lactobionic acid for parenteral dosage forms

Erythromycin Glucoheptonate

A water-soluble salt of glucoheptonic acid for parenteral dosage

forms

Dr Amged 16

Clinical Application of Erythromycin

It is used to treat

The upper part of the respiratory tract infections

Soft tissue G(+) infections

Mycoplasma pneumonia caused pneumonia

Campylobacter jejuni enteritis

Clamidia infections

Gonorrhoea

It is a good choice for penicillin-sensitive cases

Dr Amged 17

Clarithromycin

6-Methyl ether of erythromycin

Cannot undergo cyclic ketal formation so doesnrsquot cause

cramp in GI

Higher blood concentrations

More lipophilic

Lower doses with less intervals

Dr Amged 18

Azithromycin Azalide a semisynthetic macrolide with a15 membered

ring

Stable under acidic conditions because it doesnrsquot formcyclic ketal

In the treatment of urogenital infections caused by Ngonorrhoeae and Chlamidia trachomatis

Longer half-life

Dr Amged 19

Dr Amged 20

Dirithromycin

A more lipophyl prodrug with high oral absorption

Unstable 9N11O oxazine ring which easily hydrolysis to

erythromyclamine

Dirithromycin is protected against gastric acid with the enteric coated

form

Dr Amged 21

Ketolides Ketolides is a group of recently analogues of macrolides developed

to reduce side effects of macrolides and broaden their antimicrobial

spectra

The cladinose sugar in erythromycin has been replaced with a keto-

group

They are active against erythromycin resistant microorganisms

Dr Amged 22

Telithromycin

Telithromycin is orally effective in the treatment of community

acquired pneumonia acute bacterial exacerbations of chronic

bronchitis and acute sinusitis

Main structure modifications are

The cladinose sugar in erythromycin has been replaced with a keto-

group and a carbamate ring has been fused to the macrocyclic ring

The two hydroxyl groups that cause the intramolecular ketal formation in

erythromycin have been masked one as a methoxy group and the other

as part of the carbamate ring Dr Amged 23

Dr Amged 24

Miscellaneous

Fusidic Acid (Fucidin)

Fusidic acid is the only steroidal antibiotic and is isolated

from the fermentation broth of Fusidium coccineum

How does it work

It kills bacteria by interfering with the synthesis

of proteins inside the bacterial cells

Medicinal uses

Bacterial conjunctivitis and Bacterial infections

of the eye

Osteomyelitis (bone and joint infections)

Skin and soft tissue infections

Dr Amged 26

Clindamycin is the 7-chloro-7-deoxy

derivative of lincomycin with greater

antibacterial activity and better

pharmacokinetic properties

The Lincosamides

Sulphur-containing antibiotics ldquoLincomycin and

Clindamycinrdquo

Have similar antibacterial properties to the macrolides and

act in the same fashion

Dr Amged 27

Polypeptides

Polypeptidesbull These are among the most powerful bactericidal

antibiotics but unfortunately their clinical use is

limited due to undesirable side reactions

particularly renal toxicity

bull They are neutral acidic or basic in nature

bull Some of them are active against gram-positive

bacteria while others as polymyxins are active

against gram-negative

bull Colistin and bacitracin are also members of this

class

Dr Amged 29

Mechanism of action

These antibiotics act on the plasma membrane structure of bacterial cells allowing

uncontrolled movements of ions across the cell membrane

Dr Amged 30

Polymyxin B1

BacitracinDr Amged 31

Dr Amged 32

Therapeutic Agents

Erythromycin

It has been the subject of chemical

manipulations to

a) Increase the water solubility of the drug for

parenteral dosage forms

b) Increase the lipid solubility and hence chemical

stability of the drug against aqueous acidic

conditions as well as increase in oral absorption and

masking the bitter taste of the drug

Dr Amged 13

ErythromycinThe chemical manipulations are

1 Preparation of acidic salts such as glucoheptonate

lactobionate and stearate on the dimethyl amino group

2 Ester formation on the 2`-OH of the amino sugar

Ethylsuccinate and propionate are examples

Dr Amged 14

Erythromycin EstersErythromycin Ethyl Succinate

A mixed double ester prodrug of erythromycin

Better oral absorption

In oral suspensions for children without the bitter taste

Erythromycin PropionateA lipid-soluble ester of propionic acid

Better oral absorption

Dr Amged 15

Erythromycin SaltsErythromycin Stearate

A lipid-soluble salt of stearic acid

Better oral absorption

Acid-sensitive Enteric coated form is Acid-stable

In the small intestine base exchange occurs and free erythromycin

releases

Erythromycin Lactobionate

A water-soluble salt of lactobionic acid for parenteral dosage forms

Erythromycin Glucoheptonate

A water-soluble salt of glucoheptonic acid for parenteral dosage

forms

Dr Amged 16

Clinical Application of Erythromycin

It is used to treat

The upper part of the respiratory tract infections

Soft tissue G(+) infections

Mycoplasma pneumonia caused pneumonia

Campylobacter jejuni enteritis

Clamidia infections

Gonorrhoea

It is a good choice for penicillin-sensitive cases

Dr Amged 17

Clarithromycin

6-Methyl ether of erythromycin

Cannot undergo cyclic ketal formation so doesnrsquot cause

cramp in GI

Higher blood concentrations

More lipophilic

Lower doses with less intervals

Dr Amged 18

Azithromycin Azalide a semisynthetic macrolide with a15 membered

ring

Stable under acidic conditions because it doesnrsquot formcyclic ketal

In the treatment of urogenital infections caused by Ngonorrhoeae and Chlamidia trachomatis

Longer half-life

Dr Amged 19

Dr Amged 20

Dirithromycin

A more lipophyl prodrug with high oral absorption

Unstable 9N11O oxazine ring which easily hydrolysis to

erythromyclamine

Dirithromycin is protected against gastric acid with the enteric coated

form

Dr Amged 21

Ketolides Ketolides is a group of recently analogues of macrolides developed

to reduce side effects of macrolides and broaden their antimicrobial

spectra

The cladinose sugar in erythromycin has been replaced with a keto-

group

They are active against erythromycin resistant microorganisms

Dr Amged 22

Telithromycin

Telithromycin is orally effective in the treatment of community

acquired pneumonia acute bacterial exacerbations of chronic

bronchitis and acute sinusitis

Main structure modifications are

The cladinose sugar in erythromycin has been replaced with a keto-

group and a carbamate ring has been fused to the macrocyclic ring

The two hydroxyl groups that cause the intramolecular ketal formation in

erythromycin have been masked one as a methoxy group and the other

as part of the carbamate ring Dr Amged 23

Dr Amged 24

Miscellaneous

Fusidic Acid (Fucidin)

Fusidic acid is the only steroidal antibiotic and is isolated

from the fermentation broth of Fusidium coccineum

How does it work

It kills bacteria by interfering with the synthesis

of proteins inside the bacterial cells

Medicinal uses

Bacterial conjunctivitis and Bacterial infections

of the eye

Osteomyelitis (bone and joint infections)

Skin and soft tissue infections

Dr Amged 26

Clindamycin is the 7-chloro-7-deoxy

derivative of lincomycin with greater

antibacterial activity and better

pharmacokinetic properties

The Lincosamides

Sulphur-containing antibiotics ldquoLincomycin and

Clindamycinrdquo

Have similar antibacterial properties to the macrolides and

act in the same fashion

Dr Amged 27

Polypeptides

Polypeptidesbull These are among the most powerful bactericidal

antibiotics but unfortunately their clinical use is

limited due to undesirable side reactions

particularly renal toxicity

bull They are neutral acidic or basic in nature

bull Some of them are active against gram-positive

bacteria while others as polymyxins are active

against gram-negative

bull Colistin and bacitracin are also members of this

class

Dr Amged 29

Mechanism of action

These antibiotics act on the plasma membrane structure of bacterial cells allowing

uncontrolled movements of ions across the cell membrane

Dr Amged 30

Polymyxin B1

BacitracinDr Amged 31

Dr Amged 32

Erythromycin

It has been the subject of chemical

manipulations to

a) Increase the water solubility of the drug for

parenteral dosage forms

b) Increase the lipid solubility and hence chemical

stability of the drug against aqueous acidic

conditions as well as increase in oral absorption and

masking the bitter taste of the drug

Dr Amged 13

ErythromycinThe chemical manipulations are

1 Preparation of acidic salts such as glucoheptonate

lactobionate and stearate on the dimethyl amino group

2 Ester formation on the 2`-OH of the amino sugar

Ethylsuccinate and propionate are examples

Dr Amged 14

Erythromycin EstersErythromycin Ethyl Succinate

A mixed double ester prodrug of erythromycin

Better oral absorption

In oral suspensions for children without the bitter taste

Erythromycin PropionateA lipid-soluble ester of propionic acid

Better oral absorption

Dr Amged 15

Erythromycin SaltsErythromycin Stearate

A lipid-soluble salt of stearic acid

Better oral absorption

Acid-sensitive Enteric coated form is Acid-stable

In the small intestine base exchange occurs and free erythromycin

releases

Erythromycin Lactobionate

A water-soluble salt of lactobionic acid for parenteral dosage forms

Erythromycin Glucoheptonate

A water-soluble salt of glucoheptonic acid for parenteral dosage

forms

Dr Amged 16

Clinical Application of Erythromycin

It is used to treat

The upper part of the respiratory tract infections

Soft tissue G(+) infections

Mycoplasma pneumonia caused pneumonia

Campylobacter jejuni enteritis

Clamidia infections

Gonorrhoea

It is a good choice for penicillin-sensitive cases

Dr Amged 17

Clarithromycin

6-Methyl ether of erythromycin

Cannot undergo cyclic ketal formation so doesnrsquot cause

cramp in GI

Higher blood concentrations

More lipophilic

Lower doses with less intervals

Dr Amged 18

Azithromycin Azalide a semisynthetic macrolide with a15 membered

ring

Stable under acidic conditions because it doesnrsquot formcyclic ketal

In the treatment of urogenital infections caused by Ngonorrhoeae and Chlamidia trachomatis

Longer half-life

Dr Amged 19

Dr Amged 20

Dirithromycin

A more lipophyl prodrug with high oral absorption

Unstable 9N11O oxazine ring which easily hydrolysis to

erythromyclamine

Dirithromycin is protected against gastric acid with the enteric coated

form

Dr Amged 21

Ketolides Ketolides is a group of recently analogues of macrolides developed

to reduce side effects of macrolides and broaden their antimicrobial

spectra

The cladinose sugar in erythromycin has been replaced with a keto-

group

They are active against erythromycin resistant microorganisms

Dr Amged 22

Telithromycin

Telithromycin is orally effective in the treatment of community

acquired pneumonia acute bacterial exacerbations of chronic

bronchitis and acute sinusitis

Main structure modifications are

The cladinose sugar in erythromycin has been replaced with a keto-

group and a carbamate ring has been fused to the macrocyclic ring

The two hydroxyl groups that cause the intramolecular ketal formation in

erythromycin have been masked one as a methoxy group and the other

as part of the carbamate ring Dr Amged 23

Dr Amged 24

Miscellaneous

Fusidic Acid (Fucidin)

Fusidic acid is the only steroidal antibiotic and is isolated

from the fermentation broth of Fusidium coccineum

How does it work

It kills bacteria by interfering with the synthesis

of proteins inside the bacterial cells

Medicinal uses

Bacterial conjunctivitis and Bacterial infections

of the eye

Osteomyelitis (bone and joint infections)

Skin and soft tissue infections

Dr Amged 26

Clindamycin is the 7-chloro-7-deoxy

derivative of lincomycin with greater

antibacterial activity and better

pharmacokinetic properties

The Lincosamides

Sulphur-containing antibiotics ldquoLincomycin and

Clindamycinrdquo

Have similar antibacterial properties to the macrolides and

act in the same fashion

Dr Amged 27

Polypeptides

Polypeptidesbull These are among the most powerful bactericidal

antibiotics but unfortunately their clinical use is

limited due to undesirable side reactions

particularly renal toxicity

bull They are neutral acidic or basic in nature

bull Some of them are active against gram-positive

bacteria while others as polymyxins are active

against gram-negative

bull Colistin and bacitracin are also members of this

class

Dr Amged 29

Mechanism of action

These antibiotics act on the plasma membrane structure of bacterial cells allowing

uncontrolled movements of ions across the cell membrane

Dr Amged 30

Polymyxin B1

BacitracinDr Amged 31

Dr Amged 32

ErythromycinThe chemical manipulations are

1 Preparation of acidic salts such as glucoheptonate

lactobionate and stearate on the dimethyl amino group

2 Ester formation on the 2`-OH of the amino sugar

Ethylsuccinate and propionate are examples

Dr Amged 14

Erythromycin EstersErythromycin Ethyl Succinate

A mixed double ester prodrug of erythromycin

Better oral absorption

In oral suspensions for children without the bitter taste

Erythromycin PropionateA lipid-soluble ester of propionic acid

Better oral absorption

Dr Amged 15

Erythromycin SaltsErythromycin Stearate

A lipid-soluble salt of stearic acid

Better oral absorption

Acid-sensitive Enteric coated form is Acid-stable

In the small intestine base exchange occurs and free erythromycin

releases

Erythromycin Lactobionate

A water-soluble salt of lactobionic acid for parenteral dosage forms

Erythromycin Glucoheptonate

A water-soluble salt of glucoheptonic acid for parenteral dosage

forms

Dr Amged 16

Clinical Application of Erythromycin

It is used to treat

The upper part of the respiratory tract infections

Soft tissue G(+) infections

Mycoplasma pneumonia caused pneumonia

Campylobacter jejuni enteritis

Clamidia infections

Gonorrhoea

It is a good choice for penicillin-sensitive cases

Dr Amged 17

Clarithromycin

6-Methyl ether of erythromycin

Cannot undergo cyclic ketal formation so doesnrsquot cause

cramp in GI

Higher blood concentrations

More lipophilic

Lower doses with less intervals

Dr Amged 18

Azithromycin Azalide a semisynthetic macrolide with a15 membered

ring

Stable under acidic conditions because it doesnrsquot formcyclic ketal

In the treatment of urogenital infections caused by Ngonorrhoeae and Chlamidia trachomatis

Longer half-life

Dr Amged 19

Dr Amged 20

Dirithromycin

A more lipophyl prodrug with high oral absorption

Unstable 9N11O oxazine ring which easily hydrolysis to

erythromyclamine

Dirithromycin is protected against gastric acid with the enteric coated

form

Dr Amged 21

Ketolides Ketolides is a group of recently analogues of macrolides developed

to reduce side effects of macrolides and broaden their antimicrobial

spectra

The cladinose sugar in erythromycin has been replaced with a keto-

group

They are active against erythromycin resistant microorganisms

Dr Amged 22

Telithromycin

Telithromycin is orally effective in the treatment of community

acquired pneumonia acute bacterial exacerbations of chronic

bronchitis and acute sinusitis

Main structure modifications are

The cladinose sugar in erythromycin has been replaced with a keto-

group and a carbamate ring has been fused to the macrocyclic ring

The two hydroxyl groups that cause the intramolecular ketal formation in

erythromycin have been masked one as a methoxy group and the other

as part of the carbamate ring Dr Amged 23

Dr Amged 24

Miscellaneous

Fusidic Acid (Fucidin)

Fusidic acid is the only steroidal antibiotic and is isolated

from the fermentation broth of Fusidium coccineum

How does it work

It kills bacteria by interfering with the synthesis

of proteins inside the bacterial cells

Medicinal uses

Bacterial conjunctivitis and Bacterial infections

of the eye

Osteomyelitis (bone and joint infections)

Skin and soft tissue infections

Dr Amged 26

Clindamycin is the 7-chloro-7-deoxy

derivative of lincomycin with greater

antibacterial activity and better

pharmacokinetic properties

The Lincosamides

Sulphur-containing antibiotics ldquoLincomycin and

Clindamycinrdquo

Have similar antibacterial properties to the macrolides and

act in the same fashion

Dr Amged 27

Polypeptides

Polypeptidesbull These are among the most powerful bactericidal

antibiotics but unfortunately their clinical use is

limited due to undesirable side reactions

particularly renal toxicity

bull They are neutral acidic or basic in nature

bull Some of them are active against gram-positive

bacteria while others as polymyxins are active

against gram-negative

bull Colistin and bacitracin are also members of this

class

Dr Amged 29

Mechanism of action

These antibiotics act on the plasma membrane structure of bacterial cells allowing

uncontrolled movements of ions across the cell membrane

Dr Amged 30

Polymyxin B1

BacitracinDr Amged 31

Dr Amged 32

Erythromycin EstersErythromycin Ethyl Succinate

A mixed double ester prodrug of erythromycin

Better oral absorption

In oral suspensions for children without the bitter taste

Erythromycin PropionateA lipid-soluble ester of propionic acid

Better oral absorption

Dr Amged 15

Erythromycin SaltsErythromycin Stearate

A lipid-soluble salt of stearic acid

Better oral absorption

Acid-sensitive Enteric coated form is Acid-stable

In the small intestine base exchange occurs and free erythromycin

releases

Erythromycin Lactobionate

A water-soluble salt of lactobionic acid for parenteral dosage forms

Erythromycin Glucoheptonate

A water-soluble salt of glucoheptonic acid for parenteral dosage

forms

Dr Amged 16

Clinical Application of Erythromycin

It is used to treat

The upper part of the respiratory tract infections

Soft tissue G(+) infections

Mycoplasma pneumonia caused pneumonia

Campylobacter jejuni enteritis

Clamidia infections

Gonorrhoea

It is a good choice for penicillin-sensitive cases

Dr Amged 17

Clarithromycin

6-Methyl ether of erythromycin

Cannot undergo cyclic ketal formation so doesnrsquot cause

cramp in GI

Higher blood concentrations

More lipophilic

Lower doses with less intervals

Dr Amged 18

Azithromycin Azalide a semisynthetic macrolide with a15 membered

ring

Stable under acidic conditions because it doesnrsquot formcyclic ketal

In the treatment of urogenital infections caused by Ngonorrhoeae and Chlamidia trachomatis

Longer half-life

Dr Amged 19

Dr Amged 20

Dirithromycin

A more lipophyl prodrug with high oral absorption

Unstable 9N11O oxazine ring which easily hydrolysis to

erythromyclamine

Dirithromycin is protected against gastric acid with the enteric coated

form

Dr Amged 21

Ketolides Ketolides is a group of recently analogues of macrolides developed

to reduce side effects of macrolides and broaden their antimicrobial

spectra

The cladinose sugar in erythromycin has been replaced with a keto-

group

They are active against erythromycin resistant microorganisms

Dr Amged 22

Telithromycin

Telithromycin is orally effective in the treatment of community

acquired pneumonia acute bacterial exacerbations of chronic

bronchitis and acute sinusitis

Main structure modifications are

The cladinose sugar in erythromycin has been replaced with a keto-

group and a carbamate ring has been fused to the macrocyclic ring

The two hydroxyl groups that cause the intramolecular ketal formation in

erythromycin have been masked one as a methoxy group and the other

as part of the carbamate ring Dr Amged 23

Dr Amged 24

Miscellaneous

Fusidic Acid (Fucidin)

Fusidic acid is the only steroidal antibiotic and is isolated

from the fermentation broth of Fusidium coccineum

How does it work

It kills bacteria by interfering with the synthesis

of proteins inside the bacterial cells

Medicinal uses

Bacterial conjunctivitis and Bacterial infections

of the eye

Osteomyelitis (bone and joint infections)

Skin and soft tissue infections

Dr Amged 26

Clindamycin is the 7-chloro-7-deoxy

derivative of lincomycin with greater

antibacterial activity and better

pharmacokinetic properties

The Lincosamides

Sulphur-containing antibiotics ldquoLincomycin and

Clindamycinrdquo

Have similar antibacterial properties to the macrolides and

act in the same fashion

Dr Amged 27

Polypeptides

Polypeptidesbull These are among the most powerful bactericidal

antibiotics but unfortunately their clinical use is

limited due to undesirable side reactions

particularly renal toxicity

bull They are neutral acidic or basic in nature

bull Some of them are active against gram-positive

bacteria while others as polymyxins are active

against gram-negative

bull Colistin and bacitracin are also members of this

class

Dr Amged 29

Mechanism of action

These antibiotics act on the plasma membrane structure of bacterial cells allowing

uncontrolled movements of ions across the cell membrane

Dr Amged 30

Polymyxin B1

BacitracinDr Amged 31

Dr Amged 32

Erythromycin SaltsErythromycin Stearate

A lipid-soluble salt of stearic acid

Better oral absorption

Acid-sensitive Enteric coated form is Acid-stable

In the small intestine base exchange occurs and free erythromycin

releases

Erythromycin Lactobionate

A water-soluble salt of lactobionic acid for parenteral dosage forms

Erythromycin Glucoheptonate

A water-soluble salt of glucoheptonic acid for parenteral dosage

forms

Dr Amged 16

Clinical Application of Erythromycin

It is used to treat

The upper part of the respiratory tract infections

Soft tissue G(+) infections

Mycoplasma pneumonia caused pneumonia

Campylobacter jejuni enteritis

Clamidia infections

Gonorrhoea

It is a good choice for penicillin-sensitive cases

Dr Amged 17

Clarithromycin

6-Methyl ether of erythromycin

Cannot undergo cyclic ketal formation so doesnrsquot cause

cramp in GI

Higher blood concentrations

More lipophilic

Lower doses with less intervals

Dr Amged 18

Azithromycin Azalide a semisynthetic macrolide with a15 membered

ring

Stable under acidic conditions because it doesnrsquot formcyclic ketal

In the treatment of urogenital infections caused by Ngonorrhoeae and Chlamidia trachomatis

Longer half-life

Dr Amged 19

Dr Amged 20

Dirithromycin

A more lipophyl prodrug with high oral absorption

Unstable 9N11O oxazine ring which easily hydrolysis to

erythromyclamine

Dirithromycin is protected against gastric acid with the enteric coated

form

Dr Amged 21

Ketolides Ketolides is a group of recently analogues of macrolides developed

to reduce side effects of macrolides and broaden their antimicrobial

spectra

The cladinose sugar in erythromycin has been replaced with a keto-

group

They are active against erythromycin resistant microorganisms

Dr Amged 22

Telithromycin

Telithromycin is orally effective in the treatment of community

acquired pneumonia acute bacterial exacerbations of chronic

bronchitis and acute sinusitis

Main structure modifications are

The cladinose sugar in erythromycin has been replaced with a keto-

group and a carbamate ring has been fused to the macrocyclic ring

The two hydroxyl groups that cause the intramolecular ketal formation in

erythromycin have been masked one as a methoxy group and the other

as part of the carbamate ring Dr Amged 23

Dr Amged 24

Miscellaneous

Fusidic Acid (Fucidin)

Fusidic acid is the only steroidal antibiotic and is isolated

from the fermentation broth of Fusidium coccineum

How does it work

It kills bacteria by interfering with the synthesis

of proteins inside the bacterial cells

Medicinal uses

Bacterial conjunctivitis and Bacterial infections

of the eye

Osteomyelitis (bone and joint infections)

Skin and soft tissue infections

Dr Amged 26

Clindamycin is the 7-chloro-7-deoxy

derivative of lincomycin with greater

antibacterial activity and better

pharmacokinetic properties

The Lincosamides

Sulphur-containing antibiotics ldquoLincomycin and

Clindamycinrdquo

Have similar antibacterial properties to the macrolides and

act in the same fashion

Dr Amged 27

Polypeptides

Polypeptidesbull These are among the most powerful bactericidal

antibiotics but unfortunately their clinical use is

limited due to undesirable side reactions

particularly renal toxicity

bull They are neutral acidic or basic in nature

bull Some of them are active against gram-positive

bacteria while others as polymyxins are active

against gram-negative

bull Colistin and bacitracin are also members of this

class

Dr Amged 29

Mechanism of action

These antibiotics act on the plasma membrane structure of bacterial cells allowing

uncontrolled movements of ions across the cell membrane

Dr Amged 30

Polymyxin B1

BacitracinDr Amged 31

Dr Amged 32

Clinical Application of Erythromycin

It is used to treat

The upper part of the respiratory tract infections

Soft tissue G(+) infections

Mycoplasma pneumonia caused pneumonia

Campylobacter jejuni enteritis

Clamidia infections

Gonorrhoea

It is a good choice for penicillin-sensitive cases

Dr Amged 17

Clarithromycin

6-Methyl ether of erythromycin

Cannot undergo cyclic ketal formation so doesnrsquot cause

cramp in GI

Higher blood concentrations

More lipophilic

Lower doses with less intervals

Dr Amged 18

Azithromycin Azalide a semisynthetic macrolide with a15 membered

ring

Stable under acidic conditions because it doesnrsquot formcyclic ketal

In the treatment of urogenital infections caused by Ngonorrhoeae and Chlamidia trachomatis

Longer half-life

Dr Amged 19

Dr Amged 20

Dirithromycin

A more lipophyl prodrug with high oral absorption

Unstable 9N11O oxazine ring which easily hydrolysis to

erythromyclamine

Dirithromycin is protected against gastric acid with the enteric coated

form

Dr Amged 21

Ketolides Ketolides is a group of recently analogues of macrolides developed

to reduce side effects of macrolides and broaden their antimicrobial

spectra

The cladinose sugar in erythromycin has been replaced with a keto-

group

They are active against erythromycin resistant microorganisms

Dr Amged 22

Telithromycin

Telithromycin is orally effective in the treatment of community

acquired pneumonia acute bacterial exacerbations of chronic

bronchitis and acute sinusitis

Main structure modifications are

The cladinose sugar in erythromycin has been replaced with a keto-

group and a carbamate ring has been fused to the macrocyclic ring

The two hydroxyl groups that cause the intramolecular ketal formation in

erythromycin have been masked one as a methoxy group and the other

as part of the carbamate ring Dr Amged 23

Dr Amged 24

Miscellaneous

Fusidic Acid (Fucidin)

Fusidic acid is the only steroidal antibiotic and is isolated

from the fermentation broth of Fusidium coccineum

How does it work

It kills bacteria by interfering with the synthesis

of proteins inside the bacterial cells

Medicinal uses

Bacterial conjunctivitis and Bacterial infections

of the eye

Osteomyelitis (bone and joint infections)

Skin and soft tissue infections

Dr Amged 26

Clindamycin is the 7-chloro-7-deoxy

derivative of lincomycin with greater

antibacterial activity and better

pharmacokinetic properties

The Lincosamides

Sulphur-containing antibiotics ldquoLincomycin and

Clindamycinrdquo

Have similar antibacterial properties to the macrolides and

act in the same fashion

Dr Amged 27

Polypeptides

Polypeptidesbull These are among the most powerful bactericidal

antibiotics but unfortunately their clinical use is

limited due to undesirable side reactions

particularly renal toxicity

bull They are neutral acidic or basic in nature

bull Some of them are active against gram-positive

bacteria while others as polymyxins are active

against gram-negative

bull Colistin and bacitracin are also members of this

class

Dr Amged 29

Mechanism of action

These antibiotics act on the plasma membrane structure of bacterial cells allowing

uncontrolled movements of ions across the cell membrane

Dr Amged 30

Polymyxin B1

BacitracinDr Amged 31

Dr Amged 32

Clarithromycin

6-Methyl ether of erythromycin

Cannot undergo cyclic ketal formation so doesnrsquot cause

cramp in GI

Higher blood concentrations

More lipophilic

Lower doses with less intervals

Dr Amged 18

Azithromycin Azalide a semisynthetic macrolide with a15 membered

ring

Stable under acidic conditions because it doesnrsquot formcyclic ketal

In the treatment of urogenital infections caused by Ngonorrhoeae and Chlamidia trachomatis

Longer half-life

Dr Amged 19

Dr Amged 20

Dirithromycin

A more lipophyl prodrug with high oral absorption

Unstable 9N11O oxazine ring which easily hydrolysis to

erythromyclamine

Dirithromycin is protected against gastric acid with the enteric coated

form

Dr Amged 21

Ketolides Ketolides is a group of recently analogues of macrolides developed

to reduce side effects of macrolides and broaden their antimicrobial

spectra

The cladinose sugar in erythromycin has been replaced with a keto-

group

They are active against erythromycin resistant microorganisms

Dr Amged 22

Telithromycin

Telithromycin is orally effective in the treatment of community

acquired pneumonia acute bacterial exacerbations of chronic

bronchitis and acute sinusitis

Main structure modifications are

The cladinose sugar in erythromycin has been replaced with a keto-

group and a carbamate ring has been fused to the macrocyclic ring

The two hydroxyl groups that cause the intramolecular ketal formation in

erythromycin have been masked one as a methoxy group and the other

as part of the carbamate ring Dr Amged 23

Dr Amged 24

Miscellaneous

Fusidic Acid (Fucidin)

Fusidic acid is the only steroidal antibiotic and is isolated

from the fermentation broth of Fusidium coccineum

How does it work

It kills bacteria by interfering with the synthesis

of proteins inside the bacterial cells

Medicinal uses

Bacterial conjunctivitis and Bacterial infections

of the eye

Osteomyelitis (bone and joint infections)

Skin and soft tissue infections

Dr Amged 26

Clindamycin is the 7-chloro-7-deoxy

derivative of lincomycin with greater

antibacterial activity and better

pharmacokinetic properties

The Lincosamides

Sulphur-containing antibiotics ldquoLincomycin and

Clindamycinrdquo

Have similar antibacterial properties to the macrolides and

act in the same fashion

Dr Amged 27

Polypeptides

Polypeptidesbull These are among the most powerful bactericidal

antibiotics but unfortunately their clinical use is

limited due to undesirable side reactions

particularly renal toxicity

bull They are neutral acidic or basic in nature

bull Some of them are active against gram-positive

bacteria while others as polymyxins are active

against gram-negative

bull Colistin and bacitracin are also members of this

class

Dr Amged 29

Mechanism of action

These antibiotics act on the plasma membrane structure of bacterial cells allowing

uncontrolled movements of ions across the cell membrane

Dr Amged 30

Polymyxin B1

BacitracinDr Amged 31

Dr Amged 32

Azithromycin Azalide a semisynthetic macrolide with a15 membered

ring

Stable under acidic conditions because it doesnrsquot formcyclic ketal

In the treatment of urogenital infections caused by Ngonorrhoeae and Chlamidia trachomatis

Longer half-life

Dr Amged 19

Dr Amged 20

Dirithromycin

A more lipophyl prodrug with high oral absorption

Unstable 9N11O oxazine ring which easily hydrolysis to

erythromyclamine

Dirithromycin is protected against gastric acid with the enteric coated

form

Dr Amged 21

Ketolides Ketolides is a group of recently analogues of macrolides developed

to reduce side effects of macrolides and broaden their antimicrobial

spectra

The cladinose sugar in erythromycin has been replaced with a keto-

group

They are active against erythromycin resistant microorganisms

Dr Amged 22

Telithromycin

Telithromycin is orally effective in the treatment of community

acquired pneumonia acute bacterial exacerbations of chronic

bronchitis and acute sinusitis

Main structure modifications are

The cladinose sugar in erythromycin has been replaced with a keto-

group and a carbamate ring has been fused to the macrocyclic ring

The two hydroxyl groups that cause the intramolecular ketal formation in

erythromycin have been masked one as a methoxy group and the other

as part of the carbamate ring Dr Amged 23

Dr Amged 24

Miscellaneous

Fusidic Acid (Fucidin)

Fusidic acid is the only steroidal antibiotic and is isolated

from the fermentation broth of Fusidium coccineum

How does it work

It kills bacteria by interfering with the synthesis

of proteins inside the bacterial cells

Medicinal uses

Bacterial conjunctivitis and Bacterial infections

of the eye

Osteomyelitis (bone and joint infections)

Skin and soft tissue infections

Dr Amged 26

Clindamycin is the 7-chloro-7-deoxy

derivative of lincomycin with greater

antibacterial activity and better

pharmacokinetic properties

The Lincosamides

Sulphur-containing antibiotics ldquoLincomycin and

Clindamycinrdquo

Have similar antibacterial properties to the macrolides and

act in the same fashion

Dr Amged 27

Polypeptides

Polypeptidesbull These are among the most powerful bactericidal

antibiotics but unfortunately their clinical use is

limited due to undesirable side reactions

particularly renal toxicity

bull They are neutral acidic or basic in nature

bull Some of them are active against gram-positive

bacteria while others as polymyxins are active

against gram-negative

bull Colistin and bacitracin are also members of this

class

Dr Amged 29

Mechanism of action

These antibiotics act on the plasma membrane structure of bacterial cells allowing

uncontrolled movements of ions across the cell membrane

Dr Amged 30

Polymyxin B1

BacitracinDr Amged 31

Dr Amged 32

Dr Amged 20

Dirithromycin

A more lipophyl prodrug with high oral absorption

Unstable 9N11O oxazine ring which easily hydrolysis to

erythromyclamine

Dirithromycin is protected against gastric acid with the enteric coated

form

Dr Amged 21

Ketolides Ketolides is a group of recently analogues of macrolides developed

to reduce side effects of macrolides and broaden their antimicrobial

spectra

The cladinose sugar in erythromycin has been replaced with a keto-

group

They are active against erythromycin resistant microorganisms

Dr Amged 22

Telithromycin

Telithromycin is orally effective in the treatment of community

acquired pneumonia acute bacterial exacerbations of chronic

bronchitis and acute sinusitis

Main structure modifications are

The cladinose sugar in erythromycin has been replaced with a keto-

group and a carbamate ring has been fused to the macrocyclic ring

The two hydroxyl groups that cause the intramolecular ketal formation in

erythromycin have been masked one as a methoxy group and the other

as part of the carbamate ring Dr Amged 23

Dr Amged 24

Miscellaneous

Fusidic Acid (Fucidin)

Fusidic acid is the only steroidal antibiotic and is isolated

from the fermentation broth of Fusidium coccineum

How does it work

It kills bacteria by interfering with the synthesis

of proteins inside the bacterial cells

Medicinal uses

Bacterial conjunctivitis and Bacterial infections

of the eye

Osteomyelitis (bone and joint infections)

Skin and soft tissue infections

Dr Amged 26

Clindamycin is the 7-chloro-7-deoxy

derivative of lincomycin with greater

antibacterial activity and better

pharmacokinetic properties

The Lincosamides

Sulphur-containing antibiotics ldquoLincomycin and

Clindamycinrdquo

Have similar antibacterial properties to the macrolides and

act in the same fashion

Dr Amged 27

Polypeptides

Polypeptidesbull These are among the most powerful bactericidal

antibiotics but unfortunately their clinical use is

limited due to undesirable side reactions

particularly renal toxicity

bull They are neutral acidic or basic in nature

bull Some of them are active against gram-positive

bacteria while others as polymyxins are active

against gram-negative

bull Colistin and bacitracin are also members of this

class

Dr Amged 29

Mechanism of action

These antibiotics act on the plasma membrane structure of bacterial cells allowing

uncontrolled movements of ions across the cell membrane

Dr Amged 30

Polymyxin B1

BacitracinDr Amged 31

Dr Amged 32

Dirithromycin

A more lipophyl prodrug with high oral absorption

Unstable 9N11O oxazine ring which easily hydrolysis to

erythromyclamine

Dirithromycin is protected against gastric acid with the enteric coated

form

Dr Amged 21

Ketolides Ketolides is a group of recently analogues of macrolides developed

to reduce side effects of macrolides and broaden their antimicrobial

spectra

The cladinose sugar in erythromycin has been replaced with a keto-

group

They are active against erythromycin resistant microorganisms

Dr Amged 22

Telithromycin

Telithromycin is orally effective in the treatment of community

acquired pneumonia acute bacterial exacerbations of chronic

bronchitis and acute sinusitis

Main structure modifications are

The cladinose sugar in erythromycin has been replaced with a keto-

group and a carbamate ring has been fused to the macrocyclic ring

The two hydroxyl groups that cause the intramolecular ketal formation in

erythromycin have been masked one as a methoxy group and the other

as part of the carbamate ring Dr Amged 23

Dr Amged 24

Miscellaneous

Fusidic Acid (Fucidin)

Fusidic acid is the only steroidal antibiotic and is isolated

from the fermentation broth of Fusidium coccineum

How does it work

It kills bacteria by interfering with the synthesis

of proteins inside the bacterial cells

Medicinal uses

Bacterial conjunctivitis and Bacterial infections

of the eye

Osteomyelitis (bone and joint infections)

Skin and soft tissue infections

Dr Amged 26

Clindamycin is the 7-chloro-7-deoxy

derivative of lincomycin with greater

antibacterial activity and better

pharmacokinetic properties

The Lincosamides

Sulphur-containing antibiotics ldquoLincomycin and

Clindamycinrdquo

Have similar antibacterial properties to the macrolides and

act in the same fashion

Dr Amged 27

Polypeptides

Polypeptidesbull These are among the most powerful bactericidal

antibiotics but unfortunately their clinical use is

limited due to undesirable side reactions

particularly renal toxicity

bull They are neutral acidic or basic in nature

bull Some of them are active against gram-positive

bacteria while others as polymyxins are active

against gram-negative

bull Colistin and bacitracin are also members of this

class

Dr Amged 29

Mechanism of action

These antibiotics act on the plasma membrane structure of bacterial cells allowing

uncontrolled movements of ions across the cell membrane

Dr Amged 30

Polymyxin B1

BacitracinDr Amged 31

Dr Amged 32

Ketolides Ketolides is a group of recently analogues of macrolides developed

to reduce side effects of macrolides and broaden their antimicrobial

spectra

The cladinose sugar in erythromycin has been replaced with a keto-

group

They are active against erythromycin resistant microorganisms

Dr Amged 22

Telithromycin

Telithromycin is orally effective in the treatment of community

acquired pneumonia acute bacterial exacerbations of chronic

bronchitis and acute sinusitis

Main structure modifications are

The cladinose sugar in erythromycin has been replaced with a keto-

group and a carbamate ring has been fused to the macrocyclic ring

The two hydroxyl groups that cause the intramolecular ketal formation in

erythromycin have been masked one as a methoxy group and the other

as part of the carbamate ring Dr Amged 23

Dr Amged 24

Miscellaneous

Fusidic Acid (Fucidin)

Fusidic acid is the only steroidal antibiotic and is isolated

from the fermentation broth of Fusidium coccineum

How does it work

It kills bacteria by interfering with the synthesis

of proteins inside the bacterial cells

Medicinal uses

Bacterial conjunctivitis and Bacterial infections

of the eye

Osteomyelitis (bone and joint infections)

Skin and soft tissue infections

Dr Amged 26

Clindamycin is the 7-chloro-7-deoxy

derivative of lincomycin with greater

antibacterial activity and better

pharmacokinetic properties

The Lincosamides

Sulphur-containing antibiotics ldquoLincomycin and

Clindamycinrdquo

Have similar antibacterial properties to the macrolides and

act in the same fashion

Dr Amged 27

Polypeptides

Polypeptidesbull These are among the most powerful bactericidal

antibiotics but unfortunately their clinical use is

limited due to undesirable side reactions

particularly renal toxicity

bull They are neutral acidic or basic in nature

bull Some of them are active against gram-positive

bacteria while others as polymyxins are active

against gram-negative

bull Colistin and bacitracin are also members of this

class

Dr Amged 29

Mechanism of action

These antibiotics act on the plasma membrane structure of bacterial cells allowing

uncontrolled movements of ions across the cell membrane

Dr Amged 30

Polymyxin B1

BacitracinDr Amged 31

Dr Amged 32

Telithromycin

Telithromycin is orally effective in the treatment of community

acquired pneumonia acute bacterial exacerbations of chronic

bronchitis and acute sinusitis

Main structure modifications are

The cladinose sugar in erythromycin has been replaced with a keto-

group and a carbamate ring has been fused to the macrocyclic ring

The two hydroxyl groups that cause the intramolecular ketal formation in

erythromycin have been masked one as a methoxy group and the other

as part of the carbamate ring Dr Amged 23

Dr Amged 24

Miscellaneous

Fusidic Acid (Fucidin)

Fusidic acid is the only steroidal antibiotic and is isolated

from the fermentation broth of Fusidium coccineum

How does it work

It kills bacteria by interfering with the synthesis

of proteins inside the bacterial cells

Medicinal uses

Bacterial conjunctivitis and Bacterial infections

of the eye

Osteomyelitis (bone and joint infections)

Skin and soft tissue infections

Dr Amged 26

Clindamycin is the 7-chloro-7-deoxy

derivative of lincomycin with greater

antibacterial activity and better

pharmacokinetic properties

The Lincosamides

Sulphur-containing antibiotics ldquoLincomycin and

Clindamycinrdquo

Have similar antibacterial properties to the macrolides and

act in the same fashion

Dr Amged 27

Polypeptides

Polypeptidesbull These are among the most powerful bactericidal

antibiotics but unfortunately their clinical use is

limited due to undesirable side reactions

particularly renal toxicity

bull They are neutral acidic or basic in nature

bull Some of them are active against gram-positive

bacteria while others as polymyxins are active

against gram-negative

bull Colistin and bacitracin are also members of this

class

Dr Amged 29

Mechanism of action

These antibiotics act on the plasma membrane structure of bacterial cells allowing

uncontrolled movements of ions across the cell membrane

Dr Amged 30

Polymyxin B1

BacitracinDr Amged 31

Dr Amged 32

Dr Amged 24

Miscellaneous

Fusidic Acid (Fucidin)

Fusidic acid is the only steroidal antibiotic and is isolated

from the fermentation broth of Fusidium coccineum

How does it work

It kills bacteria by interfering with the synthesis

of proteins inside the bacterial cells

Medicinal uses

Bacterial conjunctivitis and Bacterial infections

of the eye

Osteomyelitis (bone and joint infections)

Skin and soft tissue infections

Dr Amged 26

Clindamycin is the 7-chloro-7-deoxy

derivative of lincomycin with greater

antibacterial activity and better

pharmacokinetic properties

The Lincosamides

Sulphur-containing antibiotics ldquoLincomycin and

Clindamycinrdquo

Have similar antibacterial properties to the macrolides and

act in the same fashion

Dr Amged 27

Polypeptides

Polypeptidesbull These are among the most powerful bactericidal

antibiotics but unfortunately their clinical use is

limited due to undesirable side reactions

particularly renal toxicity

bull They are neutral acidic or basic in nature

bull Some of them are active against gram-positive

bacteria while others as polymyxins are active

against gram-negative

bull Colistin and bacitracin are also members of this

class

Dr Amged 29

Mechanism of action

These antibiotics act on the plasma membrane structure of bacterial cells allowing

uncontrolled movements of ions across the cell membrane

Dr Amged 30

Polymyxin B1

BacitracinDr Amged 31

Dr Amged 32

Miscellaneous

Fusidic Acid (Fucidin)

Fusidic acid is the only steroidal antibiotic and is isolated

from the fermentation broth of Fusidium coccineum

How does it work

It kills bacteria by interfering with the synthesis

of proteins inside the bacterial cells

Medicinal uses

Bacterial conjunctivitis and Bacterial infections

of the eye

Osteomyelitis (bone and joint infections)

Skin and soft tissue infections

Dr Amged 26

Clindamycin is the 7-chloro-7-deoxy

derivative of lincomycin with greater

antibacterial activity and better

pharmacokinetic properties

The Lincosamides

Sulphur-containing antibiotics ldquoLincomycin and

Clindamycinrdquo

Have similar antibacterial properties to the macrolides and

act in the same fashion

Dr Amged 27

Polypeptides

Polypeptidesbull These are among the most powerful bactericidal

antibiotics but unfortunately their clinical use is

limited due to undesirable side reactions

particularly renal toxicity

bull They are neutral acidic or basic in nature

bull Some of them are active against gram-positive

bacteria while others as polymyxins are active

against gram-negative

bull Colistin and bacitracin are also members of this

class

Dr Amged 29

Mechanism of action

These antibiotics act on the plasma membrane structure of bacterial cells allowing

uncontrolled movements of ions across the cell membrane

Dr Amged 30

Polymyxin B1

BacitracinDr Amged 31

Dr Amged 32

Fusidic Acid (Fucidin)

Fusidic acid is the only steroidal antibiotic and is isolated

from the fermentation broth of Fusidium coccineum

How does it work

It kills bacteria by interfering with the synthesis

of proteins inside the bacterial cells

Medicinal uses

Bacterial conjunctivitis and Bacterial infections

of the eye

Osteomyelitis (bone and joint infections)

Skin and soft tissue infections

Dr Amged 26

Clindamycin is the 7-chloro-7-deoxy

derivative of lincomycin with greater

antibacterial activity and better

pharmacokinetic properties

The Lincosamides

Sulphur-containing antibiotics ldquoLincomycin and

Clindamycinrdquo

Have similar antibacterial properties to the macrolides and

act in the same fashion

Dr Amged 27

Polypeptides

Polypeptidesbull These are among the most powerful bactericidal

antibiotics but unfortunately their clinical use is

limited due to undesirable side reactions

particularly renal toxicity

bull They are neutral acidic or basic in nature

bull Some of them are active against gram-positive

bacteria while others as polymyxins are active

against gram-negative

bull Colistin and bacitracin are also members of this

class

Dr Amged 29

Mechanism of action

These antibiotics act on the plasma membrane structure of bacterial cells allowing

uncontrolled movements of ions across the cell membrane

Dr Amged 30

Polymyxin B1

BacitracinDr Amged 31

Dr Amged 32

Clindamycin is the 7-chloro-7-deoxy

derivative of lincomycin with greater

antibacterial activity and better

pharmacokinetic properties

The Lincosamides

Sulphur-containing antibiotics ldquoLincomycin and

Clindamycinrdquo

Have similar antibacterial properties to the macrolides and

act in the same fashion

Dr Amged 27

Polypeptides

Polypeptidesbull These are among the most powerful bactericidal

antibiotics but unfortunately their clinical use is

limited due to undesirable side reactions

particularly renal toxicity

bull They are neutral acidic or basic in nature

bull Some of them are active against gram-positive

bacteria while others as polymyxins are active

against gram-negative

bull Colistin and bacitracin are also members of this

class

Dr Amged 29

Mechanism of action

These antibiotics act on the plasma membrane structure of bacterial cells allowing

uncontrolled movements of ions across the cell membrane

Dr Amged 30

Polymyxin B1

BacitracinDr Amged 31

Dr Amged 32

Polypeptides

Polypeptidesbull These are among the most powerful bactericidal

antibiotics but unfortunately their clinical use is

limited due to undesirable side reactions

particularly renal toxicity

bull They are neutral acidic or basic in nature

bull Some of them are active against gram-positive

bacteria while others as polymyxins are active

against gram-negative

bull Colistin and bacitracin are also members of this

class

Dr Amged 29

Mechanism of action

These antibiotics act on the plasma membrane structure of bacterial cells allowing

uncontrolled movements of ions across the cell membrane

Dr Amged 30

Polymyxin B1

BacitracinDr Amged 31

Dr Amged 32

Polypeptidesbull These are among the most powerful bactericidal

antibiotics but unfortunately their clinical use is

limited due to undesirable side reactions

particularly renal toxicity

bull They are neutral acidic or basic in nature

bull Some of them are active against gram-positive

bacteria while others as polymyxins are active

against gram-negative

bull Colistin and bacitracin are also members of this

class

Dr Amged 29

Mechanism of action

These antibiotics act on the plasma membrane structure of bacterial cells allowing

uncontrolled movements of ions across the cell membrane

Dr Amged 30

Polymyxin B1

BacitracinDr Amged 31

Dr Amged 32

Mechanism of action

These antibiotics act on the plasma membrane structure of bacterial cells allowing

uncontrolled movements of ions across the cell membrane

Dr Amged 30

Polymyxin B1

BacitracinDr Amged 31

Dr Amged 32

Polymyxin B1

BacitracinDr Amged 31

Dr Amged 32

Dr Amged 32