1 Pharmaceutical Microbiology II€¦ · Antibiotics Antibiotics are natural antibacterial substances produced by microorganisms (bacteria, fungi, and actinomycetes) Extended to include

Pharm 262:

Pharmaceutical

Microbiology II

AntibioticsDR. C. AGYARE

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Reference Books

HUGO, W.B., RUSSELL, A.D. Pharmaceutical Microbiology. 6th Ed.

Malden, MA: Blackwell Science, 1998.

WALSH, G. Biopharmaceuticals: Biochemistry and Biotechnology. 2nd

Ed. New York: Wiley, 2003.

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Course content/Learning outcomes

Definitions of antibiotics

Classification of antibiotics

Mode of actions of antibiotics

Antimicrobial spectrum

Few significant/major sides effects

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Chemotherapy

Chemotherapy is the treatment or prevention of disease with chemicals

The term was coined by Paul Ehrlich

The definition has been expanded to include antibiotics.

The term now is widely applied to treatment of cancer

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Antibiotics

Antibiotics are natural antibacterial substances produced by microorganisms (bacteria, fungi, and actinomycetes)

Extended to include synthetic antimicrobial agents, such as sulfonamides and quinolones.

Antibiotics differ markedly in physical, chemical, and pharmacological properties, in antimicrobial spectra, and in mechanisms of action.

Knowledge of molecular mechanisms of bacterial replication has greatly facilitated rational development of compounds that can interfere with their replication.

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History of Antibiotics The antibacterial effect of penicillin was discovered by Alexander Fleming in 1929.

Fleming had devoted much of his career to finding methods for treating wound

infections.

A fungal colony grew as a contaminant on an agar plate streaked with

Staphylococcus aureus.

The bacterial colonies around the fungus were transparent

A fungal metabolite may be responsible

The substance was named penicillin, because the fungal contaminant was

identified as Penicillium notatum.

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History of antibiotics I

In 1941, Florey and Chain managed to produce the antibiotic on an industrial scale.

Penicillin was originally obtained, as a mixture of Penicillins known as F, G, X, and K,

from the mould Penicillium notatum.

Better yields were achieved using P. chrysogenum.

The (earlier) natural penicillins, were produced by adding side chain precursors to

the fermentation medium.

Benzylpenicillin (penicillin G) was selectively produced by adding the precursor

phenylacetic acid

Phenoxymethylpenicillin (penicillin V) was produced by adding phenoxymethyl

acetic acid.

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History of antibiotics II

The discovery of penicillin led to the search for other antibiotic-producing

microorganisms, especially from soil environments.

Streptomycin - Streptomyces griseus (soil actinomycete)

Cephalosporins - Cephalosporium acremonium

Griseofulvin - Penicillium griseofulvum

Chloramphenicol - Streptomyces venezuelae

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History of antibiotics III

In 1935, Domagk discovered that prontosil

A dye, could protect mice against several thousand times the lethal dose of haemolytic streptococci and was also effective against infections in man.

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Some Clinically Important Antibiotics

Antibiotic Producer organism Activity Site or mode of action

Penicillin Penicillium chrysogenumGram-positive

bacteriaWall synthesis

CephalosporinCephalosporium

acremoniumBroad spectrum Wall synthesis

Griseofulvin Penicillium griseofulvum Dermatophytic fungi Microtubules

Bacitracin Bacillus subtilisGram-positive

bacteriaWall synthesis

Polymyxin B Bacillus polymyxaGram-negative

bacteriaCell membrane

Amphotericin B Streptomyces nodosus Fungi Cell membrane

Erythromycin Streptomyces erythreusGram-positive

bacteriaProtein synthesis

Neomycin Streptomyces fradiae Broad spectrum Protein synthesis

Streptomycin Streptomyces griseusGram-negative

bacteriaProtein synthesis

Tetracycline Streptomyces rimosus Broad spectrum Protein synthesis

Vancomycin Streptomyces orientalisGram-positive

bacteriaWall synthesis

GentamicinMicromonospora

purpureaBroad spectrum Protein synthesis

Rifamycin Streptomyces

mediterraneiTuberculosis Protein synthesis

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Susceptibility of microorganisms to

antimicrobial agents

Successful antimicrobial therapy of an infection ultimately depends on the concentration of antibiotic at the site of infection.

This concentration must be sufficient to inhibit growth of the offending microorganism.

If host defences are intact and active, a minimum inhibitory effect, such as that provided by bacteriostatic agents may be sufficient.

If host defences are impaired, bactericidal effect may be required to eradicate the infection.

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Selective toxicity

Depends on there being exploitable biochemical differences between the

parasite/microbial cell and the host.

This is because only compounds with selective toxicity can be used clinically.

In practice, this is expressed in terms of the therapeutic index - the ratio of the toxic

dose to the therapeutic dose.

The larger the index, the better is its therapeutic value.

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Nosocomial infections

Result from pathogens that develop within a hospital or other type of clinical care

facility and are acquired by patients while they are in the facility.

Most nosocomial infections become clinically apparent while patients are still

hospitalized

However, disease onset can occur after patients have been discharged.

Infections that are incubating when patients are admitted to a hospital are not

nosocomial; they are community acquired.

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Super infection (Supra-infection)

Is usually attributed to the suppression of antibiotic-sensitive microorganisms which

normally provide natural competition to prevent the unlimited multiplication of

antibiotic-resistant microorganisms.

The administration of broad spectrum antibiotics, especially by mouth, may result in

supra-infection with Candida and other yeasts, filamentous fungi

And resistant Gram-negative bacteria, affecting the mouth, gastro-intestinal tract,

or upper respiratory tract.

Co-infection?????

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Thanks for your attention

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