PENICILLIN

B.C. MuthubharathiIII Bsc., Biotechnology

PENICILLINS• Beta- lactam antibiotics• Derivatives of 6- aminopenicillanic acid• Alteration of the side group resulted in

cpds with :• Broader spectrum of activity• Resistance to penicillinase• Stability in acid PH• Most widely effective antibiotics• Least toxic drugs known

Antibiotics are antimicrobial agents produced naturally by other microbes (usually fungi or bacteria).

The first antibiotic was discovered in 1896 by Ernest Duchesne and "rediscovered" byAlexander Flemming in 1928 from the filamentous fungus Penicilium notatum.

• The antibiotic substance, named penicillin, was not purified until the 1940s (by Florey and Chain), just in time to be used at the end of the second world war.

• Penicillin was the first important commercial product produced by an aerobic, submerged fermentation

Production of penicillin

• To be able to identify useful products from microorganisms

• To be able to identify the microorganisms used and the main stages in the production of penicillin.

• To be able to describe how Downstream processing is carried out to extract and purify the end-product of fermentation.

Downstream Processing

• Products in a fermentor are impure and dilute, so need to be purified by downstream processing.

• This usually involves filtration to separate the microbial cells from the liquid medium, followed by chemical purification and concentration of the product

• Downstream processing can account for 50% of the cost of a process

Cont.

• Downstream processing is relatively easy since penicillin is secreted into the medium (to kill other cells), so there is no need to break open the fungal cells.

• However, the product needs to be very pure, since it being used as a therapeutic medical drug, so it is dissolved and then precipitated as a potassium salt to separate it from other substances in the medium.

MECHANISM OF ACTION

They act by inhibition of bacterial cell wall synthesisThus exposing the osmotically less stable membraneThis cause lysis of bacterial cell wallThese agents are bactericidalActive against multiplying and not resting bacteriaInactive against mycobacteria, protozoa, fungi and

viruses

UsesH. Influenza infections ( otitis media, sinusitis, chronic bronchitis, pneumonia, bacterial meningitis ).M.catarrhalisE. Coli infections ( Urinary & biliary infections ).Samonella infections ( typhoid fever )Shigella infections ( ampicillin )Gonococcal infections ( alternative for penicillin in the treatment of gonorrhea )Prophlaxis of infective endocarditisDisadvantagesAmoxicillin & ampicillin alone are readily destroyed by Staph. Penicillinase.

1.Hypersensitivity reactions ( occur in 1-10% of pts; fatality occur in 0.002%) ( immediate, accelerated & late allergic rxns) Urticarial rash Fever Bronchspasm Serum sickness Exfoliative dermatitis Stevens- Johnson syndrome Anaphylaxis2. Super infections3. Diarrhoea4. May cause convulsions after high doses by i.v or in

renal failure