WHAT IS AN ANTIBIOTIC?
Antibiotics are the substances produced by microorganisms, which selectively suppress the growth or kill other microorganisms at very low concentration. Many antibiotics are chemotherapeutic agents but others are too highly toxic to be of any clinical value. Certain antibiotics like colonics are used for non therapeutic purpose. Most of the antibiotics used as chemotherapeutic agents are active against bacterial pathogens.
HOW TO PRODUCE ANTIBIOTICS?
Production of antibiotics is done in one of the largest and most important microbiological industries. Interest in utilization of antibiotics for therapy began in 1929 when Alexander Fleming found that a mold has contaminated his cultures of a pathogenic bacterium, Staphylococcus aureus, and had killed the bacteria in its immediate vicinity leaving a clear ring of lysed bacteria
The mold was a penicillium:
|Amphotericin B||Streptomyces nodosus|
|Griseofulvin||Penicillium griseofulvin, P. nigricans|
|Novobiocin||S. Niveus, S. spheroids|
|Polymyxin B||Bacillus polymyxa|
SCREENING OF ANTIBIOTIC PROCEDURES:
One of the best penicillin producing strains of penicillium was isolated from an orange purchased at a road side fruit stand. Several antibiotic actinomycetes were isolated from a manure- enriched pasture.
A useful antibiotic producing strain must produce metabolites that inhibit the growth or reproduction of pathogens. This essential property can be assayed by using test strains and examining whether the isolate being screened produces substance that inhibit the growth of these test organisms.
The search for new antibiotics still goes on, and new ones are frequently announced. Genetic engineering has opened up several new possibilities for economically important substances
The mutation and selection approach is hit or miss, where as the use of recombinant DNA technology permits the purposeful manipulation of genetic information to engineer a micro organism, which can produce high yields of a variety of products.
TYPES OF ANTIBIOTICS:
- Beta- lactum antibiotic
- Broad spectrum antibiotics (tetracycline’s)
- Amino glycoside antibiotics
- Macrolide antibiotics
- Lincosamide antibiotic
- Glycopeptide antibiotic
BETA LACTUM ANTIBIOTIC:
These are antibiotics having a beta lactum ring. The two major groups are penicillin’s and cephalosporins. Monobactams and carbapenems are relatively later additions
PENICILLINS: Penicillin was the first used antibiotic in 1941. Penicillin was originally obtained from the fungus penicillium notatum, but the present source is a high yielding mutant of penicillium chrysogenum.
CHEMISTRY AND PROPERTIES: The penicillin nucleus consist of fused thiazolidine and Beta lactum rings to which side chains are attached through an amide linkage. Penicillin G is the original penicillin used clinically.
PRODUCTION AND RECOVERY:
The various steps that are usually followed in a sequential manner are described as follows
- Once the entire fermentative procedure is accomplished i.e. at harvest, the completed penicillin fermentation culture is subjected to filtration by the help heavy duty rotary vacuum filter to get rid to the Mycelium plus other unwanted solid residues.
- The PH of the clear filtered fermented broth is carefully brought down between 2-2.5 by the addition of a calculated amount of either phosphoric acid or sulphuric acid so as to convert the resulting penicillin to its anionic form.
- The resulting fermented broth is extracted immediately by using a pod bielniak counter current solvent extract or, with an appropriate organic solvent. E.g. Amyl acetate, butyl acetate or methyl isobutyl ketone.
- Penicillin thus obtained is back extracted into aqueous medium from the careful addition of requisite quantum of Potassium hydroxide or Sodium hydroxide to give rise to the formation of the corresponding potassium or sodium salt of the penicillin
- The resulting aqueous solution, containing the respective salt of penicillin, is again acidified and re-extracted with the organic solvent methyl isobutyl ketone.
- These shifts taking place between aqueous and solvent medium help in the ultimate process of purification of the penicillin.
- The resulting solvent extract is finally subjected to a meticulous back extraction with aqueous NaOH preferably; a number of times till extraction of penicillin is completed: and from this combine of aqueous extractions different established procedures are adapted to afford the penicillin to crystallize out either as sodium or potassium penicillin.
- The crystalline penicillin thus obtained is washed, dried under vaccum and the final product must confirm to the requirements? Specifications laid down by various official compendia.
MECHANISM OF ACTION OF ANTIBIOTICS :
The beta lactum antibiotics inhibit the trans-peptidases so that cross linking( which maintains the close knit structure of the cell wall) does not take place. These enzymes and related proteins constitute the penicillin binding proteins (PBPS) which have been located in the bacterial cell membrane. Each organism has several PBPS, and these are obtained from different species differ in their affinity towards different beta lactum antibiotics. This fact probably explains their differing sensitivity to the various beta lactum antibiotics.
When susceptible bacteria divide in the presence of beta lactum antibiotic cell wall deficient (CWD) forms are produced. Because the interior of the bacterium is hyper osmotic, the CWD forms swell and burst there by lysis occur. This is how beta lactum antibiotics exert bacterial action.
PENICILLIN G (BENZYL PENICILLIN)
Penicillin G is a narrow spectrum antibiotic, activity is limited primarily to gram- positive bacteria, few gram negative ones and anaerobes.
BACTERIAL RESISTANCE: Many bacteria are inherently insensitive to penicillin G because in them the target enzymes and PBPS are located deeper under lipoprotein barrier where penicillin G is unable to penetrate or have low affinity for penicillin G. The primary mechanism of the acquired resistance is the production of penicillinase.
- Penicillinase it is a narrow spectrum beta lactumase which opens the beta lactum ring and inactivates penicillin G and some closely related congeners.
- Penicillinase has been successfully used to destroy penicillin G in patient’s blood sample so that it does not interfere with bacterial growth when such blood is cultured.
DOSE: Sodium penicillin G ( Crystalline penicillin) injection 0.5 -5 MU intramuscular or intravenous 6-12 hourly.
- pain at intramuscular injection site
- Nausea on oral injection and thrombophlebitis of injected vein are dose related expressions of irritancy.
- Mental confusion, muscular twitching, convulsions and coma.
- Hypersensitivity reactions
- Manifestations of penicillin allergy, rash, itching, urticaria and fever.
- Used in streptococcal infections like pharyngitis, otitismedia, scarlet rheumatic fever.
- Used in pneumococcal infections, meningococcal infections, Gonorrhea, syphilis, leptospirosis, diphtheria, tetanus and gas gangrene.
EXTENDED SPECTRUM PENICILLINS:
These semi synthetic penicillins are in addition active against a variety of gram negative bacilli because of improved ability to penetrate through their cell membrane. However, they are susceptible to several beta lactamases. Semi synthetic penicillins are grouped according to their spectrum of activity.
- This group includes ampicillin, its prodrug bacampicillin and amoxicillin, ampicillin it is active against all organisms sensitive to penicillin G.
- Ampicillin is more active than penicillin G for streptococcus viridans, enterococci and listeria, equally active for pneumococci, gonococci and meningococci.
USES: Used to treat
- Urinary tract infections
- Respiratory tract infections
- Typhoid fever
- Bacillary dysentery
ADVERSE EFFECTS: Diarrhea and rashes
HRITHIKA, HARIKA, Keerthi kumari