1. Commercial Production of Antibiotics
The micro-organism should grow well in submerged culture medium (liquid medium) in a special apparatus called fermentor
The antibiotic produced should be released in the liquid medium used.
To increased the production of antibiotic:
Development of a high production micro-organism strain through mutation (either by chemical or UV.means) and selection.
Optimization of fermentation process through:
Medium composition (carbon and nitrogen sours, C/N ratio, vitamins, growth hormones and any additive).
Optimum condition of fermentation (temp., PH, aeration, stirring, volume and inoculums size).

2. Commercial Production of Antibiotics
Uses of beneficial additives to the medium:
Methionine is added to Cephalsporium spp. To increases the production of cephalosporines.
Phenylacetamide to Penicillum spp. For a high production of penicillin G.
In case of production of tetracycline using Sterpt. aureofaciens, addition of mercaptothiazole (inhibits chlorination of tetracycline) to avoid production of chlortetracycline (highly irritant and very difficult to separated from tetracycline) and increase tetracycline production.

3. Commercial Production of Antibiotics
Isolation and purification of antibiotics: Most of antibiotics are released into the culture medium except nystatin, amphotericin B and griseofulvin remain inside the microorganism cells they isolated by extraction of micro-organism cells.
Most of antibiotics are obtained from growth medium by the following
Selective adsorption e.g. charcoal in case of amino glycosides antibiotics.
Selective precipitation e.g. methyl orange in case of polymyxin production.
Selective solvent - solvent extraction.

4. Clinically Important Bacteria
Aerobic, Gram-positive cocci
Staphylococcus aureus
Staphylococcus epidermidis
Streptococcus pneumoniae
Streptococcus agalactiae
Streptococcus pyogenes
Anaerobic, Gram-positive rods
Actinomyces sp.
Clostridium botulinum
Clostridium difficile
Clostridium perfringens
Clostridium tetani

5. Bacterial Classification
Aerobic, Gram-positive rods
Bacillus anthracis
Bacillus cereus
Bifidobacterium bifidum
Lactobacillus sp.
Listeria monocytogenes
Nocardia sp.
Rhodococcus equi
Erysipelothrix rhusiopathiae
Corynebacterium diptheriae
Propionibacterium acnes
Anaerobic, Gram-positive cocci
Peptostreptococcus
Aerobic, Gram-negative cocci
Neisseria gonorrhoeae
Neisseria meningitidis
Moraxella catarrhalis

6. Bacterial Classification
Vibrio vulnificus
Acinetobacter sp.
Flavobacterium sp.
Pseudomonas aeruginosa
Burkholderia cepacia
Burkholderia pseudomallei
Xanthomonas maltophilia

7. Bacterial Classification
Aerobic, Gram-negative rods
Actinobacillus sp.
Acinetobacter baumannii
Bordetella pertussis
Brucella sp.
Campylobacter sp.
Capnocytophaga sp.
Cardiobacterium hominis
Eikenella corrodens
Francisella tularensis
Haemophilus ducreyi

8. Bacterial Classification
Haemophilus influenzae
Helicobacter pylori
Kingella kingae
Legionella pneumophila
Pasteurella multocida
Klebsiella granulomatis
Citrobacter sp.
Enterobacter sp.
Escherichia coli
Klebsiella pneumoniae
Proteus sp.

9. Bacterial Classification
Salmonella enteriditis
Salmonella typhi
Shigella sp.
Serratia marcescens
Yersinia enterocolitica
Yersinia pestis
Aeromonas sp.
Plesiomonas shigelloides
Vibrio cholerae
Vibrio parahaemolyticus

10. Bacterial Classification
Vibrio vulnificus
Acinetobacter sp.
Flavobacterium sp.
Pseudomonas aeruginosa
Burkholderia cepacia
Burkholderia pseudomallei
Xanthomonas maltophilia

11. Bacterial Classification
Gram-negative spiral
Spirillum minus
Anaerobic, Gram-negative cocci
Veillonella sp.
Anaerobic, Gram-negative rods
Bacteroides fragilis
Bacteroides sp.
Prevotella sp.
Fusobacterium sp.

12. Bacterial Classification
Atypical
Borrelia burgdorferi
Borrelia recurrentis
Bartonella henselae
Chlamydia trachomatis
Chlamydophila pneumoniae
Chlamydophila psittaci
Coxiella burnetii
Ehrlichia chaffeensis
Anaplasma phagocytophilum
Legionella sp.
Leptospira sp.

13. Bacterial Classification
Mycobacterium bovis
Mycobacterium tuberculosis
Mycobacterium avium,
Mycobacterium intracellulare
Mycobacterium kansasii
Mycobacterium leprae
Mycobacterium marinum
Rickettsia rickettsii
Orientia tsutsugamushi
Treponema pallidum

14. Combination Therapy
In most cases, infection caused by a single defined organism is best treated with a single antibiotic.
When organism is exposed to two antibiotics to which it is sensitive, the response to the combination will be:
Additive
Antagonism
Synergism

15. Combination Therapy
Additive in which the antibiotics combination is more effective than either antibiotic alone or the response represents a summation of two drugs.
Antagonism, the combination of two antibiotics may produce less response than one of the drugs alone.
Synergism, a combination of two antibiotics may have a greater effect than the sum of two individual drug effect, it is usually defined as a four-fold or greater decrease in MIC of the individual antibiotic.

16. Mechanisms of Synergy
The effect of one drug permits increased entry of the second drug to its site of action inside the cell, e.g. Penicillin and amino glycosides, in which penicillin acts as inhibitor of cell wall synthesis leading to increase the entering of the amino glycoside into the bacterial cell
One of the drug inhibits the inactivation of the other drug, e.g. clavulanic acid (β-lactamase inhibitor) and penicillins.

17. Mechanisms of Synergy
The two drugs inhibit the different steps in the critical metabolic pathway of organism e.g. sulfonamides ( inhibit folic acid synthesis ) and trimethoprim ( inhibits the reduction of folic acid to THFA).
Two drugs interact with different viable enzyme systems inside the bacterial cell.

18. Advantages
Synergetic effect.
Prevention of resistance.
Very useful in mixed infection.
Disadvantages
It exposes the patient to an increased risk of drug toxicity.
It increases the therapy cost.
It sometimes be less effective than therapy with a single antibiotic.