Contents

• Antibiotics
• Discovery of Antibiotics
• The Golden age of Antibiotics
• Classification of Antibiotics
  • On the basis of chemical structure
  • On the basis of origin
  • On the basis of range of activity
  • On the basis of Mode of action
  • On the basis of effect of their activity
  • On the basis of route of administration
• References

Antibiotics

Antibiotics are chemical medicinal agents of microbial, synthetic, or semi-synthetic origin that, in low concentrations, hinder the growth of other bacteria. Antibiotics enter and adhere to key components of the bacterial cell, interfering with its capacity to survive and grow. If the bacteria are susceptible to the antibiotic, they will either cease growing or die¹.
These important components of bacteria include:
• proteins and carbohydrates in their walls.
• Important enzymes that produce new bacterial DNA or proteins.

Discovery of Antibiotics

Alexander Fleming, a Scottish bacteriologist, made the discovery on September 28, 1928. After his summer break, Fleming returned to his laboratory at St. Mary’s Hospital in London to find an unexpected sight. Some of his Petri dishes harboring the bacterium Staphylococcus aureus had become contaminated with mold. After carefully inspecting the dishes under a microscope, he discovered that the mold had formed a germ-free zone in which bacteria could not grow. Fleming determined that the mold was creating an antibacterial agent that not only prevented the growth of staphylococci but might also be used to battle infectious disorders. Later, he gave it the name Penicillin².

A decade or so later, Haward Florey and Ernst Chain identified Penicillin’s active ingredient and conducted the drug’s initial test on mice. The new medicine was ready to be utilized in Humans in 1941. Albert Alexander, a British police officer, was the first patient to be treated with Penicillin. He had cut himself on a rosebush and became fatally infected. The Noble Prize in Physiology or Medicine was shared by Fleming, Florey, and Chain in 1945. Fleming warned about the risks of improper use of Penicillin in his foresightful presentation. In 1947, there was the first documented instance of penicillin resistance³.
The 1943 introduction of streptomycin (an antibiotic produced by the soil bacterium Streptomyces griseus) by Selman Waksman, Albert Schatz, and Elizabeth Bugie was another significant discovery. The discovery of streptomycin, the first antibiotic effective against tuberculosis, earned Selman Waksman the 1952 Nobel Prize. Many of the antibiotic classes that are currently being used in clinical practice were discovered thanks to the Waksman platform, which was adopted by numerous pharmaceutical companies and enjoyed great success for 20 years⁴.

The Golden Age of Antibiotics

The period between 1940 and 1960 is often regarded as the golden age of antibiotic discovery as one-half of the antibiotics commonly used today were discovered during these years. (Source: ReACT, 2013)

Classification of Antibiotics

1. On the basis of chemical structure
2. On the basis of origin
3. On the basis of range of activity
4. On the basis of mode of action
5. On the basis of effect of activity
6. On the basis of route of administration

On the basis of chemical structure

i. Carbohydrate-containing Antibiotics/ Glycopeptides: Example: Vancomycin
ii. Pure saccharides antibiotics: Example: Streptozotocin
iii. Aminoglycosides: Example: Streptomycin
iv. N/O glycosides: Example: Chromomycin
v. Macrocyclic lactone antibiotics: Example: Erythromycin
vi. Quinolones antibiotics: Example: Fluroquinolone
vii. N-containing heterocyclic antibiotics: Example: Beta-lactam
viii. O-containing heterocyclic antibiotics: Example: Cycloserine
ix. Alicyclic antibiotics: Example: Cycloheximide
x. Aromatic antibiotics (Nitrobenzene): Example: Chloramphenicol
xi. Aliphatic amine antibiotics: Example: Spermidine
xii. Peptide antibiotics: Example: Polymyxin, Bacitracin, Gramicidin

On the basis of origin

1. Microbial origin:
   i. Bacterial origin:
   a) Bacillus polymyxa: Polymyxin
   b) Chromobacter violaceum: Bacitracin
   c) Micromonospora spp: Gentamycin
   ii. Fungal origin:
   a) Penicillium notatum: Penicillin
   b) Cephalosporin spp: Cephalosporin
   iii. Actinomycetes origin:
   a) Streptomyces griseus: Streptomycin
   b) S. venezuelae: Chloramphenicol
   c) S. erythreus: Erythromycin
   d) S. mediterranae: Rifampicin

• Semi-synthetic antibiotics: a naturally occurring antibiotic that has undergone chemical modification in the lab to increase stability.
  Examples: Amoxycillin, Ampicillin, Doxycycline, Tigecycline, Sulfonamide, etc

• Synthetic antibiotics: Antibiotics that are prepared in the laboratory mimicking natural products.
  Examples: Chloramphenicol (* it was extracted from Streptomyces venzuelae but now produced synthetically), 4-quinolones, Sulfonamide.

On the basis of range of activity

1. Narrow spectrum: Active against a somewhat smaller number of gram-positive or negative bacteria.
   Examples: Macrolides, Polymyxin
2. Moderate spectrum: Both systemic and UTI-causing Gram-negative and Gram-positive bacteria are actively targeted.
   Examples: Aminoglycosides, Sulfonamide
3. Broad spectrum: Active against both Gram-positive and gram-negative
   Examples: Beta-lactam

On the basis of Mode of action:

1. Inhibitor of cell wall synthesis: Antibiotics that target the component of bacterial cell wall mainly peptidoglycan
   Examples:
   a) Beta-lactam; Penicillin, cephalosporin, carbapenems, monobactams
   b) Bacitracin
   c) Cycloserine
   d) Phosphomycin
   e) Vancomycin
2. Inhibitor of protein synthesis: Antibiotics that target ribosomes for protein synthesis in bacteria.
   Examples:
   a) Streptomycin
   b) Aminoglycosides
   c) Fusidic acid
   d) Tetracycline
   e) Mupirocin
   f) Chloramphenicol
   g) Macrolides
3. Inhibitor of Nucleic acid synthesis: Antibiotics that target DNA/RNA synthesis.
   Examples:
   a) Quinolones
   b) Ciprofloxacin
   c) Nalidixic acid
   d) Metronidazole
   e) Nitrofurantoin
4. Inhibitor of folic acid synthesis (Folate antagonistic): Antibiotics that inhibit denovo synthesis of folate in bacteria.
   Examples:
   a) Sulfonamide
   b) Trimethoprim
5. Inhibitor of cytoplasmic membrane: Antibiotics that inhibit phospholipid synthesis that mainly present in the cell membrane of bacteria.
   Examples: Polymyxin; Colistin

On the basis of effect of their activity:

1. Bactericidal: Bactericidal agents are antibiotics that can kill bacteria.
   Examples: Aminoglycosides, Penicillin, Cephalosporin
2. Bacteriostatic: Bacteriostatic agents inhibit the growth of bacterial cells without killing them.
   Examples: Sulfonamide, tetracycline, chloramphenicol, trimethoprim, macrolides, and Lincosamide.

On the basis of route of administration:

1. Oral antibiotics: Acid-stable antibiotics, taken by mouth.
   • Examples; Penicillin V
2. Parenteral route: Intravenous administration
   • Examples; Penicillin G

References

1. SOARES GMS, FIGUEIREDO LC, FAVERI M, CORTELLI SC, DUARTE PM, FERES M. Mechanisms of action of systemic antibiotics used in periodontal treatment and mechanisms of bacterial resistance to these drugs. J Appl Oral Sci. 2012;20(3):295-304. doi:10.1590/S1678-77572012000300002
2. Antibiotic Resistance – The Silent Tsunami. ReAct. Accessed January 20, 2024. https://www.reactgroup.org/antibiotic-resistance/course-antibiotic-resistance-the-silent-tsunami/part-1/
3. The Nobel Prize in Physiology or Medicine 1945. NobelPrize.org. Accessed January 20, 2024. https://www.nobelprize.org/prizes/medicine/1945/fleming/lecture/
4. Woodruff HB. Selman A. Waksman, Winner of the 1952 Nobel Prize for Physiology or Medicine. Appl Environ Microbiol. 2014;80(1):2-8. doi:10.1128/AEM.01143-13