Classification of Antimicrobial Drugs

Antimicrobial drugs are the greatest contribution of the 20th century to therapeutics. Their advent changed the outlook of the physician about the power drugs can have on diseases. They are one of the few curative drugs. Drugs in this class differ from all others in that they are designed to inhibit/kill the infecting organism and to have no/minimal effect on the recipient. This type of therapy is generally called chemotherapy which has come to mean ‘treatment of systemic infections with specific drugs that selectively suppress the infecting microorganism without significantly affecting the host.’ The basis of selective microbial toxicity is the action of the drug on a component of the microbe (e.g. bacterial cell wall) or metabolic processes (e.g. folate synthesis) that is not found in the host, or high affinity for certain microbial biomolecules (e.g. trimethoprim for bacterial dihydrofolate reductase). Due to analogy between the malignant cell and the pathogenic microbes, treatment of neoplastic diseases with drugs is also called ‘chemotherapy’.

Anti-biotics: These are substances produced by microorganisms, which selectively suppress the growth of or kill other microorganisms at very low concentrations. This definition excludes other natural substances which also inhibit microorganisms but are produced by higher forms (e.g. antibodies) or even those produced by microbes but are needed in high concentrations (ethanol, lactic acid, H202). Initially the term ‘chemotherapeutic agent’ was restricted to synthetic compounds, but now since many antibiotics and their analogues have been synthesized, this criterion has become irrelevant; both synthetic and microbiologically produced drugs need to be included together. It would be more meaningful to use the term antimicrobial agent (AMA) to designate synthetic as well as naturally obtained drugs that attenuate microorganisms.

Antimicrobial drugs can be classified in many ways:

A. Chemical structure

  1. Sulphonamides and related drugs: Sulfadiazine and others, Sulfones-Dapsone (DDS), Para aminosalicylic acid (PAS).
  2. Diaminopyrimidines: Trimethoprim, Pyrimethamine.
  3. Quinolones: Nalidixic acid, Norfloxacin, Ciprofloxacin, Gatifloxacin, etc.
  4. Beta-Lactam antibiotics: Penicillin, Cephalosporins, Monobactams, Carbapenems.
  5. Tetracyclines: Oxytetracycline, Doxycycline, etc.
  6. Nitrobenzene derivative: Chloramphenicol,
  7. Aminoglycosides: Streptomycin, Gentamicin, Amikacin, Neomycin, etc.
  8. Macrolide antibiotics: Erythromycin, Clanthromycin, Azithromycin, etc.
  9. Lincosamide antibiotics: Lincomycn, Clindamycin.
  10. Glycopeptide antibiotics: Vancomycin, Teicoplanin.
  11. Oxazolidinone: Linezolid.
  12. Polypeptide antibiotics: Polymyxin-B, Colistin, Bacitracin, Tyrothricin.
  13. Nitrofuran derivatives: Nitrofurantoin, Furazolidone.
  14. Nitroimidazoles: Metronidazole, Tinidazole etc.
  15. Nicotinic acid derivatives: Isoniazid, Pyrazinamide, Ethionamide.
  16. Polyene antibiotics: Nystatin, Amphotericin-B, Hamycin.
  17. Azote derivatives: Miconazole, Clotrimazole, Ketoconazole, Fluconazole.
  18. Others: Rifampin, Spectinomycin, Sodfusidate, Cycloserine, Viomycin, Ethambutol, Thiacetazone, Clofazimine, Griseofulvin.

B. Mechanism of action

  1. Inhibit cell wall synthesis: Penicillins, Cephalosporins, Cycloserine, Vancomycin, Bacitracin.
  2. Cause leakage from cell membranes: Polypeptides-Polymyxins, Colistin, Bacitracin, Polyenes-Amphotericin B, Nystatin Hamycin.
  3. Inhibit protein synthesis: Tetracyclines Chloramphenicol, Erythromycin, Clindamycin, Linezolid.
  4. Cause misreading of m-RNA code and affect permeability: Aminoglycosides-Streptomycin, Gentamicin, etc.
  5. Inhibit DNA gyrase: Fluoroquinolones, Ciprofloxacin and others.
  6. Interfere with DNA function: Rifampin, Metronidazole.
  7. Interfere with DNA synthesis: Acyclovir, Zidovudine.
  8. Interfere with intermediary metabolism: Sulfonamides, Sulfones, PAS, Trimethoprim, Pyrimethamine, Ethambutol.

C. Type of organisms against which primarily active

  1. Antibacterial: Penicillin, Aminoglycosides, Erythromycin, etc.
  2. Antifungal: Griseofulvin, Amphotericin B, Ketoconazole, etc.
  3. Antiviral: Acyclovir, Amantadine, Zidovudine, etc.
  4. Antiprotozoal: Chloroquine, Pyrimethamine, Metronidazole, Diloxanide, etc.
  5. Anthelmintic: Mebendazole, Pyrantel, Niclosamide, Diethyl carbamazine, etc.

D. Spectrum of activity

Narrow-spectrum: Penicillin G, streptomycin, erythromycin.

Broad-spectrum: Tetracyclines, Chloramphenicol

The initial distinction between narrow and broad-spectrum antibiotics is no longer clear cut. Drugs with all ranges of intermediate bandwidth, eg: extended spectrum penicillin, newer cephalosporins, aminoglycosides, fluoroquinolones are now available. However, the terms ‘narrow spectrum’ and ‘broad-spectrum’ are still applied.

E. Type of action

1. Primarily bacteriostatic: Sulphonamides, Erythromycin, Tetracyclines, Ethambutol, Chloramphenicol, Clindamycin, Linezolid.

2. Primarily bactericidal: Penicillin, Cephalosporins, Aminoglycosides, Vancomycin, Polypeptides Nalidixic acid, Rifampin, Ciprofloxacin, Isoniazid, Metronidazole, Pyrazinamide, Cotrimoxazole.

Some primarily static drugs may become bactericidal at higher concentrations (as attained in the urinary tract), e.g. sulphonamides, erythromycin, nitrofurantoin. On the other hand, some bactericidal drugs, e.g cotrimoxazole, streptomycin may only be bacteriostatic under certain circumstances.

F. Antibiotics are obtained from:

  1. Fungi:  Penicillin, Cephalosporin.
  2. Bacteria: Polymyxin B, Colistin, Bacitracin.
  3. Actinomycetes: Aminoglycosides, Tetracyclines, Chloramphenicol, Griseofulvin, Tyrothricin, Aztreonam, Macrolides, Polyenes.