Antimicrobials : Classification, MOA, Uses, And Side Effects

Antimicrobials differ from all others in that they are designed to inhibit/kill the infecting organism and to have minimal or no effect on the recipient. This type of therapy is called chemotherapy; which means treatment of systemic infections with specific drugs that selectively suppress the infecting micro-organism without significantly affecting the host.

Antibiotics 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 that also inhibit microorganisms but are produced by higher forms, (e.g. antibodies).

Antimicrobials designate synthetic as well as naturally obtained drugs that attenuate microorganisms.

 Classification of Antimicrobials

Antimicrobials can be classified according to some factors in different classes. For example:

Classification according to Chemical structure:

• Sulfonamides and related drugs eg sulfadiazine and others, Sulfones such as dapsone.
• Quinolones like Ciprofloxacin, Norfloxacin...
• β Lactum antibiotics – Penicillins, Cephalosporins, monobactums, carbapenems...
• Tetracyclines - doxycycline
• Aminoglycosides –streptomycin, gentamycin, etc
• Macrolides - erythromycin...
• Azole derivatives – Miconazole, clotrimazole, Ketoconazole.

Classification according to the Mechanism of action

1. Inhibit cell wall synthesis ie penicillins, cephalosporins...
2. Inhibit protein synthesis including, tetracyclines, chloramphenicol, erythromycin...
3. Cause leakage from cell membranes - polypeptides like Amphotericin B, nystatin...
4. Inhibit DNA gyrase – Fluoroquinolones - Ciprofloxacin...
5. Interfere with DNA synthesis such as Zidovudine, acyclovir...

Classification based on Type of organism against which primarily active

1. Antibacterial - penicillins, aminoglycosides...
2. Antifungal - Ketoconazole, Amphotericin B...
3. Antiviral - Zidovudine, acyclovir...
4. Antiprotozoal - chloroquine, metronidazole...
5. Antihelmintic - mebendazole, albendazole...

According to Spectrum of activity

1. Narrow spectrum antimicrobials like penicillin G, erythromycin, streptomycin...
2. Broad-spectrum antimicrobials ie tetracyclines, chloramphenicol...

According to the type of action

1. Primarily bacteriostatic - sulfonamides, tetracyclines, chloramphenicol, erythromycin...
2. Primarily bactericidal - penicillins, aminoglycosides, rifampicin, cephalosporins...

Classification according to Source of antibiotics

1. Fungi -penicillin, cephalosporins
2. Bacteria -colistin, bacitracin

How do antibacterial substances work?

1. Bactericidal agents - Kill bacteria rapidly (e.g. aminoglycosides, polymyxin)
2. Bacteriostatic agents Prevent bacteria from replicating; but do not kill them (e.g. sulphonamides, tetracyclines, chloramphenicol).

When a drug is given at high doses to highly susceptible organisms; a normally bacteriostatic agent such as penicillin may become bactericidal.

Antibiotics and Bacterial cell wall

Many antibiotics exert their effects directly on the bacterial cell wall or must pass through it before disrupting bacterial metabolism at the intracellular level.

The cell walls of all bacteria are composed of layers of protein molecules bound together by cross-linkages, resulting in the large, complex chemical aggregate, but their fine structure depends on whether they are Gram-positive or Gram-Negative.

The fine structure of the cell wall influences susceptibility to the different groups of antibiotics; e.g. erythromycin is able to penetrate the cell wall of Gram-positive bacteria and is effective in the treatment of some staphylococcal or streptococcal infections, but it has no effect on Gram-Negative bacteria.

Gram-positive and gram-negative bacteria

With a few exceptions, bacteria may be classified as Gram Positive and Gram Negative, according to the staining technique used in laboratory identification.

Gram-negative species multiply rapidly in the presence of moisture even when provided with minimal nourishment.

Here are examples of Gram-positive and Gram-negative organisms in hospitals

Gram-Positive	Gram-Negative
Staphylococcus aureus	Haemophilus influenza
Streptococcus pyogenes	Neisseria gonorrhea
Streptococcus viridians	Neisseria meningitides
Streptococcus pneumonia	Escherichia coli, proteus, pseudomonas, klebsiella

• Anaerobic bacteria can live and multiply in the absence of free oxygen.
• In the laboratory, they require special conditions before they will grow in culture, but they are able to cause severe infections given the correct circumstances.

 What are the problems that arise with the use of antimicrobials

1. Toxicity
2. Local irritancy. This is exerted at the site of drug administration. Pain, abscess formation at the site of IM injection.
3. Systemic toxicity. Almost all antimicrobials produce dose-related and predictable organ toxicities.

•  
  • Chloramphenicol  .Bone marrow depression.
  • Tetracyclines. Liver and Kidney damage.

1. Hypersensitivity reactions Practically all antimicrobials are capable of causing hypersensitivity reactions. They are unpredictable and unrelated to dose. The whole range of reactions from rashes to anaphylactic shock can be produced. Examples penicillins, cephalosporins, sulfonamides, fluoroquinolones.
2. Drug resistance Refers to the unresponsiveness of a microorganism to antimicrobials.
3. Natural resistance Some microbes have always been resistant to certain antimicrobials. They lack the metabolic process or the target site which is affected by a particular drug. This is generally a group or species characteristic.
4. Acquired resistance The development of resistance by an organism (which was sensitive before) due to the use of antimicrobials over a period of time. This can happen with any microbe and is a major clinical problem.
5. Superinfection (Suprainfection) This refers to the appearance of a new infection as a result of antimicrobial therapy.

The use of antimicrobials causes some alterations in the normal microbial flora of the body. The normal flora contributes to host defense by elaborating substances called bacteriocins, which inhibit pathogenic organisms.

Also, ordinarily, the pathogen has to compete with the normal flora for nutrients, etc. to establish itself.

Lack of competition may allow even a normally non-pathogenic component of flora, which is not inhibited by the drug to establish itself and predominates e.g. candida.

It is commonly associated with the use of broad-spectrum antibiotics e.g. tetracyclines, chloramphenicol, newer cephalosporins.

Sites involved in superinfection are those that normally harbor commensals, i.e. intestines, respiratory and genitourinary tracts.

How to minimize superinfection

Use specific (narrow spectrum) antimicrobials whenever possible.

Do not use antimicrobials to treat trivial, self-limiting or untreatable (viral) infections.

Do not unnecessarily prolong antimicrobial therapy.

1. Nutritional deficiencies. Some of the B complex vitamins and Vitamin K synthesized by the intestinal flora are utilized by man. Prolonged use of antimicrobials that alter this flora may result in vitamin deficiencies.
2. Masking of an infection - a short course of antimicrobials may be sufficient to treat one infection but only briefly suppress another one contacted concurrently.
   The other infection will be masked initially, only to manifest later in severe form; e.g. syphilis masked by the use of a single dose of penicillin which is sufficient for gonorrhea. TB masked by a short course of streptomycin given for trivial respiratory infection.

Sulphonamides

Sulfonamides are one of the oldest groups of antibacterial agents. They differ to some extent in the range of organisms they attack, but most of their pharmacological properties are similar.

They are primarily bacteriostatic against many Gram-positive and Gram-Negative and they have been largely replaced because of the development of bacterial resistance and adverse side effects.

Mechanism of action

Many bacteria synthesize their own folic acid (FA) of which Para-aminobenzoic acid (PABA) is a constituent, and is taken up from the medium. Sulfonamides being structural analogs of PABA, inhibit bacterial folate synthetase; therefore, FA is not formed and a number of essential metabolic processes suffer.

Human beings also require FA, but they utilize preformed FA supplied in the diet and are unaffected by sulfonamides.

Available sulphonamide examples

1. Sulfadimidine. This drug is well absorbed orally and indicated for Uri
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