Sulphonamides and Drug Resistance Quiz

Antimicrobial Chemotherapy

• Antimicrobial drugs are either naturally produced or synthetically prepared.
• Naturally produced drugs (antibiotics) inhibit the growth of other microorganisms.
• Some examples of antibiotics are penicillin (produced by Penicillium fungi) and streptomycin (produced by Streptomyces bacteria)
• Synthetic antimicrobial drugs are also known as chemotherapeutics.
• Antibacterial drugs are categorized into two classes.
  • Bactericidal drugs: cause rapid, irreversible killing of microorganisms. Examples include penicillin, vancomycin, and cephalosporins. These drugs inhibit cell wall formation.
  • Bacteriostatic drugs: cause reversible inhibition of microbial growth. Examples include tetracyclines, chloramphenicol, and erythromycin. These drugs inhibit protein synthesis.

Range of Action of Antimicrobial Drugs

• Antibiotics are categorized based on their activity spectrum.
  • Drugs active against Gram-positive organisms (e.g., penicillin, erythromycin; limited spectrum)
  • Drugs active against Gram-negative organisms (e.g., nalidixic acid, polymyxin; limited spectrum)
  • Drugs active against both Gram-positive and Gram-negative organisms (e.g., ampicillin, tetracyclines, chloramphenicol; broad spectrum)

Therapeutic Index (TI) of Antimicrobial Drugs

• Therapeutic index (TI) is the ratio between the blood concentration of the drug at which it causes a lethal effect to the concentration at which it has its therapeutic effect.
• High TI = Safer drug.
• If the TI is low, careful dosage monitoring is required.

Mechanism of Action of Antimicrobial Drugs

• Ideal antimicrobial agents exhibit selective toxicity, targeting microorganisms without harming host cells.
• The mechanism of action of an antimicrobial drug depends on the inhibition of a metabolic process or structure present in the microbe, but not in the host cell.
  • Inhibition of cell wall synthesis (e.g., penicillin).
  • Inhibition of cytoplasmic membrane function (e.g., polymyxins).
  • Inhibition of protein synthesis (e.g., chloramphenicol, tetracycline).
  • Inhibition of nucleic acid synthesis (e.g., quinolones).
  • Competitive inhibition (e.g., sulphonamides).

Mechanism of Resistance to Antimicrobial Agents

• Microorganisms develop resistance to antimicrobial agents through various mechanisms.
  • Production of enzymes that inactivate the antimicrobial agent (e.g., beta-lactamase).
  • Modification of the target site of the drug (e.g., modification of LPS in gram-negative bacteria).
  • Alteration of metabolic pathways to bypass drug inhibition.
  • Acquisition of new mechanisms for drug transport to reduce uptake of drug (in gram-negative bacteria).
  • Changes to the antibiotic receptor site.

Origin of Resistance to Antimicrobial Agents

• (A) Non-genetic resistance:
  • Metabolic inactivity of certain microorganisms.
  • Loss of target structure of certain microorganisms.
• (B) Genetic resistance mechanisms:
  • Chromosomal drug-resistance: Mutations in genes that control microbial susceptibility.
  • Extra-chromosomal drug-resistance: Resistance carried by extra-chromosomal elements like plasmids or transposons.

Complications of Antimicrobial Chemotherapy

• (1) Development of Drug Resistance: inadequate dosage, prolonged use.
• (2) Drug Toxicity:
  • Selective Toxicity: damage to specific tissues (e.g. 8th cranial nerve)
  • Overdosage may cause toxic reactions
• (3) Superinfection: Suppression of normal flora leads to an overgrowth of drug-resistant pathogens.

Hypersensitivity reactions

• Drugs may act as haptens
• May lead to tissue damage
• Can cause reactions including: Anaphylactic shock, urticaria, skin rash, diarrhea, vomiting.

Chemoprophylaxis

• Chemoprophylaxis is the use of antimicrobial agents to prevent rather than cure infectious diseases.

Combined Use of Antibiotics

• Used in treatment of serious infections or tuberculosis.
• Rationale is to avoid resistance development, reduce toxicity, and maximize therapeutic benefits.

Antibiotic Policies

• Abuse of antibiotics should be avoided to prevent the emergence of antibiotic resistance, reduce costs, and prevent toxicity.

Test your knowledge about sulphonamides, their mechanism of action, and their role in drug resistance in bacteria. This quiz covers aspects of microbial cell interactions and the survival mechanisms of tubercle bacilli. Explore the implications of prolonged antibiotic treatments and the factors contributing to drug resistance.