Introduction to Antibiotics and Resistance

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Questions and Answers

What type of antibiotics specifically target a limited group of bacteria?

Narrow spectrum antibiotics (correct)

Broad spectrum antibiotics

Antivirals

Bactericidal antibiotics

Which of the following is an example of a bactericidal antibiotic?

Chloramphenicol

Clindamycin

Aminoglycosides (correct)

Erythromycin

Which antibiotics disrupt the cell membrane of bacteria?

Glycopeptides

Tetracyclines

Beta Lactams

Polymyxins (correct)

What is the primary action of bacteriostatic antibiotics?

Inhibit bacterial growth and replication Signup and view all the answers

Which class of antibiotics specifically inhibits DNA gyrase?

Quinolones Signup and view all the answers

What mechanism of resistance involves bacteria developing unresponsiveness after exposure to antibiotics?

Acquired resistance Signup and view all the answers

Which antibiotic is classified as narrow spectrum and specifically effective against mycobacteria?

Isoniazid Signup and view all the answers

Which antibiotic class acts on the 30S ribosomal subunit to inhibit protein synthesis?

Tetracyclines Signup and view all the answers

What is the primary action of beta-lactams in bacteria?

Inhibit peptidoglycan cross-linking Signup and view all the answers

Which of the following statements is true regarding vancomycin?

It inhibits cell wall synthesis in Gram-positive bacteria. Signup and view all the answers

What mechanism allows the transfer of resistance genes among bacteria through direct cell-to-cell contact?

Conjugation Signup and view all the answers

Which antibiotic does Salmonella typhi become resistant to due to modification of DNA gyrase?

Quinolones Signup and view all the answers

What is the encoded gene responsible for the resistance of Methicillin-resistant Staphylococcus aureus (MRSA) to beta-lactam antibiotics?

mecA Signup and view all the answers

Which of the following mechanisms involves bacteria pumping antibiotics outside their cells to diminish drug effectiveness?

Increased Drug Efflux Signup and view all the answers

Which of the following is a method by which bacteria can inactivate antibiotics?

Drug inactivation through enzyme production Signup and view all the answers

Study Notes

Introduction to Antibiotics and Antibiotic Resistance

Antimicrobial agents are chemical substances that kill or inhibit the growth of microorganisms.
These include antibiotics, antivirals, antifungals, and antiparasitic drugs.
Antimicrobials are toxic to microbes but not to human cells.

Classifications of Antibiotics

Spectrum of activity:
- Broad spectrum: effective against a wide variety of bacterial species. Examples include: Carbepenams, Chloramphenicol, 2nd/3rd/4th gen Cephalosporins, 3rd gen Fluoroquinolones, Broad spectrum penicillins, and Tetracyclines.
- Narrow spectrum: effective only against a single or a limited group of bacteria. Examples include: Isoniazid (active only against mycobacteria), Penicillin V and G, Lincosamides (Clindamycin), Glycopeptides (Vancomycin and Teicoplanin), and Isoniazid.
Mode of action:
- Bacteriostatic: inhibits the growth and replication of bacteria. Examples include: Chloramphenicol, Erythromycin, Clindamycin, Sulfonamides, Trimethoprim, and Tetracyclines.
- Bactericidal: kills the bacteria. Examples include: Aminoglycosides, Beta-lactams, Vancomycin, Quinolones, Rifampin, and Metronidazole.
Site of action:
- Inhibition of cell wall (e.g., Glycopeptides, Beta-lactams).
- Disturbance of cell membrane (e.g., Polymyxins, Daptomycin).
- Inhibition of protein synthesis (e.g., Aminoglycosides, Macrolides, Tetracyclines).
- Inhibition of nucleic acid (e.g., Fluoroquinolones, Rifampicin).

Target Sites for Antibiotics in Bacteria

Cell wall synthesis inhibitors:
- Beta-lactams: bind to penicillin-binding proteins (transpeptidases), inhibiting peptidoglycan cross-linking. Examples include Penicillins (e.g., Penicillin G, Ampicillin), Cephalosporins (e.g., 1st to 5th generation), Carbapenems (e.g., Imipenem, Meropenem), and Monobactam.
- Glycopeptides (e.g., Vancomycin): narrow spectrum, effective against Gram-positive bacteria.
Cell membrane inhibitors:
- Polymyxins: narrow spectrum, effective against Gram-negative bacteria.
Protein synthesis inhibitors:
- Bind to 30S or 50S ribosomes, inhibiting protein synthesis. Examples include Macrolides (e.g., erythromycin, azithromycin), Aminoglycosides (e.g., gentamycin), and Tetracyclines (e.g., tetracycline, doxycycline).
Nucleic acid inhibitors:
- Fluoroquinolones: inhibit DNA gyrase or topoisomerase. Examples include Ciprofloxacin.
Rifampicin: inhibits RNA polymerase.
Sulfonamides and trimethoprim: inhibit folic acid pathway.

Causes of Antibiotic Therapy Failure

Antibiotic .1:
- Inadequate dose
- Inadequate duration
- Wrong route of administration
- Wrong choice of antibiotics
- Use of antagonistic antibiotic combination
Bacteria .2:
- Viral infection
- Mixed bacterial infection
- Antimicrobial resistance

Drug Resistance

Natural (Intrinsic) Resistance: Bacteria naturally resist the antibiotic without previous exposure. They lack the target site of the antibiotic agent.
- Examples: Mycoplasma, Chlamydia (resist beta-lactams due to lack of cell wall peptidoglycan), and Gram-negative bacteria (resistant to Vancomycin).
Acquired Resistance: Resistance mechanisms developed after exposure to antibiotics. Resistance mechanisms include mutation of existing genes, or acquisition of new resistance genes.
- Gene transfer mechanisms like conjugation (sex pili), transduction (bacteriophage), transformation.

Modification of target sites of antibiotics

Examples: Salmonella typhi (modified DNA gyrase → quinolones resistance), Methicillin-resistant Staphylococcus aureus (MRSA) (modified penicillin-binding protein (PBP) encoded by the mecA gene).

Increased Drug Efflux

Pumping antibiotics out of the bacterial cell, making the drug unable to reach its target site.
- Examples: Gram-negative bacteria (e.g., E. coli, Pseudomonas aeruginosa) efflux beta-lactam antibiotics and tetracyclines.

Drug Inactivation

Some bacteria produce enzymes that inactivate antibiotics.
- Examples: β-lactamases (inactivate penicillin) and cephalosporinases, adenyl transferases (inactivate aminoglycosides)

Cross Resistance

Bacteria resistant to a certain antibiotic may also be resistant to other antibiotics having similar mechanism of action or chemical structure.
- Example: Macrolides (e.g., azithromycin) and Lincosamides (e.g., clindamycin).

How to Decrease Antibiotic Resistance

Avoid unnecessary antibiotic prescriptions (for viral infections).
Proper antibiotic selection.
Give empirical antibiotic first and then modify based on culture and sensitivity results.
Use antibiotics in proper route, dose, and duration.
Antibiotic recycling (stopping use for a period, then re-evaluate potency).
Establish antibiotic stewardship programs.

Antibiotic Stewardship Programs

Designed to improve how antibiotics are prescribed and used.
Ministry of health prepares guidelines for treatment and prophylaxis of infections.
List of restricted antimicrobials.
Aims: treat infections effectively (type, dose, duration, and route), protect patients from unnecessary antibiotic use, decrease antibiotic resistance.

Antibiotic Combination

Indication: Mixed infection, severe life-threatening infections (e.g., meningitis), and resistant bacteria.
Aims: Synergism—combined effect greater than individual effects (High cost, more adverse reactions).
Disadvantages: High cost, potential for more adverse effects.
Antagonism—combined effect is less than individual effects.

Questions

Q1: Aminoglycosides
Q2: Macrolides.

Reference

Lippincott Illustrated Microbiology 4th edition, Chapter 5.

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Description

This quiz covers the basics of antibiotics and their classifications, including spectrum of activity and modes of action. Understand the differences between broad and narrow-spectrum antibiotics, and learn about their effects on microbial growth. Test your knowledge on antimicrobial agents and their significance in medicine.