Antibacterial Agents and Antibiotic Resistance

Chloramphenicol

• Chloramphenicol is known for inhibiting protein synthesis in bacteria by binding to the 50S ribosomal subunit.
• A common mechanism of resistance to chloramphenicol involves the production of chloramphenicol acetyltransferases (CAT), which inactivate the antibiotic by adding acetyl groups.

Aminoglycosides

• The discovery of streptomycin, an aminoglycoside antibiotic, from Streptomyces griseus in 1944 marked a significant turning point in antibacterial drug discovery.

Antibiotic Side Effects

• A potential side effect associated with using antibiotics is the disruption of gut microbiota, which can lead to digestive issues and opportunistic infections.

Bacteriostatic vs Bactericidal Agents

• Bacteriostatic agents inhibit bacterial growth and reproduction, while bactericidal agents directly kill bacterial cells.
• Chloramphenicol is a bacteriostatic antibiotic.

Antibiotic Resistance

• The mechanism of resistance in bacterial strains generally involves genetic mutations that alter antibiotic target sites, enhance efflux pump activity, or produce enzymes that degrade or inactivate the antibiotic.
• Aminoglycosides, macrolides, and tetracyclines are all antibiotic classes that have a history of being discovered from soil microorganisms.
• Antibiotic resistance is a major global health concern, and the overuse and misuse of antibiotics contribute significantly to its development.

Cell Structure

• Prokaryotic cells are distinguished by their lack of defined nuclei and organelles.

Bactericidal Action

• Bactericidal agents primarily function by disrupting critical bacterial cell processes, such as cell wall synthesis, DNA replication, and protein synthesis.

Aminoglycoside Mechanism

• Aminoglycosides primarily exert their antibacterial effect by inhibiting protein synthesis through binding to the 30S ribosomal subunit, causing misreading of mRNA and premature chain termination.

Aminoglycoside Use

• Gentamicin is the drug of choice for most nosocomial Gram-negative infections.

Aminoglycoside Activity

• Aminoglycosides exhibit bactericidal activity, meaning they kill bacterial cells.

MIC

• MIC refers to the Minimum Inhibitory Concentration, which represents the lowest concentration of an antibiotic required to inhibit the growth of a specific bacterium.

Aminoglycoside Side Effects

• Aminoglycosides can cause ototoxicity (damage to the auditory system) and nephrotoxicity (damage to the kidneys).

Aminoglycoside Resistance

• Bacterial strains that produce modifying enzymes that alter the structure of aminoglycosides are often resistant to these antibiotics.

Time-Dependent Antibiotics

• Time-dependent antibiotics achieve their efficacy by maintaining concentrations above the minimum inhibitory concentration (MIC) for a sustained period.

Aminoglycoside Characteristics

• Aminoglycosides are not effective against anaerobic bacteria.