Antibiotics Overview: Macrolides & More

Macrolides

• Principally active against Gram-positive bacteria
• Show useful activity against penicillin-resistant strains
• Also effective against Gram-negative cocci
• Mode of action: Bacteriostatic, bind to the 50S ribosomal subunit to prevent the translocation step of bacterial protein synthesis
• Examples: Erythromycin, Azithromycin

Tetracyclines

• Broad spectrum antibiotic
• Characterized by their common octahydronaphthacene skeleton
• Examples: Tetracycline, Doxycycline, Minocycline

Lincomycins

• Known as Sulphur-containing Antibiotics
• Mode of action: Act via 50S ribosomal subunit binding and protein synthesis inhibition.
• Used in extra CNS anaerobic infections and in penicillin-sensitive patients
• Examples: Lincomycin, Clindamycin

Polypeptide Antibiotics

• Most powerful antibiotic agents but limited use due to renal toxicity.
• Used mainly locally in burns.
• Mode of action: Inhibit mucopeptide cell wall synthesis and interfere with semipermeability of the cell membrane
• Examples: Bacitracin, Gramicidin, Polymyxin

Unclassified Antibiotics

• Chloramphenicol: Used in meningitis, typhoid, and paratyphoid fever

Antibiotic Resistance

• Two types of resistance: intrinsic and acquired.
• Intrinsic resistance: Mycoplasma resistance to β-lactam antibiotics and other cell wall inhibitors due to the absence of a cell wall
• Acquired resistance occurs when a change in the bacterial genome converts a sensitive bacterium to a resistant one

Mechanisms for Acquiring Resistance

• Inactivation of the antibiotic through enzymatic breakdown (e.g., β-lactamase)
• Efflux pumping of the antibiotic out of the cell
• Modification of the antibiotic target
• Alteration of the bacterial pathway

Beta-Lactam Antibiotics

• Cell wall active agents
• Prevent the final step in the synthesis of the bacterial cell wall
• Range from very narrow spectrum to very broad spectrum

Mechanisms of Action for Beta-Lactam Antibiotics

• Beta-lactam antibiotics bind to Penicillin Binding Protein (PBP).
• Inhibition of PBP prevents the crosslinking of peptidoglycan chains.
• This prevents the bacteria from synthesizing a stable cell wall, leading to lysis (cidal effects).

Antiviral Drugs

• Antiviral agents block:
• Viral entry into or exit from the cell
• Viral replication inside the host cell

Mechanisms of Action for Antiviral Drugs

• Alter the cell’s genetic material (e.g. Acyclovir blocks viral enzymes and assembly of viral proteins)
• Prevent the newly formed virus from leaving the cell (e.g. Amantadine)

Challenges of Antiviral Therapy

• Rapid viral replication makes it difficult to develop effective antivirals.
• Rapid viral mutation can lead to drug resistance.
• Finding a drug that targets the virus without harming normal cells is difficult.

Antiviral Drug Properties

• They are virustatic, meaning they are active only against replicating viruses, and not latent viruses.

Herpes Simplex Virus (HSV) & Varicella-zoster Virus (VZV) Infections

• Herpes simplex viruses (HSV) cause repeated, blister-like lesions on the skin, genitals, and mucosal surfaces.
• HSV-type 1 is non-genital.
• HSV-type 2 causes genital infections.

Acyclovir

• Acyclovir is a guanosine analog that is primarily taken up by virus-infected cells.
• It selectively inhibits herpes virus DNA polymerase.

Clinical use of Acyclovir

• Treatment of Herpes simplex, Herpes zoster, Chickenpox and Epstain-Barr virus infections.

### Ganciclovir

• Ganciclovir is an analog of acyclovir effective against all Herpes viruses and CMV.
• Limited oral bioavailability, given intravenously.

Valacyclovir

• Valacyclovir is a prodrug of acyclovir.
• It has better bioavailability than acyclovir.

Explore the essential features of various antibiotics, including macrolides, tetracyclines, lincomycins, and polypeptide antibiotics. Learn about their modes of action, spectrum of activity, and key examples. This quiz will challenge your understanding of these important antibacterial agents.