Antimicrobial Drugs Lecture

Drugs and Antimicrobial Overview

Chapter 20: Drugs

Learning Objectives

  • List 4 mechanisms of resistance

  • List 1 test to guide chemotherapy

  • Discuss common antimicrobial drugs

  • List 5 actions of antimicrobials

  • Define spectrum of antimicrobial activity

  • Discuss the history of chemotherapy

History of Antimicrobials

  • Alexander Fleming discovered the first antibiotic, penicillin.

  • Penicillin is produced by the mold Penicillium.

  • Chemotherapy: The use of chemicals to treat a disease.

  • Antibiotic: A natural substance produced by a microbe that, in small amounts, inhibits another microbe (specifically bacteria).

  • Antimicrobial drugs: Synthetic substances that interfere with the growth of microbes.

Applying Antibiotics

  • Discussion Prompt: What happens when bacteria develop antibiotic resistance?

  • Method: Think, Pair, Share

Spectrum of Antimicrobial Activity

  • Definitions:

    • Narrow spectrum antibiotics: Drugs that affect a small range of microbial types.

    • Broad-spectrum antibiotics: Drugs that affect a wide range of gram-positive or gram-negative bacteria.

Classification of Microbial Types

  • Prokaryotes:

    • Gram-Negative

    • Gram-Positive

    • Mycobacteria

  • Eukaryotes:

    • Bacteria

    • Chlamydias, Rickettsia

    • Fungi

    • Protozoa

    • Helminths

    • Viruses

Specific Drugs and Their Targets

  • Isoniazid, Streptomycin: Target specific bacteria.

  • Penicillin G: Targets gram-positive bacteria.

  • Ketoconazole: Targets fungi.

  • Tetracycline: Broad spectrum targeting both bacterial and some eukaryotic organisms.

  • Niclosamide: Used to treat tapeworm infections.

  • Mefloquine: Used for malaria treatment.

  • Praziquantel: Targets flukes.

  • Acyclovir: Targets viruses.

Limitations of Broad-Spectrum Antibiotics

  • Discussion Prompt: Why are broad-spectrum antibiotics not as useful as initially believed?

  • Application consideration: Superinfections caused by excessive killing of normal microbiota, enabling pathogens like Candida albicans (yeast infections/thrush) to proliferate.

Actions of Antimicrobial Drugs

  • General Actions: Antimicrobials typically act by either killing microbes or inhibiting their growth.

  • Definitions:

    • Bactericidal: Kill microbes directly.

    • Bacteriostatic: Prevent microbes from growing.

  • Five General Mechanisms to Prevent Growth:

    1. Inhibition of Cell Wall Synthesis

    • Example: Penicillin prevents the synthesis of peptidoglycan.

    1. Inhibition of Protein Synthesis

    • Targets bacterial 70S ribosomes (eukaryotic cells have 80S ribosomes)

    • Drugs: Chloramphenicol, Erythromycin, Streptomycin, Tetracyclines

    1. Inhibition of Nucleic Acid Synthesis

    • Interferes with DNA replication and transcription

    • Drug: Rifampin

    1. Injury to Plasma Membrane

    • Polypeptide antibiotics change membrane permeability.

    • Antifungal drugs combine with membrane sterols to disrupt the membrane.

    1. Inhibition of Essential Metabolites

    • Drug: Sulfanilamide

    • Mechanism: Antimetabolites compete with normal substrates for an enzyme (competitive inhibition).

Remembering Actions of Antimicrobial Drugs

  1. Identify one action of antimicrobials and explain the impact on the bacterial cell.

  2. Provide an example of a drug that executes this action.

  • Method: Think, Pair, Share

Common Antimicrobial Drugs

Effects of Drug Combinations

  • Synergistic combinations: More effective when taken together.

  • Antagonistic combinations: Less effective when taken together compared to individually.

Antibacterial Antibiotics: Inhibitors of Cell Wall Synthesis

  • Penicillin:

    • A group of 50 chemically related antibiotics noting that they all contain a β-lactam ring.

    • Mechanism: Interferes with PBP (Penicillin-Binding Protein), preventing the linking of peptidoglycans and disrupting the building of the cell wall (particularly in gram-positive bacteria).

Antibacterial Antibiotics: Inhibitors of Protein Synthesis

  • Tetracyclines:

    • Produced by Streptomyces species.

    • Mechanism: Interfere with the tRNA attachment for the bacterial 70S ribosome, which is essential for protein synthesis, making these antibiotics broad-spectrum.

Antibacterial Antibiotics: Injury to Membranes

  • Lipopeptides: Affect the synthesis of bacterial plasma membranes by binding to the membrane, thus damaging it.

  • Polymyxin B:

    • Used topically; bactericidal and effective against gram-negatives.

    • Commonly combined with neomycin in nonprescription ointments.

Antifungal Drugs

  • Agents affecting fungal sterols:

    • Disrupt the synthesis of sterols, making the fungus membrane excessively permeable.

  • Azoles:

    • Imidazole: Topical; treats cutaneous mycoses.

    • Miconazole: Used as a vaginal antifungal.

    • Triazole: Treats systemic fungal infections.

Antiviral Drugs: Nucleic Acid Inhibitors

  • Nucleoside analogs: Inhibit RNA or DNA synthesis by resembling the actual products.

  • Acyclovir:

    • Increases mutation rates in viruses, which is detrimental and prevents replication.

Mechanism of Acyclovir Action

  • Acyclovir resembles the nucleoside deoxyguanosine and is converted by the altered thymidine kinase in virally infected cells into a false nucleotide that blocks DNA synthesis by inhibiting DNA polymerase.

Antiviral Drugs: Interferons

  • Interferons: Naturally produced as part of the innate immune system.

    • Produced by viral-infected cells to prevent further spread of infection.

  • Imiquimod: A drug that promotes interferon production.

Antiviral Drugs: Antiretrovirals

  • Antiretrovirals (ARV):

    • Target retroviruses, such as HIV, by inhibiting reverse transcriptase.

    • ARVs prevent viral entry, replication, assembly, and release.

    • Examples: PrEP (pre-exposure prophylaxis), PEP (post-exposure prophylaxis), ART (antiretroviral therapy).

Testing to Guide Chemotherapy

  • Diffusion Methods:

    • Tests determine effective agents against specific microbes.

  • Disk-diffusion method (Kirby-Bauer test):

    • Paper disks with the chemotherapeutic agents are placed on agar with the test organism.

    • Zone of inhibition around the disk indicates the sensitivity of the organism to the antibiotic.

Resistance to Antimicrobial Drugs

  • Superbugs: Bacteria resistant to multiple antibiotics (e.g., Methicillin-resistant Staphylococcus aureus (MRSA)).

  • Mechanisms of Resistance:

    • Bacteria can become resistant by:

    1. Blocking entry: Preventing drug uptake.

    2. Inactivation by enzymes: Degrading or modifying drugs.

    3. Alteration of target molecules: Changing binding sites on target protein.

    4. Efflux of antibiotics: Pumping out the drug before it can act.

Genetics and Resistance

  • Bacteria may acquire resistance through:

    • Mutations

    • Horizontal Gene Transfer: Including plasmids, transposons, conjugation, transduction.

Antibiotic Misuse and Its Consequences

  • Misuse includes:

    • Using outdated or weakened antibiotics.

    • Using antibiotics for viral infections (e.g., common cold).

    • Using antibiotics in animal feed.

    • Not completing the prescribed regimen.

    • Using leftover prescriptions from others.

Future of Chemotherapeutic Agents

  • Looking into the microbiome for potential new antibiotics.

    • For example, Lactobacillus spp. can inhibit the growth of MRSA in controlled conditions.