Antimicrobial Chemotherapy Lecture 5
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Questions and Answers

What is the mechanism of plasmid-mediated resistance in bacteria?

  • Bacteria produce enzymes that degrade antibiotics.
  • Bacteria gain resistance genes through horizontal gene transfer. (correct)
  • Bacteria can modify their cell surface to block antibiotics.
  • Bacteria take up free DNA from the environment.

    • Which of the following best describes enzymatic degradation of antibiotics?

  • Antibiotics are modified to enhance their efficacy.
  • Bacteria prevent antibiotics from entering their cells.
  • Bacteria use enzymes to chemically break down antibiotics. (correct)
  • Bacteria alter their ribosomes to resist antibiotics.

    • Altered drug permeability in bacteria usually results in what?

  • Uniform distribution of antibiotics throughout the bacterial cell.
  • Increased effectiveness of antibiotics.
  • Enhanced uptake of nutrients critical for survival.
  • Decreased ability of the antibiotic to reach its target site. (correct)

    • Efflux pump mechanisms contribute to antibiotic resistance by which means?

    <p>Pumping out antibiotics that have entered the bacterial cell.</p> Signup and view all the answers

    Target site modification in bacteria is a mechanism of resistance that involves what?

    <p>Bacteria alter the specific binding sites of antibiotics.</p> Signup and view all the answers

    What mechanism allows microorganisms to transport antibiotics out of the cell, contributing to drug resistance?

    <p>Efflux pumps</p> Signup and view all the answers

    Which of the following alterations in bacteria can lead to resistance against aminoglycosides?

    <p>Altered permeability</p> Signup and view all the answers

    What is a key characteristic of organisms that develop altered enzymes, making them resistant to trimethoprim?

    <p>Dihydrofolic acid reductase is less inhibited</p> Signup and view all the answers

    What type of drug resistance develops through spontaneous mutations in chromosomal loci?

    <p>Chromosomal resistance</p> Signup and view all the answers

    Which of the following best describes the altered structural target mechanism of antibiotic resistance?

    <p>Modification of ribosomal subunits</p> Signup and view all the answers

    What is a common example of nongenetic drug resistance?

    <p>Persisting mycobacterial organisms surviving in tissues</p> Signup and view all the answers

    Which mechanism explains bacteria's ability to utilize preformed folic acid to bypass sulfonamide inhibition?

    <p>Altered metabolic pathways</p> Signup and view all the answers

    What commonly leads to the resistance of bacteria against penicillins and cephalosporins?

    <p>Alteration of penicillin-binding proteins</p> Signup and view all the answers

    Which mechanism allows bacteria to produce enzymes that destroy drugs like penicillin G?

    <p>Enzymatic degradation</p> Signup and view all the answers

    What is a common characteristic of plasmid-mediated resistance?

    <p>It can be transferred between different bacteria</p> Signup and view all the answers

    Which of the following is a known consequence of altered drug permeability in bacteria?

    <p>Accumulation of drugs in resistant bacteria</p> Signup and view all the answers

    How do efflux pumps contribute to antibiotic resistance?

    <p>By actively expelling antibiotics from inside the bacterial cell</p> Signup and view all the answers

    What is a characteristic feature of target site modification as a form of resistance?

    <p>Altering the binding sites of antibiotics</p> Signup and view all the answers

    Which bacterial species is known for exhibiting resistance due to the production of aminoglycoside inactivating enzymes?

    <p>Escherichia coli</p> Signup and view all the answers

    What mechanism best describes a situation where resistance to gentamicin does not confer resistance to tobramicin?

    <p>Dissociate resistance</p> Signup and view all the answers

    Which of these methods bacteria use to resist drug action involves passing blocked metabolic reactions?

    <p>Bypassing metabolic pathways</p> Signup and view all the answers

    Which of the following statements about antibiotic resistance mechanisms is false?

    <p>Resistance mechanisms can solely rely on external environmental factors.</p> Signup and view all the answers

    What type of resistance arises when a mutation leads to Mycobacterium tuberculosis becoming resistant to streptomycin?

    <p>Acquired resistance</p> Signup and view all the answers

    What is the primary mechanism by which Carbapenems exhibit their broad spectrum of activity?

    <p>They easily penetrate bacterial cells and resist β-lactamases.</p> Signup and view all the answers

    Which antibiotic is specifically used for patients with severe allergies to penicillins?

    <p>Aztreonam</p> Signup and view all the answers

    How do β-lactamase inhibitors enhance the effectiveness of penicillins?

    <p>By binding and inactivating β-lactamase enzymes.</p> Signup and view all the answers

    Which of the following antibiotics directly inhibits peptidoglycan synthesis in bacteria?

    <p>Vancomycin</p> Signup and view all the answers

    What occurs when the integrity of the cytoplasmic membrane in bacteria is disrupted?

    <p>Macromolecules and ions leak from the cell leading to cell death.</p> Signup and view all the answers

    What is one of the characteristics of Augmentin?

    <p>It combines broad-spectrum antibiotic activity with β-lactamase inhibition.</p> Signup and view all the answers

    Which of the following best describes the role of

    <p>They must first be hydrolyzed by β-lactamases to inhibit them effectively.</p> Signup and view all the answers

    What type of antibiotic is primarily used against methicillin-resistant Staphylococcus aureus (MRSA)?

    <p>Vancomycin</p> Signup and view all the answers

    Which mechanism of resistance involves the alteration of the antibiotic's target site?

    <p>Target site modification</p> Signup and view all the answers

    What effect do detergents have on bacterial cells?

    <p>They disrupt membrane function and lead to cell death.</p> Signup and view all the answers

    Study Notes

    Antimicrobial Chemotherapy

    • Lecture 5 covered antimicrobial chemotherapy, drug resistance and prevention.
    • Topics included antimicrobial chemotherapies and their targets, drug resistance, clinical implications and prevention.
    • Historical context for antibiotic usage was discussed, starting in the 17th century.

    History

    • Drugs were used for malaria and amebiasis since the 17th century (e.g., quinine and emetine).
    • Chemotherapy as a science began in the early 20th century.
    • The first planned chemotherapeutic regimen for syphilis was developed by Paul Ehrlich.
    • The discovery of sulphonamides (prontosil rubrum) happened in 1935, marking the era of chemotherapy.
    • Selman Waksman discovered streptomycin in 1952.
    • Alexander Fleming discovered penicillin in 1929.

    Selective Toxicity

    • Selective toxicity is the ability to eliminate or inhibit the growth of microorganisms without harming the host cells.
    • Often, selective toxicity is relative rather than absolute; a drug's concentration tolerated by the host may harm the infective microorganism.
    • Examples include antibiotics that act on bacterial cell wall synthesis, which doesn't occur in eukaryotic cells. Some agents act on 70S ribosomes in bacteria, but not 80S ribosomes in eukaryotic cells.

    Antimicrobial Agents

    • Antibiotics are naturally produced microbial compounds that inhibit other microorganisms.
    • Most antibiotics are produced by fungi (e.g.,penicillin) or bacteria (e.g., streptomycetes).
    • Antimicrobials are substances used to treat infectious diseases and, unlike antibiotics, need not have a bacterial or fungal origin.

    Types of Antimicrobial Agents

    • Chemotherapeutic agents include chemically synthesized antibiotics, semi-synthetic antibiotics (chemically modified natural compounds), and synthetic antibiotics (without natural analogues).

    Antimicrobial Activity

    • Bactericidal activity is antimicrobial activity that is lethal to bacteria, killing them.
    • Bacteriostatic activity inhibits microbial growth but does not kill them.
    • Examples of bactericidal agents include aminoglycosides, beta-lactams, vancomycin, quinolones, and metronidazole.
    • Examples of bacteriostatic agents include chloramphenicol, erythromycin, clindamycin, sulfonamides, trimethoprim, and tetracyclines.

    Minimal Inhibitory Concentration (MIC)

    • MIC is the lowest antibiotic concentration that inhibits the growth of a microorganism in vitro.
    • MIC is a laboratory term expressed in micrograms per milliliter (µg/ml).

    Terms

    • Resistant/nonsusceptible organisms are not inhibited by achievable concentrations of a antimicrobial agent.
    • Sensitive/susceptible microorganisms are inhibited at achievable concentrations of the antimicrobial agent.

    Spectrum of Activity

    • Spectrum is the range of microorganisms affected by an antimicrobial agent. It can be:
      • Broad spectrum: effective against Gram-positive and Gram-negative bacteria.
      • Narrow spectrum: effective against selected microorganisms.
      • Limited spectrum: effective against a single organism or disease.

    Sources of Natural Antibiotics

    • Antibiotics are often produced by molds (e.g., penicillin) and bacteria (e.g., streptomycetes).
    • These organisms often reside in soil and form spores.
    • Antibiotics are secondary metabolites produced at the same time as sporulation.

    Therapeutic Index (TI)

    • The therapeutic index (TI) is the ratio of the dose that is toxic to a patient to the dose that is therapeutic (eliminates the infection).
    • A larger index means a safer dose for a clinical trial.
    • Examples include penicillin (high TI) and aminoglycosides (low TI).

    Mechanisms of Action of Antimicrobials

    • Inhibition of cell wall synthesis.
    • Inhibition of cell membrane function.
    • Inhibition of protein synthesis.
    • Inhibition of nucleic acid synthesis.
    • Anti-metabolite or competitive antagonism.

    Targets of Antibiotics

    • Cell Wall Synthesis: D-cycloserine, vancomycin, bacitracin, penicillins, cephalosporins, and cephamycins.
    • DNA gyrase, quinolones, metronidazole.
    • 50S and 30S ribosomal subunits: Protein synthesis inhibitors (erythromycin, tetracyclines, chloramphenicol, cindamycin, lincomycin).
    • RNA polymerase: Rifampicin.
    • Cytoplasmic membrane: polymyxins.

    Cell Wall Inhibition

    • The bacterial cell wall is a complex polymer composed of polysaccharides and polypeptide chains.
    • Contains unique amino sugars (e.g., N-acetylmuramic acid) that are not present in animal cells.
    • Many beta-lactam antibiotics inhibit cell wall synthesis by binding to penicillin-binding proteins (PBPs).

    Penicillins (Beta-Lactam Antibiotics)

    • All beta-lactam drugs are selective inhibitors of bacterial cell wall synthesis.
    • Contain a beta-lactam ring and an organic acid.
    • Inactivate bacterial proteins by interfering with the transpeptidase (PBP) reaction, preventing peptidoglycan cross-linking in the cell wall.
    • Some penicillins may be resistant to bacterial enzymes produced by certain bacteria (β-lactamases or penicillinases).

    Beta-Lactamase Inhibitors

    • Beta-lactamases are enzymes produced by some bacteria that inactivate beta-lactam antibiotics.
    • Beta-lactamase inhibitors (e.g., clavulanate, sulbactam, tazobactam) block the action of these enzymes, improving the effectiveness of beta-lactam antibiotics.

    Vancomycin (A Glycopeptide Antimicrobial)

    • Vancomycin directly binds to amino acid side chains and prevents the formation of the cross-links in peptidoglycan, which is essential to maintaining the integrity of bacterial cell walls.
    • This drug is used as either a part of or as a direct treatment against bacterial infections such as methicillin-resistant S. aureus (MRSA).

    Inhibition/Alteration of Cell Membrane Function

    • The cytoplasmic membrane's key function lies in selective permeability, active transport, controlling cell composition.
    • Disrupting the membrane leads to damage, cell death, loss of cellular components and ions.
    • Detergents and antibiotics (e.g., polymyxins) disrupt membranes that contain phosphatidylethanolamine.

    Inhibitors of Protein Synthesis

    • Aminoglycosides (e.g., gentamicin) inhibit protein synthesis by binding to 30S ribosomal subunits.
    • Tetracyclines (e.g., tetracycline) block the attachment of tRNA to mRNA.
    • Chloramphenicol (e.g., chloramphenicol) bind to 50S ribosomal subunits.
    • Macrolides (e.g., erythromycin) bind to 50S ribosomal subunits.

    Inhibitors of Nucleic Acid Synthesis

    • Rifampin: Inhibits RNA synthesis.
    • Quinolones (e.g., nalidixic acid, ciprofloxacin): Inhibit DNA synthesis by blocking DNA gyrase.

    Inhibitors of Folic Acid Metabolism

    • Sulfonamides and trimethoprim are structural analogues of para-aminobenzoic acid (PABA) interfering with folic acid synthesis in bacteria, thus inhibiting microbial growth.

    Anti-tubercular Agents

    • First-line drugs (e.g., isoniazid, rifampicin, ethambutol, pyrazinamide) are used to treat tuberculosis.
    • Second-line drugs (e.g., streptomycin, cycloserine, para-aminosalicylic acid, capreomycin) are utilized in cases of drug resistance.

    Antibiotic Resistance

    • Nongenetic causes of resistance include the limited ability of some drugs to enter bacteria or the natural survival of bacteria in tissue (e.g., mycobacteria).
    • Genetic causes include mutations in the bacterial genome or the exchange of resistance genes through plasmids (extra-chromosomal genetic elements). resistance genes can be exchanged in other ways, such as transformation, conjugation. and transduction. Mechanisms of resistance include:
      • Altered permeability
      • Enzymatic inactivation
      • Altered target molecule
      • Bypassing the metabolic pathway
      • Efflux pumps.

    Principles of Antimicrobial Therapy

    • Choice of drug.
    • Route of administration.
    • Dosage and duration.
    • Distribution.
    • Excretion / clearance.

    Criteria for an Ideal Antimicrobial Agent

    • Selective toxicity.
    • No hypersensitivity.
    • Rapid tissue penetration.
    • Resistance shouldn't develop quickly.
    • No effect on normal flora (gut flora).
    • Broad spectrum if possible.

    Antibiotic Sensitivity Testing

    • Methods are useful for determining the minimum inhibitory concentration (MIC), determining and detecting resistance mechanisms. Tests include:
      • Disc diffusion tests
      • Dilution tests -Automated tests

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    Microbiology Lecture 5: Antimicrobial Chemotherapy - October 2022 PDF

    Description

    This quiz delves into Lecture 5 on antimicrobial chemotherapy, focusing on drug resistance, prevention strategies, and the historical evolution of antibiotics from the 17th century to present. Key topics include selective toxicity and the clinical implications of antimicrobial therapies. Test your knowledge on how these developments have shaped modern medicine.

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