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Antibiotic Basics for Clinicians
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Antibiotic Basics for Clinicians

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Questions and Answers

What enables carbapenems to access the periplasm?

  • Ability to bind to PBPs
  • Resistance to -lactamases
  • Presence of outer membrane porin (correct)
  • Production of efux pumps

    • Which of the following is NOT a mechanism of carbapenem resistance?

  • Overproduction of efux pumps
  • Ability to inhibit efux pumps (correct)
  • Loss of production of outer membrane porin
  • Production of altered PBPs

    • What is the result of carbapenems binding to PBPs?

  • Increased susceptibility to other antibiotics
  • Enhanced efflux pump activity
  • Increased production of -lactamases
  • Bacterial cell death (correct)

    • Which bacteria is susceptible to developing resistance by acquiring mutations?

    <p>Pseudomonas aeruginosa</p> Signup and view all the answers

    What is a characteristic of the -lactamases produced by some bacteria?

    <p>They are capable of cleaving carbapenems</p> Signup and view all the answers

    What was the first commercially available carbapenem in the United States?

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

    What is the name of the fungus from which the first cephalosporins were derived?

    <p>Cephalosporium acremonium</p> Signup and view all the answers

    What is the term used to categorize cephalosporins?

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

    What is the common characteristic of cephalosporins and penicillins?

    <p>They are β-lactam antibiotics</p> Signup and view all the answers

    What is the name of the author who wrote about the story of penicillin discovery?

    <p>E.Lax</p> Signup and view all the answers

    Which type of bacteria is first-generation cephalosporins ineffective against?

    <p>MRSA and MRSE</p> Signup and view all the answers

    What is the title of the journal where Donowitz and Mandell published their research on beta-lactam antibiotics?

    <p>New England Journal of Medicine</p> Signup and view all the answers

    What is the primary reason first-generation cephalosporins lack activity against gram-negative bacteria?

    <p>Their side chains do not afford protection from the β-lactamases of most gram-negative bacteria</p> Signup and view all the answers

    What is the name of the book that Petri wrote about penicillins, cephalosporins, and other beta-lactam antibiotics?

    <p>The Pharmacological Basis of Therapeutics</p> Signup and view all the answers

    What is the name of the authors who wrote about piperacillin/tazobactam?

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

    Which of the following bacteria is susceptible to first-generation cephalosporins?

    <p>E. coli</p> Signup and view all the answers

    What is the structure of cephalosporins composed of?

    <p>A nucleus with two side chains</p> Signup and view all the answers

    What is the primary difference between cephamycins and true cephalosporins?

    <p>Their parent compound origin</p> Signup and view all the answers

    Which type of bacteria do first-generation cephalosporins have moderate to poor activity against?

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

    What is the main advantage of the side chains of first-generation cephalosporins?

    <p>They protect the β-lactam ring from cleavage by staphylococcal β-lactamases</p> Signup and view all the answers

    What type of bacteria are Streptococcus pyogenes and Viridans streptococci?

    <p>Gram-positive</p> Signup and view all the answers

    Which of the following bacteria is not susceptible to fifth-generation cephalosporins?

    <p>Pseudomonas aeruginosa</p> Signup and view all the answers

    What is a rare side effect of cephalosporins?

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

    Which of the following is a characteristic of fifth-generation cephalosporins?

    <p>Favorable safety profile</p> Signup and view all the answers

    What type of bacteria are Haemophilus influenzae and Neisseria spp.?

    <p>Gram-negative</p> Signup and view all the answers

    Which of the following is not an example of an anaerobic bacterium?

    <p>Streptococcus pneumoniae</p> Signup and view all the answers

    What is a common side effect of cephalosporins?

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

    Which of the following bacteria are susceptible to fifth-generation cephalosporins?

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

    What is the circled component in the structure of telavancin?

    <p>Lipophilic decylaminoethyl side chain</p> Signup and view all the answers

    What is the type of molecule shown in Figure 5-18?

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

    Which of the following functional groups is NOT present in the structure of vancomycin?

    <p>Sulfhydryl group</p> Signup and view all the answers

    What is the functional group attached to the phosphorus atom in the structure of glycopeptides?

    <p>Hydroxyl group</p> Signup and view all the answers

    What is the common functional group present in both vancomycin and telavancin?

    <p>Amino group</p> Signup and view all the answers

    What is the difference between the structures of vancomycin and telavancin?

    <p>Telavancin has a lipid tail</p> Signup and view all the answers

    What is the site of action for macrolides in bacterial cells?

    <p>50S subunit of the ribosome</p> Signup and view all the answers

    Which of the following is a mechanism of resistance to macrolides?

    <p>Enzyme-mediated ribosome binding site alteration</p> Signup and view all the answers

    Which type of bacteria have difficulty with macrolide penetration and accumulation?

    <p>Aerobic gram-negative bacteria</p> Signup and view all the answers

    What is the effect of macrolides on bacterial protein production?

    <p>Decrease protein production</p> Signup and view all the answers

    Which gene in Streptococcus pneumoniae encodes an efflux pump, contributing to macrolide resistance?

    <p>Mef gene</p> Signup and view all the answers

    What is the consequence of methylation of the ribosome binding site in bacteria?

    <p>Decreased sensitivity to macrolides</p> Signup and view all the answers

    Which of the following is a common characteristic of macrolide resistance?

    <p>Resistance to one macrolide implies resistance to all</p> Signup and view all the answers

    What is the target site for macrolides in bacterial cells?

    <p>50S subunit of the ribosome</p> Signup and view all the answers

    What is the primary mechanism of action of rifamycins?

    <p>Inhibition of bacterial RNA polymerase</p> Signup and view all the answers

    Why are rifamycins often used in combination with other agents?

    <p>To prevent the emergence of resistant strains</p> Signup and view all the answers

    What is a characteristic of rifampin?

    <p>It is the most potent inducer of the cytochrome P-450 system</p> Signup and view all the answers

    What is a use of rifampin?

    <p>All of the above</p> Signup and view all the answers

    Why is rifabutin preferred over rifampin in individuals with HIV infection?

    <p>Because it inhibits the cytochrome P-450 system to a lesser degree</p> Signup and view all the answers

    What is a consequence of rifamycin resistance?

    <p>Treatment failure</p> Signup and view all the answers

    What is the target of rifamycins in bacterial cells?

    <p>DNA/RNA tunnel of RNA polymerase</p> Signup and view all the answers

    What is the common structure of rifamycins?

    <p>An aromatic nucleus linked by an aliphatic handle on both ends</p> Signup and view all the answers

    Aminoglycosides are active against which of the following types of bacteria?

    <p>Both Gram-positive and Gram-negative bacteria</p> Signup and view all the answers

    What is the mechanism of bacterial resistance to aminoglycosides that prevents the accumulation of the antibiotic in the cytosol of the bacterium?

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

    Which of the following bacteria is NOT susceptible to aminoglycosides?

    <p>Fusobacterium nucleatum</p> Signup and view all the answers

    What is the effect of efflux pumps on aminoglycoside activity?

    <p>Prevent the accumulation of aminoglycosides in the cytosol</p> Signup and view all the answers

    Aminoglycosides are used synergistically against which of the following bacteria?

    <p>All of the above</p> Signup and view all the answers

    What is the mechanism of action of aminoglycosides?

    <p>Inhibition of protein synthesis</p> Signup and view all the answers

    Which of the following bacteria is susceptible to aminoglycosides due to its Gram-negative cell wall?

    <p>Haemophilus influenzae</p> Signup and view all the answers

    What is a common characteristic of aminoglycosides?

    <p>They have a broad spectrum of activity</p> Signup and view all the answers

    Study Notes

    Antibiotic Basics for Clinicians

    • Cephalosporins are named after the fungus Cephalosporium acremonium, which was the source of the first members of this class of antibiotics.

    Cephalosporins

    • Cephalosporins are categorized by "generation" since agents in each generation have similar spectra of activity.
    • Each cephalosporin is composed of a nucleus with two side chains.
    • They are useful in the treatment of infections caused by many strains of Staphylococcus aureus.
    • First-generation cephalosporins:
      • Cannot bind the PBPs of MRSA and MRSE or many highly penicillin-resistant Streptococcus pneumoniae.
      • Are ineffective against L. monocytogenes and the enterococci.
      • Have limited activity against aerobic and facultative gram-negative bacteria.
      • Have moderate to poor activity against anaerobes, intracellular bacteria, and spirochetes.
    • Second-generation cephalosporins:
      • Are divided into two groups: the true cephalosporins (e.g., cefuroxime) and the cephamycins (e.g., cefotetan and cefoxitin).
      • Cephamycins are derivatives of a parent compound originally isolated from the bacterium Streptomyces lactamdurans.

    Carbapenems

    • Carbapenems are adept at gaining access to the periplasm, resisting destruction by β-lactamases, and binding to PBPs to cause bacterial cell death.
    • Resistance to carbapenems occurs when bacteria:
      • Overcome the advantageous aspects of these antibiotics.
      • Acquire mutations that result in loss of production of the outer membrane porin used by carbapenems to gain access to the periplasm.
      • Overproduce efflux pumps that limit accumulation of the drugs in the periplasmic space.
      • Produce altered PBPs that do not bind these carbapenems.
      • Acquire the ability to produce extremely powerful β-lactamases that are capable of cleaving carbapenems.

    Imipenem

    • Imipenem was the first commercially available carbapenem in the United States.

    Fifth-Generation Cephalosporins

    • Have activity against:
      • Gram-positive bacteria (e.g., Streptococcus pyogenes, viridans streptococci, Streptococcus pneumoniae, Staphylococci).
      • Gram-negative bacteria (e.g., Escherichia coli, Klebsiella pneumoniae, Proteus spp., Haemophilus influenzae, Neisseria spp., some Enterobacteriaceae).
      • Anaerobic bacteria (e.g., some Clostridium spp.).

    Toxicity

    • Cephalosporins have a relatively favorable safety profile.
    • Rarely cause immediate hypersensitivity reactions consisting of rash, urticaria, or anaphylaxis.

    Glycopeptides

    • Structure of glycopeptides:
      • Vancomycin and telavancin are examples of glycopeptides.
      • Telavancin has a lipophilic decylaminoethyl side chain.

    Macrolides

    • Consist of a large cyclic core called a macrocyclic lactone ring
    • Ring is decorated with sugar residues
    • Bind tightly to the 50S subunit of the bacterial ribosome, blocking the exit of newly synthesized peptides
    • Function similarly to aminoglycosides, targeting ribosomes and preventing protein production

    Mechanisms of Macrolide Resistance

    • Inhibition of drug entry and accumulation
    • Enzyme-mediated ribosome binding site alteration (e.g., methylating the 50S ribosome)
    • Mutation of the ribosome binding site

    Aminoglycosides

    • Also active against certain mycobacteria species (e.g., Mycobacterium tuberculosis and Mycobacterium avium complex)
    • Have a similar structure with an aromatic nucleus linked by an aliphatic "handle"
    • Active against various bacteria (Table 6-4)

    Rifamycins

    • Act by inhibiting bacterial RNA polymerase
    • Nestle deep into the DNA/RNA tunnel of RNA polymerase, sterically blocking elongation of nascent mRNA molecules
    • Resistance develops relatively easily due to single mutations in the bacterial gene encoding RNA polymerase
    • Frequently used in combination regimens for the treatment of mycobacterial infections (Table 6-2)

    Rifampin

    • Used along with other antibiotics to treat staphylococcal infections
    • Effective as monotherapy for prophylaxis against Neisseria meningitidis and Haemophilus influenzae
    • Most potent inducer of the cytochrome P-450 system

    Rifabutin

    • Favored over rifampin in individuals being treated for tuberculosis and HIV infection
    • Inhibits the cytochrome P-450 system to a lesser degree than rifampin or rifapentine, making it easier to administer with antiretroviral agents

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    Test your knowledge of antibiotics, including beta-lactam antibiotics and their mechanism of action. Learn about the history of penicillin and its discovery.

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