Beta Lactam Antibiotics Overview
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Questions and Answers

What is the primary function of beta lactam antibiotics?

  • Inhibit protein synthesis in bacteria
  • Inhibit bacterial metabolism
  • Inhibit bacterial cell wall synthesis (correct)
  • Inhibit nucleic acid synthesis in bacteria

    • What structural component of penicillin is essential for its activity?

  • Aromatic ring
  • Beta lactam ring
  • Lactam bond
  • Thiazolidine ring (correct)

    • What does the historical measurement of penicillin units signify?

  • The purity of penicillin in a sample
  • The weight of penicillin in milligrams
  • The biological potency of penicillin (correct)
  • The chemical structure of penicillin

    • What is the role of Penicillin Binding Proteins (PBPs) in bacteria?

    <p>To mediate cell wall synthesis</p> Signup and view all the answers

    What is the function of the transpeptidase enzyme related to PBPs?

    <p>To form cross-links in the bacterial cell wall</p> Signup and view all the answers

    What is the primary difference between first-generation and second-generation beta-lactams regarding Gram-positive coverage?

    <p>First generation provides better coverage for Gram-positives.</p> Signup and view all the answers

    Which organisms are commonly covered by third-generation beta-lactams?

    <p>Good coverage against Gram-negative rods.</p> Signup and view all the answers

    Which beta-lactam is specifically noted to be parenteral in the first generation?

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

    What is the primary clinical limitation noted for third-generation beta-lactams?

    <p>Decreased coverage for Staphylococci.</p> Signup and view all the answers

    Which of the following best describes the spectrum of activity for second-generation beta-lactams?

    <p>Better activity against Gram-negatives and less against Gram-positives.</p> Signup and view all the answers

    Which generation of beta-lactams is developed primarily for treating nosocomial infections?

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

    Which organisms are targeted specifically by first-generation beta-lactams?

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

    What is one of the mechanisms by which bacteria develop resistance to antibiotics?

    <p>Developing high-molecular-weight PBP with decreased affinity for antibiotic.</p> Signup and view all the answers

    Beta lactamase is known for which primary function?

    <p>Opening the beta lactam ring structure and removing antibiotic activity.</p> Signup and view all the answers

    Which of the following antibiotics is commonly used with a beta lactamase inhibitor?

    <p>Amoxicillin combined with clavulanic acid (Augmentin®).</p> Signup and view all the answers

    What is a characteristic of beta lactamase inhibitors?

    <p>They generally have weak to no antibiotic activity on their own.</p> Signup and view all the answers

    Which group of penicillins is specifically resistant to beta lactamase degradation?

    <p>Beta lactamase resistant penicillins.</p> Signup and view all the answers

    Which bacterial adaptation involves removing antibiotics from within the cell?

    <p>Efflux pump development.</p> Signup and view all the answers

    Which beta-lactam antibiotic is primarily used against Gram-negative bacteria like E. coli?

    <p>Ampicillin.</p> Signup and view all the answers

    Which drug is specifically noted for being the drug of choice for treating gonorrhea?

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

    What is the main mechanism of action of vancomycin?

    <p>Inhibits cell wall biosynthesis</p> Signup and view all the answers

    Which bacteria are cefepime important against due to their beta-lactamase producing capabilities?

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

    Which of the following is NOT a characteristic of vancomycin?

    <p>Has a broad spectrum of activity against Gram-negative bacteria</p> Signup and view all the answers

    Why is cefepime considered a fourth-generation cephalosporin?

    <p>It has a broader spectrum including resistant Gram-negative strains.</p> Signup and view all the answers

    What is a common use of bacitracin?

    <p>Topical treatment for Gram-positive infections</p> Signup and view all the answers

    What is a significant factor of cefepime compared to third-generation cephalosporins?

    <p>It has more effectiveness against beta-lactamase producing bacteria.</p> Signup and view all the answers

    What is the maximum recommended trough Cp level of Vancomycin before the next dose should not be administered?

    <blockquote> <p>10 ug/mL</p> </blockquote> Signup and view all the answers

    Which of the following statements is true regarding Bacitracin?

    <p>It can be used topically and for limited intramuscular use.</p> Signup and view all the answers

    In the context of the case study, which antibiotic is suggested for the patient with left lung pneumonia and possible meningitis?

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

    What clinical condition does the patient in the case study have that influences antibiotic choice?

    <p>Allergy to amoxicillin</p> Signup and view all the answers

    What is the primary route of clearance for most penicillins?

    <p>Unmetabolized through the kidney</p> Signup and view all the answers

    Which clinical use is attributed to Pen V?

    <p>Used for minor infections due to its low bioavailability</p> Signup and view all the answers

    What is the primary adverse reaction associated with penicillin medications?

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

    Which of the following penicillins has a delayed absorption profile when administered intramuscularly?

    <p>Benzathine penicillin</p> Signup and view all the answers

    Exposure to which of the following can lead to a sensitizing reaction from penicillins?

    <p>Exposure to drugs in food</p> Signup and view all the answers

    What is the primary reason for using amoxicillin/clavulanic acid combinations?

    <p>To counteract plasmid-mediated beta-lactamase production in Gram-negative organisms</p> Signup and view all the answers

    Which of the following antibiotics is NOT typically used to treat MRSA infections?

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

    What is the mechanism through which MRSA develops resistance to beta-lactams?

    <p>Chromosomal mutation of penicillin-binding proteins to PBP-2a</p> Signup and view all the answers

    Which medication would be the drug of choice for the empirical treatment of animal bite wounds?

    <p>Amoxicillin/clavulanic acid</p> Signup and view all the answers

    What class of bacteria is most associated with causing skin and soft tissue infections in the US?

    <p>Staphylococcus aureus (non-MRSA)</p> Signup and view all the answers

    Which of the following is a consequence of the extensive use of third-generation cephalosporins?

    <p>Increased incidence of MRSA</p> Signup and view all the answers

    Which of the following is an example of a first-generation cephalosporin?

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

    Which generation of cephalosporins was developed for better coverage against Haemophilus?

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

    What is the common structural feature of cephalosporins that distinguishes them from other antibiotics?

    <p>Dihydrothiazine ring</p> Signup and view all the answers

    Which option best summarizes the coverage of fourth-generation cephalosporins?

    <p>Coverage against both Gram-positive and Gram-negative bacteria</p> Signup and view all the answers

    What is the purpose of monitoring peak and trough Cp levels during vancomycin therapy?

    <p>To minimize toxicity and ensure proper dosing</p> Signup and view all the answers

    What is a potential risk of administering vancomycin too quickly?

    <p>Development of 'Red Man Syndrome'</p> Signup and view all the answers

    What is the threshold for toxic Cp levels of vancomycin?

    <blockquote> <p>80 ug/mL</p> </blockquote> Signup and view all the answers

    Vancomycin's clearance is primarily through which organ?

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

    Which dosing consideration is important for patients with decreased creatinine clearance (CC)?

    <p>Adjust doses based on clearance rates</p> Signup and view all the answers

    What effect did improved purity of vancomycin preparations have on adverse drug reactions (ADRs)?

    <p>Reduced incidence of 'Red Man Syndrome'</p> Signup and view all the answers

    What is the significance of vancomycin distribution in synovial fluid relative to plasma?

    <p>It suggests that plasma levels are sufficient for treating joint infections</p> Signup and view all the answers

    What is indicated by trough Cp levels staying within the range of 5-10 ug/mL?

    <p>Accumulation is effectively managed</p> Signup and view all the answers

    What does semisynthetic mean?

    <p>Derived from natural sources but chemically modified</p> Signup and view all the answers

    What is the MIC for Vancomycin?

    <p>16 ug/mL</p> Signup and view all the answers

    Which medication is useful for bacteria resistant to vancomycin and does not require dose adjustment?

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

    Which of the following is an important backup drug to Vancomycin due to increased abuse and use leading to resistance?

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

    What is the drug of choice for surgical prophylaxis?

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

    Match each cephalosporin generation to its description

    <p>First Generation = active against Gram pos cocci Second Generation = good for extended Gram neg coverage Third Generation = cross the BBB and have extended Gram neg coverage Fourth Generation = coverage for all gram positive and all gram negatives</p> Signup and view all the answers

    What is Kernig's sign and what is it used for?

    <p>A test for Meningitis involving resistance to leg extension while lying down</p> Signup and view all the answers

    What does the word 'eponymous' mean?

    <p>Named after a person</p> Signup and view all the answers

    What is the cephalosporin drug of choice for meningitis?

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

    How should ceftriaxone be administered?

    <p>Intravenous injection</p> Signup and view all the answers

    What penicillins have delayed absorption after IM injection?

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

    Which penicillin is active against Pseudomonas?

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

    Which carbapenem is cilastatin given with?

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

    Study Notes

    Beta Lactam Antibiotics

    • Alexander Fleming discovered the first antibiotic, penicillin, in 1929.
    • Penicillin is derived from a Penicillium mold.
    • Penicillin and cephalosporins inhibit bacterial cell wall synthesis.
    • The Oxford Group led by Howard Florey and Ernst Chain was instrumental in developing penicillin as a chemotherapeutic agent in the 1940s.
    • Fleming, Florey, and Chain shared the Nobel Prize in 1945.
    • Penicillin was first used to treat a patient in 1941, Ann Miller, for a burn infection in 1942.
    • The beta lactam ring is essential for binding to bacterial cell walls.
    • The thiazolidine ring contributes to penicillin's pharmacokinetic properties.
    • In the past, penicillin’s potency was measured in units due to its complex mixture. 1 mg of penicillin is equivalent to 1600 units.
    • Beta Lactams inhibit bacterial cell wall synthesis by binding to a Penicillin Binding Protein (PBP) and inhibiting a transpeptidase enzyme.

    Resistance

    • Bacterial resistance to beta-lactams occurs through several mechanisms:
      • Intrinsic differences in bacterial PBPs.
      • Development of high molecular weight PBPs with reduced antibiotic affinity.
      • Efflux pumps that expel the antibiotic from the cell.
      • Production of beta-lactamase, an enzyme that degrades the antibiotic. Beta-lactamase is common in Gram-positive bacteria but less frequent in Gram-negative.

    Beta Lactamases and their Inhibitors

    • Beta-lactamases cleave the beta-lactam ring structure, rendering the antibiotic inactive.
    • Sulbactam, Clavulanic acid, and Tazobactam are beta-lactamase inhibitors.
    • These inhibitors have little to no antibiotic activity on their own and are used in combination with penicillin drugs.
    • They are not specific for all beta-lactamases; for example, Serratia produces a beta-lactamase not inhibited by Sulbactam.

    Penicillin Groups

    • Penicillin G Group: Effective against Gram-positive cocci and non-beta lactamase producing bacteria.
    • Beta-Lactamase Resistant Penicillins: Nafcillin, Oxacillin, Cloxacillin are effective against S. aureus, and S. epidermidis.
    • Extended Spectrum Penicillins: Ampicillin and Amoxicillin are effective against Gram-negative bacteria like Haemophilus influenzae, E. coli, and Proteus mirabilis. However, they can be hydrolyzed by beta-lactamase.
    • Wider Spectrum Penicillins: Cabenicillin and Ticarcillin are effective against Listeria, Proteus, Enterobacter, and Pseudomonas.

    Cephalosporin Generations

    • First Generation: Effective against Staphylococci (both beta-lactamase positive and negative), Streptococci, Gram-negative bacteria (E. coli, P. mirabilis, Shigella, Salmonella), and most anaerobes (excluding Bacteroides). Primarily oral administration.
    • Second Generation: Enhanced Gram-negative coverage, including resistant E. coli and H. influenzae, and some Bacteroides. Oral and parenteral administration.
    • Third Generation: Extensive Gram-negative coverage, including citrobacter, Serratia marcescens, and beta-lactamase positive Haemophilus and Neisseria. Some drugs cross the Blood-Brain barrier (BBB). Parenteral Administration.
    • Fourth Generation: Effective against both Gram-positive and Gram-negative bacteria, including P. aeruginosa. Crosses the BBB. Parenteral Administration.

    Other Cell Wall Inhibitors

    • Vancomycin: A cyclic peptide produced by Streptomyces orientalis. It inhibits cell wall synthesis by binding to the D-Ala-D-Ala terminus of peptidoglycan pentapeptide, preventing further elongation. Effective against Gram-positive bacteria, particularly resistant Staphylococci.
    • Bacitracin: A cyclic peptide produced by Bacillus subtilis. Effective against most Gram-positive bacteria and some Gram-negative bacteria. Available for intramuscular injection (limited use) and topical use.
    • Daptomycin: A cyclic peptide effective against various Gram-positive bacteria.

    Case Study

    • A 55-year-old male with fever, cough, and suspected pneumonia is allergic to amoxicillin.
    • Ceftriaxone, a third-generation cephalosporin with good CNS penetration and broad-spectrum activity, is recommended to treat both pneumonia and potential meningitis while avoiding the allergy.
    • Vancomycin is added as a precaution against resistant pneumococcus.

    Beta Lactam Antibiotics

    • Alexander Fleming discovered penicillin in 1929.
    • Penicillin was the first antibiotic discovered from a living species.
    • Fleming, Florey, and Chain shared the Nobel Prize in 1945 for their work on penicillin.
    • Penicillin was widely used during WWII.
    • The first patient treated with penicillin was Ann Miller in 1941.

    The Mechanism of Action

    • Beta Lactams bind to Penicillin Binding Proteins (PBPs) found in bacterial cell walls.
    • PBPs contain a transpeptidase enzyme that is inhibited by beta lactams.
    • Inhibition of bacterial cell wall synthesis leads to bacterial death.

    Penicillin

    • The beta lactam ring is required for penicillin to bind to bacterial cell walls.
    • The thiazolidine ring contributes to the pharmacokinetic properties of penicillin.
    • The older "Unit" system of measurement was used for drugs that had not yet been isolated in pure form.
    • 1 mg of penicillin is equivalent to 1600 Units.

    Resistance

    • Resistance can occur through various mechanisms such as:
      • Production of beta-lactamases
      • Alteration of PBPs
      • Reduced permeability of the bacterial cell wall
      • Efflux pumps that pump out penicillin

    Mechanism of Resistance

    • Mezlocillin, Azlocillin, and Piperacillin are effective against pseudomonas, klebsiella, and some gram-negative bacteria.

    Pharmacokinetics

    • Absorption varies among different penicillins.
    • Food can interfere with absorption, so penicillins should be administered 1-2 hours before or after meals.
    • Benzathine and procaine penicillins have delayed absorption after intramuscular injection.
    • Penicillins are mostly cleared unmetabolized by the kidneys.

    Clinical Uses

    • Penicillin G (intravenous form) is the drug of choice for treating infections caused by:
      • Streptococci
      • Meningococci
      • Enterococci
      • Penicillin-susceptible pneumococci
      • Staphylococcus aureus that do not produce beta-lactamases
      • Treponema pallidum (syphilis)
      • Other gram-positive rods
      • Gram-negative anaerobes that do not produce beta-lactamases

    Clinical Uses Continued

    • Penicillin V (oral form) is used for minor infections due to its lower bioavailability and requirement for four doses per day.
    • Amoxicillin is often used instead of penicillin V.
    • Methicillin and nafcillin are used for treating infections caused by beta-lactamase-producing staphylococci.
    • Extended-spectrum penicillins (aminopenicillins, carboxypenicillins) have similar activity to penicillin G but are better against gram-negative bacteria due to their ability to penetrate the outer plasma membrane.

    Adverse Reactions

    • Penicillins are generally safe drugs, but hypersensitivity is the most common adverse drug reaction (ADR).
    • About 5-8% of patients claim to have a penicillin allergy.
    • Less than 1% of patients who have received penicillin will have an allergic reaction with a second exposure.

    Allergic Reactions

    • Anaphylactic shock, a severe allergic reaction, occurs in about 0.05% of patients receiving penicillin.
    • Penicillin is responsible for about 75% of deaths from anaphylactic shock in the United States.
    • Allergic reactions complicate 4% of all treatment courses.

    Allergic Reactions Continued

    • Allergic reactions are found with most penicillins.
    • Reactions include: rash, fever, bronchospasm, vasculitis, serum sickness, dermatitis, anaphylaxis.
    • Exposure to penicillins in food can lead to sensitization and can lead to allergic reactions with subsequent exposures.

    Cephalosporins

    • Discovered on the Italian island of Sardinia.
    • Isolated from a mold growing in sewage outflow.
    • First isolated from the cephalosporium fungus in 1948.
    • Mostly resistant to beta-lactamases.

    Cephalosporins Continued

    • Cephalosporins are classified into generations based on their spectrum of activity:
      • First-generation: Most effective against gram-positive cocci (e.g., staphylococcus, streptococcus)
      • Second-generation: Effective against most gram-positive cocci and some gram-negative bacteria (e.g., Haemophilus)
      • Third-generation: Effective against some gram-positive cocci and most gram-negative bacteria.
      • Fourth-generation: Effective against most gram-positive and gram-negative bacteria.

    Vancomycin

    • A glycopeptide antibiotic that inhibits bacterial cell wall synthesis.
    • Poorly absorbed in the gastrointestinal tract.
    • Administered intravenously.
    • Staphylococcus aureus strains resistant to vancomycin identified in Japan in 1996.

    Vancomycin Continued

    • Vancomycin-resistant enterococci make these infections difficult to treat.
    • Therapeutic drug monitoring (TDM) is important to ensure optimal therapeutic effect and minimize toxicity.
    • Peak concentrations (Cp) should be maintained between 20-40 mcg/mL.
    • Trough concentrations should be between 5-10 mcg/mL.

    Plasma Monitoring

    • Peak Cp levels are used to determine the maximum allowable concentration and to minimize toxicity.
    • Trough Cp levels ensure the dose has cleared before the next dose is administered.
    • This helps to prevent accumulation and toxicity.
    • Dose adjustments are needed for decreased creatinine clearance levels.

    Vancomycin Continued

    • Vancomycin is widely distributed, with good penetration into synovial fluid.
    • Direct injection into infected joints is usually unnecessary.
    • Most of the drug is cleared by the kidneys.
    • Dose adjustments are necessary for decreased kidney function.

    Vancomycin Adverse Drug Reactions (ADRs)

    • ADRs have decreased in recent years because commercial preparations have become more pure.
    • "Red Man Syndrome," a rash or flushing of the face and neck due to histamine release, can occur with rapid IV infusion.
    • The incidence of "Red Man Syndrome" has decreased with slow infusions (1 g over 12 hours) and low doses (1 g).
    • Ototoxicity and nephrotoxicity are possible, and can occur with high drug concentrations.
    • Damage to the 8th cranial nerve (auditory) can lead to deafness.

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    Pharmacology I: Beta-Lactam Antibiotics PDF

    Description

    Explore the discovery and development of beta lactam antibiotics, particularly penicillin, discovered by Alexander Fleming. Understand their mechanism of action, importance in treating infections, and the challenges of bacterial resistance. This quiz will test your knowledge on the key historical figures and chemistry behind these essential medications.

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