β-Lactam Antimicrobials
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Which of the following is NOT a class of β-Lactam antimicrobials?

  • Cephalosporins
  • Penicillins
  • Macrolides (correct)
  • Carbapenems

What is the primary mechanism of action of β-lactam antibiotics?

  • Inhibiting cell wall synthesis (correct)
  • Disrupting DNA replication
  • Inhibiting protein synthesis
  • Blocking metabolic pathways

How do β-lactams inhibit cell wall synthesis?

  • Preventing RNA transcription
  • Disrupting the cell membrane
  • Interfering with ribosome function
  • Binding to Penicillin Binding Proteins (PBPs) (correct)

True or false: β-lactams are bactericidal against enterococcus.

<p>False (A)</p> Signup and view all the answers

Which factor is determinate for the efficacy of Beta-Lactams?

<p>Time above the MIC (A)</p> Signup and view all the answers

What is the most common mechanism of resistance to beta-lactam antibiotics?

<p>Enzymatic inactivation of antibiotic (C)</p> Signup and view all the answers

What strategy overcomes resistance mediated by β-lactamase?

<p>Combining the antimicrobial with a β-lactamase inhibitor (A)</p> Signup and view all the answers

Which of the following is a natural penicillin?

<p>Penicillin G (C)</p> Signup and view all the answers

Which of the following is an antistaphylococcal penicillin?

<p>Nafcillin (D)</p> Signup and view all the answers

Which bacterial species are NOT typically targeted by Ureidopenicillins?

<p>Streptococci (A)</p> Signup and view all the answers

Which of the following is an example of an aminopenicillin?

<p>Ampicillin (C)</p> Signup and view all the answers

Which of the following antibiotics has a long half-life?

<p>Ceftriaxone (A)</p> Signup and view all the answers

What is a primary advantage of cephalosporins over some other antibiotic classes?

<p>They exhibit broader spectrum of activity due to stability against β-lactamases (D)</p> Signup and view all the answers

First-generation cephalosporins are typically most effective against which type of bacteria?

<p>Gram-positive cocci (B)</p> Signup and view all the answers

Which of the following combinations includes a beta-lactamase inhibitor?

<p>Ampicillin/sulbactam (A)</p> Signup and view all the answers

Against which bacteria are penicillins effective?

<p>Streptococci (B)</p> Signup and view all the answers

Which type of infections are commonly treated with first-generation cephalosporins?

<p>Skin and skin-structure infections (C)</p> Signup and view all the answers

Second-generation cephalosporins have enhanced activity against which of the following?

<p>Gram-negative bacteria and anaerobic bacteria (D)</p> Signup and view all the answers

Which of the following is a common use for second-generation cephalosporins?

<p>Treatment of colorectal infections (D)</p> Signup and view all the answers

Third-generation cephalosporins generally have enhanced activity against:

<p>Gram-negative bacteria (B)</p> Signup and view all the answers

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

<p>Good activity against both Gram-positive and Gram-negative bacteria (D)</p> Signup and view all the answers

What range does cross-reactivity between different β-Lactams typically fall within?

<p>Between 1 and 10% (C)</p> Signup and view all the answers

For individuals with more serious allergic reactions, how does cross-reactivity appear?

<p>Cross-reactivity appears higher. (D)</p> Signup and view all the answers

For which patients is Aztreonam typically reserved?

<p>Those with serious allergies (A)</p> Signup and view all the answers

What type of hypersensitivity is antimicrobial desensitization designed to address?

<p>Type I, IgE mediated (D)</p> Signup and view all the answers

What is the general starting dose of antibiotics during antimicrobial desensitization, relative to a full dose?

<p>Generally 1/10,000 to 1/100,000 of full dose. (B)</p> Signup and view all the answers

Which of the following organisms is NOT typically covered by cephalosporins?

<p>Enterococci (C)</p> Signup and view all the answers

Which carbapenem does NOT cover Pseudomonas aeruginosa (PSAE)?

<p>Ertapenem (C)</p> Signup and view all the answers

What is a common risk factor for QT prolongation leading to Torsades de Pointes (TdP)?

<p>Female sex (D)</p> Signup and view all the answers

What is a key characteristic of aztreonam's spectrum of activity?

<p>Gram-negative ONLY (A)</p> Signup and view all the answers

For what type of infections are carbapenems often considered the 'drug of choice'?

<p>ESBLs and inducible Amp-C producers (B)</p> Signup and view all the answers

Which electrolyte abnormality is associated with an increased risk of QT prolongation?

<p>Hypokalemia (B)</p> Signup and view all the answers

According to post-marketing reports, which class of antimicrobials was most frequently associated with Torsades de Pointes?

<p>Macrolides (A)</p> Signup and view all the answers

A patient reports a penicillin allergy. Which antibiotic class would be the MOST appropriate to use, if a beta-lactam is still desired?

<p>Monobactams (B)</p> Signup and view all the answers

Which of the following factors can contribute to QT prolongation?

<p>Concurrent administration of other QT prolonging agents (B)</p> Signup and view all the answers

Which of the following is the MOST common type of allergic reaction to antimicrobials?

<p>Maculopapular rash (B)</p> Signup and view all the answers

Which patient population is MOST likely to have a high rate of hypersensitivity to Bactrim?

<p>Patients with HIV (C)</p> Signup and view all the answers

Which macrolide is considered to be the safest in terms of P450 interactions and QT prolongation?

<p>Azithromycin (C)</p> Signup and view all the answers

Which of the following quinolones has undergone the most testing regarding QT prolongation?

<p>Moxifloxacin (C)</p> Signup and view all the answers

What is a potential reason for overestimation of cross-reactivity among beta-lactam antibiotics?

<p>Inaccurate patient reporting of allergies (B)</p> Signup and view all the answers

Which of the following is a symptom of seizure activity often associated with antibiotic use?

<p>Myoclonus (D)</p> Signup and view all the answers

Which of the following antibiotic classes is known to have epileptogenic effects due to alterations in GABA activity?

<p>Penicillins (B)</p> Signup and view all the answers

Which of the following is a common adverse effect associated with quinolone antibiotics?

<p>Photosensitivity (B)</p> Signup and view all the answers

Which class of antibiotics is known to commonly cause QT prolongation?

<p>Macrolides (A)</p> Signup and view all the answers

What is the primary target of quinolone antibiotics?

<p>DNA gyrase and topoisomerase IV (A)</p> Signup and view all the answers

What is a key mechanism of action for macrolide antibiotics?

<p>Interference with protein synthesis (B)</p> Signup and view all the answers

Which type of allergic reaction involves IgE antibodies and can cause immediate hypersensitivity?

<p>Type I (B)</p> Signup and view all the answers

Flashcards

β-Lactams MOA

Inhibit bacterial cell wall synthesis by binding to Penicillin Binding Proteins (PBPs), blocking transpeptidation (cross-linking).

β-Lactam Classes

Penicillins, cephalosporins, carbapenems, and monobactams.

β-Lactam Efficacy

Time above the minimum inhibitory concentration (MIC).

β-Lactams Action

Bactericidal, meaning they kill bacteria directly.

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β-Lactams: Non-Renal Elimination

Nafcillin, oxacillin, ceftriaxone, and cefoperazone.

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Renal Function and Beta-Lactams

Many beta-lactams require monitoring due to potential kidney issues.

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Beta-Lactam Half-Life

Most beta-lactams are administered frequently due to their short half-life.

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Antibiotic Resistance Mechanisms

Bacteria can neutralize antibiotics via enzymes, modify their targets, reduce drug entry or actively pump the drug out.

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Beta-Lactamase Production

The production of enzymes that break down beta-lactam antibiotics by bacteria.

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Beta-Lactamase Inhibitors Strategy

Adding a beta-lactamase inhibitor enables the antibiotic to bypass the bacterial resistance.

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β-Lactamase Inhibitors Function

Overcome β-lactamase-mediated resistance.

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Natural Penicillins

Include Penicillin G, benzathine and VK.

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Anti-staphylococcal Penicillins

Include Nafcillin, oxacillin, methicillin and dicloxacillin.

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Ureidopenicillins

Enhanced gram-negative bacteria (GNB) coverage, including Pseudomonas aeruginosa (PSAE).

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Beta-lactamase Inhibitors

Drugs combined with beta-lactam antibiotics to protect them from breakdown by bacterial beta-lactamase enzymes, extending their spectrum of activity.

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Cephalosporin Generations

Classified into generations based on their spectrum of activity and stability against beta-lactamases.

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First-Generation Cephalosporins

Primarily target gram-positive cocci. Used for skin/soft tissue infections, surgical prophylaxis, UTIs, and endocarditis.

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Second-Generation Cephalosporins

Improved gram-negative and some anaerobic coverage while retaining some gram-positive activity. Treats RTI's.

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Third-Generation Cephalosporins

Enhanced gram-negative activity but less gram-positive and anaerobic activity.

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SPACE Bugs

Serratia, Pseudomonas, Acinetobacter, Citrobacter, Enterobacter. These bugs may show resistance to 3rd gen cephalosporins.

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Fourth and Fifth Generation Cephalosporins

Good gram-negative and gram-positive activity.

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Cefepime

4th generation cephalosporin; some stability against ESBL and Amp-C producers.

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Ceftaroline

5th generation cephalosporin; effective against MRSA.

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Carbapenems

Broadest spectrum antibiotics; effective against MSSA, Enterobacteriaceae, ESBL producers, and more.

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Ertapenem limitations

Ertapenem does not cover Pseudomonas aeruginosa or Enterococcus.

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Aztreonam

Reserved for penicillin-allergic patients; active against gram-negative bacteria only.

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Common Allergic Reaction to Antibiotics

Maculopapular rash occurring days to weeks after exposure.

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Populations with Higher Allergy Risk

Patients with HIV, CF, or mononucleosis

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β-Lactam Allergy Cross-Reactivity

Cross-reactivity between beta-lactams may be overestimated due to historical manufacturing impurities.

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β-Lactam Cross-Reactivity

Cross-reactivity between different β-Lactams ranges from 1-10%, but tends to be closer to 1% in reality.

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β-Lactam Allergy Severity

Cross-reactivity is higher in individuals with more serious reactions: 10% with rash, 20% with hives, 40-50% with anaphylaxis.

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Aztreonam Use

Since Aztreonam is missing the reactive "house portion", it less likely to cause a reaction and therefore reserved for individuals with serious allergies.

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Antimicrobial Desensitization

A procedure that allows administration of antibiotics to patients with severe allergic reactions (i.e., hives, anaphylaxis).

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Desensitization Dosing

Starting antibiotic dose during desensitization is generally 1/10,000 to 1/100,000 of the full dose and increased slowly over time.

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QTC Change

Change in QTC interval can vary among individuals due to differing susceptibilities.

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QT Prolongation

Prolongation of the QT interval, increasing the risk of Torsades de Pointes (TdP).

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TdP Risk Factors

Female sex, heart disease, hypokalemia, and drug interactions are common.

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Macrolides and TdP

Macrolides accounted for a large percentage of Torsades de Pointes cases in FDA post-marketing reports.

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QT Prolongation Multifactorial

Concurrent QT prolonging agents, electrolyte abnormalities, advanced age, cardiac disease, and organ dysfunction.

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Safest Macrolide

Azithromycin is considered the safest macrolide regarding QT prolongation due to minimal P450 interactions.

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Antibiotics & Seizures

Antibiotics can alter GABA activity, leading to increased seizure risk.

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Penicillin & Seizures

Penicillin's epileptogenic potential is exacerbated by renal insufficiency and high doses.

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Macrolide MOA

Macrolides inhibit bacterial protein synthesis by binding to the 23S rRNA of the 50S ribosomal subunit.

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Quinolone MOA

Quinolones inhibit bacterial DNA replication by targeting DNA gyrase and topoisomerase IV enzymes.

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Macrolide Spectrum

Macrolides' activity covers atypical bacteria (Legionella, Mycoplasma, Chlamydia) and some gram-positive organisms.

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Quinolone Spectrum

Quinolone's activity covers broad-spectrum Gram-negative and Gram-positive bacteria, including some atypical organisms.

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QT Prolongation Risk

Some antimicrobials can prolong the QT interval, increasing the risk of Torsades de Pointes.

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Study Notes

Beta-Lactams Structures

  • Penicillin contains these groups: beta-lactam ring, CH₃, C=0, N-H, and COOH
  • Cephalosporin contains these groups: beta-lactam ring, C=0, N-H, and R₂
  • Imipenem contains these groups: beta-lactam ring, OH, C=0, N-H, and SCH₂CH₂NH
  • Clavulanate contains these groups: beta-lactam ring, CHCH₂OH and COOH

B-lactam Structures

  • The family tree of B-lactam antibiotics includes Penicillins (1940-), Cephalosporins(1948-) Cephamycins (1971-) Cephabacins (1985-), Carbapenems (1976-), Monobactams (1981-)

Penicillin Classification

  • Natural penicillins are decent against staph and strep, but bacteria are increasingly resistant

Third generation

  • Serratia, Pseudomonas, Acinetobacter, Citrobacter, and Enterobacter are commonly referred to as "SPACE Bugs."

Cephalosporin Spectrum

  • All cephalosporins lack clinically useful activity against enterococci, Listeria monocytogenes, and atypical respiratory pathogens (Legionella, Mycoplasma, and Chlamydophila spp.).

Quinolones - Precautions

  • All quinolones can result in tendon rupture.

Spectrum and Indications

  • Cipro is ineffective for strep pneumo

Spectrum and Indications

  • Main symptoms of infections, Pneumonia,
  • Include coughing with sputum or phlegm, shortness of breath and chect pain
  • Central Nervous symptoms are headaches
  • Joint pain

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Antibacterial Pharmacology Phar506 Lecture PDF

Description

Explore the key aspects of β-Lactam antimicrobials and their mechanisms. This lesson covers their mechanism of action, resistance, and the different types of penicillins and cephalosporins. Test your knowledge of these important antibiotics.

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