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Questions and Answers
What is the primary reason for the higher production of β-lactamases in gram-positive bacteria compared to gram-negative bacteria?
What is the primary reason for the higher production of β-lactamases in gram-positive bacteria compared to gram-negative bacteria?
- Presence of β-lactamases in the inner membrane
- Higher availability of antibiotics in gram-positive bacteria
- Greater genetic variability in gram-positive bacteria
- Secretion of enzymes in larger quantities (correct)
Where are β-lactamases located in gram-negative bacteria that contribute to their resistance?
Where are β-lactamases located in gram-negative bacteria that contribute to their resistance?
- Cell wall
- Cytoplasmic membrane
- Periplasmic space (correct)
- Outer membrane vesicles
Which factor contributes to bacterial resistance to β-lactam antibiotics?
Which factor contributes to bacterial resistance to β-lactam antibiotics?
- The inability of the antibiotic to reach effective concentrations (correct)
- Increased permeability of the outer membrane
- Inherent susceptibility to other antibiotic classes
- Presence of ribosomes in the cell membrane
How is the gene for staphylococcal penicillinase commonly transferred between bacteria?
How is the gene for staphylococcal penicillinase commonly transferred between bacteria?
What type of resistance alteration is more common among gram-positive bacterial pathogens?
What type of resistance alteration is more common among gram-positive bacterial pathogens?
What is one way that bacteria can acquire resistance to β-lactam antibiotics?
What is one way that bacteria can acquire resistance to β-lactam antibiotics?
How do β-lactam antibiotics primarily exert their effect on bacteria?
How do β-lactam antibiotics primarily exert their effect on bacteria?
What structural feature of the bacterial cell wall varies significantly between gram-positive and gram-negative bacteria?
What structural feature of the bacterial cell wall varies significantly between gram-positive and gram-negative bacteria?
What genetic mechanism allows for the transfer of low-affinity PBPs among different bacterial species?
What genetic mechanism allows for the transfer of low-affinity PBPs among different bacterial species?
What mechanism is attributed to methicillin-resistant Staphylococcus aureus (MRSA) acquiring resistance?
What mechanism is attributed to methicillin-resistant Staphylococcus aureus (MRSA) acquiring resistance?
Which component is NOT found in the structure of Gram-negative bacteria?
Which component is NOT found in the structure of Gram-negative bacteria?
What role does β-Lactamase play in bacterial resistance?
What role does β-Lactamase play in bacterial resistance?
Which of the following accurately describes the peptidoglycan layer in bacteria?
Which of the following accurately describes the peptidoglycan layer in bacteria?
What is the function of porin channels in Gram-negative bacteria?
What is the function of porin channels in Gram-negative bacteria?
Which of the following structures is specific to Gram-positive bacteria?
Which of the following structures is specific to Gram-positive bacteria?
What is the primary purpose of the plasma membrane in bacteria?
What is the primary purpose of the plasma membrane in bacteria?
What is a unique feature of the cell wall in Gram-negative bacteria compared to Gram-positive bacteria?
What is a unique feature of the cell wall in Gram-negative bacteria compared to Gram-positive bacteria?
Which amino acid is NOT part of the peptidoglycan layer's structure?
Which amino acid is NOT part of the peptidoglycan layer's structure?
Which of the following β-lactamase inhibitors is coformulated with ceftazidime?
Which of the following β-lactamase inhibitors is coformulated with ceftazidime?
What type of β-lactamases do avibactam and relebactam inhibit?
What type of β-lactamases do avibactam and relebactam inhibit?
What structural component is the chief requirement for the biological activity of penicillins?
What structural component is the chief requirement for the biological activity of penicillins?
Which β-lactamase inhibitor is coformulated with meropenem?
Which β-lactamase inhibitor is coformulated with meropenem?
What is the role of multi-drug efflux pumps in gram-negative bacteria?
What is the role of multi-drug efflux pumps in gram-negative bacteria?
Which of the following statements about β-lactamase inhibitors is FALSE?
Which of the following statements about β-lactamase inhibitors is FALSE?
What drives the energy for the operation of antibiotic efflux pumps in gram-negative bacteria?
What drives the energy for the operation of antibiotic efflux pumps in gram-negative bacteria?
Study Notes
Cell Envelope Disruptors: β-Lactam, Glycopeptide, and Lipopeptide Antibacterials
- β-Lactams: A major class of antibiotics, including penicillins, cephalosporins, carbapenems, and monobactams. They share a common structure (β-lactam ring) and mechanism: inhibiting bacterial peptidoglycan cell wall synthesis.
- Mechanism of Action: β-lactams inhibit the final step in peptidoglycan synthesis, acylating the transpeptidase (penicillin-binding proteins, PBPs) by cleaving the -CO-N- bond in the β-lactam ring.
- Bacterial Resistance Mechanisms: Bacteria can develop resistance to β-lactams via mutations affecting PBP affinity for the antibiotic, decreased antibiotic concentration at the target site, or enzymatic degradation by β-lactamases.
- β-lactamase Inhibitors: Molecules that bind to β-lactamases to prevent them from inactivating β-lactam antibiotics. Examples include clavulanate, sulbactam, tazobactam, avibactam, vaborbactam, and relebactam.
- Penicillins: A subset of β-lactams with a varied spectrum, classified by their resistance to penicillinases (e.g., penicillin G, penicillinase-resistant penicillins, aminopenicillins, and antipseudomonal penicillins).
- Cephalosporins: Another β-lactam class, generally more resistant to β-lactamases than penicillins, categorized into generations of increasing gram-negative activity.
- Other β-lactam antibiotics: Carbapenems (broad spectrum, resistant to many β-lactamases), imipenem + cilastatin).
- Glycopeptides: A class of antibiotics (e.g., vancomycin, teicoplanin, lipoglycopeptides) that target bacterial cell wall synthesis.
- Mechanism of glycopeptide action: They target the D-alanyl-D-alanine terminus of peptidoglycans hindering both transpeptidase and transglycosidase function.
- Lipopeptides: A class of antibiotics (e.g., daptomycin) that disrupt bacterial cell membranes, causing depolarization, and leading to cell death.
- Mechanism of lipopeptide action: Daptomycin targets the bacterial inner membrane, leading to depolarization and cell death.
- Bacitracin: A polypeptide antibiotic effective against many Gram-positive bacteria, used topically.
β-Lactamase Inhibitors
- Clavulanic Acid: A mechanism-based inhibitor of many β-lactamases, coformulated with amoxicillin.
- Sulbactam: A β-lactamase inhibitor coformulated with ampicillin.
- Tazobactam: A β-lactamase inhibitor coformulated with piperacillin.
- Avibactam, vaborbactam, relebactam: Newer β-lactamase inhibitors with wider spectra.
Penicillins
- Penicillin G, Penicillin V: Natural penicillins effective against some Gram-positive bacteria, but easily hydrolyzed by penicillinase.
- Penicillinase-Resistant Penicillins: More stable to penicillinases.
Cephalosporins
- Generations: Categorized based on antibacterial activity against Gram-positive/negative bacteria. Later generations offer greater activity against gram-negative organisms.
- First Generation: Cefazolin, cephalexin.
- Second Generation: Cefuroxime, cefoxitin, cefotetan.
- Third Generation: Cefotaxime, ceftriaxone, cefdinir, cefpodoxime.
- Fourth Generation: Cefepime
- Fifth Generation: Ceftaroline
- Antipseudomonal: Ceftazidime, ceftolozane/tazobactam, cefepime.
Other Cell Envelope Disruptors
- Glycopeptides: Vancomycin, teicoplanin, lipoglycopeptides
- Lipopeptides: Daptomycin
- Bacitracins: Often used topically; less common in systemic use.
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