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Questions and Answers
What is a primary cause of antibiotic resistance in penicillins?
Which type of bacteria is resistant to ampicillin and amoxicillin without a β-lactamase inhibitor?
Which of the following adverse reactions is most prominent with penicillin use?
Which of these penicillin combinations is administered intravenously or intramuscularly?
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Which condition may result from penicillin use due to its effect on intestinal flora?
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What is a notable characteristic of β-lactam antibiotics in terms of allergy?
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What primarily initiates cell lysis in bacteria?
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What type of bacteria are penicillins ineffective against?
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What is the mechanism of action of penicillin?
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Which of the following natural penicillins is known for poor oral absorption?
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Which of the following penicillins is considered β-lactamase-resistant?
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What condition can amoxicillin prevent during dental surgery?
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What is the primary function of β-lactamase inhibitors like clavulanic acid?
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What are the short peptide chains associated with NAM subunits used for?
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What is a significant risk associated with methicillin use?
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What bacterial structure does penicillin specifically target?
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Which pathogen is associated with vancomycin resistance?
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What do penicillins primarily interfere with regarding bacterial cells?
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Which of the following bacteria is recognized as a carbapenem-resistant organism?
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Which feature differentiates gram-negative bacteria from gram-positive bacteria?
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Which antibiotic class is known as cell wall inhibitors?
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Which mechanism does Acinetobacter baumannii primarily use to escape antibiotic effects?
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What is the primary structure that penicillin-binding proteins (PBPs) cross-link?
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Which bacterial pathogen is known for multidrug resistance and is included in the ESKAPE pathogens?
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What is a key characteristic of water-filled channels (porins) in gram-negative bacteria?
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Study Notes
Cell Wall Inhibitors
- The cell wall of gram-positive bacteria is easily traversed by penicillin, while gram-negative bacteria have an outer lipopolysaccharide membrane that blocks these drugs.
- Penicillin-binding proteins (PBPs) are membrane proteins that cross-link peptidoglycan.
Mechanism of Action
- Penicillins interfere with cross-linking of the peptidoglycan cell wall, resulting in exposure of the osmotically less stable membrane.
- Cell lysis can occur via osmotic pressure or activation of autolysins.
- Penicillins are only effective against rapidly growing organisms that synthesize a peptidoglycan cell wall.
Bacterial Cell Wall
- The bacterial cell wall consists of repeating N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) subunits.
- The NAM subunits have short peptide chains used in cross-linking.
- Penicillin-binding protein (PBP) forms a cross-link with another strand of the bacterial cell wall.
- The PBP dissociates from the wall once the cross-link has been formed.
- Penicillin can enter PBP active sites and react with the serine group.
- The beta-lactam ring of penicillin covalently linked to the PBP permanently blocks the PBP.
Antibacterial Spectrum
-
Natural Penicillins
- Penicillin G and penicillin V
- Susceptible to beta-lactamases.
- Penicillin V has poor oral absorption and is not indicated for bacteremia.
- More acid stable than penicillin G.
-
Antistaphylococcal Penicillins (β-lactamase-resistant penicillins)
- Methicillin, nafcillin, oxacillin, and dicloxacillin.
- Restricted to the treatment of infections caused by penicillinase-producing staphylococci, including methicillin-sensitive Staphylococcus aureus (MSSA).
- Methicillin is toxic (Interstitial nephritis) and is not clinically used anymore.
- No activity against gram-negative infections.
-
Extended-spectrum Penicillins (Semisynthetic penicillins)
- Ampicillin and amoxicillin.
- Similar antibacterial spectrum to penicillin G but are more effective against gram-negative bacilli.
- Treat respiratory infections.
- Amoxicillin prevents bacterial endocarditis during dental surgery.
- Protection from enzymatic hydrolysis by β-lactamase inhibitors (clavulanic acid/sulbactam).
- MRSA can be treated with vancomycin.
-
Antipseudomonal Penicillins
- Piperacillin and ticarcillin
- Effective towards many gram-negative bacilli, but not towards Klebsiella (contains penicillinase).
Resistance
- Inactivation of antibiotic by ß-lactamase (major cause)
- Modification of target PBPs
- Impaired penetration of the drug to target PBPs
- Efflux
Pharmacokinetics of Penicillins
- Administration:
- IV or IM: Ampicillin + sulbactam, ticarcillin + clavulanic acid, piperacillin + tazobactam, nafcillin, oxacillin.
- Oral: Penicillin V, amoxicillin, dicloxacillin
- IM (Depot forms): Procaine penicillin G, benzathine penicillin G - slowly absorbed into circulation and persist at low levels.
Adverse Reactions
- Hypersensitivity (most prominent) - ranging from rashes to angioedema and anaphylaxis.
- Cross-allergic reactions occur among the β-lactam antibiotics.
- Diarrhoea - disruption of the normal balance of intestinal flora.
- Pseudomembranous colitis from Clostridium difficile and other organisms may occur with penicillin use.
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Description
Test your knowledge on the mechanisms of action of cell wall inhibitors, particularly penicillins, and their effects on gram-positive and gram-negative bacteria. This quiz covers the structure of bacterial cell walls, the role of penicillin-binding proteins, and how these antibiotics function against bacterial infections.
