L-21 Cell Wall Synthesis Inhibitors 3

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Questions and Answers

Which of the following best describes the mechanism of action of polymyxins against bacteria?

Inhibition of nucleic acid synthesis by binding to DNA gyrase.

Disruption of bacterial cell membranes through interaction with phospholipids. (correct)

Inhibition of cell wall synthesis by preventing D-alanine incorporation.

Interference with bacterial protein synthesis by binding to ribosomes.

Why are polymyxins primarily restricted to topical, ophthalmic, and otic use rather than systemic administration?

They are poorly absorbed when administered systemically.

They are rapidly metabolized in the systemic circulation.

Their effectiveness is limited to localized infections.

Their high nephrotoxicity, neurotoxicity and poor tissue distribution limit systemic use. (correct)

What is a key structural feature of cycloserine that contributes to its mechanism of action?

It is a lipopeptide which inserts into the cell membrane.

It is a glycopeptide that inhibits cell wall synthesis.

It is a cationic basic peptide.

It is a structural analogue of D-alanine. (correct)

Which of the following mechanisms best describes how vancomycin inhibits bacterial cell wall synthesis?

Directly binds to D-alanyl-D-alanine precursors, blocking peptidoglycan polymerization (C) Signup and view all the answers

Which statement best describes the mechanism of action of cycloserine?

It blocks the incorporation of D-alanine into peptidoglycans. (D) Signup and view all the answers

Which of the following is NOT a primary clinical indication for parenteral vancomycin use?

Treatment of uncomplicated UTI in women (D) Signup and view all the answers

What is the primary clinical use of cycloserine as an antibiotic?

Treatment of tuberculosis caused by M. tuberculosis resistant to first-line agents. (A) Signup and view all the answers

Why is vancomycin used orally to treat Clostridium difficile infections, while other systemic infections are treated parenterally?

Vancomycin is not absorbed systemically when given orally and acts locally in the gut. (A) Signup and view all the answers

What is a major adverse effect associated with cycloserine therapy?

CNS toxicity, including tremors, psychosis, and convulsions. (A) Signup and view all the answers

What is the primary mechanism of fosfomycin in inhibiting cell wall synthesis?

Inhibits enolpyruvate transferase, preventing formation of N-acetylmuramic acid (A) Signup and view all the answers

Which of the following is NOT a common use for a triple antibiotic ointment containing bacitracin, polymyxin, and neomycin?

Irrigation of wounds and pleural cavity. (B) Signup and view all the answers

Which characteristic of polymyxins explains their ability to disrupt bacterial cell membranes?

They are cationic basic peptides with amphipathic properties. (C) Signup and view all the answers

Which of the following best describes the clinical use of bacitracin, given its pharmacological properties?

Topical application for local bacterial infections (A) Signup and view all the answers

A patient on vancomycin develops flushing, erythema. Which adverse effect of vancomycin is most likely present?

Red man or red neck syndrome (A) Signup and view all the answers

What is a major difference in the mechanism of action of fosfomycin and vancomycin regarding bacterial cell wall synthesis?

Fosfomycin targets a precursor to cell wall synthesis while vancomycin interferes with peptidoglycan polymerization (C) Signup and view all the answers

What is the implication of plasmid-mediated resistance to vancomycin?

Resistance can be transferred horizontally, to other bacteria via plasmids (C) Signup and view all the answers

Study Notes

Cell Wall Synthesis Inhibitors (Part III): Miscellaneous Inhibitors

Vancomycin (Vancocin, Vancoled):
- A tricyclic glycopeptide used orally and parenterally
- Effective against methicillin-resistant staphylococcal infections and sepsis or endocarditis caused by Staphylococcus
- Acts by inhibiting the synthesis of cell wall phospholipids and peptidoglycan polymerization by binding to D-alanyl-D-alanine cell wall precursors
- Restricted to serious infections caused by beta-lactam-resistant Gram-positive bacteria (e.g., Streptococcus and Staphylococcus)
- Used in enterococcal infections synergistically with aminoglycosides for better bactericidal effect (especially E. faecium and E. faecalis)
- Used in Clostridium difficile-induced colitis (orally)
- Also used prophylactically in dental surgeries involving prosthetic devices
- Resistance is plasmid-mediated
- Administered intravenously (slow I.V) in systemic infections
- Excretion is primarily via glomerular filtration (more than 90%)
- Orally administered for antibiotic-induced pseudomembranous colitis
- Adverse effects include fever, chills, phlebitis, and mild ototoxicity and nephrotoxicity (risk increased with concurrent aminoglycoside use)
- "Red man" or "red neck" syndrome (histamine release-induced flushing) is a common adverse reaction
Fosfomycin (Phosphonomycin, Monurol):
- Inhibits cell wall synthesis at a very early stage
- An analog of phosphoenolpyruvate, inhibiting enolpyruvate transferase
- Prevents the formation of N-acetyl muramic acid
- Effective against both Gram-positive and Gram-negative organisms
- Approved for single, oral dose (3 grams) treatment of uncomplicated urinary tract infections (UTIs) in women
- Safe during pregnancy
Bacitracin:
- A mixture of polypeptides inhibiting cell wall synthesis
- Active against a variety of Gram-positive cocci and bacilli
- Primarily used topically due to significant nephrotoxicity if administered systemically (proteinuria, hematuria, nitrogen retention)
- Poorly absorbed, resulting in localized antibacterial activity without significant systemic toxicity
- Often combined with polymyxin and neomycin in ointment formulations for dermatologic and ophthalmic infections
- Can be employed in irrigation solutions for joints, wounds, and pleural cavities
Polymyxin B, Polymyxin E (Colistin):
- Peptides active against Gram-negative bacteria, but restricted to treating only Gram-negative infections
- Due to nephrotoxicity, only Polymyxin B is commonly used in the USA; Polymyxin B and E are used in other regions
- Bactericidal, disrupting bacterial cell membranes by attaching to them via cationic interactions
- Disrupts phospholipid-based membranes, also inactivating endotoxins
- Gram positives (e.g. Proteus, Neisseria) show resistance
- Primarily used topically and ophthalmically due to high nephro- and neurotoxicity
- Often combined with other antibiotics like Neomycin and Bacitracin for skin infections
- Rarely associated with local reactions or hypersensitivity
Cycloserine (Seromycin):
- Water-soluble antibiotic readily absorbed orally
- Active against many Gram-positive and Gram-negative bacterial strains
- Primarily used to treat tuberculosis caused by M. tuberculosis strains resistant to first line agents
- Structural analog of D-alanine, inhibits enzymes (alanine racemase and alanine synthetase) converting L-alanine to D-alanine in the peptidoglycan synthesis process
- Widely distributed in tissues, specifically in the case of Mycobacteria
- Excreted in active form via the urine
- Adverse effects include central nervous system (CNS) toxicity: Headaches, tremors, psychosis, and convulsions.
Daptomycin (Cubicin):
- Bactericidal lipopeptide antibiotic
- Disrupts bacterial cell membranes and inhibits protein and DNA synthesis
- Used for complicated skin and skin structure infections and bacteremia caused by Staphylococcus aureus, including endocarditis
- Action similar to linezolid and quinupristin/dalfopristin (for Gram-positive resistant organisms, like MRSA and VRE)
- Inactivated by pulmonary tissue, not used for pneumonia treatment
Telavancin (Vibativ):
- Bactericidal lipoglycopeptide antibiotic structure similar to vancomycin
- Dual mechanism of action similar to daptomycin and vancomycin
- Used for treating complicated skin and skin structure infections and nosocomial and ventilator-associated pneumonia caused by MRSA
- Can cause renal impairment and interfere with anticoagulation tests; contraindicated in pregnancy; associated with some cardiac abnormalities

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