Glycopeptides and Their Mechanism of Action

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Questions and Answers

Which glycopeptide antibiotic is primarily active against multi-resistant gram-positive bacteria?

Vancomycin (correct)

Fosfomycin

Cycloserine

Telavancin

What is the mechanism of action of glycopeptide antibiotics?

Block peptidoglycan cross-linking (correct)

Disrupt bacterial protein synthesis

Inhibit DNA replication

Prevent mRNA transcription

Why are glycopeptide antibiotics ineffective against gram-negative bacteria?

They are only active orally

They are not bactericidal

Their molecules are too large to penetrate the outer membrane (correct)

They inhibit protein synthesis

Which of the following antibiotics can be used orally for treating Clostridium difficile infections?

Vancomycin (D) Signup and view all the answers

What common problem is associated with Fosfomycin?

It has a high incidence of developing bacterial resistance. (D) Signup and view all the answers

In what situation is Cycloserine primarily used?

Second-line treatment for tuberculosis (D) Signup and view all the answers

Which of the following lipoglycopeptides has a prolonged half-life and is used for acute bacterial skin infections?

Oritavancin (B) Signup and view all the answers

What type of infections are telebancin, Dalbavancin, and Oritavancin typically prescribed for?

Acute bacterial skin and soft tissue infections (D) Signup and view all the answers

What effect does aminoglycosides have on bacteria?

Bactericidal (D) Signup and view all the answers

Which antibiotic class blocks tRNA binding to the ribosome?

Tetracyclines (C) Signup and view all the answers

What is the mechanism of action for chloramphenicol?

Blocks peptidyltransferase (A) Signup and view all the answers

Which of the following antibiotics can have a bactericidal effect depending on the concentration and organism?

Streptogramins (A) Signup and view all the answers

What is the primary target site for macrolides and ketolides?

50S ribosomal subunit (D) Signup and view all the answers

Which antibiotic shares a mechanism of action similar to macrolides?

Lincosamides (A) Signup and view all the answers

What is the effect of oxazolidinones on bacteria?

Both bactericidal and bacteriostatic (C) Signup and view all the answers

What causes premature release of peptide chains in streptogramins?

Disruption of peptide elongation (B) Signup and view all the answers

Which substance does bacitracin inhibit during its mechanism of action?

Regeneration of a lipid carrier (A) Signup and view all the answers

What type of infections is isoniazid primarily used to treat?

Infections with Mycobacterium tuberculosis (D) Signup and view all the answers

Why are polymyxins considered to be primarily used as a last alternative?

They are relatively neurotoxic and nephrotoxic (B) Signup and view all the answers

What mechanism do polymyxins utilize to disrupt bacterial cell membranes?

Formation of abnormal membrane openings (B) Signup and view all the answers

What structural feature allows polymyxins to specifically target gram-negative bacteria?

Negatively charged phosphate groups on lipopolysaccharides (A) Signup and view all the answers

In what form are polymyxins used to treat certain infections?

As cream or drops for external use (B) Signup and view all the answers

What serious side effect is associated with excessive use of bacitracin?

Kidney damage (A) Signup and view all the answers

What is the primary use of Streptogramins such as quinupristin/dalfopristin?

Treatment of vancomycin-resistant infections (B) Signup and view all the answers

Which characteristic distinguishes fluoroquinolones from other quinolones?

Substitution with fluorine (B) Signup and view all the answers

Which statement about the mechanisms of action of fluoroquinolones is true?

They inhibit bacterial DNA topoisomerase II and IV. (D) Signup and view all the answers

What is a key feature of the first generation of quinolones?

They are less effective than subsequent generations. (B) Signup and view all the answers

What are the common conditions treated by second generation quinolones?

Uncomplicated urinary tract infections and skin infections (B) Signup and view all the answers

Which of the following is NOT a characteristic of pseudomembranous colitis?

It is an infection of the upper respiratory tract. (A) Signup and view all the answers

What is a common adverse effect of antibiotic treatments for infections caused by Clostridium difficile?

Pseudomembranous colitis (B) Signup and view all the answers

What is the primary purpose of rifampicin in medical treatment?

For the treatment of tuberculosis (D) Signup and view all the answers

Which antibiotic is primarily effective against community-acquired pneumonia caused by penicillin-sensitive S. pneumoniae?

Levofloxacin (A) Signup and view all the answers

What notable side effect can occur due to rifampicin usage?

Urine turns orange (C) Signup and view all the answers

What mechanism do sulfonamides and trimethoprim use to affect bacteria?

Block enzyme substrates in metabolic pathways (C) Signup and view all the answers

How do bacteria develop resistance when rifampicin is used alone?

Through the appearance of resistant mutants (D) Signup and view all the answers

Which of the following conditions is treated using moxifloxacin?

Nosocomial pneumonia (A) Signup and view all the answers

What is the role of tetrahydrofolate in bacterial cells?

It's needed for the synthesis of folic acid, DNA, and RNA (D) Signup and view all the answers

What is a common usage of the combination of sulfonamides and trimethoprim?

For antibacterial synergistic effect (C) Signup and view all the answers

What is the main action of β-lactam antibiotics on bacterial cells?

Interfere with transpeptidation reactions (C) Signup and view all the answers

Which of the following penicillins is specifically obtained from the fermentation of a fungus?

Penicillin G (A) Signup and view all the answers

What is a significant disadvantage of penicillin G?

Can be hydrolyzed by β-lactamases and acids (B) Signup and view all the answers

Which term describes the proteins that β-lactams target to inhibit bacterial cell wall synthesis?

Penicillin-binding proteins (B) Signup and view all the answers

Why are semisynthetic penicillins like amoxicillin used?

They have a broader spectrum of activity (A) Signup and view all the answers

Which mechanism of action is primarily associated with antibacterial agents that inhibit cell wall synthesis?

Inhibition of cell wall synthesis (A) Signup and view all the answers

What type of antibacterial agent is isoniazid primarily classified as regarding its spectrum of action?

Narrow spectrum (C) Signup and view all the answers

Which class of antibiotics is best known for its ability to effectively interact with the bacterial cell wall?

Beta-lactams (D) Signup and view all the answers

What characteristic defines broad spectrum antibacterial agents?

They target a wide variety of microbial species. (D) Signup and view all the answers

What is a common mechanism of action used by antibacterial drugs that function as antimetabolites?

Inhibition of metabolic pathways (A) Signup and view all the answers

Which type of antibacterial agent acts on a limited group of microorganisms?

Narrow spectrum (C) Signup and view all the answers

Which function of antibacterial agents distinguishes bactericidal agents from bacteriostatic agents?

Bactericidal agents kill bacteria. (A) Signup and view all the answers

What part of bacterial cells do antibacterials that affect the cell wall primarily target?

Peptidoglycan layer (D) Signup and view all the answers

Which mechanism of action do tetracyclines operate through?

Inhibition of protein synthesis (D) Signup and view all the answers

Which stage of peptidoglycan biosynthesis involves the insertion of the disaccharide pentapeptide into the cell wall?

Transglycosylation (D) Signup and view all the answers

Why do mammalian cells generally show excellent selective toxicity to antibiotics that interfere with peptidoglycan synthesis?

They lack a cell wall. (C) Signup and view all the answers

At what stage are inhibitors of cell wall synthesis most effective?

When bacteria are actively growing (C) Signup and view all the answers

Which of the following antibacterial classes includes penicillins, cephalosporins, and carbapenems?

β-Lactam antibacterials (C) Signup and view all the answers

In which stage does the fusion of cell wall precursors through their peptides take place?

Transpeptidation (C) Signup and view all the answers

What effect do antibiotics that interfere with cell wall synthesis have on bacterial cells?

They create weak points and make cells osmotically fragile. (B) Signup and view all the answers

What is the primary function of the rigid layer of peptidoglycan in bacteria?

Provide structural support against environmental pressure (B) Signup and view all the answers

Study Notes

Glycopeptides

Vancomycin and teicoplanin are large molecules that inhibit cell wall synthesis at the second and third stages
They directly bind to the D-alanyl-D-alanine portion of the pentapeptide, leading to blocking transglycosylation and transpeptidation
This prevents peptidoglycan cross-linking, similar to the effect of β-lactams
Glycopeptides are not active against gram-negative bacteria due to their large size, which prevents them from penetrating the outer membrane
They are bactericidal and primarily effective against gram-positive bacteria, particularly against multi-resistant strains such as MRSA/MRSE
They are used for serious infections in individuals with penicillins allergies
They are not active orally, but are used to treat Clostridium difficile infections of the bowel
Lipoglycopeptides, including Telavancin (short-acting), Dalbavancin, and Oritavancin (long-acting) are derivatives of glycopeptides with long half-lives (150-250 h)
These are prescribed for acute bacterial skin and soft tissue infections, with doses ranging from twice per week to once a week

Miscellaneous Cell Wall Inhibitors

Fosfomycin:
- Inhibits the first step in peptidoglycan synthesis, preventing NAM formation from NAG
- Limited use for lower urinary tract infections (cystitis)
- High incidence of bacterial resistance
Cycloserine:
- Affects peptidoglycan synthesis by inhibiting enzymes responsible for D-alanine formation from L-alanine in the bacterial cytoplasm
- Prevents the formation of D-alanyl-D-alanine dipeptide, a crucial component of peptidoglycan
- Used as a second-line drug in tuberculosis treatment, only when first-line drugs are ineffective due to its neurological side effects
Bacitracin:
- Prevents the dephosphorylation of bactoprenol, a phospholipid responsible for transporting peptidoglycan subunits across the cell membrane
- This blocks the regeneration of the lipid carrier and inhibits cell wall synthesis
- Useful for treating superficial skin infections, but systemic use is limited due to kidney damage
Isoniazid:
- Interferes with the synthesis of mycolic acid, a component of the cell wall of acid-fast organisms (Mycobacterium tuberculosis)
- Effective in treating infections with Mycobacterium tuberculosis

Antibacterial Drugs Affecting the Bacterial Cell Membrane

Few antimicrobial compounds target the cell membrane due to the similarities between bacterial and human membranes, leading to difficulties in selective toxicity
Polymyxins:
- Polymyxin B and E (colistin) are cyclic peptides with a hydrophobic tail and positively charged amino groups
- Act like cationic detergents, disrupting the phospholipid structure of the cell membrane
- Form abnormal openings in the membrane, causing leakage
- Active against gram-negative bacteria, specifically targeting negatively charged lipopolysaccharide molecules found in their outer membranes
- Relatively neurotoxic and nephrotoxic, so used only as a last resort
- Typically used for infections caused by multi-drug resistant Pseudomonas aeruginosa or carbapenemase-producing Enterobacteriaceae
- Not absorbed orally, used for infantile diarrhea (colistin) and topically for eye infections, otitis externa

Antibacterial Drugs that Inhibit Protein Synthesis

Target various sites on both the 30S and 50S ribosomal subunits, with the overall effect of blocking protein synthesis

Antibacterial Drugs that Inhibit DNA or RNA

Quinolones:
- Synthetic broad-spectrum antibiotics with a core of two fused six-member rings (quinolone ring)
- Fluoroquinolones, with fluorine substitutions, are the primary quinolones used for bacterial infections
- Inhibit bacterial DNA replication by inhibiting topoisomerase II (DNA gyrase) and topoisomerase IV, which are essential for bacterial DNA replication but absent in human cells
- Classified into generations based on antimicrobial activity:
  - First Generation: Nalidixic acid and Cinoxacin - active against gram-negative organisms (excluding Pseudomonas species), used for uncomplicated urinary tract infections
  - Second Generation: Norfloxacin, lomefloxacin, Enofloxacin, ofloxacin, ciprofloxacin - expanded activity against Pseudomonas species and some gram-positive bacteria, used for complicated UTI, pyelonephritis, sexually transmitted diseases, prostatitis, skin and soft tissue infections
  - Third Generation: Levofloxacin, Sparfloxacin - further expanded gram-positive coverage, including penicillin-sensitive and -resistant S. pneumoniae, used for acute exacerbation of chronic bronchitis (AECB) and community-acquired pneumonia (CAP)
  - Fourth Generation: Moxifloxacin - broadest spectrum, including anaerobic coverage, used for abdominal infections, nosocomial pneumonia, pelvic infections
Rifampicin and Rifabutin:
- Bactericidal antibiotics from the rifamycin group
- Inhibit RNA synthesis by inhibiting bacterial RNA polymerase, preventing mRNA production without affecting human RNA polymerase
- Rifampicin is used primarily for tuberculosis treatment in combination with other drugs and for prophylaxis in close contacts of meningitis patients
- Given in combination due to the rapid emergence of resistant mutants
- Excreted in high concentrations in saliva, making it effective for bacterial meningitis prophylaxis due to the carriage of organisms in the throat

Antibacterial Drugs that Affect Metabolic Pathways

Sulfonamides and Trimethoprim:
- Synthetic drugs that interfere with folate metabolism by blocking enzymes needed for tetrahydrofolate synthesis
- Tetrahydrofolate is essential for the synthesis of folic acid, DNA, RNA, and amino acids
- Often given together to achieve a bactericidal synergistic effect
- Orally active and interfere with dihydrofolate reductase, an enzyme crucial for tetrahydrofolate formation

Bacterial Cell Wall

Most bacteria contain a rigid peptidoglycan layer in their cell wall, which protects the cell from rupture in hypotonic environments.
Peptidoglycan biosynthesis occurs in three stages:
- Stage 1: Cell wall precursors are synthesized in the cytoplasm.
- Stage 2: Precursors are inserted into the cell wall by a transglycosylase.
- Stage 3: Precursors are fused by a transpeptidase.
Mammalian cells lack cell walls, making antibiotics targeting peptidoglycan synthesis highly selectively toxic. They only target bacterial cells.
Antibiotics targeting cell wall synthesis are most effective against actively growing microorganisms.
Antibiotics targeting cell wall synthesis cause the cell to develop weak points and become osmotically fragile.
These antibiotics are considered bactericidal because the weakened cell is susceptible to lysis.

β-Lactam Antibacterials

β-Lactam antibiotics are characterized by the presence of a β-lactam ring in their structure, essential for antibacterial activity.
This group includes penicillins, cephalosporins, carbapenems, and monobactams.
They interfere with the transpeptidation reactions that seal the peptide crosslinks between glycan chains.
β-Lactam antibiotics inhibit penicillin-binding proteins (PBPs), which are enzymes responsible for cross-linking in bacterial cell walls.

Penicillins

Penicillin antibiotics are a large group of compounds ending in the suffix "-cillin".
Benzyl penicillin (Penicillin G) is the parent compound, and its action is restricted to gram-positive bacteria.
Natural penicillins (Penicillin G and Penicillin V) are produced by fermentation of the fungus Penicillium rubens.
Semisynthetic penicillins, like amoxicillin and ampicillin, are created by chemically modifying the main nucleus.

Penicillin Properties

Penicillin G is the best choice for sensitive bacteria due to its low toxicity and low cost. However, it can be hydrolyzed by β-lactamases and acids, is rapidly excreted in urine, and can trigger allergies.
Amoxicillin is a broader-spectrum penicillin that has a good oral bioavailability and is well-tolerated. It exhibits excellent activity against a wide range of gram-positive and gram-negative bacteria.
Ampicillin has a longer half-life than amoxicillin and is considered to be more effective against a broader range of bacteria. It is often used for meningitis and other serious infections.

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Description

This quiz explores the properties and mechanisms of glycopeptides, including vancomycin and teicoplanin. It discusses their action on cell wall synthesis, effectiveness against gram-positive bacteria, and their use in treating infections. Additionally, it covers lipoglycopeptides and their clinical relevance.