Macrolides & glycopeptide antibiotics.pdf

GLYCOPEPTIDE ANTIBIOTICS & MACROLIDES (2024) MACROLIDES Macrolides are one of the most commonly used families of antibiotics. The first macrolide antibiotic, erythromycin, was isolated in 1952 from products produced by Streptomyces er...

GLYCOPEPTIDE ANTIBIOTICS & MACROLIDES (2024) MACROLIDES Macrolides are one of the most commonly used families of antibiotics. The first macrolide antibiotic, erythromycin, was isolated in 1952 from products produced by Streptomyces erythreus. In 1991, two semisynthetic derivatives of erythromycin, azithromycin and clarithromycin, were brought to market. 1. Enumerate macrolides The macrolides include: erythromycin, clarithromycin, azithromycin and roxithromycin. 2. Describe the mechanism of action of macrolides. Macrolides inhibit RNA-dependent protein synthesis by reversibly binding to the ‘P’ site of 50S ribosomal subunits of susceptible microorganisms and induce dissociation of peptidyl transfer RNA (tRNA) from the ribosome. Thus, RNA-dependent protein synthesis is suppressed, and bacterial growth is inhibited. Macrolides are bacteriostatic at therapeutic doses, but they may be bactericidal at higher doses. 1 Page Department of Pharmacology, Manipal University College Malaysia, Melaka, Malaysia  GLYCOPEPTIDE ANTIBIOTICS & MACROLIDES (2024) 3. List the therapeutic uses of following: erythromycin, azithromycin and clarithromycin. A. Erythromycin: is effective against many of the same organisms as penicillin G, therefore, it is used in patients who are allergic to the penicillins - especially for prophylaxis against bacterial endocarditis in susceptible patients and as an alternate to penicillin in the treatment of syphilis. Respiratory tract infections of mild to moderate degree caused by Streptococcus pyogenes or Streptococcus pneumoniae. Listeriosis caused by Listeria monocytogenes. Respiratory tract infections due to Mycoplasma pneumoniae. Pertussis (whooping cough) caused by Bordetella pertussis. Diphtheria. Infections due to Corynebacterium diphtheriae, as an adjunct to antitoxin, to prevent establishment of carriers and to eradicate the organism in carriers. B. Azithromycin: Acute bacterial exacerbations of chronic obstructive pulmonary disease due to Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae Community-acquired pneumonia of mild severity due to Streptococcus pneumoniae or Haemophilus influenzae Streptococcal pharyngitis/tonsillitis due to Streptococcus pyogenes Non-gonococcal urethritis and cervicitis due to Chlamydia trachomatis (Drug of Choice) Disseminated Mycobacterium avium complex disease 2 Page Department of Pharmacology, Manipal University College Malaysia, Melaka, Malaysia  GLYCOPEPTIDE ANTIBIOTICS & MACROLIDES (2024) C. Clarithromycin: Pharyngitis/Tonsillitis due to Streptococcus pyogenes Acute maxillary sinusitis due to Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae Acute bacterial exacerbation of chronic bronchitis due to Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae Acute otitis media due to Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae Community-Acquired Pneumonia due to Haemophilus influenzae, Mycoplasma pneumoniae, Streptococcus pneumoniae, or Chlamydia pneumoniae 4. Describe the adverse effects of erythromycin a. Epigastric distress: In the acidic environment of the stomach, erythromycin is degraded to a hemiketal intermediate, a motilin- receptor agonist. Motilin activation leads to contractions of the smooth muscles of the gastrointestinal tract which manifests as abdominal discomfort and diarrhea. It may also cause nausea and vomiting b. Cholestatic jaundice: This side effect occurs especially with the estolate form of erythromycin, probably as the result of a hypersensitivity reaction to the estolate c. Hypersensitivity in the form of skin rashes, fever and eosinophilia may occur with the use of estolate salt of erythromycin d. Erythromycin has been associated with QT prolongation and ventricular arrhythmias, including ventricular tachycardia and torsades de pointes 3 Page Department of Pharmacology, Manipal University College Malaysia, Melaka, Malaysia  GLYCOPEPTIDE ANTIBIOTICS & MACROLIDES (2024) 5. Compare and contrast erythromycin and azithromycin Azithromycin is a semisynthetic derivative of erythromycin with a broader spectrum of activity. Azithromycin shows cross-resistance with erythromycin. Erythromycin & azithromycin are primarily concentrated and excreted in an active form in the bile Generic name Erythromycin Azithromycin Food affects Yes Yes absorption Poor (Enteric coating Gastric acid stability Stable required) Half-life 1-1.5 hours 40-60 hours Protein binding 70% 12 – 50% High penetration, Tissue penetration Poor especially in infected tissue. Microsomal enzyme High No inhibition Broader spectrum More active against Spectrum of activity including gram negative gram positive bacteria bacteria and chlamydia 4 Page Department of Pharmacology, Manipal University College Malaysia, Melaka, Malaysia  GLYCOPEPTIDE ANTIBIOTICS & MACROLIDES (2024) MODEL QUESTIONS 1. List macrolides used clinically. 2. Explain the mechanism of action of Erythromycin and list its adverse effects. 3. List the therapeutic uses of the following drugs with the organism involved: a. Erythromycin b. Azithromycin c. Clarithromycin 4. List the advantages and disadvantages of Azithromycin over erythromycin. 5 Page Department of Pharmacology, Manipal University College Malaysia, Melaka, Malaysia  GLYCOPEPTIDE ANTIBIOTICS & MACROLIDES (2024) GLYCOPEPTIDE ANTIBIOTICS 1. Explain the mechanism of action of vancomycin and teicoplanin. Mechanism of action of vancomycin and teicoplanin: ✓ Both have similar mechanism of action ✓ Bactericidal ✓ Acts by inhibiting cell wall synthesis Binds to D-alanyl-D-alanine portion of terminal end of peptidoglycan pentapetide (Fig 2) and prevents further elongation and cross linking of peptidoglycan layers ↓ Formation of imperfect cell wall ↓ Entry of fluid into the bacteria ↓ Bacteria swells and bursts ↓ Bactericidal action It also damages the cell membrane and alters cytoplasmic membrane permeability. Cannot diffuse through outer cell membrane due to larger molecular size → hence not effective against G-ve organisms Active against aerobic and anaerobic G +ve cocci and bacilli 2. List the uses and adverse effects of vancomycin and teicoplanin. A. Uses of vancomycin: Given intravenously in: 6 Page a. Enterococcal endocarditis: given with gentamicin Department of Pharmacology, Manipal University College Malaysia, Melaka, Malaysia  GLYCOPEPTIDE ANTIBIOTICS & MACROLIDES (2024) b. MRSA infections c. Pseudomembranous enterocolitis (PMC) caused by C. difficile ( metronidazole is the drug of choice and vancomycin is used if metronidazole is not effective): used orally B. List the adverse effects of vancomycin: Red neck syndrome (Red man syndrome) due to histamine release Ototoxicity, nephrotoxicity, rashes, neutropenia, eosinophilia, chills and fever C. List the uses of teicoplanin: Spectrum same as vancomycin Uses: same as vancomycin D. Adverse effect of teicoplanin: Bronchospasm 7 Page Department of Pharmacology, Manipal University College Malaysia, Melaka, Malaysia  GLYCOPEPTIDE ANTIBIOTICS & MACROLIDES (2024) MODEL QUESTIONS 1. Explain the mechanism of action of vancomycin and teicoplanin and mention their uses with the causative organism. 2. List drugs used each in infections caused by MRSA and pseudomonas. 8 Page Department of Pharmacology, Manipal University College Malaysia, Melaka, Malaysia