15. Macrolides. Ketolides Flashcards
List the side effects of Macrolides?
Generally non-toxic (like B-lactams) → safe in pregnancy
- Allergic reactions
- GI motility increases: mainly erythromycin - a motilin-like metabolite → diarrhea, nausea
- Acute cholestatic hepatitis: mainly with clarithromycin, rarely, probably via HS rxn
- QT prolongation: risk for TdP tachycardia
What spectrum does Macrolides cover?
Covers a similar spectrum to penicillins, but also affect some IC pathogens and Legionella.
- Mainly Gram + (pneumococci, Strep, Staph, Corynebacteria) - esp. in allergic patients. Also good for Mycoplasma, Legionella and Chlamydia (atypical pneumonias + urethritis/cervicitis), + some mycobacteria, also H. pylori and Listeria. Toxoplasma, esp. spiramycin
- Poor Gram - efficacy (no effect against enteric rods, pseudomonas, acinetobacter; some effect against H. influenzae, B. pertussis, C, jejuni and Neisseria, T. pallidum). Weak affect against anaerobes (some against oral anaerobes, but none against B. fragilis → use penicillins for these).
What is the MOA of Macrolides?
Macrolides bind to 50s ribosomal subunit (+ inhibits translocation) → bacteriostatic effect. May be bactericidal in highly susceptible Strep, C. diphtheriae and B. pertussis. Have a time-dependent effect.
What is the resistance mechanism for Macrolides?
- Degradation - by esterases (sometimes also by methylases).
- Binding Site Alteration - 50s ribosomal subunit changes → so-called “MLSB” bacteria → cross-resistance btwn abx that bind 50s subunit (Macrolides, Lincosamides such as clindamycin, Streptogramin B AKA quinupristin)
- Also via via ↓ permeability and efflux pumps.
What are the kinetics like for Macrolides?
- Mostly acid-stable, except erythromycin (uses an enteric coating)
- DO NOT enter CNS well
- Accumulate at high conc. intracellularly via an active transport mechanism - especially azithromycin!
- Active metabolite of clarithromycin is effective against H. pylori
What are the indications for Macrolides?
- DOC in community-acquired RTI (pertussis, diphtheria, pneumococci, susceptible H. flu, Mycoplasma, Legionella)
- Chlamydia - DOC is azithromycin (respiratory, genital, or neonatal infections)
- Staph or Strep infections in pt. with penicillin allergy
- H. pylori eradication
- Toxoplasma in pregnancy - spiramycin
- C. jejuni enteritis
List the Older Macrolides.
- Erythromycin
- Spiramycin
- Josamycin
- Roxithromycin
What are the indications for Erythromycin?
Erythromycin is the oldest macrolide:
- Orally given for neonatal conjunctivitis / pneumonia by C. trachomatis)
- (eyedrops for N. gonorrhoeae neonatal conjunctivitis)
- (diphtheria).
What are the indications for Spiramycin?
- Toxoplasma treatment in pregnancy
What spectrum does Clarithromycin cover and what are its indications?
Clarithromycin is a newer macrolide drug with a different spectrum. It has additional stronger effect against Gram + bacteria and part of H. pylori triple therapy (also affects M. avium).
List the newer Macrolides.
- Clarithromycin
- Azithromycin
What spectrum does Azithromycin cover?
Azithromycin has a different spectrum from other macrolides, it has a stronger effect against Gram (-).
What are the side effects of Ketolides?
- GI symptoms: diarrhea, nausea, vomiting.
- Sometimes hepatitis
- (so not used in respiratory tract infections of lower severity; only pneumonia or acute exacerbation of chronic bronchitis)
What is the MOA of Telithromycin?
Telithromycin is a semi-synthetic macrolide (ketolide) which also binds 50s → with the same spectrum as Macrolide (?). It is bactericidal with a long post-antibiotic effect + concentration dependence. It effective against some macrolide-resistant strains, including some MLSB!!!
What are the indications for Ketolides?
- Community-acquired pneumonia (Staph, Strep, Moraxella, susceptible H. flu)
- Interactions: also inhibits CYP450
