Macrolide

Aka: Macrolide, Extended Spectrum Macrolide, Telithromycin, Ketek

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II. Indications: Activity Spectrum

  1. General Activity
    1. Bacteria without cell walls (Mycoplasma, Legionella, Chlamydia)
    2. Anaerobic Bacteria are partially covered by Extended Spectrum Macrolides (not Erythromycin)
    3. Aerobic Bacteria
      1. Gram Positive Aerobes
      2. Gram Negative Aerobes (except Campylobacter, Pasteurella)
        1. Haemophilus Influenzae is covered by Extended Spectrum Macrolides, but not by Erythromycin
    4. Macrolide resistance is increasing
      1. Resistance to one Macrolide is resistance to all Macrolides
  2. Erythromycin
    1. Major indications
      1. Chlamydia pneumoniae
      2. Chlamydia Trachomatis
        1. Pneumoniae or Conjunctivitis
        2. Pelvic infection in pregnancy
      3. Legionella pneumophila
      4. Mycoplasma pneumoniae
      5. Bordetella Pertussis
      6. Corynebacterium diphtheriae
      7. Campylobacter jejuni
    2. Other organisms covered
      1. Ureaplasma Urealyticum
      2. Treponema pallidum (Syphilis)
      3. Staphylococcus
      4. Streptococcus
      5. Bacillus anthracis
      6. Clostridium species
  3. Fidaxomicin (Dificid)
    1. Indicated in Clostridioides difficile (Clostridium difficile)
    2. Narrow spectrum Antibiotic (C. difficile, Staphylococcus, Enterococcus)
  4. Extended Spectrum Agents
    1. Coverage includes organisms covered by Erythromycin
    2. Major Indications for extended spectrum agents
      1. Single dose Chlamydia Trachomatis treatment
      2. Non-tuberculous Mycobacterial infections
      3. Helicobacter infections
      4. Respiratory infections
        1. Otitis Media (Azithromycin)
          1. Not recommended due to increased resistance rates
        2. Community Acquired Pneumonia
          1. Limit to suspected Mycoplasma pneumonia or Legionella pneumonia
          2. Macrolide resistant Pneumococcus is common
          3. Consider Doxycycline as alternative
        3. Acute Sinusitis (Azithromycin)
          1. Not recommended due to growing resistance rates
        4. Streptococcal Pharyngitis
          1. Macrolides are only indicated in significant allergy to beta-lactams
    3. Clarithromycin
      1. Streptococcus Pneumoniae (Pneumococcus)
      2. Staphylococcus Aureus
      3. Toxoplasmosis gondii
      4. Mycobacterium leprae
      5. Mycobacterium Avium Complex
      6. Borrelia Burgdorferi
    4. Azithromycin
      1. Haemophilus Influenzae
      2. Moraxella catarrhalis
      3. Toxoplasmosis gondii
      4. Mycobacterium Avium Complex (Clarithromycin better)
      5. Borrelia Burgdorferi

III. Precautions

  1. Increasing Macrolide resistance for most indications (see below)
  2. QT Prolongation with Azithromycin (see below)
  3. Calcium Channel Blocker interaction with Clarithromycin (see below)
  4. Macrolides in general (including Azithromycin) may increase heart defects with first trimester exposure of 5-7 days
    1. Previously only Clarithromycin was considered a potential Teratogen (Cleft Lip association)
    2. Fan (2020) BMJ 368: m331 +PMID:32075790 [PubMed]

IV. Mechanism

  1. Activity
    1. Reversibly binds P Site on the 50s ribosomal subunit
    2. Blocks translocation of polypeptide chain, therefore inhibiting Protein synthesis
  2. Bacterial resistance mechanisms
    1. Impermeability of Bacterial outer membranes (esp. Gram Negative Organisms)
    2. Production of enzymes that alter ribosomal binding targets

V. Medications

  1. Erythromycin Oral Preparations (Take with food to reduce GI Upset)
    1. Erythromycin Base 1000 mg/day PO divided bid-qid
    2. Erythromycin Ethyl Succinate (EES)
      1. Adult: 400 mg PO qid
      2. Child: 30-50 mg/kg/day PO divided qid
  2. Erythromycin Parenteral Preparation: Erythromycin Lactobionate
    1. Dose: 15 to 20 mg/kg/day IV divided every 6 hours
    2. Maximum: 4 grams
  3. Fidaxomicin (Dificid)
    1. Indicated in Clostridioides difficile (Clostridium difficile)
    2. Narrow spectrum Antibiotic (C. difficile, Staphylococcus, Enterococcus)
      1. Does not affect Gram Negative Bacteria including normal bowel flora
    3. Minimal systemic absorption when taken orally
      1. As with oral Vancomycin, oral Fidaxomicin primarily stays in the Gastrointestinal Tract
  4. Extended Spectrum Macrolides
    1. Azithromycin
      1. Take more than 1 hour before or 2 hours after food
      2. Available in intravenous dosing
      3. Adult
        1. Day 1: 500 mg PO qd
        2. Day 2 to 5: 250 mg PO qd
      4. Child
        1. Day 1: 10 mg/kg PO qd (maximum: 500 mg)
        2. Day 2 to 5: 5 mg/kg PO qd (maximum: 250 mg)
      5. Infant under age 6 months
        1. 10 mg/kg/day for 5 days
    2. Clarithromycin
      1. Dysgeusia or Distorted Taste (20%)
      2. May take with or without food
      3. Adult: 250 to 500 mg PO bid
      4. Child: 7.5 mg/kg PO bid
    3. Telithromycin
      1. Discontinued in the United States
      2. Adult: 800 mg orally daily for 5 to 7 days
      3. Avoid in patients with Myasthenia Gravis due to risk of Respiratory Failure (FDA Black Box Warning)
      4. Similar to other Extended Spectrum Macrolides
        1. Appears to have greater activity for Pneumococcus
        2. May be used in place of other broad spectrum agents
          1. Augmentin
          2. Extended spectrum Fluoroquinolones
      5. References
        1. Fogarty (2003) J Antimicrob Chemother 51:947-55 [PubMed]

VI. Pharmacokinetics: Half Life

  1. Clarithromycin: 5 hours
  2. Telithromycin: 10 hours
  3. Azithromycin: 68 hours

VII. Adverse Effects

  1. Nausea and Vomiting
    1. Most with Erythromycin
    2. Least with Azithromycin and Clarithromycin
  2. QT Prolongation (see below)
    1. Class effect with all Macrolides
    2. Three fold increased risk of Sudden Cardiac Death while on Azithromycin
    3. Ray (2013) N Engl J Med 366(20): 1881-90 [PubMed]

VIII. Drug Interactions

  1. Interactions may also occur with extended spectrum
    1. Clarithromycin
    2. Telithromycin
    3. Less likely to occur with Azithromycin
  2. QT Prolongation (Erythromycin with an agent below)
    1. Calcium Channel Blockers increase Erythromycin level
      1. Verapamil
      2. Diltiazem
    2. Other potent CYP3A4 inhibitors
      1. Ketoconazole
      2. Itraconazole
      3. Nefazodone
      4. Protease Inhibitors
  3. References
    1. Ray (2004) N Engl J Med 351:1089-96 [PubMed]

IX. References

  1. (2013) Presc Lett 20(8): 44

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Related Studies

Ontology: Macrolides (C0282563)

Definition (MSH) A group of often glycosylated macrocyclic compounds formed by chain extension of multiple PROPIONATES cyclized into a large (typically 12, 14, or 16)-membered lactone. Macrolides belong to the POLYKETIDES class of natural products, and many members exhibit ANTIBIOTIC properties.
Definition (NCI) A term used to describe a chemical structure of a compound containing a large lactone ring, usually with a 14 or 16-membered ring structure. The prototypical compounds within the macrolide class are the erythromycin-based antibiotics; however, many compounds with this chemical structure are being developed for other diseases.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D018942
SnomedCT 428787002
English Macrolides, Macrolide (substance), Macrolide, Macrolides [Chemical/Ingredient], macrolides, macrolide
Swedish Makrolider
Czech makrolidy
Finnish Makrolidit
Russian MAKROLIDY, МАКРОЛИДЫ
Spanish macrólido, macrólido (sustancia), Macrólidos
Japanese マクロライド
Polish Makrolidy
Croatian MAKROLIDI
Norwegian Not Translated[Macrolides]
French Macrolides
German Makrolide
Italian Macrolidi
Portuguese Macrolídeos
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: telithromycin (C0907410)

Concepts Antibiotic (T195) , Organic Chemical (T109)
MSH C106791
SnomedCT 395260006, 410908003
LNC LP33364-8, MTHU016681
English telithromycin (medication), telithromycin [Chemical/Ingredient], telithromycin, (1S,2R,5R,7R,8R,9S,11R,13R,14R)-8-[(2S,3R,4S,6R)-4-dimethylamino-3-hydroxy-6-methyl-oxan-2-yl]oxy-2-ethyl-9-methoxy-1,5,7,9,11,13-hexamethyl-15-[4-(4-pyridin-3-ylimidazol-1-yl)butyl]-3,17-dioxa-15-azabicyclo[12.3.0]heptadecane-4,6,12,16-tetrone, Telithromycin (product), Telithromycin, Telithromycin (substance), TELITHROMYCIN
Spanish telitromicina (producto), telitromicina, telitromicina (sustancia)
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Ketek (C1452484)

Concepts Antibiotic (T195) , Organic Chemical (T109)
MSH C106791
English Aventis brand of telithromycin, Ketek
Derived from the NIH UMLS (Unified Medical Language System)

Related Topics in Pharmacology

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